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Sample records for adult murine offspring

  1. Prenatal exposure to lipopolysaccharide results in myocardial remodelling in adult murine offspring

    PubMed Central

    2013-01-01

    Background The epigenetic plasticity hypothesis indicates that pregnancy exposure may result in adult-onset diseases, including hypertension, diabetes and cardiovascular disease, in offspring. In a previous study, we discovered that prenatal exposure to inflammatory stimulants, such as lipopolysaccharides (LPS), could lead to hypertension in adult rat offspring. In the present study, we further demonstrate that maternal inflammation induces cardiac hypertrophy and dysfunction via ectopic over-expression of nuclear transcription factor κB (NF- κB), and pyrrolidine dithiocarbamate (PDTC) can protect cardiac function by reducing maternal inflammation. Methods Pregnant SD rats were randomly divided into three groups and intraperitoneally injected with a vehicle, LPS (0.79 mg/kg), or LPS (0.79 mg/kg) plus PDTC (100 mg/kg) at 8 to 12 days of gestation. The offspring were raised until 4 and 8 months old, at which point an echocardiographic study was performed. The left ventricular (LV) mass index and apoptosis were examined. Results At 4 months of age, the LPS offspring exhibited augmented posterior wall thickness. These rats displayed left ventricle (LV) hypertrophy and LV diastolic dysfunction as well as a higher apoptotic index, a higher level of Bax and a lower level of Bcl-2 at 8 months of age. The protein levels of NF-κB (p65) in the myocardium of the offspring were measured at this time. NF-κB protein levels were higher in the myocardium of LPS offspring. The offspring that were prenatally treated with PDTC displayed improved signs of blood pressure (BP) and LV hypertrophy. Conclusions Maternal inflammation can induce cardiac hypertrophy in offspring during aging accompanied with hypertension emergence and can be rescued by the maternal administration of PDTC (the inhibitor of NF-κB). PMID:24764457

  2. Maternal exercise during pregnancy promotes physical activity in adult offspring.

    PubMed

    Eclarinal, Jesse D; Zhu, Shaoyu; Baker, Maria S; Piyarathna, Danthasinghe B; Coarfa, Cristian; Fiorotto, Marta L; Waterland, Robert A

    2016-07-01

    Previous rodent studies have shown that maternal voluntary exercise during pregnancy leads to metabolic changes in adult offspring. We set out to test whether maternal voluntary exercise during pregnancy also induces persistent changes in voluntary physical activity in the offspring. Adult C57BL/6J female mice were randomly assigned to be caged with an unlocked (U) or locked (L) running wheel before and during pregnancy. Maternal running behavior was monitored during pregnancy, and body weight, body composition, food intake, energy expenditure, total cage activity, and running wheel activity were measured in the offspring at various ages. U offspring were slightly heavier at birth, but no group differences in body weight or composition were observed at later ages (when mice were caged without access to running wheels). Consistent with our hypothesis, U offspring were more physically active as adults. This effect was observed earlier in female offspring (at sexual maturation). Remarkably, at 300 d of age, U females achieved greater fat loss in response to a 3-wk voluntary exercise program. Our findings show for the first time that maternal physical activity during pregnancy affects the offspring's lifelong propensity for physical activity and may have important implications for combating the worldwide epidemic of physical inactivity and obesity.-Eclarinal, J. D., Zhu, S., Baker, M. S., Piyarathna, D. B., Coarfa, C., Fiorotto, M. L., Waterland, R. A. Maternal exercise during pregnancy promotes physical activity in adult offspring. PMID:27033262

  3. Care of Aging Parents by Adult Offspring.

    ERIC Educational Resources Information Center

    Ames, Barbara D.

    A prevailing myth holds that modern families, characterized by high mobility and individualistic life styles, do not care for their aging members. To assess the quantity and characteristics of the care of noninstitutionalized elderly parents by their adult children, parents and adult child pairs (N=50) responded to interviews. Specific research…

  4. Levels of maternal care in dogs affect adult offspring temperament.

    PubMed

    Foyer, Pernilla; Wilsson, Erik; Jensen, Per

    2016-01-01

    Dog puppies are born in a state of large neural immaturity; therefore, the nervous system is sensitive to environmental influences early in life. In primates and rodents, early experiences, such as maternal care, have been shown to have profound and lasting effects on the later behaviour and physiology of offspring. We hypothesised that this would also be the case for dogs with important implications for the breeding of working dogs. In the present study, variation in the mother-offspring interactions of German Shepherd dogs within the Swedish breeding program for military working dogs was studied by video recording 22 mothers with their litters during the first three weeks postpartum. The aim was to classify mothers with respect to their level of maternal care and to investigate the effect of this care on pup behaviour in a standardised temperament test carried out at approximately 18 months of age. The results show that females differed consistently in their level of maternal care, which significantly affected the adult behaviour of the offspring, mainly with respect to behaviours classified as Physical and Social Engagement, as well as Aggression. Taking maternal quality into account in breeding programs may therefore improve the process of selecting working dogs. PMID:26758076

  5. Levels of maternal care in dogs affect adult offspring temperament

    PubMed Central

    Foyer, Pernilla; Wilsson, Erik; Jensen, Per

    2016-01-01

    Dog puppies are born in a state of large neural immaturity; therefore, the nervous system is sensitive to environmental influences early in life. In primates and rodents, early experiences, such as maternal care, have been shown to have profound and lasting effects on the later behaviour and physiology of offspring. We hypothesised that this would also be the case for dogs with important implications for the breeding of working dogs. In the present study, variation in the mother-offspring interactions of German Shepherd dogs within the Swedish breeding program for military working dogs was studied by video recording 22 mothers with their litters during the first three weeks postpartum. The aim was to classify mothers with respect to their level of maternal care and to investigate the effect of this care on pup behaviour in a standardised temperament test carried out at approximately 18 months of age. The results show that females differed consistently in their level of maternal care, which significantly affected the adult behaviour of the offspring, mainly with respect to behaviours classified as Physical and Social Engagement, as well as Aggression. Taking maternal quality into account in breeding programs may therefore improve the process of selecting working dogs. PMID:26758076

  6. Japanese macaque (Macaca fuscata) mothers huddle with their young offspring instead of adult females for thermoregulation.

    PubMed

    Ueno, Masataka; Nakamichi, Masayuki

    2016-08-01

    It is unclear whom animals select to huddle with for thermoregulation. In this study, we investigated whom Japanese macaque (Macaca fuscata) mothers huddled with-their young offspring or other adult group members-when there is need for thermoregulation. We used a focal-animal sampling method, targeting 17 females at Katsuyama, Okayama Prefecture, Japan. A majority of huddling among adult females was recorded during winter season (December, January, and February). Females who had young (0- or 1-year-old) offspring huddled less frequently with other adult females compared to females who did not have young offspring in winter. However, including young offspring, the frequency of huddling with any other individuals did not differ by whether females had young offspring. Moreover, the females who did not have young offspring huddled with other adult females more often in cloudy than in sunny weather during winter season. In contrast, females who had young offspring increased huddling with their young offspring in cloudy than in sunny weather, but did not do so with other adult females. This study indicates that Japanese macaque mothers huddle with their young offspring instead of other adult females when there is need for thermoregulation. PMID:27262980

  7. Perinatal undernutrition programmes thyroid function in the adult rat offspring.

    PubMed

    Ayala-Moreno, Rosario; Racotta, Radu; Anguiano, Brenda; Aceves, Carmen; Quevedo, Lucía

    2013-12-01

    Increasing evidence suggests that alterations in early nutrition programme physiological changes in adulthood. In the present study, we determined the effects of undernutrition during gestation and lactation on the programming of thyroid function in adult rat offspring. Perinatal undernutrition was achieved by a 40% food restriction in female Wistar rats from the mating day to weaning. On postpartum day 21, the offspring of the control and food-restricted dams were weaned and given free access to a commercial diet until adulthood. The results showed that undernourished rats exhibited decreased 3,5,3'-triiodothyronine (T3) levels but had normal thyroxine (T4) and thyrotropin (TSH) levels at weaning; on day 90, these rats displayed a significant flip, exhibiting normalised T3 (total and free) and total T4 levels, but low free T4 and persistently higher TSH levels, which were maintained even on postnatal day 140. This profile was accompanied by a scarce fat depot, a lower RMR and an exacerbated sympathetic brown adipose tissue (BAT) tone (deiodinase type 2 expression) in basal conditions. Moreover, when a functional challenge (cold exposure) was applied, the restricted group exhibited partial changes in TSH (29 v. 100%) and T4 (non-response v. 17%) levels, a significant decrease in leptin levels (75 v. 32%) and the maintenance of a sympathetic BAT over-response (higher noradrenaline levels) in comparison with the control group. The findings of the present study suggest that undernutrition during the perinatal period produces permanent changes in the hypothalamus-pituitary-thyroid axis with consequent low body weight and decreased RMR and facultative thermogenesis. We hypothesise that these changes predispose individuals to exhibiting adult subclinical hypothyroidism. PMID:23800456

  8. Autobiographical memory in adult offspring of traumatized parents with and without posttraumatic stress symptoms.

    PubMed

    Wittekind, Charlotte E; Jelinek, Lena; Moritz, Steffen; Muhtz, Christoph; Berna, Fabrice

    2016-08-30

    The present study examined potential transgenerational effects of trauma on autobiographical memory in adult offspring of elderly participants with and without PTSD symptoms who were exposed to an early trauma during childhood. As traumatization is associated with reduced memory specificity for past events, we hypothesized that offspring of traumatized parents might be exposed to a less elaborative narrative style, which, in turn, might result in less specific autobiographical memories in the offspring. Results show that autobiographical memory specificity did not differ significantly between adult offspring of traumatized elderly participants with PTSD symptoms, without PTSD symptoms, and non-traumatized elderly participants. PMID:27322841

  9. Parental Depression as a Moderator of Secondary Deficits of Depression in Adult Offspring

    ERIC Educational Resources Information Center

    Timko, Christine; Cronkite, Ruth C.; Swindle, Ralph; Robinson, Rebecca L.; Sutkowi, Anne; Moos, Rudolf H.

    2009-01-01

    This study examined whether having a depressed parent intensifies the secondary deficits that often co-occur with offspring's depression symptoms. The sample was adult offspring of parents who had been diagnosed with depression 23 years earlier (N = 143) and demographically matched nondepressed parents (N = 197). Respondents completed mailed…

  10. Adult cardiorenal benefits from postnatal fish oil supplement in rat offspring of low-protein pregnancies.

    PubMed

    Catta-Preta, Mariana; Oliveira, Daniel Alves; Mandarim-de-Lacerda, Carlos Alberto; Aguila, Marcia Barbosa

    2006-12-23

    We investigated the effect of fish oil (FO) treatment on cardiorenal structure of adult offspring from low-protein pregnancies. Three month old offspring were assigned to eight groups (four male groups and four female groups, n=8 each) (NP=normal-protein diet, LP=low-protein diet): NP, LP, NP plus FO, and LP plus FO. Left ventricle and kidney were analyzed with light microscopy and stereology. The both sexes of LP offspring showed 30% lower birth weights than the respective NP offspring and high blood pressure (BP) levels in adulthood which was efficiently reduced by FO treatment. In the heart, FO treated the cardiomyocyte hypertrophy, the vascularization impairment, and decreased the cardiomyocyte loss usually observed in adult LP offspring. In the kidney, FO treated, in the male, the imbalance of the cortex-to-medulla ratio observed in both sexes of LP offspring, and reduced the glomeruli loss in the LP offspring. The positive correlation between the number of cardiomyocyte nuclei later in life and the body mass (BM) at birth was significant only in both sexes of LP offspring and this correlation disappeared in LP plus fish oil offspring. The positive correlation between the number of glomeruli later in life and the BM at birth was significant in NP male offspring and in both sexes of LP offspring. In conclusion, FO supplement, which is a rich source of n-3 fatty acids (DHA and EPA), has beneficial effects on BP control and cardiac and renal adverse remodeling usually seen in offspring of the LP pregnancies. PMID:17020772

  11. Risk for congenital anomalies in offspring of childhood, adolescent and young adult cancer survivors.

    PubMed

    Seppänen, Viivi I; Artama, Miia S; Malila, Nea K; Pitkäniemi, Janne M; Rantanen, Matti E; Ritvanen, Annukka K; Madanat-Harjuoja, Laura-Maria

    2016-10-15

    Offspring of cancer survivors (CS) may be at risk for congenital anomalies due to the mutagenic therapies received by their parents. Our population-based cohort study aimed to investigate the risk for congenital anomalies in offspring of CS compared to offspring of their siblings. Using the Finnish Cancer Registry, Central Population Register, and Hospital Discharge Register, we identified hospital contacts due to congenital anomalies in 6,862 offspring of CS (early-onset cancer between 1953 and 2004) and 35,690 offspring of siblings. Associations between congenital anomalies and cancer were evaluated using generalized linear regression modelling. The ratio of congenital anomalies in offspring of CS (3.2%) was slightly, but non-significantly, elevated compared to that in offspring of siblings (2.7%) [prevalence ratio (PR) 1.07, 95% confidence interval (CI) 0.91-1.25]. When offspring of childhood and adolescent survivors (0-19 years at cancer diagnosis) were compared to siblings' offspring, the risk for congenital anomalies was non-significantly increased (PR 1.17, 95% CI 0.92-1.49). No such increase existed for offspring of young adult survivors (20-34 years at cancer diagnosis) (PR 1.01, 95% CI 0.83-1.23). The risks for congenital anomalies were elevated among offspring of CS diagnosed with cancer in the earlier decades (1955-1964: PR 2.77, 95% C I 1.26-6.11; and 1965-1974: PR 1.55, 95% C I 0.94-2.56). In our study, we did not detect an overall elevated risk for congenital anomalies in offspring of survivors diagnosed in young adulthood. An association between cancer exposure of the parent and congenital anomalies in the offspring appeared only for those CS who were diagnosed in the earlier decades. PMID:27280956

  12. OXIDATIVE STRESS CONTRIBUTES TO SEX DIFFERENCES IN BLOOD PRESSURE IN ADULT GROWTH RESTRICTED OFFSPRING

    PubMed Central

    Ojeda, Norma B.; Hennington, Bettye Sue; Williamson, Danielle T.; Hill, Melanie L.; Betson, Nicole E.E.; Sartori-Valinotti, Julio C.; Reckelhoff, Jane F.; Royals, Thomas P.; Alexander, Barbara T.

    2013-01-01

    Numerous experimental studies suggest that oxidative stress contributes to the pathophysiology of hypertension and importantly, that oxidative stress plays a more definitive role in mediating hypertension in males than in females. Intrauterine growth-restriction induced by reduced uterine perfusion initiated at day 14 of gestation in the rat programs hypertension in adult male growth-restricted offspring; yet, female growth-restricted offspring are normotensive. The mechanisms mediating sex differences in blood pressure in adult growth-restricted offspring are not clear. Thus, this study tested the hypothesis that sex specific differences in renal oxidative stress contribute to the regulation of blood pressure in adult growth-restricted offspring. A significant increase in blood pressure measured by telemetry in male growth-restricted offspring (P<0.05) was associated with a marked increase in renal markers of oxidative stress (P<0.05). Chronic treatment with the antioxidant tempol had no effect on blood pressure in male control offspring, but it normalized blood pressure (P<0.05) and renal markers of oxidative stress (P<0.05) in male growth-restricted relative to male control. Renal markers of oxidative stress were not elevated in female growth-restricted offspring; however, renal activity of the antioxidant catalase was significantly elevated relative to female control (P<0.05). Chronic treatment with tempol did not significantly alter oxidative stress or blood pressure measured by telemetry in female offspring. Thus, these data suggest that sex differences in renal oxidative stress and antioxidant activity are present in adult growth-restricted offspring, and that oxidative stress may play a more important role in modulating blood pressure in male, but not female growth-restricted offspring. PMID:22585945

  13. Prenatal endotoxin exposure alters behavioural pain responses to lipopolysaccharide in adult offspring.

    PubMed

    Hodyl, Nicolette A; Walker, F Rohan; Krivanek, Klara M; Clifton, Vicki L; Hodgson, Deborah M

    2010-05-11

    Evidence suggests that exposure to bacterial endotoxin in early life can alter the production of pro-inflammatory cytokines in later life. This phenomenon may have significant consequences for pain and pain related behaviours as pro-inflammatory cytokines heighten pain sensitivity. This association has yet to be examined. As such, the aim of the present study was to characterize pain behaviours in adult rat offspring following prenatal endotoxin (PE) exposure. Pregnant F344 rats received endotoxin (200microg/kg, s.c.) or saline on gestational days 16, 18 and 20. Pain thresholds were assessed in the adult PE offspring (n=23) and control offspring (n=24) prior to and 4h following administration of lipopolysaccharide (LPS; 100microg/kg, s.c.). Three assays of pain were employed - the hot plate, tail immersion and von Frey tests. Results demonstrated sex-specific effects of prenatal endotoxin on the offspring, with PE males displaying unaltered pain thresholds on the von Frey test post-LPS administration (p<0.01), while male control offspring (n=24) displayed the expected hyperalgesia. Male PE offspring also displayed increased pain thresholds on the tail immersion test (p<0.01), while no change in pain sensitivity was observed in control males following LPS exposure. No difference in response was observed between the female PE and control offspring on the von Frey test, however PE female offspring displayed increased thresholds on the tail immersion test compared to baseline - an effect not observed in the control female offspring. Pain sensitivity on the hot plate test was unaffected by prenatal exposure to endotoxin. These data suggest that prenatal exposure to products associated with bacterial infection have the capacity to alter pain responses, which are evident in the adult offspring. PMID:20184906

  14. Mothers' exercise during pregnancy programs vasomotor function in adult offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The intrauterine environment is influenced by maternal behavior and known to influence lifelong atherosclerotic disease susceptibility in offspring. The purpose of this investigation was to test the hypothesis that maternal exercise during pregnancy increases endothelial function in offs...

  15. The Effects of Parental Health Shocks on Adult Offspring Smoking Behavior and Self-Assessed Health.

    PubMed

    Darden, Michael; Gilleskie, Donna

    2016-08-01

    An important avenue for smoking deterrence may be through familial ties if adult smokers respond to parental health shocks. In this paper, we merge the Original Cohort and the Offspring Cohort of the Framingham Heart Study to study how adult offspring smoking behavior and subjective health assessments vary with elder parent smoking behavior and health outcomes. These data allow us to model the smoking behavior of adult offspring over a 30-year period contemporaneously with parental behaviors and outcomes. We find strong 'like father, like son' and 'like mother, like daughter' correlations in smoking behavior. We find that adult offspring significantly curtail their own smoking following an own health shock; however, we find limited evidence that offspring smoking behavior is sensitive to parent health, with the notable exception that women significantly reduce both their smoking participation and intensity following a smoking-related cardiovascular event of a parent. We also model the subjective health assessment of adult offspring as a function of parent health, and we find that women report significantly worse health following the smoking-related death of a parent. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25981179

  16. Maternal Undernutrition Induces Premature Reproductive Senescence in Adult Female Rat Offspring

    PubMed Central

    Khorram, Omid; Keen-Rinehart, Erin; Chuang, Tsai-Der; Ross, Michael G.; Desai, Mina

    2014-01-01

    Objective To determine the effects of maternal undernutrition (MUN) on the reproductive axis of aging offspring. Design Animal (rat) study. Setting Research Laboratory. Animals Female Sprague-Dawley rats. Intervention(s) Food restriction during the second half of pregnancy in rats. Main Outcome Measures Circulating gonadotropins, Anti-Mullerian Hormone (AMH), ovarian morphology, estrous cyclicity and gene expression studies in the hypothalamus and ovary in 1 day old (P1) and aging adult offspring. Results Offspring of MUN dams had low birth weight (LBW) and by adult age developed obesity. 80% of adult LBW offspring had disruption of estrous cycle by 8 months of age with the majority of animals in persistent estrous. Ovarian morphology was consistent with acyclicity with ovaries exhibiting large cystic structures and reduced corpora lutea. There was an elevation in circulating testosterone (T), increased ovarian expression of enzymes involved in androgen synthesis, an increase in plasma Leuteinizing (LH/)/Follicle Stimulating hormone (FSH) levels, reduced estradiol (E2) levels and no changes in AMH in adult LBW offspring compared to control offspring. Hypothalamic expression of leptin receptor (OBRb), estrogen receptor-α (ER-α) and Gonadotropin Releasing hormone (GnRH) protein were altered in an age-dependent manner with increased ObRb, ER-α expression in P1 LBW hypothalami and a reversal of this expression pattern in adult LBW hypothalami. Conclusion Our data indicates that the maternal nutritional environment programs reproductive potential of the offspring through alteration of the hypothalamic-pituitary-gonadal axis. The premature reproductive senescence in LBW offspring could be secondary to development of obesity and hyperleptinemia in these animals in adult life. PMID:25439841

  17. Antenatal Antioxidant Prevents Nicotine-Mediated Hypertensive Response in Rat Adult Offspring.

    PubMed

    Xiao, DaLiao; Huang, Xiaohui; Li, Yong; Dasgupta, Chiranjib; Wang, Lei; Zhang, Lubo

    2015-09-01

    Previous studies have demonstrated that perinatal nicotine exposure increased blood pressure (BP) in adult offspring. However, the underlying mechanisms were unclear. The present study tested the hypothesis that perinatal nicotine-induced programming of hypertensive response is mediated by enhanced reactive oxygen species (ROS) in the vasculature. Nicotine was administered to pregnant rats via subcutaneous osmotic mini-pumps from Day 4 of gestation to Day 10 after birth, in the absence or presence of the ROS inhibitor N-acetyl-cysteine (NAC) in the drinking water. Experiments were conducted in 8-mo-old male offspring. Perinatal nicotine treatment resulted in a significant increase in arterial ROS production in offspring, which was abrogated by NAC. Angiotensin II (Ang II)-induced BP responses were significantly higher in nicotine-treated group than in saline-treated control group, and NAC treatment blocked the nicotine-induced increase in BP response. Consistent with that, the nicotine treatment significantly increased both Ang II-induced and phorbol [12, 13]-dibutyrate (PDBu, a Prkc activator)-induced arterial contractions in adult offspring, which were blocked by NAC treatment. In addition, perinatal nicotine treatment significantly attenuated acetylcholine-induced arterial relaxation in offspring, which was also inhibited by NAC treatment. Results demonstrate that inhibition of ROS blocks the nicotine-induced increase in arterial reactivity and BP response to vasoconstrictors in adult offspring, suggesting a key role for increased oxidative stress in nicotine-induced developmental programming of hypertensive phenotype in male offspring. PMID:26224008

  18. Maternal Smoke Exposure Impairs the Long-Term Fertility of Female Offspring in a Murine Model.

    PubMed

    Camlin, Nicole J; Sobinoff, Alexander P; Sutherland, Jessie M; Beckett, Emma L; Jarnicki, Andrew G; Vanders, Rebecca L; Hansbro, Philip M; McLaughlin, Eileen A; Holt, Janet E

    2016-02-01

    The theory of fetal origins of adult disease was first proposed in 1989, and in the decades since, a wide range of other diseases from obesity to asthma have been found to originate in early development. Because mammalian oocyte development begins in fetal life it has been suggested that environmental and lifestyle factors of the mother could directly impact the fertility of subsequent generations. Cigarette smoke is a known ovotoxicant in active smokers, yet disturbingly 13% of Australian and 12% of US women continue to smoke throughout pregnancy. The focus of our investigation was to characterize the adverse effects of smoking on ovary and oocyte quality in female offspring exposed in utero. Pregnant mice were nasally exposed to cigarette smoke for 12 wk throughout pregnancy/lactation, and ovary and oocyte quality of the F1 (maternal smoke exposed) generation was examined. Neonatal ovaries displayed abnormal somatic cell proliferation and increased apoptosis, leading to a reduction in follicle numbers. Further investigation found that altered somatic cell proliferation and reduced follicle number continued into adulthood; however, apoptosis did not. This reduction in follicles resulted in decreased oocyte numbers, with these oocytes found to have elevated levels of oxidative stress, altered metaphase II spindle, and reduced sperm-egg interaction. These ovarian and oocyte changes ultimately lead to subfertility, with maternal smoke-exposed animals having smaller litters and also taking longer to conceive. In conclusion, our results demonstrate that in utero and lactational exposure to cigarette smoke can have long-lasting effects on the fertility of the next generation of females. PMID:26764348

  19. Parental Divorce and Interpersonal Trust in Adult Offspring.

    ERIC Educational Resources Information Center

    King, Valarie

    2002-01-01

    Examines whether parental divorce is associated with offspring trust in parents, intimate partners, and others. Results reveal that although parental divorce is negatively associated with trust, these effects largely disappear once the quality of the past parent-teen relationship is taken into account. (Contains 48 references and 4 tables.) (GCP)

  20. Neuropsychological functioning in posttraumatic stress disorder following forced displacement in older adults and their offspring.

    PubMed

    Jelinek, Lena; Wittekind, Charlotte E; Moritz, Steffen; Kellner, Michael; Muhtz, Christoph

    2013-12-15

    The aim of the present study was to investigate neuropsychological performance in an untried trauma sample of older adults displaced during childhood at the end of World War II (WWII) with and without posttraumatic stress disorder (PTSD) as well as transgenerational effects of trauma and PTSD on their offspring. Displaced older adults with (n=20) and without PTSD (n=24) and nondisplaced healthy individuals (n=11) as well as one of their respective offspring were assessed with a large battery of cognitive tests (primarily targeting memory functioning). No evidence for deficits in neuropsychological performance was found in the aging group of displaced people with PTSD. Moreover, no group difference emerged in the offspring groups. Findings may be interpreted as first evidence for a rather resilient PTSD group of older adults that is available for assessment 60 years after displacement. PMID:23896354

  1. Intermittent prenatal MDMA exposure alters physiological but not mood related parameters in adult rat offspring.

    PubMed

    Adori, Csaba; Zelena, Dóra; Tímár, Júlia; Gyarmati, Zsuzsa; Domokos, Agnes; Sobor, Melinda; Fürst, Zsuzsanna; Makara, Gábor; Bagdy, György

    2010-01-20

    The recreational party drug "ecstasy" (3,4-methylenedioxymethamphetamine MDMA) is particularly popular among young adults who are in the childbearing age and thus there is a substantial risk of prenatal MDMA exposure. We applied an intermittent treatment protocol with an early first injection on pregnant Wistar rats (15 mg/kg MDMA s.c. on the E4, E11 and E18 days of gestation) to examine the potential physiological, endocrine and behavioral effects on adult male and female offspring. Prenatal MDMA-treatment provoked reduced body weight of offspring from the birth as far as the adulthood. Adult MDMA-offspring had a reduced blood-glucose concentration and hematocrit, altered relative spleen and thymus weight, had lower performance on wire suspension test and on the first trial of rotarod test. In contrast, no alteration in the locomotor activity was found. Anxiety and depression related behavioral parameters in elevated plus maze, sucrose preference or forced swimming tests were normal. MDMA-offspring had elevated concentration of the ACTH-precursor proopiomelanocortin and male MDMA-offspring exhibited elevated blood corticosterone concentration. No significant alteration was detected in the serotonergic marker tryptophan-hydroxylase and the catcholaminergic marker tyrosine-hydroxylase immunoreactive fiber densities in MDMA-offspring. The mothers exhibited reduced densities of serotonergic but not catecholaminergic fibers after the MDMA treatment. Our findings suggest that an intermittent prenatal MDMA exposure with an early first injection and a relatively low cumulative dose provokes mild but significant alterations in physical-physiological parameters and reduces motor skill learning in adulthood. In contrast, these adult offspring do not produce anxiety or depression like behavior. PMID:19782105

  2. Maternal exposure to cadmium during gestation perturbs the vascular system of the adult rat offspring

    SciTech Connect

    Ronco, Ana Maria; Montenegro, Marcela; Castillo, Paula; Urrutia, Manuel; Saez, Daniel; Hirsch, Sandra; Zepeda, Ramiro; Llanos, Miguel N.

    2011-03-01

    Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30 ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remained unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-{kappa}B expression - a transcription factor sensitive to inflammation and oxidative stress - suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.

  3. Altered engagement of autobiographical memory networks in adult offspring of postnatally depressed mothers.

    PubMed

    Macdonald, Birthe; Murray, Lynne; Moutsiana, Christina; Fearon, Pasco; Cooper, Peter J; Halligan, Sarah L; Johnstone, Tom

    2016-07-01

    Maternal depression is associated with increased risk for offspring mood and anxiety disorders. One possible impact of maternal depression during offspring development is on the emotional autobiographical memory system. We investigated the neural mechanisms of emotional autobiographical memory in adult offspring of mothers with postnatal depression (N=16) compared to controls (N=21). During fMRI, recordings of participants describing one pleasant and one unpleasant situation with their mother and with a companion, were used as prompts to re-live the situations. Compared to controls we predicted the PND offspring would show: greater activation in medial and posterior brain regions implicated in autobiographical memory and rumination; and decreased activation in lateral prefrontal cortex and decreased connectivity between lateral prefrontal and posterior regions, reflecting reduced control of autobiographical recall. For negative situations, we found no group differences. For positive situations with their mothers, PND offspring showed higher activation than controls in left lateral prefrontal cortex, right frontal pole, cingulate cortex and precuneus, and lower connectivity of right middle frontal gyrus, left middle temporal gyrus, thalamus and lingual gyrus with the posterior cingulate. Our results are consistent with adult offspring of PND mothers having less efficient prefrontal regulation of personally relevant pleasant autobiographical memories. PMID:27208693

  4. Mediators of Aggression Among Young Adult Offspring of Depressed Mothers

    PubMed Central

    Keenan-Miller, Danielle; Hammen, Constance; Brennan, Patricia A.

    2010-01-01

    The current paper explores the connection between maternal depression and offspring aggression during the transition to adulthood, expanding the scope of prior research on this topic. Both family-level factors (including parent-child relationship quality and maternal relationship quality) and youth factors (including depression history and social functioning in mid-adolescence) were tested as potential mediators in a longitudinal community sample of 710 youth at ages 15 and 20. The results suggest that maternal depression confers a risk for higher levels of aggressive behavior by offspring at age 20. Structural Equation Models suggested that the association between maternal depression and youth aggression is fully mediated by youth history of depression by mid-adolescence, even when accounting for the stability of aggression between ages 15 and 20. Parent-child relationship quality, youth social functioning, and maternal relationship quality were not unique mediators of this association. Limitations and implications are discussed. PMID:20919790

  5. Maternal immune activation affects litter success, size and neuroendocrine responses related to behavior in adult offspring.

    PubMed

    French, Susannah S; Chester, Emily M; Demas, Gregory E

    2013-07-01

    It is increasingly evident that influences other than genetics can contribute to offspring phenotype. In particular, maternal influences are an important contributing factor to offspring survival, development, physiology and behavior. Common environmental pathogens such as viral or bacterial microorganisms can induce maternal immune responses, which have the potential to alter the prenatal environment via multiple independent pathways. The effects of maternal immune activation on endocrine responses and behavior are less well studied and provide the basis for the current study. Our approach in the current study was two-pronged: 1) quantify sickness responses during pregnancy in adult female hamsters experiencing varying severity of immune responsiveness (i.e., differing doses of lipopolysaccharide [LPS]), and 2) assess the effects of maternal immune activation on offspring development, immunocompetence, hormone profiles, and social behavior during adulthood. Pregnancy success decreased with increasing doses of LPS, and litter size was reduced in LPS dams that managed to successfully reproduce. Unexpectedly, pregnant females treated with LPS showed a hypothermic response in addition to the more typical anorexic and body mass changes associated with sickness. Significant endocrine changes related to behavior were observed in the offspring of LPS-treated dams; these effects were apparent in adulthood. Specifically, offspring from LPS treated dams showed significantly greater cortisol responses to stressful resident-intruder encounters compared with offspring from control dams. Post-behavior cortisol was elevated in male LPS offspring relative to the offspring of control dams, and was positively correlated with the frequency of bites during agonistic interactions, and cortisol levels in both sexes were related to defensive behaviors, suggesting that changes in hypothalamo-pituitary-adrenal axis responsiveness may play a regulatory role in the observed behavioral

  6. Maternal Immune Activation Alters Nonspatial Information Processing in the Hippocampus of the Adult Offspring

    PubMed Central

    Ito, Hiroshi T.; Smith, Stephen E. P.; Hsiao, Elaine; Patterson, Paul H.

    2010-01-01

    The observation that maternal infection increases the risk for schizophrenia in the offspring suggests that the maternal immune system plays a key role in the etiology of schizophrenia. In a mouse model, maternal immune activation (MIA) by injection of poly(I:C) yields adult offspring that display abnormalities in a variety of behaviors relevant to schizophrenia. As abnormalities in the hippocampus are a consistent observation in schizophrenia patients, we examined synaptic properties in hippocampal slices prepared from the offspring of poly(I:C)- and saline-treated mothers. Compared to controls, CA1 pyramidal neurons from adult offspring of MIA mothers display reduced frequency and increased amplitude of miniature excitatory postsynaptic currents. In addition, the specific component of the temporoammonic pathway that mediates object-related information displays increased sensitivity to dopamine. To assess hippocampal network function in vivo, we used expression of the immediate early gene, c-Fos, as a surrogate measure of neuronal activity. Compared to controls, the offspring of poly(I:C)-treated mothers display a distinct c-Fos expression pattern in area CA1 following novel object, but not novel location, exposure. Thus, the offspring of MIA mothers may have an abnormality in modality-specific information processing. Indeed, the MIA offspring display enhanced discrimination in a novel object recognition, but not in an object location, task. Thus, analysis of object and spatial information processing at both synaptic and behavioral levels reveals a largely selective abnormality in object information processing in this mouse model. Our results suggest that altered processing of object-related information may be part of the pathogenesis of schizophrenia-like cognitive behaviors. PMID:20227486

  7. Perinatal Resveratrol Supplementation to Spontaneously Hypertensive Rat Dams Mitigates the Development of Hypertension in Adult Offspring.

    PubMed

    Care, Alison S; Sung, Miranda M; Panahi, Sareh; Gragasin, Ferrante S; Dyck, Jason R B; Davidge, Sandra T; Bourque, Stephane L

    2016-05-01

    This study was undertaken to determine whether perinatal maternal resveratrol (Resv)-a phytoalexin known to confer cardiovascular protection-could prevent the development of hypertension and improve vascular function in adult spontaneously hypertensive rat offspring. Dams were fed either a control or Resv-supplemented diet (4 g/kg diet) from gestational day 0.5 until postnatal day 21. Indwelling catheters were used to assess blood pressure and vascular function in vivo; wire myography was used to assess vascular reactivity ex vivo. Perinatal Resv supplementation in dams had no effect on fetal body weights, albeit continued maternal treatment postnatally resulted in growth restriction in offspring by postnatal day 21; growth restriction was no longer evident after 5 weeks of age. Maternal perinatal Resv supplementation prevented the onset of hypertension in adult offspring (-18 mm Hg;P=0.007), and nitric oxide synthase inhibition (withl-NG-nitroarginine methyl ester) normalized these blood pressure differences, suggesting improved nitric oxide bioavailability underlies the hemodynamic alterations in the Resv-treated offspring. In vivo and ex vivo, vascular responses to methylcholine were not different between treatment groups, but prior treatment withl-NG-nitroarginine methyl ester attenuated the vasodilation in untreated, but not Resv-treated adult offspring, suggesting a shift toward nitric oxide-independent vascular control mechanisms in the treated group. Finally, bioconversion of the inactive precursor big endothelin-1 to active endothelin-1 in isolated mesenteric arteries was reduced in Resv-treated offspring (-28%;P<0.05), and this difference could be normalized byl-NG-nitroarginine methyl ester treatment. In conclusion, perinatal maternal Resv supplementation mitigated the development of hypertension and causes persistent alterations in vascular responsiveness in spontaneously hypertensive rats. PMID:26928803

  8. Implications of maternal conditions and pregnancy course on offspring's medical problems in adult life.

    PubMed

    von Ehr, Julia; von Versen-Höynck, Frauke

    2016-10-01

    In the last decade, numerous epidemiological, clinical and experimental data show that periconceptional, perinatal and postnatal environment determines the offspring's risk for later-life chronic disease. For this phenomenon, the term "fetal" or "perinatal programming" is used. In exposed offspring already in childhood and early adulthood, metabolic and cardiovascular changes can be observed, leading to obesity, diabetes and hypertension. Nowadays, the mode of conception (e.g., in vitro fertilization), maternal metabolic conditions (e.g., undernutrition, overnutrition, diabetes) and complications during pregnancy (e.g., preeclampsia, intrauterine growth restriction) are suspected to be negative predictors for offspring's long-term health. Mechanisms responsible for these effects still remain mainly unclear, but include epigenetic, transcriptional, endoplasmic reticulum stress, and reactive oxygen species. This review presents a piece of the puzzle with regards to periconceptional and early perinatal conditions determining later-life risk for chronic adult disease. PMID:27522600

  9. Maternal complement C1q and increased odds for psychosis in adult offspring

    PubMed Central

    Severance, Emily G.; Gressitt, Kristin L.; Buka, Stephen L.; Cannon, Tyrone D.; Yolken, Robert H.

    2014-01-01

    The presence of maternal antibodies to food and infectious antigens may confer an increased risk of developing schizophrenia and psychosis in adult offspring. Complement factor C1q is an immune molecule with multiple functions including clearance of antigen-antibody complexes from circulation and mediation of synaptic pruning during fetal brain development. To determine if maternal C1q was associated with offspring schizophrenia and psychosis, we evaluated 55 matched case-control maternal serum pairs from the National Collaborative Perinatal Project. Sample pairs were composed of mothers whose offspring developed psychoses as adults and those whose offspring were free from psychiatric disease. Matching criteria for offspring included birth date, delivery hospital, race and gender, with further matching based on mother’s age. IgG markers of C1q, bovine milk casein, egg ovalbumin and wheat gluten were measured with enzyme-linked immunosorbent assays. C1q levels were compared to food antigen IgG and to previously generated data for C-reactive protein, adenovirus, herpes simplex viruses, influenza viruses, measles virus and Toxoplasma gondii. C1q was significantly elevated in case mothers with odds ratios of 2.66–6.31 (conditional logistic regressions, p≤0.008–0.05). In case mothers only, C1q was significantly correlated with antibodies to both food and infectious antigens: gluten (R2=0.26, p≤0.004), herpes simplex virus type 2 (R2=0.21, p≤0.02), adenovirus (R2=0.25, p≤0.006). In conclusion, exposure to maternal C1q activity during pregnancy may be a risk factor for the development of schizophrenia and psychosis in offspring. Prenatal measurement of maternal C1q may be an important and convergent screening tool to identify potentially deleterious immune activation from multiple sources. PMID:25195065

  10. Multigenerational effects of parental prenatal exposure to famine on adult offspring cognitive function

    PubMed Central

    Li, Jie; Na, Lixin; Ma, Hao; Zhang, Zhe; Li, Tianjiao; Lin, Liqun; Li, Qiang; Sun, Changhao; Li, Ying

    2015-01-01

    The effects of prenatal nutrition on adult cognitive function have been reported for one generation. However, human evidence for multigenerational effects is lacking. We examined whether prenatal exposure to the Chinese famine of 1959–61 affects adult cognitive function in two consecutive generations. In this retrospective family cohort study, we investigated 1062 families consisting of 2124 parents and 1215 offspring. We assessed parental and offspring cognitive performance by means of a comprehensive test battery. Generalized linear regression model analysis in the parental generation showed that prenatal exposure to famine was associated with a 8.1 (95% CI 5.8 to 10.4) second increase in trail making test part A, a 7.0 (1.5 to 12.5) second increase in trail making test part B, and a 5.5 (−7.3 to −3.7) score decrease in the Stroop color-word test in adulthood, after adjustment for potential confounders. In the offspring generation, linear mixed model analysis found no significant association between parental prenatal exposure to famine and offspring cognitive function in adulthood after adjustment for potential confounders. In conclusion, prenatal exposure to severe malnutrition is negatively associated with visual- motor skill, mental flexibility, and selective attention in adulthood. However, these associations are limited to only one generation. PMID:26333696

  11. Prevalence of adult-onset multifactorial disease among offspring of atomic bomb survivors.

    PubMed

    Fujiwara, S; Suyama, A; Cologne, J B; Akahoshi, M; Yamada, M; Suzuki, G; Koyama, K; Takahashi, N; Kasagi, E; Grant, E J; Lagarde, E; Hsu, W L; Furukawa, K; Ohishi, W; Tatsukawa, Y; Neriishi, K; Takahashi, I; Ashizawa, K; Hida, A; Imaizumi, M; Nagano, J; Cullings, H M; Katayama, H; Ross, N P; Kodama, K; Shore, R E

    2008-10-01

    The first study to examine whether parental radiation exposure leads to increased heritable risk of common adult-onset multifactorial diseases (i.e., hypertension, diabetes mellitus, hypercholesterolemia, ischemic heart disease, and stroke) was conducted among 11,951 participants in the clinical examination program out of a potential of 24,673 mail survey subjects who were offspring of survivors born from May 1946 through December 1984. Logistic regression analyses demonstrated no evidence of an association between the prevalence of multifactorial diseases in the offspring and parental radiation exposure, after adjusting for age, city, gender and various risk factors. The odds ratio (OR) for a paternal dose of 1 Gy was 0.91 [95% confidence interval (CI) 0.81-1.01, P = 0.08], and that for a maternal dose of 1 Gy was 0.98 (95% CI 0.86-1.10, P = 0.71). There was no apparent effect of parental age at exposure or of elapsed time between parental exposure and birth, but male offspring had a low odds ratio (OR = 0.76 at 1 Gy) for paternal exposure, but cautious interpretation is needed for this finding. The clinical assessment of nearly 12,000 offspring of A-bomb survivors who have reached a median age of about 50 years provided no evidence for an increased prevalence of adult-onset multifactorial diseases in relation to parental radiation exposure. PMID:19024652

  12. Intravenous gestational nicotine exposure results in increased motivation for sucrose reward in adult rat offspring

    PubMed Central

    Lacy, Ryan T.; Hord, Lauren L.; Morgan, Amanda J.; Harrod, Steven B.

    2012-01-01

    Background Prenatal tobacco smoke exposure is associated with alterations in motivated behavior in offspring, such as increased consumption of highly palatable foods and abused drugs. Animal models show that gestational nicotine (GN) exposure mediates changes in responding for sucrose and drug reward. Methods A novel, intermittent low-dose intravenous (IV) exposure model was used to administer nicotine (0.05 mg/kg/injection) or saline 3×/day to rats on gestational days 8-21. Two experiments investigated the effect of IV GN on 1) the habituation of spontaneous locomotor activity and on 2) sucrose reinforced responding in offspring. For the operant experiments, animals acquired fixed-ratio (FR-3) responding for sucrose, 26% (w/v), and were tested on varying concentrations (0, 3, 10, 30, 56%; Latin-square) according to a FR-3, and then a progressive-ratio (PR) schedule. Male and female adult offspring were used. Results IV GN did not alter birth or growth weight, or the number of pups born. No between-group differences in habituation to spontaneous locomotor activity were observed. FR testing produced an inverted U-shaped response curve, and rats showed peak responding for 10% sucrose reinforcement. Neither gestation nor sex affected responding, suggesting equivalent sensitivity to varying sucrose concentrations. PR testing revealed that GN rats showed greater motivation for sucrose reinforcement relative to controls. Conclusions A low-dose, IV GN exposure model resulted in increased motivation to respond for sucrose reinforcement in adult offspring. This suggests that using a low number of cigarettes throughout pregnancy will result in increased motivation for highly palatable foods in adult, and perhaps, adolescent offspring. PMID:22377090

  13. Maternal allergy acts synergistically with cigarette smoke exposure during pregnancy to induce hepatic fibrosis in adult male offspring.

    PubMed

    Allina, Jorge; Grabowski, Jacquelin; Doherty-Lyons, Shannon; Fiel, M Isabel; Jackson, Christine E; Zelikoff, Judith T; Odin, Joseph A

    2011-01-01

    Maternal environmental exposures during pregnancy are known to affect disease onset in adult offspring. For example, maternal asthma exacerbations during pregnancy can worsen adult asthma in the offspring. Cigarette smoking during pregnancy is associated with future onset of cardiovascular disease, obesity and diabetes. However, little is known about the effect of maternal environmental exposures on offspring susceptibility to liver disease. This pilot study examined the long-term effect of maternal allergen challenge and/or cigarette smoking during pregnancy on hepatic inflammation and fibrosis in adult mouse offspring. Ovalbumin (OVA) or phosphate-buffered saline (PBS)-sensitized/challenged CD-1 dams were exposed to mainstream cigarette smoke (MCS) or filtered air from gestational day 4 until parturition. Eight weeks postnatally, offspring were sacrificed for comparison of hepatic histology and mRNA expression. Adult male offspring of OVA-sensitized/challenged dams exposed to MCS (OSM) displayed significantly increased liver fibrosis (9.2% collagen content vs. <4% for all other treatment groups). These mice also had 1.8-fold greater collagen 1A1 mRNA levels. From the results here, we concluded that maternal allergen challenge in combination with cigarette smoke exposure during pregnancy may be an important risk factor for liver disease in adult male offspring. PMID:21718087

  14. Altered Health Outcomes in Adult Offspring of Sprague Dawley and Wistar Rats Undernourished During Early or Late Pregnancy

    EPA Science Inventory

    Gestational undernutrition in humans can result in birth weight reductions (an indicator of a suboptimal intrauterine environment) and predisposition to adult disease in offspring including high blood pressure, insulin resistance, glucose intolerance, and obesity (key components ...

  15. Maternal flaxseed diet during lactation changes adrenal function in adult male rat offspring.

    PubMed

    Figueiredo, Mariana Sarto; da Conceição, Ellen Paula Santos; de Oliveira, Elaine; Lisboa, Patricia Cristina; de Moura, Egberto Gaspar

    2015-10-14

    Flaxseed (Linum usitatissimum L.) has been a focus of interest in the field of functional foods because of its potential health benefits. However, we hypothesised that maternal flaxseed intake during lactation could induce several metabolic dysfunctions in adult offspring. In the present study, we aimed to characterise the adrenal function of adult offspring whose dams were supplemented with whole flaxseed during lactation. At birth, lactating Wistar rats were divided into two groups: rats from dams fed the flaxseed diet (FLAX) with 25% of flaxseed and controls dams. Pups received standard diet after weaning and male offspring were killed at age 180 days old to collect blood and tissues. We evaluated body weight and food intake during development, corticosteronaemia, adrenal catecholamine content, hepatic cholesterol, TAG and glycogen contents, and the protein expression of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), 11-β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and adrenaline β2 receptor at postnatal day 180 (PN180). After weaning, pups from the FLAX group had a higher body weight (+10 %) and food intake (+10%). At PN180, the FLAX offspring exhibited higher serum corticosterone (+48%) and lower adrenal catecholamine ( - 23%) contents, lower glycogen ( - 30%), higher cholesterol (4-fold increase) and TAG (3-fold-increase) contents in the liver, and higher 11β-HSD1 (+62%) protein expression. Although the protein expression of hypothalamic CRH was unaffected, the FLAX offspring had lower protein expression of pituitary ACTH ( - 34%). Therefore, induction of hypercorticosteronaemia by dietary flaxseed during lactation may be due to an increased hepatic activation of 11β-HSD1 and suppression of ACTH. The changes in the liver fat content of the FLAX group are suggestive of steatosis, in which hypercorticosteronaemia may play an important role. Thus, it is recommended that lactating women restrict the intake of flaxseed during

  16. Parent–offspring resemblance in colony-specific adult survival of cliff swallows

    USGS Publications Warehouse

    Brown, Charles R.; Roche, Erin A.; Brown, Mary Bomberger

    2015-01-01

    Survival is a key component of fitness. Species that occupy discrete breeding colonies with different characteristics are often exposed to varying costs and benefits associated with group size or environmental conditions, and survival is an integrative net measure of these effects. We investigated the extent to which survival probability of adult (≥1-year old) cliff swallows (Petrochelidon pyrrhonota) occupying different colonies resembled that of their parental cohort and thus whether the natal colony had long-term effects on individuals. Individuals were cross-fostered between colonies soon after hatching and their presence as breeders monitored at colonies in the western Nebraska study area for the subsequent decade. Colony-specific adult survival probabilities of offspring born and reared in the same colony, and those cross-fostered away from their natal colony soon after birth, were positively and significantly related to subsequent adult survival of the parental cohort from the natal colony. This result held when controlling for the effect of natal colony size and the age composition of the parental cohort. In contrast, colony-specific adult survival of offspring cross-fostered to a site was unrelated to that of their foster parent cohort or to the cohort of non-fostered offspring with whom they were reared. Adult survival at a colony varied inversely with fecundity, as measured by mean brood size, providing evidence for a survival–fecundity trade-off in this species. The results suggest some heritable variation in adult survival, likely maintained by negative correlations between fitness components. The study provides additional evidence that colonies represent non-random collections of individuals.

  17. The Effects of Breeding Protocol in C57BL/6J Mice on Adult Offspring Behaviour

    PubMed Central

    Foldi, Claire J.; Eyles, Darryl W.; McGrath, John J.; Burne, Thomas H. J.

    2011-01-01

    Animal experiments have demonstrated that a wide range of prenatal exposures can impact on the behaviour of the offspring. However, there is a lack of evidence as to whether the duration of sire exposure could affect such outcomes. We compared two widely used methods for breeding offspring for behavioural studies. The first involved housing male and female C57Bl/6J mice together for a period of time (usually 10–12 days) and checking for pregnancy by the presence of a distended abdomen (Pair-housed; PH). The second involved daily introduction of female breeders to the male homecage followed by daily checks for pregnancy by the presence of vaginal plugs (Time-mated; TM). Male and female offspring were tested at 10 weeks of age on a behavioural test battery including the elevated plus-maze, hole board, light/dark emergence, forced swim test, novelty-suppressed feeding, active avoidance and extinction, tests for nociception and for prepulse inhibition (PPI) of the acoustic startle response. We found that length of sire exposure (LSE) had no significant effects on offspring behaviour, suggesting that the two breeding protocols do not differentially affect the behavioural outcomes of interest. The absence of LSE effects on the selected variables examined does not detract from the relevance of this study. Information regarding the potential influences of breeding protocol is not only absent from the literature, but also likely to be of particular interest to researchers studying the influence of prenatal manipulations on adult behaviour. PMID:21448436

  18. Older maternal age is associated with depression, anxiety, and stress symptoms in young adult female offspring.

    PubMed

    Tearne, Jessica E; Robinson, Monique; Jacoby, Peter; Allen, Karina L; Cunningham, Nadia K; Li, Jianghong; McLean, Neil J

    2016-01-01

    The evidence regarding older parental age and incidence of mood disorder symptoms in offspring is limited, and that which exists is mixed. We sought to clarify these relationships by using data from the Western Australian Pregnancy Cohort (Raine) Study. The Raine Study provided comprehensive data from 2,900 pregnancies, resulting in 2,868 live born children. A total of 1,220 participants completed the short form of the Depression Anxiety Stress Scale (DASS-21) at the 20-year cohort follow-up. We used negative binomial regression analyses with log link and with adjustment for known perinatal risk factors to examine the extent to which maternal and paternal age at childbirth predicted continuous DASS-21 index scores. In the final multivariate models, a maternal age of 30-34 years was associated with significant increases in stress DASS-21 scores in female offspring relative to female offspring of 25- to 29-year-old mothers. A maternal age of 35 years and over was associated with increased scores on all DASS-21 scales in female offspring. Our results indicate that older maternal age is associated with depression, anxiety, and stress symptoms in young adult females. Further research into the mechanisms underpinning this relationship is needed. PMID:26569038

  19. Perinatal Nicotine Exposure Increases Angiotensin II Receptor-Mediated Vascular Contractility in Adult Offspring

    PubMed Central

    Xiao, DaLiao; Dasgupta, Chiranjib; Li, Yong; Huang, Xiaohui; Zhang, Lubo

    2014-01-01

    Previous studies have reported that perinatal nicotine exposure causes development of hypertensive phenotype in adult offspring. Aims The present study was to determine whether perinatal nicotine exposure causes an epigenetic programming of vascular Angiotensin II receptors (ATRs) and their-mediated signaling pathway leading to heightened vascular contraction in adult offspring. Main methods Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth. The experiments were conducted at 5 months of age of male offspring. Key Findings Nicotine treatment enhanced Angitension II (Ang II)-induced vasoconstriction and 20-kDa myosin light chain phosphorylation (MLC20-P) levels. In addition, the ratio of Ang II-induced tension/MLC-P was also significantly increased in nicotine-treated group compared with the saline group. Nicotine-mediated enhanced constrictions were not directly dependent on the changes of [Ca2+]i concentrations but dependent on Ca2+ sensitivity. Perinatal nicotine treatment significantly enhanced vascular ATR type 1a (AT1aR) but not AT1bR mRNA levels in adult rat offspring, which was associated with selective decreases in DNA methylation at AT1aR promoter. Contrast to the effect on AT1aR, nicotine decreased the mRNA levels of vascular AT2R gene, which was associated with selective increases in DNA methylation at AT2R promoter. Significance Our results indicated that perinatal nicotine exposure caused an epigenetic programming of vascular ATRs and their-mediated signaling pathways, and suggested that differential regulation of AT1R/AT2R gene expression through DNA methylation mechanism may be involved in nicotine-induced heightened vasoconstriction and development of hypertensive phenotype in adulthood. PMID:25265052

  20. Gestational ketogenic diet programs brain structure and susceptibility to depression & anxiety in the adult mouse offspring

    PubMed Central

    Sussman, Dafna; Germann, Jurgen; Henkelman, Mark

    2015-01-01

    Introduction The ketogenic diet (KD) has seen an increase in popularity for clinical and non-clinical purposes, leading to rise in concern about the diet's impact on following generations. The KD is known to have a neurological effect, suggesting that exposure to it during prenatal brain development may alter neuro-anatomy. Studies have also indicated that the KD has an anti-depressant effect on the consumer. However, it is unclear whether any neuro-anatomical and/or behavioral changes would occur in the offspring and persist into adulthood. Methods To fill this knowledge gap we assessed the brain morphology and behavior of 8-week-old young-adult CD-1 mice, who were exposed to the KD in utero, and were fed only a standard-diet (SD) in postnatal life. Standardized neuro-behavior tests included the Open-Field, Forced-Swim, and Exercise Wheel tests, and were followed by post-mortem Magnetic Resonance Imaging (MRI) to assess brain anatomy. Results The adult KD offspring exhibit reduced susceptibility to anxiety and depression, and elevated physical activity level when compared with controls exposed to the SD both in utero and postnatally. Many neuro-anatomical differences exist between the KD offspring and controls, including, for example, a cerebellar volumetric enlargement by 4.8%, a hypothalamic reduction by 1.39%, and a corpus callosum reduction by 4.77%, as computed relative to total brain volume. Conclusions These results suggest that prenatal exposure to the KD programs the offspring neuro-anatomy and influences their behavior in adulthood. PMID:25642385

  1. Perinatal Exposure to Perfluorooctane Sulfonate Affects Glucose Metabolism in Adult Offspring

    PubMed Central

    Wan, Hin T.; Zhao, Yin G.; Leung, Pik Y.; Wong, Chris K. C.

    2014-01-01

    Perfluoroalkyl acids (PFAAs) are globally present in the environment and are widely distributed in human populations and wildlife. The chemicals are ubiquitous in human body fluids and have a long serum elimination half-life. The notorious member of PFAAs, perfluorooctane sulfonate (PFOS) is prioritized as a global concerning chemical at the Stockholm Convention in 2009, due to its harmful effects in mammals and aquatic organisms. PFOS is known to affect lipid metabolism in adults and was found to be able to cross human placenta. However the effects of in utero exposure to the susceptibility of metabolic disorders in offspring have not yet been elucidated. In this study, pregnant CD-1 mice (F0) were fed with 0, 0.3 or 3 mg PFOS/kg body weight/day in corn oil by oral gavage daily throughout gestational and lactation periods. We investigated the immediate effects of perinatal exposure to PFOS on glucose metabolism in both maternal and offspring after weaning (PND 21). To determine if the perinatal exposure predisposes the risk for metabolic disorder to the offspring, weaned animals without further PFOS exposure, were fed with either standard or high-fat diet until PND 63. Fasting glucose and insulin levels were measured while HOMA-IR index and glucose AUCs were reported. Our data illustrated the first time the effects of the environmental equivalent dose of PFOS exposure on the disturbance of glucose metabolism in F1 pups and F1 adults at PND 21 and 63, respectively. Although the biological effects of PFOS on the elevated levels of fasting serum glucose and insulin levels were observed in both pups and adults of F1, the phenotypes of insulin resistance and glucose intolerance were only evident in the F1 adults. The effects were exacerbated under HFD, highlighting the synergistic action at postnatal growth on the development of metabolic disorders. PMID:24498028

  2. Maternal Grand Multiparity and the Risk of Severe Mental Disorders in Adult Offspring

    PubMed Central

    Lahti, Marius; Eriksson, Johan G.; Heinonen, Kati; Kajantie, Eero; Lahti, Jari; Wahlbeck, Kristian; Tuovinen, Soile; Pesonen, Anu-Katriina; Mikkonen, Maiju; Osmond, Clive; Räikkönen, Katri

    2014-01-01

    Background Previous studies have shown that maternal grand multiparity may predict an increased risk of mental disorders in young adult offspring, but whether such effects persist throughout adulthood remains unknown. The current study examined if maternal grand multiparity predicts the risks of severe mental disorders, suicides, suicide attempts and dementias throughout adult life. Methods Our study sample comprised 13243 Helsinki Birth Cohort Study 1934–1944 participants (6905 men and 6338 women). According to hospital birth records, 341 offspring were born to grand multiparous mothers. From Finnish national hospital discharge and causes of death registers, we identified 1682 participants diagnosed with mental disorders during 1969–2010. Results Maternal grand multiparity predicted significantly increased risks of mood disorders (Hazard Ratio = 1.64, p = 0.03), non-psychotic mood disorders (Hazard Ratio = 2.02, p = 0.002), and suicide attempts (Hazard Ratio = 3.94, p = 0.01) in adult offspring. Furthermore, women born to grand multiparous mothers had significantly increased risks of any severe mental disorder (Hazard Ratio = 1.79, p = 0.01), non-psychotic substance use disorders (Hazard Ratio = 2.77, p = 0.02) schizophrenia, schizotypal and delusional disorders (Hazard Ratio = 2.40, p = 0.02), mood disorders (Hazard Ratio = 2.40, p = 0.002), non-psychotic mood disorders (Hazard Ratio = 2.91, p<0.001), and suicide attempts (Hazard Ratio = 5.05, p = 0.01) in adulthood. The effects of maternal grand multiparity on offspring psychopathology risk were independent of maternal age and body mass index at childbirth, and of year of birth, sex, childhood socioeconomic position, and birth weight of the offspring. In contrast, no significant effects were found among men. Conclusions Women born to grand multiparous mothers are at an increased risk of severe mental disorders and suicide attempts across

  3. Transgenerational Effects of Parental Larval Diet on Offspring Development Time, Adult Body Size and Pathogen Resistance in Drosophila melanogaster

    PubMed Central

    Valtonen, Terhi M.; Kangassalo, Katariina; Pölkki, Mari; Rantala, Markus J.

    2012-01-01

    Environmental conditions experienced by parents are increasingly recognized to affect offspring performance. We set out to investigate the effect of parental larval diet on offspring development time, adult body size and adult resistance to the bacterium Serratia marcescens in Drosophila melanogaster. Flies for the parental generation were raised on either poor or standard diet and then mated in the four possible sex-by-parental diet crosses. Females that were raised on poor food produced larger offspring than females that were raised on standard food. Furthermore, male progeny sired by fathers that were raised on poor food were larger than male progeny sired by males raised on standard food. Development times were shortest for offspring whose one parent (mother or the father) was raised on standard and the other parent on poor food and longest for offspring whose parents both were raised on poor food. No evidence for transgenerational effects of parental diet on offspring disease resistance was found. Although paternal effects have been previously demonstrated in D. melanogaster, no earlier studies have investigated male-mediated transgenerational effects of diet in this species. The results highlight the importance of not only considering the relative contribution each parental sex has on progeny performance but also the combined effects that the two sexes may have on offspring performance. PMID:22359607

  4. Stress during first pregnancy increases seizure threshold in adult male offspring

    PubMed Central

    Pajand, Peyman; Elahdadi Salmani, Mahmoud; Shajiee, Hooman; Abiri, Hasan; Goudarzi, Iran; Abrari, Kataneh

    2014-01-01

    Objective(s): Stress induces many homeostatic aberrations which are followed by lifelong allostatic responses. Epilepsy is developed or influenced by different environmental factors, i.e. prenatal stress which makes many contradictory developmental changes in seizure threshold and intensity. We investigated the potential seizure response of the rat offspring to prenatal stress; the stress which was applied to their mothers. Materials and Methods: Nine day heterogeneous sequential stress (HSS) model was used before and during the first and before the second pregnancy. The kindling was induced using 13 IP injections of pentylenetetrazol (PTZ) every 48 hr to adult male Wistar rat's offspring. Results: The results of the present study demonstrated that, before pregnancy stress decreased the rate of kindling (P<0.05) in the offspring, while stress which was applied during pregnancy completely prevented kindling (P <0.001). Further, their convulsive latency was increased and tonic clonic seizure duration was decreased. In contrast, previous pregnancy and between pregnancies stress could not change kindling process. Although maternal separation stress did not change kindling development, it could increase convulsive intensities by elongating the duration of seizures (P<0.05) and reducing convulsion latency (P <0.05). Conclusion: It is concluded that stress detrimental effects could be prevented by stress which was applied around first pregnancy; however this beneficial effect is weakened by before second pregnancy stress. PMID:24592305

  5. The association of maternal socialization in childhood and adolescence with adult offsprings' sympathy/caring.

    PubMed

    Eisenberg, Nancy; VanSchyndel, Sarah K; Hofer, Claire

    2015-01-01

    The purpose of the study was to examine associations between mothers' socialization practices in childhood and adolescence and offsprings' (N = 32, 16 female) sympathy/concern in early adulthood. Mothers reported on their socialization practices and beliefs a total of 6 times using a Q-sort during their offsprings' childhood (between 7-8 and 11-12 years of age) and adolescence (between 13-14 and 17-18 years of age). Adult offsprings' sympathy/caring was assessed 3 times in early adulthood (at ages 19-20 to 23-24 years) and in their mid-20s to 30s (ages 25-26 to 31-32 years). In general, friends' reports of participants' sympathy/concern at ages 25-32 years related positively to mother-reported rational discipline (including inductions) and warmth and support during childhood and adolescence and negatively to mother-reported negative affect during adolescence. Self-reported sympathy/concern during early adulthood was positively related to maternal warmth and support during childhood and almost significantly negatively related to mother-reported negative affect during childhood and adolescence. Most of the relations held when the prior level of self-reported childhood empathy or adolescent sympathy was controlled. PMID:25383690

  6. Childhood maltreatment in adult offspring of Portuguese war veterans with and without PTSD

    PubMed Central

    Dias, Aida; Sales, Luisa; Cardoso, Rui M.; Kleber, Rolf

    2014-01-01

    Background The colonial war that Portugal was involved in between 1961 and 1974 had a significant impact on veterans and their families. However, it is unclear what the consequences of this war are, in particular with regard to levels of childhood maltreatment (CM) in offspring. Objective Our study aims to analyze the influences of fathers’ war exposure and posttraumatic stress disorder (PTSD) on the offspring's CM and simultaneously test the hypothesis of the intergenerational transmission of father–child CM. Method Cross-sectional data were collected, using the Childhood Trauma Questionnaire—Short Form, from 203 adult children and 117 fathers. Subjects were distributed according to three conditions based on the father's war exposure status: did not participate in war, or non-war-exposed (NW); participated in war, or war-exposed (W); and war-exposed with PTSD diagnosis (WP). The data were examined using correlations, variance/covariance, and regression analyses. Results Children of war veterans with PTSD reported more emotional and physical neglect, while their fathers reported increased emotional and physical abuse exposure during their own childhood. Significant father–child CM correlations were found in the war veteran group but less in the war veteran with PTSD group. Father CM predicted 16% of offspring CM of children of war veterans. Conclusions The father's war-related PTSD might be a risk factor for offspring neglect but potentially a protective one for the father–child abuse transmission. War-exposed fathers without PTSD did transmit their own CM experiences more often. Therefore, father's war exposure and father's war PTSD may each be important variables to take into account in the study of intergenerational transmission of CM. PMID:24505510

  7. MATERNAL EXPERIENCE OF ABUSE IN CHILDHOOD AND DEPRESSIVE SYMPTOMS IN ADOLESCENT AND ADULT OFFSPRING: A 21-YEAR LONGITUDINAL STUDY

    PubMed Central

    Roberts, Andrea L.; Chen, Ying; Slopen, Natalie; McLaughlin, Katie A.; Koenen, Karestan C.; Austin, Sydney Bryn

    2015-01-01

    Background Intergenerational effects of child abuse have been documented, but it is unknown whether maternal childhood abuse influences offspring mental health in adolescence or adulthood. Methods To examine whether maternal experience of childhood abuse is associated with depressive symptoms in adolescent and young adult offspring, we linked data from two large longitudinal cohorts of women (N = 8,882) and their offspring (N = 11,402), and we examined three possible pathways by which maternal experience of abuse might be associated with offspring depressive symptoms: maternal mental health, family characteristics, and offspring’s own experience of abuse. Results Offspring of women who experienced severe versus no childhood abuse had greater likelihood of high depressive symptoms (RR = 1.78, 95% CI = 1.47, 2.16) and persistent high depressive symptoms (RR = 2.47, 95% CI = 1.37, 4.44). Maternal mental health accounted for 20.9% and offspring’s exposure to abuse accounted for 30.3% of the elevated risk of high depressive symptoms. Disparities in offspring depressive symptoms by maternal abuse exposure were evident at age 12 years and persisted through age 31 years. Conclusions Findings provide evidence that childhood abuse adversely affects the mental health of the victim’s offspring well into adulthood. As offspring exposure to abuse and maternal mental health accounted for more than 50% of the elevated risk of high depressive symptoms among offspring of women who experienced abuse, improving maternal mental health and parenting practices may reduce offspring risk for depressive symptoms in these families. PMID:26220852

  8. Persistent Interneuronopathy in the Prefrontal Cortex of Young Adult Offspring Exposed to Ethanol In Utero

    PubMed Central

    Skorput, Alexander G. J.; Gupta, Vivek P.; Yeh, Pamela W. L.

    2015-01-01

    Gestational exposure to ethanol has been reported to alter the disposition of tangentially migrating GABAergic cortical interneurons, but much remains to be elucidated. Here we first established the migration of interneurons as a proximal target of ethanol by limiting ethanol exposure in utero to the gestational window when tangential migration is at its height. We then asked whether the aberrant tangential migration of GABAergic interneurons persisted as an enduring interneuronopathy in the medial prefrontal cortex (mPFC) later in the life of offspring prenatally exposed to ethanol. Time pregnant mice with Nkx2.1Cre/Ai14 embryos harboring tdTomato-fluorescent medial ganglionic eminence (MGE)-derived cortical GABAergic interneurons were subjected to a 3 day binge-type 5% w/w ethanol consumption regimen from embryonic day (E) 13.5–16.5, spanning the peak of corticopetal interneuron migration in the fetal brain. Our binge-type regimen increased the density of MGE-derived interneurons in the E16.5 mPFC. In young adult offspring exposed to ethanol in utero, this effect persisted as an increase in the number of mPFC layer V parvalbumin-immunopositive interneurons. Commensurately, patch-clamp recording in mPFC layer V pyramidal neurons uncovered enhanced GABA-mediated spontaneous and evoked synaptic transmission, shifting the inhibitory/excitatory balance toward favoring inhibition. Furthermore, young adult offspring exposed to the 3 day binge-type ethanol regimen exhibited impaired reversal learning in a modified Barnes maze, indicative of decreased PFC-dependent behavioral flexibility, and heightened locomotor activity in an open field arena. Our findings underscore that aberrant neuronal migration, inhibitory/excitatory imbalance, and thus interneuronopathy contribute to indelible abnormal cortical circuit form and function in fetal alcohol spectrum disorders. SIGNIFICANCE STATEMENT The significance of this study is twofold. First, we demonstrate that a time

  9. Perinatal Taurine Alters Arterial Pressure Control and Renal Function in Adult Offspring

    PubMed Central

    Roysommuti, Sanya; Lerdweeraphon, Wichaporn; Malila, Pisamai; Jirakulsomchok, Dusit; Wyss, J. Michael

    2009-01-01

    The present study investigates the effect of perinatal taurine exposure on renal function in adult, female rats on a high sugar diet. Perinatal taurine depleted (TD), supplemented (TS) or untreated control (C) female offspring were fed normal rat chow and tap water (CW,TDW or TSW) or tap water with 5% glucose (CG, TDG or TSG) after weaning. At 7–8 weeks of age, renal function was studied in the conscious, restrained rats. Mean arterial pressure was significantly higher in TDW, TDG, and TSG rats. Plasma sodium concentration was significantly lower in all glucose treated animals, but the greatest decrease was in TDW rats. Basal renal blood flow was lowest in TSW and TSG, and the responses to a saline load were also lowest in those two groups. These changes were consistent with increased renal vascular resistance. The basal glomerular filtration rate was lowest in TSW, but the responses to a saline load were similar in all of the groups. Water excretion was lower in TSG and TSW, consistent with increased renal tubular water reabsorption. These data suggest that perinatal taurine exposure alters normal renal function and renal responses to dietary sugar in adult female offspring. PMID:19239145

  10. Perinatal thiamine restriction affects central GABA and glutamate concentrations and motor behavior of adult rat offspring.

    PubMed

    Ferreira-Vieira, Talita Hélen; de Freitas-Silva, Danielle Marra; Ribeiro, Andrea Frozino; Pereira, Sílvia Rejane Castanheira; Ribeiro, Ângela Maria

    2016-03-23

    The purposes of the present study were to investigate the effects of perinatal thiamine deficiency, from the 11th day of gestation until the 5th day of lactation, on motor behavior and neurochemical parameters in adult rat offspring, using 3-month-old, adult, male Wistar rats. All rats were submitted to motor tests, using the rotarod and paw print tasks. After behavioral tests, their thalamus, cerebellum and spinal cord were dissected for glutamate and GABA quantifications by high performance liquid chromatography. The thiamine-restricted mothers (RM) group showed a significant reduction of time spent on the rotarod at 25 rpm and an increase in hind-base width. A significant decrease of glutamate concentration in the cerebellum and an increase of GABA concentrations in the thalamus were also observed. For the offspring from control mothers (CM) group there were significant correlations between thalamic GABA concentrations and both rotarod performance and average hind-base width. In addition, for rats from the RM group a significant correlation between stride length and cerebellar GABA concentration was found. These results show that the deficiency of thiamine during an early developmental period affects certain motor behavior parameters and GABA and glutamate levels in specific brain areas. Hence, a thiamine deficiency episode during an early developmental period can induce motor impairments and excitatory and inhibitory neurotransmitter changes that are persistent and detectable in later periods of life. PMID:26836141

  11. Adult and offspring size in the ocean over 17 orders of magnitude follows two life history strategies.

    PubMed

    Neuheimer, A B; Hartvig, M; Heuschele, J; Hylander, S; Kiørboe, T; Olsson, K H; Sainmont, J; Andersen, K H

    2015-12-01

    Explaining variability in offspring vs. adult size among groups is a necessary step to determine the evolutionary and environmental constraints shaping variability in life history strategies. This is of particular interest for life in the ocean where a diversity of offspring development strategies is observed along with variability in physical and biological forcing factors in space and time. We compiled adult and offspring size for 407 pelagic marine species covering more than 17 orders of magnitude in body mass including Cephalopoda, Cnidaria, Crustaceans, Ctenophora, Elasmobranchii, Mammalia, Sagittoidea, and Teleost. We find marine life following one of two distinct strategies, with offspring size being either proportional to adult size (e.g., Crustaceans, Elasmobranchii, and Mammalia) or invariant with adult size (e.g., Cephalopoda, Cnidaria, Sagittoidea, Teleosts, and possibly Ctenophora). We discuss where these two strategies occur and how these patterns (along with the relative size of the offspring) may be shaped by physical and biological constraints in the organism's environment. This adaptive environment along with the evolutionary history of the different groups shape observed life history strategies and possible group-specific responses to changing environmental conditions (e.g., production and distribution). PMID:26909435

  12. Undernutrition during pregnancy in mice leads to dysfunctional cardiac muscle respiration in adult offspring

    PubMed Central

    Beauchamp, Brittany; Thrush, A. Brianne; Quizi, Jessica; Antoun, Ghadi; McIntosh, Nathan; Al-Dirbashi, Osama Y.; Patti, Mary-Elizabeth; Harper, Mary-Ellen

    2015-01-01

    Intrauterine growth restriction (IUGR) is associated with an increased risk of developing obesity, insulin resistance and cardiovascular disease. However, its effect on energetics in heart remains unknown. In the present study, we examined respiration in cardiac muscle and liver from adult mice that were undernourished in utero. We report that in utero undernutrition is associated with impaired cardiac muscle energetics, including decreased fatty acid oxidative capacity, decreased maximum oxidative phosphorylation rate and decreased proton leak respiration. No differences in oxidative characteristics were detected in liver. We also measured plasma acylcarnitine levels and found that short-chain acylcarnitines are increased with in utero undernutrition. Results reveal the negative impact of suboptimal maternal nutrition on adult offspring cardiac energy metabolism, which may have life-long implications for cardiovascular function and disease risk. PMID:26182362

  13. Developmental fluoxetine exposure increases behavioral despair and alters epigenetic regulation of the hippocampal BDNF gene in adult female offspring.

    PubMed

    Boulle, Fabien; Pawluski, Jodi L; Homberg, Judith R; Machiels, Barbie; Kroeze, Yvet; Kumar, Neha; Steinbusch, Harry W M; Kenis, Gunter; van den Hove, Daniel L A

    2016-04-01

    A growing number of infants are exposed to selective serotonin reuptake inhibitor (SSRI) medications during the perinatal period. Perinatal exposure to SSRI medications alter neuroplasticity and increase depressive- and anxiety-related behaviors, particularly in male offspring as little work has been done in female offspring to date. The long-term effects of SSRI on development can also differ with previous exposure to prenatal stress, a model of maternal depression. Because of the limited work done on the role of developmental SSRI exposure on neurobehavioral outcomes in female offspring, the aim of the present study was to investigate how developmental fluoxetine exposure affects anxiety and depression-like behavior, as well as the regulation of hippocampal brain-derived neurotrophic factor (BDNF) signaling in the hippocampus of adult female offspring. To do this female Sprague-Dawley rat offspring were exposed to prenatal stress and fluoxetine via the dam, for a total of four groups of female offspring: 1) No Stress+Vehicle, 2) No Stress+Fluoxetine, 3) Prenatal Stress+Vehicle, and 4) Prenatal Stress+Fluoxetine. Primary results show that, in adult female offspring, developmental SSRI exposure significantly increases behavioral despair measures on the forced swim test, decreases hippocampal BDNF exon IV mRNA levels, and increases levels of the repressive histone 3 lysine 27 tri-methylated mark at the corresponding promoter. There was also a significant negative correlation between hippocampal BDNF exon IV mRNA levels and immobility in the forced swim test. No effects of prenatal stress or developmental fluoxetine exposure were seen on tests of anxiety-like behavior. This research provides important evidence for the long-term programming effects of early-life exposure to SSRIs on female offspring, particularily with regard to affect-related behaviors and their underlying molecular mechanisms. PMID:26844865

  14. Prenatal caffeine exposure induces a poor quality of articular cartilage in male adult offspring rats via cholesterol accumulation in cartilage

    PubMed Central

    Luo, Hanwen; Li, Jing; Cao, Hong; Tan, Yang; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Epidemiological investigations indicate that osteoarthritis is associated with intrauterine growth retardation (IUGR) and abnormal cholesterol metabolism. Our previous studies showed that prenatal caffeine exposure (PCE) induced chondrogenesis retardation in IUGR offspring rats. The current study sought to investigate the effects of PCE on male IUGR offspring rats’ articular cartilage, and the mechanisms associated with abnormal cholesterol metabolism. Based on the results from both male fetal and adult fed a high-fat diet (HFD) studies of rats that experienced PCE (120 mg/kg.d), the results showed a poor quality of articular cartilage and cholesterol accumulation in the adult PCE group. Meanwhile, the serum total cholesterol and low-density lipoprotein-cholesterol concentrations were increased in adult PCE offspring. We also observed lower expression of insulin-like growth factor1 (IGF1) and impaired cholesterol efflux in adult articular cartilage. Furthermore, the expression of cartilage functional genes, components of the IGF1 signaling pathway and cholesterol efflux pathway related genes were decreased in PCE fetal cartilage. In conclusion, PCE induced a poor quality of articular cartilage in male adult offspring fed a HFD. This finding was shown to be due to cholesterol accumulation in the cartilage, which may have resulted from intrauterine reduced activity of the IGF1 signaling pathway. PMID:26639318

  15. Influence of Panax ginseng on the offspring of adult rats exposed to prenatal stress

    PubMed Central

    KIM, YOUNG OCK; LEE, HWA-YOUNG; WON, HANSOL; NAH, SEONG-SU; LEE, HWA-YOUNG; KIM, HYUNG-KI; KWON, JUN-TACK; KIM, HAK-JAE

    2015-01-01

    The exposure of pregnant females to stress during a critical period of fetal brain development is an environmental risk factor for the development of schizophrenia in adult offspring. Schizophrenia is a group of common mental disorders of unclear origin, affecting approximately 1% of the global population, showing a generally young age at onset. In the present study, a repeated variable stress paradigm was applied to pregnant rats during the final week of gestation. The effects of an extract of Panax ginseng C.A. Meyer (PG) on rats exposed to prenatal stress (PNS) were investigated in terms of behavioral activity and protein expression analyses. In the behavioral tests, grooming behavior in a social interaction test, line-crossing behavior in an open-field test and swimming activity in a forced-swim test were decreased in the rats exposed to PNS compared with the non-stressed offspring; the changes in behavioral activity were reversed upon oral treatment with PG (300 mg/kg). Subsequently, western blot analysis and immunohistochemical analyses of the prefrontal cortex and hippocampus revealed that the downregulation of several neurodevelopmental genes which occurred following exposure to PNS was reversed upon treatment with PG. The current findings demonstrate that the downregulation of several genes following exposure to PNS may affect subsequent behavioral changes, and that these phenomena are reversed following treatment with PG during pregnancy. Our results suggest that oral treatment with PG reduces the incidence of psychiatric disorders, such as schizophrenia. PMID:25394395

  16. Residual effects of polychlorinated biphenyls on adult nonhuman primates and their offspring

    SciTech Connect

    Allen, J.R.; Barsotti, D.A.; Carstens, L.A.

    1980-01-01

    After 18 months of consuming a diet containing 2.5 and 5.0 ppM PCB (Aroclor 1248), during which they and their offspring experienced marked alterations in physical status, female rhesus monkeys were placed on a control diet for 1 y. During this year there was a decided improvement in their general body health and reproductive capabilities. Infants born to these animals were small at birth and during their postnatal life developed signs of PCB intoxication similar to those observed in their siblings born during the period of PCB exposure. These data indicate that the residual effects of low-level ingestion of PCBs by nonhuman primates persist for over 1 y after discontinuation of exposure. There are also indications that the fetal and neonatal monkeys born to PCB-exposed mothers are more severely affected for a longer period than are the adult female monkeys.

  17. Pathogenesis and epidemiology of Brucellosis in Yellowstone bison: serologic and culture results from adult females and their offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this prospective study was to follow the natural course of Brucella abortus infection in cohorts of seropositive and seronegative female bison and their offspring in Yellowstone National Park over a 5 year period. Specimens were collected from 53 adult, female bison at least once a...

  18. Tumors and Proliferative Lesions in Adult Offspring After Maternal Exposure to Methylarsonous Acid During Gestation in CD1 Mice

    EPA Science Inventory

    Developmental exposure to inorganic arsenic is carcinogenic in humans and mice, and adult offspring of mice exposed to inorganic arsenic can develop tumors of the lung, liver, adrenal, uterus, and ovary. It has been suggested that methylarsonous acid (MMA3+), a product of the bi...

  19. Tumors and Proliferative Lesions in Adult Offspring After Maternal Exposure to Methylarsonous Acid During Gestation in CDl Mice.

    EPA Science Inventory

    Inorganic arsenic exposure is carcinogenic in humans and rodents. When pregnant mice are exposed to inorganic arsenic in the drinking water their offspring, when adults, develop tumors and proliferative lesions at several sites, such as lung, liver, adrenal, uterus, ovary and ovi...

  20. Prenatal glucocorticoid exposure in rats: programming effects on stress reactivity and cognition in adult offspring.

    PubMed

    Zeng, Yan; Brydges, Nichola M; Wood, Emma R; Drake, Amanda J; Hall, Jeremy

    2015-01-01

    Human epidemiological studies have provided compelling evidence that prenatal exposure to stress is associated with significantly increased risks of developing psychiatric disorders in adulthood. Exposure to excessive maternal glucocorticoids may underlie this fetal programming effect. In the current study, we assessed how prenatal dexamethasone administration during the last week of gestation affects stress reactivity and cognition in adult offspring. Stress reactivity was assessed by evaluating anxiety-like behavior on an elevated plus maze and in an open field. In addition, to characterize the long-term cognitive outcomes of prenatal exposure to glucocorticoids, animals were assessed on two cognitive tasks, a spatial reference memory task with reversal learning and a delayed matching to position (DMTP) task. Our results suggest that prenatal exposure to dexamethasone had no observable effect on anxiety-like behavior, but affected cognition in the adult offspring. Prenatally dexamethasone-exposed animals showed a transient deficit in the spatial reference memory task and a trend to faster acquisition during the reversal-learning phase. Furthermore, prenatally dexamethasone-treated animals also showed faster learning of new platform positions in the DMTP task. These results suggest that fetal overexposure to glucocorticoids programs a phenotype characterized by cognitive flexibility and adaptability to frequent changes in environmental circumstances. This can be viewed as an attempt to increase the fitness of survival in a potentially hazardous postnatal environment, as predicted by intrauterine adversity. Collectively, our data suggest that prenatal exposure to dexamethasone in rats could be used as an animal model for studying some cognitive components of related psychiatric disorders. PMID:26383033

  1. Chronic prenatal ethanol exposure alters expression of central and peripheral insulin signaling molecules in adult guinea pig offspring.

    PubMed

    Dobson, Christine C; Thevasundaram, Kersh; Mongillo, Daniel L; Winterborn, Andrew; Holloway, Alison C; Brien, James F; Reynolds, James N

    2014-11-01

    Maternal ethanol consumption during pregnancy can produce a range of teratogenic outcomes in offspring. The mechanism of ethanol teratogenicity is multi-faceted, but may involve alterations in insulin and insulin-like growth factor (IGF) signaling pathways. These pathways are not only important for metabolism, but are also critically involved in neuronal survival and plasticity, and they can be altered by chronic prenatal ethanol exposure (CPEE). The objective of this study was to test the hypothesis that CPEE alters expression of insulin and IGF signaling molecules in the prefrontal cortex and liver of adult guinea pig offspring. Pregnant Dunkin-Hartley-strain guinea pigs received ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding (nutritional control) throughout gestation. Fasting blood glucose concentration was measured in male and female offspring at postnatal day 150-200, followed by euthanasia, collection of prefrontal cortex and liver, and RNA extraction. IGF-1, IGF-1 receptor (IGF-1R), IGF-2, IGF-2 receptor (IGF-2R), insulin receptor substrate (IRS)-1, IRS-2, and insulin receptor (INSR) mRNA expression levels were measured in tissues using quantitative real-time PCR. The mean maternal blood ethanol concentration was 281 ± 15 mg/dL at 1 h after the second divided dose of ethanol on GD 57. CPEE resulted in increased liver weight in adult offspring, but produced no difference in fasting blood glucose concentration compared with nutritional control. In the liver, CPEE decreased mRNA expression of IGF-1, IGF-1R, and IGF-2, and increased IRS-2 mRNA expression in male offspring only compared with nutritional control. Female CPEE offspring had decreased INSR hepatic mRNA expression compared with male CPEE offspring. In the prefrontal cortex, IRS-2 mRNA expression was increased in CPEE offspring compared with nutritional control. The data demonstrate that CPEE alters both central and peripheral expression of insulin and IGF signaling

  2. A dose-response relationship between maternal smoking during late pregnancy and adult intelligence in male offspring.

    PubMed

    Mortensen, Erik Lykke; Michaelsen, Kim Fleischer; Sanders, Stephanie A; Reinisch, June Machover

    2005-01-01

    An association between maternal smoking during pregnancy and cognitive and behavioural development has been observed in several studies, but potential effects of maternal smoking on offspring adult intelligence have not been investigated. The objective of the present study was to investigate a potential association between maternal smoking during pregnancy and offspring intelligence in young adulthood. Adult intelligence was assessed at the mean age of 18.7 years by a military draft board intelligence test (Borge Priens Prove) for 3044 singleton males from the Copenhagen Perinatal Cohort with information regarding maternal smoking during the third trimester coded into five categories (about 50% of the mothers were smokers). The following potential confounders were included as covariates in multivariable analyses: parental social status and education, single mother status, mother's height and age, number of pregnancies, and gestational age. In separate analyses, birthweight and length were also included as covariates. Maternal cigarette smoking during the third trimester, adjusted for the seven covariates, showed a negative association with offspring adult intelligence (P=0.0001). The mean difference between the no-smoking and the heaviest smoking category amounted to 0.41 standard deviation, corresponding to an IQ difference of 6.2 points [95% confidence interval 0.14, 0.68]. The association remained significant when further adjusted for birthweight and length (P=0.007). Both unadjusted and adjusted means suggested a dose-response relationship between maternal smoking during pregnancy and offspring adult intelligence. When subjects with missing data were excluded, essentially the same results were obtained in the reduced sample (n=1829). These results suggest that smoking during pregnancy may have long-term negative consequences on offspring adult intelligence. PMID:15670102

  3. Association between parental psychopathology and suicidal behavior among adult offspring: results from the cross-sectional South African Stress and Health survey

    PubMed Central

    2014-01-01

    Background Prior studies have demonstrated a link between parental psychopathology and offspring suicidal behavior. However, it remains unclear what aspects of suicidal behavior among adult offspring are predicted by specific parental mental disorders, especially in Africa. This study set out to investigate the association between parental psychopathology and suicidal behavior among their adult offspring in a South African general population sample. Method Parental psychopathology and suicidal behavior in offspring were assessed using structured interviews among 4,315 respondents from across South Africa. The WHO CIDI was used to collect data on suicidal behavior, while the Family History Research Diagnostic Criteria Interview was used to assess prior parental psychopathology. Bivariate and multivariate survival models tested the associations between the type and number parental mental disorders (including suicide) and lifetime suicidal behavior in the offspring. Associations between a range of parental disorders and the onset of subsequent suicidal behavior (suicidal ideation, plans, and attempts) among adult offspring were tested. Results The presence of parental psychopathology significantly increased the odds of suicidal behavior among their adult offspring. More specifically, parental panic disorder was associated with offspring suicidal ideation, while parental panic disorder, generalized anxiety disorder and suicide were significantly associated with offspring suicide attempts. Among those with suicidal ideation, none of the tested forms of parental psychopathology was associated with having suicide plans or attempts. There was a dose–response relationship between the number of parental disorders and odds of suicidal ideation. Conclusions Parental psychopathology increases the odds of suicidal behavior among their adult offspring in the South African context, replicating results found in other regions. Specific parental disorders predicted the onset and

  4. Prenatal nicotine exposure induces poor articular cartilage quality in female adult offspring fed a high-fat diet and the intrauterine programming mechanisms.

    PubMed

    Tie, Kai; Tan, Yang; Deng, Yu; Li, Jing; Ni, Qubo; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2016-04-01

    Prenatal nicotine exposure (PNE) induces skeletal growth retardation and dyslipidemia in offspring displaying intrauterine growth retardation (IUGR). Cholesterol accumulation resulting from cholesterol efflux dysfunction may reduce the quality of articular cartilage through fetal programming. This study evaluated the quality of articular cartilage of female adult offspring fed a high-fat diet and explored the mechanisms using a rat IUGR model established by the administration of 2.0mg/kg/d of subcutaneous nicotine from gestational days 11-20. The results demonstrated an increased OARSI (Osteoarthritis Research Society International) score and total cholesterol content, decreased serum corticosterone, and increased IGF1 and dyslipidemia with catch-up growth in PNE adult offspring. Cartilage matrix, IGF1 and cholesterol efflux pathway expression were reduced in PNE fetuses and adult offspring. Therefore, PNE induced poor articular cartilage quality in female adult offspring fed a high-fat diet via a dual programming mechanism. PMID:26769161

  5. Maternal Age at Holocaust Exposure and Maternal PTSD Independently Influence Urinary Cortisol Levels in Adult Offspring

    PubMed Central

    Bader, Heather N.; Bierer, Linda M.; Lehrner, Amy; Makotkine, Iouri; Daskalakis, Nikolaos P.; Yehuda, Rachel

    2014-01-01

    Background: Parental traumatization has been associated with increased risk for the expression of psychopathology in offspring, and maternal posttraumatic stress disorder (PTSD) appears to increase the risk for the development of offspring PTSD. In this study, Holocaust-related maternal age of exposure and PTSD were evaluated for their association with offspring ambient cortisol and PTSD-associated symptom expression. Method: Ninety-five Holocaust offspring and Jewish comparison subjects received diagnostic and psychological evaluations, and 24 h urinary cortisol was assayed by RIA. Offspring completed the parental PTSD questionnaire to assess maternal PTSD status. Maternal Holocaust exposure was identified as having occurred in childhood, adolescence, or adulthood and examined in relation to offspring psychobiology. Results: Urinary cortisol levels did not differ for Holocaust offspring and comparison subjects but differed significantly in offspring based on maternal age of exposure and maternal PTSD status. Increased maternal age of exposure and maternal PTSD were each associated with lower urinary cortisol in offspring, but did not exhibit a significant interaction. In addition, offspring PTSD-associated symptom severity increased with maternal age at exposure and PTSD diagnosis. A regression analysis of correlates of offspring cortisol indicated that both maternal age of exposure and maternal PTSD were significant predictors of lower offspring urinary cortisol, whereas childhood adversity and offspring PTSD symptoms were not. Conclusion: Offspring low cortisol and PTSD-associated symptom expression are related to maternal age of exposure, with the greatest effects associated with increased age at exposure. These effects are relatively independent of the negative consequences of being raised by a trauma survivor. These observations highlight the importance of maternal age of exposure in determining a psychobiology in offspring that is consistent with increased

  6. Association study between reward dependence and a functional BDNF polymorphism in adult women offspring of alcohol-dependent probands.

    PubMed

    Benzerouk, Farid; Gierski, Fabien; Raucher-Chéné, Delphine; Ramoz, Nicolas; Gorwood, Philip; Kaladjian, Arthur; Limosin, Frédéric

    2015-10-01

    Thirty-five healthy adult women offspring of alcohol-dependent probands (AWOA) were compared with 63 healthy controls to test whether personality dimensions on the Temperament and Character Inventory questionnaire were associated with the brain-derived neurotrophic factor Val66Met polymorphism in offspring. We found a significantly lower reward dependence score in AWOA compared with the controls. The brain-derived neurotrophic factor Val66Met polymorphism may be involved in this difference as the lower reward dependence score was found only in AWOA carrying the Val allele. PMID:26204172

  7. The influence of parental divorce and alcohol abuse on adult offspring risk of lifetime suicide attempt in the United States.

    PubMed

    Alonzo, Dana; Thompson, Ronald G; Stohl, Mahlki; Hasin, Deborah

    2014-05-01

    The influences of parental divorce and alcohol abuse on adult offspring lifetime suicide attempt have not been examined in national data. This study analyzed data from the 2001-2002 NESARC to estimate main and interaction effects of parental divorce and alcohol abuse on lifetime suicide attempt. Adjusted for controls, parental divorce and parental alcohol abuse independently increased odds of lifetime suicide attempt. The effect of parental divorce was not significantly moderated by parental alcohol abuse. Further research is needed to examine whether additional parental and offspring psychiatric and substance use covariates attenuate the association between parental divorce and lifetime suicide attempt. PMID:24827026

  8. Perinatal Exposure of Mice to the Pesticide DDT Impairs Energy Expenditure and Metabolism in Adult Female Offspring

    PubMed Central

    La Merrill, Michele; Karey, Emma; Moshier, Erin; Lindtner, Claudia; La Frano, Michael R.; Newman, John W.; Buettner, Christoph

    2014-01-01

    Dichlorodiphenyltrichloroethane (DDT) has been used extensively to control malaria, typhus, body lice and bubonic plague worldwide, until countries began restricting its use in the 1970s. Its use in malaria control continues in some countries according to recommendation by the World Health Organization. Individuals exposed to elevated levels of DDT and its metabolite dichlorodiphenyldichloroethylene (DDE) have an increased prevalence of diabetes and insulin resistance. Here we hypothesize that perinatal exposure to DDT disrupts metabolic programming leading to impaired metabolism in adult offspring. To test this, we administered DDT to C57BL/6J mice from gestational day 11.5 to postnatal day 5 and studied their metabolic phenotype at several ages up to nine months. Perinatal DDT exposure reduced core body temperature, impaired cold tolerance, decreased energy expenditure, and produced a transient early-life increase in body fat in female offspring. When challenged with a high fat diet for 12 weeks in adulthood, female offspring perinatally exposed to DDT developed glucose intolerance, hyperinsulinemia, dyslipidemia, and altered bile acid metabolism. Perinatal DDT exposure combined with high fat feeding in adulthood further impaired thermogenesis as evidenced by reductions in core temperature and in the expression of numerous RNA that promote thermogenesis and substrate utilization in the brown adipose tissue of adult female mice. These observations suggest that perinatal DDT exposure impairs thermogenesis and the metabolism of carbohydrates and lipids which may increase susceptibility to the metabolic syndrome in adult female offspring. PMID:25076055

  9. Hypoxia in early pregnancy induces cardiac dysfunction in adult offspring of Rattus norvegicus, a non-hypoxia-adapted species.

    PubMed

    Hauton, David

    2012-11-01

    Environmental stresses such as hypoxia can alter the development of the fetus that are manifested later in life, but the impact of early maternal hypoxia (MH) on cardiac performance, coronary flow and catecholamine responsiveness in adult offspring is less clear. The effects of exposure to chronic hypoxia (FIO(2)=0.12) in early intrauterine development (days E1-10) on cardiac performance of the adult offspring were estimated using the Langendorff-perfused rat heart. Cardiac dysfunction is presented as increased end-diastolic volume, with decreased ventricular stiffness in both male and female adult offspring (P<0.01 for both). While developed pressures were preserved in female MH rats, males demonstrated a decrease in systolic function, estimated as peak developed pressure (P<0.01). Challenge with dobutamine (300 nM), an adrenergic positive inotrope, increased cardiac work for control rats (P<0.01 for male and female rats) but not in MH-male rats. Coronary flow was reduced (P<0.01) and SERCA2 protein expression increased (2-fold, P<0.05) in female offspring, while eNOS protein levels were increased (2.5-fold, P<0.05) in females. This suggests gender-specific differences in compensatory responses to early MH, with female rats increasing calcium turnover to improve contractility and increasing coronary flow through increased expression of eNOS protein, partially restoring coronary perfusion while male rats show little compensation. PMID:22892476

  10. Liquid fructose in pregnancy exacerbates fructose-induced dyslipidemia in adult female offspring.

    PubMed

    Rodríguez, Lourdes; Panadero, María I; Rodrigo, Silvia; Roglans, Núria; Otero, Paola; Álvarez-Millán, Juan J; Laguna, Juan C; Bocos, Carlos

    2016-06-01

    Fructose intake from added sugars correlates with the epidemic rise in metabolic syndrome and related events. Nevertheless, consumption of beverages sweetened with fructose is not regulated in gestation. Previously, we found that maternal fructose intake produces in the progeny, when fetuses, impaired leptin signaling and hepatic steatosis and then impaired insulin signaling and hypoadiponectinemia in adult male rats. Interestingly, adult females from fructose-fed mothers did not exhibit any of these disturbances. However, we think that, actually, these animals keep a programmed phenotype hidden. Fed 240-day-old female progeny from control, fructose- and glucose-fed mothers were subjected for 3weeks to a fructose supplementation period (10% wt/vol in drinking water). Fructose intake provoked elevations in insulinemia and adiponectinemia in the female progeny independently of their maternal diet. In accordance, the hepatic mRNA levels of several insulin-responsive genes were similarly affected in the progeny after fructose intake. Interestingly, adult progeny of fructose-fed mothers displayed, in response to the fructose feeding, augmented plasma triglyceride and NEFA levels and hepatic steatosis versus the other two groups. In agreement, the expression and activity for carbohydrate response element binding protein (ChREBP), a lipogenic transcription factor, were higher after the fructose period in female descendants from fructose-fed mothers than in the other groups. Furthermore, liver fructokinase expression that has been indicated as one of those responsible for the deleterious effects of fructose ingestion was preferentially augmented in that group. Maternal fructose intake does influence the adult female offspring's response to liquid fructose and so exacerbates fructose-induced dyslipidemia and hepatic steatosis. PMID:27142744

  11. Maternal high-fat diet inversely affects insulin sensitivity in dams and young adult male rat offspring.

    PubMed

    Karbaschi, Roxana; Sadeghimahalli, Forouzan; Zardooz, Homeira

    2016-09-01

    This study attempts to further clarify the potential effects of maternal high-fat (HF) diet on glucose homeostasis in dams and young adult male rat offspring. Female rats were divided into control (CON dams) and HF (HF dams) diet groups, which received the diet 4 weeks prior to and through pregnancy and lactation periods. Blood samples were taken to determine metabolic parameters, then an intraperitoneal glucose tolerance test (IPGTT) was performed. Maternal HF diet increased intra-abdominal fat mass and plasma corticosterone level, but decreased leptin concentration in dams. In HF offspring intra-abdominal fat mass, plasma leptin, and corticosterone levels decreased. Following IPGTT, the plasma insulin level of HF dams was higher than the controls. In HF offspring plasma insulin level was not significantly different from the controls, but a steeper decrease of their plasma glucose concentration was observed. PMID:27604865

  12. Effects of a preventive parenting intervention for divorced families on the intergenerational transmission of parenting attitudes in young adult offspring.

    PubMed

    Mahrer, Nicole E; Winslow, Emily; Wolchik, Sharlene A; Tein, Jenn-Yun; Sandler, Irwin N

    2014-01-01

    This study evaluates whether the New Beginnings Program (NBP), a parenting intervention for divorced mothers, led to positive parenting attitudes in young adult offspring. Data were collected from 240 mothers (G1) and offspring (G2) at ages 9-12 and again in adolescence and young adulthood. Alternative theoretical models were tested to examine mediators of NBP effects on G2 parenting attitudes. Significant interactions between condition and baseline G1 parenting indicated that NBP improved G2's parenting attitudes for those exposed to poorer G1 parenting at program entry. Effects on G2 warm attitudes were partially mediated through program effects on G1 warm parenting. The implications of improving parenting attitudes in offspring who experience parental divorce on well-being in the next generation are discussed. PMID:24916511

  13. The possible mechanisms by which maternal hypothyroidism impairs insulin secretion in adult male offspring in rats.

    PubMed

    Karbalaei, Narges; Ghasemi, Asghar; Hedayati, Mehdi; Godini, Aliashraf; Zahediasl, Saleh

    2014-04-01

    Previous studies have recently shown that maternal hypothyroidism leads to impaired glucose metabolism and reduced insulin secretion in adult offspring in rats. The aim of this study was to locate the defect in the insulin secretion pathway induced by maternal hypothyroidism. Pregnant Wistar rats were divided into two groups; the control group consumed water, while the hypothyroid (FH) group received water containing 0.025% 6-propyl-2-thiouracil during gestation. An intravenous glucose tolerance test was carried out on 5-month-old male offspring. In in vitro studies, the effects of various secretagogues and inhibitors acting at different levels of the insulin secretion cascade were investigated, and insulin content, insulin secretion and glucokinase activity of the islets were compared. Although insulin content of the FH islets did not differ from that of control islets, insulin secretion from FH islets was reduced when it was challenged by glucose or arginine. Compared with control islets, activities of both hexokinase and glucokinase were also significantly decreased in the FH islets. Although, in both groups, increasing glibenclamide and nifedipine concentrations in the presence of 16.7 mmol l(-1) glucose increased and decreased insulin secretion, respectively, the percentage of changes in secretion of FH islets was significantly lower compared with control islets. The response of FH islets to high extracellular potassium concentration and diazoxide was also significantly lower than that of the control islets. These findings demonstrate that impaired insulin secretion in the FH group is probably related to alterations in different steps of the insulin secretion pathway and not in the insulin pool of β-cells. PMID:24097159

  14. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    SciTech Connect

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  15. Hypoxia during pregnancy in rats leads to the changes of the cerebral white matter in adult offspring

    SciTech Connect

    Wang, Lingxing; Cai, Ruowei; Lv, Guorong; Huang, Ziyang; Wang, Zhenhua

    2010-05-28

    The aim of the present study is to evaluate the effect of reduced fetal oxygen supply on cerebral white matter in the adult offspring and further assess its susceptibility to postnatal hypoxia and high-fat diet. Based on a 3 x 2 full factorial design consisting of three factors of maternal hypoxia, postnatal high-fat diet, and postnatal hypoxia, the ultrastructure of myelin, axon and capillaries were observed, and the expression of myelin basic protein (MBP), neurofilament-H+L(NF-H+L), and glial fibrillary acidic protein (GFAP) was analyzed in periventricular white matter of 16-month-old offspring. Demyelination, injured axon and damaged microvasculars were observed in maternal hypoxia offspring. The main effect of maternal hypoxia lead to decreased expression of MBP or NF-H+L, and increased expression of GFAP (all P < 0.05). Moreover, there was positive three-way interaction among maternal hypoxia, high-fat diet and postnatal hypoxia on MBP, NF-H+L or GFAP expression (all P < 0.05). In summary, our results indicated that maternal hypoxia during pregnancy in rats lead to changes of periventricular white matter in adult offspring, including demyelination, damaged axon and proliferated astroglia. This effect was amplified by high-fat diet and postnatal hypoxia.

  16. Maternal methyl-donor supplementation induces prolonged murine offspring colitis susceptibility in association with mucosal epigenetic and microbiomic changes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Developmental epigenetic changes, such as DNA methylation, have been recognized as potential pathogenic factors in inflammatory bowel diseases, the hallmark of which is an exaggerated immune response against luminal microbes. A methyl-donor (MD) diet can modify DNA methylation at select murine genom...

  17. Aerobic exercise training reduces cardiac function in adult male offspring exposed to prenatal hypoxia.

    PubMed

    Reyes, Laura M; Kirschenman, Raven; Quon, Anita; Morton, Jude S; Shah, Amin; Davidge, Sandra T

    2015-09-01

    Intrauterine growth restriction (IUGR) has been associated with increased susceptibility to myocardial ischemia-reperfusion (I/R) injury. Exercise is an effective preventive intervention for cardiovascular diseases; however, it may be detrimental in conditions of compromised health. The aim of this study was to determine whether exercise training can improve cardiac performance after I/R injury in IUGR offspring. We used a hypoxia-induced IUGR model by exposing pregnant Sprague-Dawley rats to 21% oxygen (control) or hypoxic (11% oxygen; IUGR) conditions from gestational day 15 to 21. At 10 wk of age, offspring were randomized to a sedentary group or to a 6-wk exercise protocol. Transthoracic echocardiography assessments were performed after 6 wk. Twenty-four hours after the last bout of exercise, ex vivo cardiac function was determined using a working heart preparation. With exercise training, there was improved baseline cardiac performance in male control offspring but a reduced baseline cardiac performance in male IUGR exercised offspring (P < 0.05). In male offspring, exercise decreased superoxide generation in control offspring, while in IUGR offspring, it had the polar opposite effect (interaction P ≤ 0.05). There was no effect of IUGR or exercise on cardiac function in female offspring. In conclusion, in male IUGR offspring, exercise may be a secondary stressor on cardiac function. A reduction in cardiac performance along with an increase in superoxide production in response to exercise was observed in this susceptible group. PMID:26157059

  18. Mortality in Adult Offspring of Immigrants: A Swedish National Cohort Study

    PubMed Central

    Manhica, Hélio; Toivanen, Susanna; Hjern, Anders; Rostila, Mikael

    2015-01-01

    Background Higher risks of psychiatric disorders and lower-than-average subjective health in adulthood have been demonstrated in offspring of immigrants in Sweden compared with offspring of native Swedes, and linked to relative socioeconomic disadvantage. The present study investigated mortality rates in relation to this inequity from a gender perspective. Methods We used data from national registers covering the entire Swedish population aged 18-65 years. Offspring of foreign-born parents who were either Swedish born or had received residency in Sweden before school age (<7 years) were defined as “offspring of immigrants.” We used Cox regression models to examine the association between parental country of birth and mortality between 1990 and 2008, with adjustment for education, income, age and family type. Results Male offspring of immigrants from the Middle East (HR:2.00, CI:1.66-2.26), other non-European countries (HR:1.80, CI:1.36-2.36) and Finland (HR:1.56, CI:1.48-1.65) showed an age-adjusted excess mortality risk from all causes of death when compared to offspring with Swedish-born parents. Income, but not education, greatly attenuated these increased mortality risks. No excess mortality rates were found among female offspring of immigrants, with the exception of external cause of death among offspring of Finnish immigrants. Conclusion The study demonstrates high mortality rates in male offspring of immigrants from Finland and non-European countries that are associated with economic, but not educational, disadvantage. No increased mortality rates were found among female offspring of immigrants. Future studies are needed to explain this gender differential and why income, but not education, predicts mortality in male offspring of immigrants. PMID:25706297

  19. Parental Midlife Body Shape and Association with Multiple Adult Offspring Obesity Measures: North West Adelaide Health Study

    PubMed Central

    2015-01-01

    There is compelling evidence that parental weight is a strong determinant of offspring weight status. The study used cross-sectional self-reported and measured data from a longitudinal cohort of Australian adults (n = 2128) from Stage 3 (2008–10) of the North West Adelaide Health Study (1999–2003, baseline n = 4056) to investigate the association between midlife parental body shape and four indicators of obesity and fat distribution. The analysis used measured body mass index (BMI), waist circumference (WC), waist hip ratio (WHR) and waist height ratio (WHtR) of adult offspring, together with pictograms for recall of parental body shape. Compared to both parents being a healthy weight, offspring were more likely to be overweight or obese if both parents were an unhealthy weight at age 40 (OR 2.14, 95% CI 1.67–2.76) and further, those participants whose mother was an unhealthy weight were more likely to be overweight or obese themselves (OR 1.50, 95% CI 1.14–1.98). There were similar but lower results for those with an overweight/obese father (OR 1.44, 95% CI 1.08–1.93). The effect of one or both parents being overweight or obese tended to be stronger for daughters than for sons across BMI, WC and WHtR. BMI showed the strongest association with parental body shape (OR 2.14), followed by WC (OR 1.78), WHtR (OR 1.71) and WHR (OR 1.45). WHtR (42–45%) and BMI (35–36%) provided the highest positive predictive values for overweight/obesity from parental body shape. Parental obesity increases the risk of obesity for adult offspring, both for overall body shape and central adiposity, particularly for daughters. Pictograms could potentially be used as a screening tool in primary care settings to promote healthy weight among young adults. PMID:26355742

  20. Epigenetics: Behavioral Influences on Gene Function, Part I: Maternal Behavior Permanently Affects Adult Behavior in Offspring

    ERIC Educational Resources Information Center

    Ogren, Marilee P.; Lombroso, Paul J.

    2008-01-01

    The article highlights the field of epigenetics and its relevance in determining the effects of maternal nurturing on behavioral patterns in offsprings. Results concluded that maternal behavior influences the offspring's behavior to stress in adulthood and the effects are transgenerational through epigenetic mechanisms.

  1. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats.

    PubMed

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE+ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE+HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE+HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a "two-programming" hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is "the first programming", and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as "the second programming". PMID:24275070

  2. Adult exposure to the synthetic hormone 17α-ethynylestradiol affects offspring of the gastropods Nassarius burchardi and Nassarius jonasii.

    PubMed

    Borysko, Larissa; Ross, Pauline M

    2014-05-01

    The aim of this study was to determine whether adult exposure to endocrine disrupting compounds affects offspring using trans-generational testing. Adult estuarine dwelling gastropods Nassarius burchardi and Nassarius jonasii were exposed to the synthetic estrogen 17α-ethynylestradiol (EE2) to determine the effects on the development and survival of their offspring. Adults were maintained in synthetic seawater controls and EE2 treatments (0.005, 0.05, 0.5, 50µg/L) over a sixteen week period. Egg capsules were collected from the adults following four, ten and sixteen weeks of adult exposure and transferred to different EE2 exposure scenarios. Treatment concentrations were selected to represent changes in EE2 exposure that could occur over different periods in an organism's lifecycle. Egg capsules laid by adults were therefore transferred to control or EE2 treatments (0.005, 0.05, 0.5, 5, 50, 500µg/L) to develop until hatching. The percentage of egg capsules with unviable eggs and abnormalities, number of days for hatching to occur and hatching success were measured. The veliger larvae that hatched from egg capsules following two, eight and fourteen weeks of adult exposure to EE2 and controls were used in 96h acute toxicity tests with controls and EE2 treatments at concentrations of 0.5, 5, 50, 500, 1250, 2500, 4000µg/L. Exposure of adult N. burchardi and N. jonasii to EE2 affected the percentage of egg capsules with unviable eggs, the development and hatching success of embryos and survival of veligers. These toxicity tests produced a complex set of results with different responses in developing eggs and veliger larvae to the adult EE2 treatments and length of adult exposure. This study demonstrates the importance of trans-generational testing and adult exposure scenarios in toxicity investigations. PMID:24462525

  3. Peri-conceptional obesogenic exposure induces sex-specific programming of disease susceptibilities in adult mouse offspring.

    PubMed

    Dahlhoff, M; Pfister, S; Blutke, A; Rozman, J; Klingenspor, M; Deutsch, M J; Rathkolb, B; Fink, B; Gimpfl, M; Hrabě de Angelis, M; Roscher, A A; Wolf, E; Ensenauer, R

    2014-02-01

    Vulnerability of the fetus upon maternal obesity can potentially occur during all developmental phases. We aimed at elaborating longer-term health outcomes of fetal overnutrition during the earliest stages of development. We utilized Naval Medical Research Institute (NMRI) mice to induce pre-conceptional and gestational obesity and followed offspring outcomes in the absence of any postnatal obesogenic influences. Male adult offspring developed overweight, insulin resistance, hyperleptinemia, hyperuricemia and hepatic steatosis; all these features were not observed in females. Instead, they showed impaired fasting glucose and a reduced fat mass and adipocyte size. Influences of the interaction of maternal diet∗sex concerned offspring genes involved in fatty liver disease, lipid droplet size regulation and fat mass expansion. These data suggest that a peri-conceptional obesogenic exposure is sufficient to shape offspring gene expression patterns and health outcomes in a sex- and organ-specific manner, indicating varying developmental vulnerabilities between sexes towards metabolic disease in response to maternal overnutrition. PMID:24275555

  4. Calcium supplementation reverts central adiposity, leptin, and insulin resistance in adult offspring programed by neonatal nicotine exposure.

    PubMed

    Nobre, J L; Lisboa, P C; Santos-Silva, A P; Lima, N S; Manhães, A C; Nogueira-Neto, J F; Cabanelas, A; Pazos-Moura, C C; Moura, E G; de Oliveira, E

    2011-09-01

    Obesity is a worldwide epidemic. Calcium influences energy metabolism regulation, causing body weight loss. Because maternal nicotine exposure during lactation programs for obesity, hyperleptinemia, insulin resistance (IR), and hypothyroidism, we decided to evaluate the possible effect of dietary calcium supplementation on these endocrine dysfunctions in this experimental model. Osmotic minipumps containing nicotine solution (N: 6 mg/kg per day for 14 days) or saline (C) were s.c. implanted in lactating rats 2 days after giving birth (P2). At P120, N and C offspring were subdivided into four groups: 1) C - standard diet; 2) C with calcium supplementation (CCa, 10 g calcium carbonate/kg rat chow); 3) N - standard diet; and 4) N with calcium supplementation (NCa). Rats were killed at P180. As expected, N offspring showed higher visceral and total body fat, hyperleptinemia, lower hypothalamus leptin receptor (OB-R) content, hyperinsulinemia, and higher IR index. Also, higher tyrosine hydroxylase (TH) expression (+51%), catecholamine content (+37%), and serum 25-hydroxyvitamin D(3) (+76%) were observed in N offspring. Dietary calcium supplementation reversed adiposity, hyperleptinemia, OB-R underexpression, IR, TH overexpression, and vitamin D. However, this supplementation did not reverse hypothyroidism. In NCa offspring, Sirt1 mRNA was lower in visceral fat (-37%) and higher in liver (+42%). In conclusion, dietary calcium supplementation seems to revert most of the metabolic syndrome parameters observed in adult offspring programed by maternal nicotine exposure during lactation. It is conceivable that the reduction in fat mass per se, induced by calcium therapy, is the main mechanism that leads to the increment of insulin action. PMID:21680618

  5. Thermoregulatory deficits in adult long evans rat offspring exposed perinatally to the antithyroidal drug, propylthiouracil

    EPA Science Inventory

    Developmental exposure to endocrine disrupting toxicants has been shown to alter a variety of physiological processes in mature offspring. Body (core) temperature (Tc) is a tightly regulated homeostatic system but is susceptible to disruptors of the hypothalamic-pituitary-thyroid...

  6. Maternal protein restriction impairs the transcriptional metabolic flexibility of skeletal muscle in adult rat offspring.

    PubMed

    da Silva Aragão, Raquel; Guzmán-Quevedo, Omar; Pérez-García, Georgina; Manhães-de-Castro, Raul; Bolaños-Jiménez, Francisco

    2014-08-14

    Skeletal muscle exhibits a remarkable flexibility in the usage of fuel in response to the nutrient intake and energy demands of the organism. In fact, increased physical activity and fasting trigger a transcriptional programme in skeletal muscle cells leading to a switch from carbohydrate to lipid oxidation. Impaired metabolic flexibility has been reported to be associated with obesity and type 2 diabetes, but it is not known whether the disability to adapt to metabolic demands is a cause or a consequence of these pathological conditions. Inasmuch as a poor nutritional environment during early life is a predisposing factor for the development of metabolic diseases in adulthood, in the present study, we aimed to determine the long-term effects of maternal malnutrition on the metabolic flexibility of offspring skeletal muscle. To this end, the transcriptional responses of the soleus and extensor digitorum longus muscles to fasting were evaluated in adult rats born to dams fed a control (17 % protein) or a low-protein (8 % protein, protein restricted (PR)) diet throughout pregnancy and lactation. With the exception of reduced body weight and reduced plasma concentrations of TAG, PR rats exhibited a metabolic profile that was the same as that of the control rats. In the fed state, PR rats exhibited an enhanced expression of key regulatory genes of fatty acid oxidation including CPT1a, PGC-1α, UCP3 and PPARα and an impaired expression of genes that increase the capacity for fat oxidation in response to fasting. These results suggest that impaired metabolic inflexibility precedes and may contribute to the development of metabolic disorders associated with early malnutrition. PMID:24823946

  7. Windscapes shape seabird instantaneous energy costs but adult behavior buffers impact on offspring

    PubMed Central

    2014-01-01

    Background Windscapes affect energy costs for flying animals, but animals can adjust their behavior to accommodate wind-induced energy costs. Theory predicts that flying animals should decrease air speed to compensate for increased tailwind speed and increase air speed to compensate for increased crosswind speed. In addition, animals are expected to vary their foraging effort in time and space to maximize energy efficiency across variable windscapes. Results We examined the influence of wind on seabird (thick-billed murre Uria lomvia and black-legged kittiwake Rissa tridactyla) foraging behavior. Airspeed and mechanical flight costs (dynamic body acceleration and wing beat frequency) increased with headwind speed during commuting flights. As predicted, birds adjusted their airspeed to compensate for crosswinds and to reduce the effect of a headwind, but they could not completely compensate for the latter. As we were able to account for the effect of sampling frequency and wind speed, we accurately estimated commuting flight speed with no wind as 16.6 ms?1 (murres) and 10.6 ms?1 (kittiwakes). High winds decreased delivery rates of schooling fish (murres), energy (murres) and food (kittiwakes) but did not impact daily energy expenditure or chick growth rates. During high winds, murres switched from feeding their offspring with schooling fish, which required substantial above-water searching, to amphipods, which required less above-water searching. Conclusions Adults buffered the adverse effect of high winds on chick growth rates by switching to other food sources during windy days or increasing food delivery rates when weather improved. PMID:26019870

  8. Contributions of maternal and paternal adiposity and smoking to adult offspring adiposity and cardiovascular risk: the Midspan Family Study

    PubMed Central

    Han, T S; Hart, C L; Haig, C; Logue, J; Upton, M N; Watt, G C M; Lean, M E J

    2015-01-01

    Objective Obesity has some genetic basis but requires interaction with environmental factors for phenotypic expression. We examined contributions of gender-specific parental adiposity and smoking to adiposity and related cardiovascular risk in adult offspring. Design Cross-sectional general population survey. Setting Scotland. Participants 1456 of the 1477 first generation families in the Midspan Family Study: 2912 parents (aged 45–64 years surveyed between 1972 and 1976) who had 1025 sons and 1283 daughters, aged 30–59 years surveyed in 1996. Main measures Offspring body mass index (BMI), waist circumference (WC), cardiometabolic risk (lipids, blood pressure and glucose) and cardiovascular disease as outcome measures, and parental BMI and smoking as determinants. All analyses adjusted for age, socioeconomic status and family clustering and offspring birth weight. Results Regression coefficients for BMI associations between father–son (0.30) and mother–daughter (0.33) were greater than father–daughter (0.23) or mother–son (0.22). Regression coefficient for the non-genetic, shared-environment or assortative-mating relationship between BMIs of fathers and mothers was 0.19. Heritability estimates for BMI were greatest among women with mothers who had BMI either <25 or ≥30 kg/m2. Compared with offspring without obese parents, offspring with two obese parents had adjusted OR of 10.25 (95% CI 6.56 to 13.93) for having WC ≥102 cm for men, ≥88 cm women, 2.46 (95% CI 1.33 to 4.57) for metabolic syndrome and 3.03 (95% CI 1.55 to 5.91) for angina and/or myocardial infarct (p<0.001). Neither parental adiposity nor smoking history determined adjusted offspring individual cardiometabolic risk factors, diabetes or stroke. Maternal, but not paternal, smoking had significant effects on WC in sons (OR=1.50; 95% CI 1.13 to 2.01) and daughters (OR=1.42; 95% CI 1.10 to 1.84) and metabolic syndrome OR=1.68; 95% CI 1.17 to 2.40) in sons. Conclusions There are

  9. Effect of Valeriana fauriei extract on the offspring of adult rats exposed to prenatal stress.

    PubMed

    Lee, Hwayoung; Won, Hansol; Im, Jiyun; Kim, Young Ock; Lee, Sanghyun; Cho, Ik-Hyun; Kim, Hyung-Ki; Kwon, Jun-Tack; Kim, Hak-Jae

    2016-07-01

    Exposing a pregnant female to stress is a risk factor for the development of psychiatric disorders in the offspring. In the present study, we examined the effects of an extract of Valeriana fauriei (VF) root (100 mg/kg/day, administered on postnatal days 35-56) on behavioral patterns as well as protein expression in the prefrontal cortex of the offspring of prenatally-stressed rats. Modified behavioral tests, including the forced swim test, the open field test, a social interaction test and the prepulse inhibition test were performed and many of the parameters were found to decrease in the offspring of the rats exposed to PNS compared with the offspring of the non-stressed rats. Western blot and immunohistochemical analyses of the prefrontal cortex revealed that the downregulation of several neurodevelopmental proteins in the offspring of rats dams exposed to PNS was reversed after treatment with VF extract. These findings demonstrate that the downregulation of several proteins in the prefrontal cortex of the offspring of prenatally‑stressed rats may be associated with subsequent behavioral changes, and that these phenomena recovered following VF treatment. Our results suggest that VF decreases the incidence of prenatal stress related-psychiatric disorders, such as depression and schizophrenia. PMID:27220809

  10. Low functional programming of renal AT{sub 2}R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

    SciTech Connect

    Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

    2015-09-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT{sub 2}R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT{sub 1a}R)/AT{sub 2}R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT{sub 2}R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT{sub 2}R might mediate the developmental origin of adult glomerulosclerosis. - Highlights: • Prenatal caffeine exposure induces glomerulosclerosis in adult offspring. • Prenatal caffeine

  11. Effects of number and gender of offspring on quality of life among older adults: evidence from the Korean Longitudinal Study of Aging, 2006–2012

    PubMed Central

    Kim, Jae-Hyun; Lee, Sang Gyu; Shin, Jaeyong; Cho, Kyung-Hee; Choi, Jae-Woo; Park, Eun-Cheol

    2015-01-01

    Objectives We examined correlations between number and gender of offspring and health-related quality of life (HRQoL) and quality of life (QoL) in older adults. Setting We used data from the 2006–2012 data sets of the Korean Longitudinal Study of Aging. Participants There were 10 242, 8680, 7907 and 7480 participants in 2006, 2008, 2010 and 2012, respectively. Interventions Number and gender of offspring. Primary and secondary outcome measures We measured participants’ QoL and HRQoL using a visual analogue scale developed by the Korea Labour Institute and which is similar to the EQ-VAS, a European measure. Results We estimated the HRQoL and QoL of individuals with offspring. Estimates for the HRQoL and QoL of parents with no offspring were −7.762 and −9.384, respectively (both p<0.0001) versus parents with two offspring. For parents with five or more offspring, the estimates for the HRQoL and QoL were −1.529 and 0.885, respectively (p<0.001 and p<0.017, respectively) compared with parents with two offspring. For fathers with no offspring compared with fathers with two offspring, the estimates for the HRQoL and QoL were −6.143 and −7.492, respectively (both p<0.0001). Conclusions These results suggest that number of offspring is associated with both HRQoL and QoL. Those with no offspring showed the lowest HRQoL and QoL. Although having five or more children had positive associations with QoL, it had negative associations with HRQoL. Public health services for those with poor quality of life should provide effective support programmes and services based on these findings. PMID:26063566

  12. Discrepancy in reports of support exchanges between parents and adult offspring: within- and between-family differences.

    PubMed

    Kim, Kyungmin; Zarit, Steven H; Birditt, Kira S; Fingerman, Karen L

    2014-04-01

    Using data from 929 parent-child dyads nested in 458 three-generation families (aged 76 for the oldest generation, 50 for the middle generation, and 24 for the youngest generation), this study investigated how discrepancies in reports of support that parents and their adult offspring exchanged with one another vary both within and between families, and what factors explain variations in dyadic discrepancies. We found substantial within- and between-family differences in dyadic discrepancies in reports of support exchanges. For downward exchanges (from parents to offspring), both dyad-specific characteristics within a family (e.g., gender composition, relative levels of relationship quality, and family obligation) and shared family characteristics (e.g., average levels of relationship quality) showed significant effects on dyadic discrepancies. For upward exchanges (from offspring to parents), however, only dyad-specific characteristics (e.g., gender composition, coresidence, relative levels of positive relationship quality, and family obligation) were significantly associated with discrepancies. Discrepancies in support exchanges were mainly associated with dyad-specific characteristics, but they also appeared to be influenced by family emotional environments. The use of multiple informants revealed that families differ in discrepancies in reports of exchanges, which has implications for quality of family life as well as future exchanges. PMID:24548009

  13. An embryonic atrazine exposure results in reproductive dysfunction in adult zebrafish and morphological alterations in their offspring.

    PubMed

    Wirbisky, Sara E; Weber, Gregory J; Sepúlveda, Maria S; Lin, Tsang-Long; Jannasch, Amber S; Freeman, Jennifer L

    2016-01-01

    The herbicide atrazine, a suspected endocrine disrupting chemical (EDC), frequently contaminates potable water supplies. Studies suggest alterations in the neuroendocrine system along the hypothalamus-pituitary-gonadal axis; however, most studies address either developmental, pubertal, or adulthood exposures, with few investigations regarding a developmental origins hypothesis. In this study, zebrafish were exposed to 0, 0.3, 3, or 30 parts per billion (ppb) atrazine through embryogenesis and then allowed to mature with no additional chemical exposure. Reproductive function, histopathology, hormone levels, offspring morphology, and the ovarian transcriptome were assessed. Embryonic atrazine exposure resulted in a significant increase in progesterone levels in the 3 and 30 ppb groups. A significant decrease in spawning and a significant increase in follicular atresia in the 30 ppb group were observed. In offspring, a decrease in the head length to body ratio in the 30 ppb group, along with a significant increase in head width to body ratio in the 0.3 and 3 ppb groups occurred. Transcriptomic alterations involved genes associated with endocrine system development and function, tissue development, and behavior. This study provides evidence to support atrazine as an EDC causing reproductive dysfunction and molecular alterations in adults exposed only during embryogenesis and morphological alterations in their offspring. PMID:26891955

  14. An embryonic atrazine exposure results in reproductive dysfunction in adult zebrafish and morphological alterations in their offspring

    PubMed Central

    Wirbisky, Sara E.; Weber, Gregory J.; Sepúlveda, Maria S.; Lin, Tsang-Long; Jannasch, Amber S.; Freeman, Jennifer L.

    2016-01-01

    The herbicide atrazine, a suspected endocrine disrupting chemical (EDC), frequently contaminates potable water supplies. Studies suggest alterations in the neuroendocrine system along the hypothalamus-pituitary-gonadal axis; however, most studies address either developmental, pubertal, or adulthood exposures, with few investigations regarding a developmental origins hypothesis. In this study, zebrafish were exposed to 0, 0.3, 3, or 30 parts per billion (ppb) atrazine through embryogenesis and then allowed to mature with no additional chemical exposure. Reproductive function, histopathology, hormone levels, offspring morphology, and the ovarian transcriptome were assessed. Embryonic atrazine exposure resulted in a significant increase in progesterone levels in the 3 and 30 ppb groups. A significant decrease in spawning and a significant increase in follicular atresia in the 30 ppb group were observed. In offspring, a decrease in the head length to body ratio in the 30 ppb group, along with a significant increase in head width to body ratio in the 0.3 and 3 ppb groups occurred. Transcriptomic alterations involved genes associated with endocrine system development and function, tissue development, and behavior. This study provides evidence to support atrazine as an EDC causing reproductive dysfunction and molecular alterations in adults exposed only during embryogenesis and morphological alterations in their offspring. PMID:26891955

  15. Vitamin D deficiency during various stages of pregnancy in the rat; its impact on development and behaviour in adult offspring.

    PubMed

    O'Loan, Jonathan; Eyles, Darryl W; Kesby, James; Ko, Pauline; McGrath, John J; Burne, Thomas H J

    2007-04-01

    Developmental vitamin D (DVD) deficiency alters brain development and behaviour in the rat. The aim of this study was to vary levels of vitamin D deficiency during gestation and examine the effects on developmental milestones and behaviour in adult offspring. By manipulating the withdrawal and reintroduction of vitamin D in the diet of female Sprague-Dawley rats, their offspring were subjected to four different prenatal vitamin D conditions: (a) control (normal vitamin D throughout gestation); (b) early-DVD deficiency; (c) late-DVD deficiency; and (d) full-DVD deficiency. We show that the standard measure for vitamin D status, 25(OH)D(3), can be significantly manipulated within 7 days by dietary intervention. We also show that levels of the active form of this vitamin, 1,25(OH)(2)D(3), replete within the same time frame as 25(OH)D(3) but are slower to deplete. Developmental milestones remained normal across all four dietary groups. Concerning the adult behavioural phenotype, both full- and late-DVD deficiency were associated with MK-801-induced hyperlocomotion. Overall, these data suggest that vitamin D deficiency restricted to late gestation only is sufficient to disrupt adult brain functioning in the rat. These findings suggest there may be a therapeutic window for maternal dietary intervention in the DVD model of psychosis. PMID:17276604

  16. Effects of mother's dietary exposure to acesulfame-K in Pregnancy or lactation on the adult offspring's sweet preference.

    PubMed

    Zhang, Gen-Hua; Chen, Meng-Ling; Liu, Si-Si; Zhan, Yue-Hua; Quan, Ying; Qin, Yu-Mei; Deng, Shao-Ping

    2011-11-01

    This study investigates whether mother's exposure to the artificial sweetener acesulfame-K (AK) during pregnancy or lactation affected her adult offspring's sweet preference. It was found that mother's dietary exposure to AK in pregnancy or lactation decreased the preference thresholds for AK and sucrose solutions in the adult offspring, whereas the preference pattern and the most preferred concentration for AK or sucrose solution were unchanged. Furthermore, the preference scores in the exposure groups were increased significantly when compared with the control group at a range of concentrations for AK or sucrose solution. The existence of AK and its dynamic changes within 24 h in amniotic fluid during pregnancy or in mother's milk during lactation after a single oral infusion of AK solution were revealed by the methods of reversed-phase high-performance liquid chromatography and mass spectrometry. Our data suggest that AK can be ingested by the prenatal or postnatal mice through their mother's amniotic fluid or breast milk, producing a long-dated function on the adult's sweet preference. PMID:21653241

  17. Differential expression of murine adult hemoglobins in early ontogeny

    SciTech Connect

    Wawrzyniak, C.J.; Lewis, S.E.; Popp, R.A.

    1985-01-01

    A hemoglobin mutation is described that permits study of the expression of the two adult ..beta..-globin genes throughout fetal and postnatal development. Mice with a mutation at the Hbb/sup s/, ..beta..-globin locus, were used to study the relative levels of ..beta..-s2major and ..beta..-sminor globins specified by the mutant Hbb/sup s2/ haplotype during development. At 11.5 days of gestation ..beta..-sminor comprised over 80% and ..beta..-s2major under 20% of the adult beta-globin. The relative level of ..beta..-sminor decreased through fetal development; at birth ..beta..-sminor represented 33.7% of the ..beta..-globin. The adult values of 71.0% ..beta..-s2major and 29.0% ..beta..-sminor globin are expressed in mice six days after birth. Because the two ..beta..-globin genes are expressed in mice of the Hbb/sup 2s/ haplotype, both the ..beta..-smajor and ..beta..-sminor genes must be expressed in mice of the Hbb/sup s/ haplotype. Expression of the ..beta..-sminor gene is elevated to 35.6% in Hbb/sup s2/ mice that have been bled repeatedly. Thus, the 5' ..beta..-s2major and 3' ..beta..-sminor genes of the Hbb/sup s2/ haplotype and, presumably the 5' ..beta..-smajor and 3' ..beta..-sminor genes of the Hbb/sup s/ haplotype, are regulated independently and are homologous to the 5' ..beta..-dmajor and 3' ..beta..-dminor genes of the Hbb/sup d/ haplotype. Mice of the Hbb/sup s2/ haplotype are better than mice of the Hbb/sup d/ haplotytpe for studying the mechanisms of hemoglobin switching because the Hbb/sup s2/ each of the three embryonic and two adult hemoglobins can be separated by electrophoresis. 17 refs., 3 figs.

  18. Maternal Dietary Loads of Alpha-Tocopherol Increase Synapse Density and Glial Synaptic Coverage in the Hippocampus of Adult Offspring

    PubMed Central

    Salucci, S.; Ambrogini, P.; Lattanzi, D.; Betti, M.; Gobbi, P.; Galati, C.; Galli, F.; Cuppini, R.; Minelli, A.

    2014-01-01

    An increased intake of the antioxidant α-Tocopherol (vitamin E) is recommended in complicated pregnancies, to prevent free radical damage to mother and fetus. However, the anti-PKC and antimitotic activity of α-Tocopherol raises concerns about its potential effects on brain development. Recently, we found that maternal dietary loads of α-Tocopherol through pregnancy and lactation cause developmental deficit in hippocampal synaptic plasticity in rat offspring. The defect persisted into adulthood, with behavioral alterations in hippocampus-dependent learning. Here, using the same rat model of maternal supplementation, ultrastructural morphometric studies were carried out to provide mechanistic interpretation to such a functional impairment in adult offspring by the occurrence of long-term changes in density and morphological features of hippocampal synapses. Higher density of axo-spinous synapses was found in CA1 stratum radiatum of α-Tocopherol-exposed rats compared to controls, pointing to a reduced synapse pruning. No morphometric changes were found in synaptic ultrastructural features, i.e., perimeter of axon terminals, length of synaptic specializations, extension of bouton-spine contact. Gliasynapse anatomical relationship was also affected. Heavier astrocytic coverage of synapses was observed in Tocopherol-treated offspring, notably surrounding axon terminals; moreover, the percentage of synapses contacted by astrocytic endfeet at bouton-spine interface (tripartite synapses) was increased. These findings indicate that gestational and neonatal exposure to supranutritional Tocopherol intake can result in anatomical changes of offspring hippocampus that last through adulthood. These include a surplus of axo-spinous synapses and an aberrant gliasynapse relationship, which may represent the morphological signature of previously described alterations in synaptic plasticity and hippocampus-dependent learning. PMID:24998923

  19. Intake of grape procyanidins during gestation and lactation impairs reverse cholesterol transport and increases atherogenic risk indexes in adult offspring.

    PubMed

    Del Bas, Josep Maria; Crescenti, Anna; Arola-Arnal, Anna; Oms-Oliu, Gemma; Arola, Lluís; Caimari, Antoni

    2015-12-01

    Cardiovascular disease (CVD) is one of the most prevalent noncommunicable diseases in humans. Different studies have identified dietary procyanidins as bioactive compounds with beneficial properties against CVD by improving lipid homeostasis, among other mechanisms. The aim of this work was to assess whether grape seed procyanidin consumption at a physiological dose during the perinatal period could influence the CVD risk of the offspring. Wistar rat dams were treated with a grape seed procyanidin extract (GSPE; 25mg/kg of body weight per day) or vehicle during gestation and lactation. The adult male offspring of GSPE-treated dams presented decreased high-density lipoprotein cholesterol (HDL-C) levels, increased total cholesterol-to-HDL-C ratios and an exacerbated fasting triglyceride-to-HDL-C ratios (atherogenic index of plasma) compared to the control group. Impaired reverse cholesterol transport (RCT) was evidenced by the accumulation of cholesterol in skeletal muscle and by decreased fecal excretion of cholesterol and bile acids, which was consistent with the observed mRNA down-regulation of the rate-limiting enzyme in the hepatic bile acid synthesis pathway Cyp7A1. Conversely, GSPE programming also resulted in up-regulated gene expression of different key components of the RCT process, such as hepatic Npc1, Abcg1, Abca1, Lxra, Srebp2, Lcat, Scarb1 and Pltp, and the repression of microRNA miR-33a expression, a key negative controller of hepatic RCT at the gene expression level. Our results show that maternal intake of grape procyanidins during the perinatal period impacts different components of the RCT process, resulting in increased CVD risk in the adult offspring. PMID:26365577

  20. Prenatal restraint stress decreases the expression of alpha-7 nicotinic receptor in the brain of adult rat offspring.

    PubMed

    Baier, Carlos J; Pallarés, María E; Adrover, Ezequiela; Monteleone, Melisa C; Brocco, Marcela A; Barrantes, Francisco J; Antonelli, Marta C

    2015-01-01

    Prenatal stress (PS) strongly impacts fetal brain development and function in adulthood. In normal aging and Alzheimer's disease, there is hypothalamic-pituitary-adrenal axis dysfunction and loss of cholinergic neurons and neuronal nicotinic acetylcholine receptors (nAChRs). This study investigated whether prenatal restraint stress affects nAChR expression in the brain of adult offspring. For PS, pregnant dams were placed in a plastic restrainer for 45 min, three times daily during the last week of pregnancy; controls were undisturbed. Male offspring were analyzed at postnatal day (PND) 60 (n = 4 rats per group). Western blot (WB) and fluorescence microscopy showed that PS decreased α7-AChR subunit expression (∼50%) in the frontal cortex in the adult offspring. PS decreased significantly the number of α7-AChR-expressing cells in the medial prefrontal cortex (by ∼25%) and in the sensory-motor cortex (by ∼20%) without affecting the total cell number in those areas. No alterations were found in the hippocampus by quantitative polymerase chain reaction (qPCR), or WB analysis, but a detailed fluorescence microscopy analysis showed that PS affected α7-AChR mainly in the CA3 and dentate gyrus subfields: PS decreased α7-AChR subunit expression by ∼25 and ∼30%, respectively. Importantly, PS decreased the number of α7-AChR-expressing cells and the total cell number (by ∼15 and 20%, respectively) in the dentate gyrus. PS differently affected α4-AChR: PS impaired its mRNA expression in the frontal cortex (by ∼50%), without affecting protein levels. These results demonstrate that disturbances during gestation produce long-term alterations in the expression pattern of α7-AChR in rat brain. PMID:25798813

  1. Months of asynchrony in offspring production but synchronous adult emergence: the role of diapause in an ectoparasite's life cycle.

    PubMed

    Härkönen, Laura; Kaitala, Arja

    2013-12-01

    Off-host stages of temperate zone ectoparasites must overcome two challenges: coping with unfavorable seasons and synchronizing their life cycles with host availability. In general, little is known about the seasonal cycles of insect ectoparasites of warm-blooded animals. The current study investigates the unusual phenology of a viviparous hippoboscid fly, the deer ked (Lipoptena cervi L.), that parasitizes boreal cervids. Despite months of asynchrony in offspring production, the adults emerge synchronously in mid-August across the northern boreal zone. We examined the role of diapause variation in the synchronization of life cycles by testing adult emergence success and time in relation to offspring birth month (October to April) and with respect to chilling time and photoperiod. Unexpectedly, we found that photoperiod had no role in regulating the life cycle, but diapause was maintained as long as pupae were exposed to cold. Pupae born before February needed a slightly longer exposure to high temperatures to terminate diapause if the cold period was short. Despite the apparent importance of a long period of chilling for life cycle synchrony, it was not required to terminate diapause. This finding of cold mainly preventing, rather than promoting, diapause termination is not novel among temperate insects, but it is rare. Slow diapause termination as a response to exceptionally long exposure to high, not low, temperatures seems to be a cornerstone for synchronizing the life cycle in the deer ked. PMID:24216221

  2. Maternal Exercise during Pregnancy Increases BDNF Levels and Cell Numbers in the Hippocampal Formation but Not in the Cerebral Cortex of Adult Rat Offspring.

    PubMed

    Gomes da Silva, Sérgio; de Almeida, Alexandre Aparecido; Fernandes, Jansen; Lopim, Glauber Menezes; Cabral, Francisco Romero; Scerni, Débora Amado; de Oliveira-Pinto, Ana Virgínia; Lent, Roberto; Arida, Ricardo Mario

    2016-01-01

    Clinical evidence has shown that physical exercise during pregnancy may alter brain development and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF) and absolute cell numbers in the hippocampal formation and cerebral cortex of rat pups born from mothers exercised during pregnancy. Additionally, we evaluated the cognitive abilities of adult offspring in different behavioral paradigms (exploratory activity and habituation in open field tests, spatial memory in a water maze test, and aversive memory in a step-down inhibitory avoidance task). Results showed that maternal exercise during pregnancy increased BDNF levels and absolute numbers of neuronal and non-neuronal cells in the hippocampal formation of offspring. No differences in BDNF levels or cell numbers were detected in the cerebral cortex. It was also observed that offspring from exercised mothers exhibited better cognitive performance in nonassociative (habituation) and associative (spatial learning) mnemonic tasks than did offspring from sedentary mothers. Our findings indicate that maternal exercise during pregnancy enhances offspring cognitive function (habituation behavior and spatial learning) and increases BDNF levels and cell numbers in the hippocampal formation of offspring. PMID:26771675

  3. Maternal Exercise during Pregnancy Increases BDNF Levels and Cell Numbers in the Hippocampal Formation but Not in the Cerebral Cortex of Adult Rat Offspring

    PubMed Central

    Gomes da Silva, Sérgio; de Almeida, Alexandre Aparecido; Fernandes, Jansen; Lopim, Glauber Menezes; Cabral, Francisco Romero; Scerni, Débora Amado; de Oliveira-Pinto, Ana Virgínia; Lent, Roberto; Arida, Ricardo Mario

    2016-01-01

    Clinical evidence has shown that physical exercise during pregnancy may alter brain development and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF) and absolute cell numbers in the hippocampal formation and cerebral cortex of rat pups born from mothers exercised during pregnancy. Additionally, we evaluated the cognitive abilities of adult offspring in different behavioral paradigms (exploratory activity and habituation in open field tests, spatial memory in a water maze test, and aversive memory in a step-down inhibitory avoidance task). Results showed that maternal exercise during pregnancy increased BDNF levels and absolute numbers of neuronal and non-neuronal cells in the hippocampal formation of offspring. No differences in BDNF levels or cell numbers were detected in the cerebral cortex. It was also observed that offspring from exercised mothers exhibited better cognitive performance in nonassociative (habituation) and associative (spatial learning) mnemonic tasks than did offspring from sedentary mothers. Our findings indicate that maternal exercise during pregnancy enhances offspring cognitive function (habituation behavior and spatial learning) and increases BDNF levels and cell numbers in the hippocampal formation of offspring. PMID:26771675

  4. Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure.

    PubMed

    Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

    2015-09-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT2R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT1aR)/AT2R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT2R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT2R might mediate the developmental origin of adult glomerulosclerosis. PMID:25986755

  5. Tobacco Smoking: Patterns, Health Consequences for Adults, and the Long-term Health of the Offspring

    PubMed Central

    Maritz, Gert S.; Mutemwa, Muyunda

    2012-01-01

    Tobacco use started several centuries ago and increased markedly after the invention of the cigarette making machine. Once people start smoking they find it difficult to quit the habit. This is due to the addictive effect of nicotine in tobacco smoke. Various epidemiologic and laboratory studies clearly showed that smoking is associated with various diseases such as heart diseases, asthma and emphysema and the associated increase in morbidity and mortality of smokers. Several studies implicate nicotine as the causative factor in tobacco smoke. Apart from nicotine, various carcinogens also occur in tobacco smoke resulting in an increase in the incidence of cancer in smokers. While the smoking habit is decreasing in developed countries, tobacco use increases in the developing countries. Smoking prevalence is also highest in poor communities and amongst those with low education levels. It is important to note that, although ther is a decline in the number of smokers in the developed countries, there is a three to four decades lag between the peak in smoking prevalence and the subsequent peak in smoking related mortality. It has been shown that maternal smoking induces respiratory diseases in the offspring. There is also evidence that parental smoking may program the offspring to develop certain diseases later in life. Various studies showed that maternal nicotine exposure during pregnancy and lactation via tobacco smoke of nicotine replacement therapy (NRT), program the offspring to develop compromised lung structure later in life with the consequent compromised lung function. This implies that NRT is not an option to assist pregnant or lactating smokers to quit the habit. Even paternal smoking may have an adverse effect on the health of the offspring since it has been shown that 2nd and 3rd hand smoking have adverse health consequences for those exposed to it. PMID:22980343

  6. Maternal in utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate affects the blood pressure of adult male offspring

    SciTech Connect

    Martinez–Arguelles, D.B.; McIntosh, M.; Rohlicek, C.V.; Culty, M.; Zirkin, B.R.; Papadopoulos, V.

    2013-01-01

    Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressure in the young (2 month-old) and older (6.5 month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300 mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring. Highlights: ► In utero exposure to 300 mg DEHP/kg/day decreases activity at postnatal day 60. ► In utero exposure to DEHP decreases aldosterone levels at postnatal day 200. ► In utero exposure to DEHP decreases systolic blood pressure at postnatal day 200. ► An 8% salt diet recovers the decreased blood pressure at postnatal day 200.

  7. Cocaine exposure prior to pregnancy alters the psychomotor response to cocaine and transcriptional regulation of the dopamine D1 receptor in adult male offspring.

    PubMed

    Sasaki, Aya; Constantinof, Andrea; Pan, Pauline; Kupferschmidt, Dave A; McGowan, Patrick O; Erb, Suzanne

    2014-05-15

    There is evidence that maternal experience prior to pregnancy can play an important role in behavioral, physiological, and genetic programming of offspring. Likewise, exposure to cocaine in utero can result in marked changes in central nervous system function of offspring. In this study, we examined whether exposure of rat dams to cocaine prior to pregnancy subsequently alters indices of behavior, physiology, and gene expression in offspring. Multiple outcome measures were examined in adult male offspring: (1) behavioral expression of cocaine-induced psychomotor activation; (2) levels of corticosterone in response to immobilization stress; and (3) expression of multiple genes, including dopamine receptor D1 (DRD1) and D2 (DRD2), glucocorticoid receptor (GR), and corticotropin-releasing factor (CRF), in functionally relevant brain regions. Adult Sprague-Dawley females were exposed to cocaine (15-30 mg/kg, i.p.) or saline for 10 days, and were then mated to drug naïve males of the same strain. Separate groups of adult male offspring were tested for their acute psychomotor response to cocaine (0, 15, 30 mg/kg, i.p.), corticosterone responsivity to 20 min of immobilization stress, and expression of multiple genes using quantitative PCR. Offspring of dams exposed to cocaine prior to conception exhibited increased psychomotor sensitivity to cocaine, and upregulated gene expression of DRD1 in the medial prefrontal cortex (mPFC). Neither stress-induced corticosterone levels nor gene expression of GR or CRF genes were altered. These data suggest that cocaine exposure before pregnancy can serve to enhance psychomotor sensitivity to cocaine in offspring, possibly via alterations in dopamine function that include upregulation of the DRD1. PMID:24583058

  8. Enhanced Mesenteric Arterial Responsiveness to Angiotensin II Is Androgen Receptor-Dependent in Prenatally Protein-Restricted Adult Female Rat Offspring1

    PubMed Central

    Sathishkumar, Kunju; Balakrishnan, Meena P.; Yallampalli, Chandrasekhar

    2014-01-01

    ABSTRACT Gestational protein restriction results in intrauterine growth restriction and hypertension in adult female growth-restricted rats. Enhanced vascular responsiveness to angiotensin II is observed, and blockade of the renin-angiotensin system abolishes hypertension in adult growth-restricted rats, suggesting that the renin-angiotensin system contributes to intrauterine growth restriction-induced hypertension. Moreover, growth-restricted adult rats have higher plasma testosterone levels, and antiandrogen treatment abolishes hypertension, indicating an important role for testosterone. We hypothesized that androgens may play a pivotal role in the enhanced responsiveness to Ang II and hypertension. Female offspring of pregnant rats fed 20% protein (control) or 6% protein diet (protein restricted), at 6 mo of age, were studied. Plasma testosterone and mean arterial pressure in protein-restricted offspring were significantly higher compared to controls. Flutamide treatment (10 mg/kg/day subcutaneously for 10 days) reduced mean arterial pressure in protein-restricted offspring but was without significant effect in controls. Vascular Agtr1/Agtr2 ratio was significantly higher in protein-restricted offspring, an effect that was reversed by flutamide. Flutamide treatment did not have any effect on Agtr1/Agtr2 ratio in controls. Enhanced contractile response to angiotensin II in mesenteric arteries was observed in protein-restricted offspring compared with control. Flutamide treatment reversed the enhanced contractile response to angiotensin II in protein-restricted offspring without significant effect in controls. Vascular reactivity to phenylephrine was similar between the control and protein-restricted offspring with and without flutamide treatment, suggesting that enhanced contractile response and flutamide's reversal effect is specific to angiotensin II. These results suggest that prenatally protein-restricted rats exhibit an enhanced responsiveness to angiotensin

  9. Different effects of prenatal stress on ERK2/CREB/Bcl-2 expression in the hippocampus and the prefrontal cortex of adult offspring rats.

    PubMed

    Zhu, Zeen; Sun, Hongli; Gong, Xiaojie; Li, Hui

    2016-05-25

    It has become increasingly evident that prenatal stress and its psychological and physiological concomitants are associated with the pathophysiology of mood disorders. However, the mechanisms underlying the prenatal stress-induced offspring's anxiety disorders remain unknown. We recently reported that prenatal stress enhanced anxiety-like behavior in adult offspring rat, and involved N-methyl-D-aspartate receptor subunits, including NR1 and NR2A. In the present research, using the same prenatal stress model, we measured the ERK2/CREB/Bcl-2 mRNA levels by real-time PCR. Our findings indicated that prenatal stress decreased ERK2 and CREB mRNA levels in the hippocampus and the prefrontal cortex and Bcl-2 mRNA levels in the hippocampus of offspring rat. The results showed that the abnormal ERK2, CREB, and Bcl-2 mRNA levels may be involved in the anxiety-like behavior of adult rats with prenatal stress. PMID:27096215

  10. Transmission of cultural values among Mexican-origin parents and their adolescent and emerging adult offspring.

    PubMed

    Perez-Brena, Norma J; Updegraff, Kimberly A; Umaña-Taylor, Adriana J

    2015-06-01

    The integration of the U.S. and Mexican culture is an important process associated with Mexican-origin youths' adjustment and family dynamics. The current study examined the reciprocal associations in parents' and two offspring's cultural values (i.e., familism and respect) in 246 Mexican-origin families. Overall, mothers' values were associated with increases in youths' values 5 years later. In contrast, youths' familism values were associated with increases in fathers' familism values 5 years later. In addition, developmental differences emerged where parent-to-offspring effects were more consistent for youth transitioning from early to late adolescence than for youth transitioning from middle adolescence to emerging adulthood. Finally, moderation by immigrant status revealed a youth-to-parent effect for mother-youth immigrant dyads, but not for dyads where youth were U.S.-raised. Our findings highlight the reciprocal nature of parent-youth value socialization and provide a nuanced understanding of these processes through the consideration of familism and respect values. As Mexican-origin youth represent a large and rapidly growing segment of the U.S. population, research that advances our understanding of how these youth develop values that foster family cohesion and support is crucial. PMID:25470657

  11. Maternal exposure to diets containing high fructose and saturated fats, low B vitamins, or their combination programs growth, adiposity, and insulin sensitivity in adult offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Early exposure to unfavorable nutrition programs increases risk of adult-onset diseases. In this rat study, we investigate morphological, metabolic and endocrinal phenotypes of offspring born to dams consuming isocaloric diets containing 30% fructose, 9.9% coconut fat and 0.5% cholesterol (F+SFA), m...

  12. Evaluation of possible toxic effects of spearmint (Mentha spicata) on the reproductive system, fertility and number of offspring in adult male rats

    PubMed Central

    Nozhat, Fatemeh; Alaee, Sanaz; Behzadi, Khodabakhsh; Azadi Chegini, Najmeh

    2014-01-01

    Objective: In this study we investigated the effects of spearmint (Mentha spicata Labiatae) on the reproductive system, fertility and number of offspring in adult male rats. Materials and Methods: Adult Wistar male rats in one control (C) and three experimental groups (I, II and III) received 0, 10, 20 and 40 mg/kg spearmint extract orally for 45 days, respectively. Following this treatment, the animals’ weights, and the standard weight of reproductive tissues, sperm count, sperm motility and serum testosterone concentration were measured, and reproductive tissues were examined histopathologically. To evaluate the effects of spearmint on fertility of male rats and growth of their offspring, male rats of the control and experimental groups mated with untreated female rats. Results: Results showed that spearmint did not affect the rats’ body and reproductive tissue weights. The sperm count, fast and slow progressive motility of sperm and serum testosterone concentration decreased while number of non-progressive sperm and immotile sperm increased in the experimental groups compared to the control group, but none of these changes were statistically significant. Histopathological studies showed no severe changes in reproductive tissues between control and experimental groups. Number and growth of offspring born from mating of male rats with untreated female rats showed no difference. Conclusion: We concluded that spearmint has no significant toxic effect on the reproductive system, fertility and number of offspring in adult male rats at the above mentioned dose levels. However high levels of this extract may have adverse effects on male fertility. PMID:25386406

  13. Intrauterine low-functional programming of IGF1 by prenatal nicotine exposure mediates the susceptibility to osteoarthritis in female adult rat offspring.

    PubMed

    Tie, Kai; Zhang, Xianrong; Tan, Yang; Deng, Yu; Li, Jing; Ni, Qubo; Wang, Hui; Chen, Liaobin

    2016-02-01

    This study aimed to evaluate whether female adult offspring born with intrauterine growth retardation induced by prenatal nicotine exposure (PNE) are susceptible to osteoarthritis (OA) and to explore the underlying programming mechanisms. Pregnant rats were treated with nicotine or saline at 2.0 mg/kg/d from gestational d 11 to 20. The female adult offspring with or without PNE were forced with a strenuous treadmill running for 6 wk to induce OA. Nicotine's effects on fetal articular chondrocytes were studied by exposing chondrocytes to nicotine for 10 d, and dihydro-β-erythroidine, a selective α4β2-nicotinic acetylcholine receptor (nAChR) inhibitor, was used to identify the change of nicotine's effect. For adult offspring, increased cartilage destruction and accelerated OA progression were observed in the PNE group with running; the expression of α1 chain of type II collagen (Col2A1), aggrecan, SRY-type high mobility group box 9 (Sox9), and IGF1 signaling molecules in the cartilage of PNE offspring were decreased. For fetuses, elevated serum corticosteroid and nicotine levels and suppressed IGF1 levels were observed; expression of Col2A1, aggrecan, Sox9, and IGF1 were reduced. The result of chondrocytes revealed that nicotine impeded the expression of Col2A1, aggrecan, and IGF1; blocking α4β2-nAChR rescued nicotine's suppression. In conclusion, PNE increases the susceptibility of adult offspring to OA; the potential mechanism involves IGF1 low-functional programming in articular cartilage caused directly by the action of nicotine on α4β2-nAChR. PMID:26499267

  14. Changes in synaptic transmission and protein expression in the brains of adult offspring after prenatal inhibition of the kynurenine pathway.

    PubMed

    Forrest, C M; Khalil, O S; Pisar, M; McNair, K; Kornisiuk, E; Snitcofsky, M; Gonzalez, N; Jerusalinsky, D; Darlington, L G; Stone, T W

    2013-12-19

    During early brain development, N-methyl-d-aspartate (NMDA) receptors are involved in cell migration, neuritogenesis, axon guidance and synapse formation, but the mechanisms which regulate NMDA receptor density and function remain unclear. The kynurenine pathway of tryptophan metabolism includes an agonist (quinolinic acid) and an antagonist (kynurenic acid) at NMDA receptors and we have previously shown that inhibition of the pathway using the kynurenine-3-monoxygenase inhibitor Ro61-8048 in late gestation produces rapid changes in protein expression in the embryos and effects on synaptic transmission lasting until postnatal day 21 (P21). The present study sought to determine whether any of these effects are maintained into adulthood. After prenatal injections of Ro61-8048 the litter was allowed to develop to P60 when some offspring were euthanized and the brains removed for examination. Analysis of protein expression by Western blotting revealed significantly reduced expression of the GluN2A subunit (32%) and the morphogenetic protein sonic hedgehog (31%), with a 29% increase in the expression of doublecortin, a protein associated with neurogenesis. No changes were seen in mRNA abundance using quantitative real-time polymerase chain reaction. Neuronal excitability was normal in the CA1 region of hippocampal slices but paired-pulse stimulation revealed less inhibition at short interpulse intervals. The amount of long-term potentiation was decreased by 49% in treated pups and recovery after low-frequency stimulation was delayed. The results not only strengthen the view that basal, constitutive kynurenine metabolism is involved in normal brain development, but also show that changes induced prenatally can affect the brains of adult offspring and those changes are quite different from those seen previously at weaning (P21). Those changes may be mediated by altered expression of NMDAR subunits and sonic hedgehog. PMID:24076085

  15. Young Adult Exposure to Cardiovascular Risk Factors and Risk of Events Later in Life: The Framingham Offspring Study

    PubMed Central

    Pletcher, Mark J.; Vittinghoff, Eric; Thanataveerat, Anusorn; Bibbins-Domingo, Kirsten

    2016-01-01

    Background It is unclear whether coronary heart disease (CHD) risk factor exposure during early adulthood contributes to CHD risk later in life. Our objective was to analyze whether extent of early adult exposures to systolic and diastolic blood pressure (SBP, DBP) and low-and high-density lipoprotein cholesterol (LDL, HDL) are independent predictors of CHD events later in life. Methods and Findings We used all available measurements of SBP, DBP, LDL, and HDL collected over 40 years in the Framingham Offspring Study to estimate risk factor trajectories, starting at age 20 years, for all participants. Average early adult (age 20–39) exposure to each risk factor was then estimated, and used to predict CHD events (myocardial infarction or CHD death) after age 40, with adjustment for risk factor exposures later in life (age 40+). 4860 participants contributed an average of 6.3 risk factor measurements from in-person examinations and 24.5 years of follow-up after age 40, and 510 had a first CHD event. Early adult exposures to high SBP, DBP, LDL or low HDL were associated with 8- to 30-fold increases in later life CHD event rates, but were also strongly correlated with risk factor levels later in life. After adjustment for later life levels and other risk factors, early adult DBP and LDL remained strongly associated with later life risk. Compared with DBP≤70 mmHg, adjusted hazard ratios (HRs) were 2.1 (95% confidence interval: 0.8–5.7) for DBP = 71–80, 2.6 (0.9–7.2) for DBP = 81–90, and 3.6 (1.2–11) for DBP>90 (p-trend = 0.019). Compared with LDL≤100 mg/dl, adjusted HRs were 1.5 (0.9–2.6) for LDL = 101–130, 2.2 (1.2–4.0) for LDL = 131–160, and 2.4 (1.2–4.7) for LDL>160 (p-trend = 0.009). While current levels of SBP and HDL were also associated with CHD events, we did not detect an independent association with early adult exposure to either of these risk factors. Conclusions Using a mixed modeling approach to estimation of young adult exposures

  16. Maternal Obesity in Sheep Increases Fatty Acid Synthesis, Upregulates Nutrient Transporters, and Increases Adiposity in Adult Male Offspring after a Feeding Challenge

    PubMed Central

    Long, Nathan M.; Rule, Daniel C.; Tuersunjiang, Nuermaimaiti; Nathanielsz, Peter W.; Ford, Stephen P.

    2015-01-01

    Maternal obesity in women is increasing worldwide. The objective of this study was to evaluate differences in adipose tissue metabolism and function in adult male offspring from obese and control fed mothers subjected to an ad libitum feeding challenge. We developed a model in which obese ewes were fed 150% of feed provided for controls from 60 days before mating to term. All ewes were fed to requirements during lactation. After weaning, F1 male offspring were fed only to maintenance requirements until adulthood (control = 7, obese = 6), when they were fed ad libitum for 12 weeks with intake monitored. At the end of the feeding challenge offspring were given an intravenous glucose tolerance test (IVGTT), necropsied, and adipose tissue collected. During the feeding trial F1obese males consumed more (P < 0.01), gained more weight (P < 0.01) and became heavier (P < 0.05) than F1control males. During IVGTT, Obese F1 offspring were hyperglycemic and hypoinsulinemic (P < 0.01) compared to F1 control F1. At necropsy perirenal and omental adipose depots weights were 47% and 58% greater respectively and subcutaneous fat thickness 41% greater in F1obese vs F1control males (P < 0.05). Adipocyte diameters were greater (P ≤ 0.04) in perirenal, omental and subcutaneous adipose depots in F1obese males (11, 8 and 7% increase vs. control, respectively). When adipose tissue was incubated for 2 hrs with C-14 labeled acetate, subcutaneous, perirenal, and omental adipose tissue of F1 obese males exhibited greater incorporation (290, 83, and 90% increase vs. control, respectively P < 0.05) of acetate into lipids. Expression of fatty acid transporting, binding, and syntheses mRNA and protein was increased (P < 0.05) compared to F1 control offspring. Maternal obesity increased appetite and adiposity associated with increased adipocyte diameters and increased fatty acid synthesis in over-nourished adult male offspring. PMID:25875659

  17. Transmission of Cultural Values among Mexican American Parents and their Adolescent and Emerging Adult Offspring

    PubMed Central

    Perez-Brena, Norma J.; Updegraff, Kimberly A.; Umaña-Taylor, Adriana J.

    2015-01-01

    The integration of the U.S. and Mexican culture is an important process associated with Mexican-origin youths’ adjustment and family dynamics. The current study examined the reciprocal associations in parents’ and two offspring’s cultural values (i.e., familism and respect) in 246 Mexican-origin families. Overall, mothers’ values were associated with increases in youths’ values five years later. In contrast, youths’ familism values were associated with increases in fathers’ familism values five years later. In addition, developmental differences emerged where parent-to-offspring effects were more consistent for youth transitioning from early to late adolescence than for youth transitioning from middle adolescence to emerging adulthood. Finally, moderation by immigrant-status revealed a youth-to-parent effect for mother-youth immigrant dyads, but not for dyads where youth were U.S.-raised. Our findings highlight the reciprocal nature of parent-youth value socialization and provide a nuanced understanding of these processes through the consideration of familism and respect values. As Mexican-origin youth represent a large and rapidly growing segment of the U.S. population, research that advances our understanding of how these youth develop values that foster family cohesion and support are crucial. PMID:25470657

  18. The scent of stress: environmental challenge in the peripartum environment of mice affects emotional behaviours of the adult offspring in a sex-specific manner.

    PubMed

    Lerch, S; Dormann, C; Brandwein, C; Gass, P; Chourbaji, S

    2016-06-01

    Early adverse experiences are known to influence the risk of developing psychiatric disorders later. To shed further light on the development of laboratory mice, we systematically examined the influence of a prenatal or postnatal olfactory stressor, namely unfamiliar male mouse faeces, presented to pregnant or nursing mouse dams. Maternal and offspring behaviours were then examined. Maternal behaviours relative to controls revealed changes in nest building by the pregnant dams exposed to the unfamiliar faeces. There were no differences among groups on pup retrieval or exploration by the dams. Behavioural phenotyping of male and female offspring as adults included measures of exploration, anxiety, social and depressive-like behaviours. Additionally, serum corticosterone was assessed as a marker of physiological stress response. Group differences were dependent on the sex of the adult offspring. Males raised by dams that were stressed during pregnancy presented elevated emotionality as indicated by increased numbers of faecal boluses in the open field paradigm. Consistent with the effects of prenatal stress on the males only the prenatally stressed females had higher body weights than their respective controls. Indeed, males in both experimental groups had higher circulating corticosterone levels. By contrast, female offspring of dams exposed to the olfactory stressor after parturition were more anxious in the O-maze as indicated by increased latencies in entering the exposed areas of the maze. These findings emphasize the necessity for researchers to consider the pre- and postnatal environments, even of mice with almost identical genetic backgrounds, in designing experiments and interpreting their data. PMID:26408077

  19. Chronic PFOS exposures induce life stage-specific behavioral deficits in adult zebrafish and produce malformations in F1 offspring

    PubMed Central

    Chen, Jiangfei; Huang, Changjiang; Das, Siba R.; La Du, Jane; Corvi, Margaret M.; Bai, Chenglian; Chen, Yuanhong; Tanguay, Robert L.; Dong, Qiaoxiang

    2014-01-01

    Perfluorooctanesulphonicacid (PFOS) is an organic contaminant that is ubiquitous in the environment, wildlife, and humans. Few studies have assessed the effects of chronic PFOS exposure on central nervous system function in aquatic organisms. The present study defined the behavioral effects of varying life span chronic exposures to low dose PFOS in zebrafish. The zebrafish were treated with vehicle control or 0.5μM PFOS during 1–21, 21–120, or 1–120 day post fertilization (dpf). Chronic PFOS exposure impaired the adult zebrafish behavior mode under the tapping stimulus. The movement speed of 1–120 dpf exposed fish was significantly increased compared with control, while 1–21 and 21–120 dpf exposed groups were not severely affected. PFOS residues in F1 embryos derived from parental exposure during both the 1–120 and 21–120 dpf groups was significantly higher than control, and F1 embryos in these two groups showed obvious malformations, such as uninflated swim bladder (USB) and bent spine (BS). Larvae of the parental exposed to PFOS from 1–21 or 21–120 dpf elicited a higher swim rate than control in both the light and dark periods. Embryos derived from the 1–120 dpf group showed a statistically lower speed in the light period and a higher speed in the dark period as compared with control. Though there is little PFOS residue in 1–21 dpf group, the adverse behavioral effects on both adult and F1 larvae indicate that exposure during the first 21 dpf induce long-term neurobehavior toxicity. Our findings demonstrate that chronic exposure to low dose PFOS in different life stage adversely impacts adult behavior, subsequent offspring malformation, and larval behavior. PMID:23059794

  20. Risk Factors Associated with Aortic and Carotid Intimal-Medial Thickness in Adolescents and Young Adults: the Muscatine Offspring Study

    PubMed Central

    Dawson, Jeffrey D.; Sonka, Milan; Blecha, Mary Beth; Lin, Wenjiao; Davis, Patricia H.

    2009-01-01

    Objectives To determine whether cardiovascular risk factors are associated with aortic and carotid intimal-medial thickness (aIMT and cIMT) in adolescents and young adults. Background Atherosclerotic lesions begin developing in youth, first in the distal abdominal aorta and later in the carotid arteries. Knowledge of how risk factors relate to aIMT and cIMT may help in the design of early interventions to prevent cardiovascular disease. Methods Participants were 635 members of the Muscatine Offspring cohort. The mean aIMT and cIMT were measured using an automated reading program. Results The means (SDs) of aIMT and cIMT were 0.63 (0.14) mm and 0.49 (0.04) mm, respectively. In adolescents (ages 11 to 17), aIMT was associated with triglycerides, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and waist/hip ratio, after adjusting for age, gender, and height. In young adults (ages 18 to 34), aIMT was associated with those same five risk factors, plus HDL-cholesterol and pulse pressure. In adolescents, cIMT was associated with SBP, pulse pressure, heart rate, BMI, and waist/hip ratio. In young adults, cIMT was associated total cholesterol, LDL-cholesterol, triglycerides, SBP, .DBP, BMI, waist/hip ratio, and HbA1C. In both age groups, aIMT and cIMT were significantly correlated with the PDAY coronary artery risk score. Conclusions Both aIMT and cIMT are associated with cardiovascular risk factors. Using aIMT in adolescents gives information beyond that obtained from cIMT alone. Measurement of aIMT and cIMT may help identify those at risk for premature cardiovascular disease. PMID:19520251

  1. Assessment of DNA synthesis in Islet-1{sup +} cells in the adult murine heart

    SciTech Connect

    Weinberger, Florian Mehrkens, Dennis Starbatty, Jutta Nicol, Philipp Eschenhagen, Thomas

    2015-01-02

    Highlights: • Islet-1 was expressed in the adult heart. • Islet-1-positive cells did not proliferate in the adult heart. • Sinoatrial node cells did not proliferate in the adult heart. - Abstract: Rationale: Islet-1 positive (Islet-1{sup +}) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1{sup +} cells retain proliferative activity and may therefore play a role in regenerating specialized regions in the heart. Methods and results: DNA synthesis was analyzed by the incorporation of tritiated thymidine ({sup 3}H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of {sup 3}H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1{sup +} cells. Whereas Islet{sup −} non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed. Conclusions: Islet-1{sup +} cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.

  2. Adult glucocorticoid exposure leads to transcriptional and DNA methylation changes in nuclear steroid receptors in the hippocampus and kidney of mouse male offspring.

    PubMed

    Petropoulos, Sophie; Matthews, Stephen G; Szyf, Moshe

    2014-02-01

    Synthetic glucocorticoids (sGCs) are commonly prescribed for the management of inflammatory and endocrine disorders. However, nothing is known regarding the effects of sGC on adult germline methylome and whether these effects can be transmitted to the next generation. We hypothesized that administration of sGC to adult male mice alters DNA methylation in mature sperm and modifies the transcription and methylation of steroid receptors in male F1 offspring. Adult C57BL/6 males (n = 10/group) were injected on five consecutive days with 1 mg/kg sGC (i.e., dexamethasone) or vehicle and euthanized 35 or 60 days after initial treatment or bred with control females (60 days postinitial treatment; n = 5/group). A significant increase in global non-CpG methylation was observed in F0 sperm 60 days following sGC treatment. In the hippocampus and kidney of Postnatal Day 50 (PND50) and PND240 male offspring derived from fathers exposed to sGC, significant differences in mineralocorticoid receptor (Nr3c2; Mr), estrogen alpha receptor (Nr3a1; Ers1), and glucocorticoid receptor (Nr3c1; Gr) expression were observed. Furthermore, significant demethylation in regulatory regions of Mr, Gr, and Esr1 was observed in the PND50 kidney derived from fathers exposed to sGC. This is the first demonstration that paternal pharmacological exposure to sGC can alter the expression and DNA methylation of nuclear steroid receptors in brain and somatic tissues of offspring. These findings provide proof of principle that adult male exposure to sGC can affect DNA methylation and gene expression in offspring, indicating the possibility that adult experiences that evoke increases in endogenous glucocorticoid (i.e., stress) might have similar effects. PMID:24451982

  3. Effects of Family Dysfunction and Parental Problem Drinking on Adult Offspring.

    ERIC Educational Resources Information Center

    Soukup, Dorothy Therese

    Few empirical studies have been conducted to determine the characteristics and functioning of Adult Children of Alcoholics (ACoAs). This study examined the emotional and behavioral wellness of college students (N=253) raised in a variety of family environments with varying levels of healthy/unhealthy functioning. For the purposes of this study…

  4. Label-Retaining Cells in the Adult Murine Salivary Glands Possess Characteristics of Adult Progenitor Cells

    PubMed Central

    Chibly, Alejandro M.; Querin, Lauren; Harris, Zoey; Limesand, Kirsten H.

    2014-01-01

    Radiotherapy is the primary treatment for patients with head and neck cancer, which account for roughly 500,000 annual cases worldwide. Dysfunction of the salivary glands and associated conditions like xerostomia and dysphagia are often developed by these patients, greatly diminishing their life quality. Current preventative and palliative care fail to deliver an improvement in the quality of life, thus accentuating the need for regenerative therapies. In this study, a model of label retaining cells (LRCs) in murine salivary glands was developed, in which LRCs demonstrated proliferative potential and possessed markers of putative salivary progenitors. Mice were labeled with 5-Ethynyl-2′-deoxyuridine (EdU) at postnatal day 10 and chased for 8 weeks. Tissue sections from salivary glands obtained at the end of chase demonstrated co-localization between LRCs and the salivary progenitor markers keratin 5 and keratin 14, as well as kit mRNA, indicating that LRCs encompass a heterogeneous population of salivary progenitors. Proliferative potential of LRCs was demonstrated by a sphere assay, in which LRCs were found in primary and secondary spheres and they co-localized with the proliferation marker Ki67 throughout sphere formation. Surprisingly, LRCs were shown to be radio-resistant and evade apoptosis following radiation treatment. The clinical significance of these findings lie in the potential of this model to study the mechanisms that prevent salivary progenitors from maintaining homeostasis upon exposure to radiation, which will in turn facilitate the development of regenerative therapies for salivary gland dysfunction. PMID:25238060

  5. On the evolution of intergenerational division of labor, menopause and transfers among adults and offspring.

    PubMed

    Cyrus, Chu C Y; Lee, Ronald D

    2013-09-01

    We explain how upward transfers from adult children to their elderly parents might evolve as an interrelated feature of a deepening intergenerational division of labor. Humans have a particularly long period of juvenile dependence requiring both food and care time provided mainly by younger and older adults. We suggest that the division of labor evolves to exploit comparative advantage between young and old adults in fertility, childcare and foraging. Eventually the evolving division of labor reaches a limit when the grandmother's fertility reaches zero (menopause). Continuing, it may hit another limit when the grandmother's foraging time has been reduced to her subsistence needs. Further specialization can occur only with food transfers to the grandmother, enabling her to reduce her foraging time to concentrate on additional childcare. We prove that this outcome can arise only after menopause has evolved. We describe the conditions necessary for both group selection (comparative steady state reproductive fitness) and individual selection (successful invasion by a mutation), and interpret these conditions in terms of comparative advantages. PMID:23648187

  6. On the evolution of intergenerational division of labor, menopause and transfers among adults and offspring

    PubMed Central

    Cyrus Chu, C.Y.; Lee, Ronald D.

    2013-01-01

    We explain how upward transfers from adult children to their elderly parents might evolve as an interrelated feature of a deepening intergenerational division of labor. Humans have a particularly long period of juvenile dependence requiring both food and care time provided mainly by younger and older adults. We suggest that the division of labor evolves to exploit comparative advantage between young and old adults in fertility, childcare and foraging. Eventually the evolving division of labor reaches a limit when the grandmother's fertility reaches zero (menopause). Continuing, it may hit another limit when the grandmother's foraging time has been reduced to her subsistence needs. Further specialization can occur only with food transfers to the grandmother, enabling her to reduce her foraging time to concentrate on additional childcare. We prove that this outcome can arise only after menopause has evolved. We describe the conditions necessary for both group selection (comparative steady state reproductive fitness) and individual selection (successful invasion by a mutation), and interpret these conditions in terms of comparative advantages. PMID:23648187

  7. Maternal conjugated linoleic acid supplementation reverses high-fat diet-induced skeletal muscle atrophy and inflammation in adult male rat offspring.

    PubMed

    Pileggi, C A; Segovia, S A; Markworth, J F; Gray, C; Zhang, X D; Milan, A M; Mitchell, C J; Barnett, M P G; Roy, N C; Vickers, M H; Reynolds, C M; Cameron-Smith, D

    2016-03-01

    A high-saturated-fat diet (HFD) during pregnancy and lactation leads to metabolic disorders in offspring concomitant with increased adiposity and a proinflammatory phenotype in later life. During the fetal period, the impact of maternal diet on skeletal muscle development is poorly described, despite this tissue exerting a major influence on life-long metabolic health. This study investigated the effect of a maternal HFD on skeletal muscle anabolic, catabolic, and inflammatory signaling in adult rat offspring. Furthermore, the actions of maternal-supplemented conjugated linoleic acid (CLA) on these measures of muscle phenotype were investigated. A purified control diet (CD; 10% kcal fat), a CD supplemented with CLA (CLA; 10% kcal fat, 1% total fat as CLA), a high-fat (HFD; 45% kcal fat from lard), or a HFD supplemented with CLA (HFCLA; 45% kcal fat from lard, 1% total fat as CLA) was fed ad libitum to female Sprague-Dawley rats for 10 days before mating and throughout gestation and lactation. Male offspring received a standard chow diet from weaning, and the gastrocnemius was collected for analysis at day 150. Offspring from HF and HFCLA mothers displayed lower muscular protein content accompanied by elevated monocyte chemotactic protein-1, IL-6, and IL-1β concentrations. Phosphorylation of NF-κBp65 (Ser(536)) and expression of the catabolic E3 ligase muscle ring finger 1 (MuRF1) were increased in HF offspring, an effect reversed by maternal CLA supplementation. The present study demonstrates the importance of early life interventions to ameliorate the negative effects of poor maternal diet on offspring skeletal muscle development. PMID:26632603

  8. Too risky to settle: avian community structure changes in response to perceived predation risk on adults and offspring

    USGS Publications Warehouse

    Hua, Fangyuan; Fletcher, Robert J.; Sieving, Kathryn E.; Dorazio, Robert M.

    2013-01-01

    Predation risk is widely hypothesized as an important force structuring communities, but this potential force is rarely tested experimentally, particularly in terrestrial vertebrate communities. How animals respond to predation risk is generally considered predictable from species life-history and natural-history traits, but rigorous tests of these predictions remain scarce. We report on a large-scale playback experiment with a forest bird community that addresses two questions: (i) does perceived predation risk shape the richness and composition of a breeding bird community? And (ii) can species life-history and natural-history traits predict prey community responses to different types of predation risk? On 9 ha plots, we manipulated cues of three avian predators that preferentially prey on either adult birds or offspring, or both, throughout the breeding season. We found that increased perception of predation risk led to generally negative responses in the abundance, occurrence and/or detection probability of most prey species, which in turn reduced the species richness and shifted the composition of the breeding bird community. Species-level responses were largely predicted from the key natural-history trait of body size, but we did not find support for the life-history theory prediction of the relationship between species' slow/fast life-history strategy and their response to predation risk.

  9. Ovarian dysfunctions in adult female rat offspring born to mothers perinatally exposed to low doses of bisphenol A.

    PubMed

    Santamaría, Clarisa; Durando, Milena; Muñoz de Toro, Mónica; Luque, Enrique H; Rodriguez, Horacio A

    2016-04-01

    The study of oral exposure to the environmental estrogen bisphenol A (BPA) during the perinatal period and its effects on ovarian functionality in adulthood has generated special interest. Thus, our objective was to investigate ovarian folliculogenesis and steroidogenesis in adult female rat offspring born to mothers exposed to low doses of BPA (BPA50: 50μg/kgday; BPA0.5: 0.5μg/kgday) by the oral route during gestation and breastfeeding. Ovaries from both BPA-treated groups showed reduced primordial follicle recruitment and a greater number of corpora lutea, indicating an increased number of ovulated oocytes, coupled with higher levels of mRNA expression of 3β-hydroxysteroid dehydrogenase and serum progesterone. BPA50-treated animals had lower expression of androgen receptor (AR) at different stages of the growing follicle population. BPA0.5-treated rats evidenced an imbalance of AR expression between primordial/primary follicles, with higher mRNA-follicle-stimulating hormone receptor expression. These results add to the growing evidence that folliculogenesis and steroidogenesis are targets of BPA within the ovary. PMID:26658420

  10. Prenatal Stress Enhances Excitatory Synaptic Transmission and Impairs Long-Term Potentiation in the Frontal Cortex of Adult Offspring Rats

    PubMed Central

    Sowa, Joanna; Bobula, Bartosz; Glombik, Katarzyna; Slusarczyk, Joanna; Basta-Kaim, Agnieszka; Hess, Grzegorz

    2015-01-01

    The effects of prenatal stress procedure were investigated in 3 months old male rats. Prenatally stressed rats showed depressive-like behavior in the forced swim test, including increased immobility, decreased mobility and decreased climbing. In ex vivo frontal cortex slices originating from prenatally stressed animals, the amplitude of extracellular field potentials (FPs) recorded in cortical layer II/III was larger, and the mean amplitude ratio of pharmacologically-isolated NMDA to the AMPA/kainate component of the field potential—smaller than in control preparations. Prenatal stress also resulted in a reduced magnitude of long-term potentiation (LTP). These effects were accompanied by an increase in the mean frequency, but not the mean amplitude, of spontaneous excitatory postsynaptic currents (sEPSCs) in layer II/III pyramidal neurons. These data demonstrate that stress during pregnancy may lead not only to behavioral disturbances, but also impairs the glutamatergic transmission and long-term synaptic plasticity in the frontal cortex of the adult offspring. PMID:25749097

  11. Timing of Maternal Immunization Affects Immunological and Behavioral Outcomes of Adult Offspring in Siberian Hamsters (Phodopus sungorus).

    PubMed

    French, Susannah S; Chester, Emily M; Demas, Gregory E

    2016-07-01

    Maternal influences are an important contributing factor to offspring survival, development, and behavior. Common environmental pathogens can induce maternal immune responses and affect subsequent development of offspring. There are likely sensitive periods during pregnancy when animals are particularly vulnerable to environmental disruption. Here we characterize the effects of maternal immunization across pregnancy and postpartum on offspring physiology and behavior in Siberian hamsters (Phodopus sungorus). Hamsters were injected with the antigen keyhole limpet hemocyanin (KLH) (1) prior to pairing with a male (premating), (2) at separation (postmating), (3) at midpregnancy, or (4) after birth (lactation). Maternal food intake, body mass, and immunity were monitored throughout gestation, and litters were measured weekly for growth until adulthood when social behavior, hormone concentrations, and immune responses were determined. We found that immunizations altered maternal immunity throughout pregnancy and lactation. The effects of maternal treatment differed between male and female offspring. Aggressive behavior was enhanced in offspring of both sexes born to mothers treated postmating and thus early in pregnancy relative to other stages. In contrast, maternal treatment and maternal stage differentially affected innate immunity in males and females. Offspring cortisol, however, was unaffected by maternal treatment. Collectively, these data demonstrate that maternal immunization affects offspring physiology and behavior in a time-dependent and sex-specific manner. More broadly, these findings contribute to our understanding of the effects of maternal immune activation, whether it be from environmental exposure or immunization, on immunological and behavioral responses of offspring. PMID:27320639

  12. The Association of Maternal Socialization in Childhood and Adolescence with Adult Offsprings' Sympathy/Caring

    ERIC Educational Resources Information Center

    Eisenberg, Nancy; VanSchyndel, Sarah K.; Hofer, Claire

    2015-01-01

    The purpose of the study was to examine associations between mothers' socialization practices in childhood and adolescence and offsprings' (N = 32, 16 female) sympathy/concern in early adulthood. Mothers reported on their socialization practices and beliefs a total of 6 times using a Q-sort during their offsprings' childhood…

  13. Maternal High-Fat Diet-Induced Loss of Fetal Oocytes Is Associated with Compromised Follicle Growth in Adult Rat Offspring.

    PubMed

    Tsoulis, Michael W; Chang, Pauline E; Moore, Caroline J; Chan, Kaitlyn A; Gohir, Wajiha; Petrik, James J; Vickers, Mark H; Connor, Kristin L; Sloboda, Deborah M

    2016-04-01

    Maternal obesity predisposes offspring to metabolic and reproductive dysfunction. We have shown previously that female rat offspring born to mothers fed a high-fat (HF) diet throughout pregnancy and lactation enter puberty early and display aberrant reproductive cyclicity. The mechanisms driving this reproductive phenotype are currently unknown thus we investigated whether changes in ovarian function were involved. Wistar rats were mated and randomized to: dams fed a control diet (CON) or dams fed a HF diet from conception until the end of lactation (HF). Ovaries were collected from fetuses at Embryonic Day (E) 20, and neonatal ovaries at Day 4 (P4), prepubertal ovaries at P27 and adult ovaries at P120. In a subset of offspring, the effects of a HF diet fed postweaning were evaluated. The present study shows that fetuses of mothers fed a HF diet had significantly fewer oocytes at E20, and in neonates, have reduced AMH signaling that may facilitate an increased number of assembled primordial follicles. Both prepubertally and in adulthood, ovaries show increased follicular atresia. As adults, offspring have reduced FSH responsiveness, low expression levels of estrogen receptor alpha (Eralpha), the oocyte-secreted factor, Gdf9, oocyte-specific RNA binding protein, Dazl, and high expression levels of the granulosa-cell derived factor, AMH, in antral follicles. Together, these data suggest that ovarian compromise in offspring born to HF-fed mothers may arise from changes already observable in the fetus and neonate and in the long term, associated with increased follicular atresia through adulthood. PMID:26962114

  14. The effect of maternal low-protein diet on the heart of adult offspring: role of mitochondria and oxidative stress.

    PubMed

    Nascimento, Luciana; Freitas, Cristiane M; Silva-Filho, Reginaldo; Leite, Ana Catarina R; Silva, Alessandra B; da Silva, Aline Isabel; Ferreira, Diorginis Soares; Pedroza, Anderson Apolonio; Maia, Maria Bernadete Souza; Fernandes, Mariana P; Lagranha, Claudia

    2014-08-01

    Protein restriction during perinatal and early postnatal development is associated with a greater incidence of disease in the adult, such arterial hypertension. The aim in the present study was to investigate the effect of maternal low-protein diet on mitochondrial oxidative phosphorylation capacity, mitochondrial reactive oxygen species (ROS) formation, antioxidant levels (enzymatic and nonenzymatic), and oxidative stress levels on the heart of the adult offspring. Pregnant Wistar rats received either 17% casein (normal protein, NP) or 8% casein (low protein, LP) throughout pregnancy and lactation. After weaning male progeny of these NP or LP fed rats, females were maintained on commercial chow (Labina-Purina). At 100 days post-birth, the male rats were sacrificed and heart tissue was harvested and stored at -80 °C. Our results show that restricting protein consumption in pregnant females induced decreased mitochondrial oxidative phosphorylation capacity (51% reduction in ADP-stimulated oxygen consumption and 49.5% reduction in respiratory control ratio) in their progeny when compared with NP group. In addition, maternal low-protein diet induced a significant decrease in enzymatic antioxidant capacity (37.8% decrease in superoxide dismutase activity; 42% decrease in catalase activity; 44.8% decrease in glutathione-S-transferase activity; 47.9% decrease in glutathione reductase; 25.7% decrease in glucose-6 phosphate dehydrogenase) and glutathione level (34.8% decrease) when compared with control. From these findings, we hypothesize that an increased production of ROS and decrease in antioxidant activity levels induced by protein restriction during development could potentiate the progression of metabolic and cardiac diseases in adulthood. PMID:24905448

  15. Childhood Risk Factors for Young Adult Substance Dependence Outcome in Offspring from Multiplex Alcohol Dependence Families: A Prospective Study

    PubMed Central

    Hill, Shirley Y.; Steinhauer, Stuart R.; Locke-Wellman, Jeannette; Ulrich, Richard

    2012-01-01

    Background Age of onset to begin drinking is a known risk factor for alcohol dependence. Factors have been identified that contribute to age of onset to begin regular drinking. These include reduced P300, increased postural sway, and personality variation. A longitudinal study spanning childhood to young adulthood provided the opportunity to determine if these same factors would predict the presence and onset of substance use disorders (SUD). Methods Multiplex families were identified through two or more alcohol-dependent brothers. Offspring from these multiplex or control families (n = 133) were followed annually during childhood. Using childhood predictors previously identified as risk factors for age of onset to begin drinking, SUD outcome by young adulthood was modeled. Results Familial risk status was a significant predictor of young adult SUD outcome as a main effect and as an interaction with P300 amplitude recorded before the age of 13. In adolescence (age 15), increased postural sway and familial risk predicted the SUD outcome by age 22. Analysis comparing the presence of one or both risk factors showed that those above the median for sway and below the median for P300 amplitude had substantially increased odds of developing SUD (odds ratio = 8.08 [confidence interval = 1.52– 42.83]). Conclusions Our findings indicate that among the factors predicting age of onset to begin regular drinking, P300 predicts SUD outcome across an 11-year span. The present findings provide the longest follow-up to date demonstrating that neurobiological factors in childhood are among the most salient predictors of young adult SUD outcome. PMID:19640504

  16. Identification and enrichment of colony-forming cells from the adult murine pituitary

    SciTech Connect

    Lepore, D.A.; Roeszler, K.; Wagner, J.; Ross, S.A.; Bauer, K.; Thomas, P.Q. , E-Mail: paul.thomas@mcri.edu.au

    2005-08-01

    Stem and progenitor cells have been identified in many adult tissues including bone marrow, the central nervous system, and skin. While there is direct evidence to indicate the activity of a progenitor cell population in the pituitary gland, this putative subpopulation has not yet been identified. Herein we describe the isolation and characterization of a novel clonogenic cell type in the adult murine pituitary, which we have termed Pituitary Colony-Forming Cells (PCFCs). PCFCs constitute 0.2% of pituitary cells, and generate heterogeneous colonies from single cells. PCFCs exhibit variable proliferative potential, and may exceed 11 population doublings in 14 days. Enrichment of PCFCs to 61.5-fold with 100% recovery can be obtained through the active uptake of the fluorescent dipeptide, {beta}-Ala-Lys-N{epsilon}-AMCA. PCFCs are mostly contained within the large, agranular subpopulation of AMCA{sup +} cells, and constitute 28% of this fraction, corresponding to 140.5-fold enrichment. Interestingly, the AMCA{sup +} population contains rare cells that are GH{sup +} or PRL{sup +}. GH{sup +} cells were also identified in PCFC single cell colonies, suggesting that PCFCs have the potential to differentiate into GH{sup +} cells. Together, these data show that the pituitary contains a rare clonogenic population which may correspond to the somatotrope/lactotrope progenitors suggested by previous experiments.

  17. Self-Reported Hearing Difficulties Among Adults With Normal Audiograms: The Beaver Dam Offspring Study

    PubMed Central

    Tremblay, Kelly L.; Pinto, Alex; Fischer, Mary E.; Klein, Barbara E. K.; Klein, Ronald; Levy, Sarah; Tweed, Ted S.; Cruickshanks, Karen J.

    2016-01-01

    Objective Clinicians encounter patients who report experiencing hearing difficulty (HD) even when audiometric thresholds fall within normal limits. When there is no evidence of audiometric hearing loss, it generates debate over possible biomedical and psychosocial etiologies. It is possible that self-reported HDs relate to variables within and/or outside the scope of audiology. The purpose of this study is to identify how often, on a population basis, people with normal audiometric thresholds self-report HD and to identify factors associated with such HDs. Design This was a cross-sectional investigation of participants in the Beaver Dam Offspring Study. HD was defined as a self-reported HD on a four-item scale despite having pure-tone audiometric thresholds within normal limits (<20 dB HL0.5, 1, 2, 3, 4, 6, 8 kHz bilaterally, at each frequency). Distortion product otoacoustic emissions and word-recognition performance in quiet and with competing messages were also analyzed. In addition to hearing assessments, relevant factors such as sociodemographic and lifestyle factors, environmental exposures, medical history, health-related quality of life, and symptoms of neurological disorders were also examined as possible risk factors. The Center for Epidemiological Studies-Depression was used to probe symptoms associated with depression, and the Medical Outcomes Study Short-Form 36 mental score was used to quantify psychological stress and social and role disability due to emotional problems. The Visual Function Questionnaire-25 and contrast sensitivity test were used to query vision difficulties. Results Of the 2783 participants, 686 participants had normal audiometric thresholds. An additional grouping variable was created based on the available scores of HD (four self-report questions), which reduced the total dataset to n = 682 (age range, 21–67 years). The percentage of individuals with normal audiometric thresholds who self-reported HD was 12.0% (82 of 682). The

  18. Alternatively activated macrophages determine repair of the infarcted adult murine heart

    PubMed Central

    Shiraishi, Manabu; Shintani, Yasunori; Shintani, Yusuke; Ishida, Hidekazu; Saba, Rie; Yamaguchi, Atsushi; Adachi, Hideo; Yashiro, Kenta

    2016-01-01

    Alternatively activated (also known as M2) macrophages are involved in the repair of various types of organs. However, the contribution of M2 macrophages to cardiac repair after myocardial infarction (MI) remains to be fully characterized. Here, we identified CD206+F4/80+CD11b+ M2-like macrophages in the murine heart and demonstrated that this cell population predominantly increases in the infarct area and exhibits strengthened reparative abilities after MI. We evaluated mice lacking the kinase TRIB1 (Trib1–/–), which exhibit a selective depletion of M2 macrophages after MI. Compared with control animals, Trib1–/– mice had a catastrophic prognosis, with frequent cardiac rupture, as the result of markedly reduced collagen fibril formation in the infarct area due to impaired fibroblast activation. The decreased tissue repair observed in Trib1–/– mice was entirely rescued by an external supply of M2-like macrophages. Furthermore, IL-1α and osteopontin were suggested to be mediators of M2-like macrophage–induced fibroblast activation. In addition, IL-4 administration achieved a targeted increase in the number of M2-like macrophages and enhanced the post-MI prognosis of WT mice, corresponding with amplified fibroblast activation and formation of more supportive fibrous tissues in the infarcts. Together, these data demonstrate that M2-like macrophages critically determine the repair of infarcted adult murine heart by regulating fibroblast activation and suggest that IL-4 is a potential biological drug for treating MI. PMID:27140396

  19. Long-Term Survival of Photoreceptors Transplanted into the Adult Murine Neural Retina Requires Immune Modulation

    PubMed Central

    West, Emma L.; Pearson, Rachael A.; Barker, Susie E.; Luhmann, Ulrich F. O.; Maclaren, Robert E.; Barber, Amanda C.; Duran, Yanai; Smith, Alexander J.; Sowden, Jane C.; Ali, Robin R.

    2012-01-01

    Stem cell therapy presents an opportunity to replace photoreceptors that are lost as a result of inherited and age-related degenerative disease. We have previously shown that murine postmitotic rod photoreceptor precursor cells, identified by expression of the rod-specific transcription factor Nrl, are able to migrate into and integrate within the adult murine neural retina. However, their long-term survival has yet to be determined. Here, we found that integrated Nrl.gfp+ve photoreceptors were present up to 12 months post-transplantation, albeit in significantly reduced numbers. Surviving cells had rod-like morphology, including inner/outer segments and spherule synapses. In a minority of eyes, we observed an early, marked reduction in integrated photoreceptors within 1 month post-transplantation, which correlated with increased numbers of amoeboid macrophages, indicating acute loss of transplanted cells due to an inflammatory response. In the majority of transplants, similar numbers of integrated cells were observed between 1 and 2 months post-transplantation. By 4 months, however, we observed a significant decrease in integrated cell survival. Macrophages and T cells were present around the transplantation site, indicating a chronic immune response. Immune suppression of recipients significantly increased transplanted photoreceptor survival, indicating that the loss observed in unsuppressed recipients resulted from T cell-mediated host immune responses. Thus, if immune responses are modulated, correctly integrated transplanted photoreceptors can survive for extended periods of time in hosts with partially mismatched H-2 haplotypes. These findings suggest that autologous donor cells are optimal for therapeutic approaches to repair the neural retina, though with immune suppression nonautologous donors may be effective. PMID:20857496

  20. Alteration of mitochondrial function in adult rat offspring of malnourished dams

    PubMed Central

    Reusens, Brigitte; Theys, Nicolas; Remacle, Claude

    2011-01-01

    Under-nutrition as well as over-nutrition during pregnancy has been associated with the development of adult diseases such as diabetes and obesity. Both epigenetic modifications and programming of the mitochondrial function have been recently proposed to explain how altered intrauterine metabolic environment may produce such a phenotype. This review aims to report data reported in several animal models of fetal malnutrition due to maternal low protein or low calorie diet, high fat diet as well as reduction in placental blood flow. We focus our overview on the β cell. We highlight that, notwithstanding early nutritional events, mitochondrial dysfunctions resulting from different alteration by diet or gender are programmed. This may explain the higher propensity to develop obesity and diabetes in later life. PMID:21954419

  1. Kidney Dysfunction in Adult Offspring Exposed In Utero to Type 1 Diabetes Is Associated with Alterations in Genome-Wide DNA Methylation

    PubMed Central

    Gautier, Jean-François; Porcher, Raphaël; Abi Khalil, Charbel; Bellili-Munoz, Naima; Fetita, Lila Sabrina; Travert, Florence; Choukem, Simeon-Pierre; Riveline, Jean-Pierre; Hadjadj, Samy; Larger, Etienne; Boudou, Philippe; Blondeau, Bertrand; Roussel, Ronan; Ferré, Pascal; Ravussin, Eric; Rouzet, François; Marre, Michel

    2015-01-01

    Background Fetal exposure to hyperglycemia impacts negatively kidney development and function. Objective Our objective was to determine whether fetal exposure to moderate hyperglycemia is associated with epigenetic alterations in DNA methylation in peripheral blood cells and whether those alterations are related to impaired kidney function in adult offspring. Design Twenty nine adult, non-diabetic offspring of mothers with type 1 diabetes (T1D) (case group) were matched with 28 offspring of T1D fathers (control group) for the study of their leukocyte genome-wide DNA methylation profile (27,578 CpG sites, Human Methylation 27 BeadChip, Illumina Infinium). In a subset of 19 cases and 18 controls, we assessed renal vascular development by measuring Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) at baseline and during vasodilatation produced by amino acid infusion. Results Globally, DNA was under-methylated in cases vs. controls. Among the 87 CpG sites differently methylated, 74 sites were less methylated and 13 sites more methylated in cases vs. controls. None of these CpG sites were located on a gene known to be directly involved in kidney development and/or function. However, the gene encoding DNA methyltransferase 1 (DNMT1)—a key enzyme involved in gene expression during early development–was under-methylated in cases. The average methylation of the 74 under-methylated sites differently correlated with GFR in cases and controls. Conclusion Alterations in methylation profile imprinted by the hyperglycemic milieu of T1D mothers during fetal development may impact kidney function in adult offspring. The involved pathways seem to be a nonspecific imprinting process rather than specific to kidney development or function. PMID:26258530

  2. Increased Cardiovascular Reactivity to Acute Stress and Salt-Loading in Adult Male Offspring of Fat Fed Non-Obese Rats

    PubMed Central

    Rudyk, Olena; Makra, Péter; Jansen, Eugene; Shattock, Michael J.; Poston, Lucilla; Taylor, Paul D.

    2011-01-01

    Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11) or lard-enriched (23.6% fat, n = 16) chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old) offspring cardiovascular parameters were measured (radiotelemetry). The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF) and controls (OC). However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; Δ systolic blood pressure (SBP) and Δheart rate (HR)) with a prolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week) male OF demonstrated higher SBP (p<0.05) in the awake phase (night-time) and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli. PMID:22043281

  3. Increased cardiovascular reactivity to acute stress and salt-loading in adult male offspring of fat fed non-obese rats.

    PubMed

    Rudyk, Olena; Makra, Péter; Jansen, Eugene; Shattock, Michael J; Poston, Lucilla; Taylor, Paul D

    2011-01-01

    Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11) or lard-enriched (23.6% fat, n = 16) chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old) offspring cardiovascular parameters were measured (radiotelemetry). The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF) and controls (OC). However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; Δ systolic blood pressure (SBP) and Δheart rate (HR)) with a prolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week) male OF demonstrated higher SBP (p<0.05) in the awake phase (night-time) and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli. PMID:22043281

  4. Gestational and Lactational Exposure to Atrazine via the Drinking Water Causes Specific Behavioral Deficits and Selectively Alters Monoaminergic Systems in C57BL/6 Mouse Dams, Juvenile and Adult Offspring

    PubMed Central

    Krishna, Saritha; Ye, Xiaoqin; Filipov, Nikolay M.

    2014-01-01

    Atrazine (ATR) is one of the most frequently detected pesticides in the U.S. water supply. This study aimed to investigate neurobehavioral and neurochemical effects of ATR in C57BL/6 mouse offspring and dams exposed to a relatively low (3 mg/l, estimated intake 1.4 mg/kg/day) concentration of ATR via the drinking water (DW) from gestational day 6 to postnatal day (PND) 23. Behavioral tests included open field, pole, grip strength, novel object recognition (NOR), forced swim, and marble burying tests. Maternal weight gain and offspring (PND21, 35, and 70) body or brain weights were not affected by ATR. However, ATR-treated dams exhibited decreased NOR performance and a trend toward hyperactivity. Juvenile offspring (PND35) from ATR-exposed dams were hyperactive (both sexes), spent less time swimming (males), and buried more marbles (females). In adult offspring (PND70), the only behavioral change was a sex-specific (females) decreased NOR performance by ATR. Neurochemically, a trend toward increased striatal dopamine (DA) in dams and a significant increase in juvenile offspring (both sexes) was observed. Additionally, ATR exposure decreased perirhinal cortex serotonin in the adult female offspring. These results suggest that perinatal DW exposure to ATR targets the nigrostriatal DA pathway in dams and, especially, juvenile offspring, alters dams’ cognitive performance, induces sex-selective changes involving motor and emotional functions in juvenile offspring, and decreases cognitive ability of adult female offspring, with the latter possibly associated with altered perirhinal cortex serotonin homeostasis. Overall, ATR exposure during gestation and lactation may cause adverse nervous system effects to both offspring and dams. PMID:24913803

  5. Postnatal high-fat diet leads to spatial deficit, obesity, and central and peripheral inflammation in prenatal dexamethasone adult offspring rats.

    PubMed

    Hsieh, Chih-Sung; Li, Shih-Wen; Sheen, Jiunn-Ming; Yu, Hong-Ren; Tiao, Mao-Meng; Tain, You-Lin; Su, Chung-Hao; Huang, Li-Tung

    2016-08-01

    Synthetic glucocorticoids are frequently used in clinical practice for treating pregnant women at risk of preterm delivery, but their long-term effects on the infant brain are largely unknown. Pregnant Sprague-Dawley rats were administered vehicle or dexamethasone between gestational days 14 and 21. Male offspring were then weaned onto either a standard chow or a high-fat diet. The postnatal levels of insulin-like growth factor I (IGF-1), tumor necrosis factor-α (TNF-α), and asymmetric dimethylarginine (ADMA) in the plasma, liver, and brain were examined, as well as the possible effects of prenatal dexamethasone on cognition. We found that a postnatal high-fat diet led to spatial deficits detected by the Morris water maze in adult offspring administered dexamethasone prenatally. The spatial deficit was accompanied by decreased IGF-1 mRNA and increased ADMA levels in the dorsal hippocampus. In peripheral systems, a postnatal high-fat diet resulted in decreased plasma IGF-1, increased plasma corticosterone, increased concentrations of transaminases, TNF-α mRNA, and ADMA in the liver, and associated obesity in adult offspring administered prenatal dexamethasone. In conclusion, a postnatal high-fat diet led to spatial deficits, obesity, and altered levels of IGF-1, TNF-α, and ADMA in the plasma, liver, or brain. PMID:27272689

  6. Appraisals of discriminatory events among adult offspring of Indian residential school survivors: the influences of identity centrality and past perceptions of discrimination.

    PubMed

    Bombay, Amy; Matheson, Kimberly; Anisman, Hymie

    2014-01-01

    As part of a government policy of assimilation beginning in the mid-1800s, a large proportion of Aboriginal children in Canada were forcibly removed from their homes to attend Indian Residential Schools (IRSs), a practice which continued into the 1990s. This traumatic experience had lasting negative effects not only on those who attended but also on their offspring, who were previously found to report higher levels of perceived discrimination and depressive symptoms compared with Aboriginal adults whose families were not directly affected by IRSs. In attempt to elucidate the processes involved in these previous findings, the current study (N = 399) revealed that greater levels of past perceptions of discrimination among IRS offspring, together with their greater likelihood of considering their Aboriginal heritage to be a central component of their self-concept (i.e., high identity centrality), were associated with an increased likelihood of appraising subsequent negative intergroup scenarios to be a result of discrimination and as threatening to their well-being. In turn, these altered appraisals of threat in response to the scenarios were associated with higher levels of depressive symptoms relative to non-IRS adults. The apparent reinforcing relationships between past discrimination, identity centrality, and appraisals of discrimination and threat in intergroup interactions highlight the need for interventions targeting this cycle that appears to contribute to heightened psychological distress among offspring of those who were directly victimized by collective race-based traumas. PMID:23834257

  7. Maternal dietary loads of α-tocopherol depress protein kinase C signaling and synaptic plasticity in rat postnatal developing hippocampus and promote permanent deficits in adult offspring.

    PubMed

    Betti, Michele; Ambrogini, Patrizia; Minelli, Andrea; Floridi, Alessandro; Lattanzi, Davide; Ciuffoli, Stefano; Bucherelli, Corrado; Prospero, Emilia; Frontini, Andrea; Santarelli, Lory; Baldi, Elisabetta; Benetti, Fernando; Galli, Francesco; Cuppini, Riccardo

    2011-01-01

    Vitamin E (α-tocopherol) supplementation has been tested as prophylaxis against gestational disorders associated with oxidative damage. However, recent evidence showing that high maternal α-tocopherol intake can adversely affect offspring development raises concerns on the safety of vitamin E extradosages during pregnancy. Besides acting as an antioxidant, α-tocopherol depresses cell proliferation and modulates cell signaling through inhibiting protein kinase C (PKC), a kinase that is deeply involved in neural maturation and plasticity. Possible effects of α-tocopherol loads in the maturing brain, where PKC dysregulation is associated to developmental dysfunctions, are poorly known. Here, supranutritional doses of α-tocopherol were fed to pregnant and lactating dams to evaluate the effects on PKC signaling and morphofunctional maturation in offspring hippocampus. Results showed that maternal supplementation potentiates hippocampal α-tocopherol incorporation in offspring and leads to marked decrease of PKC phosphorylation throughout postnatal maturation, accompanied by reduced phosphorylation of growth-associated protein-43 and myristoylated alanine-rich C kinase substrate, two PKC substrates involved in neural development and plasticity. Although processes of neuronal maturation, synapse formation and targeting appeared unaffected, offspring of supplemented mothers displayed a marked reduction of long-term synaptic plasticity in juvenile hippocampus. Interestingly, this impairment persisted in adulthood, when a deficit in hippocampus-dependent, long-lasting spatial memory was also revealed. In conclusion, maternal supplementation with elevated doses of α-tocopherol can influence cell signaling and synaptic plasticity in developing hippocampus and promotes permanent adverse effects in adult offspring. The present results emphasize the need to evaluate the safety of supranutritional maternal intake of α-tocopherol in humans. PMID:20382010

  8. Excess omega-3 fatty acid consumption by mothers during pregnancy and lactation caused shorter life span and abnormal ABRs in old adult offspring.

    PubMed

    Church, M W; Jen, K-L C; Anumba, J I; Jackson, D A; Adams, B R; Hotra, J W

    2010-01-01

    Consuming omega-3 fatty acids (omega-3 FA) during pregnancy and lactation is beneficial to fetal and infant development and might reduce the incidence and severity of preterm births by prolonging pregnancy. Consequently, supplementing maternal diets with large amounts of omega-3 FA is gaining acceptance. However, both over- and under-supplementation with omega-3 FA can harm offspring development. Adverse fetal and neonatal conditions in general can enhance age-related neural degeneration, shorten life span and cause other adult-onset disorders. We hypothesized that maternal over- and under-nutrition with omega-3 FA would shorten the offspring's life span and enhance neural degeneration in old adulthood. To test these hypotheses, female Wistar rats were randomly assigned to one of the three diet conditions starting from day 1 of pregnancy through the entire period of pregnancy and lactation. The three diets were Control omega-3 FA (omega-3/omega-6 ratio approximately 0.14), Excess omega-3 FA (omega-3/omega-6 ratio approximately 14.5) and Deficient omega-3 FA (omega-3/omega-6 ratio approximately 0% ratio). When possible, one male and female offspring from each litter were assessed for life span and sensory/neural degeneration (n=15 litters/group). The Excess offspring had shorter life spans compared to their Control and Deficient cohorts (mean+/-SEM=506+/-24, 601+/-14 and 585+/-21 days, poffspring had a higher incidence of presbycusis than the Control and Deficient groups (33.3, 4.3 and 4.5%, p=0.011) and a persistence of other sensory/neurological abnormalities and lower body weights in old adulthood. In conclusion, omega-3 FA over-nutrition or imbalance during pregnancy and lactation had adverse effects on life span and sensory/neurological function in old adulthood. The adverse outcomes in the Excess offspring were likely due to a "nutritional toxicity" during fetal and/or neonatal development

  9. Sleep fragmentation during late gestation induces metabolic perturbations and epigenetic changes in adiponectin gene expression in male adult offspring mice.

    PubMed

    Khalyfa, Abdelnaby; Mutskov, Vesco; Carreras, Alba; Khalyfa, Ahamed A; Hakim, Fahed; Gozal, David

    2014-10-01

    Sleep fragmentation (SF) is a common condition among pregnant women, particularly during late gestation. Gestational perturbations promote the emergence of adiposity and metabolic disease risk in offspring, most likely through epigenetic modifications. Adiponectin (AdipoQ) expression inversely correlates with obesity and insulin resistance. The effects of SF during late gestation on metabolic function and AdipoQ expression in visceral white adipose tissue (VWAT) of offspring mice are unknown. Male offspring mice were assessed at 24 weeks after dams were exposed to SF or control sleep during late gestation. Increased food intake, body weight, VWAT mass, and insulin resistance, with reductions in AdipoQ expression in VWAT, emerged in SF offspring. Increased DNMT3a and -b and global DNA methylation and reduced histone acetyltransferase activity and TET1, -2, and -3 expression were detected in VWAT of SF offspring. Reductions in 5-hydroxymethylcytosine and H3K4m3 and an increase in DNA 5-methylcytosine and H3K9m2 in the promoter and enhancer regions of AdipoQ emerged in adipocytes from VWAT and correlated with AdipoQ expression. SF during late gestation induces epigenetic modifications in AdipoQ in male offspring mouse VWAT adipocytes along with a metabolic syndrome-like phenotype. Thus, altered gestational environments elicited by SF impose the emergence of adverse, long-lasting metabolic consequences in the next generation. PMID:24812424

  10. Prenatal nicotine exposure enhances Cx43 and Panx1 unopposed channel activity in brain cells of adult offspring mice fed a high-fat/cholesterol diet

    PubMed Central

    Orellana, Juan A.; Busso, Dolores; Ramírez, Gigliola; Campos, Marlys; Rigotti, Attilio; Eugenín, Jaime; von Bernhardi, Rommy

    2014-01-01

    Nicotine, the most important neuroteratogen of tobacco smoke, can reproduce brain and cognitive disturbances per se when administered prenatally. However, it is still unknown if paracrine signaling among brain cells participates in prenatal nicotine-induced brain impairment of adult offspring. Paracrine signaling is partly mediated by unopposed channels formed by connexins hemichannels (HCs) and pannexins serving as aqueous pores permeable to ions and small signaling molecules, allowing exchange between the intra- and extracellular milieus. Our aim was to address whether prenatal nicotine exposure changes the activity of those channels in adult mice offspring under control conditions or subjected to a second challenge during young ages: high-fat/cholesterol (HFC) diet. To induce prenatal exposure to nicotine, osmotic minipumps were implanted in CF1 pregnant mice at gestational day 5 to deliver nicotine bitartrate or saline (control) solutions. After weaning, offspring of nicotine-treated or untreated pregnant mice were fed ad libitum with chow or HFC diets for 8 weeks. The functional state of connexin 43 (Cx43) and pannexin 1 (Panx1) unopposed channels was evaluated by dye uptake experiments in hippocampal slices from 11-week-old mice. We found that prenatal nicotine increased the opening of Cx43 HCs in astrocytes, and Panx1 channels in microglia and neurons only if offspring mice were fed with HFC diet. Blockade of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2) and prostaglandin E receptor 1 (EP1), ionotropic ATP receptor type 7 (P2X7) and NMDA receptors, showed differential inhibition of prenatal nicotine-induced channel opening in glial cells and neurons. Importantly, inhibition of the above mentioned enzymes and receptors, or blockade of Cx43 and Panx1 unopposed channels greatly reduced adenosine triphosphate (ATP) and glutamate release from hippocampal slices of prenatally nicotine-exposed offspring. We propose that unregulated gliotransmitter

  11. Abnormal neurological responses in young adult offspring caused by excess omega-3 fatty acid (fish oil) consumption by the mother during pregnancy and lactation.

    PubMed

    Church, M W; Jen, K-L C; Jackson, D A; Adams, B R; Hotra, J W

    2009-01-01

    Consuming omega-3 fatty acids (omega-3 FA) during pregnancy and lactation benefits fetal and infant brain development and might reduce the severity of preterm births by prolonging pregnancy. However, diets that are relatively rich in omega-3 FA can adversely affect fetal and infant development and the auditory brainstem response (ABR), a measure of brain development and sensory function. We previously examined the offspring of female rats fed excessive, adequate or deficient amounts of omega-3 FA during pregnancy and lactation. The 24-day-old offspring in the Excess group, compared to the Control group, had postnatal growth retardation and poor hearing acuity and prolonged neural transmission times as evidenced by the ABR. The Deficient group was intermediate. The current study followed these offspring to see if these poor outcomes persisted into young adulthood. Based on prior findings, we hypothesized that the Excess and Deficient offspring would "catch-up" to the Control offspring by young adulthood. Female Wistar rats received one of the three diet conditions from day 1 of pregnancy through lactation. The three diets were the Control omega-3 FA condition (omega-3/omega-6 ratio approximately 0.14), the Excess omega-3 FA condition (omega-3/omega-6 ratio approximately 14.0) and Deficient omega-3 FA condition (omega-3/omega-6 ratio approximately 0% ratio). The Control diet contained 7% soybean oil; whereas the Deficient and Excess omega-3 FA diets contained 7% safflower oil and 7% fish oil, respectively. One male and female offspring per litter were ABR-tested as young adults using tone pip stimuli of 2, 4, 8 and 16 kHz. The postnatal growth retardation and prolonged neural transmission times in the Excess and Deficient pups had dissipated by young adulthood. In contrast, the Excess group had elevated ABR thresholds (hearing loss) at all tone pip frequencies in comparison to the Control and Deficient groups. The Deficient group had worse ABR thresholds than the

  12. The nuclear factor-κB inhibitor pyrrolidine dithiocarbamate reduces polyinosinic-polycytidilic acid-induced immune response in pregnant rats and the behavioral defects of their adult offspring

    PubMed Central

    2011-01-01

    Background Epidemiological studies have indicated that maternal infection during pregnancy may lead to a higher incidence of schizophrenia in the offspring. It is assumed that the maternal infection increases the immune response, leading to neurodevelopmental disorders in the offspring. Maternal polyinosinic-polycytidilic acid (PolyI:C) treatment induces a wide range of characteristics in the offspring mimicking some schizophrenia symptoms in humans. These observations are consistent with the neurodevelopmental hypothesis of schizophrenia. Methods We examined whether suppression of the maternal immune response could prevent neurodevelopmental disorders in adult offspring. PolyI:C or saline was administered to early pregnant rats to mimic maternal infection, and the maternal immune response represented by tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) levels was determined by enzyme-linked immunosorbent assays (ELISA). The NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) was used to suppress the maternal immune response. Neurodevelopmental disorders in adult offspring were examined by prepulse inhibition (PPI), passive avoidance, and active avoidance tests. Results PolyI:C administration to early pregnant rats led to elevated serum cytokine levels as shown by massive increases in serum TNF-α and IL-10 levels. The adult offspring showed defects in prepulse inhibition, and passive avoidance and active avoidance tests. PDTC intervention in early pregnant rats suppressed cytokine increases and reduced the severity of neurodevelopmental defects in adult offspring. Conclusions Our findings suggest that PDTC can suppress the maternal immune response induced by PolyI:C and partially prevent neurodevelopmental disorders of adult offspring. PMID:22208616

  13. Paternal High Fat Diet in Rats Leads to Renal Accumulation of Lipid and Tubular Changes in Adult Offspring.

    PubMed

    Chowdhury, Sabiha S; Lecomte, Virginie; Erlich, Jonathan H; Maloney, Christopher A; Morris, Margaret J

    2016-01-01

    Along with diabetes and obesity, chronic kidney disease (CKD) is increasing across the globe. Although some data support an effect of maternal obesity on offspring kidney, the impact of paternal obesity is unknown; thus, we have studied the effect of paternal obesity prior to conception. Male Sprague Dawley rats were fed chow diet or high fat diet (HFD) for 13-14 weeks before mating with chow-fed females. Male offspring were weaned onto chow and killed at 27 weeks for renal gene expression and histology. Fathers on HFD were 30% heavier than Controls at mating. At 27 weeks of age offspring of obese fathers weighed 10% less; kidney triglyceride content was significantly increased (5.35 ± 0.84 vs. 2.99 ± 0.47 μg/mg, p < 0.05, n = 8 litters per group. Histological analysis of the kidney demonstrated signs of tubule damage, with significantly greater loss of brush border, and increased cell sloughing in offspring of obese compared to Control fathers. Acat1, involved in entry of fatty acid for beta-oxidation, was significantly upregulated, possibly to counteract increased triglyceride storage. However other genes involved in lipid metabolism, inflammation and kidney injury showed no changes. Paternal obesity was associated with renal triglyceride accumulation and histological changes in tubules, suggesting a mild renal insult in offspring, who may be at risk of developing CKD. PMID:27563922

  14. Maternal High-Salt Intake During Pregnancy Reprogrammed Renin–Angiotensin System-Mediated Cardiomyocyte Apoptosis in the Adult Offspring Heart

    PubMed Central

    Lv, Juanxiu; Zhang, Peiwen; Zhang, Yujuan; Kuang, Hanzhe; Cao, Li; Wu, Conglong; Jiang, Lin; Li, Dawei; Mao, Caiping

    2014-01-01

    Aims: Excess salt intake during pregnancy may alter fetal organ structures and functions leading to increased risks in the development of cardiovascular diseases in later life. The present study determined whether and how the prenatal high-salt (HS) diets affect renin–angiotensin system (RAS) that may mediate cardiac cell death. Methods and Results: Angiotensin II receptors, AT1 and AT2, protein expression was increased in the myocardium of the offspring exposed to prenatal HS; apoptotic cells appeared in the myocardium of the adult offspring. Mitochondrion was isolated in cell experiments, and the data showed cardiomyocyte apoptosis requiring cytochrome C release. Pretreating H9C2 cells with AT2 agonist CGP42112A induced cell apoptosis in DNA fragments and activated caspase 3. CGP42112A increased mitochondrion cytochrome C release and apoptosis in the cells. Conclusion: Both in vitro and in vivo study demonstrated that cardiomyocyte apoptosis was related to AT2 activation. Prenatal HS diets may reprogram RAS that mediates apoptosis in the offspring myocardium, and AT2 may contribute to cardiomyocyte apoptosis via the cytochrome C release pathway. PMID:23690339

  15. Sex-specific increase in susceptibility to metabolic syndrome in adult offspring after prenatal ethanol exposure with post-weaning high-fat diet.

    PubMed

    He, Zheng; Li, Jing; Luo, Hanwen; Zhang, Li; Ma, Lu; Chen, Liaobin; Wang, Hui

    2015-01-01

    Prenatal ethanol exposure (PEE) is an established risk factor for intrauterine growth retardation. The present study was designed to determine whether PEE can increase the susceptibility of high-fat diet (HFD)-induced metabolic syndrome (MS) in adult offspring in a sex-specific manner, based on a generalized linear model analysis. Pregnant Wistar rats were administered ethanol (4 g/kg.d) from gestational day 11 until term delivery. All offspring were fed either a normal diet or a HFD after weaning and were sacrificed at postnatal week 20, and blood samples were collected. Results showed that PEE reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels but enhanced serum glucose, insulin, insulin resistant index (IRI), triglyceride and total cholesterol (TC) concentrations. Moreover, the analysis showed interactions among PEE, HFD and sex. In the PEE offspring, HFD aggravated the decrease in ACTH and corticosterone levels and further increased serum glucose, insulin, triglyceride and TC levels. The changes of serum ACTH, glucose and IRI levels in the female HFD rats were greater than those in the male HFD rats. Our findings suggest that PEE enhances the susceptibility to MS induced by HFD in a sex-specific manner, which might be primarily associated with the neuroendocrine metabolic programming by PEE. PMID:26631430

  16. Maternal nicotine exposure during lactation alters food preference, anxiety-like behavior and the brain dopaminergic reward system in the adult rat offspring.

    PubMed

    Pinheiro, C R; Moura, E G; Manhães, A C; Fraga, M C; Claudio-Neto, S; Younes-Rapozo, V; Santos-Silva, A P; Lotufo, B M; Oliveira, E; Lisboa, P C

    2015-10-01

    The mesolimbic reward pathway is activated by drugs of abuse and palatable food, causing a sense of pleasure, which promotes further consumption of these substances. Children whose parents smoke are more vulnerable to present addictive-like behavior to drugs and food.We evaluated the association between maternal nicotine exposure during lactation with changes in feeding, behavior and in the dopaminergic reward system. On postnatal day (PN) 2,Wistar rat dams were implanted with minipumps releasing nicotine (N; 6 mg/kg/day, s.c.) or saline (C) for 14 days. On PN150 and PN160, offspring were divided into 4 groups for a food challenge: N and C that received standard chow(SC); and N and C that could freely self-select (SSD) between high-fat and high-sugar diets (HFD and HSD, respectively). Offspring were tested in the elevated plus maze (EPM) and open field (OF) arena on PN152–153. On PN170, offspring were euthanized for central dopaminergic analysis. SSD animals showed an increased food intake compared to SC ones and a preference for HFD. However, N-SSD animals consumed relatively more HSD than C-SSD ones. Regarding behavior, N animals showed an increase in the time spent in the EPM center and a reduction in relative activity in the OF center. N offspring presented lower dopamine receptor (D2R) and transporter (DAT) contents in the nucleus accumbens, and lower D2R in the arcuate nucleus. Postnatal exposure to nicotine increases preference for sugar and anxiety levels in the adult progeny possibly due to a decrease in dopaminergic action in the nucleus accumbens and arcuate nucleus. PMID:26048299

  17. The Proteome of Native Adult Müller Glial Cells From Murine Retina*

    PubMed Central

    Hauser, Alexandra; Lepper, Marlen Franziska; Mayo, Rebecca

    2016-01-01

    To date, the proteomic profiling of Müller cells, the dominant macroglia of the retina, has been hampered because of the absence of suitable enrichment methods. We established a novel protocol to isolate native, intact Müller cells from adult murine retinae at excellent purity which retain in situ morphology and are well suited for proteomic analyses. Two different strategies of sample preparation - an in StageTips (iST) and a subcellular fractionation approach including cell surface protein profiling were used for quantitative liquid chromatography-mass spectrometry (LC-MSMS) comparing Müller cell-enriched to depleted neuronal fractions. Pathway enrichment analyses on both data sets enabled us to identify Müller cell-specific functions which included focal adhesion kinase signaling, signal transduction mediated by calcium as second messenger, transmembrane neurotransmitter transport and antioxidant activity. Pathways associated with RNA processing, cellular respiration and phototransduction were enriched in the neuronal subpopulation. Proteomic results were validated for selected Müller cell genes by quantitative real time PCR, confirming the high expression levels of numerous members of the angiogenic and anti-inflammatory annexins and antioxidant enzymes (e.g. paraoxonase 2, peroxiredoxin 1, 4 and 6). Finally, the significant enrichment of antioxidant proteins in Müller cells was confirmed by measurements on vital retinal cells using the oxidative stress indicator CM-H2DCFDA. In contrast to photoreceptors or bipolar cells, Müller cells were most efficiently protected against H2O2-induced reactive oxygen species formation, which is in line with the protein repertoire identified in the proteomic profiling. Our novel approach to isolate intact glial cells from adult retina in combination with proteomic profiling enabled the identification of novel Müller glia specific proteins, which were validated as markers and for their functional impact in glial

  18. The Proteome of Native Adult Müller Glial Cells From Murine Retina.

    PubMed

    Grosche, Antje; Hauser, Alexandra; Lepper, Marlen Franziska; Mayo, Rebecca; von Toerne, Christine; Merl-Pham, Juliane; Hauck, Stefanie M

    2016-02-01

    To date, the proteomic profiling of Müller cells, the dominant macroglia of the retina, has been hampered because of the absence of suitable enrichment methods. We established a novel protocol to isolate native, intact Müller cells from adult murine retinae at excellent purity which retain in situ morphology and are well suited for proteomic analyses. Two different strategies of sample preparation - an in StageTips (iST) and a subcellular fractionation approach including cell surface protein profiling were used for quantitative liquid chromatography-mass spectrometry (LC-MSMS) comparing Müller cell-enriched to depleted neuronal fractions. Pathway enrichment analyses on both data sets enabled us to identify Müller cell-specific functions which included focal adhesion kinase signaling, signal transduction mediated by calcium as second messenger, transmembrane neurotransmitter transport and antioxidant activity. Pathways associated with RNA processing, cellular respiration and phototransduction were enriched in the neuronal subpopulation. Proteomic results were validated for selected Müller cell genes by quantitative real time PCR, confirming the high expression levels of numerous members of the angiogenic and anti-inflammatory annexins and antioxidant enzymes (e.g. paraoxonase 2, peroxiredoxin 1, 4 and 6). Finally, the significant enrichment of antioxidant proteins in Müller cells was confirmed by measurements on vital retinal cells using the oxidative stress indicator CM-H2DCFDA. In contrast to photoreceptors or bipolar cells, Müller cells were most efficiently protected against H2O2-induced reactive oxygen species formation, which is in line with the protein repertoire identified in the proteomic profiling. Our novel approach to isolate intact glial cells from adult retina in combination with proteomic profiling enabled the identification of novel Müller glia specific proteins, which were validated as markers and for their functional impact in glial

  19. The Synergistic Roles of the Chronic Prenatal and Offspring Stress Exposures in Impairing Offspring Learning and Memory.

    PubMed

    Tang, Wei; Cheng, Juan; Wang, Zheng-Yu; Chen, Ke-Yang; Han, Zhen-Min; Wang, Qi-Hong; Yao, Yu-You

    2016-04-23

    In Alzheimer's disease (AD), extensive experimental studies have demonstrated a negative impact of chronic stress during various stages of life (including prenatal phase) on some aspects of AD pathology. Nevertheless, presently, few studies have been involved in the learning and memory impairments, as well as neuropathology elicited by the chronic prenatal stress (CPS) and the chronic offspring stress (COS) exposures simultaneously, particularly for the adult male APPswe/PS1dE9 murine offspring. Therefore, the aim of the present study was to investigate the influence of CPS on learning and memory impairments induced by COS in 6-month-old male APPswe/PS1dE9 offspring mice and the related mechanism. Our study firstly demonstrates that 14-day exposure to CPS could exacerbate the learning and memory impairments, as well as neuropathological damages in the CA3 regions of the hippocampus and cortex neurons, which is induced by the 28-day exposure to COS in 6-month-old male APPswe/PS1dE9 offspring mice. In addition, CPS could potentiate the production of AβPP, Aβ42, and corticosterone in 6-month-old male APPswe/PS1dE9 offspring that also suffer COS. In conclusion, our novel findings strongly implicate the synergistic roles of the CPS and COS exposures in impairing offspring learning and memory. Moreover, CPS potentiating the production of Aβ42 might be mediated by glucocorticoids through increasing the expression of APP and BACE1 gene. PMID:27128656

  20. Effects of Maternal Exposure to Cadmium Oxide Nanoparticles During Pregnancy on Maternal and Offspring Kidney Injury Markers Using a Murine Model.

    PubMed

    Blum, Jason L; Edwards, Joshua R; Prozialeck, Walter C; Xiong, Judy Q; Zelikoff, Judith T

    2015-01-01

    Nanoparticles (NP) are pervasive in many areas of modern life, with little known about their potential toxicities. One commercially important NP is cadmium oxide (CdO), which is used to synthesize other Cd-containing NP, such as quantum dots. Cadmium (Cd) is a well-known nephrotoxicant, but the nephrotoxic potential of CdO NP remains unknown, particularly when exposure occurs during pregnancy. Therefore, pregnant CD-1 mice were used to examine the effects of inhaled CdO NP (230 μg CdO NP/m(3)) on maternal and neonatal renal function by examining urinary creatinine and urinary biomarkers of kidney injury, including kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL). Inhalation of CdO NP by dams produced a fivefold increase in urinary Kim-1 with no marked effect on urinary creatinine levels. Kim-1 mRNA expression peaked by gestational day (GD) 10.5, and NGAL expression increased from GD 10.5 to 17.5. In addition, histological analyses revealed proximal tubular pathology at GD 10.5. Neonatal Kim-1 mRNA expression rose between postnatal days (PND) 7 and 14, with mammary glands/milk being the apparent source of Cd for offspring. These studies demonstrate that, similar to what is seen with other Cd forms, Cd associated with inhaled CdO NP results in renal injury to both directly exposed dam and offspring. As commercial uses for nanotechnology continue to expand throughout the world, risks for unintentional exposure in the workplace increase. Given the large number of women in the industrial workforce, care needs to be taken to protect these already vulnerable populations. PMID:26090557

  1. EFFECTS OF MATERNAL EXPOSURE TO CADMIUM OXIDE NANOPARTICLES DURING PREGNANCY ON MATERNAL AND OFFSPRING KIDNEY INJURY MARKERS USING A MURINE MODEL

    PubMed Central

    Blum, Jason L.; Edwards, Joshua R.; Prozialeck, Walter C.; Xiong, Judy Q.; Zelikoff, Judith T.

    2015-01-01

    Nanoparticles (NP) are pervasive in many areas of modern life, with little known about their potential toxicities. One commercially important NP is cadmium oxide (CdO), which is used to synthesize other Cd-containing NP, such as quantum dots. Cadmium (Cd) is a well-known nephrotoxicant, but the nephrotoxic potential of CdO NP remains unknown, particularly when exposure occurs during pregnancy. Therefore, pregnant CD-1 mice were used to examine the effects of inhaled CdO NP (230 μg CdO NP/m3) on maternal and neonatal renal function by examining urinary creatinine and urinary biomarkers of kidney injury, including kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL). Inhalation of CdO NP by dams produced a fivefold increase in urinary Kim-1 with no marked effect on urinary creatinine levels. Kim-1 mRNA expression peaked by gestational day (GD) 10.5, and NGAL expression increased from GD 10.5 to 17.5. In addition, histological analyses revealed proximal tubular pathology at GD 10.5. Neonatal Kim-1 mRNA expression rose between postnatal days (PND) 7 and 14, with mammary glands/milk being the apparent source of Cd for offspring. These studies demonstrate that, similar to what is seen with other Cd forms, Cd associated with inhaled CdO NP results in renal injury to both directly exposed dam and offspring. As commercial uses for nanotechnology continue to expand throughout the world, risks for unintentional exposure in the workplace increase. Given the large number of women in the industrial workforce, care needs to be taken to protect these already vulnerable populations. PMID:26090557

  2. High-Fat Diet During Mouse Pregnancy and Lactation Targets GIP-Regulated Metabolic Pathways in Adult Male Offspring.

    PubMed

    Kruse, Michael; Keyhani-Nejad, Farnaz; Isken, Frank; Nitz, Barbara; Kretschmer, Anja; Reischl, Eva; de las Heras Gala, Tonia; Osterhoff, Martin A; Grallert, Harald; Pfeiffer, Andreas F H

    2016-03-01

    Maternal obesity is a worldwide problem associated with increased risk of metabolic diseases in the offspring. Genetic deletion of the gastric inhibitory polypeptide (GIP) receptor (GIPR) prevents high-fat diet (HFD)-induced obesity in mice due to specific changes in energy and fat cell metabolism. We investigated whether GIP-associated pathways may be targeted by fetal programming and mimicked the situation by exposing pregnant mice to control or HFD during pregnancy (intrauterine [IU]) and lactation (L). Male wild-type (WT) and Gipr(-/-) offspring received control chow until 25 weeks of age followed by 20 weeks of HFD. Gipr(-/-) offspring of mice exposed to HFD during IU/L became insulin resistant and obese and exhibited increased adipose tissue inflammation and decreased peripheral tissue substrate utilization after being reintroduced to HFD, similar to WT mice on regular chow during IU/L. They showed decreased hypothalamic insulin sensitivity compared with Gipr(-/-) mice on control diet during IU/L. DNA methylation analysis revealed increased methylation of CpG dinucleotides and differential transcription factor binding of promoter regions of genes involved in lipid oxidation in the muscle of Gipr(-/-) offspring on HFD during IU/L, which were inversely correlated with gene expression levels. Our data identify GIP-regulated metabolic pathways that are targeted by fetal programming. PMID:26631738

  3. Maternal pelvic size, fetal growth and risk of stroke in adult offspring in a large Swedish cohort.

    PubMed

    Heshmati, A; Chaparro, M P; Koupil, I

    2016-02-01

    Earlier research suggests that maternal pelvic size is associated with offspring's stroke risk in later life. We followed 6362 men and women from Uppsala, Sweden, born between 1915 and 1929 from 1964 to 2008 to assess whether maternal pelvic size was associated with incidence of thrombotic stroke (TS), haemorrhagic stroke (HS) and other stroke (OS). Offspring whose mothers had a flat pelvis had lower birth weight and birth-weight-for-gestational-age compared with those who did not. Inverse linear associations of birth-weight-for-gestational-age were observed with TS and OS. Female offspring whose mothers had a flat pelvis had increased risk of TS, but flat pelvis was not associated with other types of stroke. A smaller difference between intercristal and interspinous diameters and a smaller external conjugate diameter were independently associated with HS, whereas no pelvic measurements were associated with OS. We conclude that a smaller pelvis in women may impact the health of their offspring in adulthood. PMID:26441399

  4. Interesterified fat or palm oil as substitutes for partially hydrogenated fat during the perinatal period produces changes in the brain fatty acids profile and increases leukocyte-endothelial interactions in the cerebral microcirculation from the male offspring in adult life.

    PubMed

    Misan, Vanessa; Estato, Vanessa; de Velasco, Patricia Coelho; Spreafico, Flavia Brasil; Magri, Tatiana; Dos Santos, Raísa Magno de Araújo Ramos; Fragoso, Thaiza; Souza, Amanda S; Boldarine, Valter Tadeu; Bonomo, Isabela T; Sardinha, Fátima L C; Oyama, Lila M; Tibiriçá, Eduardo; Tavares do Carmo, Maria das Graças

    2015-08-01

    We investigated whether maternal intake of normolipidic diets with distinct fatty acid (FA) compositions alters the lipidic profile and influences the inflammatory status of the adult offsprings׳ brains. C57BL/6 female mice during pregnancy and lactation received diets containing either soybean oil (CG), partially hydrogenated vegetable fat rich in trans-fatty acids (TG), palm oil (PG), or interesterified fat (IG). After weaning, male offspring from all groups received control diet. The FA profile was measured in the offspring׳s brains at post-natal days 21 and 90. Brain functional capillary density as well as leukocyte-endothelial interactions in the cerebral post-capillary venules was assessed by intravital fluorescence microscopy at post-natal day 90. Inflammation signaling was evaluated through toll-like receptor 4 (TLR4) content in brain of the adult offspring. In the 21-day old offspring, the brains of the TG showed higher levels of trans FA and reduced levels of linoleic acid (LA) and total n-6 polyunsaturated fatty acids (PUFA). At post-natal day 90, TG and IG groups showed reduced levels of eicosapentaenoic acid (EPA) and total n-3 PUFA tended to be lower compared to CG. The offspring׳s brains exhibited an altered microcirculation with increased leukocyte rolling in groups TG, PG and IG and in TG group increased leukocyte adhesion. The TLR4 content of TG, IG and PG groups only tended to increase (23%; 20% and 35%, respectively). Maternal consumption of trans FA, palm oil or interesterified fat during pregnancy and lactation can trigger the initial steps of inflammatory pathways in the brain of offspring in adulthood. PMID:25982597

  5. Maternal diet-induced obesity programs cardiovascular dysfunction in adult male mouse offspring independent of current body weight.

    PubMed

    Blackmore, Heather L; Niu, Youguo; Fernandez-Twinn, Denise S; Tarry-Adkins, Jane L; Giussani, Dino A; Ozanne, Susan E

    2014-10-01

    Obese pregnancies are not only associated with adverse consequences for the mother but also the long-term health of her child. Human studies have shown that individuals from obese mothers are at increased risk of premature death from cardiovascular disease (CVD), but are unable to define causality. This study aimed to determine causality using a mouse model of maternal diet-induced obesity. Obesity was induced in female C57BL/6 mice by feeding a diet rich in simple sugars and saturated fat 6 weeks prior to pregnancy and throughout pregnancy and lactation. Control females were fed laboratory chow. Male offspring from both groups were weaned onto chow and studied at 3, 5, 8, and 12 weeks of age for gross cardiac morphometry using stereology, cardiomyocyte cell area by histology, and cardiac fetal gene expression using qRT-PCR. Cardiac function was assessed by isolated Langendorff technology at 12 weeks of age and hearts were analyzed at the protein level for the expression of the β1 adrenergic receptor, muscarinic type-2 acetylcholine receptor, and proteins involved in cardiac contraction. Offspring from obese mothers develop pathologic cardiac hypertrophy associated with re-expression of cardiac fetal genes. By young adulthood these offspring developed severe systolic and diastolic dysfunction and cardiac sympathetic dominance. Importantly, cardiac dysfunction occurred in the absence of any change in corresponding body weight and despite the offspring eating a healthy low-fat diet. These findings provide a causal link to explain human observations relating maternal obesity with premature death from CVD in her offspring. PMID:25051449

  6. Prenatal ethanol exposure induces the osteoarthritis-like phenotype in female adult offspring rats with a post-weaning high-fat diet and its intrauterine programming mechanisms of cholesterol metabolism.

    PubMed

    Ni, Qubo; Wang, Linlong; Wu, Yunpeng; Shen, Lang; Qin, Jun; Liu, Yansong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-10-14

    Osteoarthritis (OA) development is associated with hypercholesterolemia in adults. Our previous study demonstrated that offspring with intrauterine growth retardation (IUGR) due to prenatal ethanol exposure (PEE) had a high risk of developing hypercholesterolemia and metabolic syndrome when fed a post-weaning high-fat diet (HFD). In this study, we examined the changes in articular chondrocytes of IUGR offspring induced by PEE and explored its intrauterine programming mechanisms related to cholesterol metabolism. Using the PEE/IUGR model, serum and tibias from female fetuses and adult female offspring fed a post-weaning HFD were collected and examined for cholesterol metabolism and histology. The results showed that PEE adult offspring manifested significant catch-up growth. Their serum total cholesterol (TCH) and low-density lipoprotein-cholesterol increased and high-density lipoprotein-cholesterol decreased; the osteoarthritis-like phenotype and an increased TCH content were observed in articular cartilage; and the expression of insulin-like growth factor1 (IGF1) and cholesterol efflux pathway, including ATP-binding-cassette transporter A1 and liver X receptor, was reduced. The expression of IGF1 and cholesterol efflux pathway was also lower in the PEE fetuses. This study showed PEE could induce an enhanced susceptibility to HFD-induced OA in adult female IUGR offspring. The underlying mechanism related to cholesterol accumulation in cartilage mediated by intrauterine programming. PMID:26220516

  7. Young Offspring at Genetic Risk of Adult Psychoses: The Form of the Trajectory of IQ or Memory May Orient to the Right Dysfunction at the Right Time

    PubMed Central

    Maziade, Michel; Rouleau, Nancie; Cellard, Caroline; Battaglia, Marco; Paccalet, Thomas; Moreau, Isabel; Gagnon, Valérie; Gingras, Nathalie; Marino, Cecilia; Gilbert, Elsa; Roy, Marc-André; Mérette, Chantal

    2011-01-01

    Objective Neurocognitive dysfunctions analogous to those of adult patients have been detected in children at risk of schizophrenia and bipolar disorder. This led to the following developmental question: Do IQ and memory impairments exhibit different developmental courses from childhood to young adulthood in terms of stability or fluctuations? Methods In a high risk sample, we used a step by step sampling approach to narrow-down the early disease mechanisms. Upstream, we started with a 20-year follow-up of 48 densely affected multigenerational kindreds, including 1500 clinically characterized adult members. We then identified 400 adult members affected by a DSM-IV schizophrenia or bipolar disorder. Downstream, we finally focused on 65 offspring (of an affected parent) aged 7 to 22, who were administered a neuropsychological battery. We then constructed cross-sectional trajectories that were compared to those of controls. Results The childhood IQ deficit displayed a stability until young adulthood. The delay in visual memory exhibited a non-linear two-stage trajectory: a lagging period during childhood followed by a recuperation period from adolescence until adulthood, as supported by a significant Group x Age Periods interaction. No data suggested deterioration between 7 and 22. Conclusion In these offspring at genetic risk, the developmental trajectory of global IQ impairment may not apply to specific domains of cognition such as episodic memory. Different cognitive dysfunctions would mark different developmental courses. The shape of the trajectories might itself have a meaning and provide empirical leads for targeting the right dysfunction at the right time in future prevention research. PMID:21559460

  8. Protein Restriction During the Last Third of Pregnancy Malprograms the Neuroendocrine Axes to Induce Metabolic Syndrome in Adult Male Rat Offspring.

    PubMed

    de Oliveira, Júlio Cezar; Gomes, Rodrigo Mello; Miranda, Rosiane Aparecida; Barella, Luiz Felipe; Malta, Ananda; Martins, Isabela Peixoto; Franco, Claudinéia Conationi da Silva; Pavanello, Audrei; Torrezan, Rosana; Natali, Maria Raquel Marçal; Lisboa, Patrícia Cristina; Mathias, Paulo Cezar de Freitas; de Moura, Egberto Gaspar

    2016-05-01

    Metabolic malprogramming has been associated with low birth weight; however, the interplay between insulin secretion disruption and adrenal function upon lipid metabolism is unclear in adult offspring from protein-malnourished mothers during the last third of gestation. Thus, we aimed to study the effects of a maternal low-protein diet during the last third of pregnancy on adult offspring metabolism, including pancreatic islet function and morphophysiological aspects of the liver, adrenal gland, white adipose tissue, and pancreas. Virgin female Wistar rats (age 70 d) were mated and fed a protein-restricted diet (4%, intrauterine protein restricted [IUPR]) from day 14 of pregnancy until delivery, whereas control dams were fed a 20.5% protein diet. At age 91 d, their body composition, glucose-insulin homeostasis, ACTH, corticosterone, leptin, adiponectin, lipid profile, pancreatic islet function and liver, adrenal gland, and pancreas morphology were assessed. The birth weights of the IUPR rats were 20% lower than the control rats (P < .001). Adult IUPR rats were heavier, hyperphagic, hyperglycemic, hyperinsulinemic, hyperleptinemic, and hypercorticosteronemic (P < .05) with higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol, adiponectin, ACTH, and insulin sensitivity index levels (P < .01). The insulinotropic action of glucose and acetylcholine as well as muscarinic and adrenergic receptor function were impaired in the IUPR rats (P < .05). Maternal undernutrition during the last third of gestation disrupts the pancreatic islet insulinotropic response and induces obesity-associated complications. Such alterations lead to a high risk of metabolic syndrome, characterized by insulin resistance, visceral obesity, and lower high-density lipoprotein cholesterol. PMID:27007071

  9. Early bi-parental separation or neonatal paternal deprivation in mandarin voles reduces adult offspring paternal behavior and alters serum corticosterone levels and neurochemistry.

    PubMed

    Yu, Peng; Zhang, Hui; Li, Xibo; He, Fengqin; Tai, Fadao

    2015-07-01

    Although the effect of early social environments on maternal care in adulthood has been examined in detail, few studies have addressed the long-term effect on paternal care and its underlying neuroendocrine mechanisms. Here, using monogamous mandarin voles (Microtus mandarinus) that show high levels of paternal care, the effects of early bi-parental separation (EBPS) or neonatal paternal deprivation (NPD) on adult paternal behavior, serum corticosterone levels, and receptor mRNA expression in the nucleus accumbens (NAcc) and medial preoptic area (MPOA) were investigated. Compared to the parental care group (PC), we found that EBPS reduced crouching behavior and increased inactivity, self-grooming, and serum corticosterone levels in adult offspring; and NPD significantly reduced retrieval behavior and increased self-grooming behavior of offspring at adulthood. EBPS displayed more dopamine type I receptor (D1R) mRNA expression in the NAcc, but less oxytocin receptor (OTR) mRNA expression than PC in the MPOA. Both EBPS and NPD exhibited more mRNA expression of estrogen receptor alpha (ERα) than PC in the MPOA. In the EBPS group, increased serum corticosterone concentration was closely associated with reduced crouching behavior, and reduced expression of OTR was closely associated with altered crouching behavior and increased D1R expression. Our results provide substantial evidence that EBPS or NPD has long-term consequences and reduces paternal behavior in adult animals. Importantly the oxytocin system in the MPOA might interact with NAcc dopamine systems to regulate paternal behavior and EBPS may affect interactions between the MPOA and NAcc. PMID:26012712

  10. Offspring, 1995.

    ERIC Educational Resources Information Center

    Offspring, 1995

    1995-01-01

    These two 1995 issues of the journal "Offspring," a publication of the Michigan Council of Cooperative Nursery Schools, cover a variety of topics familiar to nursery school and day care providers including the mission of the publication. Articles are short pieces useful to practitioners and are frequently accompanied by classroom activities.…

  11. Offspring, 1996.

    ERIC Educational Resources Information Center

    Rosenthal, Marilynn, Ed.; And Others

    1996-01-01

    These two 1996 issues of the journal "Offspring," a publication of the Michigan Council of Cooperative Nursery Schools, cover a variety of topics familiar to nursery school and day care providers and pertinent to the mission of the publication. Articles are short pieces useful to parents, teachers, and others and aim to provide a forum for views…

  12. Role of cannabinoidergic mechanisms in ethanol self-administration and ethanol seeking in rat adult offspring following perinatal exposure to {delta}{sup 9}-tetrahydrocannabinol

    SciTech Connect

    Economidou, Daina; Mattioli, Laura; Ubaldi, Massimo; Lourdusamy, Anbarasu; Soverchia, Laura; Hardiman, Gary; Campolongo, Patrizia; Cuomo, Vincenzo; Ciccocioppo, Roberto

    2007-08-15

    The present study evaluated the consequences of perinatal {delta}{sup 9}-tetrahydrocannabinol ({delta}{sup 9}-THC) treatment (5 mg/kg/day by gavage), either alone or combined with ethanol (3% v/v as the only fluid available), on ethanol self-administration and alcohol-seeking behavior in rat adult offspring. Furthermore, the effect of the selective cannabinoid CB{sub 1} receptor antagonist, SR-141716A, on ethanol self-administration and on reinstatement of ethanol-seeking behavior induced either by stress or conditioned drug-paired cues was evaluated in adult offspring of rats exposed to the same perinatal treatment. Lastly, microarray experiments were conducted to evaluate if perinatal treatment with {delta}{sup 9}-tetrahydrocannabinol, ethanol or their combination causes long-term changes in brain gene expression profile in rats. The results of microarray data analysis showed that 139, 112 and 170 genes were differentially expressed in the EtOH, {delta}{sup 9}-THC, or EtOH + {delta}{sup 9}-THC group, respectively. No differences in alcohol self-administration and alcohol seeking were observed between rat groups. Intraperitoneal (IP) administration of SR-141716A (0.3-3.0 mg/kg) significantly reduced lever pressing for ethanol and blocked conditioned reinstatement of alcohol seeking. At the same doses SR-141716A failed to block foot-shock stress-induced reinstatement of alcohol seeking. The results reveal that perinatal exposure to {delta}{sup 9}-THC ethanol or their combination results in evident changes in gene expression patterns. However, these treatments do not significantly affect vulnerability to ethanol abuse in adult offspring. On the other hand, the results obtained with SR-141716A emphasize that endocannabinoid mechanisms play a major role in ethanol self-administration, as well as in the reinstatement of ethanol-seeking behavior induced by conditioned cues, supporting the idea that cannabinoid CB{sub 1} receptor antagonists may represent interesting

  13. Lipopolysaccharide exposure during late embryogenesis results in diminished locomotor activity and amphetamine response in females and spatial cognition impairment in males in adult, but not adolescent rat offspring.

    PubMed

    Batinić, Bojan; Santrač, Anja; Divović, Branka; Timić, Tamara; Stanković, Tamara; Obradović, Aleksandar Lj; Joksimović, Srđan; Savić, Miroslav M

    2016-02-15

    Numerous basic and epidemiological studies have connected prenatal maternal immune activation with the occurrence of schizophrenia and/or autism. Depending on subtle differences in protocols of the used animal model, a variety of behavioral abnormalities has been reported. This study investigated behavioral differences in Wistar rat offspring of both genders, exposed to the 100 μg/kg per day dose of lipopolysaccharide (LPS) in late embryogenesis (embryonic days 15 and 16), while tested at their adolescent and young adult age (postnatal days 40 and 60, respectively). Immune activation was confirmed by detecting high levels of TNF-α and IL-6 in dam blood withdrawn 2h after the first dose of LPS. The animals were assessed in three consecutive trials of locomotor activity (novelty exploration, response to i.p. saline injection and challenge with 0.5mg/kg amphetamine), Morris water maze and social interaction tests. Overt behavioral dysfunction was perceived in adult rats only, and these changes were gender-distinctive. When compared with control rats, LPS females displayed baseline hypolocomotion and a decreased reactivity to amphetamine, while LPS males exhibited spatial learning (acquisition trials) and memory (probe trial) impairments. Prenatal treatment did not affect the time spent in social interaction. As maternal exposure to LPS in late gestation resulted in behavioral changes in offspring in early adulthood, it may model schizophrenia-like, but not autism-like endophenotypes. However, lack of a potentiated response to amphetamine testified that this model could not mimic positive symptoms, but rather certain traits of cognitive dysfunction and deficit symptoms, in males and females, respectively. PMID:26620494

  14. A New and Fast Technique to Generate Offspring after Germ Cells Transplantation in Adult Fish: The Nile Tilapia (Oreochromis niloticus) Model

    PubMed Central

    Lacerda, Samyra M. S. N.; Batlouni, Sergio R.; Costa, Guilherme M. J.; Segatelli, Tânia M.; Quirino, Bruno R.; Queiroz, Bruno M.; Kalapothakis, Evanguedes; França, Luiz R.

    2010-01-01

    Background Germ cell transplantation results in fertile recipients and is the only available approach to functionally investigate the spermatogonial stem cell biology in mammals and probably in other vertebrates. In the current study, we describe a novel non-surgical methodology for efficient spermatogonial transplantation into the testes of adult tilapia (O. niloticus), in which endogenous spermatogenesis had been depleted with the cytostatic drug busulfan. Methodology/Principal Findings Using two different tilapia strains, the production of fertile spermatozoa with donor characteristics was demonstrated in adult recipient, which also sired progeny with the donor genotype. Also, after cryopreservation tilapia spermatogonial cells were able to differentiate to spermatozoa in the testes of recipient fishes. These findings indicate that injecting germ cells directly into adult testis facilitates and enable fast generation of donor spermatogenesis and offspring compared to previously described methods. Conclusion Therefore, a new suitable methodology for biotechnological investigations in aquaculture was established, with a high potential to improve the production of commercially valuable fish, generate transgenic animals and preserve endangered fish species. PMID:20505774

  15. Impaired hypothalamic mTOR activation in the adult rat offspring born to mothers fed a low-protein diet.

    PubMed

    Guzmán-Quevedo, Omar; Da Silva Aragão, Raquel; Pérez García, Georgina; Matos, Rhowena J B; de Sa Braga Oliveira, André; Manhães de Castro, Raul; Bolaños-Jiménez, Francisco

    2013-01-01

    Several epidemiological and experimental studies have clearly established that maternal malnutrition induces a high risk of developing obesity and related metabolic diseases in the offspring. To determine if altered nutrient sensing might underlie this enhanced disease susceptibility, here we examined the effects of perinatal protein restriction on the activation of the nutrient sensor mTOR in response to acute variations in the nutritional status of the organism. Female Wistar rats were fed isocaloric diets containing either 17% protein (control) or 8% protein (PR) throughout pregnancy and lactation. At weaning offspring received standard chow and at 4 months of age the effects of fasting or fasting plus re-feeding on the phosphorylation levels of mTOR and its downstream target S6 ribosomal protein (rpS6) in the hypothalamus were assessed by immuno-fluorescence and western blot. Under ad libitum feeding conditions, PR rats exhibited decreased mTOR and rpS6 phosphorylation in the arcuate (ARC) and ventromedial (VMH) hypothalamic nuclei. Moreover, the phosphorylation of mTOR and rpS6 in these hypothalamic nuclei decreased with fasting in control but not in PR animals. Conversely, PR animals exhibited enhanced number of pmTOR imunostained cells in the paraventricular nucleus (PVN) and fasting decreased the activation of mTOR in the PVN of malnourished but not of control rats. These alterations occurred at a developmental stage at which perinatally-undernourished animals do not show yet obesity or glucose intolerance. Collectively, our observations suggest that altered hypothalamic nutrient sensing in response to an inadequate foetal and neonatal energetic environment is one of the basic mechanisms of the developmental programming of metabolic disorders and might play a causing role in the development of the metabolic syndrome induced by malnutrition during early life. PMID:24040371

  16. Hypocellularity in the Murine Model for Down Syndrome Ts65Dn Is Not Affected by Adult Neurogenesis.

    PubMed

    López-Hidalgo, Rosa; Ballestín, Raul; Vega, Jessica; Blasco-Ibáñez, José M; Crespo, Carlos; Gilabert-Juan, Javier; Nácher, Juan; Varea, Emilio

    2016-01-01

    Down syndrome (DS) is caused by the presence of an extra copy of the chromosome 21 and it is the most common aneuploidy producing intellectual disability. Neural mechanisms underlying this alteration may include defects in the formation of neuronal networks, information processing and brain plasticity. The murine model for DS, Ts65Dn, presents reduced adult neurogenesis. This reduction has been suggested to underlie the hypocellularity of the hippocampus as well as the deficit in olfactory learning in the Ts65Dn mice. Similar alterations have also been observed in individuals with DS. To determine whether the impairment in adult neurogenesis is, in fact, responsible for the hypocellularity in the hippocampus and physiology of the olfactory bulb, we have analyzed cell proliferation and neuronal maturation in the two major adult neurogenic niches in the Ts656Dn mice: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Additionally, we carried out a study to determine the survival rate and phenotypic fate of newly generated cells in both regions, injecting 5'BrdU and sacrificing the mice 21 days later, and analyzing the number and phenotype of the remaining 5'BrdU-positive cells. We observed a reduction in the number of proliferating (Ki67 positive) cells and immature (doublecortin positive) neurons in the subgranular and SVZ of Ts65Dn mice, but we did not observe changes in the number of surviving cells or in their phenotype. These data correlated with a lower number of apoptotic cells (cleaved caspase 3 positive) in Ts65Dn. We conclude that although adult Ts65Dn mice have a lower number of proliferating cells, it is compensated by a lower level of cell death. This higher survival rate in Ts65Dn produces a final number of mature cells similar to controls. Therefore, the reduction of adult neurogenesis cannot be held responsible for the neuronal hypocellularity in the hippocampus or for the olfactory learning deficit of Ts65Dn mice. PMID

  17. Maternal influenza viral infection causes schizophrenia-like alterations of 5-HT₂A and mGlu₂ receptors in the adult offspring.

    PubMed

    Moreno, José L; Kurita, Mitsumasa; Holloway, Terrell; López, Javier; Cadagan, Richard; Martínez-Sobrido, Luis; García-Sastre, Adolfo; González-Maeso, Javier

    2011-02-01

    Epidemiological studies indicate that maternal influenza viral infection increases the risk for schizophrenia in the adult offspring. The serotonin and glutamate systems are suspected in the etiology of schizophrenia, as well as in the mechanism of action of antipsychotic drugs. The effects of hallucinogens, such as psilocybin and mescaline, require the serotonin 5-HT(2A) receptor, and induce schizophrenia-like psychosis in humans. In addition, metabotropic glutamate receptor mGlu(2/3) agonists show promise as a new treatment for schizophrenia. Here, we investigated the level of expression and behavioral function of 5-HT(2A) and mGlu(2) receptors in a mouse model of maternal influenza viral infection. We show that spontaneous locomotor activity is diminished by maternal infection with the mouse-adapted influenza A/WSN/33 (H1N1) virus. The behavioral responses to hallucinogens and glutamate antipsychotics are both affected by maternal exposure to influenza virus, with increased head-twitch response to hallucinogens and diminished antipsychotic-like effect of the glutamate agonist. In frontal cortex of mice born to influenza virus-infected mothers, the 5-HT(2A) receptor is upregulated and the mGlu(2) receptor is downregulated, an alteration that may be involved in the behavioral changes observed. Additionally, we find that the cortical 5-HT(2A) receptor-dependent signaling pathways are significantly altered in the offspring of infected mothers, showing higher c-fos, egr-1, and egr-2 expression in response to the hallucinogenic drug DOI. Identifying a biochemical alteration that parallels the behavioral changes observed in a mouse model of prenatal viral infection may facilitate targeting therapies for treatment and prevention of schizophrenia. PMID:21289196

  18. Maternal investment, life-history strategy of the offspring and adult chronic disease risk in South Asian women in the UK

    PubMed Central

    Wells, Jonathan C.K.; Yao, Pallas; Williams, Jane E; Gayner, Rebecca

    2016-01-01

    Background and objectives: Patterns of development predict cardiovascular disease (CVD) risk, and ethnic differences therein, but it remains unclear why apparently ‘adaptive plasticity’ in early life should generate health costs in later life. We hypothesized that offspring receiving low maternal investment during fetal life, the primary period of organogenesis, should predict a shorter reproductive career and develop a fast life-history strategy, prioritizing reproduction over growth and homeostatic maintenance. Methodology: We studied 58 young adult South Asian women living in the UK, a group with high susceptibility to CVD. We obtained gestational age, birth weight (BW) and menarcheal age by recall and measured anthropometry, body composition, resting metabolic rate (RMR) and blood pressure (BP). Results: BW and gestational age were inversely associated with menarcheal age, indicating that lower maternal investment is associated with faster maturation. Menarcheal age was positively associated with height but inversely with adiposity, indicating that rapid maturation prioritizes lipid stores over somatic growth. BW was inversely associated with BP, whereas adiposity was positively associated, indicating that lower maternal investment reduces BP homeostasis. BW was positively associated with RMR, whereas menarche was inversely associated, indicating that maternal investment influences adult metabolism. Conclusions and implications: Supporting our hypothesis, low maternal investment promoted faster life histories, demonstrated by earlier menarche, reduced growth and elevated adiposity. These traits were associated with poorer BP regulation. This is the first study demonstrating strategic adjustment of the balance between reproduction and metabolic health in response to the level of maternal investment during fetal life. PMID:26988862

  19. Interaction of recalled parental ADHD symptoms and rearing behavior with current attachment and emotional dysfunction in adult offspring with ADHD.

    PubMed

    Edel, Marc-Andreas; Juckel, Georg; Brüne, Martin

    2010-06-30

    Research into attachment and emotion regulation has shown that children with ADHD are at risk of developing attachment disorders and emotion regulation disturbances, which in part may be due to the rearing style of their parents. No such data exists for adults with persistent ADHD. We hypothesized that current attachment style and emotion processing of adult patients with ADHD may be influenced by the presence of parental ADHD symptoms when the now adult patients were children, assuming that ADHD symptoms of parents have an impact on their parenting style. We examined recalled parental ADHD symptoms and rearing style as well as current attachment and emotion regulation abilities in a sample of 73 adults with ADHD using several self-rating instruments. Recalled prevalence of ADHD symptoms in the mother, and less so in the father, of adult patients with ADHD was significantly associated with partly adverse parental rearing styles, current attachment problems in romantic partnerships and emotion regulation disturbances compared with adult ADHD patients without possibly affected parent. ADHD symptoms in parents of children with ADHD may present a risk factor for attachment problems and poor emotion regulation when ADHD children are grown. PMID:20452044

  20. Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring

    PubMed Central

    Khalil, Omari S; Pisar, Mazura; Forrest, Caroline M; Vincenten, Maria C J; Darlington, L Gail; Stone, Trevor W

    2014-01-01

    Glutamate receptors for N-methyl-d-aspartate (NMDA) are involved in early brain development. The kynurenine pathway of tryptophan metabolism includes the NMDA receptor agonist quinolinic acid and the antagonist kynurenic acid. We now report that prenatal inhibition of the pathway in rats with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulphonamide (Ro61-8048) produces marked changes in hippocampal neuron morphology, spine density and the immunocytochemical localisation of developmental proteins in the offspring at postnatal day 60. Golgi–Cox silver staining revealed decreased overall numbers and lengths of CA1 basal dendrites and secondary basal dendrites, together with fewer basal dendritic spines and less overall dendritic complexity in the basal arbour. Fewer dendrites and less complexity were also noted in the dentate gyrus granule cells. More neurons containing the nuclear marker NeuN and the developmental protein sonic hedgehog were detected in the CA1 region and dentate gyrus. Staining for doublecortin revealed fewer newly generated granule cells bearing extended dendritic processes. The number of neuron terminals staining for vesicular glutamate transporter (VGLUT)-1 and VGLUT-2 was increased by Ro61-8048, with no change in expression of vesicular GABA transporter or its co-localisation with vesicle-associated membrane protein-1. These data support the view that constitutive kynurenine metabolism normally plays a role in early embryonic brain development, and that interfering with it has profound consequences for neuronal structure and morphology, lasting into adulthood. PMID:24646396

  1. Impact of Diet Composition in Adult Offspring is Dependent on Maternal Diet during Pregnancy and Lactation in Rats

    PubMed Central

    Hallam, Megan C.; Reimer, Raylene A.

    2016-01-01

    The Thrifty Phenotype Hypothesis proposes that the fetus takes cues from the maternal environment to predict its postnatal environment. A mismatch between the predicted and actual environments precipitates an increased risk of chronic disease. Our objective was to determine if, following a high fat, high sucrose (HFS) diet challenge in adulthood, re-matching offspring to their maternal gestational diet would improve metabolic health more so than if there was no previous exposure to that diet. Animals re-matched to a high prebiotic fiber diet (HF) had lower body weight and adiposity than animals re-matched to a high protein (HP) or control (C) diet and also had increased levels of the satiety hormones GLP-1 and PYY (p < 0.05). Control animals, whether maintained throughout the study on AIN-93M, or continued on HFS rather than reverting back to AIN-93M, did not differ from each other in body weight or adiposity. Overall, the HF diet was associated with the most beneficial metabolic phenotype (body fat, glucose control, satiety hormones). The HP diet, as per our previous work, had detrimental effects on body weight and adiposity. Findings in control rats suggest that the obesogenic potential of the powdered AIN-93 diet warrants investigation. PMID:26784224

  2. Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring.

    PubMed

    Khalil, Omari S; Pisar, Mazura; Forrest, Caroline M; Vincenten, Maria C J; Darlington, L Gail; Stone, Trevor W

    2014-05-01

    Glutamate receptors for N-methyl-d-aspartate (NMDA) are involved in early brain development. The kynurenine pathway of tryptophan metabolism includes the NMDA receptor agonist quinolinic acid and the antagonist kynurenic acid. We now report that prenatal inhibition of the pathway in rats with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulphonamide (Ro61-8048) produces marked changes in hippocampal neuron morphology, spine density and the immunocytochemical localisation of developmental proteins in the offspring at postnatal day 60. Golgi-Cox silver staining revealed decreased overall numbers and lengths of CA1 basal dendrites and secondary basal dendrites, together with fewer basal dendritic spines and less overall dendritic complexity in the basal arbour. Fewer dendrites and less complexity were also noted in the dentate gyrus granule cells. More neurons containing the nuclear marker NeuN and the developmental protein sonic hedgehog were detected in the CA1 region and dentate gyrus. Staining for doublecortin revealed fewer newly generated granule cells bearing extended dendritic processes. The number of neuron terminals staining for vesicular glutamate transporter (VGLUT)-1 and VGLUT-2 was increased by Ro61-8048, with no change in expression of vesicular GABA transporter or its co-localisation with vesicle-associated membrane protein-1. These data support the view that constitutive kynurenine metabolism normally plays a role in early embryonic brain development, and that interfering with it has profound consequences for neuronal structure and morphology, lasting into adulthood. PMID:24646396

  3. Carbohydrate-related dietary factors and plasma adiponectin levels in healthy adults in the Framingham Offspring Cohort

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diet may influence circulating adiponectin levels by improving insulin sensitivity. We examined the associations between carbohydrate-related dietary factors and plasma adiponectin levels in healthy adults aged 26–81 y (n= 979 men and 1227 women). Dietary intakes were assessed using a FFQ. Fasting...

  4. In Vitro Colony Assays for Characterizing Tri-potent Progenitor Cells Isolated from the Adult Murine Pancreas.

    PubMed

    Tremblay, Jacob R; LeBon, Jeanne M; Luo, Angela; Quijano, Janine C; Wedeken, Lena; Jou, Kevin; Riggs, Arthur D; Tirrell, David A; Ku, H Teresa

    2016-01-01

    Stem and progenitor cells from the adult pancreas could be a potential source of therapeutic beta-like cells for treating patients with type 1 diabetes. However, it is still unknown whether stem and progenitor cells exist in the adult pancreas. Research strategies using cre-lox lineage-tracing in adult mice have yielded results that either support or refute the idea that beta cells can be generated from the ducts, the presumed location where adult pancreatic progenitors may reside. These in vivo cre-lox lineage-tracing methods, however, cannot answer the questions of self-renewal and multi-lineage differentiation-two criteria necessary to define a stem cell. To begin addressing this technical gap, we devised 3-dimensional colony assays for pancreatic progenitors. Soon after our initial publication, other laboratories independently developed a similar, but not identical, method called the organoid assay. Compared to the organoid assay, our method employs methylcellulose, which forms viscous solutions that allow the inclusion of extracellular matrix proteins at low concentrations. The methylcellulose-containing assays permit easier detection and analyses of progenitor cells at the single-cell level, which are critical when progenitors constitute a small sub-population, as is the case for many adult organ stem cells. Together, results from several laboratories demonstrate in vitro self-renewal and multi-lineage differentiation of pancreatic progenitor-like cells from mice. The current protocols describe two methylcellulose-based colony assays to characterize mouse pancreatic progenitors; one contains a commercial preparation of murine extracellular matrix proteins and the other an artificial extracellular matrix protein known as a laminin hydrogel. The techniques shown here are 1) dissociation of the pancreas and sorting of CD133(+)Sox9/EGFP(+) ductal cells from adult mice, 2) single cell manipulation of the sorted cells, 3) single colony analyses using microfluidic q

  5. Fate Analysis of Adult Hippocampal Progenitors in a Murine Model of Fetal Alcohol Spectrum Disorder (FASD)

    PubMed Central

    Kajimoto, Kenta; Allan, Andrea; Cunningham, Lee Anna

    2013-01-01

    Prenatal alcohol exposure can lead to fetal alcohol spectrum disorder (FASD) and associated behavioral impairments that may be linked to disruptions in adult hippocampal neurogenesis. Social and physical enrichment has been proposed as a potential therapeutic approach toward reversing behavioral deficits associated with FASD and is also a potent stimulator of adult hippocampal neurogenesis. In the present study, we utilized a genetic fate mapping approach in nestin-CreERT2/YFP bitransgenic mice to identify the stage-specific impact of prenatal alcohol exposure on the stepwise maturation of adult hippocampal progenitors. Using a limited alcohol access “drinking-in-the-dark” model of FASD, we confirm previous findings that moderate prenatal alcohol exposure has no effect on adult neurogenesis under standard housing conditions, but abolishes the neurogenic response to enriched environment (EE). Furthermore, we demonstrate that this effect is primarily due to failed EE-mediated survival of postmitotic neurons. Finally, we demonstrate that the neurogenic deficit is associated with impaired spatial pattern recognition, as demonstrated by delayed learning of FASD-EE mice in an A–B contextual discrimination task. These results identify a potential maturational stage-specific mechanism(s) underlying impaired neurogenic function in a preclinical model of FASD, and provide a basis for testing regulatory pathways in this model through conditional and inducible manipulation of gene expression in the adult hippocampal progenitor population. PMID:24040071

  6. Fate analysis of adult hippocampal progenitors in a murine model of fetal alcohol spectrum disorder (FASD).

    PubMed

    Kajimoto, Kenta; Allan, Andrea; Cunningham, Lee Anna

    2013-01-01

    Prenatal alcohol exposure can lead to fetal alcohol spectrum disorder (FASD) and associated behavioral impairments that may be linked to disruptions in adult hippocampal neurogenesis. Social and physical enrichment has been proposed as a potential therapeutic approach toward reversing behavioral deficits associated with FASD and is also a potent stimulator of adult hippocampal neurogenesis. In the present study, we utilized a genetic fate mapping approach in nestin-CreER(T2)/YFP bitransgenic mice to identify the stage-specific impact of prenatal alcohol exposure on the stepwise maturation of adult hippocampal progenitors. Using a limited alcohol access "drinking-in-the-dark" model of FASD, we confirm previous findings that moderate prenatal alcohol exposure has no effect on adult neurogenesis under standard housing conditions, but abolishes the neurogenic response to enriched environment (EE). Furthermore, we demonstrate that this effect is primarily due to failed EE-mediated survival of postmitotic neurons. Finally, we demonstrate that the neurogenic deficit is associated with impaired spatial pattern recognition, as demonstrated by delayed learning of FASD-EE mice in an A-B contextual discrimination task. These results identify a potential maturational stage-specific mechanism(s) underlying impaired neurogenic function in a preclinical model of FASD, and provide a basis for testing regulatory pathways in this model through conditional and inducible manipulation of gene expression in the adult hippocampal progenitor population. PMID:24040071

  7. Hypocellularity in the Murine Model for Down Syndrome Ts65Dn Is Not Affected by Adult Neurogenesis

    PubMed Central

    López-Hidalgo, Rosa; Ballestín, Raul; Vega, Jessica; Blasco-Ibáñez, José M.; Crespo, Carlos; Gilabert-Juan, Javier; Nácher, Juan; Varea, Emilio

    2016-01-01

    Down syndrome (DS) is caused by the presence of an extra copy of the chromosome 21 and it is the most common aneuploidy producing intellectual disability. Neural mechanisms underlying this alteration may include defects in the formation of neuronal networks, information processing and brain plasticity. The murine model for DS, Ts65Dn, presents reduced adult neurogenesis. This reduction has been suggested to underlie the hypocellularity of the hippocampus as well as the deficit in olfactory learning in the Ts65Dn mice. Similar alterations have also been observed in individuals with DS. To determine whether the impairment in adult neurogenesis is, in fact, responsible for the hypocellularity in the hippocampus and physiology of the olfactory bulb, we have analyzed cell proliferation and neuronal maturation in the two major adult neurogenic niches in the Ts656Dn mice: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Additionally, we carried out a study to determine the survival rate and phenotypic fate of newly generated cells in both regions, injecting 5′BrdU and sacrificing the mice 21 days later, and analyzing the number and phenotype of the remaining 5′BrdU-positive cells. We observed a reduction in the number of proliferating (Ki67 positive) cells and immature (doublecortin positive) neurons in the subgranular and SVZ of Ts65Dn mice, but we did not observe changes in the number of surviving cells or in their phenotype. These data correlated with a lower number of apoptotic cells (cleaved caspase 3 positive) in Ts65Dn. We conclude that although adult Ts65Dn mice have a lower number of proliferating cells, it is compensated by a lower level of cell death. This higher survival rate in Ts65Dn produces a final number of mature cells similar to controls. Therefore, the reduction of adult neurogenesis cannot be held responsible for the neuronal hypocellularity in the hippocampus or for the olfactory learning deficit of Ts65Dn mice

  8. Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and its implication in executive functions in adult offspring of alcohol-dependent probands.

    PubMed

    Benzerouk, Farid; Gierski, Fabien; Gorwood, Philip; Ramoz, Nicolas; Stefaniak, Nicolas; Hübsch, Bérengère; Kaladjian, Arthur; Limosin, Frédéric

    2013-06-01

    Impairment of executive functions (EFs) mediated by the prefrontal lobe is regarded as a cognitive endophenotype of alcohol dependence, being observed both in probands and in healthy offspring. Given its impact on the anatomy of the prefrontal cortex, the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism may well be involved in this specific endophenotype. Forty-six healthy adult children of alcoholics (HACA) and 82 healthy controls (HC) took part in the study. All the participants were assessed with the Diagnostic Interview for Genetic Studies, and their family histories of alcohol and substance use were assessed with the Family Informant Schedule and Criteria. The Trail Making Test, Arithmetic Switching Task, Stroop Color-Word Test and Wisconsin Card Sorting Test were administered to assess EFs. An overall executive factor score was calculated using factorial analyses. Genotyping of the BDNF Val66Met polymorphism was performed using the TaqMan® allelic discrimination assay. HACA had significantly lower EFs performance than HC. Genetic analysis showed that BDNF genotype distributions were in Hardy-Weinberg equilibrium in the HACA and HC. Genotype and allele distributions did not differ significantly between the two groups. Participants with the Met allele performed significantly more poorly than participants with the Val allele, and a group by allele interaction was observed, the BDNF Met allele being associated with a poorer executive factor score in the HACA group. These results suggest that the BDNF Val66Met polymorphism may contribute to alcohol dependence vulnerability via lower EFs performance. PMID:23582695

  9. Comparing Sexuality Communication Among Offspring of Teen Parents and Adult Parents: a Different Role for Extended Family

    PubMed Central

    Tracy, Allison J.; Richer, Amanda M.; Erkut, Sumru

    2016-01-01

    This brief report examined teenagers’ sexuality communication with their parents and extended families. It compared who teens of early parents (those who had children when they were adolescents) and teens of later parents (those who were adults when they had children) talk to about sex. Eighth grade students (N=1281) in 24 schools completed survey items about their communication about sex. Structural equation modeling was used to predict communication profiles, while adjusting for the nesting of students within schools. After controlling for teens’ age, gender, race/ethnicity, grades, parent/guardian closeness, and social desirability of survey responses, as well as family status and median family income, results showed that teens of early (teen) parents were more likely than teens of later (adult) parents to talk with both parents and extended family about sex and less likely than later parents to talk only with parents. These findings indicate that realities of teen sexuality communication for teens of early parents may extend beyond a parent-teen model to include extended family. Extended family involvement in educational outreach is a potential untapped resource to support sexual health for teens of early parents. PMID:27499816

  10. Ablating hedgehog signaling in tenocytes during development impairs biomechanics and matrix organization of the adult murine patellar tendon enthesis

    PubMed Central

    Aschbacher‐Smith, Lindsey; Lu, Yinhui; Dyment, Nathaniel A.; Liu, Chia‐Feng; Liu, Han; Wylie, Chris; Rao, Marepalli; Shearn, Jason T.; Rowe, David W.; Kadler, Karl E.; Jiang, Rulang; Butler, David L.

    2015-01-01

    ABSTRACT Restoring the native structure of the tendon enthesis, where collagen fibers of the midsubstance are integrated within a fibrocartilaginous structure, is problematic following injury. As current surgical methods fail to restore this region adequately, engineers, biologists, and clinicians are working to understand how this structure forms as a prerequisite to improving repair outcomes. We recently reported on the role of Indian hedgehog (Ihh), a novel enthesis marker, in regulating early postnatal enthesis formation. Here, we investigate how inactivating the Hh pathway in tendon cells affects adult (12‐week) murine patellar tendon (PT) enthesis mechanics, fibrocartilage morphology, and collagen fiber organization. We show that ablating Hh signaling resulted in greater than 100% increased failure insertion strain (0.10 v. 0.05 mm/mm, p<0.01) as well as sub‐failure biomechanical deficiencies. Although collagen fiber orientation appears overtly normal in the midsubstance, ablating Hh signaling reduces mineralized fibrocartilage by 32%, leading to less collagen embedded within mineralized tissue. Ablating Hh signaling also caused collagen fibers to coalesce at the insertion, which may explain in part the increased strains. These results indicate that Ihh signaling plays a critical role in the mineralization process of fibrocartilaginous entheses and may be a novel therapeutic to promote tendon‐to‐bone healing. © 2015 The Authors. Journal of Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 33:1142–1151, 2015. PMID:25807894

  11. Wnts are dispensable for differentiation and self-renewal of adult murine hematopoietic stem cells

    PubMed Central

    Kabiri, Zahra; Numata, Akihiko; Kawasaki, Akira; Tenen, Daniel G.

    2015-01-01

    Wnt signaling controls early embryonic hematopoiesis and dysregulated β-catenin is implicated in leukemia. However, the role of Wnts and their source in adult hematopoiesis is still unclear, and is clinically important as upstream Wnt inhibitors enter clinical trials. We blocked Wnt secretion in hematopoietic lineages by targeting Porcn, a membrane-bound O-acyltransferase that is indispensable for the activity and secretion of all vertebrate Wnts. Surprisingly, deletion of Porcn in Rosa-CreERT2/PorcnDel, MX1-Cre/PorcnDel, and Vav-Cre/PorcnDel mice had no effects on proliferation, differentiation, or self-renewal of adult hematopoietic stem cells. Targeting Wnt secretion in the bone marrow niche by treatment with a PORCN inhibitor, C59, similarly had no effect on hematopoiesis. These results exclude a role for hematopoietic PORCN-dependent Wnts in adult hematopoiesis. Clinical use of upstream Wnt inhibitors is not likely to be limited by effects on hematopoiesis. PMID:26089398

  12. Antenatal glucocorticoid treatment alters Na+ uptake in renal proximal tubule cells from adult offspring in a sex-specific manner

    PubMed Central

    Su, Yixin; Bi, Jianli; Figueroa, Jorge; Chappell, Mark; Rose, James C.

    2015-01-01

    We have shown a sex-specific effect of fetal programming on Na+ excretion in adult sheep. The site of this effect in the kidney is unknown. Therefore, we tested the hypothesis that renal proximal tubule cells (RPTCs) from adult male sheep exposed to betamethasone (Beta) before birth have greater Na+ uptake than do RPTCs from vehicle-exposed male sheep and that RPTCs from female sheep similarly exposed are not influenced by antenatal Beta. In isolated RPTCs from 1- to 1.5-yr-old male and female sheep, we measured Na+ uptake under basal conditions and after stimulation with ANG II. To gain insight into the mechanisms involved, we also measured nitric oxide (NO) levels, ANG II receptor mRNA levels, and expression of Na+/H+ exchanger 3. Basal Na+ uptake increased more in cells from Beta-exposed male sheep than in cells from vehicle-exposed male sheep (400% vs. 300%, P < 0.00001). ANG II-stimulated Na+ uptake was also greater in cells from Beta-exposed males. Beta exposure did not increase Na+ uptake by RPTCs from female sheep. NO production was suppressed more by ANG II in RPTCs from Beta-exposed males than in RPTCs from either vehicle-exposed male or female sheep. Our data suggest that one site of the sex-specific effect of Beta-induced fetal programming in the kidney is the RPTC and that the enhanced Na+ uptake induced by antenatal Beta in male RPTCs may be related to the suppression of NO in these cells. PMID:25834069

  13. Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection.

    PubMed

    Santos, Patrícia d'Emery Alves; Lorena, Virgínia Maria Barros de; Fernandes, Érica de Souza; Sales, Iana Rafaela Fernandes; Nascimento, Wheverton Ricardo Correia do; Gomes, Yara de Miranda; Albuquerque, Mônica Camelo Pessoa de Azevedo; Costa, Vlaudia Maria Assis; Souza, Valdênia Maria Oliveira de

    2016-02-01

    Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants. PMID:26872339

  14. Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection

    PubMed Central

    Santos, Patrícia d‘Emery Alves; de Lorena, Virgínia Maria Barros; Fernandes, Érica de Souza; Sales, Iana Rafaela Fernandes; do Nascimento, Wheverton Ricardo Correia; Gomes, Yara de Miranda; Albuquerque, Mônica Camelo Pessoa de Azevedo; Costa, Vlaudia Maria Assis; de Souza, Valdênia Maria Oliveira

    2016-01-01

    Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants. PMID:26872339

  15. PDGFRα demarcates the cardiogenic clonogenic Sca1+ stem/progenitor cell in adult murine myocardium

    PubMed Central

    Noseda, Michela; Harada, Mutsuo; McSweeney, Sara; Leja, Thomas; Belian, Elisa; Stuckey, Daniel J.; Abreu Paiva, Marta S.; Habib, Josef; Macaulay, Iain; de Smith, Adam J.; al-Beidh, Farah; Sampson, Robert; Lumbers, R. Thomas; Rao, Pulivarthi; Harding, Sian E.; Blakemore, Alexandra I. F.; Eirik Jacobsen, Sten; Barahona, Mauricio; Schneider, Michael D.

    2015-01-01

    Cardiac progenitor/stem cells in adult hearts represent an attractive therapeutic target for heart regeneration, though (inter)-relationships among reported cells remain obscure. Using single-cell qRT–PCR and clonal analyses, here we define four subpopulations of cardiac progenitor/stem cells in adult mouse myocardium all sharing stem cell antigen-1 (Sca1), based on side population (SP) phenotype, PECAM-1 (CD31) and platelet-derived growth factor receptor-α (PDGFRα) expression. SP status predicts clonogenicity and cardiogenic gene expression (Gata4/6, Hand2 and Tbx5/20), properties segregating more specifically to PDGFRα+ cells. Clonal progeny of single Sca1+ SP cells show cardiomyocyte, endothelial and smooth muscle lineage potential after cardiac grafting, augmenting cardiac function although durable engraftment is rare. PDGFRα− cells are characterized by Kdr/Flk1, Cdh5, CD31 and lack of clonogenicity. PDGFRα+/CD31− cells derive from cells formerly expressing Mesp1, Nkx2-5, Isl1, Gata5 and Wt1, distinct from PDGFRα−/CD31+ cells (Gata5 low; Flk1 and Tie2 high). Thus, PDGFRα demarcates the clonogenic cardiogenic Sca1+ stem/progenitor cell. PMID:25980517

  16. PDGFRα demarcates the cardiogenic clonogenic Sca1+ stem/progenitor cell in adult murine myocardium.

    PubMed

    Noseda, Michela; Harada, Mutsuo; McSweeney, Sara; Leja, Thomas; Belian, Elisa; Stuckey, Daniel J; Abreu Paiva, Marta S; Habib, Josef; Macaulay, Iain; de Smith, Adam J; al-Beidh, Farah; Sampson, Robert; Lumbers, R Thomas; Rao, Pulivarthi; Harding, Sian E; Blakemore, Alexandra I F; Jacobsen, Sten Eirik; Barahona, Mauricio; Schneider, Michael D

    2015-01-01

    Cardiac progenitor/stem cells in adult hearts represent an attractive therapeutic target for heart regeneration, though (inter)-relationships among reported cells remain obscure. Using single-cell qRT-PCR and clonal analyses, here we define four subpopulations of cardiac progenitor/stem cells in adult mouse myocardium all sharing stem cell antigen-1 (Sca1), based on side population (SP) phenotype, PECAM-1 (CD31) and platelet-derived growth factor receptor-α (PDGFRα) expression. SP status predicts clonogenicity and cardiogenic gene expression (Gata4/6, Hand2 and Tbx5/20), properties segregating more specifically to PDGFRα(+) cells. Clonal progeny of single Sca1(+) SP cells show cardiomyocyte, endothelial and smooth muscle lineage potential after cardiac grafting, augmenting cardiac function although durable engraftment is rare. PDGFRα(-) cells are characterized by Kdr/Flk1, Cdh5, CD31 and lack of clonogenicity. PDGFRα(+)/CD31(-) cells derive from cells formerly expressing Mesp1, Nkx2-5, Isl1, Gata5 and Wt1, distinct from PDGFRα(-)/CD31(+) cells (Gata5 low; Flk1 and Tie2 high). Thus, PDGFRα demarcates the clonogenic cardiogenic Sca1(+) stem/progenitor cell. PMID:25980517

  17. Differential vascular permeability along the forebrain ventricular neurogenic niche in the adult murine brain.

    PubMed

    Colín-Castelán, Dannia; Ramírez-Santos, Jesús; Gutiérrez-Ospina, Gabriel

    2016-02-01

    Adult neurogenesis is influenced by blood-borne factors. In this context, greater or lesser vascular permeability along neurogenic niches would expose differentially neural stem cells (NSCs), transit amplifying cells (TACs), and neuroblasts to such factors. Here we evaluate endothelial cell morphology and vascular permeability along the forebrain neurogenic niche in the adult brain. Our results confirm that the subventricular zone (SVZ) contains highly permeable, discontinuous blood vessels, some of which allow the extravasation of molecules larger than those previously reported. In contrast, the rostral migratory stream (RMS) and the olfactory bulb core (OBc) display mostly impermeable, continuous blood vessels. These results imply that NSCs, TACs, and neuroblasts located within the SVZ are exposed more readily to blood-borne molecules, including those with very high molecular weights, than those positioned along the RMS and the OBc, subregions in which every stage of neurogenesis also takes place. These observations suggest that the existence of specialized vascular niches is not a precondition for neurogenesis to occur; specialized vascular beds might be essential for keeping high rates of proliferation and/or differential differentiation of neural precursors located at distinct domains. PMID:26492830

  18. Effect of selenium on methimazole-induced liver damage and oxidative stress in adult rats and their offspring.

    PubMed

    Sefi, Mediha; Ben Amara, Ibtissem; Troudi, Afef; Soudani, Nejla; Hakim, Ahmed; Zeghal, Khaled Mounir; Boudawara, Tahia; Zeghal, Najiba

    2014-08-01

    This study aimed to investigate the protective effect of selenium (Se) on methimazole (MMI; an antithyroid drug)-induced hepatotoxicity in adult rats and their progeny. Female Wistar rats were randomly divided into four groups of six rats in each group: group I served as controls that received standard diet; group II received MMI in drinking water as 250 mg L(-1) and standard diet; group III received both MMI (250 mg L(-1), orally) and Se (0.5 mg kg(-1) of diet); group IV received Se (0.5 mg kg(-1) of diet) as sodium selenite. Treatments were started from the 14th day of pregnancy until day 14 after delivery. Exposure of rats to MMI promoted oxidative stress with an increase in liver malondialdehyde levels, advanced oxidation protein products and protein carbonyl contents and a decrease in the levels of glutathione, nonprotein thiols and vitamin C. A decrease in the activities of liver glutathione peroxidase, superoxide dismutase, catalase and lactate dehydrogenase and in the levels of plasma total protein and albumin was also observed. Plasma transaminase activities and total, direct and indirect bilirubin levels increased. Coadministration of Se through diet improved all biochemical parameters. The histopathological changes confirmed the biochemical results. Therefore, our investigation revealed that Se, a trace element with antioxidant properties, was effective in preventing MMI-induced liver damage. PMID:23047615

  19. Variable Maternal Stress in Rats Alters Locomotor Activity, Social Behavior, and Recognition Memory in the Adult Offspring

    PubMed Central

    Wilson, Christina A.; Terry, Alvin V.

    2013-01-01

    Rats repeatedly exposed to variable prenatal stress (PNS) exhibit behavioral signs that are similar to those manifested in several neuropsychiatric disorders such as deficits in attention and inhibitory control, and impairments in memory-related task performance. The purpose of the study described here was to conduct a comprehensive battery of tests to further characterize the behavioral phenotype of PNS rats as well as to evaluate the sensitivity of the model to therapeutic interventions (i.e., to compounds previously shown to have therapeutic potential in neuropsychiatric disorders). The results of this study indicated that PNS in rats is associated with: 1) increased locomotor activity and stereotypic behaviors, 2) elevated sensitivity to the psychostimulant amphetamine, 3) increased aggressive behaviors toward both adult and juvenile rats and 4) delay-dependent deficits in recognition memory. There was no evidence that PNS rats exhibited deficits in other areas of motor function/learning, sensorimotor gating, spatial learning and memory, social withdrawal, or anhedonia. In addition, the results revealed that the second generation antipsychotic risperidone attenuated amphetamine-related increases in locomotor activity in PNS rats; however, the effect was not sustained over time. Furthermore, deficits in recognition memory in PNS rats were attenuated by the norepinephrine reuptake inhibitor, atomoxetine, but not by the α7 nicotinic acetylcholine receptor partial agonist, GTS-21. This study supports the supposition that important phenomenological similarities exist between rats exposed to PNS and patients afflicted with neuropsychiatric disorders thus further establishing the face validity of the model for evaluating potential therapeutic interventions. PMID:23287801

  20. Pharmacological analysis of epithelial chloride secretion mechanisms in adult murine airways.

    PubMed

    Gianotti, Ambra; Ferrera, Loretta; Philp, Amber R; Caci, Emanuela; Zegarra-Moran, Olga; Galietta, Luis J V; Flores, Carlos A

    2016-06-15

    Defective epithelial chloride secretion occurs in humans with cystic fibrosis (CF), a genetic defect due to loss of function of CFTR, a cAMP-activated chloride channel. In the airways, absence of an active CFTR causes a severe lung disease. In mice, genetic ablation of CFTR function does not result in similar lung pathology. This may be due to the expression of an alternative chloride channel which is activated by calcium. The most probable protein performing this function is TMEM16A, a calcium-activated chloride channel (CaCC). Our aim was to assess the relative contribution of CFTR and TMEM16A to chloride secretion in adult mouse trachea. For this purpose we tested pharmacological inhibitors of chloride channels in normal and CF mice. The amplitude of the cAMP-activated current was similar in both types of animals and was not affected by a selective CFTR inhibitor. In contrast, a CaCC inhibitor (CaCCinh-A01) strongly blocked the cAMP-activated current as well as the calcium-activated chloride secretion triggered by apical UTP. Although control experiments revealed that CaCCinh-A01 also shows inhibitory activity on CFTR, our results indicate that transepithelial chloride secretion in adult mouse trachea is independent of CFTR and that another channel, possibly TMEM16A, performs both cAMP- and calcium-activated chloride transport. The prevalent function of a non-CFTR channel may explain the absence of a defect in chloride transport in CF mice. PMID:27063443

  1. Combined parental obesity augments single-parent obesity effects on hypothalamus inflammation, leptin signaling (JAK/STAT), hyperphagia, and obesity in the adult mice offspring.

    PubMed

    Ornellas, Fernanda; Souza-Mello, Vanessa; Mandarim-de-Lacerda, Carlos Alberto; Aguila, Marcia Barbosa

    2016-01-01

    We aimed to evaluate the effects of maternal and/or paternal obesity on offspring body mass, leptin signaling, appetite-regulating neurotransmitters and local inflammatory markers. C57BL/6 mice received standard chow (SC, lean groups) or high-fat diet (HF, obese groups) starting from one month of age. At three months, HF mice became obese relative to SC mice. They were then mated as follows: lean mother and lean father, lean mother and obese father, obese mother and lean father, and obese mother and obese father. The offspring received the SC diet from weaning until three months of age, when they were sacrificed. In the offspring, paternal obesity did not lead to changes in the Janus kinase (JAK)/signal transducer and activation of the transcription (STAT) pathway or feeding behavior but did induce hypothalamic inflammation. On the other hand, maternal obesity resulted in increased weight gain, hyperleptinemia, decreased leptin OBRb receptor expression, JAK/STAT pathway impairment, and increased SOCS3 signaling in the offspring. In addition, maternal obesity elevated inflammatory markers and altered NPY and POMC expression in the hypothalamus. Interestingly, combined parental obesity exacerbated the deleterious outcomes compared to single-parent obesity. In conclusion, while maternal obesity is known to program metabolic changes and obesity in offspring, the current study demonstrated that obese fathers induce hypothalamus inflammation in offspring, which may contribute to the development of metabolic syndromes in adulthood. PMID:26485293

  2. Glomerular parietal epithelial cells of adult murine kidney undergo EMT to generate cells with traits of renal progenitors.

    PubMed

    Swetha, G; Chandra, Vikash; Phadnis, Smruti; Bhonde, Ramesh

    2011-02-01

    Glomerular parietal epithelial cells (GPECs) are known to revert to embryonic phenotype in response to renal injury. However, the mechanism of de-differentiation in GPECs and the underlying cellular processes are not fully understood. In the present study, we show that cultured GPECs of adult murine kidney undergo epithelial-mesenchymal transition (EMT) to generate cells, which express CD24, CD44 and CD29 surface antigens. Characterization by qRT-PCR and immunostaining of these clonogenic cells demonstrate that they exhibit metastable phenotype with co-expression of both epithelial (cytokeratin-18) and mesenchymal (vimentin) markers. Transcript analysis by qRT-PCR revealed high expression of metanephric mesenchymal (Pax-2, WT-1, Six-1, Eya-1, GDNF) and uteric bud (Hoxb-7, C-Ret) genes in these cells, indicating their bipotent progenitor status. Incubation of GPECs with EMT blocker Prostaglandin E2, resulted in low expression of renal progenitor markers reflecting the correlation between EMT and acquired stemness in these cells. Additional in vitro renal commitment assays confirmed their functional staminality. When injected into E13.5 kidney rudiments, the cells incorporated into the developing kidney primordia and co-culture with E13.5 spinal cord resulted in branching and tubulogenesis in these cells. When implanted under renal capsule of unilaterally nephrectomized mice, these cells differentiated into immature glomeruli and vascular ducts. Our study demonstrates that EMT plays a major role in imparting plasticity to terminally differentiated GPECs by producing metastable cells with traits of kidney progenitors. The present study would improve our understanding on epithelial cell plasticity, furthering our knowledge of its role in renal repair and regeneration. PMID:19840197

  3. Metals and kidney markers in adult offspring of endemic nephropathy patients and controls: a two-year follow-up study

    PubMed Central

    Karmaus, Wilfried; Dimitrov, Plamen; Simeonov, Valeri; Tsolova, Svetla; Bonev, Angel; Georgieva, Rossitza

    2008-01-01

    Background The etiology of Balkan Endemic Nephropathy, (BEN), a tubulointerstitial kidney disease, is unknown. Although this disease is endemic in rural areas of Bosnia, Bulgaria, Croatia, Romania, and Serbia, similar manifestations are reported to occur in other regions, for instance Tunisia and Sri Lanka. A number of explanations have been stated including lignites, aristolochic acid, ochratoxin A, metals, and metalloids. Etiologic claims are often based on one or a few studies without sound scientific evidence. In this systematic study, we tested whether exposures to metals (cadmium and lead) and metalloids (arsenic and selenium) are related to Balkan Endemic Nephropathy. Methods In 2003/04 we recruited 102 adults whose parents had BEN and who resided in one of three communities (Vratza, Bistretz, or Beli Izvor, Bulgaria). A control group comprised of 99 adults having non-BEN hospitalized parents was enrolled in the study during the same time. We conducted face-to-face interviews, ultrasound kidney measurements, and determined kidney function in two consecutive investigations (2003/04 and 2004/05). Metals and metalloids were measured in urine and blood samples. To assess the agreement between these consecutive measurements, we calculated intraclass correlation coefficients. Repeated measurement data were analyzed using mixed models. Results We found that cadmium and arsenic were associated with neither kidney size nor function. Lead had a significant but negligible effect on creatinine clearance. Selenium showed a weak but significant negative association with two of the four kidney parameters, namely creatinine clearance and β2-microglobulin. It was positively related to kidney length. These associations were not restricted to the offspring of BEN patients. Adding credence to these findings are reports showing comparable kidney effects in animals exposed to selenium. Conclusion The findings of this 2-year follow-up study indicate that metals and metalloids do

  4. Dietary early-life exposure to contaminated eels does not impair spatial cognitive performances in adult offspring mice as assessed in the Y-maze and the Morris water maze.

    PubMed

    Dridi, Imen; Leroy, Delphine; Guignard, Cédric; Scholl, Georges; Bohn, Torsten; Landoulsi, Ahmed; Thomé, Jean-Pierre; Eppe, Gauthier; Soulimani, Rachid; Bouayed, Jaouad

    2014-12-01

    Many environmental contaminants are introduced via the diet and may act as neurotoxins and endocrine disrupters, especially influencing growing organisms in early life. The purpose of this study was to examine whether dietary exposure of dams to fish naturally contaminated with xenobiotics, especially with polychlorinated biphenyls (PCBs) and heavy metals (e.g., mercury and lead), resulted in cognitive function deficits in adult offspring mice. Daily, four groups of dams (n = 10/group) ingested standard diet plus paste with/without eels, during gestation and lactation, from gestational day (GD) six until post natal day (PND) 21 (weaning). Dams orally ingested a standardized amount of eel (0.8 mg kg(-1) d(-1)) containing the six non-dioxin-like (NDL) PCBs (Σ6 NDL-PCBs: 28, 52, 101, 138, 153, and 180) at 0, 85, 216, and 400 ng kg(-1) d(-1). Results showed that early-life exposure to contaminated eels did not (compared to non-exposed controls) impair immediate working memory in the Y-maze in the offspring assessed at PND 38. Furthermore, it did not significantly impact spatial learning and retention memory as measured in the Morris water maze in adult offspring mice (PND 120-123). Our results suggest that perinatal exposure to contaminated eels does not affect spatial cognitive performances, as assessed by the Y-maze and Morris water maze at adult age. Adverse effects of xenobiotics reported earlier might be camouflaged by beneficial eel constituents, such as n-3 fatty acids. However, additional studies are needed to differentiate between potential positive and negative effects following consumption of food items both rich in nutrients and contaminants. PMID:25476192

  5. Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

    SciTech Connect

    Ma, Noelle; Nicholson, Catherine J.; Wong, Michael; Holloway, Alison C.; Hardy, Daniel B.

    2014-02-15

    While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced

  6. The impact of parental educational trajectories on their adult offspring's overweight/obesity status: a study of three generations of Swedish men and women.

    PubMed

    Chaparro, M P; Koupil, Ilona

    2014-11-01

    The objective of this study was to investigate the impact of grandparental and parental education and parental educational trajectory on their adult offspring's overweight/obesity. We used register data from the Uppsala Birth Cohort Multigenerational Study, based on a representative cohort born in Sweden 1915-1929 (G1). Our sample included 5122 women and 11,204 men who were grandchildren of G1 (G3), their parents (G2), and grandparents. G3's overweight/obesity (BMI≥25 kg/m2) was based on pre-pregnancy weight/height for women before their first birth (average age=26 years), and measured weight/height at conscription for men (average age=18 years). G1's, G2's, and G3's highest educational attainment was obtained from routine registers and classified as low, intermediate, or high based on respective sample distributions. Parental (G2) educational trajectory was defined as change in education between their own and their highest educated parent (G1), classified into 5 categories: always advantaged (AA), upward trajectory (UT), stable-intermediate (SI), downward trajectory (DT), and always disadvantaged (AD). We used hierarchical gender-stratified logistic regression models adjusted for G3's age, education, year of BMI collection, lineage and G2's year of birth and income. Grandparental and parental education were negatively associated with men's odds of overweight/obesity and parental education affected women's overweight/obesity risk. Furthermore, men and women whose parents belonged to the UT, SI, DT, and AD groups had greater odds of overweight/obesity compared to men and women whose parents belonged to the AA group (adjusted for G3's age, year of BMI collection, lineage, and G2's year of birth). These associations were attenuated when further adjusting for parental income and G3's own education. Socioeconomic inequalities can have long-term consequences and impact the health of future generations. For overweight/obesity in concurrent young cohorts, this inequality

  7. Prenatal stress and early-life exposure to fluoxetine have enduring effects on anxiety and hippocampal BDNF gene expression in adult male offspring.

    PubMed

    Boulle, Fabien; Pawluski, Jodi L; Homberg, Judith R; Machiels, Barbie; Kroeze, Yvet; Kumar, Neha; Steinbusch, Harry W M; Kenis, Gunter; Van den Hove, Daniel L A

    2016-05-01

    With the growing use of selective serotonin reuptake inhibitor medications (SSRIs) for the treatment of depression during the perinatal period, questions have been raised about the longterm impact of these medications on development. We aimed to investigate how developmental SSRI exposure may alter affect-related behaviors and associated molecular processes in offspring using a rodent model of maternal stress and depression. For this purpose, prenatally stressed or non-stressed male offspring were exposed to fluoxetine (5 mg/kg/day) or vehicle, via lactation, until weaning. Primary results show that postnatal fluoxetine exposure differentially altered anxiety-like behavior by increasing anxiety in non-stressed offspring and decreasing anxiety in prenatally stressed offspring. In the hippocampus, developmental fluoxetine exposure decreased BDNF IV and TrkB mRNA expression. Prenatal stress alone also decreased escape behaviors and decreased hippocampal BDNF IV mRNA expression. These data provide important evidence for the long-term programming effects of early-life exposure to SSRIs on brain and behavior. © 2015 Wiley Periodicals, Inc. Dev Psychobiol 58: 427-438, 2016. PMID:26608001

  8. Maternal Exercise during Pregnancy Increases BDNF Levels and Cell Numbers in the Hippocampal Formation but Not in the Cerebral Cortex of Adult Rat Offspring

    ERIC Educational Resources Information Center

    Gomes da Silva, Sérgio; de Almeida, Alexandre Aparecido; Fernandes, Jansen; Lopim, Glauber Menezes; Cabral, Francisco Romero; Scerni, Débora Amado; de Oliveira-Pinto, Ana Virgínia; Lent, Roberto; Arida, Ricardo Mario

    2016-01-01

    Clinical evidence has shown that physical exercise during pregnancy may alter brain development and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF) and absolute cell…

  9. Maternal lipopolysaccharide treatment differentially affects 5-HT(2A) and mGlu2/3 receptor function in the adult male and female rat offspring.

    PubMed

    Wischhof, Lena; Irrsack, Ellen; Dietz, Frank; Koch, Michael

    2015-10-01

    Maternal infection during pregnancy increases the risk for the offspring to develop schizophrenia. However, it is still not fully understood which biochemical mechanisms are responsible for the emergence of neuropsychiatric symptoms following prenatal immune activation. The serotonin (5-hydroxytryptamine, 5-HT) and glutamate system have prominently been associated with the schizophrenia pathophysiology but also with the mechanism of antipsychotic drug actions. Here, we investigated the behavioral and cellular response to 5-HT2A and metabotropic glutamate (mGlu)2/3 receptor stimulation in male and female offspring born to lipopolysaccharide (LPS)-treated mothers. Additionally, we assessed protein expression levels of prefrontal 5-HT2A and mGlu2 receptors. Prenatally LPS-exposed male and female offspring showed locomotor hyperactivity and increased head-twitch behavior in response to the 5-HT2A receptor agonist DOI. In LPS-exposed male offspring, the mGlu2/3 receptor agonist LY379268 failed to reduce DOI-induced prepulse inhibition deficits. In LPS-males, the behavioral changes were further accompanied by enhanced DOI-induced c-Fos protein expression and an up-regulation of prefrontal 5-HT2A receptors. No changes in either 5-HT2A or mGlu2 receptor protein levels were found in female offspring. Our data support the hypothesis of an involvement of maternal infection during pregnancy contributing, at least partially, to the pathology of schizophrenia. Identifying biochemical alterations that parallel the behavioral deficits may help to improve therapeutic strategies in the treatment of this mental illness. Since most studies in rodents almost exclusively include male subjects, our data further contribute to elucidating possible gender differences in the effects of prenatal infection on 5-HT2A and mGlu2/3 receptor function. PMID:26051401

  10. Complex life cycles and offspring provisioning in marine invertebrates.

    PubMed

    Marshall, Dustin J; Keough, Michael J

    2006-10-01

    Offspring size can have pervasive effects throughout an organism's life history. Mothers can make either a few large or many small offspring, and the balance between these extremes is determined by the relationship between offspring size and performance. This relationship in turn is thought to be determined by the offspring's environment. Recently, it has become clear that events in one life-history stage can strongly affect performance in another. Given these strong carryover effects, we asked whether events in the larval phase can change the relationship between offspring size and performance in the adult phase. We manipulated the length of the larval period in the bryozoan Bugula neritina and then examined the relationship between offspring size and various parameters of adult performance under field conditions. We found that despite the adult stage being outplanted into identical conditions, different offspring sizes were predicted to be optimal, depending on the experience of those adults as larvae. This work highlights the fact that the strong phenotypic links between life-history stages may result in optimal offspring size being highly unpredictable for organisms with complex life cycles. PMID:21672775

  11. Perinatal citalopram does not prevent the effect of prenatal stress on anxiety, depressive-like behaviour and serotonergic transmission in adult rat offspring.

    PubMed

    Zohar, Inbar; Shoham, Shai; Weinstock, Marta

    2016-02-01

    It is still not clear whether the selective serotonin reuptake inhibitors frequently prescribed to depressed pregnant women improve the behavioural outcome in their children. The current study investigated whether administration of citalopram to pregnant rats could prevent anxiety and depressive-like behaviour induced by gestational stress in their offspring, and restore the expression of serotonin 1A autoreceptors in GABAergic interneurons in the medial prefrontal cortex and dorsal raphe nuclei in males, and of corticotropin-releasing factor type 2 receptors in GABAergic interneurons in the dorsal raphe nuclei in females. Activation of these receptors modulates serotonergic transmission to target areas and is reduced in a sex-dependent manner by prenatal stress. Citalopram (10 mg/kg/day), administered orally from day 7 of gestation until 21 days postpartum, prevented the increase in anxiety in stressed mothers but did not reduce anxiety and depressive-like behaviour in their offspring and even induced depressive-like behaviour in the offspring of control mothers. Citalopram failed to restore the reduction in the expression of serotonin 1A autoreceptors in the prefrontal cortex of males and in corticotropin-releasing factor type 2 receptors in the dorsal raphe nuclei of females induced by prenatal stress. Prenatal citalopram did not prevent the behavioural changes or reduction in serotonergic transmission to target areas induced by prenatal stress. It had adverse behavioural effects in the offspring of control rats, which, together with the lack of any change in prenatally-stressed rats, may be due to inhibition of the foetal serotonin transporter thereby preventing normal development of the serotonin system. PMID:26669896

  12. Association between maternal age at childbirth and child and adult outcomes in the offspring: a prospective study in five low-income and middle-income countries (COHORTS collaboration)

    PubMed Central

    Fall, Caroline H D; Sachdev, Harshpal Singh; Osmond, Clive; Restrepo-Mendez, Maria Clara; Victora, Cesar; Martorell, Reynaldo; Stein, Aryeh D; Sinha, Shikha; Tandon, Nikhil; Adair, Linda; Bas, Isabelita; Norris, Shane; Richter, Linda M

    2015-01-01

    Summary Background Both young and advanced maternal age is associated with adverse birth and child outcomes. Few studies have examined these associations in low-income and middle-income countries (LMICs) and none have studied adult outcomes in the offspring. We aimed to examine both child and adult outcomes in five LMICs. Methods In this prospective study, we pooled data from COHORTS (Consortium for Health Orientated Research in Transitioning Societies)—a collaboration of five birth cohorts from LMICs (Brazil, Guatemala, India, the Philippines, and South Africa), in which mothers were recruited before or during pregnancy, and the children followed up to adulthood. We examined associations between maternal age and offspring birthweight, gestational age at birth, height-for-age and weight-for-height Z scores in childhood, attained schooling, and adult height, body composition (body-mass index, waist circumference, fat, and lean mass), and cardiometabolic risk factors (blood pressure and fasting plasma glucose concentration), along with binary variables derived from these. Analyses were unadjusted and adjusted for maternal socioeconomic status, height and parity, and breastfeeding duration. Findings We obtained data for 22 188 mothers from the five cohorts, enrolment into which took place at various times between 1969 and 1989. Data for maternal age and at least one outcome were available for 19 403 offspring (87%). In unadjusted analyses, younger (≤19 years) and older (≥35 years) maternal age were associated with lower birthweight, gestational age, child nutritional status, and schooling. After adjustment, associations with younger maternal age remained for low birthweight (odds ratio [OR] 1·18 (95% CI 1·02–1·36)], preterm birth (1·26 [1·03–1·53]), 2-year stunting (1·46 [1·25–1·70]), and failure to complete secondary schooling (1·38 [1·18–1·62]) compared with mothers aged 20–24 years. After adjustment, older maternal age remained

  13. Both Food Restriction and High-Fat Diet during Gestation Induce Low Birth Weight and Altered Physical Activity in Adult Rat Offspring: The “Similarities in the Inequalities” Model

    PubMed Central

    Portella, André Krumel; Benetti, Carla da Silva; Noschang, Cristie; Goldani, Marcelo Zubaran; Silveira, Patrícia Pelufo

    2015-01-01

    We have previously described a theoretical model in humans, called “Similarities in the Inequalities”, in which extremely unequal social backgrounds coexist in a complex scenario promoting similar health outcomes in adulthood. Based on the potential applicability of and to further explore the “similarities in the inequalities” phenomenon, this study used a rat model to investigate the effect of different nutritional backgrounds during gestation on the willingness of offspring to engage in physical activity in adulthood. Sprague-Dawley rats were time mated and randomly allocated to one of three dietary groups: Control (Adlib), receiving standard laboratory chow ad libitum; 50% food restricted (FR), receiving 50% of the ad libitum-fed dam’s habitual intake; or high-fat diet (HF), receiving a diet containing 23% fat. The diets were provided from day 10 of pregnancy until weaning. Within 24 hours of birth, pups were cross-fostered to other dams, forming the following groups: Adlib_Adlib, FR_Adlib, and HF_Adlib. Maternal chow consumption and weight gain, and offspring birth weight, growth, physical activity (one week of free exercise in running wheels), abdominal adiposity and biochemical data were evaluated. Western blot was performed to assess D2 receptors in the dorsal striatum. The “similarities in the inequalities” effect was observed on birth weight (both FR and HF groups were smaller than the Adlib group at birth) and physical activity (both FR_Adlib and HF_Adlib groups were different from the Adlib_Adlib group, with less active males and more active females). Our findings contribute to the view that health inequalities in fetal life may program the health outcomes manifested in offspring adult life (such as altered physical activity and metabolic parameters), probably through different biological mechanisms. PMID:25738800

  14. Face-Emotion Processing in Offspring at Risk for Panic Disorder.

    ERIC Educational Resources Information Center

    Pine, Daniel S.; Klein, Rachel G.; Mannuzza, Salvatore; Moulton, John L., III; Lissek, Shmuel; Guardino, Mary; Woldehawariat, Girma

    2005-01-01

    Objective: Panic disorder (PD) has been linked to perturbed processing of threats. This study tested the hypotheses that offspring of parents with PD and offspring with anxiety disorders display relatively greater sensitivity and attention allocation to fear provocation. Method: Offspring of adults with PD, major depressive disorder (MDD), or no…

  15. Maternal protein restriction induces alterations in hepatic tumor necrosis factor-α/CYP7A1 signaling and disorders regulation of cholesterol metabolism in the adult rat offspring

    PubMed Central

    Liu, Xiaomei; Qi, Ying; Tian, Baoling; Chen, Dong; Gao, Hong; Xi, Chunyan; Xing, Yanlin; Yuan, Zhengwei

    2014-01-01

    It is well recognized that adverse events in utero impair fetal development and lead to the development of obesity and metabolic syndrome in adulthood. To investigate the mechanisms linking impaired fetal growth to increased cholesterol, an important clinical risk factor characterizing the metabolic syndrome and cardiovascular disease, we examined the impact of maternal undernutrition on tumor necrosis factor-α (TNF-α)/c-jun N-terminal kinase (JNK) signaling pathway and the cholesterol 7α-hydroxylase (CYP7A1) expression in the livers of the offspring with a protein restriction model. The male offspring with intrauterine growth restriction (IUGR) caused by the isocaloric low-protein diet showed decreased liver weight at birth and augmented circulation and hepatic cholesterol levels at 40 weeks of age. Maternal undernutrition significantly upregulated cytokine TNF-α expression and JNK phospholytion levels in the livers from fetal age to adulthood. Elevated JNK phospholytion could be linked to downregulated hepatocyte nuclear factor-4α and CYP7A1 expression, subsequently led to higher hepatic cholesterol. This work demonstrated that intrauterine malnutrition-induced IUGR might result in intrinsic disorder in hepatic TNF-α/CYP7A1 signaling, and contribute to the development of hypercholesterolemia in later life. PMID:25120278

  16. In Utero and Lactational Exposure to PCBs in Mice: Adult Offspring Show Altered Learning and Memory Depending on Cyp1a2 and Ahr Genotypes

    PubMed Central

    Curran, Christine P.; Genter, Mary Beth; Patel, Krishna V.; Schaefer, Tori L.; Skelton, Matthew R.; Williams, Michael T.; Vorhees, Charles V.

    2011-01-01

    Background: Both coplanar and noncoplanar polychlorinated biphenyls (PCBs) exhibit neurotoxic effects in animal studies, but individual congeners do not always produce the same effects as PCB mixtures. Humans genetically have > 60-fold differences in hepatic cytochrome P450 1A2 (CYP1A2)-uninduced basal levels and > 12-fold variability in aryl hydrocarbon receptor (AHR)affinity; because CYP1A2 is known to sequester coplanar PCBs and because AHR ligands include coplanar PCBs, both genotypes can affect PCB response. Objectives: We aimed to develop a mouse paradigm with extremes in Cyp1a2 and Ahr genotypes to explore genetic susceptibility to PCB-induced developmental neurotoxicity using an environmentally relevant mixture of PCBs. Methods: We developed a mixture of eight PCBs to simulate human exposures based on their reported concentrations in human tissue, breast milk, and food supply. We previously characterized specific differences in PCB congener pharmacokinetics and toxicity, comparing high-affinity–AHR Cyp1a2 wild-type [Ahrb1_Cyp1a2(+/+)], poor-affinity–AHR Cyp1a2 wild-type [Ahrd_Cyp1a2(+/+)], and high-affinity–AHR Cyp1a2 knockout [Ahrb1_Cyp1a2(–/–)] mouse lines [Curran CP, Vorhees CV, Williams MT, Genter MB, Miller ML, Nebert DW. 2011. In utero and lactational exposure to a complex mixture of polychlorinated biphenyls: toxicity in pups dependent on the Cyp1a2 and Ahr genotypes. Toxicol Sci 119:189–208]. Dams received a mixture of three coplanar and five noncoplanar PCBs on gestational day 10.5 and postnatal day (PND) 5. In the present study we conducted behavioral phenotyping of exposed offspring at PND60, examining multiple measures of learning, memory, and other behaviors. Results: We observed the most significant deficits in response to PCB treatment in Ahrb1_Cyp1a2(–/–) mice, including impaired novel object recognition and increased failure rate in the Morris water maze. However, all PCB-treated genotypes showed significant differences on

  17. Maternal Fat Feeding Augments Offspring Nephron Endowment in Mice

    PubMed Central

    Hokke, Stacey; Puelles, Victor G.; Armitage, James A.; Fong, Karen; Bertram, John F.; Cullen-McEwen, Luise A.

    2016-01-01

    Increasing consumption of a high fat 'Western' diet has led to a growing number of pregnancies complicated by maternal obesity. Maternal overnutrition and obesity have health implications for offspring, yet little is known about their effects on offspring kidney development and renal function. Female C57Bl6 mice were fed a high fat diet (HFD, 21% fat) or matched normal fat diet (NFD, 6% fat) for 6 weeks prior to pregnancy and throughout gestation and lactation. HFD dams were overweight and glucose intolerant prior to mating but not in late gestation. Offspring of NFD and HFD dams had similar body weights at embryonic day (E)15.5, E18.5 and at postnatal day (PN)21. HFD offspring had normal ureteric tree development and nephron number at E15.5. However, using unbiased stereology, kidneys of HFD offspring were found to have 20–25% more nephrons than offspring of NFD dams at E18.5 and PN21. Offspring of HFD dams with body weight and glucose profiles similar to NFD dams prior to pregnancy also had an elevated nephron endowment. At 9 months of age, adult offspring of HFD dams displayed mild fasting hyperglycaemia but similar body weights to NFD offspring. Renal function and morphology, measured by transcutaneous clearance of FITC-sinistrin and stereology respectively, were normal. This study demonstrates that maternal fat feeding augments offspring nephron endowment with no long-term consequences for offspring renal health. Future studies assessing the effects of a chronic stressor on adult mice with augmented nephron number are warranted, as are studies investigating the molecular mechanisms that result in high nephron endowment. PMID:27547968

  18. Maternal Fat Feeding Augments Offspring Nephron Endowment in Mice.

    PubMed

    Hokke, Stacey; Puelles, Victor G; Armitage, James A; Fong, Karen; Bertram, John F; Cullen-McEwen, Luise A

    2016-01-01

    Increasing consumption of a high fat 'Western' diet has led to a growing number of pregnancies complicated by maternal obesity. Maternal overnutrition and obesity have health implications for offspring, yet little is known about their effects on offspring kidney development and renal function. Female C57Bl6 mice were fed a high fat diet (HFD, 21% fat) or matched normal fat diet (NFD, 6% fat) for 6 weeks prior to pregnancy and throughout gestation and lactation. HFD dams were overweight and glucose intolerant prior to mating but not in late gestation. Offspring of NFD and HFD dams had similar body weights at embryonic day (E)15.5, E18.5 and at postnatal day (PN)21. HFD offspring had normal ureteric tree development and nephron number at E15.5. However, using unbiased stereology, kidneys of HFD offspring were found to have 20-25% more nephrons than offspring of NFD dams at E18.5 and PN21. Offspring of HFD dams with body weight and glucose profiles similar to NFD dams prior to pregnancy also had an elevated nephron endowment. At 9 months of age, adult offspring of HFD dams displayed mild fasting hyperglycaemia but similar body weights to NFD offspring. Renal function and morphology, measured by transcutaneous clearance of FITC-sinistrin and stereology respectively, were normal. This study demonstrates that maternal fat feeding augments offspring nephron endowment with no long-term consequences for offspring renal health. Future studies assessing the effects of a chronic stressor on adult mice with augmented nephron number are warranted, as are studies investigating the molecular mechanisms that result in high nephron endowment. PMID:27547968

  19. Psychiatric Disorders in Preschool Offspring of Parents with Bipolar Disorder

    PubMed Central

    Birmaher, Boris; Axelson, David; Goldstein, Benjamin; Monk, Kelly; Kalas, Catherine; Obreja, Mihaela; Hickey, Mary Beth; Iyengar, Satish; Brent, David; Shamseddeen, Wael; Diler, Rasim; Kupfer, David

    2010-01-01

    Objective To evaluate lifetime prevalence and specificity of DSM-IV psychiatric disorders and severity of depressive and manic symptoms at intake in preschool offspring of parents with Disorder I–II. Methods 121 offspring ages 2–5 years old of 83 parents with Bipolar Disorder and 102 offspring of 65 demographically matched control parents (29 with non-Bipolar psychiatric disorders and 36 without any lifetime psychopathology) were recruited. Parents with Bipolar Disorder were recruited through advertisement and adult outpatient clinics and control parents were ascertained at random from the community. Subjects were evaluated with standardized instruments. All staff were blind to parental diagnoses. Results After adjusting for within-family correlations and both biological parents’ non-Bipolar psychopathology, compared to the offspring of the control parents, offspring of parents with Bipolar Disorder, particularly those older than 4 years old, showed an 8-fold increased life-time prevalence of Attention Deficit Hyperactive Disorder (ADHD) and significantly higher rates of ≥ 2 psychiatric disorders. While only 3 offspring of parents with Bipolar Disorder had mood disorders, offspring of parents with Bipolar Disorder, especially those with ADHD and Oppositional-Defiant Disorder, had significantly more severe current manic and depressive symptomatology than the offspring of the controls. Conclusions Preschool offspring of parents with Bipolar Disorder are at increased risk for ADHD and demonstrate increased subthreshold manic and depressive symptomatology. Longitudinal follow-up is warranted to evaluate whether these children are at high-risk to develop mood and other psychiatric disorders. PMID:20080982

  20. Murine mesenchymal stem cells transplanted to the central nervous system of neonatal versus adult mice exhibit distinct engraftment kinetics and express receptors that guide neuronal cell migration.

    PubMed

    Phinney, Donald G; Baddoo, Melody; Dutreil, Maria; Gaupp, Dina; Lai, Wen Tzu; Isakova, Iryna A

    2006-06-01

    Mesenchymal stem cells (MSCs) have demonstrated efficacy as cellular vectors for treating a variety of nervous system disorders. Nevertheless, few studies have quantified MSC engraftment levels or explored the mechanisms that promote their survival and migration in nervous tissue. In this study, we compared the engraftment kinetics and anatomical distribution of murine, male MSCs injected intracranially into neonatal versus adult female mice using a real-time PCR assay that targets the mouse SRY gene. These analyses revealed that MSCs exhibited low but equivalent engraftment levels in the central nervous system (CNS) of neonatal and adult transplant recipients at 12 days post-injection. However, MSC engraftment levels were significantly greater at 60 and 150 days post-transplantation in neonates as compared to adults. Despite these differences, engrafted MSCs were widely distributed along the neuraxis of the CNS in both transplant groups. Collectively, these data indicate that proliferation, but not engraftment and migration, of MSCs in brain are regulated by the host microenvironment. Using a genomics approach, we also identified MSC subpopulations that express neural adhesion proteins and receptors that regulate neuronal cell migration in brain, including cadherin 2, neurexin 1, ninjurin 1, neogenin 1, neuropilin 2, and roundabout homolog 1 and 4. Functional studies indicate these proteins confer cell adhesion and migration of MSCs in response to the appropriate chemoattractant. On the basis of these findings, we conclude that the unique molecular composition of MSC subpopulations imparts to them an inherent capacity to engraft and migrate in brain. These subpopulations may represent more potent cellular vectors for treating CNS disorders. PMID:16846379

  1. Maternal Undernutrition Programs Offspring Adrenal Expression of Steroidogenic Enzymes

    PubMed Central

    Khorram, Naseem M.; Magee, Thomas R.; Wang, Chen; Desai, Mina; Ross, Michael; Khorram, Omid

    2011-01-01

    The aim of this study was to determine the influence of maternal undernutrition (MUN) on maternal and offspring adrenal steoridogenic enzymes. Pregnant Sprague-Dawley rats were 50% food-restricted from day 10 of gestation until delivery. Control animals received ad libitum food. Offspring were killed on day 1 of life (P1) and at 9 months. We determined the messenger RNA (mRNA) expression of steroidogneic enzymes by real-time reverse transcriptase polymerized chain reaction (RT-PCR). Maternal undernutrition inhibited maternal adrenal expression of P450 cholesterol side-chain cleavage enzyme (CYP11A1), 11 beta-hydroxylase (CYP11B1), aldosterone synthase (CYP11B2), and adrenocorticotropic hormone (ACTH) receptor (ACTH-R; MC2 gene) compared with control offspring. There was a marked downregulation in the expression of CYP11B1, CYP11B2, 11 β-hydroxysteroid dehydrogenase type 1 and 2 (HSD1 and HSD2), CYP11A1, ACTH receptor, steroidogenic acute regulatory protein (STAR), and mineralocorticoid receptor (MCR; NR3C2 gene) mRNA in P1 MUN offspring (both genders), with no changes in glucocorticoid receptor (GCR). Quantitative immunohistochemical analysis confirmed the PCR data for GCR and MCR in P1 offspring and demonstrated lower expression of leptin receptor protein (Ob-Ra/Ob-Rb) and mRNA in P1 MUN offspring. In 9-month adult male MUN offspring, the expression of HSD1, CYP11A1, CYP11B2, Ob-Ra/Ob-Rb, and GCR mRNA were significantly upregulated with a trend toward an increase in ACTH-R and a decrease in 17 alpha-hydroxylase (CYP17A1) expression. In adult female MUN offspring, similar to males, the expression of CYP11A1, ACTH-R, and Ob-Rb mRNA were increased, whereas GCR and CYP17A1 mRNA were decreased. These results indicate that the adrenal gland is a target of nutritional programming. In utero undernutrition has a global suppressive effect on maternal and P1 offspring adrenal steroidogenic enzymes in association with reduced circulating corticosterone levels in P1 offspring

  2. Cross-sectional association of dietary patterns with insulin-resistant phenotypes among adults without diabetes in the Framingham Offspring Study.

    PubMed

    Liu, Enju; McKeown, Nicola M; Newby, P K; Meigs, James B; Vasan, Ramachandran S; Quatromoni, Paula A; D'Agostino, Ralph B; Jacques, Paul F

    2009-08-01

    Cluster analysis is a valuable tool for exploring the health consequences of consuming different dietary patterns. We used this approach to examine the cross-sectional relationship between dietary patterns and insulin-resistant phenotypes, including waist circumference, BMI, fasting insulin, 2 h post-challenge insulin, insulin sensitivity index (ISI0,120), HDL-cholesterol, TAG and blood pressure, using data from the fifth examination cycle of the Framingham Offspring Study. Among 2875 participants without diabetes, we identified four dietary patterns based on the predominant sources of energy: 'Fruits, Reduced Fat Dairy and Whole Grains', 'Refined Grains and Sweets', 'Beer' and 'Soda'. After adjusting for multiple comparisons and potential confounders, compared with the 'Fruits, Reduced Fat Dairy and Whole Grains' pattern, the 'Refined Grains and Sweets' pattern had significantly higher mean waist circumference (92.4 v. 90.5 cm; P = 0.008) and BMI (27.3 v. 26.6 kg/m2; P = 0.02); the 'Soda' pattern had significantly higher mean fasting insulin concentration (31.3 v. 28.0 microU/ml; P < or = 0.001); the 'Beer' pattern had significantly higher mean HDL-cholesterol concentration (1.46 v. 1.31 mmol/l; P < 0.001). No associations were observed between dietary patterns and ISI0,120, TAG, and systolic or diastolic blood pressure. Our findings suggest that consumption of a diet rich in fruits, vegetables, whole grains and reduced-fat dairy protects against insulin-resistant phenotypes and displacing these healthy choices with refined grains, high-fat dairy, sweet baked foods, candy and sugar-sweetened soda may promote insulin-resistant phenotypes. PMID:19216828

  3. Do Parental Stressors and Avoidance Coping Mediate between Parental Depression and Offspring Depression? A 23-Year Follow-Up

    ERIC Educational Resources Information Center

    Timko, Christine; Cronkite, Ruth C.; Moos, Rudolf H.

    2010-01-01

    We examined whether parents' stressors and avoidance coping when offspring were children helped to explain associations between parent depression at baseline and offspring's avoidance coping and depression in adulthood. Self-report data were collected at baseline and 1 year from parents (N = 326) and at 23 years from adult offspring (N = 326).…

  4. Maternal and developmental immune challenges alter behavior and learning ability of offspring

    PubMed Central

    Grindstaff, Jennifer L.; Hunsaker, Veronica R.; Cox, Shelby N.

    2012-01-01

    Stimulation of the offspring immune response during development is known to influence growth and behavioral phenotype. However, the potential for maternal antibodies to block the behavioral effects of immune activation during the neonatal period has not been assessed. We challenged female zebra finches (Taeniopygia guttata) prior to egg laying and then challenged offspring during the nestling and juvenile periods with one of two antigens (keyhole limpet hemocyanin (KLH) or lipopolysaccharide (LPS)). We then tested the effects of maternal and neonatal immune challenges on offspring growth rates and neophobia and learning ability of offspring during adulthood. Neonatal immune challenge depressed growth rates. Neophobia of adult offspring was influenced by a combination of maternal treatment, offspring treatment, and offspring sex. Males challenged with LPS during the nestling and juvenile periods had reduced learning performance in a novel foraging task; however, female learning was not impacted. Offspring challenged with the same antigen as mothers exhibited similar growth suppression and behavioral changes as offspring challenged with a novel antigen. Thus, developmental immune challenges have long-term effects on the growth and behavioral phenotype of offspring. We found limited evidence that matching of maternal and offspring challenges reduces the effects of immune challenge in the altricial zebra finch. This may be a result of rapid catabolism of maternal antibodies in altricial birds. Our results emphasize the need to address sex differences in the long-term effects of developmental immune challenge and suggest neonatal immune activation may be one proximate mechanism underlying differences in adult behavior. PMID:22522078

  5. Maternal dietary restriction alters offspring's sleep homeostasis.

    PubMed

    Shimizu, Noriyuki; Chikahisa, Sachiko; Nishi, Yuina; Harada, Saki; Iwaki, Yohei; Fujihara, Hiroaki; Kitaoka, Kazuyoshi; Shiuchi, Tetsuya; Séi, Hiroyoshi

    2013-01-01

    Nutritional state in the gestation period influences fetal growth and development. We hypothesized that undernutrition during gestation would affect offspring sleep architecture and/or homeostasis. Pregnant female mice were assigned to either control (fed ad libitum; AD) or 50% dietary restriction (DR) groups from gestation day 12 to parturition. After parturition, dams were fed AD chow. After weaning, the pups were also fed AD into adulthood. At adulthood (aged 8-9 weeks), we carried out sleep recordings. Although offspring mice displayed a significantly reduced body weight at birth, their weights recovered three days after birth. Enhancement of electroencephalogram (EEG) slow wave activity (SWA) during non-rapid eye movement (NREM) sleep was observed in the DR mice over a 24-hour period without changing the diurnal pattern or amounts of wake, NREM, or rapid eye movement (REM) sleep. In addition, DR mice also displayed an enhancement of EEG-SWA rebound after a 6-hour sleep deprivation and a higher threshold for waking in the face of external stimuli. DR adult offspring mice exhibited small but significant increases in the expression of hypothalamic peroxisome proliferator-activated receptor α (Pparα) and brain-specific carnitine palmitoyltransferase 1 (Cpt1c) mRNA, two genes involved in lipid metabolism. Undernutrition during pregnancy may influence sleep homeostasis, with offspring exhibiting greater sleep pressure. PMID:23741310

  6. Maternal Exposure to Low Levels of Corticosterone during Lactation Protects against Experimental Inflammatory Colitis-Induced Damage in Adult Rat Offspring

    PubMed Central

    Petrella, Carla; Giuli, Chiara; Agostini, Simona; Bacquie, Valérie; Zinni, Manuela; Theodorou, Vassilia; Broccardo, Maria; Casolini, Paola; Improta, Giovanna

    2014-01-01

    Opposing emotional events (negative/trauma or positive/maternal care) during the postnatal period may differentially influence vulnerability to the effects of stress later in life. The development and course of intestinal disorders such as inflammatory bowel disease are negatively affected by persistent stress, but to date the role of positive life events on these pathologies has been entirely unknown. In the present study, the effect of early life beneficial experiences in the development of intestinal dysfunctions, where inflammation and stress stimuli play a primary role, was investigated. As a “positive” experimental model we used adult male rat progeny nursed by mothers whose drinking water was supplemented with moderate doses of corticosterone (CORT) (0.2 mg/ml) during the lactation period. Such animals have been generally shown to cope better with different environmental situations during life. The susceptibility to inflammatory experimental colitis induced by intracolonic infusion of TNBS (2,4,6-trinitrobenzenesulphonic acid) was investigated in CORT-nursed rats in comparison with control rats. This mild increase in maternal corticosterone during lactation induced, in CORT-nursed rats, a long lasting protective effect on TNBS-colitis, characterized by improvements in some indices of the disease (increased colonic myeloperoxidase activity, loss of body weight and food intake) and by the involvement of endogenous peripheral pathways known to participate in intestinal disorder development (lower plasma corticosterone levels and colonic mast cell degranulation, alterations in the colonic expression of both corticotrophin releasing factor/CRF and its receptor/CRH-1R). All these findings contribute to suggesting that the reduced vulnerability to TNBS-colitis in CORT-nursed rats is due to recovery from the colonic mucosal barrier dysfunction. Such long lasting changes induced by mild hormonal manipulation during lactation, making the adult also better adapted

  7. The schooling of offspring and the survival of parents.

    PubMed

    Friedman, Esther M; Mare, Robert D

    2014-08-01

    Contemporary stratification research on developed societies usually views the intergenerational transmission of educational advantage as a one-way effect from parent to child. However, parents' investment in their offspring's schooling may yield significant returns for parents themselves in later life. For instance, well-educated offspring have greater knowledge of health and technology to share with their parents and more financial means to provide for them than do their less-educated counterparts. We use data from the 1992-2006 Health and Retirement Study (HRS) to examine whether adult offspring's educational attainments are associated with parents' survival in the United States. We show that adult offspring's educational attainments have independent effects on their parents' mortality, even after controlling for parents' own socioeconomic resources. This relationship is more pronounced for deaths that are linked to behavioral factors: most notably, chronic lower respiratory disease and lung cancer. Furthermore, at least part of the association between offspring's schooling and parents' survival may be explained by parents' health behaviors, including smoking and physical activity. These findings suggest that one way to influence the health of the elderly is through their offspring. To harness the full value of schooling for health, then, a family and multigenerational perspective is needed. PMID:24917296

  8. Brain Derived Neurotrophic Factor Contributes to the Cardiogenic Potential of Adult Resident Progenitor Cells in Failing Murine Heart

    PubMed Central

    Samal, Rasmita; Ameling, Sabine; Dhople, Vishnu; Sappa, Praveen Kumar; Wenzel, Kristin; Völker, Uwe; Felix, Stephan B.; Hammer, Elke; Könemann, Stephanie

    2015-01-01

    Aims Resident cardiac progenitor cells show homing properties when injected into the injured but not to the healthy myocardium. The molecular background behind this difference in behavior needs to be studied to elucidate how adult progenitor cells can restore cardiac function of the damaged myocardium. Since the brain derived neurotrophic factor (BDNF) moderates cardioprotection in injured hearts, we focused on delineating its regulatory role in the damaged myocardium. Methods and Results Comparative gene expression profiling of freshly isolated undifferentiated Sca-1 progenitor cells derived either from heart failure transgenic αMHC-CyclinT1/Gαq overexpressing mice or wildtype littermates revealed transcriptional variations. Bdnf expression was up regulated 5-fold during heart failure which was verified by qRT-PCR and confirmed at protein level. The migratory capacity of Sca-1 cells from transgenic hearts was improved by 15% in the presence of 25ng/ml BDNF. Furthermore, BDNF-mediated effects on Sca-1 cells were studied via pulsed Stable Isotope Labeling of Amino acids in Cell Culture (pSILAC) proteomics approach. After BDNF treatment significant differences between newly synthesized proteins in Sca-1 cells from control and transgenic hearts were observed for CDK1, SRRT, HDGF, and MAP2K3 which are known to regulate cell cycle, survival and differentiation. Moreover BDNF repressed the proliferation of Sca-1 cells from transgenic hearts. Conclusion Comparative profiling of resident Sca-1 cells revealed elevated BDNF levels in the failing heart. Exogenous BDNF (i) stimulated migration, which might improve the homing ability of Sca-1 cells derived from the failing heart and (ii) repressed the cell cycle progression suggesting its potency to ameliorate heart failure. PMID:25799225

  9. Murine Typhus

    PubMed Central

    Dzul-Rosado, Karla R; Zavala Velázquez, Jorge Ernesto; Zavala-Castro, Jorge

    2012-01-01

    Rickettsia typhi: is an intracellular bacteria who causes murine typhus. His importance is reflected in the high frequency founding specific antibodies against Rickettsia typhi in several worldwide seroepidemiological studies, the seroprevalence ranging between 3-36%. Natural reservoirs of R. typhi are rats (some species belonging the Rattus Genus) and fleas (Xenopsylla cheopis) are his vector. This infection is associated with overcrowding, pollution and poor hygiene. Typically presents fever, headache, rash on trunk and extremities, in some cases may occur organ-specific complications, affecting liver, kidney, lung or brain. Initially the disease is very similar to other diseases, is very common to confuse the murine typhus with Dengue fever, therefore, ignorance of the disease is a factor related to complications or non-specific treatments for the resolution of this infection. This paper presents the most relevant information to consider about the rickettsiosis caused by Rickettsia typhi. PMID:24893060

  10. Elevated cortisol in healthy female adolescent offspring of mothers with posttraumatic stress disorder.

    PubMed

    Liu, Keke; Ruggero, Camilo J; Goldstein, Brandon; Klein, Daniel N; Perlman, Greg; Broderick, Joan; Kotov, Roman

    2016-05-01

    Offspring with maternal PTSD are at increased risk of developing PTSD themselves. Alterations in the hypothalamic-pituitary-adrenal (HPA) axis may play a role and have been noted in offspring, although evidence is mostly from adult offspring with PTSD symptoms themselves. The present study of adolescent girls (N=472) and their mothers (n=18 with lifetime PTSD versus n=454 with no PTSD) sought to determine whether healthy, non-affected offspring of mothers with PTSD would exhibit altered HPA axis function. Saliva samples were collected from the adolescent girls at waking, 30min after waking, and 8 pm on 3 consecutive days. Offspring whose mothers were diagnosed with PTSD demonstrated higher cortisol awakening response (CAR; Cohen's d=0.58) and greater total cortisol output (Cohen's d=0.62). In this preliminary study, higher cortisol levels during adolescence among offspring of mothers with PTSD may index a vulnerability in these at-risk youth. PMID:27088877

  11. Congenital anomalies in the offspring of rats after exposure of the testis to an electrostatic field.

    PubMed

    Soeradi, O; Tadjudin, M K

    1986-04-01

    The effect of electrostatic field treatment of the testis on the offspring of male rats was investigated. The results showed that treatment ranging from 1 to 7 kV caused reduced fertility, but no deaths occurred among the treated animals during the experiment. Observations at 3, 30, 60 and 90 days after exposure showed no recovery of fertility among the treated rats. Treatment with 6 or 7 kV caused congenital anomalies in the offspring, such as micropthalmy, elongation of the foreskin of the penis (praeputium-like), 'rounded face' with omnidirectional hair growth, and narrow pelvis in adult female offspring. The anomalies might be caused by changes to the genetic material in the sperm. The sex ratio of offspring in the experimental groups was not significantly different from normal, suggesting that the number of male and female offspring was unaffected by treatment. The number of offspring with experimentally linked congenital anomalies decreased with time. PMID:3793258

  12. Maternal depression during pregnancy and offspring depression in adulthood: role of child maltreatment

    PubMed Central

    Plant, Dominic T.; Pariante, Carmine M.; Sharp, Deborah; Pawlby, Susan

    2015-01-01

    Background Studies have shown that maternal depression during pregnancy predicts offspring depression in adolescence. Child maltreatment is also a risk factor for depression. Aims To investigate (a) whether there is an association between offspring exposure to maternal depression in pregnancy and depression in early adulthood, and (b) whether offspring child maltreatment mediates this association. Method Prospectively collected data on maternal clinical depression in pregnancy, offspring child maltreatment and offspring adulthood (18–25 years) DSM-IV depression were analysed in 103 mother–offspring dyads of the South London Child Development Study. Results Adult offspring exposed to maternal depression in pregnancy were 3.4 times more likely to have a DSM-IV depressive disorder, and 2.4 times more likely to have experienced child maltreatment, compared with non-exposed offspring. Path analysis revealed that offspring experience of child maltreatment mediated the association between exposure to maternal depression in pregnancy and depression in adulthood. Conclusions Maternal depression in pregnancy is a key vulnerability factor for offspring depression in early adulthood. PMID:26045352

  13. Maternal Obesity at Conception Programs Obesity in the Offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The risk of obesity in adult life is subject to programming during gestation. To examine whether in utero exposure to maternal obesity increases the risk of obesity in the offspring, we have developed an overfeeding-based model of maternal obesity in rats utilizing intragastric feeding of diets via ...

  14. Maternal overweight programs insulin and adiponectin signaling in the offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gestational exposure to maternal overweight (OW) influences the risk of obesity in adult-life. Male offspring from OW dams gain greater body weight, fat mass and develop insulin resistance when fed high fat diets (45 percent fat). In this report we identify molecular targets of maternal OW-induced p...

  15. Maternal Obesity at Conception Programs Obesity in the Offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The risk of obesity in adult-life is subject to programming during gestation. To examine whether in utero exposure to maternal obesity increases the risk of obesity in the offspring, we have developed an overfeeding-based model of maternal obesity in rats utilizing intragastric feeding of diets via ...

  16. Maternal Overweight Programs Insulin and Adiponectin Signaling in the Offspring

    PubMed Central

    Shankar, Kartik; Kang, Ping; Harrell, Amanda; Zhong, Ying; Marecki, John C.; Ronis, Martin J. J.; Badger, Thomas M.

    2010-01-01

    Gestational exposure to maternal overweight (OW) influences the risk of obesity in adult life. Male offspring from OW dams gain greater body weight and fat mass and develop insulin resistance when fed high-fat diets (45% fat). In this report, we identify molecular targets of maternal OW-induced programming at postnatal d 21 before challenge with the high-fat diet. We conducted global transcriptome profiling, gene/protein expression analyses, and characterization of downstream signaling of insulin and adiponectin pathways in conjunction with endocrine and biochemical characterization. Offspring born to OW dams displayed increased serum insulin, leptin, and resistin levels (P < 0.05) at postnatal d 21 preceding changes in body composition. A lipogenic transcriptome signature in the liver, before development of obesity, was evident in OW-dam offspring. A coordinated locus of 20 sterol regulatory element-binding protein-1-regulated target genes was induced by maternal OW. Increased nuclear levels of sterol regulatory element-binding protein-1 and recruitment to the fatty acid synthase promoter were confirmed via ELISA and chromatin immunoprecipitation analyses, respectively. Higher fatty acid synthase and acetyl coenzyme A carboxylase protein and pAKT (Thr308) and phospho-insulin receptor-β were confirmed via immunoblotting. Maternal OW also attenuated AMP kinase/peroxisome proliferator-activated receptor-α signaling in the offspring liver, including transcriptional down-regulation of several peroxisome proliferator-activated receptor-α-regulated genes. Hepatic mRNA and circulating fibroblast growth factor-21 levels were significantly lower in OW-dam offspring. Furthermore, serum levels of high-molecular-weight adiponectin (P < 0.05) were decreased in OW-dam offspring. Phosphorylation of hepatic AMP-kinase (Thr172) was significantly decreased in OW-dam offspring, along with lower AdipoR1 mRNA. Our results strongly suggest that gestational exposure to maternal

  17. Paternal fenvalerate exposure influences reproductive functions in the offspring.

    PubMed

    Xia, Dong; Parvizi, Nahid; Zhou, Yuchuan; Xu, Kesi; Jiang, Hui; Li, Rongjie; Hang, Yiqiong; Lu, Yang

    2013-11-01

    Fenvalerate (Fen), a synthetic pyrethroid insecticide, has been shown to have adverse effects on male reproductive system. Thus, the aim of the present study was to elucidate whether these adverse effects are passed from exposed male mice to their offspring. Adult male mice received Fen (10 mg/kg) daily for 30 days and mated with untreated females to produce offspring. Fenvalerate significantly changed the methylation status of angiotensin I-converting enzyme (Ace), forkhead box O3 (Foxo3a), huntingtin-associated protein 1 (Hap1), nuclear receptor subfamily 3 (Nr3c2), promyelocytic leukemia (Pml), and Prostaglandin F2 receptor negative regulator (Ptgfrn) genes in paternal mice sperm genomic DNA. Further, Fen significantly increased sperm abnormalities; serum testosterone and estradiol-17ß level in adult male (F0) and their male offspring (F1). Further, paternal Fen treatment significantly increased the length of estrous cycle, serum estradiol-17ß concentration in estrus, and progesterone levels in diestrus in female offspring (F1). These findings suggest that adverse effects of paternal Fen exposure on reproductive functions can be seen not only in treated males (F0) but also in their offsprings. PMID:23548413

  18. Exposure of pregnant rats to diverse chemicals during pregnancy causes elevated blood pressure in offspring

    EPA Science Inventory

    Objective: Global undernutrition, low protein diet or dexamethasone treatment during pregnancy has been demonstrated in animal models to result in adverse health effects including hypertension and insulln resistance in adult offspring. Most protocols that produce these effects ca...

  19. Maternal Early Life Risk Factors for Offspring Birth Weight: Findings from the Add Health Study

    PubMed Central

    Thompson, Elaine; Rue, Tessa; Guo, Yuqing

    2014-01-01

    The aim of this study was to examine the pathways that link mothers’ early life socioeconomic status (SES) and mothers’ experience of childhood maltreatment with birth weight among their later born offspring. Data were drawn from a nationally representative longitudinal survey of school-aged respondents, initially enrolled during adolescence in Wave I (1994–1995) and Wave II (1996) of the National Longitudinal Study of Adolescent Health and followed-up in adulthood in Wave III (2001–2002). Data on offspring birth weight were obtained from nulliparous females (N=1,897) who had given birth between Waves II and III. Analyses used structural equation modeling to examine the extent to which early life maternal risk predicted offspring birth weight, and demonstrated that maternal childhood SES and maternal childhood maltreatment predicted offspring birth weight through several mediated pathways. First, maternal adolescent substance use and prenatal cigarette use partially mediated the association between maternal childhood SES and offspring birth weight. Second, maternal adolescent depressive symptoms and adult SES partially mediated the association between maternal childhood SES and offspring birth weight. Third, adult SES partially mediated the association between maternal childhood SES and offspring birth weight. Fourth, maternal adolescent substance use and prenatal cigarette use partially mediated the association between maternal childhood maltreatment and offspring birth weight. Finally, maternal adolescent depressive symptoms and adult SES partially mediated the association between maternal childhood maltreatment and offspring birth weight. To our knowledge, this is the first study to identify maternal childhood maltreatment as an early life risk factor for offspring birth weight among a nationally representative sample of young women, and to demonstrate the mechanisms that link childhood SES and maltreatment to offspring birth weight. These findings

  20. Depressed parents' attachment: effects on offspring suicidal behavior in a longitudinal, family study

    PubMed Central

    MacGregor, Erica K.; Grunebaum, Michael F.; Galfalvy, Hanga C.; Melhem, Nadine; Burke, Ainsley K.; Brent, David A.; Oquendo, Maria A.; Mann, J. John

    2015-01-01

    Objective To investigate relationships of depressed parents' attachment style to offspring suicidal behavior. Method 244 parents diagnosed with a DSM-IV depressive episode completed the Adult Attachment Questionnaire at study entry. Baseline and yearly follow-up interviews of their 488 offspring tracked suicidal behavior and psychopathology. Survival analysis and marginal regression models with correlated errors for siblings investigated the relationship between parent insecure attachment traits and offspring characteristics. Data analyzed were collected 1992–2008 during a longitudinal family study completed January 31, 2014. Results Parent avoidant attachment predicted offspring suicide attempts at a trend level (p=0.083). Parent anxious attachment did not predict offspring attempts (p=0.961). In secondary analyses, anxious attachment in parents was associated with offspring impulsivity (p=0.034), and in offspring suicide attempters, was associated with greater intent (p=0.045) and lethality of attempts (p=0.003). Avoidant attachment in parents was associated with offspring impulsivity (p=0.025) and major depressive disorder (p=0.012). Parent avoidant attachment predicted a greater number of suicide attempts (p=0.048) and greater intent in offspring attempters (p=0.003). Results were comparable after adjusting for parent diagnosis of borderline personality disorder. Conclusion Insecure avoidant, but not anxious, attachment in depressed parents may predict offspring suicide attempt. Insecure parent attachment traits were associated with impulsivity and major depressive disorder in all offspring, and with more severe suicidal behavior in offspring attempters. Insecure parental attachment merits further study as a potential target to reduce risk of offspring psychopathology and more severe suicidal behavior. PMID:25098943

  1. Maternal antioxidant blocks programmed cardiovascular and behavioural stress responses in adult mice

    PubMed Central

    ROGHAIR, Robert D.; WEMMIE, John A.; VOLK, Kenneth A.; SCHOLZ, Thomas D.; LAMB, Fred S.; SEGAR, Jeffrey L.

    2013-01-01

    Intra-uterine growth restriction is an independent risk factor for adult psychiatric and cardiovascular diseases. In humans, intra-uterine growth restriction is associated with increased placental and fetal oxidative stress, as well as down-regulation of placental 11β-HSD (11β-hydroxysteroid dehydrogenase). Decreased placental 11β-HSD activity increases fetal exposure to maternal glucocorticoids, further increasing fetal oxidative stress. To explore the developmental origins of co-morbid hypertension and anxiety disorders, we increased fetal glucocorticoid exposure by administering the 11β-HSD inhibitor CBX (carbenoxolone; 12 mg · kg−1 of body weight · day−1) during the final week of murine gestation. We hypothesized that maternal antioxidant (tempol throughout pregnancy) would block glucocorticoid-programmed anxiety, vascular dysfunction and hypertension. Anxiety-related behaviour (conditioned fear) and the haemodynamic response to stress were measured in adult mice. Maternal CBX administration significantly increased conditioned fear responses of adult females. Among the offspring of CBX-injected dams, maternal tempol markedly attenuated the behavioural and cardiovascular responses to psychological stress. Compared with offspring of undisturbed dams, male offspring of dams that received daily third trimester saline injections had increased stress-evoked pressure responses that were blocked by maternal tempol. In contrast, tempol did not block CBX-induced aortic dysfunction in female mice (measured by myography and lucigenin-enhanced chemiluminescence). We conclude that maternal stress and exaggerated fetal glucocorticoid exposure enhance sex-specific stress responses, as well as alterations in aortic reactivity. Because concurrent tempol attenuated conditioned fear and stress reactivity even among the offspring of saline-injected dams, we speculate that antenatal stressors programme offspring stress reactivity in a cycle that may be broken by antenatal

  2. Intrauterine stress induces bone loss in adult offspring of C3H/HeJ mice having high bone mass phenotype but not C57BL/6J mice with low bone mass phenotype.

    PubMed

    Raygorodskaya, M; Gabet, Y; Shochat, C; Kobyliansky, E; Torchinsky, A; Karasik, D

    2016-06-01

    In this study we examined to what extent and how genetics may modify osteoporosis risk arising due to environmental stresses which act during the antenatal period of life and have the potential to induce bone loss in adulthood. C57Bl/6J (C57) and C3H/HeJ (C3H) mice were used as a model system. The mice were exposed to a single injection of 5-aza-2'-deoxycytidine (5-AZA) on day 10 of pregnancy and the structure and bone mineral density (BMD) of the femur and 3rd lumbar vertebra of 3- and 6-month-old male and female offspring were evaluated by micro-computed tomography (μCT). Besides, we also attempted to evaluate whether 5-AZA affects the expression of some osteogenic genes in the embryonic limb buds. The main observation of this study is that 5-AZA-induced loss of bone quality was registered in 6-mo-old C3H offspring but not in their C57 counterparts. We also observed that C57 and C3H embryos may differ in their response to 5-AZA-induced detrimental stimuli: whereas 5-AZA treated C3H embryos exhibited a decreased expression of Col1a1, C57 embryos exhibit a decreased expression of Sox9. Overall, our study, by thorough characterization of bone homeostasis in 3- and 6-month-old offspring of 5-AZA-exposed C57 and C3H mice, allows hypothesizing that the adaptive response to antenatal insults may be stronger in offspring inherently exhibiting a low bone mass phenotype than in offspring inherently exhibiting a high bone mass phenotype. PMID:27072519

  3. Dietary methyl donor deficiency during pregnancy in rats shapes learning and anxiety in offspring.

    PubMed

    Konycheva, Galina; Dziadek, Marie A; Ferguson, Lynnette R; Krägeloh, Christian U; Coolen, Marcel W; Davison, Michael; Breier, Bernhard H

    2011-10-01

    Two important lines of research have enhanced our understanding of the molecular role of nutrition in influencing behavior. First, exposure to an adverse environment during early life can influence the long-term behavior of the offspring. Second, regulation of the nervous system development and functioning appears to involve epigenetic mechanisms that require a continuous supply of methyl group donors in food. We hypothesized that a maternal diet during pregnancy deficient in methyl donors (MDD) may lead to altered behavior in offspring through permanent changes in hippocampal DNA methylation. We used a rat model of prenatal dietary MDD to test this hypothesis in female offspring as they aged. Prenatal MDD reduced birth weight, litter size, and newborn viability. Aged female offspring of MDD mothers showed increased anxiety and increased learning ability in comparison with control diet group offspring. To explore the role of MDD on epigenetic mechanisms in the brain of adult offspring, we studied expression and methylation of 4 selected genes coding for glucocorticoid receptor, hydroxysteroid dehydrogenase 11 type 2, neuronatin, and reelin proteins in the hippocampus. No major group differences in methylation or expression of the studied genes were detected, except for a significant down-regulation of the reelin gene in the MDD female offspring. The prenatal MDD diet caused intrauterine growth restriction, associated with long-term effects on the behavior of the offspring. However, the observed behavioral differences between the MDD and control diet offspring cannot be explained by epigenetic regulation of the specific genes investigated in this study. PMID:22074804

  4. Maternal obesity, lipotoxicity and cardiovascular diseases in offspring.

    PubMed

    Dong, Maolong; Zheng, Qijun; Ford, Stephen P; Nathanielsz, Peter W; Ren, Jun

    2013-02-01

    Maternal obesity has risen dramatically over the past 20 years, by nearly 42% in African-Americans and 29% in Caucasians. Maternal obesity is afflicted with many maternal obstetric complications in the offspring including high blood pressure, obesity, gestational diabetes and increased perinatal morbidity. Maternal nutritional environment plays a rather important role in the programming of the health set-points in the offspring such as glucose and insulin metabolism, energy balance and predisposition to metabolic disorders. In particular, maternal obesity is associated with elevated prevalence of cardiovascular diseases in the offspring. Evidence from human and experimental studies including rodents and nonhuman primates has indicated that maternal obesity or overnutrition programs offspring for an increased risk of adult obesity. Maternal obesity or fat diet exposure predisposes the onset and development of obesity, insulin resistance, cardiac hypertrophy and myocardial contractile anomalies in the offspring. A number of mechanisms including elevated hormones (leptin, insulin), nutrients (fatty acids, triglycerides and glucose) and inflammatory cytokines have been postulated to play a key role in maternal obesity-induced postnatal cardiovascular sequelae. In addition, lipotoxicity (accumulation of lipid metabolites) resulting from maternal obesity is capable of activating a number of stress signaling cascades including pro-inflammatory cytokines and oxidative stress to exacerbate maternal obesity-induced cardiovascular complications later on in adult life. This mini-review summarizes the recent knowledge with regard to the role of lipotoxicity in maternal obesity-induced change in cardiovascular function in the offspring. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism". PMID:22982026

  5. Sex roles in nest keeping - how information asymmetry contributes to parent-offspring co-adaptation.

    PubMed

    Lucass, Carsten; Fresneau, Nolwenn; Eens, Marcel; Müller, Wendt

    2016-03-01

    Parental food provisioning and offspring begging influence each other reciprocally. This makes both traits agents and targets of selection, which may ultimately lead to co-adaptation. The latter may reflect co-adapted parent and offspring genotypes or could be due to maternal effects. Maternal effects are in turn likely to facilitate in particular mother-offspring co-adaptation, further emphasized by the possibility that mothers are sometimes found to be more responsive to offspring need. However, parents may not only differ in their sensitivity, but often play different roles in postnatal care. This potentially impinges on the access to information about offspring need. We here manipulated the information on offspring need as perceived by parents by playing back begging calls at a constant frequency in the nest-box of blue tits (Cyanistes caeruleus). We measured the parental response in provisioning to our treatment, paying particular attention to sex differences in parental roles and whether such differences alter the perception of the intensity of our manipulation. This enabled us to investigate whether an information asymmetry about offspring need exists between parents and how such an asymmetry relates to co-adaptation between parental provisioning and offspring begging. Our results show that parents indeed differed in the frequency how often they perceived the playback due to the fact that females spent more time with their offspring in the nest box. Correcting for the effective exposure of an adult to the playback, the parental response in provisioning covaried more strongly (positive) with offspring begging intensity, independent of the parental sex, indicating coadaptation on the phenotypic level. Females were not more sensitive to experimentally increased offspring need than males, but they were exposed to more broadcasted begging calls. Therefore, sex differences in access to information about offspring need, due to different parental roles, have the

  6. Maternal high-fat-diet programs rat offspring liver fatty acid metabolism.

    PubMed

    Seet, Emily L; Yee, Jennifer K; Jellyman, Juanita K; Han, Guang; Ross, Michael G; Desai, Mina

    2015-06-01

    In offspring exposed in utero to a maternal diet high in fat (HF), we have previously demonstrated that despite similar birth weights, HF adult offspring at 6 months of age had significantly higher body weights, greater adiposity, and increased triacylglycerol (TAG) levels as compared to controls. We hypothesized that a maternal HF diet predisposes to offspring adiposity via a programmed increase in the synthesis of monounsaturated fatty acids in the liver and hence increased substrate availability for liver TAG synthesis. We further hypothesized that programmed changes in offspring liver fatty acid metabolism are associated with increased liver expression of the lipogenic enzyme stearoyl-CoA desaturase-1 (SCD-1). Female rats were maintained on a HF diet rich in monounsaturated fatty acids (MUFA) prior to and throughout pregnancy and lactation. After birth, newborns were nursed by the same dam, and all offspring were weaned to control diet. Plasma and liver fatty acid compositions were determined using gas chromatography/mass spectrometry. Fatty acid C16 desaturation indices of palmitoleic/palmitic and (vaccenic + palmitoleic)/palmitic and the C18 desaturation index of oleic/stearic were calculated. Liver protein abundance of SCD-1 was analyzed in newborns and adult offspring. Plasma and liver C16 desaturation indices were decreased in HF newborns, but increased in the adult offspring. Liver SCD-1 expression was increased in the HF adult offspring. These data show that the maternal HF diet during pregnancy and lactation increases offspring liver SCD-1 protein abundance and alters the liver C16 desaturase pathway. PMID:25899040

  7. Identification of novel mRNA transcripts of the nm23-M1 gene that are modulated during mouse embryo development and are differently expressed in adult murine tissues.

    PubMed

    Gervasi, F; Capozza, F; Bruno, T; Fanciulli, M; Lombardi, D

    1998-12-01

    The nm23-M1, a putative metastasis-suppressor gene, and its homologs are involved in development and differentiation. We have shown previously that in vitro neuronal cell proliferation and differentiation can be modulated by nm23-M1 expression levels. In the present study, by the yeast two-hybrid system, we have shown that, at the onset of mouse tissue differentiation, the Nm23-M1 protein forms either homodimers, or heterodimers with Nm23-M2. Furthermore, we have isolated two cDNA variants of the nm23-M1 gene in the 3'-untranslated region (UTR). The two variants related to novel mRNA transcripts that are modulated in mouse embryo and are differently expressed in adult murine tissues. PMID:9881672

  8. Excess maternal salt or fructose intake programmes sex-specific, stress- and fructose-sensitive hypertension in the offspring.

    PubMed

    Gray, Clint; Gardiner, Sheila M; Elmes, Matthew; Gardner, David S

    2016-02-28

    The Western diet is typically high in salt and fructose, which have pressor activity. Maternal diet can affect offspring blood pressure, but the extent to which maternal intake of excess salt and fructose may influence cardiovascular function of the offspring is unknown. We sought to determine the effect of moderate maternal dietary intake of salt and/or fructose on resting and stimulated cardiovascular function of the adult male and female offspring. Pregnant rats were fed purified diets (± 4% salt) and water (± 10% fructose) before and during gestation and through lactation. Male and female offspring were weaned onto standard laboratory chow. From 9 to 14 weeks of age, cardiovascular parameters (basal, circadian and stimulated) were assessed continuously by radiotelemetry. Maternal salt intake rendered opposite-sex siblings with a 25-mmHg difference in blood pressure as adults; male offspring were hypertensive (15 mmHg mean arterial pressure (MAP)) and female offspring were hypotensive (10 mmHg MAP) above and below controls, respectively. Sex differences were unrelated to endothelial nitric oxide activity in vivo, but isolation-induced anxiety revealed a significantly steeper coupling between blood pressure and heart rate in salt-exposed male offspring but not in female offspring. MAP of all offspring was refractory to salt loading but sensitive to subsequent dietary fructose, an effect exacerbated in female offspring from fructose-fed dams. Circadian analyses of pressure in all offspring revealed higher mean set-point for heart rate and relative non-dipping of nocturnal pressure. In conclusion, increased salt and fructose in the maternal diet has lasting effects on offspring cardiovascular function that is sex-dependent and related to the offspring's stress-response axis. PMID:26653028

  9. The Effect of Parents' Attitudes toward Divorce on Offspring's Attitudes: Gender and Parental Divorce as Mediating Factors

    ERIC Educational Resources Information Center

    Kapinus, Carolyn A.

    2004-01-01

    This study addresses three questions: (a) What influence do parents' attitudes toward divorce have on offspring's attitudes? (b) How are offspring's attitudes toward divorce influenced by parental divorce, and do the effects vary depending on the gender of the child? and (c) How do conditions surrounding parental divorce influence young adults'…

  10. Plasticity in offspring contaminant tolerance traits: developmental cadmium exposure trumps parental effects.

    PubMed

    Plautz, Stephanie C; Salice, Christopher J

    2013-07-01

    Parental effects are non-genotypic influences on offspring phenotype that occur via parental phenotypes or environments, while developmental plasticity is phenotypic variation that arises during development in response to environmental cues. We evaluated the relative contribution of these two sources of phenotypic variation on offspring toxicant tolerance in Physa pomilia snails exposed to cadmium. We exposed adult snails to 0, 2, or 20 μg/L cadmium for 7 days, then exposed egg masses collected from these adults to 0 or 2 μg/L cadmium in a factorial design (adult cadmium exposure × egg mass cadmium exposure). Starting at 2 days old, we recorded time to death for hatchlings exposed to 150 μg/L cadmium for 72 h at 8 h intervals. Juveniles hatched from cadmium-exposed egg masses displayed higher cadmium tolerance than juveniles from unexposed egg masses. Among juveniles from egg masses not exposed to cadmium, offspring of parents exposed to 20 μg/L cadmium had higher cadmium tolerance than offspring of parents exposed to 0 or 2 μg/L cadmium. Our results show that both parental effects and developmental plasticity can impact offspring toxicant tolerance and point to the potential importance of both processes in understanding how offspring respond to chemical contaminants. When both parents and offspring are exposed to a toxicant, our results showed that the effects of parental exposure on offspring toxicant tolerance may be eclipsed by the effects of offspring exposure during development. PMID:23661094

  11. Protective role of taurine in developing offspring affected by maternal alcohol consumption

    PubMed Central

    Ananchaipatana-Auitragoon, Pilant; Ananchaipatana-Auitragoon, Yutthana; Siripornpanich, Vorasith; Kotchabhakdi, Naiphinich

    2015-01-01

    Maternal alcohol consumption is known to affect offspring growth and development, including growth deficits, physical anomalies, impaired brain functions and behavioral disturbances. Taurine, a sulfur-containing amino acid, is essential during development, and continually found to be protective against neurotoxicity and various tissue damages including those from alcohol exposure. However, it is still unknown whether taurine can exert its protection during development of central nervous system and whether it can reverse alcohol damages on developed brain later in life. This study aims to investigate protective roles of taurine against maternal alcohol consumption on growth and development of offspring. The experimental protocol was conducted using ICR-outbred pregnant mice given 10 % alcohol, with or without maternal taurine supplementation during gestation and lactation. Pregnancy outcomes, offspring mortality and successive bodyweight until adult were monitored. Adult offspring is supplemented taurine to verify its ability to reverse damages on learning and memory through a water maze task performance. Our results demonstrate that offspring of maternal alcohol exposure, together with maternal taurine supplementation show conserved learning and memory, while that of offspring treated taurine later in life are disturbed. Taurine provides neuroprotective effects and preserves learning and memory processes when given together with maternal alcohol consumption, but not shown such effects when given exclusively in offspring. PMID:26648819

  12. Familial transmission of parental mood disorders: unipolar and bipolar disorders in offspring

    PubMed Central

    Oquendo, Maria A; Ellis, Steven P; Chesin, Megan S; Birmaher, Boris; Zelazny, Jamie; Tin, Adrienne; Melhem, Nadine; Burke, Ainsley K; Kolko, David; Greenhill, Laurence; Stanley, Barbara; Brodsky, Beth S; Mann, J John; Brent, David A

    2013-01-01

    Objectives Offspring of depressed parents are at increased risk for psychiatric disorders. Although bipolar disorder (BD) and major depressive disorder (MDD) are both found in the same families, it is not clear whether transmission to offspring of BD or MDD tends to occur from parents with the same mood disorder subtype. The primary hypothesis was that offspring of parents with BD would be at increased risk for BD and other comorbid disorders common to BD such as anxiety and substance use relative to offspring of parents with MDD. Offspring of parents with BD versus those with MDD were also hypothesized to be at greater risk for externalizing disorders, i.e., conduct disorder, attention-deficit hyperactivity disorder, or antisocial personality disorder. Methods Parents (n = 320) with mood disorders and their offspring (n = 679) were studied. Adult offspring were administered the Structured Clinical Interview for DSM-IV Axis I Disorders to establish the presence of psychopathology. Offspring aged 10 to 18-years-old were assessed with the School Aged Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version, and parents of children under age 10 completed the Child Behavioral Checklist. Data were examined using Cox Proportional Hazard regression. Results There was no difference in hazard of mood disorders in the offspring of parents with BD as compared to offspring of parents with MDD. However, a number of other parent and offspring characteristics increased risk for mood, anxiety, externalizing, and substance use disorders in offspring, including self-reported childhood abuse in parent or offspring, offspring impulsive aggression, and age of onset of parental mood disorder. Conclusions Mood disorders are highly familial independent of whether the parent’s condition is unipolar or bipolar, and considerable overlap in the familial basis of MDD and BD was found. Although parental characteristics had limited influence on risk of offspring

  13. Reliable Genetic Labeling of Adult-Born Dentate Granule Cells Using Ascl1CreERT2 and GlastCreERT2 Murine Lines

    PubMed Central

    Yang, Sung M.; Alvarez, Diego D.

    2015-01-01

    Newly generated dentate granule cells (GCs) are relevant for input discrimination in the adult hippocampus. Yet, their precise contribution to information processing remains unclear. To address this question, it is essential to develop approaches to precisely label entire cohorts of adult-born GCs. In this work, we used genetically modified mice to allow conditional expression of tdTomato (Tom) in adult-born GCs and characterized their development and functional integration. Ascl1CreERT2;CAGfloxStopTom and GlastCreERT2;CAGfloxStopTom mice resulted in indelible expression of Tom in adult neural stem cells and their lineage upon tamoxifen induction. Whole-cell recordings were performed to measure intrinsic excitability, firing behavior, and afferent excitatory connectivity. Developing GCs were also staged by the expression of early and late neuronal markers. The slow development of adult-born GCs characterized here is consistent with previous reports using retroviral approaches that have revealed that a mature phenotype is typically achieved after 6–8 weeks. Our findings demonstrate that Ascl1CreERT2 and GlastCreERT2 mouse lines enable simple and reliable labeling of adult-born GC lineages within restricted time windows. Therefore, these mice greatly facilitate tagging new neurons and manipulating their activity, required for understanding adult neurogenesis in the context of network remodeling, learning, and behavior. SIGNIFICANCE STATEMENT Our study shows that Ascl1CreERT2 and GlastCreERT2 mice lines can be used to label large cohorts of adult-born dentate granule cells with excellent time resolution. Neurons labeled in this manner display developmental and functional profiles that are in full agreement with previous findings using thymidine analogs and retroviral labeling, thus providing an alternative approach to tackle fundamental questions on circuit remodeling. Because of the massive neuronal targeting and the simplicity of this method, genetic labeling will

  14. Pre-birth world and the development of the immune system: mum's diet affects our adult health: new insight on how the diet during pregnancy permanently influences offspring health and immune fitness.

    PubMed

    Ferreira, Manuela; Veiga-Fernandes, Henrique

    2014-12-01

    Secondary lymphoid organs form in utero through an inherited and well-established developmental program. However, maternal non-heritable features can have a major impact on the gene expression of the embryo, hence influencing the future health of the offspring. Recently, maternal retinoids were shown to regulate the formation of immune structures, shedding light on the role of maternal nutrition in the genetic signature of emergent immune cells. Here we highlight evidence showing how the maternal diet influences the establishment of the immune system, and we also discuss how unbalanced maternal diets may set the response to infection and vaccination in the progeny. PMID:25382781

  15. Social and ecological factors influencing offspring survival in wild macaques

    PubMed Central

    Kerhoas, Daphne; Perwitasari-Farajallah, Dyah; Agil, Muhammad; Widdig, Anja

    2014-01-01

    Premature loss of offspring decreases direct fitness of parents. In gregarious mammals, both ecological and social variables impact offspring survival and may interact with each other in this regard. Although a number of studies have investigated factors influencing offspring loss in mammals, we still know very little on how different factors interact with one another. We therefore investigated fetal and infant mortality in 3 large groups of wild crested macaques (Macaca nigra) over a period of up to 5 years by including potential social causes such as maternal dominance rank, male immigration, between group encounters, and ecological conditions such as rainfall in a multivariate survival analysis using Cox proportional hazards model. Infant but not fetal survival was most impaired after a recent takeover of the alpha-male position by an immigrant male. Furthermore, infant survival probability increased when there was an increase in number of group adult females and rainfall. Fetal survival probability also increased with an increase of these 2 factors, but more in high-ranking than low-ranking females. Fetal survival, unlike that of infants, was also improved by an increase of intergroup encounter rates. Our study thus stresses the importance of survival analyses using a multivariate approach and encompassing more than a single offspring stage to investigate the determinants of female direct fitness. We further provide evidence for fitness costs and benefits of group living, possibly deriving from high pressures of both within- and between-group competition, in a wild primate population. PMID:25214754

  16. Risk of Suicide Attempt in Adopted and Nonadopted Offspring

    PubMed Central

    Malone, Stephen M.; Sharma, Anu; Iacono, William G.; McGue, Matt

    2013-01-01

    OBJECTIVE: We asked whether adoption status represented a risk of suicide attempt for adopted and nonadopted offspring living in the United States. We also examined whether factors known to be associated with suicidal behavior would mediate the relationship between adoption status and suicide attempt. METHODS: Participants were drawn from the Sibling Interaction and Behavior Study, which included 692 adopted and 540 nonadopted offspring and was conducted at the University of Minnesota from 1998 to 2008. Adoptees were systematically ascertained from records of 3 large Minnesota adoption agencies; nonadoptees were ascertained from Minnesota birth records. Outcome measures were attempted suicide, reported by parent or offspring, and factors known to be associated with suicidal behavior including psychiatric disorder symptoms, personality traits, family environment, and academic disengagement. RESULTS: The odds of a reported suicide attempt were ∼4 times greater in adoptees compared with nonadoptees (odds ratio: 4.23). After adjustment for factors associated with suicidal behavior, the odds of reporting a suicide attempt were reduced but remained significantly elevated (odds ratio: 3.70). CONCLUSIONS: The odds for reported suicide attempt are elevated in individuals who are adopted relative to those who are not adopted. The relationship between adoption status and suicide attempt is partially mediated by factors known to be associated with suicidal behavior. Continued study of the risk of suicide attempt in adopted offspring may inform the larger investigation of suicidality in all adolescents and young adults. PMID:24019414

  17. Maternal obesity characterized by gestational diabetes increases the susceptibility of rat offspring to hepatic steatosis via a disrupted liver metabolome

    PubMed Central

    Pereira, Troy J; Fonseca, Mario A; Campbell, Kristyn E; Moyce, Brittany L; Cole, Laura K; Hatch, Grant M; Doucette, Christine A; Klein, Julianne; Aliani, Michel; Dolinsky, Vernon W

    2015-01-01

    Maternal obesity is associated with a high risk for gestational diabetes mellitus (GDM), which is a common complication of pregnancy. The influence of maternal obesity and GDM on the metabolic health of the offspring is poorly understood. We hypothesize that GDM associated with maternal obesity will cause obesity, insulin resistance and hepatic steatosis in the offspring. Female Sprague-Dawley rats were fed a high-fat (45%) and sucrose (HFS) diet to cause maternal obesity and GDM. Lean control pregnant rats received low-fat (LF; 10%) diets. To investigate the interaction between the prenatal environment and postnatal diets, rat offspring were assigned to LF or HFS diets for 12 weeks, and insulin sensitivity and hepatic steatosis were evaluated. Pregnant GDM dams exhibited excessive gestational weight gain, hyperinsulinaemia and hyperglycaemia. Offspring of GDM dams gained more weight than the offspring of lean dams due to excess adiposity. The offspring of GDM dams also developed hepatic steatosis and insulin resistance. The postnatal consumption of a LF diet did not protect offspring of GDM dams against these metabolic disorders. Analysis of the hepatic metabolome revealed increased diacylglycerol and reduced phosphatidylethanolamine in the offspring of GDM dams compared to offspring of lean dams. Consistent with altered lipid metabolism, the expression of CTP:phosphoethanolamine cytidylyltransferase, and peroxisomal proliferator activated receptor-α mRNA was reduced in the livers of GDM offspring. GDM exposure programs gene expression and hepatic metabolite levels and drives the development of hepatic steatosis and insulin resistance in young adult rat offspring. Key points Gestational diabetes mellitus is a common complication of pregnancy, but its effects on the offspring are poorly understood. We developed a rat model of diet-induced gestational diabetes mellitus that recapitulates many of the clinical features of the disease, including excessive gestational

  18. Programming of stress-related behavior and epigenetic neural gene regulation in mice offspring through maternal exposure to predator odor

    PubMed Central

    St-Cyr, Sophie; McGowan, Patrick O.

    2015-01-01

    Perinatal stress mediated through the mother can lead to long-term alterations in stress-related phenotypes in offspring. The capacity for adaptation to adversity in early life depends in part on the life history of the animal. This study was designed to examine the behavioral and neural response in adult offspring to prenatal exposure to predator odor: an ethologically-relevant psychological stressor. Pregnant mice were exposed daily to predator odors or distilled water control over the second half of the pregnancy. Predator odor exposure lead to a transient decrease in maternal care in the mothers. As adults, the offspring of predator odor-exposed mothers showed increased anti-predator behavior, a predator-odor induced decrease in activity and, in female offspring, an increased corticosterone (CORT) response to predator odor exposure. We found a highly specific response among stress-related genes within limbic brain regions. Transcript abundance of Corticotropin-releasing hormone receptor 1 (CRHR1) was elevated in the amygdala in adult female offspring of predator odor-exposed mothers. In the hippocampus of adult female offspring, decreased Brain-derived neurotrophic factor (BDNF) transcript abundance was correlated with a site-specific decrease in DNA methylation in Bdnf exon IV, indicating the potential contribution of this epigenetic mechanism to maternal programming by maternal predator odor exposure. These data indicate that maternal predator odor exposure alone is sufficient to induce an altered stress-related phenotype in adulthood, with implications for anti-predator behavior in offspring. PMID:26082698

  19. Parental age and characteristics of the offspring.

    PubMed

    Liu, Yongsheng; Zhi, Mingxing; Li, Xiuju

    2011-01-01

    The relations of an offspring to its parents are complex, and the ways in which a parent may influence the characteristics of its offspring are many. This review focuses on the relations of parental age to intelligence, health outcomes, longevity and other characteristics of offspring. Many researchers have demonstrated that children of older parents tend to be more intelligent than do children of younger parents, although there are also some negative findings. Either teenage or advanced parental age is associated with risk of birth and health outcomes in offspring. Parental age at birth displays a negative association with offspring longevity. Parental age can also influence dominant characters, sex ratio, personality and development process of the offspring. To fully analyze the influence of parental age on the offspring is of great significance in deciding the optimal age for parenthood. PMID:20887815

  20. A method for high purity intestinal epithelial cell culture from adult human and murine tissues for the investigation of innate immune function

    PubMed Central

    Graves, Christina L.; Harden, Scott W.; LaPato, Melissa; Nelson, Michael; Amador, Byron; Sorenson, Heather; Frazier, Charles J.; Wallet, Shannon M.

    2015-01-01

    Intestinal epithelial cells (IECs) serve as an important physiologic barrier between environmental antigens and the host intestinal immune system. Thus, IECs serve as a first line of defense and may act as sentinel cells during inflammatory insults. Despite recent renewed interest in IEC contributions to host immune function, the study of primary IEC has been hindered by lack of a robust culture technique, particularly for small intestinal and adult tissues. Here, a novel adaptation for culture of primary IEC is described for human duodenal organ donor tissue as well as duodenum and colon of adult mice. These epithelial cell cultures display characteristic phenotypes and are of high purity. In addition, the innate immune function of human primary IEC, specifically with regard to Toll-like receptor (TLR) expression and microbial ligand responsiveness, is contrasted with a commonly used intestinal epithelial cell line (HT-29). Specifically, TLR expression at the mRNA level and production of cytokine (IFNγ and TNFα) in response to TLR agonist stimulation is assessed. Differential expression of TLRs as well as innate immune responses to ligand stimulation is observed in human-derived cultures compared to that of HT-29. Thus, use of this adapted method to culture primary epithelial cells from adult human donors and from adult mice will allow for more appropriate studies of IECs as innate immune effectors. PMID:25193428

  1. Early postnatal treatment with soluble epoxide hydrolase inhibitor or 15-deoxy-Δ(12,14)-prostagandin J2 prevents prenatal dexamethasone and postnatal high saturated fat diet induced programmed hypertension in adult rat offspring.

    PubMed

    Lu, Pei-Chen; Sheen, Jiunn-Ming; Yu, Hong-Ren; Lin, Yu-Ju; Chen, Chih-Cheng; Tiao, Mao-Meng; Tsai, Ching-Chou; Huang, Li-Tung; Tain, You-Lin

    2016-07-01

    Prenatal dexamethasone (DEX) exposure, postnatal high-fat (HF) intake, and arachidonic acid pathway are closely related to hypertension. We tested whether a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) therapy can rescue programmed hypertension in the DEX+HF two-hit model. Four groups of Sprague Dawley rats were studied: control, DEX+HF, AUDA, and 15dPGJ2. Dexamethasone (0.1mg/kg body weight) was intraperitoneally administered to pregnant rats from gestational day 16-22. Male offspring received high-fat diet (D12331, Research Diets) from weaning to 4 months of age. In AUDA group, mother rats received 25mg/L in drinking water during lactation. In the 15dPGJ2 group, male offspring received 15dPGJ2 1.5mg/kg BW by subcutaneous injection once daily for 1 week after birth. We found postnatal HF diet aggravated prenatal DEX-induced programmed hypertension, which was similarly prevented by early treatment with AUDA or 15dPGJ2. The beneficial effects of AUDA and 15d-PGJ2 therapy include inhibition of SEH, increases of renal angiotensin converting enzyme-2 (ACE2) and angiotensin II type 2 receptor (AT2R) protein levels, and restoration of nitric oxide bioavailability. Better understanding of the impact of arachidonic acid pathway in the two-hit model will help prevent programmed hypertension in children exposed to corticosteroids and postnatal HF intake. PMID:27210044

  2. Learning of your parent’s BRCA mutation during adolescence or early adulthood: a study of offspring experiences

    PubMed Central

    Bradbury, Angela R.; Patrick-Miller, Linda; Pawlowski, Kimberly; Ibe, Comfort N.; Cummings, Shelly A.; Hlubocky, Fay; Olopade, Olufunmilayo I.; Daugherty, Christopher K.

    2015-01-01

    Objective To examine the experience, comprehension and perceptions of learning of a parent’s BRCA mutation during adolescence and early adulthood, and explore the impact on offspring’s physical and psychosocial well-being. Methods Semi-structured interviews were completed with 22 adult offspring who learned of their parent’s BRCA mutation prior to age 25 years. Data were summarized using qualitative methods and response proportions. Results Offspring reports of the content shared varied; discussion of cancer risks and offspring genetic testing were described more frequently than risk modification strategies. The majority of offspring reported a good understanding of the information shared and no negative aspects for learning this information. Some offspring reported changing their health behaviors after learning of the familial mutation; many tobacco users stopped smoking. Offspring interest in genetic counseling surrounding parent disclosure and genetic testing during adulthood were high. Conclusions Some offspring understand and respond adaptively to early communication of a genetic risk for cancer, and disclosure may foster improved health behaviors during adolescence and young adulthood. Further research is necessary to evaluate how offspring conceptualize and utilize genetic risk and to identify the biopsychosocial factors predictive of adaptive/maladaptive responses to early disclosure of hereditary risk for adult cancer. PMID:18702049

  3. Risk of emotional disorder in offspring of depressed parents: gender differences in the effect of a second emotionally affected parent.

    PubMed

    Landman-Peeters, Karlien M C; Ormel, Johan; Van Sonderen, Eric L P; Den Boer, Johan A; Minderaa, Ruud B; Hartman, Catharina A

    2008-01-01

    In offspring of depressed parents a second parent with emotional problems is likely to increase risk of emotional disorder. This effect may however differ between sons and daughters and between offspring of depressed fathers and offspring of depressed mothers. In adolescent and young-adult offspring of parents with major depressive disorder, this study examined the effects of a second affected parent, offspring gender, gender of the depressed parent and their interactions on risk of depression and anxiety disorder. We found that daughters had a higher risk of depression and anxiety than sons and that offspring of depressed mothers had a higher risk of anxiety than offspring of depressed fathers. In addition to these main effects, we found an interaction between parent and offspring gender inasmuch that sons of depressed fathers had the lowest risk of depression and anxiety relative to the other groups. A second affected parent tended to increase risk of depression and significantly increased risk of anxiety. However, this effect of a second affected parent on offspring anxiety was most prominent in daughters when the second affected parent was the father, whereas risk in sons did not increase if the father was affected as well. Our results indicate that paternal and maternal depression similarly and additively increase daughters' risk of emotional disorder, but that sons' risk only increases with maternal depression. Intergenerational transmission of emotional disorder seems strongest when the female gender is involved, either in the form of a daughter or a depressed mother. PMID:17941098

  4. Maternal Forced Swimming Reduces Cell Proliferation in the Postnatal Dentate Gyrus of Mouse Offspring.

    PubMed

    Wasinski, Frederick; Estrela, Gabriel R; Arakaki, Aline M; Bader, Michael; Alenina, Natalia; Klempin, Friederike; Araújo, Ronaldo C

    2016-01-01

    Physical exercise positively affects the metabolism and induces proliferation of precursor cells in the adult brain. Maternal exercise likewise provokes adaptations early in the offspring. Using a high-intensity swimming protocol that comprises forced swim training before and during pregnancy, we determined the effect of maternal swimming on the mouse offspring's neurogenesis. Our data demonstrate decreased proliferation in sublayers of the postnatal dentate gyrus in offspring of swimming mother at postnatal day (P) 8 accompanied with decreased survival of newly generated cells 4 weeks later. The reduction in cell numbers was predominantly seen in the hilus and molecular layer. At P35, the reduced amount of cells was also reflected by a decrease in the population of newly generated immature and mature neurons of the granule cell layer. Our data suggest that forced maternal swimming at high-intensity has a negative effect on the neurogenic niche development in postnatal offspring. PMID:27621701

  5. Maternal Forced Swimming Reduces Cell Proliferation in the Postnatal Dentate Gyrus of Mouse Offspring

    PubMed Central

    Wasinski, Frederick; Estrela, Gabriel R.; Arakaki, Aline M.; Bader, Michael; Alenina, Natalia; Klempin, Friederike; Araújo, Ronaldo C.

    2016-01-01

    Physical exercise positively affects the metabolism and induces proliferation of precursor cells in the adult brain. Maternal exercise likewise provokes adaptations early in the offspring. Using a high-intensity swimming protocol that comprises forced swim training before and during pregnancy, we determined the effect of maternal swimming on the mouse offspring's neurogenesis. Our data demonstrate decreased proliferation in sublayers of the postnatal dentate gyrus in offspring of swimming mother at postnatal day (P) 8 accompanied with decreased survival of newly generated cells 4 weeks later. The reduction in cell numbers was predominantly seen in the hilus and molecular layer. At P35, the reduced amount of cells was also reflected by a decrease in the population of newly generated immature and mature neurons of the granule cell layer. Our data suggest that forced maternal swimming at high-intensity has a negative effect on the neurogenic niche development in postnatal offspring. PMID:27621701

  6. Sex Dimorphism in Late Gestational Sleep Fragmentation and Metabolic Dysfunction in Offspring Mice

    PubMed Central

    Khalyfa, Abdelnaby; Carreras, Alba; Almendros, Isaac; Hakim, Fahed; Gozal, David

    2015-01-01

    Background: Excessive sleep fragmentation (SF) is common in pregnant women. Adult-onset metabolic disorders may begin during early development and exhibit substantial sex dimorphism. We hypothesized that metabolic dysfunction induced by gestational SF in male mice would not be apparent in female littermates. Methods: Body weight and food consumption were measured weekly in male and female offspring after late gestational SF or control sleep (SC). At 20 weeks, plasma leptin, adiponectin, lipid profiles, and insulin and glucose tolerance tests were assessed. Leptin and adiponectin, M1, and M2 macrophage messenger RNA expression and polarity were examined. Adiponectin gene promoter methylation levels in several tissues were assessed. Results: Food intake, body weight, visceral fat mass, and insulin resistance were higher, and adiponectin levels lower in male but not female offspring exposed to gestational SF. However, dyslipidemia was apparent in both male and female offspring exposed to SF, albeit of lesser magnitude. In visceral fat, leptin messenger RNA expression was selectively increased and adiponectin expression was decreased in male offspring exposed to gestational SF, but adiponectin was increased in exposed female offspring. Differences in adipokine expression also emerged in liver, subcutaneous fat, and muscle. Increased M1 macrophage markers were present in male offspring exposed to SF (SFOM) while increased M2 markers emerged in SF in female offspring (SFOF). Similarly, significant differences emerged in the methylation patterns of adiponectin promoter in SFOM and SFOF. Conclusion: Gestational sleep fragmentation increases the susceptibility to obesity and metabolic syndrome in male but not in female offspring, most likely via epigenetic changes. Thus, sleep perturbations impose long-term detrimental effects to the fetus manifesting as sex dimorphic metabolic dysfunction in adulthood. Citation: Khalyfa A, Carreras A, Almendros I, Hakim F, Gozal D. Sex

  7. Coadaptation of offspring begging and parental provisioning--an evolutionary ecological perspective on avian family life.

    PubMed

    Estramil, Natalia; Eens, Marcel; Müller, Wendt

    2013-01-01

    Offspring begging and parental provisioning are the two central social behaviours expressed during the period of parental care. Both behaviours influence each other and it is, therefore, hypothesized that they should ultimately become (genetically) correlated, stabilized by fitness costs to parents and/or offspring. By reciprocally exchanging entire clutches in canaries (Serinus canaria), we tested (1) whether there is covariation between these behaviours and (2) whether a mismatch--as introduced by cross-fostering--entails costs. Begging was scored in a standardized begging test and parental provisioning was measured via (a) the actual feeding rate and (b) using the growth rate of the foster nestlings as a proxy. Costs were established in terms of future reproductive investment in subsequent clutches and offspring growth. We found a positive and significant phenotypic covariation between offspring begging and parental feeding when using the growth rate as a proxy and, to a lesser extent, in case of the parental feeding rate. Female parents suffered no future reproductive costs when feeding foster nestlings that were more demanding than their own nestlings. Neither growth measured amongst all offspring nor the reproductive investment measured amongst the female offspring as adults was influenced by their begging behaviour. However, the reproductive investment of female offspring tended to depend on the parental qualities of their foster parents. Thus, offspring may only be able to extract resources within the limit of generosity of their foster parents. This suggests parental control of feeding, which is also supported by the positive covariation between offspring begging and parental feeding. PMID:23894662

  8. Maternal protein restriction during gestation impairs female offspring pancreas development in the rat.

    PubMed

    Calzada, Lizbeth; Morales, Angélica; Sosa-Larios, Tonantzin C; Reyes-Castro, Luis A; Rodríguez-González, Guadalupe L; Rodríguez-Mata, Verónica; Zambrano, Elena; Morimoto, Sumiko

    2016-08-01

    A maternal low-protein (LP) diet programs fetal pancreatic islet β-cell development and function and predisposes offspring to metabolic dysfunction later in life. We hypothesized that maternal protein restriction during pregnancy differentially alters β- and α-cell populations in offspring by modifying islet ontogeny and function throughout life. We aimed to investigate the effect of an LP maternal diet on pancreatic islet morphology and cellular composition in female offspring on postnatal days (PNDs) 7, 14, 21, 36, and 110. Mothers were divided into 2 groups: during pregnancy, the control group (C) was fed a diet containing 20% casein, and the LP group was fed an isocaloric diet with 10% casein. Offspring pancreases were obtained at each PND and then processed. β and α cells were detected by immunohistochemistry, and cellular area and islet size were quantified. Islet cytoarchitecture and total area were similar in C and LP offspring at all ages studied. At the early ages (PNDs 7-21), the proportion of β cells was lower in LP than C offspring. The proportion of α cells was lower in LP than C offspring on PND 14 and higher on PND 21. The β/α-cell ratio was lower in LP compared with C offspring on PNDs 7 and 21 and higher on PND 36 (being similar on PNDs 14 and 110). We concluded that maternal protein restriction during pregnancy modifies offspring islet cell ontogeny by altering the proportions of islet sizes and by reducing the number of β cells postnatally, which may impact pancreatic function in adult life. PMID:27440540

  9. Coadaptation of Offspring Begging and Parental Provisioning - An Evolutionary Ecological Perspective on Avian Family Life

    PubMed Central

    Estramil, Natalia; Eens, Marcel; Müller, Wendt

    2013-01-01

    Offspring begging and parental provisioning are the two central social behaviours expressed during the period of parental care. Both behaviours influence each other and it is, therefore, hypothesized that they should ultimately become (genetically) correlated, stabilized by fitness costs to parents and/or offspring. By reciprocally exchanging entire clutches in canaries (Serinus canaria), we tested (1) whether there is covariation between these behaviours and (2) whether a mismatch - as introduced by cross-fostering - entails costs. Begging was scored in a standardized begging test and parental provisioning was measured via (a) the actual feeding rate and (b) using the growth rate of the foster nestlings as a proxy. Costs were established in terms of future reproductive investment in subsequent clutches and offspring growth. We found a positive and significant phenotypic covariation between offspring begging and parental feeding when using the growth rate as a proxy and, to a lesser extent, in case of the parental feeding rate. Female parents suffered no future reproductive costs when feeding foster nestlings that were more demanding than their own nestlings. Neither growth measured amongst all offspring nor the reproductive investment measured amongst the female offspring as adults was influenced by their begging behaviour. However, the reproductive investment of female offspring tended to depend on the parental qualities of their foster parents. Thus, offspring may only be able to extract resources within the limit of generosity of their foster parents. This suggests parental control of feeding, which is also supported by the positive covariation between offspring begging and parental feeding. PMID:23894662

  10. Elk3 deficiency causes transient impairment in post-natal retinal vascular development and formation of tortuous arteries in adult murine retinae.

    PubMed

    Weinl, Christine; Wasylyk, Christine; Garcia Garrido, Marina; Sothilingam, Vithiyanjali; Beck, Susanne C; Riehle, Heidemarie; Stritt, Christine; Roux, Michel J; Seeliger, Mathias W; Wasylyk, Bohdan; Nordheim, Alfred

    2014-01-01

    Serum Response Factor (SRF) fulfills essential roles in post-natal retinal angiogenesis and adult neovascularization. These functions have been attributed to the recruitment by SRF of the cofactors Myocardin-Related Transcription Factors MRTF-A and -B, but not the Ternary Complex Factors (TCFs) Elk1 and Elk4. The role of the third TCF, Elk3, remained unknown. We generated a new Elk3 knockout mouse line and showed that Elk3 had specific, non-redundant functions in the retinal vasculature. In Elk3(-/-) mice, post-natal retinal angiogenesis was transiently delayed until P8, after which it proceeded normally. Interestingly, tortuous arteries developed in Elk3(-/-) mice from the age of four weeks, and persisted into late adulthood. Tortuous vessels have been observed in human pathologies, e.g. in ROP and FEVR. These human disorders were linked to altered activities of vascular endothelial growth factor (VEGF) in the affected eyes. However, in Elk3(-/-) mice, we did not observe any changes in VEGF or several other potential confounding factors, including mural cell coverage and blood pressure. Instead, concurrent with the post-natal transient delay of radial outgrowth and the formation of adult tortuous arteries, Elk3-dependent effects on the expression of Angiopoietin/Tie-signalling components were observed. Moreover, in vitro microvessel sprouting and microtube formation from P10 and adult aortic ring explants were reduced. Collectively, these results indicate that Elk3 has distinct roles in maintaining retinal artery integrity. The Elk3 knockout mouse is presented as a new animal model to study retinal artery tortuousity in mice and human patients. PMID:25203538

  11. Elk3 Deficiency Causes Transient Impairment in Post-Natal Retinal Vascular Development and Formation of Tortuous Arteries in Adult Murine Retinae

    PubMed Central

    Weinl, Christine; Wasylyk, Christine; Garcia Garrido, Marina; Sothilingam, Vithiyanjali; Beck, Susanne C.; Riehle, Heidemarie; Stritt, Christine; Roux, Michel J.; Seeliger, Mathias W.; Wasylyk, Bohdan; Nordheim, Alfred

    2014-01-01

    Serum Response Factor (SRF) fulfills essential roles in post-natal retinal angiogenesis and adult neovascularization. These functions have been attributed to the recruitment by SRF of the cofactors Myocardin-Related Transcription Factors MRTF-A and -B, but not the Ternary Complex Factors (TCFs) Elk1 and Elk4. The role of the third TCF, Elk3, remained unknown. We generated a new Elk3 knockout mouse line and showed that Elk3 had specific, non-redundant functions in the retinal vasculature. In Elk3(−/−) mice, post-natal retinal angiogenesis was transiently delayed until P8, after which it proceeded normally. Interestingly, tortuous arteries developed in Elk3(−/−) mice from the age of four weeks, and persisted into late adulthood. Tortuous vessels have been observed in human pathologies, e.g. in ROP and FEVR. These human disorders were linked to altered activities of vascular endothelial growth factor (VEGF) in the affected eyes. However, in Elk3(−/−) mice, we did not observe any changes in VEGF or several other potential confounding factors, including mural cell coverage and blood pressure. Instead, concurrent with the post-natal transient delay of radial outgrowth and the formation of adult tortuous arteries, Elk3-dependent effects on the expression of Angiopoietin/Tie-signalling components were observed. Moreover, in vitro microvessel sprouting and microtube formation from P10 and adult aortic ring explants were reduced. Collectively, these results indicate that Elk3 has distinct roles in maintaining retinal artery integrity. The Elk3 knockout mouse is presented as a new animal model to study retinal artery tortuousity in mice and human patients. PMID:25203538

  12. Predator-Specific Effects on Incubation Behaviour and Offspring Growth in Great Tits

    PubMed Central

    Basso, Alessandra; Richner, Heinz

    2015-01-01

    In birds, different types of predators may target adults or offspring differentially and at different times of the reproductive cycle. Hence they may also differentially influence incubation behaviour and thus embryonic development and offspring phenotype. This is poorly understood, and we therefore performed a study to assess the effects of the presence of either a nest predator or a predator targeting adults and offspring after fledging on female incubation behaviour in great tits (Parus major), and the subsequent effects on offspring morphological traits. We manipulated perceived predation risk during incubation using taxidermic models of two predators: the short-tailed weasel posing a risk to incubating females and nestlings, and the sparrowhawk posing a risk to adults and offspring after fledging. To disentangle treatment effects induced during incubation from potential carry-over effects of parental behaviour after hatching, we cross-fostered whole broods from manipulated nests with broods from unmanipulated nests. Both predator treatments lead to a reduced on- and off-bout frequency, to a slower decline in on-bout temperature as incubation advanced and showed a negative effect on nestling body mass gain. At the current state of knowledge on predator-induced variation in incubation patterns alternative hypotheses are feasible, and the findings of this study will be useful for guiding future research. PMID:25830223

  13. In utero transplantation of adult bone marrow decreases perinatal lethality and rescues the bone phenotype in the knockin murine model for classical, dominant osteogenesis imperfecta.

    PubMed

    Panaroni, Cristina; Gioia, Roberta; Lupi, Anna; Besio, Roberta; Goldstein, Steven A; Kreider, Jaclynn; Leikin, Sergey; Vera, Juan Carlos; Mertz, Edward L; Perilli, Egon; Baruffaldi, Fabio; Villa, Isabella; Farina, Aurora; Casasco, Marco; Cetta, Giuseppe; Rossi, Antonio; Frattini, Annalisa; Marini, Joan C; Vezzoni, Paolo; Forlino, Antonella

    2009-07-01

    Autosomal dominant osteogenesis imperfecta (OI) caused by glycine substitutions in type I collagen is a paradigmatic disorder for stem cell therapy. Bone marrow transplantation in OI children has produced a low engraftment rate, but surprisingly encouraging symptomatic improvements. In utero transplantation (IUT) may hold even more promise. However, systematic studies of both methods have so far been limited to a recessive mouse model. In this study, we evaluated intrauterine transplantation of adult bone marrow into heterozygous BrtlIV mice. Brtl is a knockin mouse with a classical glycine substitution in type I collagen [alpha1(I)-Gly349Cys], dominant trait transmission, and a phenotype resembling moderately severe and lethal OI. Adult bone marrow donor cells from enhanced green fluorescent protein (eGFP) transgenic mice engrafted in hematopoietic and nonhematopoietic tissues differentiated to trabecular and cortical bone cells and synthesized up to 20% of all type I collagen in the host bone. The transplantation eliminated the perinatal lethality of heterozygous BrtlIV mice. At 2 months of age, femora of treated Brtl mice had significant improvement in geometric parameters (P < .05) versus untreated Brtl mice, and their mechanical properties attained wild-type values. Our results suggest that the engrafted cells form bone with higher efficiency than the endogenous cells, supporting IUT as a promising approach for the treatment of genetic bone diseases. PMID:19414862

  14. EphB2 and EphB3 play an important role in the lymphoid seeding of murine adult thymus.

    PubMed

    Alfaro, David; García-Ceca, Javier; Farias-de-Oliveira, Desio A; Terra-Granado, Eugenia; Montero-Herradón, Sara; Cotta-de-Almeida, Vinicius; Savino, Wilson; Zapata, Agustín

    2015-12-01

    Adult thymuses lacking either ephrin type B receptor 2 (EphB2) or EphB3, or expressing a truncated form of EphB2, the forward signal-deficient EphB2LacZ, have low numbers of early thymic progenitors (ETPs) and are colonized in vivo by reduced numbers of injected bone marrow (BM) lineage-negative (Lin(-)) cells. Hematopoietic progenitors from these EphB mutants showed decreased capacities to colonize wild type (WT) thymuses compared with WT precursors, with EphB2(-/-) cells exhibiting the greatest reduction. WT BM Lin(-) cells also showed decreased colonizing capacity into mutant thymuses. The reduction was also more severe in EphB2(-/-) host thymuses, with a less severe phenotype in the EphB2LacZ thymus. These results suggest a major function for forward signaling through EphB2 and, to a lesser extent, EphB3, in either colonizing progenitor cells or thymic stromal cells, for in vivo adult thymus recruitment. Furthermore, the altered expression of the molecules involved in thymic colonization that occurs in the mutant thymus correlates with the observed colonizing capacities of different mutant mice. Reduced production of CCL21 and CCL25 occurred in the thymus of the 3 EphB-deficient mice, but their expression, similar to that of P-selectin, on blood vessels, the method of entry of progenitor cells into the vascular thymus, only showed a significant reduction in EphB2(-/-) and EphB3(-/-) thymuses. Decreased migration into the EphB2(-/-) thymuses correlated also with reduced expression of both ephrinB1 and ephrinB2, without changes in the EphB2LacZ thymuses. In the EphB3(-/-) thymuses, only ephrinB1 expression appeared significantly diminished, confirming the relevance of forward signals mediated by the EphB2-ephrinB1 pair in cell recruitment into the adult thymus. PMID:25810451

  15. Adult murine prostate basal and luminal cells are self-sustained lineages that can both serve as targets for prostate cancer initiation

    PubMed Central

    Choi, Nahyun; Zhang, Boyu; Zhang, Li; Ittmann, Michael; Xin, Li

    2012-01-01

    Summary The prostate epithelial lineage hierarchy and the cellular origin for prostate cancer remain inadequately defined. Using a lineage tracing approach, we show that adult rodent prostate basal and luminal cells are independently self-sustained in vivo. Disrupting the tumor suppressor Pten in either lineage led to prostate cancer initiation. However, the cellular composition and onset dynamics of the resulting tumors are distinctive. Prostate luminal cells are more responsive to Pten null-induced mitogenic signaling. In contrast, basal cells are resistant to direct transformation. Instead, loss of Pten activity induces the capability of basal cells to differentiate into transformation-competent luminal cells. Our study suggests that deregulation of epithelial differentiation is a critical step for the initiation of prostate cancers of basal cell origin. PMID:22340597

  16. Vaccination of adult and newborn mice of a resistant strain (C57BL/6J) against challenge with leukemias induced by Moloney murine leukemia virus

    SciTech Connect

    Reif, A.E.

    1985-01-01

    Adult or newborn C57BL/6J mice were immunized with isogenic Moloney strain MuLV-induced leukemia cells irradiated with 10,000 rads or treated with low concentrations of formalin. Groups of immunized and control mice were challenged with a range of doses of viable leukemia cells, and tumor deaths were recorded for 90 days after challenge. Then, the doses of challenge cells which produced 50% tumor deaths were calculated for immunized and control mice. The logarithm of their ratio quantified the degree of protection provided by immunization. For adult C57BL/6J mice, a single immunization with MuLV-induced leukemia cells was not effective; either cells plus Bacillus Calmette-Guerin or Corynebacterium parvum, or else two immunizations with irradiated leukemia cells were needed to produce statistically significant increases in the values of the doses of challenge cells which produced 50% tumor deaths. Cross-protection was obtained by immunization with other isogenic MuLV-induced leukemias, but not by immunization with isogenic carcinogen-induced tumors or with an isogenic spontaneous leukemia. For newborn mice, a single injection of irradiated leukemia cells provided 1.3 to 1.5 logs of protection, and admixture of B. Calmette-Guerin or C. parvum increased this protection to 2.4 to 2.7 logs. Since irradiated and frozen-thawed MuLV-induced leukemia cells contained viable MuLV, leukemia cells treated with 0.5 or 1.0% formalin were tested as an alternative. A single injection of formalin-treated isogenic leukemia cells admixed with C. parvum provided between 1.7 and 2.8 logs of protection. These results demonstrate that a single vaccination of newborn animals against a highly antigenic virally induced leukemia produces strong protection against a subsequent challenge with viable leukemia cells.

  17. Infectious Offspring: How Birds Acquire and Transmit an Avian Polyomavirus in the Wild

    PubMed Central

    Potti, Jaime; Blanco, Guillermo; Lemus, Jesús Á.; Canal, David

    2007-01-01

    Detailed patterns of primary virus acquisition and subsequent dispersal in wild vertebrate populations are virtually absent. We show that nestlings of a songbird acquire polyomavirus infections from larval blowflies, common nest ectoparasites of cavity-nesting birds, while breeding adults acquire and renew the same viral infections via cloacal shedding from their offspring. Infections by these DNA viruses, known potential pathogens producing disease in some bird species, therefore follow an ‘upwards vertical’ route of an environmental nature mimicking horizontal transmission within families, as evidenced by patterns of viral infection in adults and young of experimental, cross-fostered offspring. This previously undescribed route of viral transmission from ectoparasites to offspring to parent hosts may be a common mechanism of virus dispersal in many taxa that display parental care. PMID:18060070

  18. Scaling of Foraminifera Parent and Offspring Size through the Phanerozoic

    NASA Astrophysics Data System (ADS)

    Guo, D.; Holme, F.; Payne, J.; Skotheim, J.

    2011-12-01

    Since before the 1940s, scientists have studied the scaling of body mass with metabolic rate, heart rate, fecundity, cardiac cycling rate, and numerous other traits. Like these traits, offspring mass scales with parent body mass for plants and animals. However, the relationship is not well documented in single-celled organisms. In our study, we examined how adult size scales with embryo size in fusulinid foraminifera. Fusulinids, and most other foraminifera, are an exceptional study group because the proloculus (the initial shell chamber) can be used to measure the size of the daughter cell at the time it became independent of its parent. We find that proloculus size increases with adult test size across fusulinid species. This pattern may result because the genomic sizes and the cellular machinery necessary for a larger adult size place limits on how small the initial daughter cell can be.

  19. Parent-Offspring Correlations in Pedometer-Assessed Physical Activity

    PubMed Central

    Jacobi, David; Caille, Agnès; Borys, Jean-Michel; Lommez, Agnès; Couet, Charles; Charles, Marie-Aline; Oppert, Jean-Michel

    2011-01-01

    Background Physical activity is a major component of a healthy lifestyle in youth and adults. To identify determinants of this complex behavior is an important research objective in the process of designing interventions to promote physical activity at population level. In addition to individual determinants, there is evidence documenting familial influences on physical activity. However, the few studies that have addressed this issue with objective measures did not provide data on parent-offspring physical activity relationships throughout childhood and adolescence. The purpose of this study was to assess familial correlations in pedometer-assessed physical activity. Methods We measured ambulatory activity in 286 French nuclear families (283 mothers, 237 fathers, and 631 children aged 8–18 years) by pedometer recordings (Yamax Digiwalker DW 450) over a week. Correlations were computed with their 95% confidence intervals (CI) for spouse pairs, siblings, mother-offspring, and father-offspring. Data were expressed as steps per day and computed both for the full recording period and separately for weekdays and weekends. Results The correlations were the highest between siblings (r = 0.28, 95%CI: 0.17–0.38). Parent–offspring correlations were significant in mothers (r = 0.21, 95%CI: 0.12–0.30), especially between mothers and daughters (r = 0.24, 95%CI: 0.12–0.36 vs. r = 0.18, 95%CI: 0.05–0.31 for sons), but were almost nonexistent in fathers. Correlations were generally higher on weekend days compared to weekdays. Mother-offspring correlations did not decrease with increasing age of children (r = 0.17, 95%CI: 0.00–0.34 in 8–11-year-olds, r = 0.20, 95%CI: 0.07–0.33 in 12–15-year-olds, and r = 0.25, 95%CI: 0.07–0.39 in ≥16-year-olds). Finally, between-spouse correlations were significant only during weekend days (r = 0.14, 95%CI: 0.01–0.27). Conclusion Ambulatory activity correlated within families, with a

  20. Associations of Maternal Pre-pregnancy Body Mass Index and Gestational Weight Gain with Offspring Longitudinal Change in BMI

    PubMed Central

    Lawrence, Gabriella M.; Shulman, Shani; Hochner, Hagit; Sitlani, Colleen M.; Burger, Ayala; Savitsky, Bella; Granot-Hershkovitz, Einat; Lumley, Thomas; Kwok, Pui-Yan; Hasselson, Stephanie; Enquobahrie, Daniel; Wander, Pandora L.; Manor, Orly; Siscovick, David S.; Friedlander, Yechiel

    2013-01-01

    Introduction Studies demonstrate associations between changes in obesity-related phenotypes and cardiovascular risk. While maternal pre-pregnancy BMI (mppBMI) and gestational weight gain (GWG) may be associated with adult offspring adiposity, no study has examined associations with obesity changes. Objectives We examined associations of mppBMI and GWG with longitudinal change in offspring's BMI (ΔBMI), and assessed whether associations are explained by offspring genetics. Design and Methods We used a birth cohort of 1400 adults, with data at birth, age 17 and 32. After genotyping offspring, we created genetic scores, predictive of exposures and outcome, and fit linear regression models with and without scores to examine the associations of mppBMI and GWG with ΔBMI. Results A one SD change in mppBMI and GWG was associated with a 0.83 and a 0.75 kg/m2 increase in ΔBMI respectively. The association between mppBMI and offspring ΔBMI was slightly attenuated (12%) with the addition of genetic scores. In the GWG model, a significant substantial 28.2% decrease in the coefficient was observed. Conclusions This study points to an association between maternal excess weight in pregnancy and offspring BMI change from adolescence to adulthood. Genetic factors may account, in part, for the GWG/ΔBMI association. These findings broaden observations that maternal obesity-related phenotypes have long-term consequences for offspring health. PMID:24124160

  1. The Murine Lung Microbiome Changes During Lung Inflammation and Intranasal Vancomycin Treatment

    PubMed Central

    Barfod, Kenneth Klingenberg; Vrankx, Katleen; Mirsepasi-Lauridsen, Hengameh Chloé; Hansen, Jitka Stilund; Hougaard, Karin Sørig; Larsen, Søren Thor; Ouwenhand, Arthur C.; Krogfelt, Karen Angeliki

    2015-01-01

    Most microbiome research related to airway diseases has focused on the gut microbiome. This is despite advances in culture independent microbial identification techniques revealing that even healthy lungs possess a unique dynamic microbiome. This conceptual change raises the question; if lung diseases could be causally linked to local dysbiosis of the local lung microbiota. Here, we manipulate the murine lung and gut microbiome, in order to show that the lung microbiota can be changed experimentally. We have used four different approaches: lung inflammation by exposure to carbon nano-tube particles, oral probiotics and oral or intranasal exposure to the antibiotic vancomycin. Bacterial DNA was extracted from broncho-alveolar and nasal lavage fluids, caecum samples and compared by DGGE. Our results show that: the lung microbiota is sex dependent and not just a reflection of the gut microbiota, and that induced inflammation can change lung microbiota. This change is not transferred to offspring. Oral probiotics in adult mice do not change lung microbiome detectible by DGGE. Nasal vancomycin can change the lung microbiome preferentially, while oral exposure does not. These observations should be considered in future studies of the causal relationship between lung microbiota and lung diseases. PMID:26668669

  2. The Murine Lung Microbiome Changes During Lung Inflammation and Intranasal Vancomycin Treatment.

    PubMed

    Barfod, Kenneth Klingenberg; Vrankx, Katleen; Mirsepasi-Lauridsen, Hengameh Chloé; Hansen, Jitka Stilund; Hougaard, Karin Sørig; Larsen, Søren Thor; Ouwenhand, Arthur C; Krogfelt, Karen Angeliki

    2015-01-01

    Most microbiome research related to airway diseases has focused on the gut microbiome. This is despite advances in culture independent microbial identification techniques revealing that even healthy lungs possess a unique dynamic microbiome. This conceptual change raises the question; if lung diseases could be causally linked to local dysbiosis of the local lung microbiota. Here, we manipulate the murine lung and gut microbiome, in order to show that the lung microbiota can be changed experimentally. We have used four different approaches: lung inflammation by exposure to carbon nano-tube particles, oral probiotics and oral or intranasal exposure to the antibiotic vancomycin. Bacterial DNA was extracted from broncho-alveolar and nasal lavage fluids, caecum samples and compared by DGGE. Our results show that: the lung microbiota is sex dependent and not just a reflection of the gut microbiota, and that induced inflammation can change lung microbiota. This change is not transferred to offspring. Oral probiotics in adult mice do not change lung microbiome detectible by DGGE. Nasal vancomycin can change the lung microbiome preferentially, while oral exposure does not. These observations should be considered in future studies of the causal relationship between lung microbiota and lung diseases. PMID:26668669

  3. Offspring ADHD as a Risk Factor for Parental Marital Problems: Controls for Genetic and Environmental Confounds

    PubMed Central

    Schermerhorn, Alice C.; D’Onofrio, Brian M.; Slutske, Wendy S.; Emery, Robert E.; Turkheimer, Eric; Harden, K. Paige; Heath, Andrew C.; Martin, Nicholas G.

    2013-01-01

    Background Previous studies have found that child attention-deficit/hyperactivity disorder (ADHD) is associated with more parental marital problems. The reasons for this association are unclear, however. The association might be due to genetic or environmental confounds that contribute to both marital problems and ADHD. Method Data were drawn from the Australian Twin Registry, including 1296 individual twins, their spouses, and offspring. We studied adult twins who were discordant for offspring ADHD. Using a discordant twin pairs design, we examined the extent to which genetic and environmental confounds, as well as measured parental and offspring characteristics, explain the ADHD-marital problems association. Results Offspring ADHD predicted parental divorce and marital conflict. The associations were also robust when comparing differentially exposed identical twins to control for unmeasured genetic and environmental factors, when controlling for measured maternal and paternal psychopathology, when restricting the sample based on timing of parental divorce and ADHD onset, and when controlling for other forms of offspring psychopathology. Each of these controls rules out alternative explanations for the association. Conclusion The results of the current study converge with those of prior research in suggesting that factors directly associated with offspring ADHD increase parental marital problems. PMID:22958575

  4. Cloning of murine ferrochelatase.

    PubMed Central

    Brenner, D A; Frasier, F

    1991-01-01

    Ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1) catalyzes the last step in the heme biosynthetic pathway, the chelation of ferrous iron and protoporphyrin to form heme. The activity of ferrochelatase is deficient in the inherited disease protoporphyria. In this study, murine ferrochelatase cDNAs were obtained by screening cDNA libraries with an oligonucleotide probe. The derived amino acid sequence of murine ferrochelatase has 47% identity with the recently cloned Saccharomyces cerevisiae ferrochelatase, but it is not significantly similar to other published sequences. Results of Southern blotting are consistent with a single murine ferrochelatase gene, while Northern blotting demonstrates two ferrochelatase transcripts in all tissues examined. The ferrochelatase protein and mRNAs have different relative concentrations in different tissues. The cloning of murine ferrochelatase cDNAs provides the basis for future studies on ferrochelatase gene expression and on the identification of the molecular defect in protoporphyria. Images PMID:1704134

  5. Vitamin D status during Pregnancy and Aspects of Offspring Health

    PubMed Central

    Ponsonby, Anne-Louise; Lucas, Robyn M.; Lewis, Sharon; Halliday, Jane

    2010-01-01

    Low maternal vitamin D levels during pregnancy have been linked to various health outcomes in the offspring, ranging from periconceptional effects to diseases of adult onset. Maternal and infant cord 25(OH)D levels are highly correlated. Here, we review the available evidence for these adverse health effects. Most of the evidence has arisen from observational epidemiological studies, but randomized controlled trials are now underway. The evidence to date supports that women should be monitored and treated for vitamin D deficiency during pregnancy but optimal and upper limit serum 25(OH)D levels during pregnancy are not known. PMID:22254029

  6. Sense and antisense transcripts of the developmentally regulated murine hsp70.2 gene are expressed in distinct and only partially overlapping areas in the adult brain

    NASA Technical Reports Server (NTRS)

    Murashov, A. K.; Wolgemuth, D. J.

    1996-01-01

    We have examined the spatial pattern of expression of a member of the hsp70 gene family, hsp70.2, in the mouse central nervous system. Surprisingly, RNA blot analysis and in situ hybridization revealed abundant expression of an 'antisense' hsp70.2 transcript in several areas of adult mouse brain. Two different transcripts recognized by sense and antisense riboprobes for the hsp70.2 gene were expressed in distinct and only partially overlapping neuronal populations. RNA blot analysis revealed low levels of the 2.7 kb transcript of hsp70.2 in several areas of the brain, with highest signal in the hippocampus. Abundant expression of a slightly larger (approximately 2.8 kb) 'antisense' transcript was detected in several brain regions, notably in the brainstem, cerebellum, mesencephalic tectum, thalamus, cortex, and hippocampus. In situ hybridization revealed that the sense and antisense transcripts were both predominantly neuronal and localized to the same cell types in the granular layer of the cerebellum, trapezoid nucleus of the superior olivary complex, locus coeruleus and hippocampus. The hsp70.2 antisense transcripts were particularly abundant in the frontal cortex, dentate gyrus, subthalamic nucleus, zona incerta, superior and inferior colliculi, central gray, brainstem, and cerebellar Purkinje cells. Our findings have revealed a distinct cellular and spatial localization of both sense and antisense transcripts, demonstrating a new level of complexity in the function of the heat shock genes.

  7. Isolation and expansion of adult cardiac stem/progenitor cells in the form of cardiospheres from human cardiac biopsies and murine hearts.

    PubMed

    Chimenti, Isotta; Gaetani, Roberto; Barile, Lucio; Forte, Elvira; Ionta, Vittoria; Angelini, Francesco; Frati, Giacomo; Messina, Elisa; Giacomello, Alessandro

    2012-01-01

    The successful isolation and ex vivo expansion of resident cardiac stem/progenitor cells from human heart biopsies has allowed us to study their biological characteristics and their applications in therapeutic approaches for the repair of ischemic/infarcted heart, the preparation of tissue-engineered cardiac grafts and, possibly, the design of cellular kits for drug screening applications. From the first publication of the original method in 2004, several adjustments and slight changes have been introduced to optimize and adjust the procedure to the evolving experimental and translational needs. Moreover, due to the wide applicability of such a method (which is based on the exploitation of intrinsic functional properties of cells with regenerative properties that are present in most tissues), the key steps of this procedure have been used to derive several kinds of tissue-specific adult stem cells for preclinical or clinical purposes.In order to define the original procedure, complete with the up-to-date modifications introduced through the years, an exhaustive description of the current protocol is performed in this chapter, with particular attention in highlighting critical steps and troubleshoots. The procedure described here consists of modular steps, that could be employed to derive cells from any kind of tissue biopsy, and needs to be considered the gold standard of all the so-called "explant methods" or "cardiosphere methods," and it represents a milestone in the clinical translation of autologous cell therapy. PMID:22610568

  8. Effective treatment of a murine model of adult T-cell leukemia using 211At-7G7/B6 and its combination with unmodified anti-Tac (daclizumab) directed toward CD25.

    PubMed

    Zhang, Zhuo; Zhang, Meili; Garmestani, Kayhan; Talanov, Vladimir S; Plascjak, Paul S; Beck, Barbara; Goldman, Carolyn; Brechbiel, Martin W; Waldmann, Thomas A

    2006-08-01

    Adult T-cell leukemia (ATL) consists of an overabundance of T cells, which express CD25. Therapeutic efficacy of astatine-211 ((211)At)-labeled murine monoclonal antibody 7G7/B6 alone and in combination with daclizumab was evaluated in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice given injections of MET-1 human T-cell leukemia cells. Daclizumab and 7G7/B6 are directed toward different epitopes of CD25. Either a single dose of 12 microCi (0.444 MBq) (211)At-7G7/B6 per mouse given intravenously or receptor-saturating doses of daclizumab given at 100 microg weekly for 4 weeks intravenously inhibited tumor growth as monitored by serum levels of human beta-2 microglobulin (beta(2)mu) and by prolonged survival of leukemia-bearing mice compared with the control groups (P < .001). The combination of 2 agents enhanced the antitumor effect when compared with groups treated with 12 microCi (0.444 MBq) of (211)At-7G7/B6 (P < .05) or daclizumab alone (P < .05). The median survival duration of the PBS group was 62.6 days and 61.5 days in the radiolabeled nonspecific antibody (211)At-11F11-treated group. In contrast, 91% of mice in the combination group survived through day 94. These results that demonstrate a significantly improved therapeutic efficacy by combining (211)At-7G7/B6 with daclizumab support a clinical trial of this regimen in patients with ATL. PMID:16569769

  9. Maternal obesity alters endoplasmic reticulum homeostasis in offspring pancreas.

    PubMed

    Soeda, Jumpei; Mouralidarane, Angelina; Cordero, Paul; Li, Jiawei; Nguyen, Vi; Carter, Rebeca; Kapur, Sabrina R; Pombo, Joaquim; Poston, Lucilla; Taylor, Paul D; Vinciguerra, Manlio; Oben, Jude A

    2016-06-01

    The prevalence of non-alcoholic fatty pancreas disease (NAFPD) is increasing in parallel with obesity rates. Stress-related alterations in endoplasmic reticulum (ER), such as the unfolded protein response (UPR), are associated with obesity. The aim of this study was to investigate ER imbalance in the pancreas of a mice model of adult and perinatal diet-induced obesity. Twenty female C57BL/6J mice were assigned to control (Con) or obesogenic (Ob) diets prior to and during pregnancy and lactation. Their offspring were weaned onto Con or Ob diets up to 6 months post-partum. Then, after sacrifice, plasma biochemical analyses, gene expression, and protein concentrations were measured in pancreata. Offspring of Ob-fed mice had significantly increased body weight (p < 0.001) and plasma leptin (p < 0.001) and decreased insulin (p < 0.01) levels. Maternal obesogenic diet decreased the total and phosphorylated Eif2α and increased spliced X-box binding protein 1 (XBP1). Pancreatic gene expression of downstream regulators of UPR (EDEM, homocysteine-responsive endoplasmic reticulum-resident (HERP), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP)) and autophagy-related proteins (LC3BI/LC3BII) were differently disrupted by obesogenic feeding in both mothers and offspring (from p < 0.1 to p < 0.001). Maternal obesity and Ob feeding in their offspring alter UPR in NAFPD, with involvement of proapoptotic and autophagy-related markers. Upstream and downstream regulators of PERK, IRE1α, and ATF6 pathways were affected differently following the obesogenic insults. PMID:26979740

  10. Trends in dietary carbohydrate consumption from 1991 to 2008 in the Framingham Heart Study Offspring Cohort

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The intake of carbohydrates has been evaluated cross-sectionally, but not longitudinally in an ageing American adult population. The aim of the present study was to examine trends in the intake of dietary carbohydrates and their major food sources among the Framingham Heart Study Offspring (FOS) coh...

  11. Epigenetic Patterns Modulate the Connection between Developmental Dynamics of Parenting and Offspring Psychosocial Adjustment

    ERIC Educational Resources Information Center

    Naumova, Oksana Yu.; Hein, Sascha; Suderman, Matthew; Barbot, Baptiste; Lee, Maria; Raefski, Adam; Dobrynin, Pavel V.; Brown, Pamela J.; Szyf, Moshe; Luthar, Suniya S.; Grigorenko, Elena L.

    2016-01-01

    This study attempted to establish and quantify the connections between parenting, offspring psychosocial adjustment, and the epigenome. The participants, 35 African American young adults (19 females and 16 males; age = 17-29.5 years), represented a subsample of a 3-wave longitudinal 15-year study on the developmental trajectories of low-income…

  12. Epigenome-wide DNA methylation analysis implicates neuronal and inflammatory signaling pathways in adult murine hepatic tumorigenesis following perinatal exposure to bisphenol A.

    PubMed

    Weinhouse, Caren; Sartor, Maureen A; Faulk, Christopher; Anderson, Olivia S; Sant, Karilyn E; Harris, Craig; Dolinoy, Dana C

    2016-07-01

    Developmental exposure to the endocrine-active compound bisphenol A (BPA) has been linked to epigenotoxic and potential carcinogenic effects in rodent liver, prostate, and mammary glands. A dose-dependent increase in hepatic tumors in 10-month mice perinatally exposed to one of three doses of BPA (50 ng, 50 µg, or 50 mg BPA/kg chow) was previously reported. These tumors represent early-onset disease and lack classical sexual dimorphism in incidence. Here, adult epigenome-wide liver DNA methylation profiles to identify gene promoters associated with perinatal BPA exposure and disease in 10-month mice with and without liver tumors were investigated. Mice with hepatic tumors showed 12,822 (1.8%) probes with differential methylation as compared with non-tumor animals, of which 8,656 (67.5%) were hypomethylated. A significant enrichment of differential methylation in Gene Ontology (GO) terms and biological processes related to morphogenesis and development, and epigenomic alteration were observed. Pathway enrichment revealed a predominance of hypermethylated neuronal signaling pathways linked to energy regulation and metabolic function, supporting metabolic consequences in the liver via BPA-induced disruption of neuronal signaling pathways. Hypothesis-driven pathway analysis revealed mouse and human genes linked to BPA exposure related to intracellular Jak/STAT and MAPK signaling pathways. Taken together, these findings are indicators of the relevance of the hepatic tumor phenotype seen in BPA-exposed mice to human health. This work demonstrated that epigenome-wide discovery experiments in animal models were effective tools for identification and understanding of paralagous epimutations salient to human disease. Environ. Mol. Mutagen. 57:435-446, 2016. © 2016 Wiley Periodicals, Inc. PMID:27334623

  13. Maternally derived carotenoid pigments affect offspring survival, sex ratio, and sexual attractiveness in a colorful songbird

    NASA Astrophysics Data System (ADS)

    McGraw, K. J.; Adkins-Regan, E.; Parker, R. S.

    2005-08-01

    In egg-laying animals, mothers can influence the development of their offspring via the suite of biochemicals they incorporate into the nourishing yolk (e.g. lipids, hormones). However, the long-lasting fitness consequences of this early nutritional environment have often proved elusive. Here, we show that the colorful carotenoid pigments that female zebra finches ( Taeniopygia guttata) deposit into egg yolks influence embryonic and nestling survival, the sex ratio of fledged offspring, and the eventual ornamental coloration displayed by their offspring as adults. Mothers experimentally supplemented with dietary carotenoids prior to egg-laying incorporated more carotenoids into eggs, which, due to the antioxidant activity of carotenoids, rendered their embryos less susceptible to free-radical attack during development. These eggs were subsequently more likely to hatch, fledge offspring, produce more sons than daughters, and produce sons who exhibited more brightly colored carotenoid-based beak pigmentation. Provisioned mothers also acquired more colorful beaks, which directly predicted levels of carotenoids found in eggs, thus indicating that these pigments may function not only as physiological ‘damage-protectants’ in adults and offspring but also as morphological signals of maternal reproductive capabilities.

  14. Maternal testosterone exposure increases anxiety-like behavior and impacts the limbic system in the offspring

    PubMed Central

    Hu, Min; Richard, Jennifer Elise; Maliqueo, Manuel; Kokosar, Milana; Fornes, Romina; Benrick, Anna; Jansson, Thomas; Ohlsson, Claes; Wu, Xiaoke; Skibicka, Karolina Patrycja; Stener-Victorin, Elisabet

    2015-01-01

    During pregnancy, women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring. This study investigated whether maternal androgen excess causes anxiety-like behavior in offspring mimicking anxiety disorders in PCOS. The PCOS phenotype was induced in rats following prenatal androgen (PNA) exposure. PNA offspring displayed anxiety-like behavior in the elevated plus maze, which was reversed by flutamide [androgen receptor (AR) blocker] and tamoxifen [selective estrogen receptor (ER) modulator]. Circulating sex steroids did not differ between groups at adult age. The expression of serotonergic and GABAergic genes associated with emotional regulation in the amygdala was consistent with anxiety-like behavior in female, and partly in male PNA offspring. Furthermore, AR expression in amygdala was reduced in female PNA offspring and also in females exposed to testosterone in adult age. To determine whether AR activation in amygdala affects anxiety-like behavior, female rats were given testosterone microinjections into amygdala, which resulted in anxiety-like behavior. Together, these data describe the anxiety-like behavior in PNA offspring and adult females with androgen excess, an impact that seems to occur during fetal life, and is mediated via AR in amygdala, together with changes in ERα, serotonergic, and GABAergic genes in amygdala and hippocampus. The anxiety-like behavior following testosterone microinjections into amygdala demonstrates a key role for AR activation in this brain area. These results suggest that maternal androgen excess may underpin the risk of developing anxiety disorders in daughters and sons of PCOS mothers. PMID:26578781

  15. Maternal testosterone exposure increases anxiety-like behavior and impacts the limbic system in the offspring.

    PubMed

    Hu, Min; Richard, Jennifer Elise; Maliqueo, Manuel; Kokosar, Milana; Fornes, Romina; Benrick, Anna; Jansson, Thomas; Ohlsson, Claes; Wu, Xiaoke; Skibicka, Karolina Patrycja; Stener-Victorin, Elisabet

    2015-11-17

    During pregnancy, women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring. This study investigated whether maternal androgen excess causes anxiety-like behavior in offspring mimicking anxiety disorders in PCOS. The PCOS phenotype was induced in rats following prenatal androgen (PNA) exposure. PNA offspring displayed anxiety-like behavior in the elevated plus maze, which was reversed by flutamide [androgen receptor (AR) blocker] and tamoxifen [selective estrogen receptor (ER) modulator]. Circulating sex steroids did not differ between groups at adult age. The expression of serotonergic and GABAergic genes associated with emotional regulation in the amygdala was consistent with anxiety-like behavior in female, and partly in male PNA offspring. Furthermore, AR expression in amygdala was reduced in female PNA offspring and also in females exposed to testosterone in adult age. To determine whether AR activation in amygdala affects anxiety-like behavior, female rats were given testosterone microinjections into amygdala, which resulted in anxiety-like behavior. Together, these data describe the anxiety-like behavior in PNA offspring and adult females with androgen excess, an impact that seems to occur during fetal life, and is mediated via AR in amygdala, together with changes in ERα, serotonergic, and GABAergic genes in amygdala and hippocampus. The anxiety-like behavior following testosterone microinjections into amygdala demonstrates a key role for AR activation in this brain area. These results suggest that maternal androgen excess may underpin the risk of developing anxiety disorders in daughters and sons of PCOS mothers. PMID:26578781

  16. Assessing the offspring of workaholic parents: the Children of Workaholics Screening Test.

    PubMed

    Robinson, B E; Carroll, J J

    1999-06-01

    This study reports initial stages in the development of a self-report instrument that measures offsprings' mental disposition toward their parents' work habits. In an initial sitting, a battery of tests was administered to 207 young adults to assess the reliability and validity of the Children of Workaholics Screening Test. After a 2-wk. interval, the test was administered again. Test-retest reliability, split-half reliability, and concurrent validity are reported. The findings provide strong support for the utility of the Children of Workaholics Screening Test for assessing the offspring of workaholic parents. PMID:10485093

  17. Sex-Specific Programming of Hypertension in Offspring of Late Gestation Diabetic Rats

    PubMed Central

    Katkhuda, Ragheed; Peterson, Emily S.; Roghair, Robert D.; Norris, Andrew W.; Scholz, Thomas D.; Segar, Jeffrey L.

    2013-01-01

    Background The intrauterine environment strongly influences adult disease susceptibility. We utilized a rat model of third trimester maternal diabetes to test the hypothesis that adult offspring exposed to hyperglycemia in utero display increased blood pressure and alterations in vascular responsiveness. Methods Diabetes was induced by streptozotocin injection to pregnant rats on gestation day 13 (term 21 day) and partially controlled with insulin injections. Hemodynamic function was evaluated in 6–12 month old offspring. Results Male but not female offspring of diabetic mothers (ODM) had significantly increased blood pressure compared to controls, heart rate was similar. For both sexes, heart rate baroreflex responses were similar as were in vivo hemodynamic responses to angiotensin II, NOS inhibition and ganglionic blockade. Aortic contractility to angiotensin II was similar in both groups. NOS inhibition and the Cu/Zn superoxide dismutase (SOD) inhibitor diethyldithiocarbamate but not the SOD-mimetic Tempol significantly increased contractile responses to angiotensin II in controls but not ODM. NADPH stimulated superoxide production was greater in male ODM than controls (p<0.05). Conclusions Exposure to hyperglycemia in utero results in sex specific cardiovascular changes in adult offspring. Impaired NO - reactive oxygen species signaling may play a significant role in the hemodynamic phenotype of ODM. PMID:22805998

  18. Development of anxiety-like behavior via hippocampal IGF-2 signaling in the offspring of parental morphine exposure: effect of enriched environment.

    PubMed

    Li, Chang-Qi; Luo, Yan-Wei; Bi, Fang-Fang; Cui, Tao-Tao; Song, Ling; Cao, Wen-Yu; Zhang, Jian-Yi; Li, Fang; Xu, Jun-Mei; Hao, Wei; Xing, Xiao-Wei; Zhou, Fiona H; Zhou, Xin-Fu; Dai, Ru-Ping

    2014-11-01

    Opioid addiction is a major social, economic, and medical problem worldwide. Long-term adverse consequences of chronic opiate exposure not only involve the individuals themselves but also their offspring. Adolescent maternal morphine exposure results in behavior and morphologic changes in the brain of their adult offspring. However, few studies investigate the effect of adult opiate exposure on their offspring. Furthermore, the underlying molecular signals regulating the intergenerational effects of morphine exposure are still elusive. We report here that morphine exposure of adult male and female rats resulted in anxiety-like behavior and dendritic retraction in the dentate gyrus (DG) region of the hippocampus in their adult offspring. The behavior and morphologic changes were concomitant with the downregulation of insulin-like growth factor (IGF)-2 signaling in the granular zone of DG. Overexpression of hippocampal IGF-2 by bilateral intra-DG injection of lentivirus encoding the IGF-2 gene prevented anxiety-like behaviors in the offspring. Furthermore, exposure to an enriched environment during adolescence corrected the reduction of hippocampal IGF-2 expression, normalized anxiety-like behavior and reversed dendritic retraction in the adult offspring. Thus, parental morphine exposure can lead to the downregulation of hippocampal IGF-2, which contributed to the anxiety and hippocampal dendritic retraction in their offspring. An adolescent-enriched environment experience prevented the behavior and morphologic changes in their offspring through hippocampal IGF-2 signaling. IGF-2 and an enriched environment may be a potential intervention to prevention of anxiety and brain atrophy in the offspring of parental opioid exposure. PMID:24889368

  19. The maternal environment affects offspring viability via an indirect effect of yolk investment on offspring size.

    PubMed

    Warner, Daniel A; Lovern, Matthew B

    2014-01-01

    Environmental conditions that reproductive females experience can influence patterns of offspring provisioning and fitness. In particular, prey availability can influence maternal reproduction and, in turn, affect the viability of their offspring. Although such maternal effects are widespread, the mechanisms by which these effects operate are poorly understood. We manipulated the amount of prey available to female brown anole lizards (Anolis sagrei) to evaluate how this factor affects patterns of reproductive investment (total egg output, egg size, yolk steroids) and offspring viability (morphology, growth, survival). Experimental reduction of yolk in a subset of eggs enabled us to evaluate a potential causal mechanism (yolk investment) that mediates the effect of maternal prey availability on offspring viability. We show that limited prey availability significantly reduced egg size, which negatively influenced offspring size, growth, and survival. Experimental yolk removal from eggs directly reduced offspring size, which, in turn, negatively affected offspring growth and survival. These findings show that maternal environments (i.e., low prey) can affect offspring fitness via an indirect effect of yolk investment on offspring size and highlight the complex set of indirect effects by which maternal effects can operate. PMID:24642545

  20. Evaluation of Glycemic and Lipid Profile of Offspring of Diabetic Wistar Rats Treated with Malpighia emarginata Juice

    PubMed Central

    Barbalho, Sandra M.; Damasceno, Débora C.; Spada, Ana Paula Machado; Palhares, Miréia; Martuchi, Karla Aparecida; Oshiiwa, Marie; Sazaki, Viviane; da Silva, Vanessa Sellis

    2011-01-01

    Knowing that maternal diabetes is related to hyperglycemia and fetal hyperinsulinemia, which affect the lipid metabolism, the aim of this study was to evaluate the effects of Malpighia emarginata (acerola) juice on the glycemic and lipid profile of offspring of diabetic and nondiabetic Wistar rats. The adult offspring of non-diabetic dams and of dams with severe streptozotocin-induced diabetes were divided into groups: G1, offspring (of control dams) treated with water, G2, offspring (of diabetic dams) treated with water, G3, male offspring (of control dams) treated with acerola juice, and G4, male offspring (of diabetic dams) treated with acerola juice. The offspring of diabetic dams treated with acerola juice showed significantly decreased levels of glucose, cholesterol, triglycerides, and increased HDL-c. The use of acerola juice is a potential strategy to aid in the prevention of DM and dyslipidemia and its complications or to act as an auxiliary in the treatment of these diseases. PMID:21318139

  1. Ontogeny of tetrodotoxin levels in blue-ringed octopuses: maternal investment and apparent independent production in offspring of Hapalochlaena lunulata.

    PubMed

    Williams, Becky L; Hanifin, Charles T; Brodie, Edmund D; Caldwell, Roy L

    2011-01-01

    Many organisms provision offspring with antipredator chemicals. Adult blue-ringed octopuses (Hapalochlaena spp.) harbor tetrodotoxin (TTX), which may be produced by symbiotic bacteria. Regardless of the ultimate source, we find that females invest TTX into offspring and offspring TTX levels are significantly correlated with female TTX levels. Because diversion of TTX to offspring begins during the earliest stages of egg formation, when females are still actively foraging and looking for mates, females may face an evolutionary tradeoff between provisioning larger stores of TTX in eggs and retaining that TTX for their own defense and offense (venom). Given that total TTX levels appear to increase during development and that female TTX levels correlate with those of offspring, investment may be an active adaptive process. Even after eggs have been laid, TTX levels continue to increase, suggesting that offspring or their symbionts begin producing TTX independently. The maternal investment of TTX in offspring of Hapalochlaena spp. represents a rare examination of chemical defenses, excepting ink, in cephalopods. PMID:21165679

  2. High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring

    PubMed Central

    de Castro Barbosa, Thais; Ingerslev, Lars R.; Alm, Petter S.; Versteyhe, Soetkin; Massart, Julie; Rasmussen, Morten; Donkin, Ida; Sjögren, Rasmus; Mudry, Jonathan M.; Vetterli, Laurène; Gupta, Shashank; Krook, Anna; Zierath, Juleen R.; Barrès, Romain

    2015-01-01

    Objectives Chronic and high consumption of fat constitutes an environmental stress that leads to metabolic diseases. We hypothesized that high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa and metabolism of the offspring. Methods F0-male rats fed either HFD or chow diet for 12 weeks were mated with chow-fed dams to generate F1 and F2 offspring. Motile spermatozoa were isolated from F0 and F1 breeders to determine DNA methylation and small non-coding RNA (sncRNA) expression pattern by deep sequencing. Results Newborn offspring of HFD-fed fathers had reduced body weight and pancreatic beta-cell mass. Adult female, but not male, offspring of HFD-fed fathers were glucose intolerant and resistant to HFD-induced weight gain. This phenotype was perpetuated in the F2 progeny, indicating transgenerational epigenetic inheritance. The epigenome of spermatozoa from HFD-fed F0 and their F1 male offspring showed common DNA methylation and small non-coding RNA expression signatures. Altered expression of sperm miRNA let-7c was passed down to metabolic tissues of the offspring, inducing a transcriptomic shift of the let-7c predicted targets. Conclusion Our results provide insight into mechanisms by which HFD transgenerationally reprograms the epigenome of sperm cells, thereby affecting metabolic tissues of offspring throughout two generations. PMID:26977389

  3. Metabolic Profile of Offspring from Diabetic Wistar Rats Treated with Mentha piperita (Peppermint)

    PubMed Central

    Barbalho, Sandra M.; Damasceno, Débora C.; Spada, Ana Paula Machado; da Silva, Vanessa Sellis; Martuchi, Karla Aparecida; Oshiiwa, Marie; Machado, Flávia M. V. Farinazzi; Mendes, Claudemir Gregório

    2011-01-01

    This study aimed at evaluating glycemia and lipid profile of offspring from diabetic Wistar rats treated with Mentha piperita (peppermint) juice. Male offspring from nondiabetic dams (control group: 10 animals treated with water and 10 treated with peppermint juice) and from dams with streptozotocin-induced severe diabetes (diabetic group: 10 animals treated with water and 10 treated with peppermint juice) were used. They were treated during 30 days, and, after the treatment period, levels of glycemia, triglycerides, total cholesterol, and fractions were analyzed in the adult phase. The offspring from diabetic dams treated with peppermint showed significantly reduced levels of glucose, cholesterol, LDL-c, and triglycerides and significant increase in HDL-c levels. The use of the M. piperita juice has potential as culturally appropriate strategy to aid in the prevention of DM, dyslipidemia, and its complications. PMID:21647314

  4. Acute stress in pregnant rats: effects on growth rate, learning, and memory capabilities of the offspring.

    PubMed

    Lordi, B; Protais, P; Mellier, D; Caston, J

    1997-11-01

    Growth rate of the offspring of female rats stressed by the presence of a cat at the 10th or the 19th gestational day was lower than that of controls whereas footshocks administered at the same periods did not significantly influence growth rate of the young. Whatever the nature of the stress and the time when it was administered to the mother, the death rate of the young rats was much greater than that in controls. When adult, the offspring of stressed mothers exhibited learning and memory impairments in a delayed alternation task as well as in passive avoidance conditioning. Alteration of these cognitive functions is interpreted in terms of subtle dysfunctions in the development of the nervous system through modifications of the hormonal components of the mothers, particularly eventual alterations of the nervous system biochemistry of the offspring. PMID:9333204

  5. Responsiveness of cerebral and hepatic cytochrome P450s in rat offspring prenatally exposed to lindane

    SciTech Connect

    Johri, Ashu; Yadav, Sanjay; Dhawan, Alok; Parmar, Devendra

    2008-08-15

    ABSTRACT: Prenatal exposure to low doses of lindane has been shown to affect the ontogeny of xenobiotic metabolizing cytochrome P450s (CYPs), involved in the metabolism and neurobehavioral toxicity of lindane. Attempts were made in the present study to investigate the responsiveness of CYPs in offspring prenatally exposed to lindane (0.25 mg/kg b. wt.; 1/350th of LD{sub 50}; p. o. to mother) when challenged with 3-methylcholanthrene (MC) or phenobarbital (PB), inducers of CYP1A and 2B families or a sub-convulsant dose of lindane (30 mg/kg b. wt., p. o.) later in life. Prenatal exposure to lindane was found to produce an increase in the mRNA and protein expression of CYP1A1, 1A2, 2B1, 2B2 isoforms in brain and liver of the offspring at postnatal day 50. The increased expression of the CYPs in the offspring suggests the sensitivity of the CYPs during postnatal development, possibly, to low levels of lindane, which may partition into mother's milk. A higher increase in expression of CYP1A and 2B isoenzymes and their catalytic activity was observed in animals pretreated prenatally with lindane and challenged with MC (30 mg/kg, i. p. x 5 days) or PB (80 mg/kg, i. p. x 5 days) when young at age (approx. 7 weeks) compared to animals exposed to MC or PB alone. Further, challenge of the control and prenatally exposed offspring with a single sub-convulsant dose of lindane resulted in an earlier onset and increased incidence of convulsions in the offspring prenatally exposed to lindane have demonstrated sensitivity of the CYPs in the prenatally exposed offspring. Our data assume significance as the subtle changes in the expression profiles of hepatic and cerebral CYPs in rat offspring during postnatal development could modify the adult response to a later exposure to xenobiotics.

  6. Polyandry and fitness of offspring reared under varying nutritional stress in decorated crickets.

    PubMed

    Sakaluk, Scott K; Schaus, Jennifer M; Eggert, Anne-Katrin; Snedden, W Andrew; Brady, Pamela L

    2002-10-01

    Females, by mating with more than one male in their lifetime, may reduce their risk of receiving sperm from genetically incompatible sires or increase their prospects of obtaining sperm from genetically superior sires. Although there is evidence of both kinds of genetic benefits in crickets, their relative importance remains unclear, and the extent to which experimentally manipulated levels of polyandry in the laboratory correspond to those that occur in nature remain unknown. We measured lifetime polyandry of free-living female decorated crickets, Gryllodes sigillatus, and conducted an experiment to determine whether polyandry leads to an increase in offspring viability. We experimentally manipulated both the levels of polyandry and opportunities for females to select among males, randomly allocating the offspring of experimental females to high-food-stress or low-food-stress regimes to complete their development. Females exhibited a high degree of polyandry, mating on average with more than seven different males during their lifetime and up to as many as 15. Polyandry had no effect on either the developmental time or survival of offspring. However, polyandrous females produced significantly heavier sons than those of monandrous females, although there was no difference in the adult mass of daughters. There was no significant interaction between mating treatment and offspring nutritional regimen in their effects on offspring mass, suggesting that benefits accruing to female polyandry are independent of the environment in which offspring develop. The sex difference in the extent to which male and female offspring benefit via their mother's polyandry may reflect possible differences in the fitness returns from sons and daughters. The larger mass gain shown by sons of polyandrous females probably leads to their increased reproductive success, either because of their increased success in sperm competition or because of their increased life span. PMID:12449487

  7. Enhanced anxiety in the male offspring of sires that self-administered cocaine.

    PubMed

    White, Samantha L; Vassoler, Fair M; Schmidt, Heath D; Pierce, R Christopher; Wimmer, Mathieu E

    2016-07-01

    We previously showed that paternal cocaine exposure reduced the reinforcing efficacy of cocaine in male offspring. Here, we sought to determine whether paternal cocaine experience could also influence anxiety levels in offspring. Male rats were allowed to self-administer cocaine (controls received saline passively) for 60 days and then were bred with naïve females. Measures of anxiety and cocaine-induced anxiogenic effects were assessed in the adult offspring. Cocaine-sired male offspring exhibited increased anxiety-like behaviors, as measured using the novelty-induced hypophagia and defensive burying tasks, relative to saline-sired males. In contrast, sire cocaine experience had no effect on anxiety-like behaviors in female offspring. When challenged with an anxiogenic (but not anorectic) dose of cocaine (2.5 mg/kg, i.p.), anxiety-like behavior was enhanced in all animals to an equal degree regardless of sire drug experience. Since anxiety and depression are often co-morbid, we also assessed measures of depressive-like behavior. Sire cocaine experience had no effect on depression-like behaviors, as measured by the forced swim task, among male offspring. In a separate group of naïve littermates, select neuronal correlates of anxiety were measured. Male offspring of cocaine-experienced sires showed increased mRNA and protein expression of corticotropin-releasing factor receptor 2 in the hippocampus. Together, these results indicate that cocaine-experienced sires produce male progeny that have increased baseline anxiety, which is unaltered by subsequent cocaine exposure. PMID:25923597

  8. Autonomic and Renal Alterations in the Offspring of Sleep-Restricted Mothers During Late Pregnancy

    PubMed Central

    Raimundo, Joyce R S; Bergamaschi, Cassia T; Campos, Ruy R; Palma, Beatriz D; Tufik, Sergio; Gomes, Guiomar N

    2016-01-01

    OBJECTIVES: Considering that changes in the maternal environment may result in changes in progeny, the aim of this study was to investigate the influence of sleep restriction during the last week of pregnancy on renal function and autonomic responses in male descendants at an adult age. METHODS: After confirmation of pregnancy, female Wistar rats were randomly assigned to either a control or a sleep restriction group. The sleep-restricted rats were subjected to sleep restriction using the multiple platforms method for over 20 hours per day between the 14th and 20th day of pregnancy. After delivery, the litters were limited to 6 offspring that were designated as offspring from control and offspring from sleep-restricted mothers. Indirect measurements of systolic blood pressure (BPi), renal plasma flow, glomerular filtration rate, glomerular area and number of glomeruli per field were evaluated at three months of age. Direct measurements of cardiovascular function (heart rate and mean arterial pressure), cardiac sympathetic tone, cardiac parasympathetic tone, and baroreflex sensitivity were evaluated at four months of age. RESULTS: The sleep-restricted offspring presented increases in BPi, glomerular filtration rate and glomerular area compared with the control offspring. The sleep-restricted offspring also showed higher basal heart rate, increased mean arterial pressure, increased sympathetic cardiac tone, decreased parasympathetic cardiac tone and reduced baroreflex sensitivity. CONCLUSIONS: Our data suggest that reductions in sleep during the last week of pregnancy lead to alterations in cardiovascular autonomic regulation and renal morpho-functional changes in offspring, triggering increases in blood pressure.

  9. The Influence of Parental Psychopathology on Offspring Suicidal Behavior across the Lifespan

    PubMed Central

    Borges, Guilherme; Viana, Maria Carmen

    2015-01-01

    Suicide tends to occur in families, and parental psychopathology has been linked to offspring suicidal behaviors. This study explores the influence of parental mental disorders across the lifespan. Data are from the Sao Paulo Megacity Mental Health Survey, a cross-sectional household study with a representative sample of the adult population living in the Sao Paulo Metropolitan Area, Brazil (N=2,942). Survival models examined bivariate and multivariate associations between a range of parental disorders and offspring suicidality. After controlling for comorbidity, number of mental disorders and offspring psychopathology, we found that parental psychopathology influences suicidal behaviors throughout most part of the life cycle, from childhood until young adult years. Generalized anxiety disorder (GAD) and antisocial personality were associated with offspring suicidal ideation (OR 1.8 and 1.9, respectively), panic and GAD predicted suicidal attempts (OR 2.3 and 2.7, respectively), and panic was related to the transition from ideation to attempts (OR 2.7). Although noticed in many different stages of the lifespan, this influence is most evident during adolescence. In this period, depression and antisocial personality increased the odds of suicidal ideation (OR 5.1 and 3.2, respectively), and depression, panic disorder, GAD and substance abuse predicted suicidal attempts (OR varying from 1.7 to 3.8). In short, parental disorders characterized by impulsive-aggression and anxiety-agitation were the main predictors of offspring suicidality across the lifespan. This clinically relevant intergenerational transmission of suicide risk was independent of offspring mental disorders, and this underscores the need for a family approach to psychopathology. PMID:26230321

  10. N-Acetylcysteine Prevents Programmed Hypertension in Male Rat Offspring Born to Suramin-Treated Mothers.

    PubMed

    Tain, You-Lin; Hsu, Chien-Ning; Lee, Chien-Te; Lin, Yu-Ju; Tsai, Ching-Chou

    2016-07-01

    Adulthood hypertension can be programmed by preeclampsia. Preeclampsia is associated with an imbalance in vasoactive factors, including nitric oxide (NO), hydrogen sulfide (H2S), and renin-angiotensin system (RAS). We examined whether maternal N-acetylcysteine (NAC) therapy prevented maternal suramin treatment-induced programmed hypertension in offspring and explored the effects of this therapy on NO, H2S, and RAS pathways in the kidneys. Pregnant Sprague-Dawley rats were intraperitoneally administered 60 mg/kg suramin alone on Gestational Days 10 and 11 and were treated with or without 1% NAC through drinking water during the entire pregnancy and lactation period. Male offspring were divided into four groups (n = 8-10/group): control, suramin, NAC, and suramin plus NAC. All rat offspring were euthanized at 12 wk of age. Maternal suramin treatment induced programmed hypertension in male offspring, which was prevented by maternal NAC therapy. Suramin-induced programmed hypertension was associated with increased plasma asymmetric dimethylarginine (ADMA, an NO synthase inhibitor) level, decreased plasma l-arginine-to-ADMA ratio, and decreased renal dimethylarginine dimethylaminohydrolase (an ADMA-metabolizing enzyme) activity. Protective effects of NAC against suramin-induced programmed hypertension were associated with an increase in plasma glutathione level, increase in renal 3-mercaptopyruvate sulfurtransferase level, and restoration of suramin-induced reduction in H2S synthesis in the kidneys. Suramin treatment exerted negligible effect on the RAS pathway in the adult male offspring kidneys. Our data suggested interplay among suramin, ADMA-NO pathway, and H2S synthesis pathway in programmed hypertension. Furthermore, NAC administration in pregnant rats with hypertension prevented programmed hypertension in adult offspring. PMID:27251093

  11. Role of maternal 5-HT1A receptor in programming offspring emotional and physical development

    PubMed Central

    van Velzen, Annelies; Toth, Miklos

    2010-01-01

    Serotonin1A receptor (5-HT1AR) deficiency has been associated with anxiety and depression and mice with genetic receptor inactivation exhibit heightened anxiety. We have reported that 5-HT1AR is not only a genetic but also a maternal “environmental” factor in the development of anxiety in Swiss-Webster mice. Here we tested if the emergence of maternal genotype dependent adult anxiety is preceded by early behavioral abnormalities or if it is manifested following a normal emotional development. Pups born to null or heterozygote mothers had significantly reduced ultrasonic vocalization between postnatal day (P) 4 and 12 indicating an influence of the maternal genotype. The offspring’s own genotype had an effect limited to P4. Furthermore, we observed reduced weight gain in the null offspring of null but not heterozygote mothers indicating that a complete maternal receptor deficiency compromises offspring physical development. Except a short perinatal deficit during the dark period, heterozygote females displayed normal maternal behavior which, with the early appearance of ultrasonic vocalization deficit, suggests a role for 5-HT1AR during pre/perinatal development. Consistent with this notion, adult anxiety in the offspring is determined during the pre/perinatal period. In contrast to heterozygote females, null mothers exhibited impaired pup retrieval and nest building that may explain the reduced weight gain of their offspring. Taken together, our data indicate an important role for the maternal 5-HT1AR in regulating offspring emotional and physical development. Since reduced receptor binding has been reported in depression, including postpartum depression, reduced 5-HT1AR function in mothers may influence the emotional development of their offspring. PMID:20633050

  12. Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery.

    PubMed

    Guénard, Frédéric; Deshaies, Yves; Cianflone, Katherine; Kral, John G; Marceau, Picard; Vohl, Marie-Claude

    2013-07-01

    Obesity and overnutrition during pregnancy affect fetal programming of adult disease. Children born after maternal bariatric gastrointestinal bypass surgery (AMS) are less obese and exhibit improved cardiometabolic risk profiles carried into adulthood compared with siblings born before maternal surgery (BMS). This study was designed to analyze the impact of maternal weight loss surgery on methylation levels of genes involved in cardiometabolic pathways in BMS and AMS offspring. Differential methylation analysis between a sibling cohort of 25 BMS and 25 AMS (2-25 y-old) offspring from 20 mothers was conducted to identify biological functions and pathways potentially involved in the improved cardiometabolic profile found in AMS compared with BMS offspring. Links between gene methylation and expression levels were assessed by correlating genomic findings with plasma markers of insulin resistance (fasting insulin and homeostatic model of insulin resistance). A total of 5,698 genes were differentially methylated between BMS and AMS siblings, exhibiting a preponderance of glucoregulatory, inflammatory, and vascular disease genes. Statistically significant correlations between gene methylation levels and gene expression and plasma markers of insulin resistance were consistent with metabolic improvements in AMS offspring, reflected in genes involved in diabetes-related cardiometabolic pathways. This unique clinical study demonstrates that effective treatment of a maternal phenotype is durably detectable in the methylome and transcriptome of subsequent offspring. PMID:23716672

  13. Diofenolan induces male offspring production through binding to the juvenile hormone receptor in Daphnia magna.

    PubMed

    Abe, Ryoko; Toyota, Kenji; Miyakawa, Hitoshi; Watanabe, Haruna; Oka, Tomohiro; Miyagawa, Shinichi; Nishide, Hiroyo; Uchiyama, Ikuo; Tollefsen, Knut Erik; Iguchi, Taisen; Tatarazako, Norihisa

    2015-02-01

    Juvenile hormone (JH) and JH agonists have been reported to induce male offspring production in various daphnid species including Daphnia magna. We recently established a short-term in vivo screening assay to detect chemicals having male offspring induction activity in adult D. magna. Diofenolan has been developed as a JH agonist for insect pest control, but its male offspring induction activity in daphnids has not been investigated yet. In this study, we found that the insect growth regulator (IGR) diofenolan exhibited a potent male offspring induction activity at low ng/L to μg/L concentrations, as demonstrated by the short-term in vivo screening assay and the recently developed TG211 ANNEX 7 test protocol. A two-hybrid assay performed using the D. magna JH receptor confirmed that diofenolan had a strong JH activity. Global whole body transcriptome analysis of D. magna exposed to 10 ng/L diofenolan showed an up-regulation of JH-responsive genes and modulation of several genes involved in the ecdysone receptor signaling pathway. These results clearly demonstrate that diofenolan has strong JH activity and male offspring induction activity, and that a combination of modified standardized regulatory testing protocols and rapid in vitro and in vivo screening assays are able to identify potential endocrine disruptors in D. magna. The observation that diofenolan modulates multiple endocrine signaling pathways in D. magna suggests that further investigation of potential interference with growth, development and reproduction is warranted. PMID:25506888

  14. In Utero Nutritional Manipulation Provokes Dysregulated Adipocytokines Production in F1 Offspring in Rats

    PubMed Central

    Hanafi, Mervat Y.; Saleh, Moustafa M.; Kamel, Maher A.

    2016-01-01

    Background. Intrauterine environment plays a pivotal role in the origin of fatal diseases such as diabetes. Diabetes and obesity are associated with low-grade inflammatory state and dysregulated adipokines production. This study aims to investigate the effect of maternal obesity and malnutrition on adipokines production (adiponectin, leptin, and TNF-α) in F1 offspring in rats. Materials and Methods. Wistar rats were allocated in groups: F1 offspring of control mothers under control diet (CF1-CD) and under high-fat diet (CF1-HCD), F1 offspring of obese mothers under CD (OF1-CD) and under HCD (OF1-HCD), and F1 offspring of malnourished mothers under CD (MF1-CD) and under HCD (MF1-HCD). Every 5 weeks postnatally, blood samples were obtained for biochemical analysis. Results. At the end of the 30-week follow-up, OF1-HCD and MF1-HCD exhibited hyperinsulinemia, moderate dyslipidemia, insulin resistance, and impaired glucose homeostasis compared to CF1-CD and CF1-HCD. OF1-HCD and MF1-HCD demonstrated low serum levels of adiponectin and high levels of leptin compared to CF1-CD and CF1-HCD. OF1-CD, OF1-HCD, and MF1-HCD had elevated serum levels of TNF-α compared to CF1-CD and CF1-HCD (p < 0.05). Conclusion. Maternal nutritional manipulation predisposes the offspring to development of insulin resistance in their adult life, probably via instigating dysregulated adipokines production. PMID:27200209

  15. Paternal alcohol consumption in the rat impairs spatial learning performance in male offspring.

    PubMed

    Wozniak, D F; Cicero, T J; Kettinger, L; Meyer, E R

    1991-01-01

    Pubescent (30 day old) male rats were maintained on an alcohol liquid diet containing 35% ethanol-derived calories (ALC) for 39 days or were pairfed an isocaloric control diet (PF). The concentration of alcohol in the diet was gradually increased to permit adaptation, then stabilized and then gradually tapered to prevent an alcohol withdrawal syndrome. Following a drug-free period (2 weeks), the males were mated with nontreated females. Offspring were evaluated on several developmental indices and on various learning/memory tasks to assess functional deficits in adulthood. Offspring sired by ALC-treated males did not differ from the offspring of PF males on several developmental parameters including body weights, when developmental landmarks appeared, or on tests of sensorimotor development. As adults, male offspring groups did not differ on tests of activity or on an object exploration/recognition task. However, male offspring of ALC-treated males demonstrated impaired acquisition performance (days and errors to criterion) on a win-shift spatial discrimination in an eight-arm radial maze and on a win-stay discrimination (days to criterion) conducted in a T-maze at a later age. The radial maze results were replicated in a subsequent experiment using different groups of rats. PMID:1796134

  16. Long-Term Consequences for Offspring of Paternal Diabetes and Metabolic Syndrome

    PubMed Central

    Linares Segovia, Benigno; Gutiérrez Tinoco, Maximiliano; Izquierdo Arrizon, Angeles; Guízar Mendoza, Juan Manuel; Amador Licona, Norma

    2012-01-01

    Background. Recent studies have reported an increase in the prevalence of obesity and metabolic syndrome in children and adolescents. However, few have focused how diabetes mellitus and metabolic syndrome together in parents can influence on obesity and metabolic disturbances in offspring. Objective. To know the risk obesity and metabolic disturbance in children, adolescents, and young adults whose parents have diabetes mellitus and metabolic syndrome. Methods. A comparative survey was made in healthy children of parents with diabetes mellitus and metabolic syndrome compared with offspring of healthy parents. We performed anthropometry and evaluated blood pressure, glucose, total cholesterol, HDL cholesterol, and triglycerides levels in plasma. We registered parent antecedents to diabetes mellitus and metabolic syndrome and investigated the prevalence of overweight, obesity, and metabolic disturbances in offspring. Results. We studied 259 subjects of 7 to 20 years of age. The prevalence of overweight and obesity was 27% and 37%, respectively. The highest proportion of BMI >95th of the entire group was found in offspring with both diabetic parents. Glucose and total cholesterol levels were lower in the group with healthy parents compared with the group with diabetic mother and metabolic syndrome but with healthy father. HDL cholesterol was higher in the group with both healthy parents than in the group with diabetic mother and metabolic syndrome but healthy father. Conclusions. The offspring of parents with diabetes plus metabolic syndrome showed higher proportion of variables related to metabolic syndrome compared with healthy parents. PMID:23193389

  17. Maternal dexamethasone exposure ameliorates cognition and tau pathology in the offspring of triple transgenic AD mice.

    PubMed

    Di Meco, A; Joshi, Y B; Lauretti, E; Praticò, D

    2016-03-01

    Dysregulation of stress hormones, such as glucocorticoids, in adult life increases the risk to develop Alzheimer's disease (AD). However, the effect of prenatal glucocorticoids exposure on AD development in the offspring remains unknown. We studied how gestational dexamethasone exposure influences the AD-like phenotype in the offspring of triple transgenic AD mice (3 × Tg). To this end, female mice received dexamethasone or vehicle during the entire pregnancy time in the drinking water. Offspring from vehicle-treated 3 × Tg (controls) were compared with offspring from dexamethasone-treated 3 × Tg later in life for their memory, learning ability and brain pathology. Compared with controls, offspring from dexamethasone-treated mothers displayed improvement in their memory as assessed by fear conditioning test, both in the cue and recall phases. The same animals had a significant reduction in the insoluble fraction of tau, which was associated with an increase in autophagy. In addition, they showed an activation of the transcription factor cellular response element-binding protein and an increase in brain-derived neurotrophic factor and c-FOS protein levels, key regulators of synaptic plasticity and memory. We conclude that dexamethasone exposure during pregnancy provides long-lasting protection against the onset and development of the AD-like phenotype by improving cognition and tau pathology. PMID:26077691

  18. Human and murine erythropoiesis

    PubMed Central

    An, Xiuli; Schulz, Vincent P.; Mohandas, Narla; Gallagher, Patrick G.

    2015-01-01

    Purpose of review Research into the fundamental mechanisms of erythropoiesis has provided critical insights into inherited and acquired disorders of the erythrocyte. Studies of human erythropoiesis have primarily utilized in-vitro systems, whereas murine models have provided insights from in-vivo studies. This report reviews recent insights into human and murine erythropoiesis gained from transcriptome-based analyses. Recent findings The availability of high-throughput genomic methodologies has allowed attainment of detailed gene expression data from cells at varying developmental and differentiation stages of erythropoiesis. Transcriptome analyses of human and murine reveal both stage and species-specific similarities and differences across terminal erythroid differentiation. Erythroid-specific long noncoding RNAs exhibit poor sequence conservation between human and mouse. Genome-wide analyses of alternative splicing reveal that complex, dynamic, stage-specific programs of alternative splicing program are utilized during terminal erythroid differentiation. Transcriptome data provide a significant resource for understanding mechanisms of normal and perturbed erythropoiesis. Understanding these processes will provide innovative strategies to detect, diagnose, prevent, and treat hematologic disease. Summary Understanding the shared and different mechanisms controlling human and murine erythropoiesis will allow investigators to leverage the best model system to provide insights in normal and perturbed erythropoiesis. PMID:25719574

  19. Chronic prenatal stress epigenetically modifies spinal cord BDNF expression to induce sex specific visceral hypersensitivity in offspring

    PubMed Central

    Winston, John H.; Li, Qingjie; Sarna, Sushil K.

    2014-01-01

    Background Irritable bowel syndrome (IBS) is a heterogeneous disorder with abdomen pain as one of the primary symptoms. The etiology of IBS remains unknown. Epidemiological studies found that a subset of these patients have a history of adverse early-life events. We tested the hypothesis that chronic prenatal stress (CPS) epigenetically enhances brain-derived neurotrophic factor (BDNF) in spinal cord to aggravate colon sensitivity to colorectal distension (CRD) differentially in male and female offspring. Methods We used heterotypic intermittent chronic stress (HeICS) protocols in pregnant dams from E11 until delivery. Results CPS induced significant visceral hypersensitivity (VHS) to CRD in male and female offspring. A second exposure to HeICS in adult offspring exacerbated VHS greater in female offspring that persisted longer than in male offspring. CPS upregulated BDNF expression in the lumbar-sacral dorsal horn that correlated with the exacerbation of VHS in female, but not in male offspring. The upregulation of BDNF was due to a significant increase in RNA Pol II binding, histone H3 acetylation and significant decrease in histone deacetylase 1 association with the core promoter of BDNF in female offspring. Other chronic prenatal and neonatal stress protocols were less effective than HeICS. Conclusion & Inferences The development of visceral hypersensitivity, which contributes to the symptom of intermittent abdominal pain, is a two-step process, chronic in utero stress followed by chronic stress in adult-life. This two-step process induces aggravated and persistent colon hypersensitivity in female than in male offspring. Our preclinical model explains several clinical features in IBS patients. PMID:24588943

  20. Cues of maternal condition influence offspring selfishness.

    PubMed

    Wong, Janine W Y; Lucas, Christophe; Kölliker, Mathias

    2014-01-01

    The evolution of parent-offspring communication was mostly studied from the perspective of parents responding to begging signals conveying information about offspring condition. Parents should respond to begging because of the differential fitness returns obtained from their investment in offspring that differ in condition. For analogous reasons, offspring should adjust their behavior to cues/signals of parental condition: parents that differ in condition pay differential costs of care and, hence, should provide different amounts of food. In this study, we experimentally tested in the European earwig (Forficula auricularia) if cues of maternal condition affect offspring behavior in terms of sibling cannibalism. We experimentally manipulated female condition by providing them with different amounts of food, kept nymph condition constant, allowed for nymph exposure to chemical maternal cues over extended time, quantified nymph survival (deaths being due to cannibalism) and extracted and analyzed the females' cuticular hydrocarbons (CHC). Nymph survival was significantly affected by chemical cues of maternal condition, and this effect depended on the timing of breeding. Cues of poor maternal condition enhanced nymph survival in early broods, but reduced nymph survival in late broods, and vice versa for cues of good condition. Furthermore, female condition affected the quantitative composition of their CHC profile which in turn predicted nymph survival patterns. Thus, earwig offspring are sensitive to chemical cues of maternal condition and nymphs from early and late broods show opposite reactions to the same chemical cues. Together with former evidence on maternal sensitivities to condition-dependent nymph chemical cues, our study shows context-dependent reciprocal information exchange about condition between earwig mothers and their offspring, potentially mediated by cuticular hydrocarbons. PMID:24498046

  1. Role of sensory, social, and hormonal signals from the mother on the development of offspring.

    PubMed

    Melo, Angel I

    2015-01-01

    For mammals, sensory, social, and hormonal experience early in life is essential for the continuity of the infant's development. These experiences come from the mother through maternal care, and have enduring effects on the physiology and behavior of the adult organism. Disturbing the mother-offspring interaction by maternal deprivation (neglect) or exposure to adverse events as chronic stress, maltreatment, or sexual abuse has negative effects on the mental, psychological, physiological, and behavioral health. Indeed, these kinds of negative experiences can be the source of some neuropsychiatric diseases as depression, anxiety, impulsive aggression, and antisocial behavior. The purpose of this chapter is to review the most relevant evidence that supports the participation of cues from the mother and/or littermates during the postnatal preweaning period for the development of nervous system of the offspring. These findings come from the most frequently utilized experimental paradigms used in animal models, such as natural variations in maternal behavior, handling, partial maternal deprivation, and total maternal deprivation and artificial rearing. Through the use of these experimental procedures, it is possible to positively (handling paradigm), or negatively (maternal deprivation paradigms), affect the offspring's development. Finally, this chapter reviews the importance of the hormones that pups ingest through the maternal milk during early lactation on the development of several physiological systems, including the immune, endocrine systems, as well as on the adult behavior of the offspring. PMID:25287543

  2. Combined effect of maternal serotonin transporter genotype and prenatal stress in modulating offspring social interaction

    PubMed Central

    Jones, Karen L.; Smith, Ryan M.; Edwards, Kristin S.; Givens, Bennet; Beversdorf, David Q.

    2010-01-01

    Several studies suggest that prenatal stress is a possible risk factor in the development of autism spectrum disorders. However, many children exposed to stress prenatally are born healthy and develop typically, suggesting that other factors must contribute to autism. Genes that contribute to stress reactivity may, therefore, exacerbate prenatal stress-mediated behavioral changes in the adult offspring. One candidate gene linked to increased stress reactivity encodes the serotonin transporter. Specifically, an insertion/deletion (long/short allele) polymorphism upstream of the serotonin transporter gene correlates with differential expression and function of the serotonin transporter and a heightened response to stressors. Heterozygous serotonin transporter knockout mice show reductions in serotonin transporter expression similar to the human short polymorphism. In this study, the role of prenatal stress and maternal serotonin transporter genotype were assessed in mice to determine whether their combined effect produces reductions in social behavior in the adult offspring. Pregnant serotonin transporter heterozygous knockout and wild-type dams were placed in either a control condition or subjected to chronic variable stress. The adult offspring were subsequently assessed for social interaction and anxiety using a 3-chamber social approach task, ultrasonic vocalization detection, elevated-plus maze and an open field task. Results indicated that prenatal stress and reduced serotonin transporter expression of the dam may have the combined effect of producing changes in social interaction and social interest in the offspring consistent with those observed in autism spectrum disorder. This data indicates a possible combined effect of maternal serotonin transporter genotype and prenatal stress contributing to the production of autistic-like behaviors in offspring. PMID:20470877

  3. Maternal Melatonin Therapy Rescues Prenatal Dexamethasone and Postnatal High-Fat Diet Induced Programmed Hypertension in Male Rat Offspring

    PubMed Central

    Tain, You-Lin; Sheen, Jiunn-Ming; Yu, Hong-Ren; Chen, Chih-Cheng; Tiao, Mao-Meng; Hsu, Chien-Ning; Lin, Yu-Ju; Kuo, Kuang-Che; Huang, Li-Tung

    2015-01-01

    Prenatal dexamethasone (DEX) exposure and high-fat (HF) intake are linked to hypertension. We examined whether maternal melatonin therapy prevents programmed hypertension synergistically induced by prenatal DEX plus postnatal HF in adult offspring. We also examined whether DEX and melatonin causes renal programming using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received intraperitoneal dexamethasone (0.1 mg/kg) or vehicle from gestational day 16 to 22. In the melatonin-treatment groups (M), rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Male offspring were assigned to five groups: control, DEX, HF, DEX+HF, and DEX+HF+M. Male offspring in the HF group were fed a HF diet from weaning to 4 months of age. Prenatal DEX and postnatal HF diet synergistically induced programmed hypertension in adult offspring, which melatonin prevented. Maternal melatonin treatment modified over 3000 renal transcripts in the developing offspring kidney. Our NGS data indicate that PPAR signaling and fatty acid metabolism are two significantly regulated pathways. In addition, maternal melatonin therapy elicits longstanding alterations on renal programming, including regulation of the melatonin signaling pathway and upregulation of Agtr1b and Mas1 expression in the renin-angiotensin system (RAS), to protect male offspring against programmed hypertension. Postnatal HF aggravates prenatal DEX induced programmed hypertension in adult offspring, which melatonin prevented. The protective effects of melatonin on programmed hypertension is associated with regulation of the RAS and melatonin receptors. The long-term effects of maternal melatonin therapy on renal transcriptome require further clarification. PMID:26696906

  4. Perinatal bisphenol A exposure promotes hyperactivity, lean body composition, and hormonal responses across the murine life course.

    PubMed

    Anderson, Olivia S; Peterson, Karen E; Sanchez, Brisa N; Zhang, Zhenzhen; Mancuso, Peter; Dolinoy, Dana C

    2013-04-01

    The development of adult-onset diseases is influenced by perinatal exposure to altered environmental conditions. One such exposure, bisphenol A (BPA), has been associated with obesity and diabetes, and consequently labeled an obesogen. Using an isogenic murine model, we examined the effects of perinatal exposure through maternal diet to 50 ng (n=20), 50 μg (n=21), or 50 mg (n=18) BPA/kg diet, as well as controls (n=20) on offspring energy expenditure, spontaneous activity, and body composition at 3, 6, and 9 mo of age, and hormone levels at 9 and 10 mo of age. Overall, exposed females and males exhibited increased energy expenditure (P<0.001 and 0.001, respectively) throughout the life course. In females, horizontal and vertical activity increased (P=0.07 and 0.06, respectively) throughout the life course. Generally, body composition measures were not different throughout the life course in exposed females or males (all P>0.44), although body fat and weight decreased in exposed females at particular ages (all P<0.08). Milligram-exposed females had improved glucose, insulin, adiponectin, and leptin profiles (all P<0.10). Thus, life-course analysis illustrates that BPA is associated with hyperactive and lean phenotypes. Variability across studies may be attributable to differential exposure duration and timing, dietary fat and phytoestrogen content, or lack of sophisticated phenotyping across the life course. PMID:23345456

  5. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway.

    PubMed

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development. PMID:26434683

  6. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway

    NASA Astrophysics Data System (ADS)

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-10-01

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development.

  7. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway

    PubMed Central

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development. PMID:26434683

  8. Impact of hypericum (St.-John's-wort) given prenatally on cognition of mice offspring.

    PubMed

    Rayburn, W F; Gonzalez, C L; Christensen, H D; Harkins, T L; Kupiec, T C

    2001-01-01

    This study investigated the cognitive impact of prenatal exposure to the herbal antidepressant hypericum in CD-1 mice. Hypericum (182 mg/kg/day) or a placebo was consumed in food bars for 2 weeks before mating and throughout gestation. The hypericin content in our hypericum formulation was in the middle range of standardized hypericum products. One offspring per gender from each litter (hypericum 13, placebo 12) was tested on each of the following tasks: juvenile runway with adult memory, adult Morris maze, adult passive avoidance, or adult straight water runway followed by a dry Cincinnati maze. Learning occurred in both genders in all tasks (P<.003) with no significant differences between treatments at the final trial. Female offspring exposed to hypericum, rather than to a placebo, required more time to learn the Morris maze task (P<.05). Postlearning sessions did not show any significant differences. In conclusion, prenatal exposure to a therapeutic dose of hypericum did not have a major impact on certain cognitive tasks in mice offspring. PMID:11792531

  9. Maternal nutritional manipulations program adipose tissue dysfunction in offspring.

    PubMed

    Lecoutre, Simon; Breton, Christophe

    2015-01-01

    Based on the concept of Developmental Origin of Health and Disease, both human and animal studies have demonstrated a close link between nutrient supply perturbations in the fetus or neonate (i.e., maternal undernutrition, obesity, gestational diabetes and/or rapid catch-up growth) and increased risk of adult-onset obesity. Indeed, the adipose tissue has been recognized as a key target of developmental programming in a sex-and depot-specific manner. Despite different developmental time windows, similar mechanisms of adipose tissue programming have been described in rodents and in bigger mammals (sheep, primates). Maternal nutritional manipulations reprogram offspring's adipose tissue resulting in series of alterations: enhanced adipogenesis and lipogenesis, impaired sympathetic activity with reduced noradrenergic innervations and thermogenesis as well as low-grade inflammation. These changes affect adipose tissue development, distribution and composition predisposing offspring to fat accumulation. Modifications of hormonal tissue sensitivity (i.e., leptin, insulin, glucocorticoids) and/or epigenetic mechanisms leading to persistent changes in gene expression may account for long-lasting programming across generations. PMID:26029119

  10. Vascular dysfunction in the offspring of AT1 receptor antibody-positive pregnant rats during high-salt diet.

    PubMed

    Zhang, Xi; Zhang, Su-Li; Xiong, Hai-Yan; DU, Yun-Hui; Quan, Lin; Yang, Jie; Ma, Xiu-Rui; Liu, Hui-Rong

    2011-04-25

    Antibody against the angiotensin AT1 receptor (AT1-Ab) could disturb placental development. The placenta is the key organ between mother and fetus. Placental damage will seriously impair fetal growth and development in utero, leading to intrauterine growth restriction (IUGR). Based on the fetal origins of adult disease (FOAD) hypothesis, IUGR could increase a propensity to develop adult onset cardiovascular disease (CVD). The present study was designed to determine whether vascular function has changed in the adult offspring of AT1-Ab positive pregnant rats. Twenty four female rats (8-week-old, AT1-Ab negative) were randomly divided into two groups, immunized and vehicle groups. Immunized group received active immunization to establish AT1-Ab-positive model, while vehicle group was subjected to Freund's adjuvant without antigen. After 8 weeks of immunization, the antibody titers in sera from the female rats were detected by enzyme-linked immunosorbent assay (ELISA). Then all the female rats were mated with normal Wistar male rats and became pregnant. Immunized/vehicle group offspring rats (I offspring/V offspring) were raised to 40-week-old under standard chow feeding. Then the two groups' offspring rats were given a high-salt diet for 12 weeks (4% NaCl in chow feeding). Systolic blood pressure (SBP) was measured dynamically by noninvasive blood pressure system. The vascular ring experiment was performed to detect vascular function and reactivity. As detected by ELISA, the titers of antibody peaked at the 8th week (OD values: 2.75 ± 0.08 vs 0.33 ± 0.01, P < 0.01 vs vehicle group at the same time point). There was no significant difference of SBP between the two groups' offspring rats during the high-salt diet (P > 0.05). Isolated thoracic aortic rings of I offspring had significantly decreased constriction under norepinephrine treatment (P < 0.01 vs V offspring) and significantly decreased dilation under acetylcholine treatment (P < 0.05 vs V offspring). These

  11. Maternal consumption of Lake Ontario salmon in rats produces behavioral changes in the offspring.

    PubMed

    Daly, H B; Stewart, P W; Lunkenheimer, L; Sargent, D

    1998-01-01

    The current study assessed the effects of maternal, paternal, or combined parental consumption of Lake Ontario salmon in rats on the behavior of their offspring. Adult female Sprague-Dawley rats were put on a 30 day diet of either ground rat chow containing 30% Lake Ontario salmon (LAKE) or 30% Pacific Ocean salmon (OCEAN). These females were then mated with adult male rats similarly exposed (LAKE or OCEAN). An additional control group of males and females who were fed ground rat chow (MASH) only were also mated. These pairing combinations resulted in five offspring groups: LAKE-LAKE, LAKE-OCEAN, OCEAN-LAKE, OCEAN-OCEAN, MASH-MASH. When the offspring reached 80 days of age, they were tested for reactivity to frustrative nonreward using runway successive negative contrast, which has been repeatedly shown to be increased in adult rats fed Ontario salmon. Consistent with previous work, results showed that the behavior of the OCEAN-OCEAN rats did not differ from the MASH-MASH group, indicating that a salmon diet per se does not cause behavioral change. However, the offspring of dams who consumed Lake Ontario salmon (LAKE-LAKE and OCEAN-LAKE) showed an increased depression effect relative to controls. There was little evidence of a paternal effect. A follow-up experiment employed cross-fostering to determine the relative contribution of pre- and/or postnatal exposure to Lake Ontario salmon consumption on offspring behavior. Rat pups were cross-fostered to or from dams who consumed Lake Ontario salmon during gestation and parturition. Results from two separate replications indicated that prenatal (LAKE to OCEAN) exposure alone or postnatal (OCEAN to LAKE) exposure alone produced a large increase in successive negative contrast relative to controls (OCEAN to OCEAN). These data are strong evidence of behavioral changes produced by maternal consumption of Lake Ontario salmon in the offspring rat. Further, they indicate that either prenatal or postnatal exposure alone is

  12. Maternal Influences over Offspring Allergic Responses

    PubMed Central

    2015-01-01

    Asthma occurs as a result of complex interactions of environmental and genetic factors. Clinical studies and animal models of asthma indicate offspring of allergic mothers have increased risk of development of allergies. Environmental factors including stress-induced corticosterone and vitamin E isoforms during pregnancy regulate the risk for offspring development of allergy. In this review, we discuss mechanisms for the development of allergic disease early in life, environmental factors that may impact the development of risk for allergic disease early in life, and how the variation in global prevalence of asthma may be explained, at least in part, by some environmental components. PMID:25612797

  13. Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota

    PubMed Central

    Munyaka, Peris Mumbi; Eissa, N.; Bernstein, Charles Noah; Khafipour, Ehsan; Ghia, Jean-Eric

    2015-01-01

    Background and aims Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB) therapy can increase offspring susceptibility to experimental colitis through alteration of the gut microbiota. Methods Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight or with saline starting six days before due date. At 7 weeks, fecal samples were collected from male offspring after which they received 4% dextran sulfate sodium (DSS) in drinking water for 5 days. Disease activity index, histology, colonic IL-6, IL-1β and serum C-reactive protein (CRP) were determined. The V3-V4 region of colonic and fecal bacterial 16S rRNA was sequenced. Alpha-, beta-diversity and differences at the phylum and genus levels were determined, while functional pathways of classified bacteria were predicted. Results ATB influenced fecal bacterial composition and hence bacterial functional pathways before induction of colitis. After induction of colitis, ATB increased onset of clinical disease, histologic score, and colonic IL-6. In addition, ATB decreased fecal microbial richness, changed fecal and colon microbial composition, which was accompanied by a modification of microbial functional pathways. Also, several taxa were associated with ATB at lower taxonomical levels. Conclusions The results support the hypothesis that antepartum antibiotics modulate offspring intestinal bacterial colonization and increase susceptibility to develop colonic inflammation in a murine model of colitis, and may guide future interventions to restore physiologic intestinal colonization in offspring born by antibiotic-exposed mothers. PMID:26605545

  14. Excess body weight during pregnancy and offspring obesity: potential mechanisms.

    PubMed

    Paliy, Oleg; Piyathilake, Chandrika J; Kozyrskyj, Anita; Celep, Gulcin; Marotta, Francesco; Rastmanesh, Reza

    2014-03-01

    The rates of child and adult obesity have increased in most developed countries over the past several decades. The health consequences of obesity affect both physical and mental health, and the excess body weight can be linked to an elevated risk for developing type 2 diabetes, cardiovascular problems, and depression. Among the factors that can influence the development of obesity are higher infant weights and increased weight gain, which are associated with higher risk for excess body weight later in life. In turn, mother's excess body weight during and after pregnancy can be linked to the risk for offspring overweight and obesity through dietary habits, mode of delivery and feeding, breast milk composition, and through the influence on infant gut microbiota. This review considers current knowledge of these potential mechanisms that threaten to create an intergenerational cycle of obesity. PMID:24103493

  15. Anti-ulcer treatment during pregnancy induces food allergy in mouse mothers and a Th2-bias in their offspring

    PubMed Central

    Schöll, Isabella; Ackermann, Ute; Özdemir, Cevdet; Blümer, Nicole; Dicke, Tanja; Sel, Serdar; Sel, Sarper; Wegmann, Michael; Szalai, Krisztina; Knittelfelder, Regina; Untersmayr, Eva; Scheiner, Otto; Garn, Holger; Jensen-Jarolim, Erika; Renz, Harald

    2010-01-01

    The treatment of dyspeptic disorders with anti-acids leads to an increased risk of sensitization against food allergens. As these drugs are taken by 30–50% of pregnant women due to reflux and heartburn, we aimed here to investigate the impact of maternal therapy with anti-acids on the immune response in the offspring in a murine model. Codfish extract as model allergen was fed with or without sucralfate, an anti-acid drug, to pregnant BALB/c mice during pregnancy and lactation. These mothers developed a codfish-specific allergic response shown as high IgG1 and IgE antibody levels and positive skin tests. In the next step we analyzed whether this maternal sensitization impacts a subsequent sensitization in the offspring. Indeed, in stimulated splenocytes of these offspring we found a relative Th2-dominance, because the Th1- and T-regulatory cytokines were significantly suppressed. Our data provide evidence that the anti-acid drug sucralfate supports sensitization against food in pregnant mice and favors a Th2-milieu in their offspring. From these results we propose that anti-acid treatment during pregnancy could be responsible for the increasing number of sensitizations against food allergens in young infants. PMID:17227952

  16. Anti-ulcer treatment during pregnancy induces food allergy in mouse mothers and a Th2-bias in their offspring.

    PubMed

    Schöll, Isabella; Ackermann, Ute; Ozdemir, Cevdet; Blümer, Nicole; Dicke, Tanja; Sel, Serdar; Sel, Sarper; Wegmann, Michael; Szalai, Krisztina; Knittelfelder, Regina; Untersmayr, Eva; Scheiner, Otto; Garn, Holger; Jensen-Jarolim, Erika; Renz, Harald

    2007-04-01

    The treatment of dyspeptic disorders with anti-acids leads to an increased risk of sensitization against food allergens. As these drugs are taken by 30-50% of pregnant women due to reflux and heartburn, we aimed here to investigate the impact of maternal therapy with anti-acids on the immune response in the offspring in a murine model. Codfish extract as model allergen was fed with or without sucralfate, an anti-acid drug, to pregnant BALB/c mice during pregnancy and lactation. These mothers developed a codfish-specific allergic response shown as high IgG1 and IgE antibody levels and positive skin tests. In the next step we analyzed whether this maternal sensitization impacts a subsequent sensitization in the offspring. Indeed, in stimulated splenocytes of these offspring we found a relative Th2-dominance, because the Th1- and T-regulatory cytokines were significantly suppressed. Our data provide evidence that the anti-acid drug sucralfate supports sensitization against food in pregnant mice and favors a Th2-milieu in their offspring. From these results we propose that anti-acid treatment during pregnancy could be responsible for the increasing number of sensitizations against food allergens in young infants. PMID:17227952

  17. Maternal investment mediates offspring life history variation with context-dependent fitness consequences.

    PubMed

    Moore, Michael P; Landberg, Tobias; Whiteman, Howard H

    2015-09-01

    Maternal effects, such as per capita maternal investment, often interact with environmental conditions to strongly affect traits expressed early in ontogeny. However, their impact on adult life history traits and fitness components is relatively unknown. Theory predicts that lower per capita maternal investment will have strong fitness costs when the offspring develop in unfavorable conditions, yet few studies have experimentally manipulated per capita maternal investment and followed offspring through adulthood. We used a surgical embryonic yolk removal technique to investigate how per capita maternal investment interacted with an important ecological factor, larval density, to mediate offspring life history traits through reproductive maturity in an amphibian, Ambystoma talpoideum. We predicted that increased larval density would reinforce the life history variation induced by differences in per capita investment (i.e., Controls vs. Reduced Yolk), with Reduced larvae ultimately expressing traits associated with lower fitness than Controls when raised at high densities. We found that Reduced individuals were initially smaller and more developed, caught up in size to Controls within the first month of the larval stage, but were smaller at the end of the larval stage in low densities. Reduced individuals also were more likely to undergo metamorphosis at high densities and mature 'females invested in more eggs for their body sizes than Controls. Together, our results do not support our hypothesis, but instead indicate that Reduced individuals express traits associated with higher fitness when they develop in high-density environments, but lower fitness in low-density environments. The observed life history and fitness patterns are consistent with the "maternal match" hypothesis, which predicts that when the maternal environment (e.g., high density) results in phenotypic variation that is transmitted to the offspring (e.g., reduced per capita yolk investment), and

  18. Maternal high-fat diet consumption impairs exercise performance in offspring.

    PubMed

    Walter, Isabel; Klaus, Susanne

    2014-01-01

    The aim of the present study was to scrutinise the influence of maternal high-fat diet (mHFD) consumption during gestation and lactation on exercise performance and energy metabolism in male mouse offspring. Female C3H/HeJ mice were fed either a semi-synthetic high-fat diet (HFD; 40 % energy from fat) or a low-fat diet (LFD; 10 % energy from fat) throughout gestation and lactation. After weaning, male offspring of both groups received the LFD. At the age of 7·5 weeks half of the maternal LFD (n 20) and the mHFD (n 21) groups were given access to a running wheel for 28 d as a voluntary exercise training opportunity. We show that mHFD consumption led to a significantly reduced exercise performance (P < 0·05) and training efficiency (P < 0·05) in male offspring. There were no effects of maternal diet on offspring body weight. Lipid and glucose metabolism was disturbed in mHFD offspring, with altered regulation of cluster of differentiation 36 (CD36) (P < 0·001), fatty acid synthase (P < 0·05) and GLUT1 (P < 0·05) gene expression in skeletal muscle. In conclusion, maternal consumption of a HFD is linked to decreased exercise performance and training efficiency in the offspring. We speculate that this may be due to insufficient muscle energy supply during prolonged exercise training. Further, this compromised exercise performance might increase the risk of obesity development in adult life. PMID:26101629

  19. Diet-Induced Maternal Obesity Alters Insulin Signalling in Male Mice Offspring Rechallenged with a High-Fat Diet in Adulthood

    PubMed Central

    de Fante, Thaís; Simino, Laís Angélica; Reginato, Andressa; Payolla, Tanyara Baliani; Vitoréli, Débora Cristina Gustavo; de Souza, Monique; Torsoni, Márcio Alberto; Milanski, Marciane; Torsoni, Adriana Souza

    2016-01-01

    Modern lifestyle has resulted in an increase in the prevalence of obesity and its comorbidities in pregnant women and the young population. It has been well established that the consumption of a high-fat diet (HFD) has many direct effects on glucose metabolism. However, it is important to assess whether maternal consumption of a HFD during critical periods of development can lead to metabolic changes in the offspring metabolism. This study evaluated the potential effects of metabolic programming on the impairment of insulin signalling in recently weaned offspring from obese dams. Additionally, we investigated if early exposure to an obesogenic environment could exacerbate the impairment of glucose metabolism in adult life in response to a HFD. Swiss female mice were fed with Standard Chow (SC) or a HFD during gestation and lactation and tissues from male offspring were analysed at d28 and d82. Offspring from obese dams had greater weight gain and higher adiposity and food intake than offspring from control dams. Furthermore, they showed impairment in insulin signalling in central and peripheral tissues, which was associated with the activation of inflammatory pathways. Adipose tissue was ultimately the most affected in adult offspring after HFD rechallenge; this may have contributed to the metabolic deregulation observed. Overall, our results suggest that diet-induced maternal obesity leads to increased susceptibility to obesity and impairment of insulin signalling in offspring in early and late life that cannot be reversed by SC consumption, but can be aggravated by HFD re-exposure. PMID:27479001

  20. Diet-Induced Maternal Obesity Alters Insulin Signalling in Male Mice Offspring Rechallenged with a High-Fat Diet in Adulthood.

    PubMed

    Fante, Thaís de; Simino, Laís Angélica; Reginato, Andressa; Payolla, Tanyara Baliani; Vitoréli, Débora Cristina Gustavo; Souza, Monique de; Torsoni, Márcio Alberto; Milanski, Marciane; Torsoni, Adriana Souza

    2016-01-01

    Modern lifestyle has resulted in an increase in the prevalence of obesity and its comorbidities in pregnant women and the young population. It has been well established that the consumption of a high-fat diet (HFD) has many direct effects on glucose metabolism. However, it is important to assess whether maternal consumption of a HFD during critical periods of development can lead to metabolic changes in the offspring metabolism. This study evaluated the potential effects of metabolic programming on the impairment of insulin signalling in recently weaned offspring from obese dams. Additionally, we investigated if early exposure to an obesogenic environment could exacerbate the impairment of glucose metabolism in adult life in response to a HFD. Swiss female mice were fed with Standard Chow (SC) or a HFD during gestation and lactation and tissues from male offspring were analysed at d28 and d82. Offspring from obese dams had greater weight gain and higher adiposity and food intake than offspring from control dams. Furthermore, they showed impairment in insulin signalling in central and peripheral tissues, which was associated with the activation of inflammatory pathways. Adipose tissue was ultimately the most affected in adult offspring after HFD rechallenge; this may have contributed to the metabolic deregulation observed. Overall, our results suggest that diet-induced maternal obesity leads to increased susceptibility to obesity and impairment of insulin signalling in offspring in early and late life that cannot be reversed by SC consumption, but can be aggravated by HFD re-exposure. PMID:27479001

  1. Alterations in hepatic gene expression and genome-wide DNA methylation in rat offspring exposed to maternal obesity in utero

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adult offspring from obese (OB) rat dams gain greater body weight and fat mass than controls when fed HFD. At PND21, we examined energy expenditure (EE) (indirect calorimetry), hepatic gene expression (microarrays), and changes in genome-wide and global DNA methylation (enrichment-coupled DNA seque...

  2. Maternal inflammation activated ROS-p38 MAPK predisposes offspring to heart damages caused by isoproterenol via augmenting ROS generation

    PubMed Central

    Zhang, Qi; Deng, Yafei; Lai, Wenjing; Guan, Xiao; Sun, Xiongshan; Han, Qi; Wang, Fangjie; Pan, Xiaodong; Ji, Yan; Luo, Hongqin; Huang, Pei; Tang, Yuan; Gu, Liangqi; Dan, Guorong; Yu, Jianhua; Namaka, Michael; Zhang, Jianxiang; Deng, Youcai; Li, Xiaohui

    2016-01-01

    Maternal inflammation contributes to the increased incidence of adult cardiovascular disease. The current study investigated the susceptibility of cardiac damage responding to isoproterenol (ISO) in adult offspring that underwent maternal inflammation (modeled by pregnant Sprague-Dawley rats with lipopolysaccharides (LPS) challenge). We found that 2 weeks of ISO treatment in adult offspring of LPS-treated mothers led to augmented heart damage, characterized by left-ventricular systolic dysfunction, cardiac hypertrophy and myocardial fibrosis. Mechanistically, prenatal exposure to LPS led to up-regulated expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, antioxidant enzymes, and p38 MAPK activity in left ventricular of adult offspring at resting state. ISO treatment exaggerated ROS generation, p38 MAPK activation but down-regulated reactive oxygen species (ROS) elimination capacity in the left ventricular of offspring from LPS-treated mothers, while antioxidant N-acetyl-L-cysteine (NAC) reversed these changes together with improved cardiac functions. The p38 inhibitor SB202190 alleviated the heart damage only via inhibiting the expression of NADPH oxidases. Collectively, our data demonstrated that prenatal inflammation programs pre-existed ROS activation in the heart tissue, which switches on the early process of oxidative damages on heart rapidly through a ROS-p38 MAPK-NADPH oxidase-ROS positive feedback loop in response to a myocardial hypertrophic challenge in adulthood. PMID:27443826

  3. Maternal inflammation activated ROS-p38 MAPK predisposes offspring to heart damages caused by isoproterenol via augmenting ROS generation.

    PubMed

    Zhang, Qi; Deng, Yafei; Lai, Wenjing; Guan, Xiao; Sun, Xiongshan; Han, Qi; Wang, Fangjie; Pan, Xiaodong; Ji, Yan; Luo, Hongqin; Huang, Pei; Tang, Yuan; Gu, Liangqi; Dan, Guorong; Yu, Jianhua; Namaka, Michael; Zhang, Jianxiang; Deng, Youcai; Li, Xiaohui

    2016-01-01

    Maternal inflammation contributes to the increased incidence of adult cardiovascular disease. The current study investigated the susceptibility of cardiac damage responding to isoproterenol (ISO) in adult offspring that underwent maternal inflammation (modeled by pregnant Sprague-Dawley rats with lipopolysaccharides (LPS) challenge). We found that 2 weeks of ISO treatment in adult offspring of LPS-treated mothers led to augmented heart damage, characterized by left-ventricular systolic dysfunction, cardiac hypertrophy and myocardial fibrosis. Mechanistically, prenatal exposure to LPS led to up-regulated expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, antioxidant enzymes, and p38 MAPK activity in left ventricular of adult offspring at resting state. ISO treatment exaggerated ROS generation, p38 MAPK activation but down-regulated reactive oxygen species (ROS) elimination capacity in the left ventricular of offspring from LPS-treated mothers, while antioxidant N-acetyl-L-cysteine (NAC) reversed these changes together with improved cardiac functions. The p38 inhibitor SB202190 alleviated the heart damage only via inhibiting the expression of NADPH oxidases. Collectively, our data demonstrated that prenatal inflammation programs pre-existed ROS activation in the heart tissue, which switches on the early process of oxidative damages on heart rapidly through a ROS-p38 MAPK-NADPH oxidase-ROS positive feedback loop in response to a myocardial hypertrophic challenge in adulthood. PMID:27443826

  4. Offspring insulin and adiponectin signaling are targets of in utero programming following exposure to maternal overweight during gestation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The risk of obesity in adult-life is subject to programming during gestation. To examine whether in utero exposure to maternal overweight (OW) increases the risk of obesity in the offspring, we developed an overfeeding-based model of maternal OW in rats utilizing intragastric feeding of diets via to...

  5. Evidence for sympathetic origins of hypertension in juvenile offspring of obese rats.

    PubMed

    Samuelsson, Anne-Maj; Morris, Abigail; Igosheva, Natalia; Kirk, Shona L; Pombo, Joaquim M C; Coen, Clive W; Poston, Lucilla; Taylor, Paul D

    2010-01-01

    Maternal obesity in rodents is associated with increased adiposity, impaired glucose tolerance, and hypertension in adult offspring. In this study we investigated the influence of maternal obesity in the rat on blood pressure and blood pressure regulatory pathways in juvenile and adult offspring. Obesity was induced before pregnancy in female Sprague-Dawley rats by feeding a highly palatable energy-dense diet. In juvenile animals (30 days of age), before the onset of obesity and hyperleptinemia, basal nighttime mean arterial pressure was significantly raised in the offspring of obese dams (OffOb) relative to offspring of controls (OffCon; mean arterial pressure, males: OffOb, 121.8+/-0.6 mm Hg versus OffCon, 115.0+/-0.5 mm Hg, n=6, P<0.01; females: OffOb, 125.4+/-0.4 mm Hg versus OffCon, 114.4+/-0.5 mm Hg, n=6, P<0.001), as was the mean arterial pressure response to restraint stress (P<0.01). The pressor response to a leptin challenge was enhanced in OffOb rats (Deltamean arterial pressure: OffOb, 9.7+/-0.8 mm Hg versus OffCon, 5.3+/-1.3 mm Hg; n=8; P<0.05). Renal tissue norepinephrine content (P<0.001) and renin expression (P<0.05) were markedly raised. Analysis of heart rate variability revealed an increased low:high frequency ratio in OffOb versus OffCon rats (P<0.05). At 90 days, hypertension in OffOb rats persisted and was abolished by alpha1- and beta-adrenergic blockade, and cardiovascular responses to phenylephrine or sodium nitroprusside indicated altered baroreceptor function. The exaggerated pressor response to leptin in OffOb rats was maintained. Hypertension in the offspring of obese rats may arise from persistent sympathoexcitatory hyperresponsiveness acquired in early stages of development. PMID:19901159

  6. Cortactin is implicated in murine zygotic development

    PubMed Central

    Yu, Dan; Zhang, Helin; Blanpied, Thomas A.; Smith, Elizabeth; Zhan, Xi

    2009-01-01

    Cortactin is a cortex-enriched protein implicated in Arp2/3 complex-mediated actin polymerization. However, the physiological role of cortactin remains unknown. We have generated a mouse strain in which the allele of murine cortactin was disrupted by a gene trapping vector. The resulting heterozygous mice developed normally and were fertile, but embryonic fibroblasts derived from heterozygous animals displayed partial impairment in PDGF-induced membrane ruffling. No homozygous offspring or early embryos even at the two-cell stage were detected. Analysis of oocytes revealed a gradual decrease in the detection of homozygous zygotes after fertilization. In normal oocytes arrested at meiotic metaphase II (MII), cortactin immunoreactivity was detected in an apical layer that overlies the maternal chromosome and overlaps with a polarized cortex enriched with actin. The formation of the polarized cortactin layer was diminished upon treatment with latrunculin B, an actin polymerization inhibitor. After resumption of meiosis II, the majority of cortactin protein was accumulated into the second polar body. Microinjection of MII-arrested eggs with either cortactin antibody or RNA encoding a cortactin mutant deficient in Arp2/3 complex binding disrupted the integrity of the actin cap and inhibited emission of the second polar body triggered by parthenogenesis. Our data suggest that cortactin plays an important role in the mechanics of asymmetric division in oocytes. PMID:20004659

  7. Paternal BPA exposure in early life alters Igf2 epigenetic status in sperm and induces pancreatic impairment in rat offspring.

    PubMed

    Mao, Zhenxing; Xia, Wei; Chang, Huailong; Huo, Wenqian; Li, Yuanyuan; Xu, Shunqing

    2015-11-01

    Exposure to endocrine disruptors in utero appears to alter epigenetics in the male germ-line and subsequently promote adult-onset disease in subsequent generations. Fetal exposure to bisphenol A (BPA), a highly prevalent endocrine disruptor in environment, has been shown to alter epigenetic modification and result in glucose intolerance in adulthood. However, whether fetal exposure to BPA can induce epigenetic modification and phenotypic changes in their subsequent offspring are still unclear. The present study was designed to investigate whether exposure to BPA in early life induced glucose intolerance in the offspring through male germ line, and the underlying epigenetic molecular basis. F0 pregnant SD rats were received corn oil or 40 μg/kg/day of BPA during gestation and lactation. F1 male rats were maintained to generate F2 offspring by mating with untreated female rats. Both the F1 rats after weaning and the F2 offspring were not received any other treatments. Our results showed that male F2 offspring in the BPA group exhibited glucose intolerance and β-cell dysfunction. Decreased expression of Igf2 and associated hypermethylation of Igf2 were observed in islets of male F2 offspring. In addition, similar effects were observed in female F2 animals, but the effects were more pronounced in males. Moreover, abnormal expression and methylation of Igf2 was observed in sperm of adult F1 male rats, indicating that epigenetic modification in germ cells can be partly progressed to the next generation. Overall, our study suggests that BPA exposure during early life can result in generational transmission of glucose intolerance and β-cell dysfunction in the offspring through male germ line, which is associated with hypermethylation of Igf2 in islets. The changes of epigenetics in germ cells may contribute to this generational transmission. PMID:26276081

  8. Inbreeding depression in an insect with maternal care: influences of family interactions, life stage and offspring sex.

    PubMed

    Meunier, J; Kölliker, M

    2013-10-01

    Although inbreeding is commonly known to depress individual fitness, the severity of inbreeding depression varies considerably across species. Among the factors contributing to this variation, family interactions, life stage and sex of offspring have been proposed, but their joint influence on inbreeding depression remains poorly understood. Here, we demonstrate that these three factors jointly shape inbreeding depression in the European earwig, Forficula auricularia. Using a series of cross-breeding, split-clutch and brood size manipulation experiments conducted over two generations, we first showed that sib mating (leading to inbred offspring) did not influence the reproductive success of earwig parents. Second, the presence of tending mothers and the strength of sibling competition (i.e. brood size) did not influence the expression of inbreeding depression in the inbred offspring. By contrast, our results revealed that inbreeding dramatically depressed the reproductive success of inbred adult male offspring, but only had little effect on the reproductive success of inbred adult female offspring. Overall, this study demonstrates limited effects of family interactions on inbreeding depression in this species and emphasizes the importance of disentangling effects of sib mating early and late during development to better understand the evolution of mating systems and population dynamics. PMID:23981229

  9. Low taurine, gamma-aminobutyric acid and carnosine levels in plasma of diabetic pregnant rats: consequences for the offspring.

    PubMed

    Aerts, L; Van Assche, F A

    2001-01-01

    Gestational diabetes compromises fetal development and induces a diabetogenic effect in the offspring, including the development of gestational diabetes and the transmission of the effect to the next generation. Changes are not limited to glucose and insulin metabolism, and appear to be modulated by alterations at the hypothalamo-hypophyseal axis. In the present work, serum concentrations are given for the non-protein amino-acids taurine and gamma-aminobutyric acid (GABA), both neurotransmitters essential for normal brain development, and for the endogenous neuroprotector carnosine, a known anti-oxydans. Taurine levels are significantly below normal values in mildly diabetic mothers, in their fetal and adult offspring, virgin and pregnant, and in the fetuses of these pregnant offspring. GABA and carnosine levels are at the limit of detection in the diabetic mothers and their offspring at every stage. It is concluded that the low taurine, GABA and carnosine levels in diabetic mothers and their fetuses might compromise the normal structural and functional development of the fetal brain. When adult, these offspring present a deficiency of the circulating levels of these neurotransmitters involved in the hypothalamo-hypophyseal regulation of insulin secretion. This might contribute to the development of impaired glucose tolerance and gestational diabetes, thereby transmitting the effect to the next generation. PMID:11234622

  10. Offspring size in a resident species affects community assembly.

    PubMed

    Davis, Kurt; Marshall, Dustin J

    2014-03-01

    Offspring size is a trait of fundamental importance that affects the ecology and evolution of a range of organisms. Despite the pervasive impact of offspring size for those offspring, the influence of offspring size on other species in the broader community remains unexplored. Such community-wide effects of offspring size are likely, but they have not been anticipated by theory or explored empirically. For a marine invertebrate community, we manipulated the size and density of offspring of a resident species (Watersipora subtorquata) in the field and examined subsequent community assembly around that resident species. Communities that assembled around larger offspring were denser and less diverse than communities that assembled around smaller offspring. Differences in niche usage by colonies from smaller and larger offspring may be driving these community-level effects. Our results suggest that offspring size is an important but unexplored source of ecological variation and that life-history theory must accommodate the effects of offspring size on community assembly. Life-history theory often assumes that environmental variation drives intraspecific variation in offspring size, and our results show that the converse can also occur. PMID:26046291

  11. Maternal high-fat diet induces obesity and adrenal and thyroid dysfunction in male rat offspring at weaning.

    PubMed

    Franco, J G; Fernandes, T P; Rocha, C P D; Calviño, C; Pazos-Moura, C C; Lisboa, P C; Moura, E G; Trevenzoli, I H

    2012-11-01

    Maternal nutritional status affects the future development of offspring. Both undernutrition and overnutrition in critical periods of life (gestation or lactation) may cause several hormonal changes in the pups and programme obesity in the adult offspring. We have shown that hyperleptinaemia during lactation results in central leptin resistance, higher adrenal catecholamine secretion, hyperthyroidism, and higher blood pressure and heart rate in the adult rats. Here, we evaluated the effect of a maternal isocaloric high-fat diet on breast milk composition and its impact on leptinaemia, energy metabolism, and adrenal and thyroid function of the offspring at weaning. We hypothesised that the altered source of fat in the maternal diet even under normal calorie intake would disturb the metabolism of the offspring. Female Wistar rats were fed a normal (9% fat; C group) or high-fat diet (29% fat as lard; HF group) for 8 weeks before mating and during pregnancy and lactation. HF mothers presented increased total body fat content after 8 weeks (+27%, P < 0.05) and a similar fat content at the end of lactation. In consequence, the breast milk from the HF group had higher concentration of protein (+18%, P < 0.05), cholesterol (+52%, P < 0.05) and triglycerides (+86%, P < 0.05). At weaning, HF offspring had increased body weight (+53%, P < 0.05) and adiposity (2 fold, P < 0.05), which was associated with lower β3-adrenoreceptor content in adipose tissue (-40%, P < 0.05). The offspring also presented hyperglycaemia (+30%, P < 0.05) and hyperleptinaemia (+62%, P < 0.05). In the leptin signalling pathway in the hypothalamus, we found lower p-STAT3/STAT3 (-40%, P < 0.05) and SOCS3 (-55%, P < 0.05) content in the arcuate nucleus, suggesting leptin resistance. HF offspring also had higher adrenal catecholamine content (+17%, P < 0.05), liver glycogen content (+50%, P < 0.05) and hyperactivity of the thyroid axis at weaning. Our results suggest that a high fat diet increases

  12. Maternal high-fat diet induces obesity and adrenal and thyroid dysfunction in male rat offspring at weaning

    PubMed Central

    Franco, J G; Fernandes, T P; Rocha, C P D; Calviño, C; Pazos-Moura, C C; Lisboa, P C; Moura, E G; Trevenzoli, I H

    2012-01-01

    Maternal nutritional status affects the future development of offspring. Both undernutrition and overnutrition in critical periods of life (gestation or lactation) may cause several hormonal changes in the pups and programme obesity in the adult offspring. We have shown that hyperleptinaemia during lactation results in central leptin resistance, higher adrenal catecholamine secretion, hyperthyroidism, and higher blood pressure and heart rate in the adult rats. Here, we evaluated the effect of a maternal isocaloric high-fat diet on breast milk composition and its impact on leptinaemia, energy metabolism, and adrenal and thyroid function of the offspring at weaning. We hypothesised that the altered source of fat in the maternal diet even under normal calorie intake would disturb the metabolism of the offspring. Female Wistar rats were fed a normal (9% fat; C group) or high-fat diet (29% fat as lard; HF group) for 8 weeks before mating and during pregnancy and lactation. HF mothers presented increased total body fat content after 8 weeks (+27%, P < 0.05) and a similar fat content at the end of lactation. In consequence, the breast milk from the HF group had higher concentration of protein (+18%, P < 0.05), cholesterol (+52%, P < 0.05) and triglycerides (+86%, P < 0.05). At weaning, HF offspring had increased body weight (+53%, P < 0.05) and adiposity (2 fold, P < 0.05), which was associated with lower β3-adrenoreceptor content in adipose tissue (−40%, P < 0.05). The offspring also presented hyperglycaemia (+30%, P < 0.05) and hyperleptinaemia (+62%, P < 0.05). In the leptin signalling pathway in the hypothalamus, we found lower p-STAT3/STAT3 (−40%, P < 0.05) and SOCS3 (−55%, P < 0.05) content in the arcuate nucleus, suggesting leptin resistance. HF offspring also had higher adrenal catecholamine content (+17%, P < 0.05), liver glycogen content (+50%, P < 0.05) and hyperactivity of the thyroid axis at weaning. Our results suggest that a high fat diet increases

  13. PROGRAMMING OF GROWTH, INSULIN RESISTANCE AND VASCULAR DYSFUNCTION IN OFFSPRING OF LATE GESTATION DIABETIC RATS

    PubMed Central

    Segar, Emily M.; Norris, Andrew W.; Yao, Jian-Rong; Hu, Shanming; Koppenhafer, Stacia L.; Roghair, Robert D.; Segar, Jeffrey L.; Scholz, Thomas D.

    2010-01-01

    The offspring of diabetic mothers (ODM) have an increased risk of developing metabolic and cardiovascular dysfunction. However, few studies have focused on susceptibility to disease in offspring of mothers developing diabetes during pregnancy. We developed an animal model of late-gestation diabetic pregnancy and characterized metabolic and vascular function in the offspring. Diabetes was induced by streptozotocin (50 mg/kg, i.p.) in pregnant rats on gestational day 13 and partially controlled by twice-daily injections of insulin. At 2 months of age, ODM had slightly better glucose tolerance than controls (p < 0.05), however, by 6 months of age this trend reversed. Hyperinsulinemic-euglycemic clamp revealed insulin resistance in male ODM (p < 0.05). In 6-8 mo old female ODM, aortas showed significantly enhanced contractility to potassium chloride (KCl), endothelin-1 (ET-1) and noradrenaline (NA). No differences in responses to endothelin-1 and noradrenaline were apparent with co-administration of NG-nitro-L-arginine (L-NNA). Relaxation to acetylcholine but not nitroprusside was significantly impaired in female ODM. In contrast, males displayed no between group differences in response to vasoconstrictors while relaxation to nitroprusside and acetylcholine was greater in ODM compared to control animals. Thus, development of diabetes during pregnancy programs gender specific insulin resistance and vascular dysfunction in adult offspring. PMID:19203348

  14. Drug treatment of malaria infections can reduce levels of protection transferred to offspring via maternal immunity

    PubMed Central

    Staszewski, Vincent; Reece, Sarah E.; O'Donnell, Aidan J.; Cunningham, Emma J. A.

    2012-01-01

    Maternally transferred immunity can have a fundamental effect on the ability of offspring to deal with infection. However, levels of antibodies in adults can vary both quantitatively and qualitatively between individuals and during the course of infection. How infection dynamics and their modification by drug treatment might affect the protection transferred to offspring remains poorly understood. Using the rodent malaria parasite Plasmodium chabaudi, we demonstrate that curing dams part way through infection prior to pregnancy can alter their immune response, with major consequences for offspring health and survival. In untreated maternal infections, maternally transferred protection suppressed parasitaemia and reduced pup mortality by 75 per cent compared with pups from naïve dams. However, when dams were treated with anti-malarial drugs, pups received fewer maternal antibodies, parasitaemia was only marginally suppressed, and mortality risk was 25 per cent higher than for pups from dams with full infections. We observed the same qualitative patterns across three different host strains and two parasite genotypes. This study reveals the role that within-host infection dynamics play in the fitness consequences of maternally transferred immunity. Furthermore, it highlights a potential trade-off between the health of mothers and offspring suggesting that anti-parasite treatment may significantly affect the outcome of infection in newborns. PMID:22357264

  15. Perinatal exposure to 4-nonylphenol affects adipogenesis in first and second generation rats offspring.

    PubMed

    Zhang, Hong-Yu; Xue, Wei-Yan; Li, Yuan-Yuan; Ma, Yue; Zhu, Ying-Shuang; Huo, Wen-Qian; Xu, Bing; Xia, Wei; Xu, Shun-Qing

    2014-03-01

    Maternal exposure to 4-nonylphenol (4-NP) during pregnancy was shown to alter adipogenesis in rodents, yet whether the effects are restricted to 4-NP-exposed offspring only or can be transmitted to the next generation are not known. Pregnant Wistar rats received either vehicle or 4-NP (5, 25 and 125μg/kg/day) from gestation to postnatal day 21. F1 pups were subjected to blood biochemistry tests, or killed to obtain their gonadal fat to determine gene expression. Some F1 adult female rats were mated with F1 males from control group to obtain F2 pups, but without any exposure to 4-NP in the perinatal stage. F2 pups underwent studies similar to those performed on F1 pups. Serum total cholesterol, leptin levels were significantly elevated, the quantity and size of fat cells were increased, gene expression of key regulators of adipogenesis and lipogenic pathway of fat tissue were perturbed by 4-NP (p<0.05 or p<0.01). In addition, the expression of mRNA levels and protein of ERα were downregulated in adipose tissue in the two generation offspring. Perinatal exposure to 4-NP affects the adipogenesis in both male and female F1 offspring, and this effect can be progressed to the F2 offspring through the maternal line. PMID:24388992

  16. Prenatal Exposure to Lamotrigine: Effects on Postnatal Development and Behaviour in Rat Offspring

    PubMed Central

    Sathiya, Sekar; Ganesh, Murugan; Kalaivani, Periyathambi; Ranju, Vijayan; Janani, Srinivasan; Pramila, Bakthavachalam; Saravana Babu, Chidambaram

    2014-01-01

    Use of antiepileptic drugs (AEDs) in pregnancy warrants various side effects and also deleterious effects on fetal development. The present study was carried out to assess the effects of prenatal exposure to lamotrigine (LTG) on postnatal development and behavioural alterations of offspring. Adult male and female Sprague Dawley rats weighing 150–180 g b. wt. were allowed to copulate and pregnancy was confirmed by vaginal cytology. Pregnant rats were treated with LTG (11.5, 23, and 46 mg/kg, p.o) from gestational day 3 (GND 3) and this treatment continued till postnatal day 11 (PND 11). Offspring were separated from their dam on day 21 following parturition. LTG, at 46 mg/kg, p.o, produced severe clinical signs of toxicity leading to death of dam between GND 15 and 17. LTG, at 11.5 and 23 mg/kg, p.o, showed significant alterations in offspring's incisors eruption and vaginal opening when compared to age matched controls. LTG (23 mg/kg, p.o) exposed female offspring expressed hyperactive behaviour and decreased GABA-A receptor expression when compared to control rats. These results reveal that prenatal exposure to LTG may impart differential postnatal behavioural alterations between male and female rats which paves way for further investigations. PMID:24967313

  17. Effects of experimentally manipulated yolk thyroid hormone levels on offspring development in a wild bird species.

    PubMed

    Ruuskanen, Suvi; Darras, Veerle M; Visser, Marcel E; Groothuis, Ton G G

    2016-05-01

    Maternal effects are a crucial mechanism in a wide array of taxa to generate phenotypic variation, thereby affecting offspring development and fitness. Maternally derived thyroid hormones (THs) are known to be essential for offspring development in mammalian and fish models, but have been largely neglected in avian studies, especially in respect to natural variation and an ecological context. We studied, for the first time in a wild species and population, the effects of maternally derived THs on offspring development, behavior, physiology and fitness-related traits by experimental elevation of thyroxine and triiodothyronine in ovo within the physiological range in great tits (Parus major). We found that elevated yolk TH levels had a sex-specific effect on growth, increasing male and decreasing female growth, relative to controls, and this effect was similar throughout the nestling period. Hatching or fledging success, motor coordination behavior, stress reactivity and resting metabolic rate were not affected by the TH treatment. We conclude that natural variation in maternally derived THs may affect some offspring traits in a wild species. As this is the first study on yolk thyroid hormones in a wild species and population, more such studies are needed to investigate its effects on pre-hatching development, and juvenile and adult fitness before generalizations on the importance of maternally derived yolk thyroid hormones can be made. However, this opens a new, interesting avenue for further research in the field of hormone mediated maternal effects. PMID:27056104

  18. Maternal lead exposure during lactation persistently impairs testicular development and steroidogenesis in male offspring.

    PubMed

    Wang, Hua; Ji, Yan-Li; Wang, Qun; Zhao, Xian-Feng; Ning, Huan; Liu, Ping; Zhang, Cheng; Yu, Tao; Zhang, Ying; Meng, Xiu-Hong; Xu, De-Xiang

    2013-12-01

    Lead (Pb) is a testicular toxicant. In the present study, we investigated the effects of maternal Pb exposure during lactation on testicular development and steroidogenesis in male offspring. Maternal mice were exposed to different concentration of lead acetate (200 or 2000 ppm) through drinking water from postnatal day (PND) 0 to PND21. As expected, a high concentration of Pb was measured in the kidneys and liver of pups whose mothers were exposed to Pb during lactation. In addition, maternal Pb exposure during lactation elevated, to a less extent, Pb content in testes of weaning pups. Testis weight in weaning pups was significantly decreased when maternal mice were exposed to Pb during lactation. The level of serum and testicular T was reduced in Pb-exposed pups. The expression of P450scc, P450(17α) and 17β-HSD, key enzymes for T synthesis, was down-regulated in testes of weaning pups whose mothers were exposed to Pb during lactation. Interestingly, the level of serum and testicular T remained decreased in adult offspring whose mothers were exposed to Pb during lactation. Importantly, the number of spermatozoa was significantly reduced in Pb-exposed male offspring. Taken together, these results suggest that Pb could be transported from dams to pups through milk. Maternal Pb exposure during lactation persistently disrupts testicular development and steroidogenesis in male offspring. PMID:22806249

  19. Elevation of 11β-hydroxysteroid dehydrogenase type 2 activity in Holocaust survivor offspring: evidence for an intergenerational effect of maternal trauma exposure

    PubMed Central

    Bierer, Linda M.; Bader, Heather N.; Daskalakis, Nikolaos P.; Lehrner, Amy; Makotkine, Iouri; Seckl, Jonathan R.; Yehuda, Rachel

    2014-01-01

    Background Adult offspring of Holocaust survivors comprise an informative cohort in which to study intergenerational transmission of the effects of trauma exposure. Lower cortisol and enhanced glucocorticoid sensitivity have been previously demonstrated in Holocaust survivors with PTSD, and in offspring of Holocaust survivors in association with maternal PTSD. In other work, reduction in the activity of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), which inactivates cortisol, was identified in Holocaust survivors in comparison to age-matched, unexposed Jewish controls. Therefore, we investigated glucocorticoid metabolism in offspring of Holocaust survivors to evaluate if similar enzymatic decrements would be observed that might help to explain glucocorticoid alterations previously shown for Holocaust offspring. Methods Holocaust offspring (n=85) and comparison subjects (n=27) were evaluated with clinical diagnostic interview and self-rating scales, and asked to collect a 24-hr urine sample from which concentrations of cortisol and glucocorticoid metabolites were assayed by GCMS. 11β-HSD-2 activity was determined as the ratio of urinary cortisone to cortisol. Results Significantly reduced cortisol excretion was observed in Holocaust offspring compared to controls (p=.046), as had been shown for Holocaust survivors. However, 11β-HSD-2 activity was elevated for offspring compared to controls (p=.008), particularly among those whose mothers had been children, rather than adolescents or adults, during World War II (p=.032). The effect of paternal Holocaust exposure could not be reliably investigated in the current sample. Conclusions The association of offspring 11β-HSD-2 activity with maternal age at Holocaust exposure is consistent with the influence of glucocorticoid programming. Whereas a long standing reduction in 11β-HSD-2 activity among survivors is readily interpreted in the context of Holocaust related deprivation, understanding the

  20. Bipolar offspring: a window into bipolar disorder evolution.

    PubMed

    Chang, Kiki; Steiner, Hans; Dienes, Kimberly; Adleman, Nancy; Ketter, Terence

    2003-06-01

    Children of parents with bipolar disorder (bipolar offspring) represent a rich cohort for study with potential for illumination of prodromal forms of bipolar disorder. Due to their high-risk nature, bipolar offspring may present phenomenological, temperamental, and biological clues to early presentations of bipolar disorder. This article reviews the evidence for establishing bipolar offspring as a high-risk cohort, the studies which point to possible prodromal states in bipolar offspring, biological findings in bipolar offspring which may be indicators of even higher risk for bipolar disorder, initial attempts at early intervention in prodromal pediatric bipolar disorder, and implications for future research. PMID:12788239

  1. A mathematical model on the optimal timing of offspring desertion.

    PubMed

    Seno, Hiromi; Endo, Hiromi

    2007-06-01

    We consider the offspring desertion as the optimal strategy for the deserter parent, analyzing a mathematical model for its expected reproductive success. It is shown that the optimality of the offspring desertion significantly depends on the offsprings' birth timing in the mating season, and on the other ecological parameters characterizing the innate nature of considered animals. Especially, the desertion is less likely to occur for the offsprings born in the later period of mating season. It is also implied that the offspring desertion after a partially biparental care would be observable only with a specific condition. PMID:17328918

  2. Perinatal maternal feeding with an energy dense diet and/or micronutrient mixture drives offspring fat distribution depending on the sex and growth stage.

    PubMed

    Cordero, P; Gonzalez-Muniesa, P; Milagro, F I; Campion, J; Martinez, J A

    2015-10-01

    Maternal nutrition during pregnancy and lactation influences offspring development and health. Novel studies have described the effects on next generation obesity-related features depending on maternal macro- and micro-nutrient perinatal feeding. We hypothesized that the maternal obesogenic diet during pregnancy and lactation programs an obese phenotype, while maternal micronutrient supplementation at these stages could partially prevent these features. Thus, the aim was to assess the influence of a perinatal maternal feeding with an obesogenic diet enriched in fat and sucrose and a micronutrient supplementation during pregnancy and lactation on offspring growth and obese phenotypical features during life course. Female Wistar rats were assigned to four dietary groups during pregnancy and lactation: control, control supplemented with micronutrients (choline, betaine, folic acid and vitamin B12 ), high-fat sucrose (HFS) and HFS supplemented. At weaning, the offspring were transferred to a chow diet, and weight and fat mass were measured at weeks 3, 12 and 20. At birth, both male and female offspring from mothers fed the obesogenic diet showed lower body weight (-5 and -6%, respectively), while only female offspring weight decreased by maternal micronutrient supplementation (-5%). During lactation, maternal HFS diet was associated with increased body weight, while micronutrient supplementation protected against body weight gain. Whole body fat mass content increased at weeks 3, 12 and 20 (from 16 to 65%) due to maternal HFS diet. Maternal micronutrient supplementation decreased offspring fat mass content at week 3 (-8%). Male offspring showed higher adiposity than females at weeks 12 and 20. In conclusion, maternal HFS feeding during pregnancy and lactation was associated with a low offspring weight at birth and obese phenotypical features during adult life in a sex- and time-dependent manner. Furthermore, maternal methyl donor supplementation protected against body

  3. Pathways to Suicide-Related Behavior in Offspring of Mothers With Depression: The Role of Offspring Psychopathology

    PubMed Central

    Hammerton, Gemma; Zammit, Stanley; Mahedy, Liam; Pearson, Rebecca M.; Sellers, Ruth; Thapar, Anita; Collishaw, Stephan

    2015-01-01

    Objective Offspring of mothers with depression are a high-risk group for the development of suicide-related behavior. These offspring are therefore a priority for preventive interventions; however, pathways contributing to risk, including specific aspects of offspring psychopathology, remain unclear. The aim of this study was to examine whether offspring symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), disruptive behavior disorder (DBD), attention-deficit/hyperactivity disorder (ADHD), and alcohol abuse independently mediate the association between maternal depression and offspring suicide-related behavior. Method Data were used from a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Three distinct classes of depression symptoms across the mothers’ first 11 years of their child’s life were identified (minimal, moderate, chronic-severe). Offspring psychopathology was assessed at age 15 years and suicide-related behavior at age 16 years. Data were analyzed using structural equation modeling. Results There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms in comparison to offspring of mothers with minimal symptoms (odds ratio = 3.04, 95% CI = 2.19, 4.21). This association was independently mediated by offspring MDD, GAD, and DBD symptoms. The same mechanisms were found for offspring of mothers with moderate depression symptoms over time. Results were similar for offspring suicide attempt except for additional evidence of an indirect effect through offspring ADHD symptoms. Conclusion Findings highlight that suicide prevention efforts in offspring of mothers with depression should not only be targeted at offspring with MDD; it is also important to consider offspring with other forms of psychopathology. PMID:25901775

  4. Paternal B Vitamin Intake Is a Determinant of Growth, Hepatic Lipid Metabolism and Intestinal Tumor Volume in Female Apc1638N Mouse Offspring

    PubMed Central

    Sabet, Julia A.; Park, Lara K.; Iyer, Lakshmanan K.; Tai, Albert K.; Koh, Gar Yee; Pfalzer, Anna C.; Parnell, Laurence D.; Mason, Joel B.; Liu, Zhenhua; Byun, Alexander J.; Crott, Jimmy W.

    2016-01-01

    Background The importance of maternal nutrition to offspring health and risk of disease is well established. Emerging evidence suggests paternal diet may affect offspring health as well. Objective In the current study we sought to determine whether modulating pre-conception paternal B vitamin intake alters intestinal tumor formation in offspring. Additionally, we sought to identify potential mechanisms for the observed weight differential among offspring by profiling hepatic gene expression and lipid content. Methods Male Apc1638N mice (prone to intestinal tumor formation) were fed diets containing replete (control, CTRL), mildly deficient (DEF), or supplemental (SUPP) quantities of vitamins B2, B6, B12, and folate for 8 weeks before mating with control-fed wild type females. Wild type offspring were euthanized at weaning and hepatic gene expression profiled. Apc1638N offspring were fed a replete diet and euthanized at 28 weeks of age to assess tumor burden. Results No differences in intestinal tumor incidence or burden were found between male Apc1638N offspring of different paternal diet groups. Although in female Apc1638N offspring there were no differences in tumor incidence or multiplicity, a stepwise increase in tumor volume with increasing paternal B vitamin intake was observed. Interestingly, female offspring of SUPP and DEF fathers had a significantly lower body weight than those of CTRL fed fathers. Moreover, hepatic trigylcerides and cholesterol were elevated 3-fold in adult female offspring of SUPP fathers. Weanling offspring of the same fathers displayed altered expression of several key lipid-metabolism genes. Hundreds of differentially methylated regions were identified in the paternal sperm in response to DEF and SUPP diets. Aside from a few genes including Igf2, there was a striking lack of overlap between these genes differentially methylated in sperm and differentially expressed in offspring. Conclusions In this animal model, modulation of

  5. Studies of offspring of parents with bipolar disorder.

    PubMed

    Chang, Kiki; Steiner, Hans; Ketter, Terence

    2003-11-15

    Children and adolescents who are the biological offspring of individuals with bipolar disorder (BD) (bipolar offspring) represent a population rich in potential for revealing important aspects in the development of BD. Multiple cross-sectional assessments of psychopathology in bipolar offspring have confirmed high incidences of BD, as well as mood and behavioral disorders, and other psychopathology in this population. Longitudinal studies of offspring have begun to shed light on precursors of BD development. Other assessments of bipolar offspring have included dimensional reports of psychiatric and psychosocial functioning, temperament assessments, and descriptions of family environments and parenting styles. Neurobiological studies in bipolar offspring are just beginning to yield findings that may be related to the underlying neuropathophysiology of BD. The future holds promise for longitudinal studies of bipolar offspring incorporating all of these facets, including genetic analyses, to further elucidate the factors involved in the evolution of BD. PMID:14601034

  6. Epigenetic regulation in murine offspring as a novel mechanism for transmaternal asthma protection induced by microbes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bronchial asthma is a chronic inflammatory disease resulting from complex gene-environment interactions. Natural microbial exposure has been identified as an important environmental condition that provides asthma protection in a prenatal window of opportunity. Epigenetic regulation is an important m...

  7. Just Spraying Adult Mosquitoes Won't Curb Zika

    MedlinePlus

    ... html Just Spraying Adult Mosquitoes Won't Curb Zika: Study Lab work suggests larvicide also needed to ... 2016 (HealthDay News) -- Female mosquitoes can transmit the Zika virus to their eggs and offspring, and this ...

  8. Parasite Stress Predicts Offspring Sex Ratio

    PubMed Central

    Dama, Madhukar Shivajirao

    2012-01-01

    In this study, I predict that the global variation of offspring sex ratio might be influenced in part by the level of parasite stress. From an energetic standpoint, higher gestational costs of producing a male offspring could decrease male births in a population with limited resources. This implies that, any factor that limits the parental resources could be expected to favor female offspring production. Human sex ratio at birth (SRB) is believed to be influenced by numerous socioeconomic, biological, and environmental factors. Here, I test a prediction that parasite stress, by virtue of its effects on the general health condition, may limit the parental investment ability and therefore could influence the SRB at the population level. The statistical analysis supports this prediction, and show that the level of parasite stress has a significant inverse relation with population SRB across the world. Further, this relation is many-folds stronger than the association of SRB with other factors, like; polygyny, fertility, latitude, and son-preference. Hence, I propose that condition affecting ability of parasites (but not adaptive significance) could be a likely causal basis for the striking variation of SRB across populations. PMID:23049967

  9. Does multiple paternity influence offspring disease resistance?

    PubMed

    Thonhauser, K E; Raveh, S; Thoß, M; Penn, D J

    2016-06-01

    It has been suggested that polyandry allows females to increase offspring genetic diversity and reduce the prevalence and susceptibility of their offspring to infectious diseases. We tested this hypothesis in wild-derived house mice (Mus musculus) by experimentally infecting the offspring from 15 single- and 15 multiple-sired litters with two different strains of a mouse pathogen (Salmonella Typhimurium) and compared their ability to control infection. We found a high variation in individual infection resistance (measured with pathogen loads) and significant differences among families, suggesting genetic effects on Salmonella resistance, but we found no difference in prevalence or infection resistance between single- vs. multiple-sired litters. We found a significant sex difference in infection resistance, but surprisingly, males were more resistant to infection than females. Also, infection resistance was correlated with weight loss during infection, although only for females, indicating that susceptibility to infection had more harmful health consequences for females than for males. To our knowledge, our findings provide the first evidence for sex-dependent resistance to Salmonella infection in house mice. Our results do not support the hypothesis that multiple-sired litters are more likely to survive infection than single-sired litters; however, as we explain, additional studies are required before ruling out this hypothesis. PMID:26949230

  10. Effect of maternal diabetes on female offspring

    PubMed Central

    Martins, Juliana de Oliveira; Panício, Maurício Isaac; Dantas, Marcos Paulo Suehiro; Gomes, Guiomar Nascimento

    2014-01-01

    Objective To evaluate the effect of maternal diabetes on the blood pressure and kidney function of female offspring, as well as if such changes exacerbate during pregnancy. Methods Diabetes mellitus was induced in female rats with the administration of streptozotocin in a single dose, one week before mating. During pregnancy, blood pressure was measured through plethysmography. On the 20th day of pregnancy, the animals were placed for 24 hours in metabolic cages to obtain urine samples. After the animals were removed from the cages, blood samples were withdrawn. One month after pregnancy, new blood and urine sample were collected. Kidney function was evaluated through proteinuria, plasma urea, plasma creatinine, creatinine excretion rate, urinary flow, and creatinine clearance. Results The female offspring from diabetic mothers showed an increase in blood pressure, and a decrease in glomerular filtration rate in relation to the control group. Conclusion Hyperglycemia during pregnancy was capable of causing an increase in blood pressure and kidney dysfunction in the female offspring. PMID:25628190

  11. Remarkable Shifts in Offspring Provisioning during Gestation in a Live-Bearing Cnidarian

    PubMed Central

    Mercier, Annie; Sun, Zhao; Parrish, Christopher C.; Hamel, Jean-François

    2016-01-01

    Animals display diverse means of producing and provisioning offspring, from eggs to embryos and juveniles. While external development predominates, many forms of embryonic incubation have evolved, including placentation in mammals and a number of understudied variants in basal metazoans that could help understand evolutionary diversification. Here we studied the brooding sea anemone Aulactinia stella, using behavioural, morphological and biochemical indicators of offspring phenotype to characterize gestation and elucidate parental and sibling relationships. The pronounced variance in juvenile weight within broods was not strongly related to any of the typical external predictors (adult weight, clutch size, sampling date, environmental conditions). Lipid concentration was significantly higher in the tissues of the small juveniles than in those of large juveniles or adult, and fatty acid profiles tended to set small juveniles apart. Finally, intra-brood feeding on external resources was documented in larger juveniles. These results are consistent with ontogenetic shifts in nutrition, from vitellogenic provisioning to post-zygotic nourishment to a prenatal form of nursing upon acquisition of feeding organs, highlighting matrotrophic and conflict-driven mechanisms acting on offspring phenotype during gestation. PMID:27104375

  12. Remarkable Shifts in Offspring Provisioning during Gestation in a Live-Bearing Cnidarian.

    PubMed

    Mercier, Annie; Sun, Zhao; Parrish, Christopher C; Hamel, Jean-François

    2016-01-01

    Animals display diverse means of producing and provisioning offspring, from eggs to embryos and juveniles. While external development predominates, many forms of embryonic incubation have evolved, including placentation in mammals and a number of understudied variants in basal metazoans that could help understand evolutionary diversification. Here we studied the brooding sea anemone Aulactinia stella, using behavioural, morphological and biochemical indicators of offspring phenotype to characterize gestation and elucidate parental and sibling relationships. The pronounced variance in juvenile weight within broods was not strongly related to any of the typical external predictors (adult weight, clutch size, sampling date, environmental conditions). Lipid concentration was significantly higher in the tissues of the small juveniles than in those of large juveniles or adult, and fatty acid profiles tended to set small juveniles apart. Finally, intra-brood feeding on external resources was documented in larger juveniles. These results are consistent with ontogenetic shifts in nutrition, from vitellogenic provisioning to post-zygotic nourishment to a prenatal form of nursing upon acquisition of feeding organs, highlighting matrotrophic and conflict-driven mechanisms acting on offspring phenotype during gestation. PMID:27104375

  13. Maternal body size influences offspring immune configuration in an oviparous snake

    PubMed Central

    Brown, Gregory P.

    2016-01-01

    Like most ectothermic vertebrates, keelback snakes (Tropidonophis mairii) do not exhibit parental care. Thus, offspring must possess an immune system capable of dealing with challenges such as pathogens, without assistance from an attendant parent. We know very little about immune system characteristics of neonatal reptiles, including the magnitude of heritability and other maternal influences. To identify sources of variation in circulating white blood cell (WBC) concentrations and differentials, we examined blood smears from 246 hatchling snakes and their field-caught mothers. WBC concentrations were lower in hatchlings than in adults, and hatchlings had more basophils and fewer azurophils than adults. A hatchling keelback's WBC differential was also influenced by its sex and body size. Although hatchling WBC measures exhibited negligible heritability, they were strongly influenced by maternal body size and parasite infection (but not by maternal body condition, relative clutch mass or time in captivity). Larger mothers produced offspring with more azurophils and fewer lymphocytes. The mechanisms and consequences of WBC variation are currently unknown, but if these maternal effects enhance offspring fitness, the impact of maternal body size on reproductive success may be greater than expected simply from allometric increases in the numbers and sizes of progeny. PMID:27069670

  14. Maternal Immune Activation Leads to Selective Functional Deficits in Offspring Parvalbumin Interneurons

    PubMed Central

    Canetta, Sarah; Bolkan, Scott; Padilla-Coreano, Nancy; Song, LouJin; Sahn, Ryan; Harrison, Neil; Gordon, Joshua A.; Brown, Alan; Kellendonk, Christoph

    2015-01-01

    Summary Abnormalities in prefrontal GABAergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders including schizophrenia, bipolar disorder, anxiety disorders and depression. While primarily histological abnormalities have been observed in patients and in animal models of psychiatric disease, evidence for abnormalities in functional neurotransmission at the level of specific interneuron populations has been lacking in animal models and is difficult to establish in human patients. Using an animal model of a psychiatric disease risk factor, prenatal maternal immune activation (MIA), we found reduced functional GABAergic transmission in the medial prefrontal cortex (mPFC) of adult MIA offspring. Decreased transmission was selective for interneurons expressing PV, and was not observed in calretinin-expressing neurons. This deficit in PV function in MIA offspring was associated with increased anxiety-like behavior and impairments in attentional set shifting, but did not affect working memory. Furthermore, cell-type specific optogenetic inhibition of mPFC PV interneurons was sufficient to impair attentional set shifting and enhance anxiety levels. Finally, we found that in vivo mPFC gamma oscillations, which are supported by PV interneuron function, were linearly correlated with the degree of anxiety displayed in adult mice, and that this correlation was disrupted in MIA offspring. These results demonstrate a selective functional vulnerability of PV interneurons to maternal immune activation, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders. PMID:26830140

  15. Depot- and sex-specific effects of maternal obesity in offspring's adipose tissue.

    PubMed

    Lecoutre, Simon; Deracinois, Barbara; Laborie, Christine; Eberlé, Delphine; Guinez, Céline; Panchenko, Polina E; Lesage, Jean; Vieau, Didier; Junien, Claudine; Gabory, Anne; Breton, Christophe

    2016-07-01

    According to the Developmental Origin of Health and Disease (DOHaD) concept, alterations of nutrient supply in the fetus or neonate result in long-term programming of individual body weight (BW) setpoint. In particular, maternal obesity, excessive nutrition, and accelerated growth in neonates have been shown to sensitize offspring to obesity. The white adipose tissue may represent a prime target of metabolic programming induced by maternal obesity. In order to unravel the underlying mechanisms, we have developed a rat model of maternal obesity using a high-fat (HF) diet (containing 60% lipids) before and during gestation and lactation. At birth, newborns from obese dams (called HF) were normotrophs. However, HF neonates exhibited a rapid weight gain during lactation, a key period of adipose tissue development in rodents. In males, increased BW at weaning (+30%) persists until 3months of age. Nine-month-old HF male offspring was normoglycemic but showed mild glucose intolerance, hyperinsulinemia, and hypercorticosteronemia. Despite no difference in BW and energy intake, HF adult male offspring was predisposed to fat accumulation showing increased visceral (gonadal and perirenal) depots weights and hyperleptinemia. However, only perirenal adipose tissue depot exhibited marked adipocyte hypertrophy and hyperplasia with elevated lipogenic (i.e. sterol-regulated element binding protein 1 (Srebp1), fatty acid synthase (Fas), and leptin) and diminished adipogenic (i.e. peroxisome proliferator-activated receptor gamma (Pparγ), 11β-hydroxysteroid dehydrogenase type 1 (11β-Hds1)) mRNA levels. By contrast, very few metabolic variations were observed in HF female offspring. Thus, maternal obesity and accelerated growth during lactation program offspring for higher adiposity via transcriptional alterations of visceral adipose tissue in a depot- and sex-specific manner. PMID:27122310

  16. Association of Parental Hypertension With Arterial Stiffness in Nonhypertensive Offspring: The Framingham Heart Study.

    PubMed

    Andersson, Charlotte; Quiroz, Rene; Enserro, Danielle; Larson, Martin G; Hamburg, Naomi M; Vita, Joseph A; Levy, Daniel; Benjamin, Emelia J; Mitchell, Gary F; Vasan, Ramachandran S

    2016-09-01

    High arterial stiffness seems to be causally involved in the pathogenesis of hypertension. We tested the hypothesis that offspring of parents with hypertension may display higher arterial stiffness before clinically manifest hypertension, given that hypertension is a heritable condition. We compared arterial tonometry measures in a sample of 1564 nonhypertensive Framingham Heart Study third-generation cohort participants (mean age: 38 years; 55% women) whose parents were enrolled in the Framingham Offspring Study. A total of 468, 715, and 381 participants had 0 (referent), 1, and 2 parents with hypertension. Parental hypertension was associated with greater offspring mean arterial pressure (multivariable-adjusted estimate=2.9 mm Hg; 95% confidence interval, 1.9-3.9, and 4.2 mm Hg; 95% confidence interval, 2.9-5.5, for 1 and 2 parents with hypertension, respectively; P<0.001 for both) and with greater forward pressure wave amplitude (1.6 mm Hg; 95% confidence interval, 0.6-2.7, and 1.9 mm Hg; 95% confidence interval, 0.6-3.2, for 1 and 2 parents with hypertension, respectively; P=0.003 for both). Carotid-femoral pulse wave velocity and augmentation index displayed similar dose-dependent relations with parental hypertension in sex-, age-, and height-adjusted models, but associations were attenuated on further adjustment. Offspring with at least 1 parent in the upper quartile of augmentation index and carotid-femoral pulse wave velocity had significantly higher values themselves (P≤0.02). In conclusion, in this community-based sample of young, nonhypertensive adults, we observed greater arterial stiffness in offspring of parents with hypertension. These observations are consistent with higher vascular stiffness at an early stage in the pathogenesis of hypertension. PMID:27456526

  17. Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring.

    PubMed

    Ceccanti, Mauro; Coccurello, Roberto; Carito, Valentina; Ciafrè, Stefania; Ferraguti, Giampiero; Giacovazzo, Giacomo; Mancinelli, Rosanna; Tirassa, Paola; Chaldakov, George N; Pascale, Esterina; Ceccanti, Marco; Codazzo, Claudia; Fiore, Marco

    2016-07-01

    Ethanol (EtOH) exposure during pregnancy induces cognitive and physiological deficits in the offspring. However, the role of paternal alcohol exposure (PAE) on offspring EtOH sensitivity and neurotrophins has not received much attention. The present study examined whether PAE may disrupt nerve growth factor (NGF) and/or brain-derived neurotrophic factor (BDNF) and affect EtOH preference/rewarding properties in the male offspring. CD1 sire mice were chronically addicted for EtOH or administered with sucrose. Their male offsprings when adult were assessed for EtOH preference by a conditioned place preference paradigm. NGF and BDNF, their receptors (p75(NTR) , TrkA and TrkB), dopamine active transporter (DAT), dopamine receptors D1 and D2, pro-NGF and pro-BDNF were also evaluated in brain areas. PAE affected NGF levels in frontal cortex, striatum, olfactory lobes, hippocampus and hypothalamus. BDNF alterations in frontal cortex, striatum and olfactory lobes were found. PAE induced a higher susceptibility to the EtOH rewarding effects mostly evident at the lower concentration (0.5 g/kg) that was ineffective in non-PAE offsprings. Moreover, higher ethanol concentrations (1.5 g/kg) produced an aversive response in PAE animals and a significant preference in non-PAE offspring. PAE affected also TrkA in the hippocampus and p75(NTR) in the frontal cortex. DAT was affected in the olfactory lobes in PAE animals treated with 0.5 g/kg of ethanol while no differences were found on D1/D2 receptors and for pro-NGF or pro-BDNF. In conclusion, this study shows that: PAE affects NGF and BDNF expression in the mouse brain; PAE may induce ethanol intake preference in the male offspring. PMID:25940002

  18. Effects of paternal age and offspring cognitive ability in early adulthood on the risk of schizophrenia and related disorders.

    PubMed

    Sørensen, Holger J; Pedersen, Carsten B; Nordentoft, Merete; Mortensen, Preben B; Ehrenstein, Vera; Petersen, Liselotte

    2014-12-01

    Advanced paternal age (APA) and intelligence quotient (IQ) are both associated with the risk of schizophrenia spectrum disorder (SSD) in young adult offspring. We hypothesized that the offspring SSD risk gradient associated with paternal age is mediated by offspring IQ. We investigated joint and separate associations of paternal age and offspring IQ with the risk of SSD. We used IQ routinely measured at conscription in Danish males (n=138,966) from cohorts born in 1955-84 and in 1976-1993 and followed them from a year after the conscription through 2010. We used Cox regression to estimate the incidence rate ratio (IRR) of SSD. During the follow-up, 528 men developed SSD (incidence rate [IR] 5.2 and 8.6 per 10,000 person-years in the first and second cohorts, respectively). APA was associated with higher risk of SSD (IRR, 1.32; 95% CI, 1.10-1.60 per a ten-year increase in paternal age). A higher IQ was associated with lower SSD risk (IRR, 0.68; 95% confidence interval [CI], 0.63-0.74 per one SD increase). The IR of SSD was higher among persons who were draft-exempt for health reasons (<20% of the men). Overall, there was little evidence of lower premorbid IQ in APA-related SSD (individuals who developed SSD and were also offspring of older fathers). Our results do not support the notion that risk gradient for offspring SSD associated with paternal age is mediated by offspring IQ. PMID:25445626

  19. Shared Neurocognitive Dysfunctions in Young Offspring at Extreme Risk for Schizophrenia or Bipolar Disorder in Eastern Quebec Multigenerational Families

    PubMed Central

    Maziade, Michel; Rouleau, Nancie; Gingras, Nathalie; Boutin, Pierrette; Paradis, Marie-Eve; Jomphe, Valérie; Boutin, Julie; Létourneau, Karine; Gilbert, Elsa; Lefebvre, Andrée-Anne; Doré, Marie-Claire; Marino, Cecilia; Battaglia, Marco; Mérette, Chantal; Roy, Marc-André

    2009-01-01

    Background: Adult patients having schizophrenia (SZ) or bipolar disorder (BP) may have in common neurocognitive deficits. Former evidence suggests impairments in several neuropsychological functions in young offspring at genetic risk for SZ or BP. Moreover, a dose-response relation may exist between the degree of familial loading and cognitive impairments. This study examines the cognitive functioning of high-risk (HR) offspring of parents having schizophrenia (HRSZ) and high-risk offspring of parents having bipolar disorder (HRBP) descending from densely affected kindreds. Methods: The sample consisted of 45 young offspring (mean age of 17.3 years) born to a parent having SZ or BP descending from large multigenerational families of Eastern Québec that are densely affected by SZ or BP and followed up since 1989. The offspring were administered a lifetime best-estimate diagnostic procedure (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]) and an extensive standard neuropsychological battery. Raw scores were compared with age- and gender-matched controls. Results: The offspring displayed differences in memory and executive functions when compared with controls. Moderate to large effect sizes (Cohen d) ranging from 0.65 to 1.25 (for IQ and memory) were observed. Several of the cognitive dysfunctions were present in both HRSZ and HRBP, even when considering DSM-IV clinical status. Conclusions: HRSZ and HRBP shared several aspects of their cognitive impairment. Our data suggest that the extremely high genetic and familial loading of these HRs may have contributed to a quantitatively increased magnitude of the cognitive impairments in both HR subgroups, especially in memory. These offspring at heightened risk present difficulties in processing information that warrant preventive research. PMID:18550590

  20. Maternal Vitamin D Deficiency Programs Reproductive Dysfunction in Female Mice Offspring Through Adverse Effects on the Neuroendocrine Axis.

    PubMed

    Nicholas, Cari; Davis, Joseph; Fisher, Thomas; Segal, Thalia; Petti, Marilena; Sun, Yan; Wolfe, Andrew; Neal-Perry, Genevieve

    2016-04-01

    Vitamin D (VitD) deficiency affects more than 1 billion people worldwide with a higher prevalence in reproductive-aged women and children. The physiological effects of maternal VitD deficiency on the reproductive health of the offspring has not been studied. To determine whether maternal VitD deficiency affects reproductive physiology in female offspring, we monitored the reproductive physiology of C57BL/6J female offspring exposed to diet-induced maternal VitD deficiency at three specific developmental stages: 1) in utero, 2) preweaning, or 3) in utero and preweaning. We hypothesized that exposure to maternal VitD deficiency disrupts reproductive function in exposed female offspring. To test this hypothesis, we assessed vaginal opening and cytology and ovary and pituitary function as well as gonadotropin and gonadal steroid levels in female offspring. The in utero, preweaning, and in utero and preweaning VitD deficiency did not affect puberty. However, all female mice exposed to maternal VitD deficiency developed prolonged and irregular estrous cycles characterized by oligoovulation and extended periods of diestrus. Despite similar gonadal steroid levels and GnRH neuron density, females exposed to maternal VitD deficiency released less LH on the evening of proestrus. When compared with control female offspring, there was no significant difference in the ability of females exposed to maternal VitD deficiency to respond robustly to exogenous GnRH peptide or controlled ovarian hyperstimulation. These findings suggest that maternal VitD deficiency programs reproductive dysfunction in adult female offspring through adverse effects on hypothalamic function. PMID:26741195

  1. Early hepatic insult in the offspring of obese maternal mice.

    PubMed

    Bringhenti, Isabele; Ornellas, Fernanda; Martins, Marcela Anjos; Mandarim-de-Lacerda, Carlos Alberto; Aguila, Marcia Barbosa

    2015-02-01

    We hypothesized that the maternal obesity initiates metabolic disorders associated with oxidative stress in the liver of offspring since early life. Mouse's mothers were assigned into 2 groups according to the diet offered (n = 10 per group): standard chow (SC) or high-fat diet (HF). The results revealed that HF offspring had an increase in body mass at day 10 (+25%, P < .05) and in glucose levels (+25%, P < .0001). Hepatic triacylglycerol was increased in HF offspring at day 1 and day 10 compared with SC offspring (+30%, P < .01 and +40%, P < .01) as was hepatic steatosis (+110%, P < .001; +145%, P < .0001). Fatty acid synthase was increased in HF offspring at day 1 (+450%, P < .01) and peroxisome proliferator activator receptor-γ was elevated at day 1 and day 10 (+140%, P < .01; +2741%, P < .01). Peroxisome proliferator activator receptor-α was diminished in HF offspring at day 10 compared with SC offspring (-100%, P < .01). Moreover, carnitine palmitoyl-CoA transferase-1 was decreased in HF offspring at day 1 and day 10 (-80%, P < .01; -60%, P < .05). In the HF offspring (compared with the SC offspring), the catalase and the superoxide dismutase were significantly lower in both days 1 and 10 (P < .05). In 10-day-old offspring, glutathione peroxidase 1 and glutathione reductase were lower in HF offspring than in SC offspring (P < .0001). Our findings suggest that the maternal obesity in mice induces an early oxidative dysfunction coupled with hepatic steatosis and might contribute to progressive liver injury later in life. PMID:25582085

  2. Dimensional psychopathology in preschool offspring of parents with bipolar disorder

    PubMed Central

    Maoz, Hagai; Goldstein, Tina; Axelson, David A.; Goldstein, Benjamin I.; Fan, Jieyu; Hickey, Mary Beth; Monk, Kelly; Sakolsky, Dara; Diler, Rasim S.; Brent, David; Iyengar, Satish; Kupfer, David J.; Birmaher, Boris

    2014-01-01

    Background The purpose of this study is to compare the dimensional psychopathology, as ascertained by parental report, in preschool offspring of parents with bipolar disorder (BP) and offspring of community control parents. Methods 122 preschool offspring (mean age 3.3 years) of 84 parents with BP, with 102 offspring of 65 control parents (36 healthy, 29 with non-BP psychopathology), were evaluated using the Child Behavior Checklist (CBCL), the CBCL-Dysregulation Profile (CBCL-DP), the Early Childhood Inventory (ECI-4), and the Emotionality Activity Sociability (EAS) survey. Teachers’ Report Forms (TRF) were available for 51 preschoolers. Results After adjusting for confounders, offspring of parents with BP showed higher scores in the CBCL total, externalizing, somatic, sleep, aggressive, and CBCL-DP subscales; the ECI-4 sleep problem scale; and the EAS total and emotionality scale. The proportion of offspring with CBCL T-scores ≥2 SD above the norm was significantly higher on most CBCL subscales and the CBCL-DP in offspring of parents with BP compared to offspring of controls even after excluding offspring with attention deficit hyperactivity disorder and/or oppositional defiant disorder. Compared to offspring of parents with BP-I, offspring of parents with BP-II showed significantly higher scores in total and most CBCL subscales, the ECI-4 anxiety and sleep scales and the EAS emotionality scale. For both groups of parents, there were significant correlations between CBCL and TRF scores (r = .32–.38, p-values ≤.02). Conclusions Independent of categorical axis-I psychopathology and other demographic or clinical factors in both biological parents, preschool offspring of parents with BP have significantly greater aggression, mood dysregulation, sleep disturbances, and somatic complaints compared to offspring of control parents. Interventions to target these symptoms are warranted. PMID:24372351

  3. Chronic Sleep Restriction during Pregnancy - Repercussion on Cardiovascular and Renal Functioning of Male Offspring

    PubMed Central

    Lima, Ingrid L. B.; Rodrigues, Aline F. A. C.; Bergamaschi, Cássia T.; Campos, Ruy R.; Hirata, Aparecida E.; Tufik, Sergio; Xylaras, Beatriz D. P.; Visniauskas, Bruna; Chagas, Jair R.; Gomes, Guiomar N.

    2014-01-01

    Changes in the maternal environment can induce fetal adaptations that result in the progression of chronic diseases in the offspring. The objective of the present study was to evaluate the effects of maternal chronic sleep restriction on blood pressure, renal function and cardiac baroreflex response on male offspring at adult age. Female 3-month-old Wistar rats were divided in two experimental groups: control (C) and chronic sleep restricted (CSR). Pregnancy was confirmed by vaginal smear. Chronic sleep restricted females were subjected to sleep restriction by the multiple platform technique for 20 h daily, between the 1st and 20th day of pregnancy. After birth, the litters were reduced to 6 rats per mother, and were designated as offspring from control (OC) and offspring from chronic sleep restricted (OCSR). Indirect blood pressure (BPi – tail cuff) was measured by plethysmography in male offspring at 3 months old. Following, the renal function and cardiac baroreflex response were analyzed. Values of BPi in OCSR were significantly higher compared to OC [OC: 127±2.6 (19); OCSR: 144±2.5 (17) mmHg]. The baroreflex sensitivity to the increase of blood pressure was reduced in OCSR [Slope: OC: −2.6±0.15 (9); OCRS: −1.6±0.13 (9)]. Hypothalamic activity of ACE2 was significantly reduced in OCSR compared to OC [OC: 97.4±15 (18); OSR: 60.2±3.6 (16) UAF/min/protein mg]. Renal function alteration was noticed by the increase in glomerular filtration rate (GFR) observed in OCSR [OC: 6.4±0.2 (10); OCSR: 7.4±0.3 (7)]. Chronic sleep restriction during pregnancy caused in the offspring hypertension, altered cardiac baroreflex response, reduced ACE-2 activity in the hypothalamus and renal alterations. Our data suggest that the reduction of sleeping time along the pregnancy is able to modify maternal homeostasis leading to functional alterations in offspring. PMID:25405471

  4. Pre-reproductive maternal enrichment influences rat maternal care and offspring developmental trajectories: behavioral performances and neuroplasticity correlates

    PubMed Central

    Cutuli, Debora; Caporali, Paola; Gelfo, Francesca; Angelucci, Francesco; Laricchiuta, Daniela; Foti, Francesca; De Bartolo, Paola; Bisicchia, Elisa; Molinari, Marco; Farioli Vecchioli, Stefano; Petrosini, Laura

    2015-01-01

    Environmental enrichment (EE) is a widely used paradigm for investigating the influence of complex stimulations on brain and behavior. Here we examined whether pre-reproductive exposure to EE of female rats may influence their maternal care and offspring cognitive performances. To this aim, from weaning to breeding age enriched females (EF) were reared in enriched environments. Females reared in standard conditions were used as controls. At 2.5 months of age all females were mated and reared in standard conditions with their offspring. Maternal care behaviors and nesting activity were assessed in lactating dams. Their male pups were also behaviorally evaluated at different post-natal days (pnd). Brain BDNF, reelin and adult hippocampal neurogenesis levels were measured as biochemical correlates of neuroplasticity. EF showed more complex maternal care than controls due to their higher levels of licking, crouching and nest building activities. Moreover, their offspring showed higher discriminative (maternal odor preference T-maze, pnd 10) and spatial (Morris Water Maze, pnd 45; Open Field with objects, pnd 55) performances, with no differences in social abilities (Sociability test, pnd 35), in comparison to controls. BDNF levels were increased in EF frontal cortex at pups' weaning and in their offspring hippocampus at pnd 21 and 55. No differences in offspring reelin and adult hippocampal neurogenesis levels were found. In conclusion, our study indicates that pre-reproductive maternal enrichment positively influences female rats' maternal care and cognitive development of their offspring, demonstrating thus a transgenerational transmission of EE benefits linked to enhanced BDNF-induced neuroplasticity. PMID:25814946

  5. Pre-reproductive maternal enrichment influences rat maternal care and offspring developmental trajectories: behavioral performances and neuroplasticity correlates.

    PubMed

    Cutuli, Debora; Caporali, Paola; Gelfo, Francesca; Angelucci, Francesco; Laricchiuta, Daniela; Foti, Francesca; De Bartolo, Paola; Bisicchia, Elisa; Molinari, Marco; Farioli Vecchioli, Stefano; Petrosini, Laura

    2015-01-01

    Environmental enrichment (EE) is a widely used paradigm for investigating the influence of complex stimulations on brain and behavior. Here we examined whether pre-reproductive exposure to EE of female rats may influence their maternal care and offspring cognitive performances. To this aim, from weaning to breeding age enriched females (EF) were reared in enriched environments. Females reared in standard conditions were used as controls. At 2.5 months of age all females were mated and reared in standard conditions with their offspring. Maternal care behaviors and nesting activity were assessed in lactating dams. Their male pups were also behaviorally evaluated at different post-natal days (pnd). Brain BDNF, reelin and adult hippocampal neurogenesis levels were measured as biochemical correlates of neuroplasticity. EF showed more complex maternal care than controls due to their higher levels of licking, crouching and nest building activities. Moreover, their offspring showed higher discriminative (maternal odor preference T-maze, pnd 10) and spatial (Morris Water Maze, pnd 45; Open Field with objects, pnd 55) performances, with no differences in social abilities (Sociability test, pnd 35), in comparison to controls. BDNF levels were increased in EF frontal cortex at pups' weaning and in their offspring hippocampus at pnd 21 and 55. No differences in offspring reelin and adult hippocampal neurogenesis levels were found. In conclusion, our study indicates that pre-reproductive maternal enrichment positively influences female rats' maternal care and cognitive development of their offspring, demonstrating thus a transgenerational transmission of EE benefits linked to enhanced BDNF-induced neuroplasticity. PMID:25814946

  6. Enzyme Changes in the Offspring of Female Rats due to Long-Term Administration of Cyclic AMP and Insulin before Pregnancy.

    PubMed

    Strumilo, S A; Czyzewska, U; Siemieniuk, M; Strumilo, J; Tylicki, A

    2016-07-01

    We studied the effects of insulin and cAMP on the offspring of female rats after daily treatment with these substances over 4 weeks. In adult offspring from cAMP-treated females, activities of pyruvate kinase and glucose-6-phosphate dehydrogenase decreased in the liver and brain and activities of NADP-dependent malate dehydrogenase and 6-phosphogluconate dehydrogenase decreased in the liver. In the offspring of insulin-treated females, we observed only activation of glucose-6-phosphate dehydrogenase and malate dehydrogenase in the liver and only in females. Enzyme activity probably correlates with their content, as no changes in their kinetic properties were observed under these conditions. Long-term hormone treatment before pregnancy can affect the expression of genes for some enzymes in the offspring due to transmission of epigenetic signals by the ovum. However, further studies are required to confirm this mechanism. PMID:27502537

  7. Effects of perinatal methylphenidate (MPH) treatment in male and female Sprague-Dawley offspring.

    PubMed

    Panos, John J; Law, C Delbert; Ferguson, Sherry A

    2014-01-01

    MPH is a common treatment for adult Attention Deficit Hyperactivity Disorder (ADHD). However, little information exists regarding its safety during pregnancy and thus, women with ADHD face difficult decisions regarding continued use during pregnancy. Here, Sprague-Dawley rats were orally treated 3 ×/day with 0 (control), 6 (low), 18 (mid), or 42 (high) mg MPH/kg/day (i.e., 0, 2, 6, or 14 mg/kg at each treatment time) on gestational days 6-21. On postnatal days (PNDs) 1-21, all offspring/litter were orally treated 2 ×/day with the same dose. Righting reflex (PNDs 3-6) and slant board performance (PNDs 8-11) were assessed. T3, T4, E2, testosterone, LH and corticosterone were measured at PND 22. Separate pregnant dams and resulting litters were used for serum MPH measurements. MPH treatment had mild, but significant, effects on gestational body weight and food intake. Birth weight of high MPH offspring was 5% more than controls (p<0.0500). Relative to same-sex controls on PNDs 1-22, low and mid MPH males weighed more (p<0.0094), low MPH females weighed more (p<0.0001), while high MPH females weighed less (p<0.0397). PND 22 serum E2 levels were significantly decreased (20-25%) in high MPH males and females (p<0.0500). Behavioral performance was unaffected by treatment. Serum MPH levels of the low MPH pregnant dams were within the range produced by therapeutic MPH doses in adults; however, offspring levels in all groups were substantially higher. These results indicate that developmental MPH treatment has mild effects on gestational body weight and food intake and offspring preweaning body weight. Potential functional consequences of decreased serum E2 levels are not clear, but may impact later behavior or physiology. PMID:24444667

  8. Complex offspring size effects: variations across life stages and between species

    PubMed Central

    Sun, Zhao; Hamel, Jean-François; Parrish, Christopher C; Mercier, Annie

    2015-01-01

    Classical optimality models of offspring size and number assume a monotonically increasing relationship between offspring size and performance. In aquatic organisms with complex life cycles, the size–performance function is particularly hard to grasp because measures of performance are varied and their relationships with size may not be consistent throughout early ontogeny. Here, we examine size effects in premetamorphic (larval) and postmetamorphic (juvenile) stages of brooding marine animals and show that they vary contextually in strength and direction during ontogeny and among species. Larger offspring of the sea anemone Urticina felina generally outperformed small siblings at the larval stage (i.e., greater settlement and survival rates under suboptimal conditions). However, results differed when analyses were conducted at the intrabrood versus across-brood levels, suggesting that the relationship between larval size and performance is mediated by parentage. At the juvenile stage (15 months), small offspring were less susceptible than large ones to predation by subadult nudibranchs and both sizes performed similarly when facing adult nudibranchs. In a sympatric species with a different life history (Aulactinia stella), all juveniles suffered similar predation rates by subadult nudibranchs, but smaller juveniles performed better (lower mortalities) when facing adult nudibranchs. Size differences in premetamorphic performance of U. felina were linked to total lipid contents of larvae, whereas size-specific predation of juvenile stages followed the general predictions of the optimal foraging strategy. These findings emphasize the challenge in gathering empirical support for a positive monotonic size–performance function in taxa that exhibit complex life cycles, which are dominant in the sea. PMID:25798228

  9. Parental effects enhance risk tolerance and performance in offspring.

    PubMed

    Donelan, Sarah C; Trussell, Geoffrey C

    2015-08-01

    Predation risk can strongly influence community dynamics through its effects on prey foraging decisions that often involve habitat shifts (i.e., from risky to refuge habitats). Although the within-generation effects of risk on prey are well appreciated, the effects of parental experience with risk on offspring decision-making and growth are poorly understood. The capacity of parents to prepare their offspring for potential risk exposure may be adaptive when the likelihood of eventual risk exposure is high and be instrumental in shaping how offspring allocate their foraging effort and habitat use. Using a simple rocky intertidal food chain, we examined the influence of parental exposure to predator risk cues on the behavior, foraging, and tissue maintenance of offspring exposed to the presence and absence of risk. We found that offspring of risk-experienced parents were bolder. When confronted with risk, these offspring spent more time out of refuge habitat, foraged more, and maintained more tissue than offspring of risk-free parents. Thus, parental experience with risk was most important when offspring were exposed to risk. These results suggest that the effects of parental experience with predation risk on offspring traits strongly shape the transmission of risk effects in ecological communities. PMID:26405730

  10. As-resistance in laboratory-reared F1, F2 and F3 generation offspring of the earthworm Lumbricus rubellus inhabiting an As-contaminated mine soil.

    PubMed

    Langdon, C J; Morgan, A J; Charnock, J M; Semple, K T; Lowe, C N

    2009-11-01

    Previous studies provided no unequivocal evidence demonstrating that field populations of Lumbricus rubellus Hoffmeister (1843), exhibit genetically inherited resistance to As-toxicity. In this study F1, F2 and F3 generation offspring derived from adults inhabiting As-contaminated field soil were resistant when exposed to 2000 mg kg(-1) sodium arsenate. The offspring of uncontaminated adults were not As-resistant. Cocoon viability was 80% for F1 and 82% for F2 offspring from As-contaminated adults and 59% in the F1 control population. High energy synchrotron analysis was used to determine whether ligand complexation of As differed in samples of: resistant mine-site adults, the resistant F1 and F2 offspring of the mine-site earthworms exposed to the LC(25) sodium arsenate (700 mg kg(-1)) of the F1 parental generation; and adult L. rubellus from an uncontaminated site exposed to LC(25) concentrations of sodium arsenate (50 mg kg(-1)). XANES and EXAFS indicated that As was present as a sulfur-coordinated species. PMID:19501438

  11. Sex-Differences in the Metabolic Health of Offspring of Parents with Diabetes: A Record-Linkage Study

    PubMed Central

    Aldhous, Marian C.; Reynolds, Rebecca M.; Campbell, Archie; Linksted, Pamela; Lindsay, Robert S.; Smith, Blair H.; Seckl, Jonathan R.; Porteous, David J.; Norman, Jane E.

    2015-01-01

    Maternal diabetes in pregnancy affects offspring health. The impact of parental diabetes on offspring health is unclear. We investigated the impact of parental diabetes on the metabolic-health of adult-offspring who did not themselves have diabetes. Data from the Generation Scotland: Scottish Family Health Study, a population-based family cohort, were record-linked to subjects’ own diabetes medical records. From F0-parents, we identified F1-offspring of: mothers with diabetes (OMD, n = 409), fathers with diabetes (OFD, n = 468), no parent with diabetes (ONoPD, n = 2489). Metabolic syndrome, body, biochemical measurements and blood-pressures were compared between F1-offspring groups by sex. A higher proportion of female OMD had metabolic syndrome than female OFD or ONoPD (P<0.0001). In female offspring, predictors of metabolic syndrome were: having a mother with diabetes (OR = 1.78, CI 1.03–3.07, [reference ONoPD]), body mass index (BMI, OR = 1.21, CI 1.13–1.30) and age (OR = 1.03, CI 1.01–1.06). In male offspring, predictors of metabolic syndrome were: BMI (OR = 1.18, CI 1.09–1.29) and percent body-fat (OR = 1.12, CI 1.05–1.19). In both sexes, OMD had higher blood-pressures than OFD (P<0.0001). In females, OMD had higher glucose (P<0.0001) and percent body-fat (P<0.0001) compared with OFD or ONoPD. OMD and OFD both had increased waist-measurements (P<0.0001), BMI (P<0.0001) and percent body-fat (P<0.0001) compared with ONoPD. Female OMD and OFD had lower HDL-cholesterol levels (P<0.0001) than female ONoPD. Parental diabetes is associated with higher offspring-BMI and body-fat. In female offspring, maternal diabetes increased the odds of metabolic syndrome, even after adjusting for BMI. Further investigations are required to determine the mechanisms involved. PMID:26308734

  12. Females allocate differentially to offspring size and number in response to male effects on female and offspring fitness.

    PubMed

    Kindsvater, Holly K; Alonzo, Suzanne H

    2014-03-22

    Female investment in offspring size and number has been observed to vary with the phenotype of their mate across diverse taxa. Recent theory motivated by these intriguing empirical patterns predicted both positive (differential allocation) and negative (reproductive compensation) effects of mating with a preferred male on female investment. These predictions, however, focused on total reproductive effort and did not distinguish between a response in offspring size and clutch size. Here, we model how specific paternal effects on fitness affect maternal allocation to offspring size and number. The specific mechanism by which males affect the fitness of females or their offspring determines whether and how females allocated differentially. Offspring size is predicted to increase when males benefit offspring survival, but decrease when males increase offspring growth rate. Clutch size is predicted to increase when males contribute to female resources (e.g. with a nuptial gift) and when males increase offspring growth rate. The predicted direction and magnitude of female responses vary with female age, but only when per-offspring paternal benefits decline with clutch size. We conclude that considering specific paternal effects on fitness in the context of maternal life-history trade-offs can help explain mixed empirical patterns of differential allocation and reproductive compensation. PMID:24478292

  13. Analysis of murine HOXA-2 activity in Drosophila melanogaster.

    PubMed

    Percival-Smith, A; Bondy, J A

    1999-01-01

    The murine HOXA-2 protein shares amino acid sequence similarity with Drosophila Proboscipedia (PB). In this paper, we test whether HOXA-2 and PB are functionally equivalent in Drosophila. In Drosophila, PB inhibits SCR activity required for larval T1 beard formation and adult tarsus formation and is required for maxillary palp and proboscis formation. HOXA-2 expressed from a heat-shock promoter weakly suppressed SCR activity required for T1 beard formation. But interestingly neither PB nor HOXA-2 expressed from a heat-shock promoter suppressed murine HOXA-5 activity, the murine SCR homologue, from inducing ectopic T1 beards in T2 and T3, indicating that HOXA-5 does not interact with PB. HOXA-2 activity expressed from the Tubulin alpha 1 promoter modified the pb null phenotype resulting in a proboscis-to-arista transformation, indicating that HOXA-2 was able to suppress SCR activity required for tarsus formation. However, HOXA-2 expressed from a Tubulin alpha 1 promoter was unable to direct maxillary palp determination when either ectopically expressed in the antenna or in the maxillary palp primordia of a pb null mutant. HOXA-2 was also unable to rescue pseudotrachea formation in a pb null mutant. These results indicate that the only activity that PB and HOXA-2 weakly share is the inhibition of SCR activity, and that murine HOXA-5 and Drosophila SCR do not share inhibition by PB activity. PMID:10322642

  14. Cloning and expression analysis of murine phospholipase D1.

    PubMed Central

    Colley, W C; Altshuller, Y M; Sue-Ling, C K; Copeland, N G; Gilbert, D J; Jenkins, N A; Branch, K D; Tsirka, S E; Bollag, R J; Bollag, W B; Frohman, M A

    1997-01-01

    Activation of phosphatidylcholine-specific phospholipase D(PLD) occurs as part of the complex signal-transduction cascade initiated by agonist stimulation of tyrosine kinase and G-protein-coupled receptors. A variety of mammalian PLD activities have been described, and cDNAs for two PLDs recently reported (human PLD1 and murine PLD2). We describe here the cloning and chromosomal localization of murine PLD1. Northern-blot hybridization and RNase protection analyses were used to examine the expression of murine PLD1 and PLD2 ina variety of cell lines and tissues. PLD1 and PLD2 were expressed in all RNA samples examined, although the absolute expression of each isoform varied, as well as the ratio of PLD1 to PLD2. Moreover, in situ hybridization of adult brain and murine embryo sections revealed high levels of expression of individual PLDs in some cell types and no detectable expression in others. Thus the two PLDs probably carry out distinct roles in restricted subsets of cells rather than ubiquitous roles in all cells. PMID:9307024

  15. The origins of altruism in offspring care.

    PubMed

    Preston, Stephanie D

    2013-11-01

    The current review aims to unify existing views of altruism through an examination of the biological bases of a fundamental form of giving: altruistic responding. Altruistic responding is most salient during heroic acts of helping but is also observed any time one perceives another's distress or need, which in turn motivates one to help at a current cost to the self. Such aid is simple, observable across species, and rooted in the instincts and circuits that evolved to maximize inclusive fitness through the care of helpless offspring. By design, the system already biases aid to both kin and nonkin under conditions that are largely adaptive. These inherent benefits are also buttressed in primates and humans by known, later-arriving benefits to helping in group-living animals. Evidence for the proposed homology between altruistic responding and offspring retrieval is presented through 10 key shared factors. Conceptually, both require (a) participation by nonmothers, (b) motor competence and expertise, (c) an adaptive opponency between avoidance and approach, and a facilitating role of (d) neonatal vulnerability, (e) salient distress, and (f) rewarding close contact. Physiologically, they also share neurohormonal support from (g) oxytocin, (h) the domain-general mesolimbocortical system, (i) the cingulate cortex, and (j) the orbitofrontal cortex. The framework intermixes ultimate and proximate levels of analysis and unifies existing views by assuming that even complex human behaviors reflect ancient mammalian neural systems that evolved to solve key problems in adaptive ways, with far-reaching consequences for even our most venerated human traits. PMID:23458432

  16. Gestational hypothyroxinemia and cognitive function in offspring.

    PubMed

    Kasatkina, E P; Samsonova, L N; Ivakhnenko, V N; Ibragimova, G V; Ryabykh, A V; Naumenko, L L; Evdokimova, Yu A

    2006-07-01

    The effects of gestational hypothyroxinemia on the neurointellectual prognosis of children in the first year of life living in an industrial city (megalopolis) with mild iodine deficiency were studied in 13 children of mothers with thyroid hormone-corrected gestational hypothyroxinemia in the first trimester and 10 children of mothers with normal levels of free thyroxine by assessing cognitive functions at ages six, nine, and 12 months using the Gnome mental development scale. The results showed that maternal free thyroxine levels at the early stages (5-9 weeks) of pregnancy correlated significantly with the coefficients of mental development among the children at ages 6, 9, and 12 months, i.e., represented one of the factors defining the neuropsychological development of offspring. Early (not later than nine weeks) correction of gestational hypothyroxinemia with levothyroxine at a mean daily dose of at lest 1.2 microg/kg improved the neurointellectual prognosis of the offspring, increasing the coefficient of mental development of children to 92-97 points during the first year of life, i.e., to the level of development of mental functions of children born to mothers with normal thyroxine levels. PMID:16783515

  17. Mother-Offspring Transmission and Age-Dependent Accumulation of Simian Foamy Virus in Wild Chimpanzees

    PubMed Central

    Blasse, Anja; Calvignac-Spencer, Sébastien; Merkel, Kevin; Goffe, Adeelia S.; Boesch, Christophe; Mundry, Roger

    2013-01-01

    Simian foamy viruses (SFVs) are thought to infect virtually any adult nonhuman primate (NHP). While many data have accumulated about patterns of codivergence with their hosts and cross-species transmission events, little is known about the modalities of SFV transmission within NHP species, especially in the wild. Here we provide a detailed investigation of the dynamics of SFV circulation in a wild community of Western chimpanzees (Pan troglodytes verus). We demonstrate that mother-offspring (vertical) SFV transmission is common and hypothesize that it accounts for a number of primary infections. We also show that multiple infections with several chimpanzee-specific SFV strains (i.e., superinfection) commonly happen in adult chimpanzees, which might point to adult-specific aggressive behaviors as a lifelong source of SFV infection. Our data give evidence for complex SFV dynamics in wild chimpanzees, even at a single community scale, and show that linking wild NHP social interactions and their microorganisms' dynamics is feasible. PMID:23449796

  18. Mice age - Does the age of the mother predict offspring behaviour?

    PubMed

    Lerch, Sandra; Brandwein, Christiane; Dormann, Christof; Gass, Peter; Chourbaji, Sabine

    2015-08-01

    Increasing paternal age is known to be associated with a great variety of psychiatric disorders such as schizophrenia or autism. Hence the factor "age" may be taken as strategic tool to analyse specific scientific hypotheses. Additionally, this finding also needs to be addressed in rather pragmatically performed breeding protocols of model organisms, since otherwise artefacts may challenge the validity of the results. Our study was performed to investigate influences of advanced age of mouse dams (30 vs. 16weeks) on maternal- and offspring behaviour. Adult offspring of both sexes was analysed in a test battery comprising paradigms for exploration, anxiety and depressive-like behaviours. Final blood sampling was conducted for stressphysiological analysis. Interestingly, advanced age of the mothers was associated with increased nest-building quality while maternal activity was unaffected. Moreover "maternal (mice) age" (MA) affected emotionality in the offspring, which became apparent in the dark-light box and the social recognition paradigm. These findings not only emphasize MA to model a potent risk factor with regard to emotional stability, but also underscore the vast necessity to include information about breeding protocols into the methods section of any animal study. PMID:25914174

  19. Maternal Obesity and Developmental Programming of Metabolic Disorders in Offspring: Evidence from Animal Models

    PubMed Central

    Li, M.; Sloboda, D. M.; Vickers, M. H.

    2011-01-01

    The incidence of obesity and overweight has reached epidemic proportions in the developed world as well as in those countries transitioning to first world economies, and this represents a major global health problem. Concern is rising over the rapid increases in childhood obesity and metabolic disease that will translate into later adult obesity. Although an obesogenic nutritional environment and increasingly sedentary lifestyle contribute to our risk of developing obesity, a growing body of evidence links early life nutritional adversity to the development of long-term metabolic disorders. In particular, the increasing prevalence of maternal obesity and excess maternal weight gain has been associated with a heightened risk of obesity development in offspring in addition to an increased risk of pregnancy-related complications. The mechanisms that link maternal obesity to obesity in offspring and the level of gene-environment interactions are not well understood, but the early life environment may represent a critical window for which intervention strategies could be developed to curb the current obesity epidemic. This paper will discuss the various animal models of maternal overnutrition and their importance in our understanding of the mechanisms underlying altered obesity risk in offspring. PMID:21969822

  20. Effect of maternal exposure to Tityus bahiensis scorpion venom during lactation on the offspring of rats.

    PubMed

    Martins, Adriana do Nascimento; Nencioni, Ana Leonor Abrahão; Dorce, Ana Leticia Coronado; Paulo, Maria Eliza F V; Frare, Eduardo Osório; Dorce, Valquíria Abrão Coronado

    2016-01-01

    Scorpion stings are a public health problem in Brazil and lactating women may be affected. We aimed to study the effects of Tityus bahiensis venom in the offspring of rats treated during lactation. Mothers received a subcutaneous injection of saline (1.0ml/kg) or venom (2.5mg/kg) or an intraperitoneal injection of LPS (lipopolysaccharide) (100μg/kg) on postnatal (PN) days 2 (PN2), 10 (PN10) or 16 (PN16). The offspring were evaluated during the childhood and adulthood. Pups showed a delay in physical and reflexological development, and a decrease in motor activity. Adults displayed low anxiety. There was an increase in the number of viable neuronal cells in hippocampal areas CA1 and CA4. The levels of IFN-γ (interferon-gamma) increased in the experimental groups. Several of the parameters analyzed showed important differences between the sexes. Thus, the scorpion venom affects the development in the offspring of mothers envenomed during the lactation. PMID:26746106

  1. Sex, offspring and carcass determine antimicrobial peptide expression in the burying beetle

    PubMed Central

    Jacobs, Chris G. C.; Steiger, Sandra; Heckel, David G.; Wielsch, Natalie; Vilcinskas, Andreas; Vogel, Heiko

    2016-01-01

    The burying beetle Nicrophorus vespilloides has emerged as a model system for the investigation of adaptations that allow the utilization of carrion as a diet and as a resource for reproduction. The survival of beetles and their offspring given their exposure to soil-dwelling and cadaver-borne microbes requires mechanisms that reduce bacterial contamination in the diet and that achieve sanitation of the microhabitat. To explore the role of antimicrobial peptides (AMPs) in this context, we analyzed burying beetle males and females at different stages of their breeding cycle using the RNA-Seq and proteomics approaches. To address variation in immune functions, we investigated the impact of adult sex, the presence or absence of offspring (social context), and the presence of carrion (environmental context) on the expression of the identified immune effector genes. We found that particular AMPs are sex-specific and tightly regulated by the presence of a carcass or offspring and identified the two most context-dependent antimicrobial proteins in anal secretions. The context-specific expression dynamics of particular AMPs and lysozymes reveals a complex regulatory system, reflecting adaptations to specific ecological niches. This study highlights how burying beetles cope with microorganisms found on carrion and identifies candidates for both internal and external immunity. PMID:27139635

  2. Sex, offspring and carcass determine antimicrobial peptide expression in the burying beetle.

    PubMed

    Jacobs, Chris G C; Steiger, Sandra; Heckel, David G; Wielsch, Natalie; Vilcinskas, Andreas; Vogel, Heiko

    2016-01-01

    The burying beetle Nicrophorus vespilloides has emerged as a model system for the investigation of adaptations that allow the utilization of carrion as a diet and as a resource for reproduction. The survival of beetles and their offspring given their exposure to soil-dwelling and cadaver-borne microbes requires mechanisms that reduce bacterial contamination in the diet and that achieve sanitation of the microhabitat. To explore the role of antimicrobial peptides (AMPs) in this context, we analyzed burying beetle males and females at different stages of their breeding cycle using the RNA-Seq and proteomics approaches. To address variation in immune functions, we investigated the impact of adult sex, the presence or absence of offspring (social context), and the presence of carrion (environmental context) on the expression of the identified immune effector genes. We found that particular AMPs are sex-specific and tightly regulated by the presence of a carcass or offspring and identified the two most context-dependent antimicrobial proteins in anal secretions. The context-specific expression dynamics of particular AMPs and lysozymes reveals a complex regulatory system, reflecting adaptations to specific ecological niches. This study highlights how burying beetles cope with microorganisms found on carrion and identifies candidates for both internal and external immunity. PMID:27139635

  3. Maternal Omega-3 Supplementation Increases Fat Mass in Male and Female Rat Offspring

    PubMed Central

    Muhlhausler, Beverly Sara; Miljkovic, Dijana; Fong, Laura; Xian, Cory J.; Duthoit, Emmanuelle; Gibson, Robert A.

    2011-01-01

    Adipogenesis and lipogenesis are highly sensitive to the nutritional environment in utero and in early postnatal life. Omega-3 long chain polyunsaturated fatty acids (LCPUFA) inhibit adipogenesis and lipogenesis in adult rats, however it is not known whether supplementing the maternal diet with omega-3 LCPUFA results in reduced fat deposition in the offspring. Female Albino Wistar rats were fed either a standard chow (Control, n = 10) or chow designed to provide ∼15 mg/kg/day of omega-3 LCPUFA, chiefly as docosahexaenoic acid (DHA), throughout pregnancy and lactation (Omega-3, n = 11) and all pups were weaned onto a commercial rat chow. Blood and tissues were collected from pups at 3 and 6 weeks of age and weights of visceral and subcutaneous fat depots recorded. The expression of adipogenic and lipogenic genes in the subcutaneous and visceral fat depots were determined using quantitative real time reverse transcription-PCR. Birth weight and postnatal growth were not different between groups. At 6 weeks of age, total percentage body fat was significantly increased in both male (5.09 ± 0.32% vs. 4.56 ± 0.2%, P < 0.04) and female (5.15 ± 0.37% vs. 3.89 ± 0.36%, P < 0.04) offspring of omega-3 dams compared to controls. The omega-3 LCPUFA content of erythrocyte phospholipids (as a% of total fatty acids) was higher in omega-3 offspring (6.7 ± 0.2% vs. 5.6 ± 0.2%, P < 0.001). There was no effect of maternal omega-3 LCPUFA supplementation on the expression of adipogenic or lipogenic genes in the offspring in either the visceral or subcutaneous fat depots. We have therefore established that an omega-3 rich environment during pregnancy and lactation in a rodent model increases fat accumulation in both male and female offspring, particularly in subcutaneous depots, but that this effect is not mediated via upregulation adipogenic/lipogenic gene transcription. These data suggest that maternal n−3 LCPUFA

  4. Murine typhus in travelers returning from Indonesia.

    PubMed Central

    Parola, P.; Vogelaers, D.; Roure, C.; Janbon, F.; Raoult, D.

    1998-01-01

    We report the first three documented cases of murine typhus imported into Europe from Indonesia, discuss clues for the diagnosis of the disease, and urge that murine fever be considered in the diagnosis of febrile disease in travelers. PMID:9866749

  5. Antibacterial activity of recombinant murine beta interferon.

    PubMed Central

    Fujiki, T; Tanaka, A

    1988-01-01

    Recombinant murine beta interferon was protective and therapeutic for mice against Listeria monocytogenes infection in vivo. The recombinant murine beta interferon caused enhanced H2O2 release by macrophages in vivo, but not in vitro. PMID:3343048

  6. Prenatal stress induces alterations in cerebellar nitric oxide that are correlated with deficits in spatial memory in rat's offspring.

    PubMed

    Maur, Damián G; Romero, Carolina B; Burdet, Berenice; Palumbo, María L; Zorrilla-Zubilete, María A

    2012-12-01

    Prenatal stress (PS) has been linked to abnormal cognitive, behavioral and psychosocial outcomes in both animals and humans. Since PS has been shown to induce a cerebellar cytoarchitectural disarrangement and cerebellar abnormalities that have been linked to an impairment of behavioral functions, the aim of the present work was to investigate whether the exposure to PS in a period in which the cerebellum is still immature can induce behavioral deficits in the adult and whether this alterations are correlated with changes in nitric oxide (NO) and cellular oxidative mechanisms in offspring's cerebellum. Our results show impairments in spatial memory and territory discrimination in PS adult rats. PS offspring also displayed alterations in cerebellar nitric oxide synthase (NOS) expression and activity. Moreover, a correlation between spatial memory deficits and the increase in NOS activity was found. The results found here may point to a role of cerebellar NO in the behavioral alterations induced by stress during early development stages. PMID:23022609

  7. Environmental and parental influences on offspring health and growth in great tits (Parus major).

    PubMed

    Pickett, Simon R A; Weber, Sam B; McGraw, Kevin J; Norris, Ken J; Evans, Matthew R

    2013-01-01

    Sexual selection requires both that there is heritable variation in traits related to fitness, and that either some of this variation is linked to traits of the parents, and/or that there are direct benefits of choosing particular individuals as mates. This suggests that if direct benefits are important offspring performance should be predicted by traits of the rearing adults. But if indirect benefits are more significant offspring performance should be predicted by traits of the adults at the nest-of-origin. We conducted cross-fostering experiments in great tits (Parus major) over four years, in two of which we manipulated environmental conditions by providing supplemental food. In a third year, some nestlings were directly supplemented with carotenoids. Nestlings in broods whose rearing adults received supplemental food were heavier and had improved immune responses even when controlling for body mass. Nestling immune function was related to measures of the yellow plumage color of both the rearing male and the putative father. Nestling body mass was influenced by the coloration of both the rearing female and the genetic mother. Our results suggest that features of both their social and putative genetic parents influence nestling health and growth. From this it would appear that females could be gaining both direct and indirect benefits through mate choice of male plumage traits and that it would be possible for males to similarly gain through mate choice of female traits. PMID:23936081

  8. The effects of unrelated offspring whistle calls on capybaras (Hydrochoerus hydrochaeris).

    PubMed

    Dos Santos, E; Tokumaru, R S; Nogueira-Filho, S L G; Nogueira, S S C

    2014-08-01

    Parent-offspring vocal communication, such as the isolation call, is one of the essential adaptations in mammals that adjust parental responsiveness. Thus, our aim was to test the hypothesis that the function of the capybara infants' whistle is to attract conspecifics. We designed a playback experiment to investigate the reaction of 20 adult capybaras (seven males and 13 females) to pups' whistle calls - recorded from unrelated offspring - or to bird song, as control. The adult capybaras promptly responded to playback of unrelated pup whistles, while ignoring the bird vocalisation. The adult capybaras took, on average, 2.6 ± 2.5 seconds (s) to show a response to the whistles, with no differences between males and females. However, females look longer (17.0 ± 12.9 s) than males (3.0 ± 7.2 s) toward the sound source when playing the pups' whistle playback. The females also tended to approach the playback source, while males showed just a momentary interruption of ongoing behaviour (feeding). Our results suggest that capybara pups' whistles function as the isolation call in this species, but gender influences the intensity of the response. PMID:25627382

  9. Environmental and Parental Influences on Offspring Health and Growth in Great Tits (Parus major)

    PubMed Central

    Pickett, Simon R. A.; Weber, Sam B.; McGraw, Kevin J.; Norris, Ken J.; Evans, Matthew R.

    2013-01-01

    Sexual selection requires both that there is heritable variation in traits related to fitness, and that either some of this variation is linked to traits of the parents, and/or that there are direct benefits of choosing particular individuals as mates. This suggests that if direct benefits are important offspring performance should be predicted by traits of the rearing adults. But if indirect benefits are more significant offspring performance should be predicted by traits of the adults at the nest-of-origin. We conducted cross-fostering experiments in great tits (Parus major) over four years, in two of which we manipulated environmental conditions by providing supplemental food. In a third year, some nestlings were directly supplemented with carotenoids. Nestlings in broods whose rearing adults received supplemental food were heavier and had improved immune responses even when controlling for body mass. Nestling immune function was related to measures of the yellow plumage color of both the rearing male and the putative father. Nestling body mass was influenced by the coloration of both the rearing female and the genetic mother. Our results suggest that features of both their social and putative genetic parents influence nestling health and growth. From this it would appear that females could be gaining both direct and indirect benefits through mate choice of male plumage traits and that it would be possible for males to similarly gain through mate choice of female traits. PMID:23936081

  10. Amygdala Volume in Offspring from Multiplex for Alcohol Dependence Families: The Moderating Influence of Childhood Environment and 5-HTTLPR Variation

    PubMed Central

    Hill, Shirley Y; Wang, Shuhui; Carter, Howard; McDermott, Michael D; Zezza, Nicholas; Stiffler, Scott

    2014-01-01

    Background The increased susceptibility for developing alcohol dependence seen in offspring from families with alcohol dependence may be related to structural and functional differences in brain circuits that influence emotional processing. Early childhood environment, genetic variation in the serotonin transporter-linked polymorphic region (5-HTTLPR) of the SLCA4 gene and allelic variation in the Brain Derived Neurotrophic Factor (BDNF) gene have each been reported to be related to volumetric differences in the temporal lobe especially the amygdala Methods Magnetic resonance imaging was used to obtain amygdala volumes for 129 adolescent/young adult individuals who were either High-Risk (HR) offspring from families with multiple cases of alcohol dependence (N=71) or Low-Risk (LR) controls (N=58). Childhood family environment was measured prospectively using age-appropriate versions of the Family Environment Scale during a longitudinal follow-up study. The subjects were genotyped for Brain-Derived Neurotrophic Factor (BDNF) Val66Met and the serotonin transporter polymorphism (5-HTTLPR). Two family environment scale scores (Cohesion and Conflict), genotypic variation, and their interaction were tested for their association with amygdala volumes. Personal and prenatal exposure to alcohol and drugs were considered in statistical analyses in order to more accurately determine the effects of familial risk group differences. Results Amygdala volume was reduced in offspring from families with multiple alcohol dependent members in comparison to offspring from control families. High-Risk offspring who were carriers of the S variant of the 5-HTTLPR polymorphism had reduced amygdala volume in comparison to those with an LL genotype. Larger amygdala volume was associated with greater family cohesion but only in Low-Risk control offspring. Conclusions Familial risk for alcohol dependence is an important predictor of amygdala volume even when removing cases with significant

  11. Environmental stimulation rescues maternal high fructose intake-impaired learning and memory in female offspring: Its correlation with redistribution of histone deacetylase 4.

    PubMed

    Wu, Kay L H; Wu, Chih-Wei; Tain, You-Lin; Huang, Li-Tung; Chao, Yung-Mei; Hung, Chun-Ying; Wu, Jin-Cheng; Chen, Siang-Ru; Tsai, Pei-Chia; Chan, Julie Y H

    2016-04-01

    Impairment of learning and memory has been documented in the later life of offspring to maternal consumption with high energy diet. Environmental stimulation enhances the ability of learning and memory. However, potential effects of environmental stimulation on the programming-associated deficit of learning and memory have not been addressed. Here, we examined the effects of enriched-housing on hippocampal learning and memory in adult female offspring rats from mother fed with 60% high fructose diet (HFD) during pregnancy and lactation. Impairment of spatial learning and memory performance in HFD group was observed in offspring at 3-month-old. Hippocampal brain-derived neurotrophic factor (BDNF) was decreased in the offspring. Moreover, the HFD group showed an up-regulation of histone deacetylase 4 (HDAC4) in the nuclear fractions of hippocampal neurons. Stimulation to the offspring for 4weeks after winning with an enriched-housing environment effectively rescued the decrease in cognitive function and hippocampal BDNF level; alongside a reversal of the increased distribution of nuclear HDAC4. Together these results suggest that later life environmental stimulation effectively rescues the impairment of hippocampal learning and memory in female offspring to maternal HFD intake through redistributing nuclear HDAC4 to increase BDNF expression. PMID:26872592

  12. Prenatal acoustic communication programs offspring for high posthatching temperatures in a songbird.

    PubMed

    Mariette, Mylene M; Buchanan, Katherine L

    2016-08-19

    In many species, embryos can perceive and learn external sounds. Yet, the possibility that parents may use these embryonic capacities to alter their offspring's developmental trajectories has not been considered. Here, we demonstrate that zebra finch parents acoustically signal high ambient temperatures (above 26°C) to their embryos. We show that exposure of embryos to these acoustic cues alone adaptively alters subsequent nestling begging and growth in response to nest temperature and influences individuals' reproductive success and thermal preferences as adults. These findings have implications for our understanding of maternal effects, phenotypic plasticity, developmental programming, and the adaptation of endothermic species to a warming world. PMID:27540172

  13. Immunosuppressive effect of murine cytomegalovirus.

    PubMed Central

    Loh, L; Hudson, J B

    1980-01-01

    Murine cytomegalovirus suppressed the ability of spleen cells to respond to mitogens in vitro. The degree of suppression was proportional to the multiplicity of infection. This effect could not be explained by cytolysis of lymphocytes, an alteration in the kinetics of the response to mitogen, or a direct competition between virions and mitogen molecules for cell-surface receptors. Nor was it due to simple contact between cell and virus, since ultraviolet-inactivated murine cytomegalovirus failed to suppress the response to mitogens. Reconstitution experiments were performed which involved mixing various combinations of infected and uninfected macrophages and lymphocytes. Under these conditions, it was found that the infected macrophages and lymphocytes. Under these conditions, it was found that the infected macrophages had an impaired capacity to mediate the response ot T lymphocytes to concanavalin A. This suggests that murine cytomegalovirus may cause immunosuppression indirectly by interfering with macrophage function. PMID:6244228

  14. The sperm of aging male bustards retards their offspring's development.

    PubMed

    Preston, Brian T; Saint Jalme, Michel; Hingrat, Yves; Lacroix, Frederic; Sorci, Gabriele

    2015-01-01

    Understanding whether the sperm of older males has a diminished capacity to produce successful offspring is a key challenge in evolutionary biology. We investigate this issue using 10 years of reproductive data on captive long-lived houbara bustards (Chlamydotis undulata), where the use of artificial insemination techniques means parents can only influence offspring quality via their gametes. Here we show that paternal aging reduces both the likelihood that eggs hatch and the rate at which chicks grow, with older males producing the lightest offspring after the first month. Surprisingly, this cost of paternal aging on offspring development is of a similar scale to that associated with maternal aging. Fitting with predictions on germline aging, the sperm of immature males produce the fastest growing offspring. Our findings thus indicate that any good genes benefit that might be offered by older 'proven' males will be eroded by aging of their germline DNA. PMID:25647605

  15. Offspring recognition by mother crab spiders with extreme maternal care

    PubMed Central

    Evans, T. A.

    1998-01-01

    Maternal care is provided by several spider species, but there are no reports of mother spiders recognizing their young, which suggests that maternal care can be exploited by unrelated individuals. Diaea ergandros, a crab spider with extreme, sacrificial maternal care, does accept unrelated spiderlings (ca. 43.9% of spiderlings) into its nest in areas of high nest density. However, a field and a laboratory experiment with mother spiders and natural and adoptive spiderlings demonstrated that mothers did recognize their own offspring. Recognition was not expressed in survival as adopted (unrelated) spiderlings had similar survival rate to that of natural offspring. Instead it was displayed in growth; mother D. ergandros caught large prey items for their own offspring, but not for adopted spiderlings, and so natural offspring grew more than adopted spiderlings. Also, mothers produced trophic oocytes, which are important for the sacrificial care that influences spiderling survival, only when they lived with their own offspring.

  16. The sperm of aging male bustards retards their offspring's development

    PubMed Central

    Preston, Brian T.; Saint Jalme, Michel; Hingrat, Yves; Lacroix, Frederic; Sorci, Gabriele

    2015-01-01

    Understanding whether the sperm of older males has a diminished capacity to produce successful offspring is a key challenge in evolutionary biology. We investigate this issue using 10 years of reproductive data on captive long-lived houbara bustards (Chlamydotis undulata), where the use of artificial insemination techniques means parents can only influence offspring quality via their gametes. Here we show that paternal aging reduces both the likelihood that eggs hatch and the rate at which chicks grow, with older males producing the lightest offspring after the first month. Surprisingly, this cost of paternal aging on offspring development is of a similar scale to that associated with maternal aging. Fitting with predictions on germline aging, the sperm of immature males produce the fastest growing offspring. Our findings thus indicate that any good genes benefit that might be offered by older ‘proven' males will be eroded by aging of their germline DNA. PMID:25647605

  17. Production of donor-derived offspring by allogeneic transplantation of spermatogonia in the yellowtail (Seriola quinqueradiata).

    PubMed

    Morita, Tetsuro; Kumakura, Naoki; Morishima, Kagayaki; Mitsuboshi, Toru; Ishida, Masashi; Hara, Takashi; Kudo, Satomi; Miwa, Misako; Ihara, Shoko; Higuchi, Kentaro; Takeuchi, Yutaka; Yoshizaki, Goro

    2012-06-01

    Although the yellowtail (Seriola quinqueradiata) is the fish most commonly farmed in Japan, breeding of this species has not yet started. This is primarily due to the lack of sufficiently sophisticated methods for manipulating gametogenesis, which makes it difficult to collect gametes from specific dams and sires. If it were possible to produce large numbers of surrogate fish by transplanting germ cells isolated from donor individuals harboring desirable genetic traits, then the probability of acquiring gametes carrying the donor-derived haplotype would increase, and breeding programs involving this species might increase as a result. As a first step, we established a method for the allogeneic transplantation of yellowtail spermatogonia and the production of donor-derived offspring. Donor cells were collected from immature (10-month-old) yellowtail males with testes containing abundant type A spermatogonia, labeled with PKH26 fluorescent dye, and transferred into the peritoneal cavities of 8-day-old larvae. Fluorescence observation at 28 days post-transplantation revealed that PKH26-labeled cells were incorporated into recipients' gonads. To assess whether donor-derived spermatogonia could differentiate into functional gametes in the allogeneic recipient gonads, gametes collected from nine male and four female adult recipients were fertilized with wild-type eggs and milt. Analysis of microsatellite DNA markers confirmed that some of the first filial (F(1)) offspring were derived from donor fish, with the average contribution of donor-derived F(1) offspring being 66% and the maximum reaching 99%. These findings confirmed that our method was effective for transplanting yellowtail spermatogonia into allogeneic larvae to produce donor-derived offspring. PMID:22460666

  18. Levels of the inflammation marker YKL-40 in young adults exposed to intrauterine hyperglycemia.

    PubMed

    Kelstrup, Louise; Dejgaard, Thomas F; Clausen, Tine D; Mathiesen, Elisabeth R; Hansen, Torben; Vestergaard, Henrik; Damm, Peter

    2016-04-01

    Plasma levels of the inflammatory marker YKL-40 were investigated in 597 adult offspring born to women with and without diabetes during pregnancy. No association between fetal exposure to maternal hyperglycemia and levels of YKL-40 was found. However, female sex and increasing BMI in the offspring were associated to YKL-40. PMID:27103369

  19. Culture, Parental Conflict, Parental Marital Status, and the Subjective Well-Being of Young Adults.

    ERIC Educational Resources Information Center

    Gohm, Carol L.; Oishi, Shigehiro; Darlington, Janet; Diener, Ed

    1998-01-01

    Study 1 found that subjective well-being was negatively associated with marital conflict among offspring of never-divorced and remarried parents. Study 2 found that the negative association of divorce and of marital conflict with the life satisfaction of the offspring did not differ for adopted young adults. (Author/MKA)

  20. Maternal nutrient restriction affects properties of skeletal muscle in offspring

    PubMed Central

    Zhu, Mei J; Ford, Stephen P; Means, Warrie J; Hess, Bret W; Nathanielsz, Peter W; Du, Min

    2006-01-01

    Maternal nutrient restriction (NR) affects fetal development with long-term consequences on postnatal health of offspring, including predisposition to obesity and diabetes. Most studies have been conducted in fetuses in late gestation, and little information is available on the persistent impact of NR from early to mid-gestation on properties of offspring skeletal muscle, which was the aim of this study. Pregnant ewes were subjected to 50% NR from day 28–78 of gestation and allowed to deliver. The longissimus dorsi muscle was sampled from 8-month-old offspring. Maternal NR during early to mid-gestation decreased the number of myofibres in the offspring and increased the ratio of myosin IIb to other isoforms by 17.6 ± 4.9% (P < 0.05) compared with offspring of ad libitum fed ewes. Activity of carnitine palmitoyltransferase-1, a key enzyme controlling fatty acid oxidation, was reduced by 24.7 ± 4.5% (P < 0.05) in skeletal muscle of offspring of NR ewes and would contribute to increased fat accumulation observed in offspring of NR ewes. Intramuscular triglyceride content (IMTG) was increased in skeletal muscle of NR lambs, a finding which may be linked to predisposition to diabetes in offspring of NR mothers, since enhanced IMTG predisposes to insulin resistance in skeletal muscle. Proteomic analysis by two-dimensional gel electrophoresis demonstrated downregulation of several catabolic enzymes in 8-month-old offspring of NR ewes. These data demonstrate that the early to mid-gestation period is important for skeletal muscle development. Impaired muscle development during this stage of gestation affects the number and composition of fibres in offspring which may lead to long-term physiological consequences, including predisposition to obesity and diabetes. PMID:16763001

  1. A methyl-seq analyses of rat offspring liver reveals maternal obesity-induced alterations in dna methylation status at weaning

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exposure to maternal obesity (MO) increases the risk of obesity in adult-life. MO was induced in rats by overfeeding via total enteral nutrition. Male offspring from obese rats gain greater body weight, fat mass and develop insulin resistance when fed high fat diets. However the mechanisms underlyin...

  2. Gestational stress induces depressive-like and anxiety-like phenotypes through epigenetic regulation of BDNF expression in offspring hippocampus.

    PubMed

    Zheng, Yu; Fan, Weidong; Zhang, Xianquan; Dong, Erbo

    2016-01-01

    Exposure to stressful life events during pregnancy exerts profound effects on neurodevelopment and increases the risk for several neurodevelopmental disorders including major depression. The mechanisms underlying the consequences of gestational stress are complex and remain to be elucidated. This study investigated the effects of gestational stress on depressive-like behavior and epigenetic modifications in young adult offspring. Gestational stress was induced by a combination of restraint and 24-hour light disturbance to pregnant dams throughout gestation. Depressive-like and anxiety-like behaviors of young adult offspring were examined. The expression and promoter methylation of brain derived neurotrophic factor (BDNF) were measured using RT-qPCR, Western blot, methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP). In addition, the expressions of histone deacetylases (HDACs) and acetylated histone H3 lysine 14 (AcH3K14) were also analyzed. Our results show that offspring from gestational stress dams exhibited depressive-like and anxiety-like behaviors. Biochemically, stress-offspring showed decreased expression of BDNF, increased expression of DNMT1, HDAC1, and HDAC2, and decreased expression of AcH3K14 in the hippocampus as compared to non-stress offspring. Data from MeDIP and ChIP assays revealed an increased methylation as well as decreased binding of AcH3K14 on specific BDNF promoters. Pearson analyses indicated that epigenetic changes induced by gestational stress were correlated with depressive-like and anxiety-like behaviors. These data suggest that gestational stress may be a suitable model for understanding the behavioral and molecular epigenetic changes observed in patients with depression. PMID:26890656

  3. Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid receptor gene in Holocaust survivor offspring

    PubMed Central

    Desarnaud, Frank; Bader, Heather N.; Makotkine, Iouri; Flory, Janine D.; Bierer, Linda M.; Meaney, Michael J.

    2014-01-01

    Objective Differential effects of maternal and paternal PTSD have been observed in adult offspring of Holocaust survivors in both glucocorticoid receptor sensitivity and vulnerability to psychiatric disorder. The current study examined the relative influences of maternal and paternal PTSD on DNA methylation of the exon 1F promoter of the glucocorticoid receptor gene (NR3C1) in peripheral blood mononuclear cells (PBMCs), and its relationship to glucocorticoid receptor sensitivity, in Holocaust offspring. Method Adult offspring with at least one Holocaust survivor parent (n=80), and demographically similar participants without parental Holocaust exposure or PTSD (n=15) completed clinical interviews, self-report measures, and biological procedures. Blood samples were collected for analysis of glucocorticoid receptor gene exon 1F (GR-1F) promoter methylation and cortisol levels in response to low-dose dexamethasone, and two-way analysis of covariance was performed using maternal and paternal PTSD as main effects. Hierarchical-clustering analysis was used to permit visualization of maternal vs. paternal PTSD effects on clinical variables. Results A significant interaction demonstrated that in the absence of maternal PTSD, offspring with paternal PTSD showed higher GR-1F promoter methylation, whereas offspring with both maternal and paternal PTSD showed lower methylation. Lower GR-1F promoter methylation was significantly associated with greater post-dexamethasone cortisol suppression. The clustering analysis confirmed that maternal and paternal PTSD effects were differentially associated with clinical indicators. Conclusions This is the first study to demonstrate alterations of GR-1F promoter methylation in relation to parental PTSD and neuroendocrine outcomes. The moderation of paternal PTSD effects by maternal PTSD suggests different mechanisms for the intergenerational transmission of trauma-related vulnerabilities. PMID:24832930

  4. Reproduction of Varroa destructor and offspring mortality in worker and drone brood cells of Africanized honey bees.

    PubMed

    Calderón, R A; Ureña, S; van Veen, J W

    2012-04-01

    Varroa destructor is known to be the most serious parasite of Apis mellifera worldwide. In order to reproduce varroa females enter worker or drone brood shortly before the cell is sealed. From March to December 2008, the reproductive rate and offspring mortality (mature and immature stages), focusing on male absence and male mortality of V. destructor, was investigated in naturally infested worker and drone brood of Africanized honey bees (AHB) in Costa Rica. Data were obtained from 388 to 403 single infested worker and drone brood cells, respectively. Mite fertility in worker and drone brood cells was 88.9 and 93.1%, respectively. There was no difference between the groups (X(2) = 3.6, P = 0.06). However, one of the most significant differences in mite reproduction was the higher percentage of mites producing viable offspring in drone cells (64.8%) compared to worker cells (37.6%) (X(2) = 57.2, P < 0.05). A greater proportion of mites in worker brood cells produced non-viable female offspring. Mite offspring mortality in both worker and drone cells was high in the protonymph stage (mobile and immobile). A significant finding was the high rate of male mortality. The worker and drone brood revealed that 23.9 and 6.9%, respectively, of the adult male offspring was found dead. If the absence (missing) of the male and adult male mortality are taken together the percentage of cells increased to 40.0 and 21.3% in worker and drone cells, respectively (X(2) = 28.8, P < 0.05). The absence of the male or male mortality in a considerable number of worker cells naturally infested with varroa is the major factor in our study which reduces the production of viable daughters in AHB colonies in Costa Rica. PMID:22270116

  5. Gestational and postpartum corticosterone exposure to the dam affects behavioral and endocrine outcome of the offspring in a sexually-dimorphic manner.

    PubMed

    Brummelte, Susanne; Lieblich, Stephanie E; Galea, Liisa A M

    2012-01-01

    Exposure to high levels of glucocorticoids in utero and during the postpartum period has a detrimental effect on brain development. We created an animal model of postpartum stress/depression based on administering high levels of corticosterone (CORT) to the dams during the postpartum period which caused behavioral changes and reduced hippocampal cell proliferation in the offspring. As the consequences of early exposure to glucocorticoids may depend on the dose and the developmental stage of the offspring, the present study was conducted to investigate the effects of low (10 mg/kg) or high levels of CORT (40 mg/kg) given to dams either during gestation, postpartum or across both gestation and postpartum on the outcome of the offspring. Male and female offspring were weighed throughout the experiment, tested in a series of behavioral tests (forced swim test, open field, elevated plus maze) and basal and restraint stress CORT levels were examined in adolescence or young adulthood. Results show that maternal CORT exposure, regardless of when administered, significantly attenuated body weight gain until adulthood in the offspring. Offspring exposed to low maternal CORT, but not high maternal CORT, during the postpartum had higher basal levels of CORT as young adults. Further, male and female offspring of dams exposed to high maternal CORT in utero showed more depressive-like behavior in the forced swim test, while males of dams exposed to high maternal CORT postpartum exhibited more anxiety-like behavior in the elevated plus maze. Taken together, maternal glucocorticoid exposure have long lasting effects on male and female offspring's behavioral and neuroendocrine measures in adolescence and adulthood depending on the time of exposure to glucocorticoids. This article is part of a Special Issue entitled 'Anxiety and Depression'. PMID:21867716

  6. Suppression of Wnt1-induced mammary tumor growth and lower serum insulin in offspring exposed to maternal blueberry diet suggest early dietary influence on developmental programming

    PubMed Central

    Simmen, Rosalia C.M.

    2013-01-01

    Despite the well-accepted notion that early maternal influences persist beyond fetal life and may underlie many adult diseases, the risks imposed by the maternal environment on breast cancer development and underlying biological mechanisms remain poorly understood. In this study, we investigated whether early exposure to blueberry (BB) via maternal diet alters oncogene Wnt1-induced mammary tumorigenesis in offspring. Wnt1-transgenic female mice were exposed to maternal Casein (CAS, control) or blueberry-supplemented (CAS + 3%BB) diets throughout pregnancy and lactation. Offspring were weaned to CAS and mammary tumor development was followed until age 8 months. Tumor incidence and latency were similar for both groups; however, tumor weight at killing and tumor volume within 2 weeks of initial detection were lower (by 50 and 60%, respectively) in offspring of BB- versus control-fed dams. Dietary BB exposure beginning at weaning did not alter mammary tumor parameters. Tumors from maternal BB-exposed offspring showed higher tumor suppressor (Pten and Cdh1) and lower proproliferative (Ccnd1), anti-apoptotic (Bcl2) and proangiogenic (Figf, Flt1 and Ephb4) transcript levels, and displayed attenuated microvessel density. Expression of Pten and Cdh1 genes was also higher in mammary tissues of maternal BB-exposed offspring. Mammary tissues and tumors of maternal BB-exposed offspring showed increased chromatin-modifying enzyme Dnmt1 and Ezh2 transcript levels. Body weight, serum insulin and serum leptin/adiponectin ratio were lower for maternal BB-exposed than control tumor-bearing offspring. Tumor weights and serum insulin were positively correlated. Results suggest that dietary influences on the maternal environment contribute to key developmental programs in the mammary gland to modify breast cancer outcome in adult progeny. PMID:23144318

  7. Paternal age and mental health of offspring.

    PubMed

    Malaspina, Dolores; Gilman, Caitlin; Kranz, Thorsten Manfred

    2015-06-01

    The influence of paternal age on the risk for sporadic forms of Mendelian disorders is well known, but a burgeoning recent literature demonstrates, in addition, a paternal age effect for complex neuropsychiatric conditions, including schizophrenia, autism, bipolar disorder, and even for learning potential, expressed as intelligence. Mental illness is costly to patients, their family, and the public health system, accounting for the largest portion of disability costs in our economy. The delayed onset of neuropsychiatric conditions and lack of physical manifestations at birth are common frequencies in the population that have obscured the recognition that a portion of the risks for mental conditions is associated with paternal age. Identification of these risk pathways may be leveraged for knowledge about mental function and for future screening tests. However, only a small minority of at-risk offspring are likely to have such a psychiatric or learning disorder attributable to paternal age, including the children of older fathers. PMID:25956369

  8. Fruit Flies Medicate Offspring After Seeing Parasites

    PubMed Central

    Kacsoh, Balint Z.; Lynch, Zachary R.; Mortimer, Nathan T.; Schlenke, Todd A.

    2013-01-01

    Hosts have numerous defenses against parasites, of which behavioral immune responses are an important but under-appreciated component. Here we describe a behavioral immune response Drosophila melanogaster utilizes against endoparasitoid wasps. We found that when flies see wasps they switch to laying eggs in alcohol-laden food sources that protect hatched larvae from infection. This oviposition behavior change, mediated by neuropeptide F, is retained long after wasps are removed. Flies respond to diverse female larval endoparasitoids but not to pupal endoparasitoids or males, showing they maintain specific wasp search images. Furthermore, the response evolved multiple times across the genus Drosophila. Our data reveal a behavioral immune response based on anticipatory medication of offspring, and outline a non-associative memory paradigm based on innate parasite recognition by the host. PMID:23430653

  9. Persistent sex-by-environment effects on offspring fitness and sex-ratio adjustment in a wild bird population.

    PubMed

    Bowers, E Keith; Thompson, Charles F; Sakaluk, Scott K

    2015-03-01

    A major component of sex-allocation theory, the Trivers-Willard model (TWM), posits that sons and daughters are differentially affected by variation in the rearing environment. In many species, the amount of parental care received is expected to have differing effects on the fitness of males and females. When this occurs, the TWM predicts that selection should favour adjustment of the offspring sex ratio in relation to the expected fitness return from offspring. However, evidence for sex-by-environment effects is mixed, and little is known about the adaptive significance of producing either sex. Here, we test whether offspring sex ratios vary according to predictions of the TWM in the house wren (Troglodytes aedon, Vieillot). We also test the assumption of a sex-by-environment effect on offspring using two experiments, one in which we manipulated age differences among nestlings within broods, and another in which we held nestling age constant but manipulated brood size. As predicted, females with high investment ability overproduced sons relative to those with lower ability. Males were also overproduced early within breeding seasons. In our experiments, the body mass of sons was more strongly affected by the sibling-competitive environment and resource availability than that of daughters: males grew heavier than females when reared in good conditions but were lighter than females when in poor conditions. Parents rearing broods with 1:1 sex ratios were more productive than parents rearing broods biased more strongly towards sons or daughters, suggesting that selection favours the production of mixed-sex broods. However, differences in the condition of offspring as neonates persisted to adulthood, and their reproductive success as adults varied with the body mass of sons, but not daughters, prior to independence from parental care. Thus, selection should favour slight but predictable variations in the sex ratio in relation to the quality of offspring that parents are

  10. Persistent sex-by-environment effects on offspring fitness and sex-ratio adjustment in a wild bird population

    PubMed Central

    Bowers, E. Keith; Thompson, Charles F.; Sakaluk, Scott K.

    2014-01-01

    Summary A major component of sex-allocation theory, the Trivers-Willard Model (TWM), posits that sons and daughters are differentially affected by variation in the rearing environment. In many species, the amount of parental care received is expected to have differing effects on the fitness of males and females. When this occurs, the TWM predicts that selection should favour adjustment of the offspring sex ratio in relation to the expected fitness return from offspring. However, evidence for sex-by-environment effects is mixed and little is known about the adaptive significance of producing either sex. Here, we test whether offspring sex ratios vary according to predictions of the TWM in the house wren (Troglodytes aedon, Vieillot). We also test the assumption of a sex-by-environment effect on offspring using two experiments, one in which we manipulated age-differences among nestlings within broods, and another in which we held nestling age constant but manipulated brood size. As predicted, females with high investment ability over-produced sons relative to those with lower ability. Males were also over-produced early within breeding seasons. In our experiments, the body mass of sons was more strongly affected by the sibling-competitive environment and resource availability than that of daughters: males grew heavier than females when reared in good conditions but were lighter than females when in poor conditions. Parents rearing broods with 1:1 sex ratios were more productive than parents rearing broods biased more strongly towards sons or daughters, suggesting that selection favours the production of mixed-sex broods. However, differences in the condition of offspring as neonates persisted to adulthood, and their reproductive success as adults varied with the body mass of sons, but not daughters, prior to independence from parental care. Thus, selection should favour slight but predictable variations in the sex ratio in relation to the quality of offspring that

  11. Antimicrobial proteins of murine macrophages.

    PubMed Central

    Hiemstra, P S; Eisenhauer, P B; Harwig, S S; van den Barselaar, M T; van Furth, R; Lehrer, R I

    1993-01-01

    Three murine microbicidal proteins (MUMPs) were purified from cells of the murine macrophage cell line RAW264.7 that had been activated by gamma interferon. Similar proteins were also present in nonactivated RAW264.7 cells, in cells of the murine macrophage cell line J774A.1, and in resident and activated murine peritoneal macrophages. MUMP-1, MUMP-2, and MUMP-3 killed Salmonella typhimurium, Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, Mycobacterium fortuitum, and Cryptococcus neoformans in vitro. MUMP-1 resembled an H1 histone but was unusual because its N-terminal residue (serine) was not N acetylated. Although MUMP-2 was N terminally blocked, its high lysine/arginine ratio and its reactivity with an antibody to H1 histones suggested that it also belonged to the H1 histone family. MUMP-3 was identical to histone H2B in 30 of 30 amino-terminal residues. Although the antimicrobial properties of histones have been recognized for decades, this is the first evidence that such proteins may endow the lysosomal apparatus of macrophages with nonoxidative antimicrobial potential. Other MUMPs, including some with a more restricted antimicrobial spectrum and one that appeared to be induced in RAW264.7 cells after gamma interferon stimulation, were noted but remain to be characterized. Images PMID:8514411

  12. Relationships between Body Size and Parasitic Fitness and Offspring Performance of Sclerodermus pupariae Yang et Yao (Hymenoptera: Bethylidae).

    PubMed

    Gao, Shangkun; Tang, Yanlong; Wei, Ke; Wang, Xiaoyi; Yang, Zhongqi; Zhang, Yanlong

    2016-01-01

    The relationship between body size and fitness in parasitoid wasps has several effects on parasitic ability, reproductive behavior in female wasps, and progeny fitness. Female wasps with various body sizes were obtained by mass-rearing a gregarious ectoparasitoid, Sclerodermus pupariae, which is one of the excellent parasites to control the larvae and pupae of Buprestidae and Cerambycidae. We investigated the effects of body size of adult females introduced on Thyestilla gebleri (Coleoptera: Cerambycidae) larvae on their paralysis time, pre-oviposition period, oviposition period and fecundity, and the related fitness of their offspring. Results showed that small female wasps needed more time to paralyze a host and had a higher mortality rate than large female wasps. More offspring were produced by large female wasps than by small female wasps, and the percentage and body size of female offspring was not affected by maternal body size. The duration of the egg stage was not affected by foundress size, nor was that of the pupal stage, but the duration of the larval stage and generation time of small female wasps was longer than that of large females. Our findings suggest that the parasitic fitness and offspring performance are affected by maternal size, and there is need to choose reasonable body size of female wasps, to optimally utilize mass rearing and to control target pests with the lowest mortality cost. PMID:27367523

  13. Gestational Hypothyroidism Improves the Ability of the Female Offspring to Clear Streptococcus pneumoniae Infection and to Recover From Pneumococcal Pneumonia.

    PubMed

    Nieto, Pamela A; Peñaloza, Hernán F; Salazar-Echegarai, Francisco J; Castellanos, Raquel M; Opazo, Maria Cecilia; Venegas, Luis; Padilla, Oslando; Kalergis, Alexis M; Riedel, Claudia A; Bueno, Susan M

    2016-06-01

    Maternal thyroid hormones are essential for proper fetal development. A deficit of these hormones during gestation has enduring consequences in the central nervous system of the offspring, including detrimental learning and impaired memory. Few studies have shown that thyroid hormone deficiency has a transient effect in the number of T and B cells in the offspring gestated under hypothyroidism; however, there are no studies showing whether maternal hypothyroidism during gestation impacts the response of the offspring to infections. In this study, we have evaluated whether adult mice gestated in hypothyroid mothers have an altered response to pneumococcal pneumonia. We observed that female mice gestated in hypothyroidism have increased survival rate and less bacterial dissemination to blood and brain after an intranasal challenge with Streptococcus pneumoniae. Further, these mice had higher amounts of inflammatory cells in the lungs and reduced production of cytokines characteristic of sepsis in spleen, blood, and brain at 48 hours after infection. Interestingly, mice gestated in hypothyroid mothers had basally increased vascular permeability in the lungs. These observations suggest that gestational hypothyroidism alters the immune response and the physiology of lungs in the offspring, increasing the resistance to respiratory bacterial infections. PMID:27035652

  14. Relationships between Body Size and Parasitic Fitness and Offspring Performance of Sclerodermus pupariae Yang et Yao (Hymenoptera: Bethylidae)

    PubMed Central

    Gao, Shangkun; Tang, Yanlong; Wei, Ke; Wang, Xiaoyi; Yang, Zhongqi; Zhang, Yanlong

    2016-01-01

    The relationship between body size and fitness in parasitoid wasps has several effects on parasitic ability, reproductive behavior in female wasps, and progeny fitness. Female wasps with various body sizes were obtained by mass–rearing a gregarious ectoparasitoid, Sclerodermus pupariae, which is one of the excellent parasites to control the larvae and pupae of Buprestidae and Cerambycidae. We investigated the effects of body size of adult females introduced on Thyestilla gebleri (Coleoptera: Cerambycidae) larvae on their paralysis time, pre–oviposition period, oviposition period and fecundity, and the related fitness of their offspring. Results showed that small female wasps needed more time to paralyze a host and had a higher mortality rate than large female wasps. More offspring were produced by large female wasps than by small female wasps, and the percentage and body size of female offspring was not affected by maternal body size. The duration of the egg stage was not affected by foundress size, nor was that of the pupal stage, but the duration of the larval stage and generation time of small female wasps was longer than that of large females. Our findings suggest that the parasitic fitness and offspring performance are affected by maternal size, and there is need to choose reasonable body size of female wasps, to optimally utilize mass rearing and to control target pests with the lowest mortality cost. PMID:27367523

  15. Influence of maternal overnutrition and gestational diabetes on the programming of metabolic health outcomes in the offspring: experimental evidence.

    PubMed

    Pereira, Troy J; Moyce, Brittany L; Kereliuk, Stephanie M; Dolinsky, Vernon W

    2015-10-01

    The incidence of obesity and type 2 diabetes mellitus have risen across the world during the past few decades and has also reached an alarming level among children. In addition, women are currently more likely than ever to enter pregnancy obese. As a result, the incidence of gestational diabetes mellitus is also on the rise. While diet and lifestyle contribute to these trends, population health data show that maternal obesity and diabetes during pregnancy during critical stages of development are major factors that contribute to the development of chronic disease in adolescent and adult offspring. Fetal programming of metabolic function, through physiological and (or) epigenetic mechanisms, may also have an intergenerational effect, and as a result may perpetuate metabolic disorders in the next generation. In this review, we summarize the existing literature that characterizes how maternal obesity and gestational diabetes mellitus contribute to metabolic and cardiovascular disorders in the offspring. In particular, we focus on animal studies that investigate the molecular mechanisms that are programmed by the gestational environment and lead to disease phenotypes in the offspring. We also review interventional studies that prevent disease with a developmental origin in the offspring. PMID:25673017

  16. Long-term toxicity of reduced graphene oxide nanosheets: Effects on female mouse reproductive ability and offspring development.

    PubMed

    Xu, Shun; Zhang, Zheyu; Chu, Maoquan

    2015-06-01

    Reduced graphene oxide (rGO) nanosheets have emerged as novel materials for cancer therapeutics. Their toxicity has attracted much attention since these nanomaterials may have great potential for clinical cancer treatment. Here we report the influence of rGO exposure on female mouse reproductive ability and offspring development. Mouse dams were injected with small or large rGO nanosheets at different doses and time points, pre- or post-fertilization. The sex hormone levels of adult female mice did not significantly change compared with the control group after intravenous injection with either small or large rGO, even at a high dose (25 mg/kg). Mouse dams could produce healthy offspring after treatment with rGO nanosheets before pregnancy and at an early gestational stage (∼6 days). Despite the successful delivery of offspring, malformed fetuses were found among rGO-injected dam litters. All mice had abortions when injected with low (6.25 mg/kg) or intermediate (12.5 mg/kg) doses at a late gestational stage (∼20 days); the majority of pregnant mice died when injected with the high dose of rGO at this stage of pregnancy. Interestingly, all surviving rGO-injected mouse mothers gave birth to another litter of healthy pups. The results presented in this work are important for a deeper understanding of the toxicity of rGO nanosheets on female reproductivity and their offspring development. PMID:25907052

  17. Maternal high-fat hypercaloric diet during pregnancy results in persistent metabolic and respiratory abnormalities in offspring

    PubMed Central

    Griffiths, Pamela S.; Walton, Cheryl; Samsell, Lennie; Perez, Miriam K.; Piedimonte, Giovanni

    2016-01-01

    Background: We have shown in a previous population-based study significant correlation between childhood asthma and early abnormalities of lipid and glucose metabolism. This study's specific aim was to determine whether maternal nutrition in pregnancy affects postnatal metabolic and respiratory outcomes in the offspring. Methods: On gestation day 1, dams were switched from standard chow to either high-fat hypercaloric diet or control diet. Terminal experiments were performed on newborn and weanling offspring of dams fed the study diet during gestation and lactation, and on adult offspring maintained on the same diet as their mother. Results: Pups born from high-fat hypercaloric diet (HFD) dams developed metabolic abnormalities persistent throughout development. Cytokine expression analysis of lung tissues from newborns born to HFD dams revealed a strong proinflammatory pattern. Gene expression of neurotrophic factors and receptors was upregulated in lungs of weanlings born to HFD dams, and this was associated to higher respiratory system resistance and lower compliance at baseline, as well as hyperreactivity to aerosolized methacholine. Furthermore, HFD dams delivered pups prone to develop more severe disease after respiratory syncytial virus (RSV) infection. Conclusion: Maternal nutrition in pregnancy is a critical determinant of airway inflammation and hyperreactivity in offspring and also increases risk for bronchiolitis independent from prepregnancy nutrition. PMID:26539661

  18. Maternal Obesity Promotes Diabetic Nephropathy in Rodent Offspring.

    PubMed

    Glastras, Sarah J; Tsang, Michael; Teh, Rachel; Chen, Hui; McGrath, Rachel T; Zaky, Amgad A; Pollock, Carol A; Saad, Sonia

    2016-01-01

    Maternal obesity is known to increase the risk of obesity and diabetes in offspring. Though diabetes is a key risk factor for the development of chronic kidney disease (CKD), the relationship between maternal obesity and CKD has not been clearly defined. In this study, a mouse model of maternal obesity was employed to determine the impact of maternal obesity on development of diabetic nephropathy in offspring. Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow diet. At postnatal Week 8, offspring were randomly administered low dose streptozotocin (STZ, 55 mg/kg/day for five days) to induce diabetes. Assessment of renal damage took place at postnatal Week 32. We found that offspring of obese mothers had increased renal fibrosis, inflammation and oxidative stress. Importantly, offspring exposed to maternal obesity had increased susceptibility to renal damage when an additional insult, such as STZ-induced diabetes, was imposed. Specifically, renal inflammation and oxidative stress induced by diabetes was augmented by maternal obesity. Our findings suggest that developmental programming induced by maternal obesity has implications for renal health in offspring. Maternal obesity should be considered a risk factor for CKD. PMID:27277011

  19. Maternal Obesity Promotes Diabetic Nephropathy in Rodent Offspring

    PubMed Central

    Glastras, Sarah J.; Tsang, Michael; Teh, Rachel; Chen, Hui; McGrath, Rachel T.; Zaky, Amgad A.; Pollock, Carol A.; Saad, Sonia

    2016-01-01

    Maternal obesity is known to increase the risk of obesity and diabetes in offspring. Though diabetes is a key risk factor for the development of chronic kidney disease (CKD), the relationship between maternal obesity and CKD has not been clearly defined. In this study, a mouse model of maternal obesity was employed to determine the impact of maternal obesity on development of diabetic nephropathy