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Sample records for affect fetal growth

  1. Magnesium and fetal growth

    SciTech Connect

    Weaver, K.

    1988-01-01

    Fetal growth retardation and premature labor are major problems in perinatal medicine today and account for a great deal of the observed fetal morbidity. While the neonatal death rate has steadily declined over the past decade, there has been a lack of concommitant decrease in these two leading problems. Magnesium (Mg/sup ++/) plays a major role in both of these areas of concern. The fact that it is used as a treatment for premature labor has led investigators to look at low Mg/sup ++/ as a possible cause of this poorly understood phenomenon. The second major cause of small for gestational age infants is intrauterine growth retardation, a condition which may be of either fetal or maternal origin. In either case, Mg/sup ++/ may be implicated since it exerts a strong influence on the underlying pathophysiology of placental failure and maternal hypertension. Both of these conditions are mediated by vascular and platelet hyperactivity as well as by and increase in the ration of thromboxane to prostacyclin. Studies in both the human and animal species are beginning to show how Mg/sup ++/ interacts in these conditions to produce such a damaging fetal outcome. The recent use of Doppler velocimetry of the developing fetus has shown reduced fetal vascular and maternal uterine vascular compliance as early as 14 weeks of gestation in those who would be so affected.

  2. Role of the Placental Vitamin D Receptor in Modulating Feto-Placental Growth in Fetal Growth Restriction and Preeclampsia-Affected Pregnancies

    PubMed Central

    Murthi, Padma; Yong, Hannah E. J.; Ngyuen, Thy P. H.; Ellery, Stacey; Singh, Harmeet; Rahman, Rahana; Dickinson, Hayley; Walker, David W.; Davies-Tuck, Miranda; Wallace, Euan M.; Ebeling, Peter R.

    2016-01-01

    Fetal growth restriction (FGR) is a common pregnancy complication that affects up to 5% of pregnancies worldwide. Recent studies demonstrate that Vitamin D deficiency is implicated in reduced fetal growth, which may be rescued by supplementation of Vitamin D. Despite this, the pathway(s) by which Vitamin D modulate fetal growth remains to be investigated. Our own studies demonstrate that the Vitamin D receptor (VDR) is significantly decreased in placentae from human pregnancies complicated by FGR and contributes to abnormal placental trophoblast apoptosis and differentiation and regulation of cell-cycle genes in vitro. Thus, Vitamin D signaling is important for normal placental function and fetal growth. This review discusses the association of Vitamin D with fetal growth, the function of Vitamin D and its receptor in pregnancy, as well as the functional significance of a placental source of Vitamin D in FGR. Additionally, we propose that for Vitamin D to be clinically effective to prevent and manage FGR, the molecular mechanisms of Vitamin D and its receptor in modulating fetal growth requires further investigation. PMID:26924988

  3. Placental CLIC3 is increased in fetal growth restriction and pre-eclampsia affected human pregnancies.

    PubMed

    Murthi, P; Stevenson, J L; Money, T T; Borg, A J; Brennecke, S P; Gude, N M

    2012-09-01

    Chloride intracellular channel (CLIC) proteins constitute a subgroup of the glutathione-S-transferase (GSTs) superfamily. In humans, the CLIC family of proteins consists of six members, designated CLIC 1-6, which have a conserved C-terminal 240 residue module and one major transmembrane domain. CLIC proteins regulate fundamental cellular processes including regulation of chloride ion concentration, stabilization of cell membrane potential, trans-epithelial transport, regulation of cell volume and stimulation of apoptotic processes in response to cellular stress. Previously, we described the expression profile of a member of the CLIC family of proteins, CLIC3, in human placentae and fetal membranes. In the current study, we determined CLIC3 expression in placentae from pregnancies complicated with either fetal growth restriction (FGR, n=19), pre-eclampsia (PE, n=16) or both FGR and PE combined (n=12) compared to gestation-matched controls (n=13) using real-time PCR and a CLIC3 specific immunoassay. Significantly increased CLIC3 mRNA and protein were detected in placental extracts from pregnancies with FGR, PE and PE with FGR compared to controls. Our results suggest that increased expression of CLIC3 may play a role in abnormal placental function associated with the human pregnancy disorders FGR and PE. PMID:22795578

  4. Stillbirth and fetal growth restriction.

    PubMed

    Bukowski, Radek

    2010-09-01

    The association between stillbirth and fetal growth restriction is strong and supported by a large body of evidence and clinically employed for the stillbirth prediction. However, although assessment of fetal growth is a basis of clinical practice, it is not trivial. Essentially, fetal growth is a result of the genetic growth potential of the fetus and placental function. The growth potential is the driving force of fetal growth, whereas the placenta as the sole source of nutrients and oxygen might become the rate limiting element of fetal growth if its function is impaired. Thus, placental dysfunction may prevent the fetus from reaching its full genetically determined growth potential. In this sense fetal growth and its aberration provides an insight into placental function. Fetal growth is a proxy for the test of the effectiveness of placenta, whose function is otherwise obscured during pregnancy.

  5. Limited and excess dietary protein during gestation affects growth and compositional traits in gilts and impairs offspring fetal growth.

    PubMed

    Rehfeldt, C; Lang, I S; Görs, S; Hennig, U; Kalbe, C; Stabenow, B; Brüssow, K-P; Pfuhl, R; Bellmann, O; Nürnberg, G; Otten, W; Metges, C C

    2011-02-01

    < 0.01) and greater fat content (P = 0.02 to 0.04) in LP and less fat content (P = 0.02 to 0.04) in HP gilts. Fetal litter weight and number, and embryonic survival at 64 dpc were not affected by the diets. These results indicated that gestation diets containing protein at 50 and 250% of recommendations and differing in protein:carbohydrate ratio led to marked changes in protein and fat metabolism in gilts resulting in fetal growth retardation of 15%, which mainly occurred during the second half of gestation.

  6. Hormonal Control of Fetal Growth.

    ERIC Educational Resources Information Center

    Cooke, Paul S.; Nicoll, Charles S.

    1983-01-01

    Summarizes recent research on hormonal control of fetal growth, presenting data obtained using a new method for studying the area. Effects of endocrine ablations and congenital deficiencies, studies of hormone/receptor levels, in-vitro techniques, hormones implicated in promoting fetal growth, problems with existing methodologies, and growth of…

  7. Prenatal Depression Restricts Fetal Growth

    PubMed Central

    Diego, Miguel A.; Field, Tiffany; Hernandez-Reif, Maria; Schanberg, Saul; Kuhn, Cynthia; Gonzalez-Quintero, Victor Hugo

    2009-01-01

    Objective To identify whether prenatal depression is a risk factor for fetal growth restriction. Methods Midgestation (18-20 weeks GA) estimated fetal weight and urine cortisol and birth weight and gestational age at birth data were collected on a sample of 40 depressed and 40 non-depressed women. Estimated fetal weight and birthweight data were then used to compute fetal growth rates. Results Depressed women had a 13% greater incidence of premature delivery (Odds Ratio (OR) = 2.61) and 15% greater incidence of low birthweight (OR = 4.75) than non-depressed women. Depressed women also had elevated prenatal cortisol levels (p = .006) and fetuses who were smaller (p = .001) and who showed slower fetal growth rates (p = .011) and lower birthweights (p = .008). Mediation analyses further revealed that prenatal maternal cortisol levels were a potential mediator for the relationship between maternal symptoms of depression and both gestational age at birth and the rate of fetal growth. After controlling for maternal demographic variables, prenatal maternal cortisol levels were associated with 30% of the variance in gestational age at birth and 14% of the variance in the rate of fetal growth. Conclusion Prenatal depression was associated with adverse perinatal outcomes, including premature delivery and slower fetal growth rates. Prenatal maternal cortisol levels appear to play a role in mediating these outcomes. PMID:18723301

  8. Intrauterine Cannabis Exposure Affects Fetal Growth Trajectories: The Generation R Study

    ERIC Educational Resources Information Center

    El Marroun, Hanan; Tiemeier, Henning; Steegers, Eric A. P.; Jaddoe, Vincent W. V.; Hofman, Albert; Verhulst, Frank C.; van den Brink, Wim; Huizink, Anja C.

    2009-01-01

    Objective: Cannabis is the most commonly consumed illicit drug among pregnant women. Intrauterine exposure to cannabis may result in risks for the developing fetus. The importance of intrauterine growth on subsequent psychological and behavioral child development has been demonstrated. This study examined the relation between maternal cannabis use…

  9. Dietary protein during gestation affects maternal insulin-like growth factor, insulin-like growth factor binding protein, leptin concentrations, and fetal growth in heifers.

    PubMed

    Sullivan, T M; Micke, G C; Perkins, N; Martin, G B; Wallace, C R; Gatford, K L; Owens, J A; Perry, V E A

    2009-10-01

    The influence of supplemental protein during gestation on maternal hormones and fetal growth was determined in composite beef heifers. At AI, 118 heifers were stratified by BW within each composite genotype (BeefX = 1/2 Senepol, 1/4 Brahman, 1/8 Charolais, 1/8 Red Angus and CBX = 1/2 Senepol, 1/4 Brahman, 1/4 Charolais) into 4 treatment groups: high high (HH = 1.4 kg CP/d for first and second trimesters of gestation), high low (HL = 1.4 kg of CP/d for first trimester and 0.4 kg of CP/d for second trimester), low high (lowH = 0.4 kg CP/d for first trimester and 1.4 kg of CP/d and for second trimester), or low low (LL = 0.4 kg CP/d for first and second trimesters). Maternal plasma IGF-I and -II, total IGFBP, and leptin concentrations were determined at 14 d before AI and at d 28, 82, 179, and 271 post-AI (mean gestation length 286 d), and leptin concentrations were also determined at calving. Increased dietary protein increased maternal plasma IGF-I (P < 0.001 on d 28, 82, and 179), IGF-II (P = 0.01 on d 82; P = 0.04 on d 271), and total IGFBP (P = 0.002 on d 82; P = 0.005 on d 179; P = 0.03 on d 271). Maternal plasma IGF-I at d 271 was negatively associated with calf crown-rump length at birth (P = 0.003). BeefX had greater birth weight calves (P = 0.01), greater IGF-II (P < 0.001), increased ratios of IGF-I:total IGFBP (P = 0.008) and IGF-II:total IGFBP (P < 0.001), and reduced total IGFBP compared with CBX (P = 0.02). Increased dietary protein during second trimester increased maternal plasma leptin at calving (P = 0.005). Maternal plasma leptin near term was positively associated with heifer BCS (P = 0.02) and with calf birth weight (P = 0.04), and at calving was positively associated with heifer age at AI (P = 0.02). These findings suggest that maternal dietary protein, age, and genotype influence plasma concentrations of metabolic hormones and fetal growth in Bos indicus-influenced heifers. PMID:19617516

  10. Uterine artery blood flow, fetal hypoxia and fetal growth

    PubMed Central

    Browne, Vaughn A.; Julian, Colleen G.; Toledo-Jaldin, Lillian; Cioffi-Ragan, Darleen; Vargas, Enrique; Moore, Lorna G.

    2015-01-01

    Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100–4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success. PMID:25602072

  11. Uterine artery blood flow, fetal hypoxia and fetal growth.

    PubMed

    Browne, Vaughn A; Julian, Colleen G; Toledo-Jaldin, Lillian; Cioffi-Ragan, Darleen; Vargas, Enrique; Moore, Lorna G

    2015-03-01

    Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100-4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success.

  12. Fetal sex and race modify the predictors of fetal growth.

    PubMed

    Reynolds, Simone A; Roberts, James M; Bodnar, Lisa M; Haggerty, Catherine L; Youk, Ada O; Catov, Janet M

    2015-04-01

    The objective of this study is unknown if fetal sex and race modify the impact of maternal pre-pregnancy body mass index (BMI), and smoking on fetal growth. The authors studied markers of fetal growth in singleton offspring of 8,801 primiparous, normotensive women, enrolled in the Collaborative Perinatal Project. The authors tested for departures from additivity between sex/race and each predictor. The head-to-chest circumference ratio (HCC) decreased more, while birthweight and ponderal index (PI) increased more for each 1 kg/m(2) increase in pre-pregnancy BMI among term females versus males (P = 0.07, P < 0.01 and P = 0.08, interaction respectively). For term offspring of White compared with Black women, smoking independent of "dose" was associated with larger reductions in growth (165 g vs. 68 g reduction in birthweight, P < 0.01, interaction), greater reduction in fetal placental ratio (P < 0.01, interaction), PI (P < 0.01, interaction), and greater increase in HCC (P = 0.02), respectively. The association of BMI and smoking with fetal size appeared to be reversed in term versus preterm infants. Our study provides evidence that the associations of pre-pregnancy BMI and smoking are not constant across sex and race. This finding may be relevant to sex and race differences in neonatal and long term health outcomes. PMID:25030701

  13. Thyroid hormones in fetal growth and prepartum maturation.

    PubMed

    Forhead, A J; Fowden, A L

    2014-06-01

    The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are essential for normal growth and development of the fetus. Their bioavailability in utero depends on development of the fetal hypothalamic-pituitary-thyroid gland axis and the abundance of thyroid hormone transporters and deiodinases that influence tissue levels of bioactive hormone. Fetal T4 and T3 concentrations are also affected by gestational age, nutritional and endocrine conditions in utero, and placental permeability to maternal thyroid hormones, which varies among species with placental morphology. Thyroid hormones are required for the general accretion of fetal mass and to trigger discrete developmental events in the fetal brain and somatic tissues from early in gestation. They also promote terminal differentiation of fetal tissues closer to term and are important in mediating the prepartum maturational effects of the glucocorticoids that ensure neonatal viability. Thyroid hormones act directly through anabolic effects on fetal metabolism and the stimulation of fetal oxygen consumption. They also act indirectly by controlling the bioavailability and effectiveness of other hormones and growth factors that influence fetal development such as the catecholamines and insulin-like growth factors (IGFs). By regulating tissue accretion and differentiation near term, fetal thyroid hormones ensure activation of physiological processes essential for survival at birth such as pulmonary gas exchange, thermogenesis, hepatic glucogenesis, and cardiac adaptations. This review examines the developmental control of fetal T4 and T3 bioavailability and discusses the role of these hormones in fetal growth and development with particular emphasis on maturation of somatic tissues critical for survival immediately at birth.

  14. Fetal growth potential and pregnancy outcome.

    PubMed

    Bukowski, Radek

    2004-02-01

    Although the association of fetal growth restriction and adverse pregnancy outcomes is well known, lack of sensitivity limits its clinical value. To a large extent, this limitation is a result of traditionally used method to define growth restriction by comparing fetal or birth weight to population norms. The use of population norms, by virtue of their inability to fully consider individual variation, results in high false positive and negative rates. An alternative, calculating fetal individually optimal growth potential, based on physiological determinants of individual growth, is superior in predicting adverse outcomes of pregnancy. Impairment of fetal growth potential identifes some adverse pregnancy outcomes that are not associated with growth restrction defined by population norms. When compared with traditional population-based norms, fetal growth potential is a better predictor of several important adverse outcomes of pregnancy which include: stillbirth, neonatal mortality and morbidity, and long-term adverse neonatal outcomes like neonatal encephalopathy, cerebral palsy and cognitive abilities. Impairment of individual growth potential is also strongly associated with spontaneous preterm delivery. Although definitive interventional trials have not been conducted as yet to validate the clinical value of fetal growth potential, many observational studies, conducted in various populations, indicate its significant promise in this respect.

  15. Fetal growth and neurobehavioral outcomes in childhood.

    PubMed

    Chatterji, Pinka; Lahiri, Kajal; Kim, Dohyung

    2014-12-01

    Using a sample of sibling pairs from a nationally representative U.S. survey, we examine the effects of the fetal growth rate on a set of neurobehavioral outcomes in childhood measured by parent-reported diagnosed developmental disabilities and behavior problems. Based on models that include mother fixed effects, we find that the fetal growth rate, a marker for the fetal environment, is negatively associated with lifetime diagnosis of developmental delay. We also find that the fetal growth rate is negatively associated with disruptive behaviors among male children. These results suggest that developmental disabilities and problem behaviors may play a role in explaining the well-documented association between birth weight and human capital outcomes measured in adulthood. PMID:25464342

  16. Fetal Growth and Neurobehavioral Outcomes in Childhood

    PubMed Central

    Chatterji, Pinka; Lahiri, Kajal; Kim, Dohyung

    2014-01-01

    Using a sample of sibling pairs from a nationally representative U.S. survey, we examine the effects of the fetal growth rate on a set of neurobehavioral outcomes in childhood measured by parent-reported diagnosed developmental disabilities and behavior problems. Based on models that include mother fixed effects, we find that the fetal growth rate, a marker for the fetal environment, is negatively associated with lifetime diagnosis of developmental delay. We also find that the fetal growth rate is negatively associated with disruptive behaviors among male children. These results suggest that developmental disabilities and problem behaviors may play a role in explaining the well-documented association between birth weight and human capital outcomes measured in adulthood. PMID:25464342

  17. Nutritional regulation of the placental lactogen receptor in fetal liver: Implications for fetal metabolism and growth

    SciTech Connect

    Freemark, M.; Comer, M.; Mularoni, T.; D'Ercole, A.J.; Grandis, A.; Kodack, L. )

    1989-09-01

    We have recently identified and purified from fetal liver a distinct receptor that mediates the effects of placental lactogen (PL) on amino acid transport, glycogen synthesis, and somatomedin production in fetal tissues. At present, the factors that regulate the number and affinity of PL receptors in the fetus are unknown. Since maternal nutrition plays a critical role in fetal metabolism and growth, we have examined the role of nutrition in the regulation of the PL receptor in fetal lambs. Pregnant ewes at 123-126 days gestation were fed ad libitum (FED), fasted for 3 days (FASTED), or fasted for 3 days and then refed for an additional 3 days (REFED). The ewes were then killed, and the binding of (125I)ovine (o) PL to hepatic microsomes from the fetal lambs was examined. Maternal fasting caused a 60-75% reduction in the specific binding of oPL to fetal liver; the effect of fasting was reversed in part by refeeding. The decrease in oPL binding resulted from an 80% reduction in the number of fetal oPL-binding sites (Scatchard analysis); there were no changes in the affinity of the oPL receptor (Kd, 0.6 nM), the subunit structure of the receptor, or the degree of occupancy of the receptor in vivo by endogenous fetal hormones. The specific bindings of GH (0.6%), PRL (0.3%), and insulin (35%) to fetal liver were not affected by maternal fasting, indicating that caloric restriction exerted a specific effect on oPL binding in the fetus. The number of fetal oPL-binding sites was positively correlated with the fetal liver glycogen content (r = 0.69; P less than 0.01) and the fetal plasma concentrations of glucose (r = 0.68; P less than 0.01) and insulin-like growth factor-I (r = 0.74; P less than 0.001), suggesting a role for the PL receptor in the regulation of fetal carbohydrate metabolism and growth.

  18. Assessment of fetal growth by customized growth charts.

    PubMed

    Gaillard, Romy; Jaddoe, Vincent W V

    2014-01-01

    Customized fetal growth charts take account of the individual variation in the fetal growth potential based on non-pathological maternal and fetal characteristics. Application of these customized weight charts might improve the distinction between pathological growth-restricted fetuses and fetuses that are small but have reached their growth potential. Current models for customized growth standards have been based on birth weight and fetal growth data. Variables used for customization are gestational age, maternal age, parity, ethnicity, height, weight and fetal sex. Thus far, it remains controversial whether these maternal and fetal characteristics used for customization are strong enough predictors for fetal growth on an individual level and are truly physiological characteristics. The currently available customized growth charts might be of benefit for use in epidemiological studies and clinical practice. Further studies are needed to validate these customized growth models and to examine whether and to what extend they improve identification of children that are at risk for morbidity in the perinatal period and later in life.

  19. Maternal HCV infection is associated with intrauterine fetal growth disturbance

    PubMed Central

    Huang, Qi-tao; Hang, Li-lin; Zhong, Mei; Gao, Yun-fei; Luo, Man-ling; Yu, Yan-hong

    2016-01-01

    Abstract Since the evidence regarding the association between maternal hepatitis C virus (HCV) infection and impaired intrauterine fetal growth had not been conclusive, the aim of the present study was to evaluate the risk of maternal HCV infection in association with intrauterine fetal growth restriction (IUGR) and/or low birth weight infants (LBW). We performed an extensive literature search of PubMed, MEDLINE, and EMBASE through December 1, 2015. The odds ratios (ORs) of HCV infection and IUGR/LBW were calculated and reported with 95% confidence intervals (95% CIs). Statistical analysis was performed using RevMen 5.3 and Stata 10.0. Seven studies involving 4,185,414 participants and 5094 HCV infection cases were included. Significant associations between HCV infection and IUGR (OR = 1.53, 95% CI: 1.40–1.68, fixed effect model) as well as LBW were observed (OR = 1.97, 95% CI: 1.43–2.71, random effect model). The results still indicated consistencies after adjusting for multiple risk factors which could affect fetal growth, including maternal age, parity, maternal smoking, alcohol abuse, drugs abuse, coinfected with HBV/HIV and preeclampsia. Our findings suggested that maternal HCV infection was significantly associated with an increased risk of impaired intrauterine fetal growth. In clinical practice, a closer monitoring of intrauterine fetal growth by a series of ultrasound might be necessary for HCV-infected pregnant population. PMID:27583932

  20. Placental adaptations to the maternal-fetal environment: implications for fetal growth and developmental programming.

    PubMed

    Sandovici, Ionel; Hoelle, Katharina; Angiolini, Emily; Constância, Miguel

    2012-07-01

    The placenta is a transient organ found in eutherian mammals that evolved primarily to provide nutrients for the developing fetus. The placenta exchanges a wide array of nutrients, endocrine signals, cytokines and growth factors with the mother and the fetus, thereby regulating intrauterine development. Recent studies show that the placenta is not just a passive organ mediating maternal-fetal exchange. It can adapt its capacity to supply nutrients in response to intrinsic and extrinsic variations in the maternal-fetal environment. These dynamic adaptations are thought to occur to maximize fetal growth and viability at birth in the prevailing conditions in utero. However, some of these adaptations may also affect the development of individual fetal tissues, with patho-physiological consequences long after birth. Here, this review summarizes current knowledge on the causes, possible mechanisms and consequences of placental adaptive responses, with a focus on the regulation of transporter-mediated processes for nutrients. This review also highlights the emerging roles that imprinted genes and epigenetic mechanisms of gene regulation may play in placental adaptations to the maternal-fetal environment.

  1. Enalapril decreases cardiac mass and fetal gene expression without affecting the expression of endothelin-1, transforming growth factor β-1, or cardiotrophin-1 in the healthy normotensive rat.

    PubMed

    Mackovicova, Katarina; Gazova, Andrea; Kucerova, Dana; Gajdacova, Beata; Klimas, Jan; Ochodnicky, Peter; Goncalvesova, Eva; Kyselovic, Jan; Krenek, Peter

    2011-03-01

    Angiotensin II can induce cardiac hypertrophy by stimulating the release of growth factors. ACE inhibitors reduce angiotensin II levels and cardiac hypertrophy, but their effects on the healthy heart are largely unexplored. We hypothesized that ACE inhibition decreases left ventricular mass in normotensive animals and that this is associated with altered expression of cardiac fetal genes, growth factors, and endothelial nitric oxide synthase (eNOS). Wistar rats (n = 7 per group) were orally administered with enalapril twice daily for a total daily dose of 5 mg·kg(-1)·d(-1) (ENAP5) or 15 mg·kg(-1)·d(-1) (ENAP15) or vehicle. Systolic blood pressure was measured by the tail-cuff method. Left ventricular expression of cardiac myosin heavy chain-α (MYH6) and -β (MYH7), atrial natriuretic peptide (ANP), endothelin-1 (ET-1), transforming growth factor β-1 (TGFβ-1), cardiotrophin-1 (CT-1), and renal renin were examined by real-time PCR, and eNOS using Western blot. Blood pressure was decreased only in ENAP15 animals (p < 0.05 vs. Control), whereas left ventricular mass decreased after both doses of enalapril (p < 0.05 vs. Control). MYH7 and ANP were reduced in ENAP15, while no changes in ET-1, TGFβ-1, CT-1, and MYH6 mRNA or eNOS protein were observed. Renal renin dose-dependently increased after enalapril treatment. Enalapril significantly decreased left ventricular mass even after 1 week treatment in the normotensive rat. This was associated with a decreased expression of the fetal genes MYH7 and ANP, but not expression of ET-1, CT-1, or TGFβ-1. PMID:21423293

  2. Consanguinity and fetal growth in Pakistani Moslems.

    PubMed

    Honeyman, M M; Bahl, L; Marshall, T; Wharton, B A

    1987-03-01

    There is conflicting evidence about the effect of parental consanguinity on fetal growth. Previous studies have not always allowed for other factors that are known to affect birth weight, in particular, gestational age, parity, and maternal height. We have therefore studied this question in the Pakistani Moslem population in Birmingham. Babies born to parents who were first cousins were on average 80 g lighter than those born to unrelated parents, but this difference was not significant for the size of the sample studied. Nor were there any differences in the other measurements of the babies. After expressing birth weight in terms of centiles for gestational age, sex, parity, and maternal height, however, while there was no difference in the overall distribution of centiles, there were more poorly grown babies--that is, weight below the 10th centile--in the first cousin group. We conclude that parental consanguinity is associated with an increase in the number of poorly grown babies but that the overall effect on mean birth weight is small. PMID:3566315

  3. Sexual dimorphism in epigenomic responses of stem cells to extreme fetal growth.

    PubMed

    Delahaye, Fabien; Wijetunga, N Ari; Heo, Hye J; Tozour, Jessica N; Zhao, Yong Mei; Greally, John M; Einstein, Francine H

    2014-10-10

    Extreme fetal growth is associated with increased susceptibility to a range of adult diseases through an unknown mechanism of cellular memory. We tested whether heritable epigenetic processes in long-lived CD34(+) haematopoietic stem/progenitor cells showed evidence for re-programming associated with the extremes of fetal growth. Here we show that both fetal growth restriction and over-growth are associated with global shifts towards DNA hypermethylation, targeting cis-regulatory elements in proximity to genes involved in glucose homeostasis and stem cell function. We find a sexually dimorphic response; intrauterine growth restriction is associated with substantially greater epigenetic dysregulation in males, whereas large for gestational age growth predominantly affects females. The findings are consistent with extreme fetal growth interacting with variable fetal susceptibility to influence cellular ageing and metabolic characteristics through epigenetic mechanisms, potentially generating biomarkers that could identify infants at higher risk for chronic disease later in life.

  4. Sexual dimorphism in epigenomic responses of stem cells to extreme fetal growth.

    PubMed

    Delahaye, Fabien; Wijetunga, N Ari; Heo, Hye J; Tozour, Jessica N; Zhao, Yong Mei; Greally, John M; Einstein, Francine H

    2014-01-01

    Extreme fetal growth is associated with increased susceptibility to a range of adult diseases through an unknown mechanism of cellular memory. We tested whether heritable epigenetic processes in long-lived CD34(+) haematopoietic stem/progenitor cells showed evidence for re-programming associated with the extremes of fetal growth. Here we show that both fetal growth restriction and over-growth are associated with global shifts towards DNA hypermethylation, targeting cis-regulatory elements in proximity to genes involved in glucose homeostasis and stem cell function. We find a sexually dimorphic response; intrauterine growth restriction is associated with substantially greater epigenetic dysregulation in males, whereas large for gestational age growth predominantly affects females. The findings are consistent with extreme fetal growth interacting with variable fetal susceptibility to influence cellular ageing and metabolic characteristics through epigenetic mechanisms, potentially generating biomarkers that could identify infants at higher risk for chronic disease later in life. PMID:25300954

  5. Sexual dimorphism in epigenomicresponses of stem cells to extreme fetal growth

    PubMed Central

    Delahaye, Fabien; Wijetunga, N. Ari; Heo, Hye J.; Tozour, Jessica N.; Zhao, Yong Mei; Greally, John M.; Einstein, Francine H.

    2014-01-01

    Extreme fetal growth is associated with increased susceptibility to a range of adult diseases through an unknown mechanism of cellular memory. We tested whether heritable epigenetic processes in long-lived CD34+ hematopoietic stem/progenitor cells (HSPCs) showed evidence for re-programming associated with the extremes of fetal growth. Here we show that both fetal growth restriction and over-growth are associated with global shifts towards DNA hypermethylation, targeting cis-regulatory elements in proximity to genes involved in glucose homeostasis and stem cell function. We find a sexually dimorphic response; intrauterine growth restriction (IUGR) is associated with substantially greater epigenetic dysregulation in males, whereas large for gestational age (LGA) growth predominantly affects females. The findings are consistent with extreme fetal growth interacting with variable fetal susceptibility to influence cellular aging and metabolic characteristics through epigenetic mechanisms, potentially generating biomarkers that could identify infants at higher risk for chronic disease later in life. PMID:25300954

  6. Psychosocial factors and intrauterine fetal growth: a prospective study.

    PubMed

    Aarts, M C; Vingerhoets, A J

    1993-12-01

    This study focused on the possible role of psychosocial factors on intrauterine fetal growth. Pregnant women (n = 236) completed questionnaires on daily stressors and psychosomatic symptoms three times during pregnancy; in the 11-12th week, the 23-24th week and the 35-36th week. In addition, information was obtained on the quality of the marital relationship, social support, social class, physical work load, weight of the biological parents and life-style variables (including smoking, alcohol and coffee consumption). Birth weight corrected for gestational age, sex and parity was utilized as an index of intrauterine fetal growth. This dependent measure did not appear to be affected by exposure to daily stressors or disturbed maternal well-being on any of the measuring points. Smoking appeared to be the best predictor of fetal growth, together with maternal weight and the family's socioeconomic status. These variables accounted for 10.6% of the variance. It is postulated that the absence of a relationship between stressors and fetal development may be due to the buffering effects of adequate emotional support provided by the partners and the further social network. PMID:8142979

  7. A review of contemporary modalities for identifying abnormal fetal growth.

    PubMed

    O'Connor, C; Stuart, B; Fitzpatrick, C; Turner, M J; Kennelly, M M

    2013-04-01

    Detecting aberrant fetal growth has long been an important goal of modern obstetrics. Failure to diagnose abnormal fetal growth results in perinatal morbidity or mortality. However, the erroneous diagnosis of abnormal growth may lead to increased maternal anxiety and unnecessary obstetric interventions. We review the aetiology of deviant fetal growth and its implications both for the neonatal period and later in adult life. We examine maternal factors that may influence fetal growth such as obesity, glycaemic control and body composition. We discuss novel ways to improve our detection of abnormal fetal growth with a view to optimising antenatal care and clinical outcomes. These include using customised centiles or individualised growth assessment methods to improve accuracy. The role of fetal subcutaneous measurements as a surrogate marker of the nutritional status of the baby is also discussed. Finally, we investigate the role of Doppler measurements in identifying growth-restricted babies.

  8. Impact of placental insufficiency on fetal skeletal muscle growth.

    PubMed

    Brown, Laura D; Hay, William W

    2016-11-01

    Intrauterine growth restriction (IUGR) caused by placental insufficiency is one of the most common and complex problems in perinatology, with no known cure. In pregnancies affected by placental insufficiency, a poorly functioning placenta restricts nutrient supply to the fetus and prevents normal fetal growth. Among other significant deficits in organ development, the IUGR fetus characteristically has less lean body and skeletal muscle mass than their appropriately-grown counterparts. Reduced skeletal muscle growth is not fully compensated after birth, as individuals who were born small for gestational age (SGA) from IUGR have persistent reductions in muscle mass and strength into adulthood. The consequences of restricted muscle growth and accelerated postnatal "catch-up" growth in the form of adiposity may contribute to the increased later life risk for visceral adiposity, peripheral insulin resistance, diabetes, and cardiovascular disease in individuals who were formerly IUGR. This review will discuss how an insufficient placenta results in impaired fetal skeletal muscle growth and how lifelong reductions in muscle mass might contribute to increased metabolic disease risk in this vulnerable population.

  9. Human fetal growth and organ development: 50 years of discoveries.

    PubMed

    Pardi, Giorgio; Cetin, Irene

    2006-04-01

    Knowledge about human fetal growth and organ development has greatly developed in the last 50 years. Anatomists and physiologists had already described some crucial aspects, for example, the circulation of blood during intrauterine life through the fetal heart, the liver as well as the placenta. However, only in the last century physiologic studies were performed in animal models. In the human fetus, the introduction of ultrasound and Doppler velocimetry has provided data about the growth and development of the fetus and of the circulation through the different fetal districts. Moreover, in the last 2 decades we have learned about fetal oxygenation and fetal nutrient supply caused by the availability of fetal blood samples obtained under relatively steady state conditions. These studies, together with studies using stable isotope methodologies, have clarified some aspects of the supply of the major nutrients for the fetus such as glucose, amino acids, and fatty acids. At the same time, the relevance of placental function has been recognized as a major determinant of fetal diseases leading to intrauterine growth restriction. More recently, the availability of new tools such as 3-dimensional ultrasound and magnetic resonance imaging, have made possible the evaluation of the growth and development of fetal organs. This knowledge in the healthy fetus will improve the ability of clinicians to recognize abnormal phenotypes of the different fetal organs, thus allowing to stage fetal diseases.

  10. Maternal Stress and Affect Influence Fetal Neurobehavioral Development.

    ERIC Educational Resources Information Center

    DiPietro, Janet A.; Hilton, Sterling C.; Hawkins, Melissa; Costigan, Kathleen A.; Pressman, Eva K.

    2002-01-01

    Investigated associations between maternal psychological and fetal neurobehavioral functioning with data provided at 24, 30, and 36 weeks gestation. Found that fetuses of women who were more affectively intense, appraised their lives as more stressful, and reported more pregnancy-specific hassles were more active across gestation. Fetuses of women…

  11. Malaria and Fetal Growth Alterations in the 3rd Trimester of Pregnancy: A Longitudinal Ultrasound Study

    PubMed Central

    Schmiegelow, Christentze; Minja, Daniel; Oesterholt, Mayke; Pehrson, Caroline; Suhrs, Hannah Elena; Boström, Stéphanie; Lemnge, Martha; Magistrado, Pamela; Rasch, Vibeke; Nielsen, Birgitte Bruun; Lusingu, John; Theander, Thor G.

    2013-01-01

    Background Pregnancy associated malaria is associated with decreased birth weight, but in-utero evaluation of fetal growth alterations is rarely performed. The objective of this study was to investigate malaria induced changes in fetal growth during the 3rd trimester using trans-abdominal ultrasound. Methods An observational study of 876 pregnant women (398 primi- and secundigravidae and 478 multigravidae) was conducted in Tanzania. Fetal growth was monitored with ultrasound and screening for malaria was performed regularly. Birth weight and fetal weight were converted to z-scores, and fetal growth evaluated as fetal weight gain from the 26th week of pregnancy. Results Malaria infection only affected birth weight and fetal growth among primi- and secundigravid women. Forty-eight of the 398 primi- and secundigravid women had malaria during pregnancy causing a reduction in the newborns z-score of −0.50 (95% CI: −0.86, −0.13, P = 0.008, multiple linear regression). Fifty-eight percent (28/48) of the primi- and secundigravidae had malaria in the first half of pregnancy, but an effect on fetal growth was observed in the 3rd trimester with an OR of 4.89 for the fetal growth rate belonging to the lowest 25% in the population (95%CI: 2.03–11.79, P<0.001, multiple logistic regression). At an individual level, among the primi- and secundigravidae, 27% experienced alterations of fetal growth immediately after exposure but only for a short interval, 27% only late in pregnancy, 16.2% persistently from exposure until the end of pregnancy, and 29.7% had no alterations of fetal growth. Conclusions The effect of malaria infections was observed during the 3rd trimester, despite infections occurring much earlier in pregnancy, and different mechanisms might operate leading to different patterns of growth alterations. This study highlights the need for protection against malaria throughout pregnancy and the recognition that observed changes in fetal growth might be a

  12. Effects of Environmental Exposures on Fetal and Childhood Growth Trajectories.

    PubMed

    Zheng, Tongzhang; Zhang, Jie; Sommer, Kathryn; Bassig, Bryan A; Zhang, Xichi; Braun, Jospeh; Xu, Shuangqing; Boyle, Peter; Zhang, Bin; Shi, Kunchong; Buka, Stephen; Liu, Siming; Li, Yuanyuan; Qian, Zengmin; Dai, Min; Romano, Megan; Zou, Aifen; Kelsey, Karl

    2016-01-01

    Delayed fetal growth and adverse birth outcomes are some of the greatest public health threats to this generation of children worldwide because these conditions are major determinants of mortality, morbidity, and disability in infancy and childhood and are also associated with diseases in adult life. A number of studies have investigated the impacts of a range of environmental conditions during pregnancy (including air pollution, endocrine disruptors, persistent organic pollutants, heavy metals) on fetal and child development. The results, while provocative, have been largely inconsistent. This review summarizes up to date epidemiologic studies linking major environmental pollutants to fetal and child development and suggested future directions for further investigation. PMID:27325067

  13. [Effect of bee pollen on maternal nutrition and fetal growth].

    PubMed

    Xie, Y; Wan, B; Li, W

    1994-12-01

    Plant pollen collected by the honeybee is called bee pollen, which is a natural nutrient. We studied the effects of the bee pollen of Brassia campestres L. on maternal nutrition and fetal growth. Pregnant Sprague-Dawley rats at O-d were divided randomly into three groups. The control group (C) was fed with a diet. The other two groups (A) and (B) were fed with the diet plus bee pollen 20 g/kg.d-1 and 10 g/kg.d-1, respectively. All the dams in each group took a diet and drank water and libitm. Pollen-fed dams in both groups (A) and (B) had greater body weight and higher levels of haemoglobin, total protein, serum iron and albumin (P < 0.01, P < 0.05). Fetuses of pollen-fed dams had greater body weight (P < 0.01) and lower death rate (P < 0.005). No gross external, visceral and skeletal malformations were observed in the fetuses. These results suggested that bee pollen could improve maternal nutrition without affecting normal fetal development. It is a practical and effective nutrient during pregnancy.

  14. Placental Responses to Changes in the Maternal Environment Determine Fetal Growth

    PubMed Central

    Dimasuay, Kris Genelyn; Boeuf, Philippe; Powell, Theresa L.; Jansson, Thomas

    2016-01-01

    Placental responses to maternal perturbations are complex and remain poorly understood. Altered maternal environment during pregnancy such as hypoxia, stress, obesity, diabetes, toxins, altered nutrition, inflammation, and reduced utero-placental blood flow may influence fetal development, which can predispose to diseases later in life. The placenta being a metabolically active tissue responds to these perturbations by regulating the fetal supply of nutrients and oxygen and secretion of hormones into the maternal and fetal circulation. We have proposed that placental nutrient sensing integrates maternal and fetal nutritional cues with information from intrinsic nutrient sensing signaling pathways to balance fetal demand with the ability of the mother to support pregnancy by regulating maternal physiology, placental growth, and placental nutrient transport. Emerging evidence suggests that the nutrient-sensing signaling pathway mechanistic target of rapamycin (mTOR) plays a central role in this process. Thus, placental nutrient sensing plays a critical role in modulating maternal–fetal resource allocation, thereby affecting fetal growth and the life-long health of the fetus. PMID:26858656

  15. Prenatal diagnosis of a placental infarction hematoma associated with fetal growth restriction, preeclampsia and fetal death: clinicopathological correlation.

    PubMed

    Aurioles-Garibay, Alma; Hernandez-Andrade, Edgar; Romero, Roberto; Qureshi, Faisal; Ahn, Hyunyoung; Jacques, Suzanne M; Garcia, Maynor; Yeo, Lami; Hassan, Sonia S

    2014-01-01

    The lesion termed 'placental infarction hematoma' is associated with fetal death and adverse perinatal outcome. Such a lesion has been associated with a high risk of fetal death and abruption placentae. The fetal and placental hemodynamic changes associated with placental infarction hematoma have not been reported. This paper describes a case of early and severe growth restriction with preeclampsia, and progressive deterioration of the fetal and placental Doppler parameters in the presence of a placental infarction hematoma.

  16. Impaired fetal thymic growth precedes clinical preeclampsia: a case-control study.

    PubMed

    Eviston, David P; Quinton, Ann E; Benzie, Ron J; Peek, Michael J; Martin, Andrew; Nanan, Ralph K

    2012-06-01

    In preeclampsia the maternal adaptive immune system undergoes specific changes, which are different from the physiological processes associated with healthy pregnancy. Whether preeclampsia also affects the fetal immune system is difficult to investigate, due to limited access to the fetus. We hypothesized that if preeclampsia affects the fetal adaptive immune system this might be associated with early changes in thymic growth. In this case-control study, 53 preeclamptic and 120 healthy control pregnancies were matched for maternal age, gestational age and smoking. Fetal thymus diameter was measured as the greatest width perpendicular to a line connecting sternum and spine based on ultrasound images taken at 17-21 weeks gestation. Independent of fetal and maternal anthropometric measures, thymuses were found to be smaller in preeclamptic pregnancies than healthy controls (16.2 mm versus 18.3 mm, respectively, mean difference=2.1 mm, 95% CI: 0.8-3.3, p<0.001), and the odds of developing preeclampsia was estimated to be 0.72 (95% CI: 0.60-0.86, p<0.001) lower for each 1 mm increase in thymus diameter. There was no correlation between the onset of preeclampsia and fetal thymus size. This is the first study to suggest that fetal thymus growth is reduced before the clinical onset of preeclampsia and precedes any described fetal anomalies or maternal immunological changes associated with preeclampsia. We propose that the fetal adaptive immune system is either passively affected by maternal processes preceding clinical preeclampsia or is actively involved in initiating preeclampsia in later pregnancy.

  17. Fetal growth in muskoxen determined by transabdominal ultrasonography.

    PubMed

    Pharr, J W; Rowell, J E; Flood, P F

    1994-07-01

    A 5 MHz commercial sector scanner was used to monitor 13 muskox pregnancies and establish normal fetal growth curves. Examinations were carried out between 40 and 197 days of gestation and pregnancy could be detected throughout the period. Early pregnancies were found by scanning lateral to the udder but as pregnancy progressed the fetus was found closer to the dam's umbilicus. Measurements of cranial and abdominal diameters taken at about two week intervals in seven uncomplicated pregnancies in four cows were used to construct fetal growth curves. These can be reliably used in the reproductive management of muskoxen. In addition a series of regressions based on measurements of the fetuses of muskoxen killed in the Arctic are provided. These allow cranial and abdominal diameters to be related to fetal weight and crown-rump length. PMID:7954117

  18. Growth curve analysis of placental and fetal growth influenced by adjacent fetal sex status under crowded uterine conditions in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Intrauterine position and sex of adjacent fetuses in litter bearing species have been implicated in physiological and behavioral differences in males and females. Our objective was to establish growth curves for fetal and placental weight gain as influenced by sex status of flanking fetuses under cr...

  19. Fetal Genotype for the Xenobiotic Metabolizing Enzyme "NQO1" Influences Intrauterine Growth among Infants Whose Mothers Smoked during Pregnancy

    ERIC Educational Resources Information Center

    Price, Thomas S.; Grosser, Tilo; Plomin, Robert; Jaffee, Sara R.

    2010-01-01

    Maternal smoking during pregnancy retards fetal growth and depresses infant birth weight. The magnitude of these effects may be moderated by fetal genotype. The current study investigated maternal smoking, fetal genotype, and fetal growth in a large population sample of dizygotic twins. Maternal smoking retarded fetal growth in a dose-dependent…

  20. Increased fetal myocardial sensitivity to insulin-stimulated glucose metabolism during ovine fetal growth restriction

    PubMed Central

    Barry, James S; Rozance, Paul J; Brown, Laura D; Anthony, Russell V; Thornburg, Kent L

    2016-01-01

    Unlike other visceral organs, myocardial weight is maintained in relation to fetal body weight in intrauterine growth restriction (IUGR) fetal sheep despite hypoinsulinemia and global nutrient restriction. We designed experiments in fetal sheep with placental insufficiency and restricted growth to determine basal and insulin-stimulated myocardial glucose and oxygen metabolism and test the hypothesis that myocardial insulin sensitivity would be increased in the IUGR heart. IUGR was induced by maternal hyperthermia during gestation. Control (C) and IUGR fetal myocardial metabolism were measured at baseline and under acute hyperinsulinemic/euglycemic clamp conditions at 128–132 days gestation using fluorescent microspheres to determine myocardial blood flow. Fetal body and heart weights were reduced by 33% (P = 0.008) and 30% (P = 0.027), respectively. Heart weight to body weight ratios were not different. Basal left ventricular (LV) myocardial blood flow per gram of LV tissue was maintained in IUGR fetuses compared to controls. Insulin increased LV myocardial blood flow by ∼38% (P < 0.01), but insulin-stimulated LV myocardial blood flow in IUGR fetuses was 73% greater than controls. Similar to previous reports testing acute hypoxia, LV blood flow was inversely related to arterial oxygen concentration (r2 = 0.71) in both control and IUGR animals. Basal LV myocardial glucose delivery and uptake rates were not different between IUGR and control fetuses. Insulin increased LV myocardial glucose delivery (by 40%) and uptake (by 78%) (P < 0.01), but to a greater extent in the IUGR fetuses compared to controls. During basal and hyperinsulinemic–euglycemic clamp conditions LV myocardial oxygen delivery, oxygen uptake, and oxygen extraction efficiency were not different between groups. These novel results demonstrate that the fetal heart exposed to nutrient and oxygen deprivation from placental insufficiency appears to maintain myocardial energy

  1. Extrinsic Factors Influencing Fetal Deformations and Intrauterine Growth Restriction

    PubMed Central

    Moh, Wendy; Graham, John M.; Wadhawan, Isha; Sanchez-Lara, Pedro A.

    2012-01-01

    The causes of intrauterine growth restriction (IUGR) are multifactorial with both intrinsic and extrinsic influences. While many studies focus on the intrinsic pathological causes, the possible long-term consequences resulting from extrinsic intrauterine physiological constraints merit additional consideration and further investigation. Infants with IUGR can exhibit early symmetric or late asymmetric growth abnormality patterns depending on the fetal stage of development, of which the latter is most common occurring in 70–80% of growth-restricted infants. Deformation is the consequence of extrinsic biomechanical factors interfering with normal growth, functioning, or positioning of the fetus in utero, typically arising during late gestation. Biomechanical forces play a critical role in the normal morphogenesis of most tissues. The magnitude and direction of force impact the form of the developing fetus, with a specific tissue response depending on its pliability and stage of development. Major uterine constraining factors include primigravida, small maternal size, uterine malformation, uterine fibromata, early pelvic engagement of the fetal head, aberrant fetal position, oligohydramnios, and multifetal gestation. Corrective mechanical forces similar to those that gave rise to the deformation to reshape the deformed structures are often used and should take advantage of the rapid postnatal growth to correct form. PMID:22888434

  2. Acidic fibroblast growth factor and keratinocyte growth factor stimulate fetal rat pulmonary epithelial growth.

    PubMed

    Deterding, R R; Jacoby, C R; Shannon, J M

    1996-10-01

    We have shown that pulmonary epithelial growth and differentiation can occur if pulmonary mesenchyme is replaced with a mixture of growth factors [total growth medium (TGM)] that consists of adult rat bronchoalveolar lavage fluid, insulin, epidermal growth factor (EGF), cholera toxin (CT), acidic fibroblast growth factor (aFGF), and fetal bovine serum. In the present study, we have defined the importance of specific components of TGM. Day 14 fetal rat distal lung epithelium, devoid of mesenchyme, was enrobed in growth factor-depleted Matrigel and cultured for 5 days in various soluble factors. We found that deleting aFGF or CT from TGM significantly reduced DNA synthesis. Epithelial proliferation was not significantly different when keratinocyte growth factor (KGF) replaced aFGF in TGM. KGF, however, required the presence of a basal medium containing CT, insulin, and serum for optimal proliferation. We then added specific growth factors to the basal medium and showed that aFGF and KGF were more potent mitogens than EGF, transforming growth factor-alpha, and hepatocyte growth factor. Additionally, basal medium + KGF also allowed progression to a distal alveolar phenotype. We conclude that aFGF and KGF may be important mediators in epithelial-mesenchymal interactions. PMID:8897895

  3. Maternal parity, fetal and childhood growth, and cardiometabolic risk factors.

    PubMed

    Gaillard, Romy; Rurangirwa, Akashi A; Williams, Michelle A; Hofman, Albert; Mackenbach, Johan P; Franco, Oscar H; Steegers, Eric A P; Jaddoe, Vincent W V

    2014-08-01

    We examined the associations of maternal parity with fetal and childhood growth characteristics and childhood cardiometabolic risk factors in a population-based prospective cohort study among 9031 mothers and their children. Fetal and childhood growth were repeatedly measured. We measured childhood anthropometrics, body fat distribution, left ventricular mass, blood pressure, blood lipids, and insulin levels at the age of 6 years. Compared with nulliparous mothers, multiparous mothers had children with higher third trimester fetal head circumference, length and weight growth, and lower risks of preterm birth and small-size-for-gestational-age at birth but a higher risk of large-size-for-gestational-age at birth (P<0.05). Children from multiparous mothers had lower rates of accelerated infant growth and lower levels of childhood body mass index, total fat mass percentage, and total and low-density lipoprotein cholesterol than children of nulliparous mothers (P<0.05). They also had a lower risk of childhood overweight (odds ratio, 0.75 [95% confidence interval, 0.63–0.88]). The risk of childhood clustering of cardiometabolic risk factors was not statistically significantly different (odds ratio, 0.82; 95% confidence interval, 0.64–1.05). Among children from multiparous mothers only, we observed consistent trends toward a lower risk of childhood overweight and lower cholesterol levels with increasing parity (P<0.05). In conclusion, offspring from nulliparous mothers have lower fetal but higher infant growth rates and higher risks of childhood overweight and adverse metabolic profile. Maternal nulliparity may have persistent cardiometabolic consequences for the offspring. PMID:24866145

  4. Fetal cell-free DNA fraction in maternal plasma is affected by fetal trisomy.

    PubMed

    Suzumori, Nobuhiro; Ebara, Takeshi; Yamada, Takahiro; Samura, Osamu; Yotsumoto, Junko; Nishiyama, Miyuki; Miura, Kiyonori; Sawai, Hideaki; Murotsuki, Jun; Kitagawa, Michihiro; Kamei, Yoshimasa; Masuzaki, Hideaki; Hirahara, Fumiki; Saldivar, Juan-Sebastian; Dharajiya, Nilesh; Sago, Haruhiko; Sekizawa, Akihiko

    2016-07-01

    The purpose of this noninvasive prenatal testing (NIPT) study was to compare the fetal fraction of singleton gestations by gestational age, maternal characteristics and chromosome-specific aneuploidies as indicated by z-scores. This study was a multicenter prospective cohort study. Test data were collected from women who underwent NIPT by the massively parallel sequencing method. We used sequencing-based fetal fraction calculations in which we estimated fetal DNA fraction by simply counting the number of reads aligned within specific autosomal regions and applying a weighting scheme derived from a multivariate model. Relationships between fetal fractions and gestational age, maternal weight and height, and z-scores for chromosomes 21, 18 and 13 were assessed. A total of 7740 pregnant women enrolled in the study, of which 6993 met the study criteria. As expected, fetal fraction was inversely correlated with maternal weight (P<0.001). The median fetal fraction of samples with euploid result (n=6850) and trisomy 21 (n=70) were 13.7% and 13.6%, respectively. In contrast, the median fetal fraction values for samples with trisomies 18 (n=35) and 13 (n=9) were 11.0% and 8.0%, respectively. The fetal fraction of samples with trisomy 21 NIPT result is comparable to that of samples with euploid result. However, the fetal fractions of samples with trisomies 13 and 18 are significantly lower compared with that of euploid result. We conclude that it may make detecting these two trisomies more challenging. PMID:26984559

  5. Genotype and fetal size affect maternal-fetal amino acid status and fetal endocrinology in Large White × Landrace and Meishan pigs.

    PubMed

    Ashworth, Cheryl J; Nwagwu, Margaret O; McArdle, Harry J

    2013-01-01

    This study compared maternal plasma amino acid concentrations, placental protein secretion in vitro and fetal body composition and plasma amino acid and hormone concentrations in feto-placental units from the smallest and a normally-sized fetus carried by Large White × Landrace or Meishan gilts on Day 100 of pregnancy. Compared with Large White × Landrace, Meishan placental tissue secreted more protein and Meishan fetuses contained relatively more fat and protein, but less moisture. Fetal plasma concentrations of insulin, triiodothryonine, thyroxine and insulin-like growth factor (IGF)-II were higher in Meishan than Large White × Landrace fetuses. In both breeds, fetal cortisol concentrations were inversely related to fetal size, whereas concentrations of IGF-I were higher in average-sized fetuses. Concentrations of 10 amino acids were higher in Large White × Landrace than Meishan gilts, while glutamine concentrations were higher in Meishan gilts. Concentrations of alanine, aspartic acid, glutamic acid and threonine were higher in Meishan than Large White × Landrace fetuses. Average-sized fetuses had higher concentrations of asparagine, leucine, lysine, phenylalanine, threonine, tyrosine and valine than the smallest fetus. This study revealed novel genotype and fetal size differences in porcine maternal-fetal amino acid status and fetal hormone and metabolite concentrations.

  6. Fetal ADH2*3, maternal alcohol consumption, and fetal growth.

    PubMed

    Arfsten, Darryl P; Silbergeld, Ellen K; Loffredo, Christopher A

    2004-01-01

    There is some evidence suggesting the allele for alcohol dehydrogenase 2*3 (ADH2*3) is associated with a protective effect against alcohol-related intrauterine growth retardation (IUGR). This study was conducted to explore the affect of the ADH2*3 allele on fetal growth. Bloodspots (n = 1016) belonging to individual infants of a subgroup of the Baltimore-Washington Infant Study (BWIS) were assayed for the presence of the ADH2*3 allele by a polymerase chain reaction (PCR)-based method. Infants genotyped for ADH2*3 were those for whom bloodspots were identified and obtained from the Maryland Newborn Screening Program. The effect of ADH2*3 and maternal alcohol consumption on intrauterine growth was explored by multivariable linear regression analysis. Twenty-six percent of the 306 blood spots belonging to African-American infants were positive for ADH2*3 (4% were homozygous and 22% were heterozygous). Only a small percentage of bloodspots for Caucasian (1.3%) were positive for the ADH2*3 allele. Consequently, further analysis concentrated on gene-exposure interactions for African-American infants. It was found that the incidence of being small-for-gestation-age (SGA) was lower for ADH2*3-positive infants (2.5% versus 8.8%; p = .08). SGA infants had elevated odds for being ADH2*3 negative (OR: 3.15, 95% C.I.: 0.70-14.26) and for being born to mothers that consumed alcohol during pregnancy (OR: 2.31, 95% C.I.: 0.77-6.91). A negative trend between maternal alcohol consumption and mean offspring birthweight was found; however, ADH2*3 did not have a significant impact on mean birthweight for infants born to mothers that drank during pregnancy. These results could be interpreted as possible support for the hypothesis that ADH2 genotype in the infant may impact risk for alcohol-related IUGR. However, this study has limitations in that it is a "nested study of convenience" and involves a relatively small number of infants born to mothers reporting moderate to heavy alcohol

  7. Intrauterine growth restriction: effects of physiological fetal growth determinants on diagnosis.

    PubMed

    Haram, Kjell; Søfteland, Eirik; Bukowski, Radek

    2013-01-01

    The growth of the fetus, which is strongly associated with the outcome of pregnancy, reflects interplay of several physiological and pathological factors. The assessment of fetal growth is based on comparison of birthweight (BW) or estimated fetal weight (EFW) to standards which define reference ranges at a spectrum of gestational ages. Most birthweight standards do not take into account effects of physiological determinants of fetal growth. Additionally, gestational age in many standards is based on the menstrual history and is often inaccurate. Fetal growth norms should be based on an early ultrasound estimate of gestational age. Customized standards, which have included only ultrasound-dated pregnancies, seem to be superior to population-based birthweight norms in predicting perinatal mortality and morbidity. Adjustment for individual variation in customized growth curves reduces false-positive diagnosis of IUGR and may lead to a very significant reduction in intervention for suspected IUGR. Customized growth potential identifies better the risk for adverse outcome than the currently used national standards, but customized charts may fail in detecting growth-restricted stillbirth. An individual's birthweight is the sum of physiological and pathological influences operating during pregnancy. Growth potential norms are a better discriminator of aberrations of fetal growth than population, ultrasound, and customized norms.

  8. NOTE: Trends of discordant fetal growth in monochorionic twin pregnancies

    NASA Astrophysics Data System (ADS)

    van Gemert, Martin J. C.; Umur, Asli

    2000-08-01

    We derived simple analytical relations representing trends of discordant fetal growth in monochorionic twins developing the twin-twin transfusion syndrome from an approximation of previously developed model equations. In severe twin-twin transfusion syndrome cases, the difference between the estimated fetal weights of both twins increases proportional to (t-5)5 (t denotes gestational age in weeks) and the sum of both weights increases proportional to t3. Hence, the ratio between the difference of estimated fetal weights and the average of the two weights (difference average ratio) increases in proportion to (t-5)5/t3. In mild cases, the difference between estimated fetal weights as well as the sum of the two weights increases proportional to t3. Therefore, the difference average ratio becomes a constant. Comparison with clinical data of severe and mild cases showed surprisingly good agreement except after laser coagulation of placental anastomoses. These relations may therefore enable us to distinguish between severe and mild developing twin-twin transfusion syndrome cases.

  9. IGF2 DNA methylation is a modulator of newborn's fetal growth and development.

    PubMed

    St-Pierre, Julie; Hivert, Marie-France; Perron, Patrice; Poirier, Paul; Guay, Simon-Pierre; Brisson, Diane; Bouchard, Luigi

    2012-10-01

    The insulin-like growth factor 2 (IGF2) gene, located within a cluster of imprinted genes on chromosome 11p15, encodes a fetal and placental growth factor affecting birth weight. DNA methylation variability at the IGF2 gene locus has been previously reported but its consequences on fetal growth and development are still mostly unknown in normal pediatric population. We collected one hundred placenta biopsies from 50 women with corresponding maternal and cord blood samples and measured anthropometric indices, blood pressure and metabolic phenotypes using standardized procedures. IGF2/H19 DNA methylation and IGF2 circulating levels were assessed using sodium bisulfite pyrosequencing and ELISA, respectively. Placental IGF2 (DMR0 and DMR2) DNA methylation levels were correlated with newborn's fetal growth indices, such as weight, and with maternal IGF2 circulating concentration at the third trimester of pregnancy, whereas H19 (DMR) DNA methylation levels were correlated with IGF2 levels in cord blood. The maternal genotype of a known IGF2/H19 polymorphism (rs2107425) was associated with birth weight. Taken together, we showed that IGF2/H19 epigenotype and genotypes independently account for 31% of the newborn's weight variance. No association was observed with maternal diabetic status, glucose concentrations or prenatal maternal body mass index. This is the first study showing that DNA methylation at the IGF2/H19 genes locus may act as a modulator of IGF2 newborn's fetal growth and development within normal range. IGF2/H19 DNA methylation could represent a cornerstone in linking birth weight and fetal metabolic programming of late onset obesity.

  10. Intrauterine position affects fetal weight and crown-rump length throughout gestation.

    PubMed

    Jang, Y D; Ma, Y L; Lindemann, M D

    2014-10-01

    To investigate the effect of intrauterine positions on fetal growth throughout gestation, data from a total of 65 gilts (n = 784 fetuses) that were slaughtered at assigned days of gestation (d 43, 58, 73, 91, 101, and 108) on a project to evaluate fetal mineral deposition were used. Placenta units were removed from the uterus, and position, sex, weight, and crown-rump length (CRL) of each fetus were recorded. Fetuses were classified into 5 categories within a uterine horn for the absolute intrauterine position: the ovarian end (OE) of the uterine horn, next to the ovarian end (NOE), the middle (MD), next to the cervical end (NCE), and the cervical end (CE), and also classified for the relative fetal position with respect to the sex of adjacent fetuses. Fetuses at the OE and NOE of the uterine horn tended to be heavier (P = 0.06) and longer (P < 0.05) than those at the MD of the uterine horn at d 58 of gestation. Fetuses at the OE of the uterine horn were also heavier and longer than those at the MD and NCE of the uterine horn at d 101 and 108 of gestation (P < 0.05). Fetuses at the CE of the uterine horn were intermediate in weight and length. There were no major effects of adjacent fetal sex (fetuses surrounded by the opposite sexes) in weight or length. Male fetuses were heavier than female fetuses at d 43, 58, 73, and 108 of gestation (P < 0.05) and longer than female fetuses at d 58 (P = 0.06), 73 (P < 0.05), 101 (P = 0.07), and 108 (P < 0.05) of gestation. Fetal weight was highly correlated with CRL at all gestational ages (P < 0.01). These results indicate that 1) the absolute intrauterine position affects fetal growth more than the sex of the adjacent fetus in the uterine horn, 2) each end of the uterine horn (OE and CE) has heavier fetuses than the MD, and 3) male pigs grow faster than female pigs even before birth.

  11. Early rapid growth, early birth: Accelerated fetal growth and spontaneous late preterm birth

    PubMed Central

    Kusanovic, Juan Pedro; Erez, Offer; Espinoza, Jimmy; Gotsch, Francesca; Goncalves, Luis; Hassan, Sonia; Gomez, Ricardo; Nien, Jyh Kae; Frongillo, Edward A.; Romero, Roberto

    2011-01-01

    The past two decades in the United States have seen a 24 % rise in spontaneous late preterm delivery (34 to 36 weeks) of unknown etiology. This study tested the hypothesis that fetal growth was identical prior to spontaneous preterm (n=221, median gestational age at birth 35.6 weeks) and term (n=3706) birth among pregnancies followed longitudinally in Santiago, Chile. The hypothesis was not supported: Preterm-delivered fetuses were significantly larger than their term-delivered peers by mid-second trimester in estimated fetal weight, head, limb and abdominal dimensions, and they followed different growth trajectories. Piecewise regression assessed time-specific differences in growth rates at 4-week intervals from 16 weeks. Estimated fetal weight and abdominal circumference growth rates faltered at 20 weeks among the preterm-delivered, only to match and/or exceed their term-delivered peers at 24–28 weeks. After an abrupt decline at 28 weeks attenuating growth rates in all dimensions, fetuses delivered preterm did so at greater population-specific sex and age-adjusted weight than their peers from uncomplicated pregnancies (p<0.01). Growth rates predicted birth timing: one standard score of estimated fetal weight increased the odds ratio for preterm birth from 2.8 prior to 23 weeks, to 3.6 (95% confidence interval, 1.82–7.11, p<0.05) between 23 and 27 weeks. After 27 weeks, increasing size was protective (OR: 0.56, 95% confidence interval, 0.38–0.82, p=0.003). These data document, for the first time, a distinctive fetal growth pattern across gestation preceding spontaneous late preterm birth, identify the importance of mid-gestation for alterations in fetal growth, and add perspective on human fetal biological variability. PMID:18988282

  12. Fetal growth velocity: kinetic, clinical, and biological aspects.

    PubMed Central

    Bertino, E.; Di Battista, E.; Bossi, A.; Pagliano, M.; Fabris, C.; Aicardi, G.; Milani, S.

    1996-01-01

    With the aim of determining fetal growth kinetics, prenatal data were analysed which had been longitudinally collected in the framework of a perinatal growth survey. The sample comprised 238 singleton normal pregnancies, selected in Genoa and Turin (between 1987 and 1990), and repeatedly assessed by ultrasound scans (five to nine per pregnancy). Five morphometric traits were considered: BPD (biparietal diameter), OFD (occipitofrontal diameter), HC (head circumference), FDL (femur diaphysis length) and AC (abdomen circumference). Growth rate seemed to increase in the early part of the second trimester, and decrease subsequently: velocity peaks were steeper and earlier for head diameters and circumference (about 18 weeks) than for femur length (20 weeks) and abdomen circumference (22 weeks). Velocity standards were traced using a longitudinal two-stage linear model: this ensures unbiased description of the shape of the growth curve, even when growth kinetics are asynchronous, and efficient estimation of the outer centiles--the most useful for diagnostic purposes. PMID:8653429

  13. Normative biometrics for fetal ocular growth using volumetric MRI reconstruction

    PubMed Central

    Velasco-Annis, Clemente; Gholipour, Ali; Afacan, Onur; Prabhu, Sanjay P.; Estroff, Judy A.; Warfield, Simon K.

    2015-01-01

    Objective To determine normative ranges for fetal ocular biometrics between 19 and 38 weeks gestational age (GA) using volumetric MRI reconstruction. Method 3D images of 114 healthy fetuses between 19 and 38 weeks GA were created using super-resolution volume reconstructions from MRI slice acquisitions. These 3D images were semi-automatically segmented to measure fetal orbit volume, binocular distance (BOD), interocular distance (IOD), and ocular diameter (OD). Results All biometry correlated with GA (Volume, CC = 0.9680; BOD, CC = 0.9552; OD, CC = 0.9445; and IOD, CC = 0.8429), and growth curves were plotted against linear and quadratic growth models. Regression analysis showed quadratic models to best fit BOD, IOD and OD, and a linear model to best fit volume. Conclusion Orbital volume had the greatest correlation with GA, though BOD and OD also showed strong correlation. The normative data found in this study may be helpful for the detection of congenital fetal anomalies with more consistent measurements than are currently available. PMID:25601041

  14. Comparative Analysis of Normal versus Fetal Growth Restriction in Pregnancy: The Significance of Maternal Body Mass Index, Nutritional Status, Anemia, and Ultrasonography Screening

    PubMed Central

    Sawant, Laxmichaya D.; Venkat, Shirin

    2013-01-01

    Fetal growth restriction or intrauterine growth restriction is one of the leading causes of perinatal mortality and morbidity in newborns. Fetal growth restriction is a complex multifactorial condition resulting from several fetal and maternal disorders. The objective of this study was twofold: first to examine the correlation between maternal parameters such as body mass index (BMI), nutritional status, anemia, and placental weight and diameter, and their effects on fetal growth and then to evaluate the effect of early screening by ultrasonography (USG) on the outcome of growth restricted pregnancies. In this study, 53 cases of fetal growth restriction were compared to 53 normal fetuses delivered in consecutive sequence. Growth restricted fetuses were delivered earlier in gestation, when compared with normal growth fetuses. Maternal anemia and malnutrition have significant association with the fetal growth restriction. Maternal anthropometry, such as low BMI, had effects on placental diameter and weight, which, in turn, adversely affected fetal weight. Thus, early USG screening along with robust screening for maternal BMI, nutritional status, and anemia can assist the obstetric team in providing early diagnosis, prompt intervention, and better outcome in pregnancy with fetal growth restriction. PMID:25763389

  15. Fetal growth and subsequent maternal risk of thyroid cancer.

    PubMed

    Crump, Casey; Sundquist, Jan; Sieh, Weiva; Winkleby, Marilyn A; Sundquist, Kristina

    2016-03-01

    Thyroid cancer has peak incidence among women of reproductive age, and growth factors, which have procarcinogenic properties, may play an important etiologic role. However, the association between fetal growth rate during a woman's pregnancy and her subsequent risk of thyroid cancer has not been previously examined. We conducted a national cohort study of 1,837,634 mothers who had a total of 3,588,497 live-births in Sweden in 1973-2008, followed up for thyroid cancer incidence through 2009. There were 2,202 mothers subsequently diagnosed with thyroid cancer in 36.8 million person-years of follow-up. After adjusting for maternal age, height, weight, smoking, and sociodemographic factors, high fetal growth (birth weight standardized for gestational age and sex) was associated with a subsequent increased risk of thyroid cancer in the mother (incidence rate ratio [IRR] per additional 1 standard deviation, 1.05; 95% CI, 1.01-1.09; p = 0.02). Each 1,000 g increase in the infant's birth weight was associated with a 13% increase in the mother's subsequent risk of thyroid cancer (IRR, 1.13; 95% CI, 1.05-1.22; p = 0.001). These findings appeared to involve both papillary and follicular subtypes, and did not vary significantly by the mother's height, weight or smoking status. In this large national cohort study, high fetal growth during a woman's pregnancy was independently associated with a subsequent increased risk of her developing thyroid cancer. If confirmed, these findings suggest an important role of maternal growth factors in the development of thyroid cancer, and potentially may help facilitate the identification of high-risk subgroups of women.

  16. Fetal hydantoin syndrome: inhibition of placental folic acid transport as a potential mechanism for fetal growth retardation in the rat

    SciTech Connect

    Will, M.; Barnard, J.A.; Said, H.M.; Ghishan, F.K.

    1985-04-01

    Maternal hydantoin ingestion during pregnancy results in a well defined clinical entity termed ''fetal hydantoin syndrome''. The clinical characteristics of this syndrome includes growth retardation, and congenital anomalies. Because folic acid is essential for protein synthesis and growth, and since hydantoin interferes with intestinal transport of folic acid, the authors postulated that part of the fetal hydantoin syndrome may be due to inhibition of placental folic acid by maternal hydantoin. Therefore, they studied in vivo placental folate transport in a well-established model for fetal hydantoin syndrome in the rat. Our results indicate that maternal hydantoin ingestion, significantly decreased fetal weight and placental and fetal uptake of folate compared to controls. To determine whether maternal hydantoin ingestion has a generalized or specific effect on placental function, they examined placental and fetal zinc transport in the same model. Our results indicate that zinc transport is not altered by hydantoin ingestion. They conclude that maternal hydantoin ingestion results in fetal growth retardation which may be due in part to inhibition of placental folate transport.

  17. Insulin-like growth factors in embryonic and fetal growth and skeletal development (Review).

    PubMed

    Agrogiannis, Georgios D; Sifakis, Stavros; Patsouris, Efstratios S; Konstantinidou, Anastasia E

    2014-08-01

    The insulin-like growth factors (IGF)-I and -II have a predominant role in fetal growth and development. IGFs are involved in the proliferation, differentiation and apoptosis of fetal cells in vitro and the IGF serum concentration has been shown to be closely correlated with fetal growth and length. IGF transcripts and peptides have been detected in almost every fetal tissue from as early in development as pre‑implantation to the final maturation stage. Furthermore, IGFs have been demonstrated to be involved in limb morphogenesis. However, although ablation of Igf genes in mice resulted in growth retardation and delay in skeletal maturation, no impact on outgrowth and patterning of embryonic limbs was observed. Additionally, various molecular defects in the Igf1 and Igf1r genes in humans have been associated with severe intrauterine growth retardation and impaired skeletal maturation, but not with truncated limbs or severe skeletal dysplasia. The conflicting data between in vitro and in vivo observations with regard to bone morphogenesis suggests that IGFs may not be the sole trophic factors involved in fetal skeletal growth and that redundant mechanisms may exist in chondro- and osteogenesis. Further investigation is required in order to elucidate the functions of IGFs in skeletal development.

  18. Chronic Protein Restriction in Mice Impacts Placental Function and Maternal Body Weight before Fetal Growth.

    PubMed

    Gonzalez, Paula N; Gasperowicz, Malgorzata; Barbeito-Andrés, Jimena; Klenin, Natasha; Cross, James C; Hallgrímsson, Benedikt

    2016-01-01

    Mechanisms of resource allocation are essential for maternal and fetal survival, particularly when the availability of nutrients is limited. We investigated the responses of feto-placental development to maternal chronic protein malnutrition to test the hypothesis that maternal low protein diet produces differential growth restriction of placental and fetal tissues, and adaptive changes in the placenta that may mitigate impacts on fetal growth. C57BL/6J female mice were fed either a low-protein diet (6% protein) or control isocaloric diet (20% protein). On embryonic days E10.5, 17.5 and 18.5 tissue samples were prepared for morphometric, histological and quantitative RT-PCR analyses, which included markers of trophoblast cell subtypes. Potential endocrine adaptations were assessed by the expression of Prolactin-related hormone genes. In the low protein group, placenta weight was significantly lower at E10.5, followed by reduction of maternal weight at E17.5, while the fetuses became significantly lighter no earlier than at E18.5. Fetal head at E18.5 in the low protein group, though smaller than controls, was larger than expected for body size. The relative size and shape of the cranial vault and the flexion of the cranial base was affected by E17.5 and more severely by E18.5. The junctional zone, a placenta layer rich in endocrine and energy storing glycogen cells, was smaller in low protein placentas as well as the expression of Pcdh12, a marker of glycogen trophoblast cells. Placental hormone gene Prl3a1 was altered in response to low protein diet: expression was elevated at E17.5 when fetuses were still growing normally, but dropped sharply by E18.5 in parallel with the slowing of fetal growth. This model suggests that nutrients are preferentially allocated to sustain fetal and brain growth and suggests the placenta as a nutrient sensor in early gestation with a role in mitigating impacts of poor maternal nutrition on fetal growth. PMID:27018791

  19. Chronic Protein Restriction in Mice Impacts Placental Function and Maternal Body Weight before Fetal Growth.

    PubMed

    Gonzalez, Paula N; Gasperowicz, Malgorzata; Barbeito-Andrés, Jimena; Klenin, Natasha; Cross, James C; Hallgrímsson, Benedikt

    2016-01-01

    Mechanisms of resource allocation are essential for maternal and fetal survival, particularly when the availability of nutrients is limited. We investigated the responses of feto-placental development to maternal chronic protein malnutrition to test the hypothesis that maternal low protein diet produces differential growth restriction of placental and fetal tissues, and adaptive changes in the placenta that may mitigate impacts on fetal growth. C57BL/6J female mice were fed either a low-protein diet (6% protein) or control isocaloric diet (20% protein). On embryonic days E10.5, 17.5 and 18.5 tissue samples were prepared for morphometric, histological and quantitative RT-PCR analyses, which included markers of trophoblast cell subtypes. Potential endocrine adaptations were assessed by the expression of Prolactin-related hormone genes. In the low protein group, placenta weight was significantly lower at E10.5, followed by reduction of maternal weight at E17.5, while the fetuses became significantly lighter no earlier than at E18.5. Fetal head at E18.5 in the low protein group, though smaller than controls, was larger than expected for body size. The relative size and shape of the cranial vault and the flexion of the cranial base was affected by E17.5 and more severely by E18.5. The junctional zone, a placenta layer rich in endocrine and energy storing glycogen cells, was smaller in low protein placentas as well as the expression of Pcdh12, a marker of glycogen trophoblast cells. Placental hormone gene Prl3a1 was altered in response to low protein diet: expression was elevated at E17.5 when fetuses were still growing normally, but dropped sharply by E18.5 in parallel with the slowing of fetal growth. This model suggests that nutrients are preferentially allocated to sustain fetal and brain growth and suggests the placenta as a nutrient sensor in early gestation with a role in mitigating impacts of poor maternal nutrition on fetal growth.

  20. Dissection of Genetic Factors Modulating Fetal Growth in Cattle Indicates a Substantial Role of the Non-SMC Condensin I Complex, Subunit G (NCAPG) Gene

    PubMed Central

    Eberlein, Annett; Takasuga, Akiko; Setoguchi, Kouji; Pfuhl, Ralf; Flisikowski, Krzysztof; Fries, Ruedi; Klopp, Norman; Fürbass, Rainer; Weikard, Rosemarie; Kühn, Christa

    2009-01-01

    The increasing evidence of fetal developmental effects on postnatal life, the still unknown fetal growth mechanisms impairing offspring generated by somatic nuclear transfer techniques, and the impact on stillbirth and dystocia in conventional reproduction have generated increasing attention toward mammalian fetal growth. We identified a highly significant quantitative trait locus (QTL) affecting fetal growth on bovine chromosome 6 in a specific resource population, which was set up by consistent use of embryo transfer and foster mothers and, thus, enabled dissection of fetal-specific genetic components of fetal growth. Merging our data with results from other cattle populations differing in historical and geographical origin and with comparative data from human whole-genome association mapping suggests that a nonsynonymous polymorphism in the non-SMC condensin I complex, subunit G (NCAPG) gene, NCAPG c.1326T>G, is the potential cause of the identified QTL resulting in divergent bovine fetal growth. NCAPG gene expression data in fetal placentomes with different NCAPG c.1326T>G genotypes, which are in line with recent results about differential NCAPG expression in placentomes from studies on assisted reproduction techniques, indicate that the NCAPG locus may give valuable information on the specific mechanisms regulating fetal growth in mammals. PMID:19720859

  1. Management of Fetal Growth Arrest in One of Dichorionic Twins: Three Cases and a Literature Review

    PubMed Central

    Kaku, Shoji; Kimura, Fuminori; Murakami, Takashi

    2015-01-01

    Progressive fetal growth restriction (FGR) is often an indication for delivery. In dichorionic diamniotic (DD) twin pregnancy with growth restriction only affecting one fetus (selective fetal growth restriction: sFGR), the normal twin is also delivered prematurely. There is still not enough evidence about the optimal timing of delivery for DD twins with sFGR in relation to discordance and gestational age. We report three sets of DD twins with sFGR (almost complete growth arrest affecting one fetus for ≥2 weeks) before 30 weeks of gestation. The interval from growth arrest to delivery was 21–24 days and the discordance was 33.7–49.8%. A large-scale study showed no difference of overall mortality or the long-term outcome between immediate and delayed delivery for FGR, while many studies have identified a risk of developmental delay following delivery of the normal growth fetus before 32 weeks. Therefore, delivery of DD twins with sFGR should be delayed if the condition of the sFGR fetus permits in order to increase the gestational age of the normal growth fetus. PMID:26839551

  2. Fetal Growth and Risk of Stillbirth: A Population-Based Case–Control Study

    PubMed Central

    Bukowski, Radek; Hansen, Nellie I.; Willinger, Marian; Reddy, Uma M.; Parker, Corette B.; Pinar, Halit; Silver, Robert M.; Dudley, Donald J.; Stoll, Barbara J.; Saade, George R.; Koch, Matthew A.; Rowland Hogue, Carol J.; Varner, Michael W.; Conway, Deborah L.; Coustan, Donald; Goldenberg, Robert L.

    2014-01-01

    Background Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth. Methods and Findings We conducted a population-based case–control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95% CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95% CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (<5th and >95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing

  3. Imprinted gene expression in fetal growth and development.

    PubMed

    Lambertini, L; Marsit, C J; Sharma, P; Maccani, M; Ma, Y; Hu, J; Chen, J

    2012-06-01

    Experimental studies showed that genomic imprinting is fundamental in fetoplacental development by timely regulating the expression of the imprinted genes to overlook a set of events determining placenta implantation, growth and embryogenesis. We examined the expression profile of 22 imprinted genes which have been linked to pregnancy abnormalities that may ultimately influence childhood development. The study was conducted in a subset of 106 placenta samples, overrepresented with small and large for gestational age cases, from the Rhode Island Child Health Study. We investigated associations between imprinted gene expression and three fetal development parameters: newborn head circumference, birth weight, and size for gestational age. Results from our investigation show that the maternally imprinted/paternally expressed gene ZNF331 inversely associates with each parameter to drive smaller fetal size, while paternally imprinted/maternally expressed gene SLC22A18 directly associates with the newborn head circumference promoting growth. Multidimensional Scaling analysis revealed two clusters within the 22 imprinted genes which are independently associated with fetoplacental development. Our data suggest that cluster 1 genes work by assuring cell growth and tissue development, while cluster 2 genes act by coordinating these processes. Results from this epidemiologic study offer solid support for the key role of imprinting in fetoplacental development.

  4. Fetal growth and the ethnic origins of type 2 diabetes.

    PubMed

    Skilton, Michael R

    2015-03-01

    Birthweight is known to differ by ethnicity, with South Asian, black African and Caribbean, and Hispanic ethnic groups having lower birthweight on average, when compared with people of white European ethnicity. Birthweight is the most frequently used proxy of fetal growth, and represents the net effect of a host of genetic, physiological and pathophysiological factors. These same ethnic groups that have lower average birthweight also tend to have a higher prevalence of type 2 diabetes in adulthood. It is not unreasonable to propose that the well-established inverse association between birthweight and risk of type 2 diabetes may at least partially contribute to these differences in prevalence of type 2 diabetes between ethnic groups. This hypothesis would rely on the mechanisms that drive the ethnic differences in birthweight aligning with those that modify the risk of type 2 diabetes. In this issue of Diabetologia (DOI: 10.1007/s00125-014-3474-7), Nightingale et al have furthered this field by determining whether ethnic differences in markers of cardio-metabolic risk are consistent with the differences in birthweight in an ethnically diverse cohort of children. The likely contribution of fetal growth to ethnic differences in risk of type 2 diabetes and cardiovascular disease is discussed, particularly in light of the magnitude of the birthweight differences, as are implications for the prevention of type 2 diabetes. PMID:25567103

  5. Iron supplementation, maternal packed cell volume, and fetal growth.

    PubMed Central

    Hemminki, E; Rimpelä, U

    1991-01-01

    Previous studies have found that there is a correlation between mothers' haemoglobin concentration or packed cell volume and infants' birth weight, and that iron supplementation increases mothers' haemoglobin concentration. The purpose of this study, using the data of a large randomised trial on iron prophylaxis during pregnancy, was to find out whether iron supplementation causes fetal growth to deteriorate. At their first antenatal visit, 2912 pregnant women were randomised into non-routine iron and routine iron supplementation. The mean length of gestation was shorter in the non-routine group. Birth weight did not differ between the groups, but due to longer gestations boys in the group receiving routine iron were taller than in the non-routine group. In both groups, whether studied by various values of packed cell volume or correlation coefficients, the lower the packed cell volume, the heavier and taller the infant and heavier the placenta. These negative correlations could be seen even with a packed cell volume measured early in pregnancy. Standardising for blood pressure did not influence the correlation coefficients. The correlation between a high ratio for packed cell volume and poor fetal growth thus may not be caused by iron supplementation, nor mediated by blood pressure, but by some other mechanism. PMID:2025036

  6. Maternal HCV infection is associated with intrauterine fetal growth disturbance: A meta-analysis of observational studies.

    PubMed

    Huang, Qi-Tao; Hang, Li-Lin; Zhong, Mei; Gao, Yun-Fei; Luo, Man-Ling; Yu, Yan-Hong

    2016-08-01

    Since the evidence regarding the association between maternal hepatitis C virus (HCV) infection and impaired intrauterine fetal growth had not been conclusive, the aim of the present study was to evaluate the risk of maternal HCV infection in association with intrauterine fetal growth restriction (IUGR) and/or low birth weight infants (LBW). We performed an extensive literature search of PubMed, MEDLINE, and EMBASE through December 1, 2015. The odds ratios (ORs) of HCV infection and IUGR/LBW were calculated and reported with 95% confidence intervals (95% CIs). Statistical analysis was performed using RevMen 5.3 and Stata 10.0. Seven studies involving 4,185,414 participants and 5094 HCV infection cases were included. Significant associations between HCV infection and IUGR (OR = 1.53, 95% CI: 1.40-1.68, fixed effect model) as well as LBW were observed (OR = 1.97, 95% CI: 1.43-2.71, random effect model). The results still indicated consistencies after adjusting for multiple risk factors which could affect fetal growth, including maternal age, parity, maternal smoking, alcohol abuse, drugs abuse, coinfected with HBV/HIV and preeclampsia. Our findings suggested that maternal HCV infection was significantly associated with an increased risk of impaired intrauterine fetal growth. In clinical practice, a closer monitoring of intrauterine fetal growth by a series of ultrasound might be necessary for HCV-infected pregnant population. PMID:27583932

  7. Birth Weight, Birth Length, and Gestational Age as Indicators of Favorable Fetal Growth Conditions in a US Sample

    PubMed Central

    Bollen, Kenneth A.

    2016-01-01

    The “fetal origins” hypothesis suggests that fetal conditions not only affect birth characteristics such as birth weight and gestational age, but also have lifelong health implications. Despite widespread interest in this hypothesis, few methodological advances have been proposed to improve the measurement and modeling of fetal conditions. A Statistics in Medicine paper by Bollen, Noble, and Adair examined favorable fetal growth conditions (FFGC) as a latent variable. Their study of Filipino children from Cebu provided evidence consistent with treating FFGC as a latent variable that largely mediates the effects of mother’s characteristics on birth weight, birth length, and gestational age. This innovative method may have widespread utility, but only if the model applies equally well across diverse settings. Our study assesses whether the FFGC model of Cebu replicates and generalizes to a very different population of children from North Carolina (N = 705) and Pennsylvania (N = 494). Using a series of structural equation models, we find that key features of the Cebu analysis replicate and generalize while we also highlight differences between these studies. Our results support treating fetal conditions as a latent variable when researchers test the fetal origins hypothesis. In addition to contributing to the substantive literature on measuring fetal conditions, we also discuss the meaning and challenges involved in replicating prior research. PMID:27097023

  8. Birth Weight, Birth Length, and Gestational Age as Indicators of Favorable Fetal Growth Conditions in a US Sample.

    PubMed

    Camerota, Marie; Bollen, Kenneth A

    2016-01-01

    The "fetal origins" hypothesis suggests that fetal conditions not only affect birth characteristics such as birth weight and gestational age, but also have lifelong health implications. Despite widespread interest in this hypothesis, few methodological advances have been proposed to improve the measurement and modeling of fetal conditions. A Statistics in Medicine paper by Bollen, Noble, and Adair examined favorable fetal growth conditions (FFGC) as a latent variable. Their study of Filipino children from Cebu provided evidence consistent with treating FFGC as a latent variable that largely mediates the effects of mother's characteristics on birth weight, birth length, and gestational age. This innovative method may have widespread utility, but only if the model applies equally well across diverse settings. Our study assesses whether the FFGC model of Cebu replicates and generalizes to a very different population of children from North Carolina (N=705) and Pennsylvania (N=494). Using a series of structural equation models, we find that key features of the Cebu analysis replicate and generalize while we also highlight differences between these studies. Our results support treating fetal conditions as a latent variable when researchers test the fetal origins hypothesis. In addition to contributing to the substantive literature on measuring fetal conditions, we also discuss the meaning and challenges involved in replicating prior research. PMID:27097023

  9. Chronic ethanol exposure and folic acid supplementation: fetal growth and folate status in the maternal and fetal guinea pig.

    PubMed

    Hewitt, Amy J; Knuff, Amber L; Jefkins, Matthew J; Collier, Christine P; Reynolds, James N; Brien, James F

    2011-05-01

    Chronic ethanol exposure (CEE) can produce developmental abnormalities in the CNS of the embryo and developing fetus. Folic acid (FA) is an important nutrient during pregnancy and low folate status exacerbates ethanol-induced teratogenicity. This study tested the hypotheses that (1) CEE depletes folate stores in the mother and fetus; and (2) maternal FA supplementation maintains folate stores. CEE decreased fetal body, brain, hippocampus weights, and brain to body weight ratio but not hippocampus to body weight ratio. These effects of CEE were not mitigated by maternal FA administration. The FA regimen prevented the CEE-induced decrease of term fetal liver folate. However, it did not affect maternal liver folate or fetal RBC folate at term, and did not mitigate the nutritional deficit-induced decrease of term fetal hippocampus folate. This study suggests that maternal FA supplementation may have differential effects on folate status in the mother and the fetus. PMID:21315145

  10. Chronic ethanol exposure and folic acid supplementation: fetal growth and folate status in the maternal and fetal guinea pig.

    PubMed

    Hewitt, Amy J; Knuff, Amber L; Jefkins, Matthew J; Collier, Christine P; Reynolds, James N; Brien, James F

    2011-05-01

    Chronic ethanol exposure (CEE) can produce developmental abnormalities in the CNS of the embryo and developing fetus. Folic acid (FA) is an important nutrient during pregnancy and low folate status exacerbates ethanol-induced teratogenicity. This study tested the hypotheses that (1) CEE depletes folate stores in the mother and fetus; and (2) maternal FA supplementation maintains folate stores. CEE decreased fetal body, brain, hippocampus weights, and brain to body weight ratio but not hippocampus to body weight ratio. These effects of CEE were not mitigated by maternal FA administration. The FA regimen prevented the CEE-induced decrease of term fetal liver folate. However, it did not affect maternal liver folate or fetal RBC folate at term, and did not mitigate the nutritional deficit-induced decrease of term fetal hippocampus folate. This study suggests that maternal FA supplementation may have differential effects on folate status in the mother and the fetus.

  11. Fetal growth and impaired glucose tolerance in men and women.

    PubMed

    Phipps, K; Barker, D J; Hales, C N; Fall, C H; Osmond, C; Clark, P M

    1993-03-01

    A follow-up study was carried out to determine whether reduced fetal growth is associated with the development of impaired glucose tolerance in men and women aged 50 years. Standard oral glucose tolerance tests were carried out on 140 men and 126 women born in Preston (Lancashire, UK) between 1935 and 1943, whose size at birth had been measured in detail. Those subjects found to have impaired glucose tolerance or non-insulin-dependent diabetes mellitus had lower birthweight, a smaller head circumference and were thinner at birth. They also had a higher ratio of placental weight to birthweight. The prevalence of impaired glucose tolerance or diabetes fell from 27% in subjects who weighed 2.50 kg (5.5 pounds) or less at birth to 6% in those who weighed more than 3.41 kg (7.5 pounds) (p < 0.002 after adjusting for body mass index). Plasma glucose concentrations taken at 2-h in the glucose tolerance test fell progressively as birthweight increased (p < 0.004), as did 2-h plasma insulin concentrations (p < 0.001). The trends with birthweight were independent of duration of gestation and must therefore be related to reduced rates of fetal growth. These findings confirm the association between impaired glucose tolerance in adult life and low birthweight previously reported in Hertfordshire (UK), and demonstrate it in women as well as men. It is suggested that the association reflects the long-term effects of reduced growth of the endocrine pancreas and other tissues in utero. This may be a consequence of maternal undernutrition. PMID:8462770

  12. Prenatal caffeine intake differently affects synaptic proteins during fetal brain development.

    PubMed

    Mioranzza, Sabrina; Nunes, Fernanda; Marques, Daniela M; Fioreze, Gabriela T; Rocha, Andréia S; Botton, Paulo Henrique S; Costa, Marcelo S; Porciúncula, Lisiane O

    2014-08-01

    Caffeine is the psychostimulant most consumed worldwide. However, little is known about its effects during fetal brain development. In this study, adult female Wistar rats received caffeine in drinking water (0.1, 0.3 and 1.0 g/L) during the active cycle in weekdays, two weeks before mating and throughout pregnancy. Cerebral cortex and hippocampus from embryonic stages 18 or 20 (E18 or E20, respectively) were collected for immunodetection of the following synaptic proteins: brain-derived neurotrophic factor (BDNF), TrkB receptor, Sonic Hedgehog (Shh), Growth Associated Protein 43 (GAP-43) and Synaptosomal-associated Protein 25 (SNAP-25). Besides, the estimation of NeuN-stained nuclei (mature neurons) and non-neuronal nuclei was verified in both brain regions and embryonic periods. Caffeine (1.0 g/L) decreased the body weight of embryos at E20. Cortical BDNF at E18 was decreased by caffeine (1.0 g/L), while it increased at E20, with no major effects on TrkB receptors. In the hippocampus, caffeine decreased TrkB receptor only at E18, with no effects on BDNF. Moderate and high doses of caffeine promoted an increase in Shh in both brain regions at E18, and in the hippocampus at E20. Caffeine (0.3g/L) decreased GAP-43 only in the hippocampus at E18. The NeuN-stained nuclei increased in the cortex at E20 by lower dose and in the hippocampus at E18 by moderate dose. Our data revealed that caffeine transitorily affect synaptic proteins during fetal brain development. The increased number of NeuN-stained nuclei by prenatal caffeine suggests a possible acceleration of the telencephalon maturation. Although some modifications in the synaptic proteins were transient, our data suggest that caffeine even in lower doses may alter the fetal brain development. PMID:24862851

  13. Maternal calcium metabolic stress and fetal growth123

    PubMed Central

    Scholl, Theresa O; Chen, Xinhua; Stein, T Peter

    2014-01-01

    Background: Suboptimal maternal calcium intake and vitamin D status may or may not adversely influence fetal growth. Objective: It was hypothesized that maternal calcium metabolic stress in early pregnancy, rather than suboptimal calcium intake or insufficient vitamin D, influences the risk of small-for-gestational-age (SGA) births and other aspects of fetal growth. Stress to calcium metabolism was defined as elevated intact parathyroid hormone (PTH) (>62 pg/mL) accompanied by a very low calcium intake [<60% of the Estimated Average Requirement (EAR)] or insufficient 25-hydroxyvitamin D [25(OH)D] (<20 ng/mL). Design: This was a prospective cohort study of 1116 low-income and minority gravidae at entry to care of 13.8 ± 5.6 wk (mean ± SD). Results: The PTH concentration depended on circulating 25(OH)D and total calcium intake. When 25(OH)D was insufficient, even a high calcium intake (which equaled or exceeded the Recommended Dietary Allowance) was unable to maintain PTH or to moderate the proportion of patients with an elevated PTH. When examined one at a time, very low calcium intake (<60% of EAR), very low 25(OH)D (<12 ng/mL), and elevated PTH (>62 pg/mL) each had a small but significant association with birth weight. Elevated PTH was also related to birth length and risk of SGA birth. Elevated PTH accompanied by insufficient 25(OH)D or very low calcium intake was associated with a 2- to 3-fold increased risk of SGA birth and a significantly lower birth weight, birth length, and head circumference, even after women who developed preeclampsia were excluded. Infants born to gravidae with insufficient 25(OH)D or very low calcium intake without elevated PTH or with elevated PTH alone were unaffected. Conclusion: Maternal calcium metabolic stress, rather than low calcium intake or insufficient vitamin D, has an adverse influence on fetal growth. This trial was registered at clinicaltrials.gov as NIH 0320070046. PMID:24500145

  14. Heifer nutrition during early- and mid-pregnancy alters fetal growth trajectory and birth weight.

    PubMed

    Micke, G C; Sullivan, T M; Soares Magalhaes, R J; Rolls, P J; Norman, S T; Perry, V E A

    2010-01-01

    Maternal nutrient intake during gestation can alter fetal growth. Whilst this has been studied extensively in the sheep, less is known about effects in the bovine. Composite-breed beef heifers were allocated to either a high (H/-=76 MJ metabolisable energy (ME) and 1.4 kg crude protein (CP)) or low (L/-=62 MJ ME and 0.4 kg CP daily) nutritional treatment at artificial insemination. Half of each nutritional group changed to an opposite nutritional group at the end of the first trimester (-/H=82 MJ ME and 1.4 kg CP; -/L=62 MJ ME and 0.4 kg CP daily), resulting in 4 treatment groups: HH (n=16); HL (n=19); LH (n=17); LL (n=19). During the third trimester all heifers were fed the same diets. Fetuses were measured at 4-weekly intervals beginning at day 39 of gestation. Calves were also measured at birth for physical body variables. Low maternal nutrient intake was associated with decreased crown-rump length at day 39 (P<0.01) and increased thoracic diameter at day 95 (P<0.01). Umbilical cord diameter was reduced in L/- fetuses in the first trimester (P<0.05) but was greater in -/L fetuses in the second trimester compared to their respective H counterparts (P<0.05). Calf birth weight was decreased in association with -/L maternal diets (P<0.05). In conclusion, fetal development of cattle may be affected by maternal nutrition as early as day 39 of gestation. This may be followed by either compensatory fetal growth, or alternatively, preferential fetal tissue growth that is dependant upon maternal nutrition. Clearly, calf birth weight may be altered by maternal nutrition during mid-gestation.

  15. Brief Report: A Preliminary Study of Fetal Head Circumference Growth in Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Whitehouse, Andrew J. O.; Hickey, Martha; Stanley, Fiona J.; Newnham, John P.; Pennell, Craig E.

    2011-01-01

    Fetal head circumference (HC) growth was examined prospectively in children with autism spectrum disorder (ASD). ASD participants (N = 14) were each matched with four control participants (N = 56) on a range of parameters known to influence fetal growth. HC was measured using ultrasonography at approximately 18 weeks gestation and again at birth…

  16. Sildenafil citrate increases fetal weight in a mouse model of fetal growth restriction with a normal vascular phenotype.

    PubMed

    Dilworth, Mark Robert; Andersson, Irene; Renshall, Lewis James; Cowley, Elizabeth; Baker, Philip; Greenwood, Susan; Sibley, Colin Peter; Wareing, Mark

    2013-01-01

    Fetal growth restriction (FGR) is defined as the inability of a fetus to achieve its genetic growth potential and is associated with a significantly increased risk of morbidity and mortality. Clinically, FGR is diagnosed as a fetus falling below the 5(th) centile of customised growth charts. Sildenafil citrate (SC, Viagra™), a potent and selective phosphodiesterase-5 inhibitor, corrects ex vivo placental vascular dysfunction in FGR, demonstrating potential as a therapy for this condition. However, many FGR cases present without an abnormal vascular phenotype, as assessed by Doppler measures of uterine/umbilical artery blood flow velocity. Thus, we hypothesized that SC would not increase fetal growth in a mouse model of FGR, the placental-specific Igf2 knockout mouse, which has altered placental exchange capacity but normal placental blood flow. Fetal weights were increased (by 8%) in P0 mice following maternal SC treatment (0.4 mg/ml) via drinking water. There was also a trend towards increased placental weight in treated P0 mice (P = 0.056). Additionally, 75% of the P0 fetal weights were below the 5(th) centile, the criterion used to define human FGR, of the non-treated WT fetal weights; this was reduced to 51% when dams were treated with SC. Umbilical artery and vein blood flow velocity measures confirmed the lack of an abnormal vascular phenotype in the P0 mouse; and were unaffected by SC treatment. (14)C-methylaminoisobutyric acid transfer (measured to assess effects on placental nutrient transporter activity) per g placenta was unaffected by SC, versus untreated, though total transfer was increased, commensurate with the trend towards larger placentas in this group. These data suggest that SC may improve fetal growth even in the absence of an abnormal placental blood flow, potentially affording use in multiple sub-populations of individuals presenting with FGR.

  17. Growth in Inuit children exposed to polychlorinated biphenyls and lead during fetal development and childhood

    PubMed Central

    Dallaire, Renée; Dewailly, Éric; Ayotte, Pierre; Forget-Dubois, Nadine; Jacobson, Sandra W.; Jacobson, Joseph L.; Muckle, Gina

    2014-01-01

    Background Because of their geographical location and traditional lifestyle, Canadian Inuit children are highly exposed to polychlorinated biphenyls (PCBs) and lead (Pb), environmental contaminants that are thought to affect fetal and child growth. We examined the associations of these exposures with the fetal and postnatal growth of Inuit children. Methods We conducted a prospective cohort study among Inuit from Nunavik (Arctic Québec). Mothers were recruited at their first prenatal visit; children (n = 290) were evaluated at birth and at 8–14 years of age. Concentrations of PCB 153 and Pb were determined in umbilical cord and child blood. Weight, height and head circumference were measured at birth and during childhood. Results Cord blood PCB 153 concentrations were not associated with anthropometric measurements at birth or school age, but child blood PCB 153 concentrations were associated with reduced weight, height and head circumference during childhood. There was no association between cord Pb levels and anthropometric outcomes at birth, but cord blood Pb was related to smaller height and a tendency to a smaller head circumference during childhood. Interpretation Our results suggest that chronic exposure to PCBs during childhood is negatively associated with skeletal growth and weight, while prenatal Pb exposure is related to reduce growth during childhood. This study is the first to link prenatal Pb exposure to poorer growth in school-age children. PMID:25042032

  18. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth.

    PubMed

    Aye, Irving L M H; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2015-10-13

    Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity. PMID:26417088

  19. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth

    PubMed Central

    Aye, Irving L. M. H.; Rosario, Fredrick J.; Powell, Theresa L.; Jansson, Thomas

    2015-01-01

    Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity. PMID:26417088

  20. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth.

    PubMed

    Aye, Irving L M H; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2015-10-13

    Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity.

  1. Structural equation modeling and nested ANOVA: Effects of lead exposure on maternal and fetal growth in rats

    SciTech Connect

    Hamilton, J.D. ); O'Flaherty, E.J.; Shukla, R.; Gartside, P.S. ); Ross, R. )

    1994-01-01

    This study provided an assessment of the effects of lead on early growth in rats based on structural equation modeling and nested analysis of variance (ANOVA). Structural equation modeling showed that lead in drinking water (250, 500, or 1000 ppm) had a direct negative effect on body weight and tail length (i.e., growth) in female rats during the first week of exposure. During the following 2 weeks of exposure, high correlation between growth measurements taken over time resulted in reduced early postnatal growth. By the fourth week of exposure, reduced growth was not evident. Mating began after 8 weeks of exposure, and exposure continued during gestation. Decreased fetal body weight was detected when the effects of litter size, intrauterine position, and sex were controlled in a nested ANOVA. Lead exposure did not appear to affect fetal skeletal development, possibly because lead did not alter maternal serum calcium and phosphorus levels. The effect of lead on individual fetal body weight suggests that additional studies are needed to examine the effect of maternal lead exposure on fetal development and early postnatal growth. 24 refs., 4 figs., 6 tabs.

  2. Sildenafil citrate for the management of fetal growth restriction and oligohydramnios

    PubMed Central

    Choudhary, Rana; Desai, Kavita; Parekh, Hetal; Ganla, Kedar

    2016-01-01

    Fetal growth restriction (FGR) and preeclampsia are the major causes of neonatal morbidity and mortality, which affect up to 8% of all pregnancies. The pathogenesis in FGR is an abnormal trophoblastic invasion leading to compromised uteroplacental circulation. However, in spite of this understanding and identification of high-risk patients, the management options are limited. There are some new studies which have demonstrated the role of sildenafil citrate in improving vasodilatation of small myometrial vessels and therefore improvement in amniotic fluid index, fetal weight, and even uterine and umbilical artery Doppler patterns. We report here the case of a 31-year-old female with infertility and preconceptional thin endometrium responding well to sildenafil citrate, followed by conception. However, she presented with an early-onset FGR at 26 weeks of gestation, and again after treatment with sildenafil citrate, showed improvement in amniotic fluid index and fetal weight, finally resulting in delivery of a full-term healthy baby with uneventful neonatal course. PMID:27563258

  3. Sildenafil citrate for the management of fetal growth restriction and oligohydramnios.

    PubMed

    Choudhary, Rana; Desai, Kavita; Parekh, Hetal; Ganla, Kedar

    2016-01-01

    Fetal growth restriction (FGR) and preeclampsia are the major causes of neonatal morbidity and mortality, which affect up to 8% of all pregnancies. The pathogenesis in FGR is an abnormal trophoblastic invasion leading to compromised uteroplacental circulation. However, in spite of this understanding and identification of high-risk patients, the management options are limited. There are some new studies which have demonstrated the role of sildenafil citrate in improving vasodilatation of small myometrial vessels and therefore improvement in amniotic fluid index, fetal weight, and even uterine and umbilical artery Doppler patterns. We report here the case of a 31-year-old female with infertility and preconceptional thin endometrium responding well to sildenafil citrate, followed by conception. However, she presented with an early-onset FGR at 26 weeks of gestation, and again after treatment with sildenafil citrate, showed improvement in amniotic fluid index and fetal weight, finally resulting in delivery of a full-term healthy baby with uneventful neonatal course. PMID:27563258

  4. The impact of a human IGF-II analog ([Leu27]IGF-II) on fetal growth in a mouse model of fetal growth restriction

    PubMed Central

    Charnock, Jayne C.; Dilworth, Mark R.; Aplin, John D.; Sibley, Colin P.; Westwood, Melissa

    2015-01-01

    Enhancing placental insulin-like growth factor (IGF) availability appears to be an attractive strategy for improving outcomes in fetal growth restriction (FGR). Our approach was the novel use of [Leu27]IGF-II, a human IGF-II analog that binds the IGF-II clearance receptor IGF-IIR in fetal growth-restricted (FGR) mice. We hypothesized that the impact of [Leu27]IGF-II infusion in C57BL/6J (wild-type) and endothelial nitric oxide synthase knockout (eNOS−/−; FGR) mice would be to enhance fetal growth and investigated this from mid- to late gestation; 1 mg·kg−1·day−1 [Leu27]IGF-II was delivered via a subcutaneous miniosmotic pump from E12.5 to E18.5. Fetal and placental weights recorded at E18.5 were used to generate frequency distribution curves; fetuses <5th centile were deemed growth restricted. Placentas were harvested for immunohistochemical analysis of the IGF system, and maternal serum was collected for measurement of exogenously administered IGF-II. In WT pregnancies, [Leu27]IGF-II treatment halved the number of FGR fetuses, reduced fetal(P = 0.028) and placental weight variations (P = 0.0032), and increased the numbers of pups close to the mean fetal weight (131 vs. 112 pups within 1 SD). Mixed-model analysis confirmed litter size to be negatively correlated with fetal and placental weight and showed that [Leu27]IGF-II preferentially improved fetal weight in the largest litters, as defined by number. Unidirectional 14CMeAIB transfer per gram placenta (System A amino acid transporter activity) was inversely correlated with fetal weight in [Leu27]IGF-II-treated WT animals (P < 0.01). In eNOS−/− mice, [Leu27]IGF-II reduced the number of FGR fetuses(1 vs. 5 in the untreated group). The observed reduction in FGR pup numbers in both C57 and eNOS−/− litters suggests the use of this analog as a means of standardizing and rescuing fetal growth, preferentially in the smallest offspring. PMID:26530156

  5. Human fetal weight and placental weight growth curves. A mathematical analysis from a population at sea level.

    PubMed

    Bonds, D R; Mwape, B; Kumar, S; Gabbe, S G

    1984-01-01

    A mathematical analysis of human fetal and placental growth curves was made on data collected prospectively from a population at sea level. Both the fetal and placental growth curves can best be described by a form of the logistic equation inhibited growth model. The fetal growth rate reaches its maximum approximately 4 weeks after the placental growth rate has reached its maximum. Growth rate constants were calculated for several populations at various altitudes. PMID:6733167

  6. Progesterone and HMOX-1 promote fetal growth by CD8+ T cell modulation

    PubMed Central

    Solano, María Emilia; Kowal, Mirka Katharina; O’Rourke, Greta Eugenia; Horst, Andrea Kristina; Modest, Kathrin; Plösch, Torsten; Barikbin, Roja; Remus, Chressen Catharina; Berger, Robert G.; Jago, Caitlin; Ho, Hoang; Sass, Gabriele; Parker, Victoria J.; Lydon, John P.; DeMayo, Francesco J.; Hecher, Kurt; Karimi, Khalil; Arck, Petra Clara

    2015-01-01

    Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies in Western societies. IUGR is a strong predictor of reduced short-term neonatal survival and impairs long-term health in children. Placental insufficiency is often associated with IUGR; however, the molecular mechanisms involved in the pathogenesis of placental insufficiency and IUGR are largely unknown. Here, we developed a mouse model of fetal-growth restriction and placental insufficiency that is induced by a midgestational stress challenge. Compared with control animals, pregnant dams subjected to gestational stress exhibited reduced progesterone levels and placental heme oxygenase 1 (Hmox1) expression and increased methylation at distinct regions of the placental Hmox1 promoter. These stress-triggered changes were accompanied by an altered CD8+ T cell response, as evidenced by a reduction of tolerogenic CD8+CD122+ T cells and an increase of cytotoxic CD8+ T cells. Using progesterone receptor– or Hmox1-deficient mice, we identified progesterone as an upstream modulator of placental Hmox1 expression. Supplementation of progesterone or depletion of CD8+ T cells revealed that progesterone suppresses CD8+ T cell cytotoxicity, whereas the generation of CD8+CD122+ T cells is supported by Hmox1 and ameliorates fetal-growth restriction in Hmox1 deficiency. These observations in mice could promote the identification of pregnancies at risk for IUGR and the generation of clinical interventional strategies. PMID:25774501

  7. Placental phenotype and resource allocation to fetal growth are modified by the timing and degree of hypoxia during mouse pregnancy

    PubMed Central

    Higgins, J. S.; Vaughan, O. R.; Fernandez de Liger, E.; Fowden, A. L.

    2015-01-01

    Key points Hypoxia is a major cause of fetal growth restriction, particularly at high altitude, although little is known about its effects on placental phenotype and resource allocation to fetal growth.In the present study, maternal hypoxia induced morphological and functional changes in the mouse placenta, which depended on the timing and severity of hypoxia, as well as the degree of maternal hypophagia.Hypoxia at 13% inspired oxygen induced beneficial changes in placental morphology, nutrient transport and metabolic signalling pathways associated with little or no change in fetal growth, irrespective of gestational age.Hypoxia at 10% inspired oxygen adversely affected placental phenotype and resulted in severe fetal growth restriction, which was due partly to maternal hypophagia.There is a threshold between 13% and 10% inspired oxygen, corresponding to altitudes of ∼3700 m and 5800 m, respectively, at which the mouse placenta no longer adapts to support fetal resource allocation. This has implications for high altitude human pregnancies. Abstract The placenta adapts its transport capacity to nutritional cues developmentally, although relatively little is known about placental transport phenotype in response to hypoxia, a major cause of fetal growth restriction. The present study determined the effects of both moderate hypoxia (13% inspired O2) between days (D)11 and D16 or D14 and D19 of pregnancy and severe hypoxia (10% inspired O2) from D14 to D19 on placental morphology, transport capacity and fetal growth on D16 and D19 (term∼D20.5), relative to normoxic mice in 21% O2. Placental morphology adapted beneficially to 13% O2; fetal capillary volume increased at both ages, exchange area increased at D16 and exchange barrier thickness reduced at D19. Exposure to 13% O2 had no effect on placental nutrient transport on D16 but increased placental uptake and clearance of 3H‐methyl‐d‐glucose at D19. By contrast, 10% O2 impaired fetal vascularity

  8. Does bleeding affect fetal Doppler parameters during genetic amniocentesis?

    PubMed Central

    İskender, Cantekin; Tarım, Ebru; Çok, Tayfun; Kalaycı, Hakan; Parlakgümüş, Ayşe; Yalçınkaya, Cem

    2014-01-01

    Objective The aim of this study was to investigate the relationship between fetal Doppler parameters and bleeding at insertion points during amniocentesis. Material and Methods This prospective study was conducted between July 2010 and February 2011. A total of 215 amniocentesis procedures were performed during this period. Five patients with Down syndrome were excluded from the study. The remaining 210 patients were divided into Group 1 (bleeding at insertion site) and Group 2 as a control group. One needle type was used for all patients. Umbilical artery resistance index (UARI), umbilical artery pulsatility index (UAPI), middle cerebral artery resistance index (MCARI), middle cerebral artery pulsatility index (MCA PI), and middle cerebral artery peak systolic velocity (MCAPSV) were measured immediately and before and after amniocentesis. Results Bleeding at the insertion point during amniocentesis did not significantly change the UARI (34% increase for Group 1 and 46.5% increase for Group 2, p=0.238), the MCARI (52% increase for Group 1 and 45% increase for Group 2, p=0.622), or the MCAPSV (37% increase for Group 1 and 49% increase for Group 2, p=0.199). UARI, MCARI, MCA PI, and MCAPSV were not significantly altered following amniocentesis in Groups 1 and 2. There was a significant increase in UAPI following amniocentesis only in Group 2. Conclusion Bleeding during genetic amniocentesis did not change umbilical artery and middle cerebral artery Doppler parameters. PMID:24976776

  9. Fetal Hemodynamics and Fetal Growth Indices by Ultrasound in Late Pregnancy and Birth Weight in Gestational Diabetes Mellitus

    PubMed Central

    Liu, Fang; Liu, Yong; Lai, Ya-Ping; Gu, Xiao-Ning; Liu, Dong-Mei; Yang, Min

    2016-01-01

    Background: The offspring of women with gestational diabetes mellitus (GDM) are prone to macrosomia. However, birth weight is difficult to be correctly estimated by ultrasound because of fetal asymmetric growth characteristics. This study aimed to investigate the correlations between fetal hemodynamics, fetal growth indices in late pregnancy, and birth weight in GDM. Methods: A total of 147 women with GDM and 124 normal controls (NC) were enrolled in this study. Fetal hemodynamic indices, including the systolic/diastolic ratio (S/D), resistance index (RI), pulsatility index (PI) of umbilical artery (UA), middle cerebral artery (MCA), and renal artery (RA), were collected. Fetal growth indices, including biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length, were also measured by ultrasound. Birth weight, newborn gender, and maternal clinical data were collected. Results: The independent samples t-test showed that BPD, HC, and AC were larger in GDM than in NC (P < 0.05). Fetal hemodynamic indices of the UA and MCA were lower (P < 0.05), but those of the RA were higher (P < 0.001) in GDM than in NC. Birth weight was higher in GDM than in NC (P < 0.001). Pearson's correlation analysis showed that hemodynamic indices of the UA were negatively correlated with birth weight, BPD, HC, and AC in both groups (P < 0.05). MCA (S/D, PI, and RI) was negatively correlated with birth weight, HC, and AC in GDM (r = −0.164, −0.206, −0.200, −0.226, −0.189, −0.179, −0.196, −0.177, and − 0.172, respectively, P < 0.05), but there were no correlations in NC (P > 0.05). RA (S/D, PI, and RI) was positively correlated with birth weight in GDM (r = 0.168, 0.207, and 0.184, respectively, P < 0.05), but there were no correlations in NC (P > 0.05). Conclusion: Fetal hemodynamic indices in late pregnancy might be helpful for estimating newborn birth weight in women with GDM. PMID:27569240

  10. Altered cytokine network in gestational diabetes mellitus affects maternal insulin and placental-fetal development.

    PubMed

    Wedekind, Lauren; Belkacemi, Louiza

    2016-01-01

    Pregnancy is characterized by an altered inflammatory profile, compared to the non-pregnant state with an adequate balance between pro-and anti-inflammatory cytokines needed for normal development. Cytokines are small secreted proteins expressed mainly in immunocompetent cells in the reproductive system. From early developmental stages onward, the secretory activity of placenta cells clearly contributes to increase local as well as systemic levels of cytokines. The placental production of cytokines may affect mother and fetus independently. In turn because of this unique position at the maternal fetal interface, the placenta is also exposed to the regulatory influence of cytokines from maternal and fetal circulations, and hence, may be affected by changes in any of these. Gestational diabetes mellitus (GDM) is associated with an overall alteration of the cytokine network. This review discusses the changes that occur in cytokines post GDM and their negative effects on maternal insulin and placental-fetal development. PMID:27230834

  11. Relation of FTO gene variants to fetal growth trajectories: Findings from the Southampton Women's survey

    PubMed Central

    Barton, S.J.; Mosquera, M.; Cleal, J.K.; Fuller, A.S.; Crozier, S.R.; Cooper, C.; Inskip, H.M.; Holloway, J.W.; Lewis, R.M.; Godfrey, K.M.

    2016-01-01

    Introduction Placental function is an important determinant of fetal growth, and fetal growth influences obesity risk in childhood and adult life. Here we investigated how FTO and MC4R gene variants linked with obesity relate to patterns of fetal growth and to placental FTO expression. Methods Southampton Women's Survey children (n = 1990) with measurements of fetal growth from 11 to 34 weeks gestation were genotyped for common gene variants in FTO (rs9939609, rs1421085) and MC4R (rs17782313). Linear mixed-effect models were used to analyse relations of gene variants with fetal growth. Results Fetuses with the rs9939609 A:A FTO genotype had faster biparietal diameter and head circumference growth velocities between 11 and 34 weeks gestation (by 0.012 (95% CI 0.005 to 0.019) and 0.008 (0.002–0.015) standard deviations per week, respectively) compared to fetuses with the T:T FTO genotype; abdominal circumference growth velocity did not differ between genotypes. FTO genotype was not associated with placental FTO expression, but higher placental FTO expression was independently associated with larger fetal size and higher placental ASCT2, EAAT2 and y + LAT2 amino acid transporter expression. Findings were similar for FTO rs1421085, and the MC4R gene variant was associated with the fetal growth velocity of head circumference. Discussion FTO gene variants are known to associate with obesity but this is the first time that the risk alleles and placental FTO expression have been linked with fetal growth trajectories. The lack of an association between FTO genotype and placental FTO expression adds to emerging evidence of complex biology underlying the association between FTO genotype and obesity. PMID:26907388

  12. Uteroplacental adenovirus vascular endothelial growth factor gene therapy increases fetal growth velocity in growth-restricted sheep pregnancies.

    PubMed

    Carr, David J; Wallace, Jacqueline M; Aitken, Raymond P; Milne, John S; Mehta, Vedanta; Martin, John F; Zachary, Ian C; Peebles, Donald M; David, Anna L

    2014-04-01

    Fetal growth restriction (FGR) occurs in ∼8% of pregnancies and is a major cause of perinatal mortality and morbidity. There is no effective treatment. FGR is characterized by reduced uterine blood flow (UBF). In normal sheep pregnancies, local uterine artery (UtA) adenovirus (Ad)-mediated overexpression of vascular endothelial growth factor (VEGF) increases UBF. Herein we evaluated Ad.VEGF therapy in the overnourished adolescent ewe, an experimental paradigm in which reduced UBF from midgestation correlates with reduced lamb birthweight near term. Singleton pregnancies were established using embryo transfer in adolescent ewes subsequently offered a high intake (n=45) or control intake (n=12) of a complete diet to generate FGR or normal fetoplacental growth, respectively. High-intake ewes were randomized midgestation to receive bilateral UtA injections of 5×10¹¹ particles Ad.VEGF-A165 (n=18), control vector Ad.LacZ (n=14), or control saline (n=13). Fetal growth/well-being were evaluated using serial ultrasound. UBF was monitored using indwelling flowprobes until necropsy at 0.9 gestation. Vasorelaxation, neovascularization within the perivascular adventitia, and placental mRNA expression of angiogenic factors/receptors were examined using organ bath analysis, anti-vWF immunohistochemistry, and qRT-PCR, respectively. Ad.VEGF significantly increased ultrasonographic fetal growth velocity at 3-4 weeks postinjection (p=0.016-0.047). At 0.9 gestation fewer fetuses were markedly growth-restricted (birthweight >2SD below contemporaneous control-intake mean) after Ad.VEGF therapy. There was also evidence of mitigated fetal brain sparing (lower biparietal diameter-to-abdominal circumference and brain-to-liver weight ratios). No effects were observed on UBF or neovascularization; however, Ad.VEGF-transduced vessels demonstrated strikingly enhanced vasorelaxation. Placental efficiency (fetal-to-placental weight ratio) and FLT1/KDR mRNA expression were increased in the

  13. Prenatal sodium arsenite affects early development of serotonergic neurons in the fetal rat brain.

    PubMed

    Senuma, Mika; Mori, Chisato; Ogawa, Tetsuo; Kuwagata, Makiko

    2014-11-01

    Prenatal arsenite exposure has been associated with developmental disorders in children, including reduced IQ and language abnormalities. Animal experiments have also shown that exposure to arsenite during development induced developmental neurotoxicity after birth. However, the evidence is not enough, and the mechanism is poorly understood, especially on the exposure during early brain development. This study assessed effects of sodium (meta) arsenite shortly after exposure on early developing fetal rat brains. Pregnant rats were administered 50 mg/L arsenite in their drinking water or 20 mg/kg arsenite orally using a gastric tube, on gestational days (GD) 9-15. Fetal brains were examined on GD16. Pregnant rats administered 20 mg/kg arsenite showed reductions in maternal body weight gain and food consumption during treatment, but not with 50 mg/L arsenite. Arsenite did not affect fetal development, as determined by body weight, mortality and brain size. Arsenite also did not induce excessive cell death or affect neural cell division in any region of the fetal neuroepithelium. Thyrosine hydroxylase immunohistochemistry revealed no difference in the distribution of catecholaminergic neurons between fetuses of arsenite treated and control rats. However, reductions in the number of serotonin positive cells in the fetal median and dorsal raphe nuclei were observed following maternal treatment with 20mg/kg arsenite. Image analysis showed that the serotonin positive areas decreased in all fetal mid- and hind-brain areas without altering distribution patterns. Maternal stress induced by arsenite toxicity did not alter fetal development. These results suggest that arsenite-induced neurodevelopmental toxicity involves defects in the early development of the serotonin nervous system.

  14. Fetal urinoma and prenatal hydronephrosis: how is renal function affected?

    PubMed Central

    Oktar, Tayfun; Salabaş, Emre; Kalelioğlu, İbrahim; Atar, Arda; Ander, Haluk; Ziylan, Orhan; Has, Recep; Yüksel, Atıl

    2013-01-01

    Objective: In our study, the functional prognosis of kidneys with prenatal urinomas were investigated. Material and methods: Between 2006 and 2010, fetal urinomas were detected in 19 fetuses using prenatal ultrasonography (US), and the medical records were reviewed retrospectively. Of the 19 cases, the follow-up data were available for 10 fetuses. The gestational age at diagnosis, prognosis of urinomas, clinical course and renal functions were recorded. Postnatal renal functions were assessed with renal scintigraphy. Results: Unilateral urinomas and increased parenchyma echogenicity in the ipsilateral kidney were detected in all of the fetuses. Of the 10 fetuses with follow-up data, the option of termination was offered in 6 cases of anhydramnios, including 3 cases with signs of infravesical obstruction (a possible posterior urethral valve (PUV) and poor prognostic factors and 3 cases with unilateral hydronephrosis and increased echogenicity in the contralateral kidney. Only one family agreed the termination. The other 5 fetuses died during the early postnatal period. The average postnatal follow-up period in the 4 surviving fetuses was 22.5 months (8–38 months). One patient with a PUV underwent ablation surgery during the early postnatal period. In the postnatal period, none of the 4 kidneys that were ipsilateral to the urinoma were functional on scintigraphic evaluation. The urinomas disappeared in 3 cases. Nephrectomy was performed in one case due to recurrent urinary tract infections. Conclusion: In our study, no function was detected in the ipsilateral kidney of surviving patients with urinomas. Upper urinary tract dilatation accompanied by a urinoma is a poor prognostic factor for renal function. PMID:26328088

  15. Characterization of fetal growth by repeated ultrasound measurements in the wild guinea pig (Cavia aperea).

    PubMed

    Schumann, K; Guenther, A; Göritz, F; Jewgenow, K

    2014-08-01

    Fetal growth during pregnancy has previously been studied in the domesticated guinea pig (Cavia aperea f. porcellus) after dissecting pregnant females, but there are no studies describing the fetal growth in their wild progenitor, the wild guinea pig (C aperea). In this study, 50 pregnancies of wild guinea pig sows were investigated using modern ultrasound technique. The two most common fetal growth parameters (biparietal diameter [BPD] and crown-rump-length [CRL]) and uterine position were measured. Data revealed similar fetal growth patterns in the wild guinea pig and domesticated guinea pig in the investigated gestation period, although they differ in reproductive milestones such as gestation length (average duration of pregnancy 68 days), average birth weight, and litter mass. In this study, pregnancy lasted on average 60.2 days with a variance of less than a day (0.96 days). The measured fetal growth parameters are strongly correlated with each (R = 0.91; P < 0.001) other and with gestational age (BPD regression equation y = 0.04x - 0.29; P < 0.001 and CRL regression equation y = 0.17x - 2.21; P < 0.01). Furthermore, fetuses in the most frequent uterine positions did not differ in their growth parameters and were not influenced by the mother ID. Our results imply that ultrasound measurement of a single fetal growth parameter is sufficient to reliably estimate gestational age in the wild guinea pig.

  16. Elevated maternal serum folate in the third trimester and reduced fetal growth: a longitudinal study.

    PubMed

    Takimoto, Hidemi; Hayashi, Fumi; Kusama, Kaoru; Kato, Noriko; Yoshiike, Nobuo; Toba, Mikayo; Ishibashi, Tomoko; Miyasaka, Naoyuki; Kubota, Toshiro

    2011-01-01

    This study aimed to examine the association of fetal growth and elevated third trimester maternal serum folate due to folic acid (FA) supplement intake. Dietary intake, use of FA supplements, weight, and blood biomarkers of B-vitamins (serum folate, pyridoxal, vitamin B(12), and plasma total homocysteine) were observed in 33 healthy pregnant women at the third trimester (average gestational age 35 wk). Birth outcomes were assessed through hospital birth records. Infant anthropometry and maternal blood biomarkers were followed up at 1 mo postpartum. Fourteen women were taking FA supplements at the third trimester. Dietary intake was similar among FA users and non-users, but serum folate and pyridoxal were significantly higher in users (11.6±6.7 vs. 6.1±3.2 ng/mL, and 13.8±21.7 vs. 3.2±1.4 ng/mL, respectively). Plasma total homocystein (tHcy) was higher in non-users compared to users, but not significantly. Nine FA users and eight non-users had low serum vitamin B(12) values (<203 pg/mL). Nine FA users and all non-users had low serum pyridoxal values (<7.0 ng/mL). Infant birthweight was significantly lower in users compared to non-users (2,894±318 vs. 3,154±230 g). At 1 mo postpartum, infant weight and length were similar between FA users and non-users, but infant weight gain was larger in users. Higher serum folate values due to FA use in the third trimester was related to reduced fetal size. Excess FA under low vitamin B(6) and B(12) status may affect fetal growth. PMID:21697631

  17. Hepatocyte growth factor is a mouse fetal Leydig cell terminal differentiation factor.

    PubMed

    Ricci, Giulia; Guglielmo, Maria Cristina; Caruso, Maria; Ferranti, Francesca; Canipari, Rita; Galdieri, Michela; Catizone, Angela

    2012-06-01

    The hepatocyte growth factor (HGF) is a pleiotropic cytokine and a well-known regulator of mouse embryonic organogenesis. In previous papers, we have shown the expression pattern of HGF and its receptor, C-MET, during the different stages of testis prenatal development. We demonstrated that C-MET is expressed in fetal Leydig cells (FLCs) and that HGF stimulates testosterone secretion in organ culture of late fetal testes. In the present study, we analyzed the proliferation rate, apoptotic index, and differentiation of FLCs in testicular organ culture of 17.5 days postcoitum (17.5 dpc) embryos to clarify the physiological role of HGF in late testis organogenesis. Based on our data, we conclude the following: 1) HGF acts as an antiapoptotic factor that is able to reduce the number of apoptotic FLCs and testicular caspase-3 active fragment; 2) HGF does not affect FLC proliferation; 3) HGF significantly increases expression of insulin-like 3 (INSL3), a marker of Leydig cell terminal differentiation, without affecting 3beta-hydroxysteroid dehydrogenase (3betaHSD) expression; 4) HGF significantly decreases the expression of nestin, a marker of Leydig cell progenitors; and 5) HGF significantly increases the number of fully developed FLCs. Taken together, these observations demonstrate that HGF is able to act in vitro as a survival and differentiation factor in FLC population.

  18. Maternal Lipids Are as Important as Glucose for Fetal Growth

    PubMed Central

    Kulkarni, Smita R.; Kumaran, Kalyanaraman; Rao, Shobha R.; Chougule, Suresh D.; Deokar, Tukaram M.; Bhalerao, Ankush J.; Solat, Vishnu A.; Bhat, Dattatray S.; Fall, Caroline H.D.; Yajnik, Chittaranjan S.

    2013-01-01

    OBJECTIVE To study the relationship between maternal circulating fuels and neonatal size and compare the relative effects of glucose and lipids. RESEARCH DESIGN AND METHODS The Pune Maternal Nutrition Study (1993–1996) investigated the influence of maternal nutrition on fetal growth. We measured maternal body size and glucose and lipid concentrations during pregnancy and examined their relationship with birth size in full-term babies using correlation and regression techniques. RESULTS The mothers (n = 631) were young (mean age 21 years), short (mean height 151.9 cm), and thin (BMI 18.0 kg/m2) but were relatively more adipose (body fat 21.1%). Their diet was mostly vegetarian. Between 18 and 28 weeks’ gestation, fasting glucose concentrations remained stable, whereas total cholesterol and triglyceride concentrations increased and HDL-cholesterol concentrations decreased. The mean birth weight of the offspring was 2666 g. Total cholesterol and triglycerides at both 18 and 28 weeks and plasma glucose only at 28 weeks were associated directly with birth size. One SD higher maternal fasting glucose, cholesterol, and triglyceride concentrations at 28 weeks were associated with 37, 54, and 36 g higher birth weights, respectively (P < 0.05 for all). HDL-cholesterol concentrations were unrelated to newborn measurements. The results were similar if preterm deliveries also were included in the analysis (total n = 700). CONCLUSIONS Our results suggest an influence of maternal lipids on neonatal size in addition to the well-established effect of glucose. Further research should be directed at defining the clinical relevance of these findings. PMID:23757425

  19. Dietary protein during gestation affects circulating indicators of placental function and fetal development in heifers.

    PubMed

    Sullivan, T M; Micke, G C; Magalhaes, R S; Martin, G B; Wallace, C R; Green, J A; Perry, V E A

    2009-04-01

    The influences of nutritional protein during the first and second trimesters of pregnancy on placental hormones and fetal growth were determined in composite beef heifers. At artificial insemination, heifers were stratified by weight within each composite genotype into 4 treatment groups: High High (HH=1.4kg crude protein (CP)/day for first and second trimesters of gestation; n=16), High Low (HL=1.4kg CP/day for first trimester and 0.4kg CP/day for second trimester; n=19), Low High (LH=0.4kg CP/day for first trimester and 1.4kg CP/day for second trimester; n=17) or Low Low (LL=0.4kg CP/day for first and second trimesters; n=19). Maternal plasma bovine pregnancy associated glycoprotein (bPAG) and progesterone (P4) were determined at gestation day (gd) 28, 82, 179 and 271 (mean gestation length 286 days) in addition to P4 at term. Estrone sulphate (ES) and bovine placental lactogen (bPL) concentrations were measured at gd 124, 179, 236 and 271 and at term in addition to ES at gd 82. Low dietary protein increased placental function as indicated by increased bPAG (P<0.001) and ES (P=0.02) concentrations in first trimester and increased bPL concentrations (P=0.01) in the second trimester of gestation. In the third trimester, when dietary treatment had ceased, placental function was no longer associated with previous dietary treatments. Dam genotype affected placental function as measured by bPL (P<0.001) and ES concentrations (P=0.02). Calf gender, heifer age and maternal insulin-like growth factor (IGF)-I, -II and leptin did not affect hormonal indicators or circulating markers of placental function. Enhanced placental function during the third trimester, as measured by ES, was associated with increased calf birth weight (P=0.003).

  20. Urinary phthalate metabolite and bisphenol A associations with ultrasound and delivery indices of fetal growth.

    PubMed

    Ferguson, Kelly K; Meeker, John D; Cantonwine, David E; Chen, Yin-Hsiu; Mukherjee, Bhramar; McElrath, Thomas F

    2016-09-01

    Growth of the fetus is highly sensitive to environmental perturbations, and disruption can lead to problems in pregnancy as well as later in life. This study investigates the relationship between maternal exposure to common plasticizers in pregnancy and fetal growth. Participants from a longitudinal birth cohort in Boston were recruited early in gestation and followed until delivery. Urine samples were collected at up to four time points and analyzed for concentrations of phthalate metabolites and bisphenol A (BPA). Ultrasound scans were performed at four time points during pregnancy for estimation of growth parameters, and birthweight was recorded at delivery. Growth measures were standardized to a larger population. For the present analysis we examined cross-sectional and repeated measures associations between exposure biomarkers and growth estimates in 482 non-anomalous singleton pregnancies. Cross-sectional associations between urinary phthalate metabolites or BPA and growth indices were imprecise. However, in repeated measures models, we observed significant inverse associations between di-2-ethylhexyl phthalate (DEHP) metabolites and estimated or actual fetal weight. An interquartile range increase in summed DEHP metabolites was associated with a 0.13 standard deviation decrease in estimated or actual fetal weight (95% confidence interval=-0.23, -0.03). Associations were consistent across different growth parameters (e.g., head circumference, femur length), and by fetal sex. No consistent associations were observed for other phthalate metabolites or BPA. Maternal exposure to DEHP during pregnancy was associated with decreased fetal growth, which could have repercussive effects. PMID:27320326

  1. Comparison of placental growth factor and fetal flow Doppler ultrasonography to identify fetal adverse outcomes in women with hypertensive disorders of pregnancy: an observational study

    PubMed Central

    2013-01-01

    Background Hypertensive disorders of pregnancy and intrauterine growth restriction (IUGR) are leading causes of maternal and perinatal morbidity and mortality. Failure to detect intrauterine growth restriction in women at high risk has been highlighted as a significant avoidable cause of serious fetal outcome. In this observational study we compare fetal flow using Doppler ultrasonography with a new test for placental growth factor (PlGF) to predict fetal adverse events. Methods Eighty-nine women with hypertensive disorders of pregnancy (24 with chronic hypertension, 17 with gestational hypertension, 12 with HELLP syndrome, 19 with preeclampsia and 17 with superimposed preeclampsia) were enrolled. A single maternal blood sample to measure free PlGF (Alere Triage) taken before 35 weeks of pregnancy was compared to the last Doppler ultrasound measurement of fetal flow before delivery. PlGF was classified as normal (PlGF≥100 pg/ml), low (12fetal flow was defined as either signs of centralisation of the fetal circulation or diastolic block or reverse flow in the umbilical artery or descending aorta; this was a criterion for delivery. Fetal outcomes were intrauterine growth restriction and birth before 37 weeks of pregnancy. Results In total 61/89 women had a preterm birth and 22 infants had IUGR. Of those who delivered preterm, 20/20 women with abnormal fetal flow and 36/41 (87.8%) women with normal fetal flow had low or very low PlGF. Of those infants with IUGR, 22/22 had low or very low maternal PlGF and 10/22 had abnormal fetal flow. Conclusions PlGF may provide useful information before 35th gestational week to identify fetuses requiring urgent delivery, and those at risk of later adverse outcomes not identified by fetal flow Doppler ultrasonography. PMID:23937721

  2. Proline metabolism in the conceptus: implications for fetal growth and development.

    PubMed

    Wu, G; Bazer, F W; Datta, S; Johnson, G A; Li, P; Satterfield, M C; Spencer, T E

    2008-11-01

    Although there are published studies of proline biochemistry and nutrition in cultured cells and postnatal animals, little is known about proline metabolism and function in the conceptus (embryo/fetus, associated placental membranes, and fetal fluids). Because of the invasive nature of biochemical research on placental and fetal growth, animal models are often used to test hypotheses of biological importance. Recent evidence from studies with pigs and sheep shows that proline is a major substrate for polyamine synthesis via proline oxidase, ornithine aminotransferase, and ornithine decarboxylase in placentae. Both porcine and ovine placentae have a high capacity for proline catabolism and polyamine production. In addition, allantoic and amniotic fluids contain enzymes to convert proline into ornithine, which is delivered through the circulation to placental tissues. There is exquisite metabolic coordination among integrated pathways that support highest rates of polyamine synthesis and concentrations in placentae during early gestation when placental growth is most rapid. Interestingly, reduced placental and fetal growth are associated with reductions in placental proline transport, proline oxidase activity, and concentrations of polyamines in gestating dams with either naturally occurring or malnutrition-induced growth retardation. Conversely, increasing proline availability in maternal plasma through nutritional or pharmacological modulation in pigs and sheep enhances concentrations of proline and polyamines in placentae and fetal fluids, as well as fetal growth. These novel findings suggest an important role for proline in conceptus metabolism, growth and development, as well as a potential treatment for intrauterine growth restriction, which is a significant problem in both human medicine and animal agriculture.

  3. Endocrine regulation of human fetal growth: the role of the mother, placenta, and fetus.

    PubMed

    Murphy, Vanessa E; Smith, Roger; Giles, Warwick B; Clifton, Vicki L

    2006-04-01

    The environment in which the fetus develops is critical for its survival and long-term health. The regulation of normal human fetal growth involves many multidirectional interactions between the mother, placenta, and fetus. The mother supplies nutrients and oxygen to the fetus via the placenta. The fetus influences the provision of maternal nutrients via the placental production of hormones that regulate maternal metabolism. The placenta is the site of exchange between mother and fetus and regulates fetal growth via the production and metabolism of growth-regulating hormones such as IGFs and glucocorticoids. Adequate trophoblast invasion in early pregnancy and increased uteroplacental blood flow ensure sufficient growth of the uterus, placenta, and fetus. The placenta may respond to fetal endocrine signals to increase transport of maternal nutrients by growth of the placenta, by activation of transport systems, and by production of placental hormones to influence maternal physiology and even behavior. There are consequences of poor fetal growth both in the short term and long term, in the form of increased mortality and morbidity. Endocrine regulation of fetal growth involves interactions between the mother, placenta, and fetus, and these effects may program long-term physiology.

  4. Developmental changes in polyamines and autophagic marker levels in normal and growth-restricted fetal pigs.

    PubMed

    Zhu, Y H; Lin, G; Dai, Z L; Zhou, T J; Yuan, T L; Feng, C P; Chen, F; Wu, G Y; Wang, J J

    2015-07-01

    Polyamines are essential for embryonic and fetal survival, growth, and development. Additionally, polyamines may induce autophagy in mammalian cells. However, little is known about the availability of polyamines or autophagy in the porcine conceptus with intrauterine growth restriction (IUGR). The present study was performed to evaluate the developmental changes of polyamine concentrations in IUGR and normal porcine fetuses as well as autophagic marker levels in the fetal intestinal mucosa during the second half of gestation when most fetal growth occurs. Allantoic fluid (ALF), amniotic fluid (AMF), umbilical vein, and the small-intestinal mucosa were obtained from both IUGR and normal fetal pigs at d 60, 90, and 110 of gestation. Concentrations of polyamines in fetal fluids as well as protein abundances of microtubule-associated protein light chain 3B (LC3B), an autophagic marker, in the fetal small-intestinal mucosa were determined. Concentrations of polyamines varied greatly in different fetal compartments and changed substantially with advancing gestation. Concentrations of polyamines in IUGR fetal fluids and the small-intestinal mucosa were markedly different from those in their normal counterparts at d 60 and 90 of gestation, whereas most of the differences were not detected by late (d 110) gestation. Specifically, polyamine levels were lower in the umbilical vein plasma but higher in ALF and AMF from IUGR fetuses. Furthermore, enhanced levels of an autophagic marker were observed in the small-intestinal mucosa of IUGR fetuses throughout mid and late gestation in association with abnormal spermidine levels in fetal plasma. These findings support the notion that enhanced autophagy may be an important survival mechanism in IUGR fetuses. Collectively, our findings provide a new framework for future studies to define the roles for polyamines in the prevention and treatment of IUGR in both human medicine and animal production.

  5. A computational model of the fetal circulation to quantify blood redistribution in intrauterine growth restriction.

    PubMed

    Garcia-Canadilla, Patricia; Rudenick, Paula A; Crispi, Fatima; Cruz-Lemini, Monica; Palau, Georgina; Camara, Oscar; Gratacos, Eduard; Bijnens, Bart H; Bijens, Bart H

    2014-06-01

    Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this brain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental understanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has been limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since they allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be directly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed, including the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow personalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to understand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery (MCA) flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this affects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the proposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The results support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance between increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying the balance between cerebral and peripheral-placental remodeling

  6. A Computational Model of the Fetal Circulation to Quantify Blood Redistribution in Intrauterine Growth Restriction

    PubMed Central

    Garcia-Canadilla, Patricia; Rudenick, Paula A.; Crispi, Fatima; Cruz-Lemini, Monica; Palau, Georgina; Camara, Oscar; Gratacos, Eduard; Bijens, Bart H.

    2014-01-01

    Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this brain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental understanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has been limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since they allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be directly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed, including the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow personalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to understand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery (MCA) flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this affects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the proposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The results support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance between increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying the balance between cerebral and peripheral-placental remodeling

  7. Effects of maternal drinking and marijuana use on fetal growth and development.

    PubMed

    Hingson, R; Alpert, J J; Day, N; Dooling, E; Kayne, H; Morelock, S; Oppenheimer, E; Zuckerman, B

    1982-10-01

    A study of 1,690 mother/child pairs at Boston City Hospital was conducted to assess the impact of maternal alcohol consumption on fetal development when confounding variables were controlled. Level of maternal drinking prior to pregnancy was associated with shorter duration of gestation. Lower maternal weight change, history of maternal illnesses, cigarette smoking, and marijuana use, however, were more consistently related to adverse fetal growth and development. New findings in this study include a negative association between maternal marijuana use during pregnancy and fetal growth. Also when confounding variables were controlled, women who used marijuana during pregnancy were five times more likely to deliver infants with features considered compatible with the fetal alcohol syndrome.

  8. Cadmium Associated With Inhaled Cadmium Oxide Nanoparticles Impacts Fetal and Neonatal Development and Growth

    PubMed Central

    Blum, Jason L.; Xiong, Judy Q.; Hoffman, Carol; Zelikoff, Judith T.

    2012-01-01

    One industrially important metal oxide nanoparticle (NP) is cadmium oxide (CdO). A study was performed using timed-pregnant CD-1 mice to determine if Cd associated with inhaled CdO NP could reach the placenta and adversely affect the developing fetus and/or neonate. Pregnant mice were exposed by inhalation either every other day to 100 μg of freshly generated CdO/m3 (exposure 1) or daily to 230 μg CdO/m3 (exposure 2). In each exposure, mice were exposed to CdO NP or carrier gas (control) for 2.5 h from 4.5 days post coitus (dpc) through 16.5 dpc. At 17.5 dpc, fetuses and placentas from both exposures 1 and 2 were collected, measured, and weighed. A subgroup from the second exposure was allowed to give birth, and neonates were weighed daily until weaning. Cadmium in the uterus and placenta, as well as in other maternal organs, was elevated in NP-treated mice, but was undetectable in fetuses at 17.5 dpc. Daily inhalation of 230 μg CdO NP/m3 decreased the incidence of pregnancy (i.e., no evidence of implantation) by 23%, delayed maternal weight gain, altered placental weight, and decreased fetal length, as well as delayed neonatal growth. This study demonstrates that inhalation of CdO NP during pregnancy adversely affects reproductive fecundity and alters fetal and postnatal growth of the developing offspring. PMID:22240978

  9. The role and interaction of imprinted genes in human fetal growth

    PubMed Central

    Moore, Gudrun E.; Ishida, Miho; Demetriou, Charalambos; Al-Olabi, Lara; Leon, Lydia J.; Thomas, Anna C.; Abu-Amero, Sayeda; Frost, Jennifer M.; Stafford, Jaime L.; Chaoqun, Yao; Duncan, Andrew J.; Baigel, Rachel; Brimioulle, Marina; Iglesias-Platas, Isabel; Apostolidou, Sophia; Aggarwal, Reena; Whittaker, John C.; Syngelaki, Argyro; Nicolaides, Kypros H.; Regan, Lesley; Monk, David; Stanier, Philip

    2015-01-01

    Identifying the genetic input for fetal growth will help to understand common, serious complications of pregnancy such as fetal growth restriction. Genomic imprinting is an epigenetic process that silences one parental allele, resulting in monoallelic expression. Imprinted genes are important in mammalian fetal growth and development. Evidence has emerged showing that genes that are paternally expressed promote fetal growth, whereas maternally expressed genes suppress growth. We have assessed whether the expression levels of key imprinted genes correlate with fetal growth parameters during pregnancy, either early in gestation, using chorionic villus samples (CVS), or in term placenta. We have found that the expression of paternally expressing insulin-like growth factor 2 (IGF2), its receptor IGF2R, and the IGF2/IGF1R ratio in CVS tissues significantly correlate with crown–rump length and birthweight, whereas term placenta expression shows no correlation. For the maternally expressing pleckstrin homology-like domain family A, member 2 (PHLDA2), there is no correlation early in pregnancy in CVS but a highly significant negative relationship in term placenta. Analysis of the control of imprinted expression of PHLDA2 gave rise to a maternally and compounded grand-maternally controlled genetic effect with a birthweight increase of 93/155 g, respectively, when one copy of the PHLDA2 promoter variant is inherited. Expression of the growth factor receptor-bound protein 10 (GRB10) in term placenta is significantly negatively correlated with head circumference. Analysis of the paternally expressing delta-like 1 homologue (DLK1) shows that the paternal transmission of type 1 diabetes protective G allele of rs941576 single nucleotide polymorphism (SNP) results in significantly reduced birth weight (−132 g). In conclusion, we have found that the expression of key imprinted genes show a strong correlation with fetal growth and that for both genetic and genomics data analyses

  10. Syncytiotrophoblast Functions and Fetal Growth Restriction during Placental Malaria: Updates and Implication for Future Interventions

    PubMed Central

    Kidima, Winifrida B.

    2015-01-01

    Syncytiotrophoblast lines the intervillous space of the placenta and plays important roles in fetus growth throughout gestation. However, perturbations at the maternal-fetal interface during placental malaria may possibly alter the physiological functions of syncytiotrophoblast and therefore growth and development of the embryo in utero. An understanding of the influence of placental malaria on syncytiotrophoblast function is paramount in developing novel interventions for the control of placental pathology associated with placental malaria. In this review, we discuss how malaria changes syncytiotrophoblast function as evidenced from human, animal, and in vitro studies and, further, how dysregulation of syncytiotrophoblast function may impact fetal growth in utero. We also formulate a hypothesis, stemming from epidemiological observations, that nutrition may override pathogenesis of placental malaria-associated-fetal growth restriction. We therefore recommend studies on nutrition-based-interventional approaches for high placental malaria-risk women in endemic areas. More investigations on the role of nutrition on placental malaria pathogenesis are needed. PMID:26587536

  11. Assessment of in vivo fetal growth and placental vascular function in a novel intrauterine growth restriction model of progressive uterine artery occlusion in guinea pigs.

    PubMed

    Herrera, Emilio A; Alegría, René; Farias, Marcelo; Díaz-López, Farah; Hernández, Cherie; Uauy, Ricardo; Regnault, Timothy R H; Casanello, Paola; Krause, Bernardo J

    2016-03-15

    Intra-uterine growth restriction (IUGR) is associated with short and long-term metabolic and cardiovascular alterations. Mice and rats have been extensively used to study the effects of IUGR, but there are notable differences in fetal and placental physiology relative to those of humans that argue for alternative animal models. This study proposes that gradual occlusion of uterine arteries from mid-gestation in pregnant guinea pigs produces a novel model to better assess human IUGR. Fetal biometry and in vivo placental vascular function were followed by sonography and Doppler of control pregnant guinea pigs and sows submitted to surgical placement of ameroid constrictors in both uterine arteries (IUGR) at mid-gestation (35 days). The ameroid constrictors induced a reduction in the fetal abdominal circumference growth rate (0.205 cm day(-1) ) compared to control (0.241 cm day(-1) , P < 0.001) without affecting biparietal diameter growth. Umbilical artery pulsatility and resistance indexes at 10 and 20 days after surgery were significantly higher in IUGR animals than controls (P < 0.01). These effects were associated with a decrease in the relative luminal area of placental chorionic arteries (21.3 ± 2.2% vs. 33.2 ± 2.7%, P < 0.01) in IUGR sows at near term. Uterine artery intervention reduced fetal (∼30%), placental (∼20%) and liver (∼50%) weights (P < 0.05), with an increased brain to liver ratio (P < 0.001) relative to the control group. These data demonstrate that the ameroid constrictor implantations in uterine arteries in pregnant guinea pigs lead to placental vascular dysfunction and altered fetal growth that induces asymmetric IUGR. PMID:26719023

  12. Periconceptional growth hormone treatment alters fetal growth and development in lambs.

    PubMed

    Koch, J M; Wilmoth, T A; Wilson, M E

    2010-05-01

    Research in the area of fetal programming has focused on intrauterine growth restriction. Few studies have attempted to examine programming mechanisms that ultimately lead to lambs with a greater potential for postnatal growth. We previously demonstrated that treatment of ewes with GH at the time of breeding led to an increase in birth weight. Therefore, the objective of this study was to determine the effects of a single injection of sustained-release GH given during the periconceptional period on fetal growth and development and to determine if the GH axis would be altered in these offspring. Estrus was synchronized using 2 injections of PGF(2alpha); at the time of the second injection, ewes assigned to treatment were also given an injection of sustained-release GH. A maternal jugular vein sample was taken weekly to analyze IGF-I as a proxy for GH to estimate the duration of the treatment effect. In ewes treated with GH, IGF-I increased (P < 0.05) by wk 1 and remained elevated until wk 4 postinjection. Lambs were weighed, crown-rump length and abdominal girth were determined, and a plasma sample was collected. In a subset of male lambs, liver, heart, and brain weights were obtained, as well as left and right ventricular wall thicknesses. On postnatal d 100, a subset of ewe lambs were weighed and challenged with an intravenous injection of GHRH. Lambs from treated ewes had increased (P < 0.05) birth weight and abdominal girth compared with control lambs; however, there was no difference in crown-rump length. Expression of GH receptor and IGF-I were increased (P < 0.05) in lambs gestated by GH-treated ewes compared with control ewes. The left ventricular wall was thinner (P < 0.05) from lambs in the GH-treated group compared with control lambs. On postnatal d 100, those ewe lambs born to ewes treated with GH continued to be heavier (P < 0.05) and had no IGF-I response to GHRH challenge. In conclusion, treating ewes with a single injection of GH appeared to alter

  13. Fetal growth restriction and 18-year growth and nutritional status: Aboriginal birth cohort 1987-2007.

    PubMed

    Sayers, Susan; Mott, Susan; Singh, Gurmeet

    2011-01-01

    The main objective of the work is to compare the growth and nutritional status of Australian Aboriginal term infants born with (n = 81) and without fetal growth restriction (n = 260). A prospective birth cohort study of 341 Aboriginal babies from the Top End of the Northern Territory of Australia was recruited at birth (1987-1990) and re-examined at a mean age of 18.3 years (2006-2008) for outcome measures of growth and nutrition status. Those with growth restriction at birth were 3 cm shorter (P = 0.0026) and 9 kg lighter (P = 0.0001) with head circumferences 0.95 cm smaller (P = 0.0008) than those without growth restriction. The proportions of growth restricted participants with body mass index <18.5 kg/m(2) were significantly greater (P = 0.028), and those with BMI > 25 kg/m(2) and with fat percentage >85th percentile were significantly smaller (P = 0.012 and 0.004, respectively). In this cohort, those Aboriginal babies born smaller and lighter have remained smaller and lighter at 18 years of age. However, the highest risk of later chronic noncommunicable disease has been reported in subjects who were born small and become relatively larger in later life. The continued study of this Aboriginal birth cohort will give us an opportunity to determine if and when in later life the effects of birth weight are modified by environmental nutritional factors.

  14. Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences

    PubMed Central

    Dean, Afshan; van den Driesche, Sander; Wang, Yili; McKinnell, Chris; Macpherson, Sheila; Eddie, Sharon L.; Kinnell, Hazel; Hurtado-Gonzalez, Pablo; Chambers, Tom J.; Stevenson, Kerrie; Wolfinger, Elke; Hrabalkova, Lenka; Calarrao, Ana; Bayne, Rosey AL; Hagen, Casper P.; Mitchell, Rod T.; Anderson, Richard A.; Sharpe, Richard M.

    2016-01-01

    Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development and reproductive function in resulting offspring (F1) or in the F2 generation. Exposure to either analgesic reduced F1 fetal GC number in both sexes and altered the tempo of fetal GC development sex-dependently, with delayed meiotic entry in oogonia but accelerated GC differentiation in males. These effects persisted in adult F1 females as reduced ovarian and litter size, whereas F1 males recovered normal GC numbers and fertility by adulthood. F2 offspring deriving from an analgesic-exposed F1 parent also exhibited sex-specific changes. F2 males exhibited normal reproductive development whereas F2 females had smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise concerns that analgesic use in pregnancy could potentially affect fertility of resulting daughters and grand-daughters. PMID:26813099

  15. Sex differences in fetal growth responses to maternal height and weight

    PubMed Central

    Gotsch, Francesca; Kusanovic, Juan Pedro; Gomez, Ricardo; Nien, Jyh Kae; Frongillo, Edward A.; Romero, Roberto

    2012-01-01

    Sex differences in fetal growth have been reported, but how this happens remains to be described. It is unknown if fetal growth rates, a reflection of genetic and environmental factors, express sexually dimorphic sensitivity to the mother herself. This analysis investigated homogeneity of male and female growth responses to maternal height and weight. The study sample included 3495 uncomplicated singleton pregnancies followed longitudinally. Analytic models regressed fetal and neonatal weight on tertiles of maternal height and weight, and modification by sex was investigated (n=1814 males, n=1681 females) with birth gestational age, maternal parity and smoking as covariates. Sex modified the effects of maternal height and weight on fetal growth rates and birth weight. Among boys, tallest maternal height influenced fetal weight growth prior to 18 gestational weeks of age (p=0.006), pre-pregnancy maternal weight and BMI subsequently had influence (p<0.001); this was not found among girls. Additionally, interaction terms between sex, maternal height, and maternal weight identified that males were more sensitive to maternal weight among shorter mothers (p=0.003), and more responsive to maternal height among lighter mothers (p<=0.03), compared to females. Likewise, neonatal birth weight dimorphism varied by maternal phenotype. A male advantage of 60 grams occurred among neonates of the shortest and lightest mothers (p=0.08), compared to 150 and 191 grams among short and heavy mothers, and tall and light weight mothers, respectively (p=0.01). Sex differences in response to maternal size are underappreciated sources of variation in fetal growth studies and may reflect differential growth strategies. PMID:19950190

  16. Associations of Maternal Retinal Vasculature with Subsequent Fetal Growth and Birth Size

    PubMed Central

    Li, Ling-Jun; Aris, Izzuddin; Su, Lin Lin; Tint, Mya Thway; Cheung, Carol Yim-Lui; Ikram, M. Kamran; Gluckman, Peter; Godfrey, Keith M.; Tan, Kok Hian; Yeo, George; Yap, Fabian; Kwek, Kenneth; Saw, Seang-Mei; Chong, Yap-Seng; Wong, Tien-Yin; Lee, Yung Seng

    2015-01-01

    Objective We aimed to study the maternal retinal microvasculature at mid-trimester and its relationship with subsequent fetal growth and birth size. Methods We recruited 732 pregnant women aged 18-46 years in the first trimester with singleton pregnancies. All had retinal photography and fetal scan performed at 26-28 weeks gestation, and subsequent fetal scan at 32-34 weeks gestation. Infant anthropometric measurements were done at birth. Retinal microvasculature was measured using computer software from the retinal photographs. Results In multiple linear regression models, each 10 μm narrowing in maternal retinal arteriolar caliber was associated with decreases of 1.36 mm in fetal head circumference at 32-34 weeks gestation, as well as decreases of 1.50 mm and 2.30 mm in infant head circumference and birth length at delivery, respectively. Each standard deviation decrease in maternal retinal arteriolar fractal dimension was associated with decreases of 1.55 mm in fetal head circumference at 32-34 weeks gestation, as well as decreases of 1.08 mm and 46.42 g in infant head circumference and birth weight at delivery, respectively. Conclusions Narrower retinal arteriolar caliber and a sparser retinal vascular network in mothers, reflecting a suboptimal uteroplacental microvasculature during mid-pregnancy, were associated with poorer fetal growth and birth size. PMID:25909909

  17. Maternal testosterone and placental function: Effect of electroacupuncture on placental expression of angiogenic markers and fetal growth.

    PubMed

    Fornes, Romina; Hu, Min; Maliqueo, Manuel; Kokosar, Milana; Benrick, Anna; Carr, David; Billig, Håkan; Jansson, Thomas; Manni, Luigi; Stener-Victorin, Elisabet

    2016-09-15

    Women with polycystic ovary syndrome (PCOS) have elevated circulating androgens during pregnancy and are at an increased risk of adverse pregnancy outcomes. Here we tested the hypotheses that maternal androgen excess decrease placental and fetal growth, and placental expression of markers of steroidogenesis, angiogenesis and sympathetic activity, and that acupuncture with low-frequency electrical stimulation prevents these changes. Pregnant rats were exposed to vehicle or testosterone on gestational day (GD)15-19. Low-frequency electroacupuncture (EA) or handling, as a control for the EA procedure, was given to control or testosterone exposed dams on GD16-20. On GD21, blood pressure was measured and maternal blood, fetuses and placentas collected. Placental steroid receptor expression and proteins involved in angiogenic, neurotrophic and adrenergic signaling were analyzed. EA did not affect any variables in control rats except maternal serum corticosterone, which was reduced. EA in testosterone exposed dams compared with controls increased systolic pressure by 30%, decreased circulating norepinephrine and corticosterone, fetal and placental weight and placental VEGFR1 and proNGF protein expression, and increased the VEGFA/VEGFR1 ratio, mature NGF (mNGF) and the mNGF/proNGF ratio. In conclusion, low-frequency EA in control animals did not have any negative influence on any of the studied variables. In contrast, EA in pregnant dams exposed to testosterone increased blood pressure and impaired placental growth and function, leading to decreased fetal growth. PMID:27208621

  18. Periconception folic acid supplementation, fetal growth and the risks of low birth weight and preterm birth: the Generation R Study.

    PubMed

    Timmermans, Sarah; Jaddoe, Vincent W V; Hofman, Albert; Steegers-Theunissen, Régine P M; Steegers, Eric A P

    2009-09-01

    Countries worldwide, including the Netherlands, recommend that women planning pregnancy use a folic acid supplement during the periconception period. Some countries even fortify staple foods with folic acid. These recommendations mainly focus on the prevention of neural tube defects, despite increasing evidence that folic acid may also influence birth weight. We examined whether periconception folic acid supplementation affects fetal growth and the risks of low birth weight, small for gestational age (SGA) and preterm birth, in the Generation R Study in Rotterdam, the Netherlands. Main outcome measures were fetal growth measured in mid- and late pregnancy by ultrasound, birth weight, SGA and preterm birth in relation to periconception folic supplementation (0.4-0.5 mg). Data on 6353 pregnancies were available. Periconception folic acid supplementation was positively associated with fetal growth. Preconception folic acid supplementation was associated with 68 g higher birth weight (95 % CI 37.2, 99.0) and 13 g higher placental weight (95 % CI 1.1, 25.5), compared to no folic acid supplementation. In these analyses parity significantly modified the effect estimates. Start of folic acid supplementation after pregnancy confirmation was associated with a reduced risk of low birth weight (OR 0.61, 95 % CI 0.40, 0.94). Similarly, reduced risks for low birth weight and SGA were observed for women who started supplementation preconceptionally, compared to those who did not use folic acid (OR 0.43, 95 % CI 0.28, 0.69 and OR 0.40, 95 % CI 0.22, 0.72). In conclusion, periconception folic acid supplementation is associated with increased fetal growth resulting in higher placental and birth weight, and decreased risks of low birth weight and SGA.

  19. Neurobehavioral determinants of nutritional security in fetal growth-restricted individuals.

    PubMed

    Portella, André Krumel; Silveira, Patrícia Pelufo

    2014-12-01

    Fetal growth restriction results from a failure to achieve a higher growth potential and has been associated with many maternal conditions, such as chronic diseases (infections, hypertension, and some cases of diabetes and obesity), exposures (tobacco smoke, drugs), and malnutrition. This early adversity induces a series of adaptive physiological responses aimed at improving survival, but imposing increased risk for developing chronic nontransmittable diseases (obesity, type II diabetes, cardiovascular disease) in the long term. Recently, mounting evidence has shown that fetal growth impairment is related to altered feeding behavior and preferences through the life course. When living in countries undergoing nutritional transition, in which individuals experience the coexistence of underweight and overweight problems (the "double burden of malnutrition"), fetal growth-restricted children can be simultaneously growth restricted and overweight-a double burden of malnutrition at the individual level. Considering food preferences as an important aspect of nutrition security, we will summarize the putative neurobiological mechanisms at the core of the relationship between fetal growth and nutrition security over the life course and the evidence linking early life adversity to later food preferences.

  20. Gestational Dietary Protein Is Associated with Sex Specific Decrease in Blood Flow, Fetal Heart Growth and Post-Natal Blood Pressure of Progeny

    PubMed Central

    2015-01-01

    Study Overview The incidence of adverse pregnancy outcomes is higher in pregnancies where the fetus is male. Sex specific differences in feto-placental perfusion indices identified by Doppler assessment have recently been associated with placental insufficiency and fetal growth restriction. This study aims to investigate sex specific differences in placental perfusion and to correlate these changes with fetal growth. It represents the largest comprehensive study under field conditions of uterine hemodynamics in a monotocous species, with a similar long gestation period to the human. Primiparous 14mo heifers in Australia (n=360) and UK (n=180) were either individually or group fed, respectively, diets with differing protein content (18, 14, 10 or 7% crude protein (CP)) from 60d prior to 98 days post conception (dpc). Fetuses and placentae were excised at 98dpc (n = 48). Fetal development an median uterine artery blood flow were assessed monthly from 36dpc until term using B-mode and Doppler ultrasonography. MUA blood flow to the male feto-placental unit increased in early pregnancy associated with increased fetal growth. Protein restriction before and shortly after conception (-60d up to 23dpc) increased MUA diameter and indices of velocity during late pregnancy, reduced fetal heart weight in the female fetus and increased heart rate at birth, but decreased systolic blood pressure at six months of age. Conclusion and Significance Sex specific differences both in feto-placental Doppler perfusion indices and response of these indices to dietary perturbations were observed. Further, maternal diet affected development of fetal cardiovascular system associated with altered fetal haemodynamics in utero, with such effects having a sex bias. The results from this study provide further insight into the gender specific circulatory differences present in the fetal period and developing cardiovascular system. PMID:25915506

  1. Organochlorine Compounds and Ultrasound Measurements of Fetal Growth in the INMA Cohort (Spain)

    PubMed Central

    Lopez-Espinosa, Maria-Jose; Murcia, Mario; Iñiguez, Carmen; Vizcaino, Esther; Costa, Olga; Fernández-Somoano, Ana; Basterrechea, Mikel; Lertxundi, Aitana; Guxens, Mònica; Gascon, Mireia; Goñi-Irigoyen, Fernando; Grimalt, Joan O.; Tardón, Adonina; Ballester, Ferran

    2015-01-01

    Background Several studies have reported decreases in birth size associated with exposure to organochlorine compounds (OCs), but uncertainties remain regarding the critical windows of prenatal exposure and the effects on fetal body segments. Objective We examined the relationship between prenatal OC concentrations and fetal anthropometry. Methods We measured 4,4´-dichlorodiphenyldichloroethylene (4,4´-DDE), hexachlorobenzene (HCB), and polychlorinated biphenyl (PCB) congeners (138, 153, and 180) in 2,369 maternal and 1,140 cord serum samples in four Spanish cohorts (2003–2008). We used linear mixed models to obtain longitudinal growth curves for estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), and femur length (FL) adjusted by parental and fetal characteristics. We calculated standard deviation (SD) scores of growth at 0–12, 12–20, and 20–34 weeks of gestation as well as size at gestational week 34 for the four parameters. We studied the association between OCs and the fetal outcomes by cohort-specific linear models and subsequent meta-analyses. Results PCBs were associated with a reduction in AC up to mid-pregnancy, and BPD and FL from gestational week 20 onward. An inverse association was also found between HCB and AC growth in early pregnancy. The reduction of these parameters ranged from –4% to –2% for a doubling in the OC concentrations. No association between 4,4´-DDE and fetal growth was observed. Conclusions To our knowledge, this is the first study to report an association between prenatal exposure to some PCBs and HCB and fetal growth: AC during the first two trimesters of pregnancy, and BPD and FL later in pregnancy. Citation Lopez-Espinosa MJ, Murcia M, Iñiguez C, Vizcaino E, Costa O, Fernández-Somoano A, Basterrechea M, Lertxundi A, Guxens M, Gascon M, Goñi-Irigoyen F, Grimalt JO, Tardón A, Ballester F. 2016. Organochlorine compounds and ultrasound measurements of fetal growth in the INMA cohort

  2. The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

    SciTech Connect

    Ergaz, Zivanit; Shoshani-Dror, Dana; Guillemin, Claire; Neeman-azulay, Meytal; Fudim, Liza; Weksler-Zangen, Sarah; Stodgell, Christopher J.; Miller, Richard K.; Ornoy, Asher

    2012-12-01

    High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1 ppm or 2 ppm of copper throughout their pregnancy. Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1 ppm and 2 ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 α among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity. -- Highlights: ► High sucrose low copper diet restricted fetal growth in the Cohen diabetic rat model ► Maternal copper blood levels directly correlated with fetal liver copper content ► Copper supplementation decreased embryonic resorption in the inbred strains ► Copper supplementation reduced hyperglycemia in the sucrose sensitive inbred strain ► Copper supplementation alleviated growth restriction and

  3. Zinc-deficient diet decreases fetal long bone growth through decreased bone matrix formation in mice.

    PubMed

    Kim, Jung-Tak; Baek, Sang-Heum; Lee, Sang-Han; Park, Eui Kyun; Kim, Eun-Cheol; Kwun, In-Sook; Shin, Hong-In

    2009-02-01

    This study evaluated the effects of zinc on skeletal development during fetal development in pregnant ICR mice fed a zinc-deficient (3 mg/kg) or zinc-adequate (30 mg/kg) diet. We also included a group pair-fed with the zinc-deficient group to control for decreased appetite due to zinc deficiency. Developing fetuses at embryonic day 18.5 were removed by cesarean section, and the skeletal development was evaluated by histological analysis as well as by body weight and longitudinal growth measurement. Reduced maternal food intake in the zinc-deficient and pair-fed groups resulted in a marked and significant (P < .05) decrease in fetal weight compared to that of the zinc-adequate group. However, fetal length retardation in the pair-fed group was less marked than in the zinc-deficient group, suggesting that reduced supply of zinc from maternal circulation may play a role in longitudinal growth through skeletal development. The fetal developing tibia of the zinc-deficient group showed marked shortening of diaphysis and a mild narrowing of the hypertrophic chondrocyte zone width with increased osteoclast number, but there was no influence on the mineralization of bone matrix. This may be the result of reduced activation of osteoblasts and maturation of chondrocytes with increased osteoclastic activity, suggesting that zinc deficiency during the fetal development has a greater impact on the matrix formation of bone than the mineralization of bone matrix.

  4. Maternal Obesity Affects Fetal Neurodevelopmental and Metabolic Gene Expression: A Pilot Study

    PubMed Central

    Edlow, Andrea G.; Vora, Neeta L.; Hui, Lisa; Wick, Heather C.; Cowan, Janet M.; Bianchi, Diana W.

    2014-01-01

    Objective One in three pregnant women in the United States is obese. Their offspring are at increased risk for neurodevelopmental and metabolic morbidity. Underlying molecular mechanisms are poorly understood. We performed a global gene expression analysis of mid-trimester amniotic fluid cell-free fetal RNA in obese versus lean pregnant women. Methods This prospective pilot study included eight obese (BMI≥30) and eight lean (BMI<25) women undergoing clinically indicated mid-trimester genetic amniocentesis. Subjects were matched for gestational age and fetal sex. Fetuses with abnormal karyotype or structural anomalies were excluded. Cell-free fetal RNA was extracted from amniotic fluid and hybridized to whole genome expression arrays. Genes significantly differentially regulated in 8/8 obese-lean pairs were identified using paired t-tests with the Benjamini-Hochberg correction (false discovery rate of <0.05). Biological interpretation was performed with Ingenuity Pathway Analysis and the BioGPS gene expression atlas. Results In fetuses of obese pregnant women, 205 genes were significantly differentially regulated. Apolipoprotein D, a gene highly expressed in the central nervous system and integral to lipid regulation, was the most up-regulated gene (9-fold). Apoptotic cell death was significantly down-regulated, particularly within nervous system pathways involving the cerebral cortex. Activation of the transcriptional regulators estrogen receptor, FOS, and STAT3 was predicted in fetuses of obese women, suggesting a pro-estrogenic, pro-inflammatory milieu. Conclusion Maternal obesity affects fetal neurodevelopmental and metabolic gene expression as early as the second trimester. These findings may have implications for postnatal neurodevelopmental and metabolic abnormalities described in the offspring of obese women. PMID:24558408

  5. Spontaneous Preterm Delivery, Particularly with Reduced Fetal Growth, is Associated with DNA Hypomethylation of Tumor Related Genes

    PubMed Central

    Chen, Xinhua; Bai, Guang; Scholl, Theresa O

    2016-01-01

    Background Preterm delivery and sub-optimal fetal growth are associated with each other and affect both mother and infant. Our aim was to determine (i) whether there are detectable differences in DNA methylation between early and late gestation and (ii) whether changes in DNA methylation from entry are associated with spontaneous preterm delivery with and without reduced fetal growth. Methods We conducted a case-control study nested within a large prospective cohort. Gene specific methylation was measured by Methyl-Profiler PCR Array in a Human Breast Cancer Signature Panel of 24 genes from maternal peripheral leukocytes genomic DNA at entry and 3rd trimester (sampled at 16 and 30 weeks of gestation, respectively). Clonal bisulfite DNA sequencing was performed to confirm the changes in selected genes (CYP1B1, GADD45A and CXCL12). Multivariable analysis was used for data analysis. Results There was significantly decrease in DNA methylation in 15 of 24 genes during the 3rd trimester in cases of spontaneous preterm delivery (n=23) as compared to the controls (n=19) (p<0.05–p<0.01 for each gene). Similar results were observed by bisulfite sequencing for 3 genes. The change in DNA methylation between late and early gestation was significantly different in cases (overall decrease in methylation was −4.0 ± 1.5%) compared to the controls (overall increase in methylation was 12.6 ± 2.19%, p<0.0001). A graded pattern of DNA methylation was observed in 15 genes. Cases who delivered preterm with reduced fetal growth had the lowest level of methylation, cases delivering preterm without reduced fetal growth were next and term controls were highest in methylation (p for trend <0.05 to p<0.01 for each gene). Cases of preterm delivery also had significantly lower dietary choline intake. Conclusions These data suggest that epigenetic modification is associated with an increased risk of spontaneous preterm delivery, spontaneous preterm delivery with reduced fetal growth in

  6. Enhanced or Reduced Fetal Growth Induced by Embryo Transfer into Smaller or Larger Breeds Alters Post-Natal Growth and Metabolism in Pre-Weaning Horses

    PubMed Central

    Peugnet, Pauline; Wimel, Laurence; Duchamp, Guy; Sandersen, Charlotte; Camous, Sylvaine; Guillaume, Daniel; Dahirel, Michèle; Dubois, Cédric; Jouneau, Luc; Reigner, Fabrice; Berthelot, Valérie; Chaffaux, Stéphane; Tarrade, Anne; Serteyn, Didier; Chavatte-Palmer, Pascale

    2014-01-01

    In equids, placentation is diffuse and nutrient supply to the fetus is determined by uterine size. This correlates with maternal size and affects intra-uterine development and subsequent post-natal growth, as well as insulin sensitivity in the newborn. Long-term effects remain to be described. In this study, fetal growth was enhanced or restricted through ET using pony (P), saddlebred (S) and draft (D) horses. Control P-P (n = 21) and S-S (n = 28) pregnancies were obtained by AI. Enhanced and restricted pregnancies were obtained by transferring P or S embryos into D mares (P-D, n = 6 and S-D, n = 8) or S embryos into P mares (S-P, n = 6), respectively. Control and experimental foals were raised by their dams and recipient mothers, respectively. Weight gain, growth hormones and glucose homeostasis were investigated in the foals from birth to weaning. Fetal growth was enhanced in P-D and these foals remained consistently heavier, with reduced T3 concentrations until weaning compared to P-P. P-D had lower fasting glucose from days 30 to 200 and higher insulin secretion than P-P after IVGTT on day 3. Euglycemic clamps in the immediate post-weaning period revealed no difference in insulin sensitivity between P-D and P-P. Fetal growth was restricted in S-P and these foals remained consistently lighter until weaning compared to S-D, with elevated T3 concentrations in the newborn compared to S-S. S-P exhibited higher fasting glycemia than S-S and S-D from days 30 to 200. They had higher maximum increment in plasma glucose than S-D after IVGTT on day 3 and clamps on day 200 demonstrated higher insulin sensitivity compared to S-D. Neither the restricted nor the enhanced fetal environment affected IGF-1 concentrations. Thus, enhanced and restricted fetal and post-natal environments had combined effects that persisted until weaning. They induced different adaptive responses in post-natal glucose metabolism: an early insulin-resistance was induced in

  7. Maternal uterine natural killer cells nurture fetal growth: in medio stat virtus.

    PubMed

    Colucci, Francesco; Kieckbusch, Jens

    2015-02-01

    Much research in reproductive immunology is preoccupied with maternal tolerance of the semi-allogeneic fetus. This inevitably leads to the assumption that the maternal immune system should be suppressed, similarly to the immunosuppression needed to avoid rejection of an allograft. However, the parallels with transplantation immunology are misleading, and we discuss how interactions between variable immune system genes expressed on maternal natural killer (NK) cells and on the fetal trophoblast modulate fetal growth. Exaggerated suppression or activation of maternal NK cells associates with both extremes of birth weight.

  8. Effect of maternal activity during gestation on maternal behavior, fetal growth, umbilical blood flow, and farrowing characteristics in pigs.

    PubMed

    Harris, E K; Berg, E P; Berg, E L; Vonnahme, K A

    2013-02-01

    Yorkshire gilts either remained in their individual stall from d 40 to term (CON; n = 7) or were subjected to exercise for 30 min 3 times per week from mid to late gestation (EX; n = 7) to determine the impact of increased maternal activity during gestation on maternal behavior, fetal growth, umbilical blood flow, and parturition. In parity 1, maternal body composition (10th rib back fat and LM area), maternal behavior, and farrowing characteristics were recorded. In parities 1 and 2, fetal growth, fetal heart rate, pulsatility index and resistance index, and umbilical blood flow were monitored beginning at d 39 of gestation continuing to d 81 of gestation. Exercise continued until d 104. Gilts allowed to exercise sat less (P < 0.01), stood more (P < 0.01), tended (P = 0.06) to lie down less, and had fewer postural changes (P < 0.01) compared with CON gilts. Umbilical blood flow increased (P < 0.01) in EX compared with CON gilts. Moreover, gilts had greater (P < 0.01) umbilical blood flow in their first parity compared with their second. Indices of vascular resistance were not affected (P ≥ 0.15) by maternal treatment; however, EX gilts reached peak pulsatility index earlier than CON gilts (56.2 vs. 64.3 ± 3.6 d). Fetal weights, piglet birth weights, placental weight, interval between piglet births, and blood lactate of newborn piglets were unaffected (P ≥ 0.15) by maternal treatment. Although maternal exercise during gestation in the pig increased umbilical blood flow and appeared to reduce maternal restlessness, impacts on offspring development in postnatal life are not known. PMID:23148241

  9. Effect of maternal activity during gestation on maternal behavior, fetal growth, umbilical blood flow, and farrowing characteristics in pigs.

    PubMed

    Harris, E K; Berg, E P; Berg, E L; Vonnahme, K A

    2013-02-01

    Yorkshire gilts either remained in their individual stall from d 40 to term (CON; n = 7) or were subjected to exercise for 30 min 3 times per week from mid to late gestation (EX; n = 7) to determine the impact of increased maternal activity during gestation on maternal behavior, fetal growth, umbilical blood flow, and parturition. In parity 1, maternal body composition (10th rib back fat and LM area), maternal behavior, and farrowing characteristics were recorded. In parities 1 and 2, fetal growth, fetal heart rate, pulsatility index and resistance index, and umbilical blood flow were monitored beginning at d 39 of gestation continuing to d 81 of gestation. Exercise continued until d 104. Gilts allowed to exercise sat less (P < 0.01), stood more (P < 0.01), tended (P = 0.06) to lie down less, and had fewer postural changes (P < 0.01) compared with CON gilts. Umbilical blood flow increased (P < 0.01) in EX compared with CON gilts. Moreover, gilts had greater (P < 0.01) umbilical blood flow in their first parity compared with their second. Indices of vascular resistance were not affected (P ≥ 0.15) by maternal treatment; however, EX gilts reached peak pulsatility index earlier than CON gilts (56.2 vs. 64.3 ± 3.6 d). Fetal weights, piglet birth weights, placental weight, interval between piglet births, and blood lactate of newborn piglets were unaffected (P ≥ 0.15) by maternal treatment. Although maternal exercise during gestation in the pig increased umbilical blood flow and appeared to reduce maternal restlessness, impacts on offspring development in postnatal life are not known.

  10. Temporal pattern of accelerated lung growth after tracheal occlusion in the fetal rabbit.

    PubMed Central

    De Paepe, M. E.; Johnson, B. D.; Papadakis, K.; Sueishi, K.; Luks, F. I.

    1998-01-01

    Tracheal occlusion in utero is a potent stimulus of fetal lung growth. We describe the early growth mechanics of fetal lungs and type II pneumocytes after tracheal ligation (TL). Fetal rabbits underwent TL at 24 days gestational age (DGA; late pseudoglandular stage; term = 31 to 33 days) and were sacrificed at time intervals ranging from 1 to 5 days after TL. Lung growth was measured by stereological volumetry and bromodeoxyuridine (BrdU) pulse labeling. Pneumocyte II population kinetics were analyzed using a combination of anti-surfactant protein A and BrdU immunohistochemistry and computer-assisted morphometry. Nonoperated littermates served as controls. TL resulted in dramatically enhanced lung growth (lung weight/body weight was 5.00 +/- 0.81% in TL versus 2.52 +/- 0.13% in controls at 29 DGA; P < 0.001, unpaired Student's t-test). Post-TL lung growth was characterized by a 3-day lag-phase typified by relative stagnation of growth, followed by distension of airspaces, increased cell proliferation, and accelerated architectural and cellular maturation by postligation days 4 and 5. During the proliferation phase, the replicative activity of type II cells was markedly increased (type II cell BrdU labeling index was 10.0 +/- 4.1% in TL versus 1.1 +/- 0.3% for controls at 29 DGA; P < 0.02), but their numerical density decreased (3.0 +/- 0.5 x 10(-3)/microm2 in TL versus 4.5 +/- 0.3 x 10(-3)/microm2 in controls at 29 DGA; P < 0.02), suggesting accelerated terminal differentiation to type I cells. In conclusion, post-TL lung development is characterized by a well defined temporal pattern of lung growth and maturation. The rabbit model lends itself well to study the regulatory mechanisms underlying accelerated fetal lung growth after TL. Images Figure 2 Figure 4 Figure 6 Figure 8 Figure 9 PMID:9422535

  11. The use of ultrasound measurements in environmental epidemiological studies of air pollution and fetal growth

    PubMed Central

    Smarr, Melissa M.; Vadillo-Ortega, Felipe; Castillo-Castrejon, Marisol; O’Neill, Marie S.

    2015-01-01

    Purpose of review Recently, several international research groups have suggested that studies about environmental contaminants and adverse pregnancy outcomes should be designed to elucidate potential underlying biological mechanisms. The purpose of this review is to examine the epidemiological studies addressing maternal exposure to air pollutants and fetal growth during gestation as assessed by ultrasound measurements. Recent findings The six studies published to date found that exposure to certain ambient air pollutants during pregnancy is negatively associated with the growth rates and average attained size of fetal parameters belonging to the growth profile. Fetal parameters may respond to maternal air pollution exposures uniquely, and this response may vary by pollutant and timing of gestational exposure. Current literature suggests that mean changes in head circumference, abdominal circumference, femur length, and biparietal diameter are negatively associated with early-pregnancy exposures to ambient and vehicle-related air pollution. Summary The use of more longitudinal studies, employing ultrasound measures to assess fetal outcomes, may assist with the better understanding of mechanisms responsible for air pollution-related pregnancy outcomes. PMID:23399571

  12. Fetal dexamethasone exposure accelerates development of renal function: relationship to dose, cell differentiation and growth inhibition.

    PubMed

    Slotkin, T A; Seidler, F J; Kavlock, R J; Gray, J A

    1992-02-01

    Fetal exposure to high doses of glucocorticoids slows cellular development and impairs organ performance, in association with growth retardation. Nevertheless, low doses of glucocorticoids may enhance cell differentiation and accelerate specific functions. The current study examined this apparent paradox in the developing rat kidney, using doses of dexamethasone that span the threshold for growth impairment: 0.05 or 0.2 mg/kg given on gestational days 17, 18 and 19. At the lower dose, which did not significantly retard body growth, the postnatal development of tubular reabsorptive capabilities for sodium, potassium, osmotic particles, water and urea was accelerated. These effects were less notable at the higher dose, which caused initial body growth impairment. The selectivity toward promotion of tubular function was evidenced by the absence of effect of either dose of dexamethasone on development of glomerular filtration rate. Because of the wide spectrum of dexamethasone's effects on tubular function, we also assessed fetal kidney adenylate cyclase as a means of detecting altered cell differentiation in the prenatal period during which dexamethasone was given. Either glucocorticoid dose increased the total adenylate cyclase catalytic activity (assessed with forskolin). Thus, the net effect of fetal dexamethasone exposure on development of renal excretory capabilities probably represents the summation of promoted cell differentiation and slowed development consequent to growth retardation. At low dose levels, the former effect predominates, leading to enhanced functional development, whereas higher doses that interfere with general growth and development can offset the direct promotional effect.

  13. Maternal Administration of Sildenafil Citrate Alters Fetal and Placental Growth and Fetal-Placental Vascular Resistance in the Growth-Restricted Ovine Fetus.

    PubMed

    Oyston, Charlotte; Stanley, Joanna L; Oliver, Mark H; Bloomfield, Frank H; Baker, Philip N

    2016-09-01

    Intrauterine growth restriction (IUGR) causes short- and long-term morbidity. Reduced placental perfusion is an important pathogenic component of IUGR; substances that enhance vasodilation in the uterine circulation, such as sildenafil citrate (sildenafil), may improve placental blood flow and fetal growth. This study aimed to examine the effects of sildenafil in the growth-restricted ovine fetus. Ewes carrying singleton pregnancies underwent insertion of vascular catheters, and then, they were randomized to receive uterine artery embolization (IUGR) or to a control group. Ewes in the IUGR group received a daily infusion of sildenafil (IUGR+SC; n=10) or vehicle (IUGR+V; n=8) for 21 days. The control group received no treatment (n=9). Umbilical artery blood flow was measured using Doppler ultrasound and the resistive index (RI) calculated. Fetal weight, biometry, and placental weight were obtained at postmortem after treatment completion. Umbilical artery RI in IUGR+V fell less than in controls; the RI of IUGR+SC was intermediate to that of the other 2 groups (mean±SEM for control versus IUGR+V versus IUGR+SC: ∆RI, 0.09±0.03 versus -0.01±0.02 versus 0.03±0.02; F(2, 22)=4.21; P=0.03). Compared with controls, lamb and placental weights were reduced in IUGR+V but not in IUGR+SC (control versus IUGR+V versus IUGR+SC: fetal weight, 4381±247 versus 3447±235 versus 3687±129 g; F(2, 24)=5.49; P=0.01 and placental weight: 559.7±35.0 versus 376.2±32.5 versus 475.2±42.5 g; F(2, 24)=4.64; P=0.01). Sildenafil may be a useful adjunct in the management of IUGR. An increase in placental weight and fall in fetal-placental resistance suggests that changes to growth are at least partly mediated by changes to placental growth rather than alterations in placental efficiency.

  14. Maternal Administration of Sildenafil Citrate Alters Fetal and Placental Growth and Fetal-Placental Vascular Resistance in the Growth-Restricted Ovine Fetus.

    PubMed

    Oyston, Charlotte; Stanley, Joanna L; Oliver, Mark H; Bloomfield, Frank H; Baker, Philip N

    2016-09-01

    Intrauterine growth restriction (IUGR) causes short- and long-term morbidity. Reduced placental perfusion is an important pathogenic component of IUGR; substances that enhance vasodilation in the uterine circulation, such as sildenafil citrate (sildenafil), may improve placental blood flow and fetal growth. This study aimed to examine the effects of sildenafil in the growth-restricted ovine fetus. Ewes carrying singleton pregnancies underwent insertion of vascular catheters, and then, they were randomized to receive uterine artery embolization (IUGR) or to a control group. Ewes in the IUGR group received a daily infusion of sildenafil (IUGR+SC; n=10) or vehicle (IUGR+V; n=8) for 21 days. The control group received no treatment (n=9). Umbilical artery blood flow was measured using Doppler ultrasound and the resistive index (RI) calculated. Fetal weight, biometry, and placental weight were obtained at postmortem after treatment completion. Umbilical artery RI in IUGR+V fell less than in controls; the RI of IUGR+SC was intermediate to that of the other 2 groups (mean±SEM for control versus IUGR+V versus IUGR+SC: ∆RI, 0.09±0.03 versus -0.01±0.02 versus 0.03±0.02; F(2, 22)=4.21; P=0.03). Compared with controls, lamb and placental weights were reduced in IUGR+V but not in IUGR+SC (control versus IUGR+V versus IUGR+SC: fetal weight, 4381±247 versus 3447±235 versus 3687±129 g; F(2, 24)=5.49; P=0.01 and placental weight: 559.7±35.0 versus 376.2±32.5 versus 475.2±42.5 g; F(2, 24)=4.64; P=0.01). Sildenafil may be a useful adjunct in the management of IUGR. An increase in placental weight and fall in fetal-placental resistance suggests that changes to growth are at least partly mediated by changes to placental growth rather than alterations in placental efficiency. PMID:27432857

  15. Fetal, neonatal, infant, and child international growth standards: an unprecedented opportunity for an integrated approach to assess growth and development.

    PubMed

    Garza, Cutberto

    2015-07-01

    The recent publication of fetal growth and gestational age-specific growth standards by the International Fetal and Newborn Growth Consortium for the 21st Century Project and the previous publication by the WHO of infant and young child growth standards based on the WHO Multicentre Growth Reference Study enable evaluations of growth from ∼9 wk gestation to 5 y. The most important features of these projects are the prescriptive approach used for subject selection and the rigorous testing of the assertion that growth is very similar among geographically and ethnically diverse nonisolated populations when health, nutrition, and other care needs are met and the environment imposes minimal constraints on growth. Both studies documented that with adequate controls, the principal source of variability in growth during gestation and early childhood resides among individuals. Study sites contributed much less to observed variability. The agreement between anthropometric measurements common to both studies also is noteworthy. Jointly, these studies provide for the first time, to my knowledge, a conceptually consistent basis for worldwide and localized assessments and comparisons of growth performance in early life. This is an important contribution to improving the health care of children across key periods of growth and development, especially given the appropriate interest in pursuing "optimal" health in the "first 1000 d," i.e., the period covering fertilization/implantation, gestation, and postnatal life to 2 y of age.

  16. Morpho-functional characteristics of rat fetal thyroid gland are affected by prenatal dexamethasone exposure.

    PubMed

    Manojlović-Stojanoski, Milica N; Filipović, Branko R; Nestorović, Nataša M; Šošić-Jurjević, Branka T; Ristić, Nataša M; Trifunović, Svetlana L; Milošević, Verica Lj

    2014-06-01

    Thyroid hormones (TH) and glucocorticoids strongly contribute to the maturation of fetal tissues in the preparation for extrauterine life. Influence of maternal dexamethasone (Dx) administration on thyroid glands morpho-functional characteristics of near term rat fetuses was investigated applying unbiased stereology. On the 16th day of pregnancy dams received 1.0mg/Dx/kg/b.w., followed by 0.5mg/Dx/kg/b.w. on the 17th and 18th days of gestation. The control females received the same volume of saline. The volume of fetal thyroid was estimated using Cavalieri's principle; the physical/fractionator design was applied for the determination of absolute number of follicular cells in mitosis and immunohistochemically labeled C cells; C cell volume was measured using the planar rotator. The functional activity of thyroid tissue was provided from thyroglobulin (Tg) and thyroperoxidase (TPO) immunohistochemical staining. Applying these design-based modern stereological methods it was shown that Dx treatment of gravid females led to a significant decrease of fetal thyroid gland volume in 19- and 21-day-old fetuses, due to decreased proliferation of follicular cells. The Tg and TPO immunohistochemistry demonstrated that intensive TH production starts and continues during the examined period in control and Dx-exposed fetuses. Under the influence of Dx the absolute number of C cells was lower in both groups of near term fetuses, although unchanged relation between the two populations of endocrine cells, follicular and C cells suggesting that structural relationships within the gland are preserved. In conclusion maternal glucocorticoid administration at the thyroid gland level exerts growth-inhibitory and maturational promoting effects in near term rat fetuses.

  17. Fetal deficiency of lin28 programs life-long aberrations in growth and glucose metabolism.

    PubMed

    Shinoda, Gen; Shyh-Chang, Ng; Soysa, T Yvanka de; Zhu, Hao; Seligson, Marc T; Shah, Samar P; Abo-Sido, Nora; Yabuuchi, Akiko; Hagan, John P; Gregory, Richard I; Asara, John M; Cantley, Lewis C; Moss, Eric G; Daley, George Q

    2013-08-01

    LIN28A/B are RNA binding proteins implicated by genetic association studies in human growth and glucose metabolism. Mice with ectopic over-expression of Lin28a have shown related phenotypes. Here, we describe the first comprehensive analysis of the physiologic consequences of Lin28a and Lin28b deficiency in knockout (KO) mice. Lin28a/b-deficiency led to dwarfism starting at different ages, and compound gene deletions showed a cumulative dosage effect on organismal growth. Conditional gene deletion at specific developmental stages revealed that fetal but neither neonatal nor adult deficiency resulted in growth defects and aberrations in glucose metabolism. Tissue-specific KO mice implicated skeletal muscle-deficiency in the abnormal programming of adult growth and metabolism. The effects of Lin28b KO could be rescued by Tsc1 haplo-insufficiency in skeletal muscles. Our data implicate fetal expression of Lin28a/b in the regulation of life-long effects on metabolism and growth, and demonstrate that fetal Lin28b acts at least in part via mTORC1 signaling.

  18. Synaptic development and neuronal myelination are altered with growth restriction in fetal guinea pigs.

    PubMed

    Piorkowska, Karolina; Thompson, Jennifer; Nygard, Karen; Matushewski, Brad; Hammond, Robert; Richardson, Bryan

    2014-01-01

    This study examines aberrant synaptogenesis and myelination of neuronal connections as possible links to neurological sequelae in growth-restricted fetuses. Pregnant guinea pig sows were subjected to uterine blood flow restriction or sham surgeries at midgestation. The animals underwent necropsy at term with fetuses grouped according to body weight and brain-to-liver weight ratios as follows: appropriate for gestational age (n = 12); asymmetrically fetal growth restricted (aFGR; n = 8); symmetrically fetal growth restricted (sFGR; n = 8), and large for gestational age (n = 8). Fetal brains were perfusion fixed and paraffin embedded to determine immunoreactivity for synaptophysin and synaptopodin as markers of synaptic development and maturation, respectively, and for myelin basic protein as a marker for myelination, which was further assessed using Luxol fast blue staining. The most pertinent findings were that growth-restricted guinea pig fetuses exhibited reduced synaptogenesis and synaptic maturation as well as reduced myelination, which were primarily seen in subareas of the hippocampus and associated efferent tracts. These neurodevelopmental changes were more pronounced in the sFGR compared to the aFGR animals. Accordingly, altered hippocampal development involving synaptogenesis and myelination may represent a mechanism by which cognitive deficits manifest in human growth-restricted offspring in later life.

  19. Effect of placental factors on growth and function of the human fetal adrenal in vitro

    SciTech Connect

    Riopel, L.; Branchaud, C.L.; Goodyer, C.G.; Zweig, M.; Lipowski, L.; Adkar, V.; Lefebvre, Y. )

    1989-11-01

    Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: (1) maximal response to PM was 2-5 times greater; (2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; (3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland.

  20. Birth Weight, Intrauterine Growth Retardation and Fetal Susceptibility to Porcine Reproductive and Respiratory Syndrome Virus

    PubMed Central

    Ladinig, Andrea; Foxcroft, George; Ashley, Carolyn; Lunney, Joan K.; Plastow, Graham; Harding, John C. S.

    2014-01-01

    The severity of porcine reproductive and respiratory syndrome was compared in pregnant gilts originating from high and low birth weight litters. One-hundred and eleven pregnant gilts experimentally infected with porcine reproductive and respiratory syndrome virus on gestation day 85 (±1) were necropsied along with their fetuses 21 days later. Ovulation rates and litter size did not differ between groups, but fetuses from low birth weight gilts were shorter, lighter and demonstrated evidence of asymmetric growth with large brain:organ weight ratios (i.e. brain sparing). The number of intrauterine growth retarded fetuses, defined by brain:organ weight ratios greater than 1 standard deviation from the mean, was significantly greater in low, compared to high, birth weight gilts. Although γδ T cells significantly decreased over time in high compared to low birth weight gilts, viral load in serum and tissues, gilt serum cytokine levels, and litter outcome, including the percent dead fetuses per litter, did not differ by birth weight group. Thus, this study provided no substantive evidence that the severity of porcine reproductive and respiratory syndrome is affected by dam birth weight. However, intrauterine growth retarded fetuses had lower viral loads in both fetal thymus and in endometrium adjacent to the umbilical stump. Crown rump length did not significantly differ between fetuses that survived and those that died at least one week prior to termination. Taken together, this study clearly demonstrates that birth weight is a transgenerational trait in pigs, and provides evidence that larger fetuses are more susceptible to transplacental PRRSv infection. PMID:25275491

  1. Vitamin B12: one carbon metabolism, fetal growth and programming for chronic disease.

    PubMed

    Rush, E C; Katre, P; Yajnik, C S

    2014-01-01

    This review brings together human and animal studies and reviews that examine the possible role of maternal vitamin B12 (B12) on fetal growth and its programming for susceptibility to chronic disease. A selective literature review was undertaken to identify studies and reviews that investigate these issues, particularly in the context of a vegetarian diet that may be low in B12 and protein and high in carbohydrate. Evidence is accumulating that maternal B12 status influences fetal growth and development. Low maternal vitamin B12 status and protein intake are associated with increased risk of neural tube defect, low lean mass and excess adiposity, increased insulin resistance, impaired neurodevelopment and altered risk of cancer in the offspring. Vitamin B12 is a key nutrient associated with one carbon metabolic pathways related to substrate metabolism, synthesis and stability of nucleic acids and methylation of DNA which regulates gene expression. Understanding of factors regulating maternal-fetal one carbon metabolism and its role in fetal programming of non communicable diseases could help design effective interventions, starting with maternal nutrition before conception.

  2. Maternal L-glutamine supplementation prevents prenatal alcohol exposure-induced fetal growth restriction in an ovine model.

    PubMed

    Sawant, Onkar B; Wu, Guoyao; Washburn, Shannon E

    2015-06-01

    Prenatal alcohol exposure is known to cause fetal growth restriction and disturbances in amino acid bioavailability. Alterations in these parameters can persist into adulthood and low birth weight can lead to altered fetal programming. Glutamine has been associated with the synthesis of other amino acids, an increase in protein synthesis and it is used clinically as a nutrient supplement for low birth weight infants. The aim of this study was to explore the effect of repeated maternal alcohol exposure and L-glutamine supplementation on fetal growth and amino acid bioavailability during the third trimester-equivalent period in an ovine model. Pregnant sheep were randomly assigned to four groups, saline control, alcohol (1.75-2.5 g/kg), glutamine (100 mg/kg, three times daily) or alcohol + glutamine. In this study, a weekend binge drinking model was followed where treatment was done 3 days per week in succession from gestational day (GD) 109-132 (normal term ~147). Maternal alcohol exposure significantly reduced fetal body weight, height, length, thoracic girth and brain weight, and resulted in decreased amino acid bioavailability in fetal plasma and placental fluids. Maternal glutamine supplementation successfully mitigated alcohol-induced fetal growth restriction and improved the bioavailability of glutamine and glutamine-related amino acids such as glycine, arginine, and asparagine in the fetal compartment. All together, these findings show that L-glutamine supplementation enhances amino acid availability in the fetus and prevents alcohol-induced fetal growth restriction.

  3. Adaptations in placental phenotype support fetal growth during undernutrition of pregnant mice.

    PubMed

    Coan, P M; Vaughan, O R; Sekita, Y; Finn, S L; Burton, G J; Constancia, M; Fowden, A L

    2010-02-01

    Undernutrition during pregnancy reduces birth weight and programmes adult phenotype with consequences for life expectancy, but its effects on the phenotype of the placenta, responsible for supplying nutrients for fetal growth, remain largely unknown. Using molecular, morphological and functional analyses, placental phenotype was examined in mice during restriction of dietary intake to 80% of control from day 3 of pregnancy. At day 16, undernutrition reduced placental, but not fetal, weight in association with decreased junctional zone volume and placental expression of glucose transporter Slc2a1. At day 19, both placental and fetal weights were reduced in undernourished mice (91% and 87% of control, respectively, P < 0.01), as were the volume and surface area of the labyrinthine zone responsible for placental nutrient transfer (85% and 86%, respectively, P < 0.03). However, unidirectional materno-fetal clearance of tracer glucose was maintained and methyl-aminoisobutyric acid increased 166% (P < 0.005) per gram of undernourished placenta, relative to controls. This was associated with an 18% and 27% increased placental expression of glucose and system A amino acid transporters Slc2a1 and Slc38a2, respectively, at day 19 (P < 0.04). At both ages, undernutrition decreased expression of the placental specific transcript of the Igf2 gene by 35% (P < 0.01), although methylation of its promoter was unaffected. The placenta, therefore, adapts to help maintain fetal growth when its own growth is compromised by maternal undernutrition. Consequently, placental phenotype is responsive to environmental conditions and may help predict the risk of adult disease programmed in utero.

  4. Methyl Donor Deficiency Affects Fetal Programming of Gastric Ghrelin Cell Organization and Function in the Rat

    PubMed Central

    Bossenmeyer-Pourié, Carine; Blaise, Sébastien; Pourié, Grégory; Tomasetto, Catherine; Audonnet, Sandra; Ortiou, Sandrine; Koziel, Violette; Rio, Marie-Christine; Daval, Jean-Luc; Guéant, Jean-Louis; Beck, Bernard

    2010-01-01

    Methyl donor deficiency (MDD) during pregnancy influences intrauterine development. Ghrelin is expressed in the stomach of fetuses and influences fetal growth, but MDD influence on gastric ghrelin is unknown. We examined the gastric ghrelin system in MDD-induced intrauterine growth retardation. By using specific markers and approaches (such as periodic acid–Schiff, bromodeoxyuridine, homocysteine, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling, immunostaining, reverse transcription-polymerase chain reaction), we studied the gastric oxyntic mucosa cellular organization and ghrelin gene expression in the mucosa in 20-day-old fetuses and weanling pups, and plasma ghrelin concentration in weanling rat pups of dams either normally fed or deprived of choline, folate, vitamin B6, and vitamin B12 during gestation and suckling periods. MDD fetuses weighed less than controls; the weight deficit reached 57% at weaning (P < 0.001). Both at the end of gestation and at weaning, they presented with an aberrant gastric oxyntic mucosa formation with loss of cell polarity, anarchic cell migration, abnormal progenitor differentiation, apoptosis, and signs of surface layer erosion. Ghrelin cells were abnormally located in the pit region of oxyntic glands. At weaning, plasma ghrelin levels were decreased (−28%; P < 0.001) despite unchanged mRNA expression in the stomach. This decrease was associated with lower body weight. Taken together, these data indicate that one mechanism through which MDD influences fetal programming is the remodeling of gastric cellular organization, leading to dysfunction of the ghrelin system and dramatic effects on growth. PMID:19948829

  5. High Fat Diet Induced Developmental Defects in the Mouse: Oocyte Meiotic Aneuploidy and Fetal Growth Retardation/Brain Defects

    PubMed Central

    Purcell, Scott H.; Chi, Maggie; Jimenez, Patricia T.; Grindler, Natalia; Schedl, Tim; Moley, Kelle H.

    2012-01-01

    Background Maternal obesity is associated with poor outcomes across the reproductive spectrum including infertility, increased time to pregnancy, early pregnancy loss, fetal loss, congenital abnormalities and neonatal conditions. Furthermore, the proportion of reproductive-aged woman that are obese in the population is increasing sharply. From current studies it is not clear if the origin of the reproductive complications is attributable to problems that arise in the oocyte or the uterine environment. Methodology/Principal Findings We examined the developmental basis of the reproductive phenotypes in obese animals by employing a high fat diet mouse model of obesity. We analyzed very early embryonic and fetal phenotypes, which can be parsed into three abnormal developmental processes that occur in obese mothers. The first is oocyte meiotic aneuploidy that then leads to early embryonic loss. The second is an abnormal process distinct from meiotic aneuploidy that also leads to early embryonic loss. The third is fetal growth retardation and brain developmental abnormalities, which based on embryo transfer experiments are not due to the obese uterine environment but instead must be from a defect that arises prior to the blastocyst stage. Conclusions/Significance Our results suggest that reproductive complications in obese females are, at least in part, from oocyte maternal effects. This conclusion is consistent with IVF studies where the increased pregnancy failure rate in obese women returns to the normal rate if donor oocytes are used instead of autologous oocytes. We postulate that preconceptional weight gain adversely affects pregnancy outcomes and fetal development. In light of our findings, preconceptional counseling may be indicated as the preferable, earlier target for intervention in obese women desiring pregnancy and healthy outcomes. PMID:23152876

  6. Fetal Echocardiography and Pulsed-wave Doppler Ultrasound in a Rabbit Model of Intrauterine Growth Restriction

    PubMed Central

    Hodges, Ryan; Endo, Masayuki; La Gerche, Andre; Eixarch, Elisenda; DeKoninck, Philip; Ferferieva, Vessilina; D'hooge, Jan; Wallace, Euan M.; Deprest, Jan

    2013-01-01

    Fetal intrauterine growth restriction (IUGR) results in abnormal cardiac function that is apparent antenatally due to advances in fetoplacental Doppler ultrasound and fetal echocardiography. Increasingly, these imaging modalities are being employed clinically to examine cardiac function and assess wellbeing in utero, thereby guiding timing of birth decisions. Here, we used a rabbit model of IUGR that allows analysis of cardiac function in a clinically relevant way. Using isoflurane induced anesthesia, IUGR is surgically created at gestational age day 25 by performing a laparotomy, exposing the bicornuate uterus and then ligating 40-50% of uteroplacental vessels supplying each gestational sac in a single uterine horn. The other horn in the rabbit bicornuate uterus serves as internal control fetuses. Then, after recovery at gestational age day 30 (full term), the same rabbit undergoes examination of fetal cardiac function. Anesthesia is induced with ketamine and xylazine intramuscularly, then maintained by a continuous intravenous infusion of ketamine and xylazine to minimize iatrogenic effects on fetal cardiac function. A repeat laparotomy is performed to expose each gestational sac and a microultrasound examination (VisualSonics VEVO 2100) of fetal cardiac function is performed. Placental insufficiency is evident by a raised pulsatility index or an absent or reversed end diastolic flow of the umbilical artery Doppler waveform. The ductus venosus and middle cerebral artery Doppler is then examined. Fetal echocardiography is performed by recording B mode, M mode and flow velocity waveforms in lateral and apical views. Offline calculations determine standard M-mode cardiac variables, tricuspid and mitral annular plane systolic excursion, speckle tracking and strain analysis, modified myocardial performance index and vascular flow velocity waveforms of interest. This small animal model of IUGR therefore affords examination of in utero cardiac function that is

  7. Fetal calf serum-mediated inhibition of neurite growth from ciliary ganglion neurons in vitro.

    PubMed

    Davis, G E; Skaper, S D; Manthorpe, M; Moonen, G; Varon, S

    1984-01-01

    Embryonic chick ciliary ganglion (CG) neurons cultured in fetal calf serum-containing medium have been previously reported to extend neurites on polyornithine (PORN) substrata precoated with a neurite-promoting factor (PNPF) from rat schwannoma-conditioned medium. On PORN substrata alone, however, no neuritic growth occurred. This was interpreted as evidence that PORN was an incompetent substratum for ciliary neuritic growth. In this study, we now find that an untreated PORN substratum allows neuritic growth in serum-free defined medium. When PNPF was added to PORN, a more rapid and extensive neuritic response occurred. After 5 hr of culture, a 60% neuritic response occurred on PNPF/PORN, whereas no neurons initiated neurites until 10-12 hr on PORN. The inhibitory effect of fetal calf serum noted above on PORN could be obtained in part by pretreating the substratum with serum for 1 hr. Maximal inhibitory effects in the PORN pretreatment were achieved after 30 min and were not further improved by treatments up to 4 hr. Bovine serum albumin was also found to inhibit neurite growth on PORN to about 60% of the inhibition obtained by an equivalent amount of serum protein. Fetal calf serum was shown to cause a 15% reduction in the percentage of neurons bearing neurites after its addition to 18-hr serum-free PORN cultures and to cause statistically significant reductions in neurite lengths measured 2 hr later.

  8. Fetal calf serum-mediated inhibition of neurite growth from ciliary ganglion neurons in vitro.

    PubMed

    Davis, G E; Skaper, S D; Manthorpe, M; Moonen, G; Varon, S

    1984-01-01

    Embryonic chick ciliary ganglion (CG) neurons cultured in fetal calf serum-containing medium have been previously reported to extend neurites on polyornithine (PORN) substrata precoated with a neurite-promoting factor (PNPF) from rat schwannoma-conditioned medium. On PORN substrata alone, however, no neuritic growth occurred. This was interpreted as evidence that PORN was an incompetent substratum for ciliary neuritic growth. In this study, we now find that an untreated PORN substratum allows neuritic growth in serum-free defined medium. When PNPF was added to PORN, a more rapid and extensive neuritic response occurred. After 5 hr of culture, a 60% neuritic response occurred on PNPF/PORN, whereas no neurons initiated neurites until 10-12 hr on PORN. The inhibitory effect of fetal calf serum noted above on PORN could be obtained in part by pretreating the substratum with serum for 1 hr. Maximal inhibitory effects in the PORN pretreatment were achieved after 30 min and were not further improved by treatments up to 4 hr. Bovine serum albumin was also found to inhibit neurite growth on PORN to about 60% of the inhibition obtained by an equivalent amount of serum protein. Fetal calf serum was shown to cause a 15% reduction in the percentage of neurons bearing neurites after its addition to 18-hr serum-free PORN cultures and to cause statistically significant reductions in neurite lengths measured 2 hr later. PMID:6481819

  9. Exposure to ergot alkaloids during gestation reduces fetal growth in sheep

    PubMed Central

    Duckett, Susan K.; Andrae, John G.; Pratt, Scott L.

    2014-01-01

    Tall fescue [Lolium arundinaceum (Schreb.) Darbysh; Schedonorus phoenix (Scop.) Holub] is the primary cool season perennial grass in the eastern U.S. Most tall fescue contains an endophyte (Neotyphodium coenophialum), which produces ergot alkaloids that cause vasoconstriction and could restrict blood flow to the fetus in pregnant animals. The objective of this study was to examine fetal growth during maternal exposure to ergot alkaloids during gestation. Pregnant ewes (n = 16) were randomly assigned to one of two dietary treatments: (1) endophyte-infected (N. coenophialum) tall fescue seed (E+; 0.8 ug of ergovaline /g diet DM) and (2) endophyte-free tall fescue seed (E−; 0.0 ug of ergovaline/g diet DM). Birth weight of lambs was reduced by 37% for E+ compared to E−. Organ and muscle weights were also lighter for E+ than E−. Exposure to ergot alkaloids in utero reduces fetal growth and muscle development. PMID:25191653

  10. [Weight/head circumference ratio at birth for assessing fetal growth].

    PubMed

    Gonçalves, Fabiana Cristina Lima da Silva Pastich; Lira, Pedro Israel Cabral de; Eickmann, Sophie Helena; Lima, Marilia de Carvalho

    2015-09-01

    The objective of this study was to use weight/head circumference ratio at birth to assess fetal growth. A retrospective cohort study was conducted in Zona da Mata, Pernambuco State, Brazil, with 915 term infants. Infants' anthropometric measurements and data on prenatal care, smoking during pregnancy, family income, and maternal schooling and nutritional status were collected in the first 24 hours after birth. Infants were classified as proportionate (weight/head circumference ratio ≥ 0.90) versus disproportionate (< 0.90). Lower mean weight/head circumference ratio was associated with maternal smoking, younger age, inadequate prenatal care, and low BMI, height, and triceps skinfold thickness. Mean weight, length, head and chest circumference, arm circumference, and triceps skinfold thickness were lower among infants with disproportionate weight/head circumference ratio, independently of sex. In conclusion, weight/head circumference ratio and birth weight are important indicators of fetal growth. PMID:26578023

  11. Fetal growth retardation in cigarette-smoking mothers is not due to decreased maternal food intake.

    PubMed

    Haworth, J C; Ellestad-Sayed, J J; King, J; Dilling, L A

    1980-07-15

    To determine whether the fetal growth-retarding effect of maternal cigarette smoking could be due to a lower dietary intake in smokers than in nonsmokers, the energy and nutrient intake of 302 smoking and 234 nonsmoking women were assessed toward the end of the last trimester of pregnancy. The women were from two socioeconomic groups which differed greatly in age, height, education, family income, racial origin, and pregnancy weight gain. Within each group, smokers had significantly smaller infants, but pregnancy weight gain was not different. Daily dietary intake of the smokers was not less than that of the nonsmokers; in fact, for some nutrients it was significantly greater. Therefore, fetal growth retardation due to smoking is not caused by the mother's diminished intake of food. PMID:7395936

  12. Exposure to Ergot Alkaloids During Gestation Reduces Fetal Growth in Sheep

    NASA Astrophysics Data System (ADS)

    Duckett, Susan; Pratt, Scott; Andrae, John

    2014-08-01

    Tall fescue [Lolium arundinaceum (Schreb.) Darbysh; Schedonorus phoenix (Scop.) Holub] is the primary cool season perennial grass in the eastern U.S. Most tall fescue contains an endophyte (Neotyphodium coenophialum), which produces ergot alkaloids that cause vasoconstriction and could restrict blood flow to the fetus in pregnant animals. The objective of this study was to examine fetal growth during maternal exposure to ergot alkaloids during gestation. Pregnant ewes (n = 16) were randomly assigned to one of two dietary treatments: 1) endophyte-infected (Neotyphodium coenophialum) tall fescue seed (E+; 0.8 ug of ergovaline /g diet DM) and 2) endophyte-free tall fescue seed (E-; 0.0 ug of ergovaline/g diet DM). Birth weight of lambs was reduced by 37% for E+ compared to E-. Organ and muscle weights were also lighter for E+ than E-. Exposure to ergot alkaloids in utero reduces fetal growth and muscle development.

  13. Peri-implantation and late gestation maternal undernutrition differentially affect fetal sheep skeletal muscle development

    PubMed Central

    Costello, Paula M; Rowlerson, Anthea; Astaman, Nur Aida; Anthony, Fred Erick W; Sayer, Avan Aihie; Cooper, Cyrus; Hanson, Mark A; Green, Lucy R

    2008-01-01

    Poor prenatal nutrition is associated with a greater risk of adult glucose intolerance and insulin insensitivity in the offspring. Skeletal muscle is the primary tissue for glucose utilization, and insulin resistance in muscle is the earliest identifiable abnormality in the pre-diabetic patient. We investigated the effect of early and late gestation undernutrition on structure and markers of growth and glucose metabolism regulation in the fetal triceps brachii (TB, slow- and fast-twitch myofibres) and soleus (slow-twitch myofibres) muscles. Pregnant sheep were fed 100% nutrient requirements (C, n = 8) or a restricted diet peri-implantation (PI, n = 9; 40%, 1–31 days gestation (dGA) (term ∼147)) or in late gestation (L, n = 6; 50%, 104–127 dGA). At 127 ± 1 dGA we measured myofibre and capillary density in the fetal TB and soleus muscles, and mRNA levels in the TB of insulin receptor (InsR), glucose transporter-4 (GLUT-4) and type 1 insulin-like growth factor receptor (IGF-1R). Total myofibre and capillary densities were lower in the TB, but not the soleus, of PI and L fetuses. The predominant effect in the L group was on slow-twitch myofibres. In TB, InsR, GLUT-4 and IGF-1R mRNA levels were greater in L group fetuses. Our finding of reduced myofibre density is consistent with a redistribution of resources at the expense of specific peripheral tissues by early and late gestation undernutrition which may be mediated by a decrease in capillary density. The increase in key regulatory components of glucose uptake following late gestation undernutrition may constitute a short-term compensation to maintain glucose homeostasis in the face of fewer type I (insulin-sensitive) myofibres. However, together these adaptations may influence the risk of later metabolic disease and thus our findings have implications for future strategies aimed at improving maternal diet. PMID:18339691

  14. INFANT EMOTIONAL WITHDRAWAL: A PRECURSOR OF AFFECTIVE AND COGNITIVE DISTURBANCE IN FETAL ALCOHOL SPECTRUM DISORDERS

    PubMed Central

    Molteno, Christopher D.; Jacobson, Joseph L.; Carter, R. Colin; Dodge, Neil C.; Jacobson, Sandra W.

    2013-01-01

    Objectives To test the hypothesis that emotional withdrawal is an early indicator of affective disorder in infants heavily exposed prenatally to alcohol, which is independent of alcohol-related effects on mother-infant interaction and temperament and discriminated between children later diagnosed with fetal alcohol syndrome (FAS) and partial FAS (PFAS) and predicted cognitive and affective outcomes at 5 and 9 years. Methods The sample consisted of Cape Coloured (mixed ancestry) infants, whose mothers were interviewed during pregnancy regarding their alcohol consumption using a timeline follow-back approach. Infant emotional withdrawal (n = 85) was assessed on the Alarm Distress Baby Scale at 6.5 months. Mother-infant interaction was evaluated from video recordings during free play and infant feeding at 6.5 months (n = 127). Infant temperament was assessed by maternal report on the EAS Temperament Survey at 13 months (n = 119). Socio-demographic and psychological correlates of maternal alcohol use and infant iron deficiency were examined as potential confounders. The children were diagnosed for FAS/PFAS by expert dysmorphologists at 5 years; cognitive and affective function, at 5 and 9 years. Results Prenatal alcohol exposure was associated with increased infant emotional withdrawal and decreased activity, but unrelated to mother-infant interaction or any other temperament measures. Children later diagnosed with FAS and PFAS at 5 years exhibited more emotional withdrawal and less responsivity and activity as infants. Infant withdrawal, responsivity, quality of interaction, and maternal sensitivity also predicted poorer IQ and affective response at 5 and 9 years. When all four infant affective measures were examined simultaneously in a regression analysis, only infant emotional withdrawal persisted as a significant predictor of 9-year IQ. Conclusions This study is the first to document a direct effect of fetal alcohol exposure on emotional withdrawal in infancy

  15. Maternal nutrition modifies trophoblast giant cell phenotype and fetal growth in mice

    PubMed Central

    Watkins, Adam J; Lucas, Emma S; Marfy-Smith, Stephanie; Bates, Nicola; Kimber, Susan J; Fleming, Tom P

    2015-01-01

    Mammalian placentation is dependent upon the action of trophoblast cells at the time of implantation. Appropriate fetal growth, regulated by maternal nutrition and nutrient transport across the placenta, is a critical factor for adult offspring long-term health. We have demonstrated that a mouse maternal low-protein diet (LPD) fed exclusively during preimplantation development (Emb-LPD) increases offspring growth but programmes adult cardiovascular and metabolic disease. In this study, we investigate the impact of maternal nutrition on post-implantation trophoblast phenotype and fetal growth. Ectoplacental cone explants were isolated at day 8 of gestation from female mice fed either normal protein diet (NPD: 18% casein), LPD (9% casein) or Emb-LPD and cultured in vitro. We observed enhanced spreading and cell division within proliferative and secondary trophoblast giant cells (TGCs) emerging from explants isolated from LPD-fed females when compared with NPD and Emb-LPD explants after 24 and 48 h. Moreover, both LPD and Emb-LPD explants showed substantial expansion of TGC area during 24–48 h, not observed in NPD. No difference in invasive capacity was observed between treatments using Matrigel transwell migration assays. At day 17 of gestation, LPD- and Emb-LPD-fed conceptuses displayed smaller placentas and larger fetuses respectively, resulting in increased fetal:placental ratios in both groups compared with NPD conceptuses. Analysis of placental and yolk sac nutrient signalling within the mammalian target of rapamycin complex 1 pathway revealed similar levels of total and phosphorylated downstream targets across groups. These data demonstrate that early post-implantation embryos modify trophoblast phenotype to regulate fetal growth under conditions of poor maternal nutrition. PMID:25755287

  16. Stimulation of DNA and Collagen Synthesis by Autologous Growth Factor in Cultured Fetal Rat Calvaria

    NASA Astrophysics Data System (ADS)

    Canalis, Ernesto; Peck, William A.; Raisz, Lawrence G.

    1980-11-01

    Conditioned medium derived from organ or cell cultures prepared from 19- to 21-day fetal rat calvaria stimulated the incorporation of [3H]proline into collagen and of [3H]thymidine into DNA in organ cultures of the same tissue. Addition of cortisol enhanced the effect on collagen but not on DNA synthesis. These effects appeared to be due to a nondialyzable and heat-stable growth factor.

  17. In Utero Programming of Later Adiposity: The Role of Fetal Growth Restriction

    PubMed Central

    Sarr, Ousseynou; Yang, Kaiping; Regnault, Timothy R. H.

    2012-01-01

    Intrauterine growth restriction (IUGR) is strongly associated with obesity in adult life. The mechanisms contributing to the onset of IUGR-associated adult obesity have been studied in animal models and humans, where changes in fetal adipose tissue development, hormone levels and epigenome have been identified as principal areas of alteration leading to later life obesity. Following an adverse in utero development, IUGR fetuses display increased lipogenic and adipogenic capacity in adipocytes, hypoleptinemia, altered glucocorticoid signalling, and chromatin remodelling, which subsequently all contribute to an increased later life obesity risk. Data suggest that many of these changes result from an enhanced activity of the adipose master transcription factor regulator, peroxisome proliferator-activated receptor-γ (PPARγ) and its coregulators, increased lipogenic fatty acid synthase (FAS) expression and activity, and upregulation of glycolysis in fetal adipose tissue. Increased expression of fetal hypothalamic neuropeptide Y (NPY), altered hypothalamic leptin receptor expression and partitioning, reduced adipose noradrenergic sympathetic innervations, enhanced adipose glucocorticoid action, and modifications in methylation status in the promoter of hepatic and adipose adipogenic and lipogenic genes in the fetus also contribute to obesity following IUGR. Therefore, interventions that inhibit these fetal developmental changes will be beneficial for modulation of adult body fat accumulation. PMID:23251802

  18. From the α to the ω-3: Breaking the link between impaired fetal growth and adult cardiovascular disease.

    PubMed

    Skilton, Michael R; Phang, Melinda

    2016-01-01

    Atherosclerotic vascular disease is an important cause of premature morbidity and mortality. An extensive body of epidemiologic data links impaired fetal growth, evidenced by reductions in birth weight, with a higher risk for cardiovascular disease in adulthood. This association appears to be at least partially independent of established cardiovascular risk factors, such as hypertension and type 2 diabetes. There is currently no clinically established strategy to prevent cardiovascular events secondary to being born with poor fetal growth. This review summarizes recent evidence that suggests that ω-3 polyunsaturated fatty acids may be beneficial for this indication; in particular being associated with more marked reductions in blood pressure and subclinical atherosclerosis in people who were born with poor fetal growth, than in those with healthy birth weight. Possible mechanisms, and the evidence base required to support the implementation of dietary guidelines specific to people born with impaired fetal growth are also described.

  19. From the α to the ω-3: Breaking the link between impaired fetal growth and adult cardiovascular disease.

    PubMed

    Skilton, Michael R; Phang, Melinda

    2016-01-01

    Atherosclerotic vascular disease is an important cause of premature morbidity and mortality. An extensive body of epidemiologic data links impaired fetal growth, evidenced by reductions in birth weight, with a higher risk for cardiovascular disease in adulthood. This association appears to be at least partially independent of established cardiovascular risk factors, such as hypertension and type 2 diabetes. There is currently no clinically established strategy to prevent cardiovascular events secondary to being born with poor fetal growth. This review summarizes recent evidence that suggests that ω-3 polyunsaturated fatty acids may be beneficial for this indication; in particular being associated with more marked reductions in blood pressure and subclinical atherosclerosis in people who were born with poor fetal growth, than in those with healthy birth weight. Possible mechanisms, and the evidence base required to support the implementation of dietary guidelines specific to people born with impaired fetal growth are also described. PMID:27025974

  20. Fetal growth and body size genes and risk of childhood acute lymphoblastic leukemia.

    PubMed

    Chokkalingam, Anand P; Metayer, Catherine; Scelo, Ghislaine; Chang, Jeffrey S; Schiffman, Joshua; Urayama, Kevin Y; Ma, Xiaomei; Hansen, Helen M; Feusner, James H; Barcellos, Lisa F; Wiencke, John K; Wiemels, Joseph L; Buffler, Patricia A

    2012-09-01

    Accumulating evidence suggests that childhood acute lymphoblastic leukemia (ALL) may be initiated in utero or early in the postnatal period. High birth weight (or rapid fetal growth) is associated with risk of ALL, but the mechanisms are not understood. In a population-based epidemiologic study of childhood ALL, we utilized a haplotype-based approach to assess the role of eight genes involved in fetal growth and body size regulation in 377 childhood ALL cases and 448 controls. We found significant haplotype associations with risk of childhood ALL for IGF1 among non-Hispanics and Hispanics together (p = 0.002), for IGF2 among Hispanics (p = 0.040), and for IGF2R among Hispanics and non-Hispanics (p = 0.051 and 0.009, respectively). No haplotype associations were observed for IGF1R or the studied genes involved in body size regulation, including LEP, LEPR, GHRL, and NPY. Our study is the first to identify an association between the genes involved in the IGF axis and risk of childhood ALL. These findings for childhood ALL emphasize the importance of fetal growth, when lymphoid progenitor cells are not yet fully differentiated and therefore more susceptible to malignant transformation. Additional studies are needed to confirm these findings and identify specific causal variants.

  1. Prenatal Exposure to Polybrominated Flame Retardants and Fetal Growth in the INMA Cohort (Spain)

    PubMed Central

    2015-01-01

    Our aim was to investigate the relation between PBDEs and fetal growth or newborn anthropometry in a Spanish cohort (2003–2008). PBDE congeners (BDE-47, -99, -153, -154, and -209) were determined in serum of 670 mothers at gestational week 12 and in 534 umbilical cord samples. Abdominal circumference (AC), estimated fetal weight (EFW), femur length (FL), and biparietal diameter (BPD) during gestation were measured by ultrasounds. At birth, weight (BW), head circumference (HC), and length (BL) were also measured. We assessed growth in the intervals between 12–20 and 20–34 weeks of gestation and size at birth by standard deviation (SD)-scores adjusted for constitutional characteristics. We conducted multivariate linear regression analyses between PBDE congeners and their sum (ΣPBDEs) and outcomes. We found statistically significant inverse associations between ΣPBDEs and AC, EFW, and BPD at weeks 20–34 and HC at birth. Regarding congeners, the association was clearer with BDE-99, with inverse associations being found with AC, EFW, and BPD at weeks 20–34, and with BW and HC at delivery. These outcomes decreased between 1.3% and 3.5% for each 2-fold PBDE increase. Concerning matrices, we found statistically significant inverse associations with BPD, HC, and BW when using maternal serum, and for AC and EFW with cord serum. In conclusion, PBDEs may impair fetal growth in late pregnancy and reduce birth size. PMID:26181825

  2. Non-occupational exposure to paint fumes during pregnancy and fetal growth in a general population.

    PubMed

    Sørensen, Mette; Andersen, Anne-Marie N; Raaschou-Nielsen, Ole

    2010-05-01

    Occupational exposure to organic solvents during pregnancy has been associated with reduced fetal growth. Though organic solvents in the form of paint fumes are also found in the home environment, no studies have investigated the effect of such exposure in a general population. We studied associations between residential exposure to paint fumes during pregnancy and fetal growth within the Danish National Birth Cohort which consecutively recruited pregnant women from 1996 to 2002 from all over Denmark. Around the 30th pregnancy week, 19,000 mothers were interviewed about use of paint in their residence during pregnancy. The mothers were also asked about smoking habits and alcohol consumption during pregnancy, pre-pregnancy weight, height, parity and occupation. Information on birth weight and gestational age was obtained from national registers. We found that 45% of the mothers had been exposed to paint fumes in their residence during pregnancy. We found a statistically significant inverse relationship between exposure to paint fumes and the risk of being small for gestational age. There were no statistically significant associations between exposure to paint fumes and birth weight and risk of preterm birth after adjustment for potential confounders. Our results suggest that there are no causal relationship between non-occupational exposure to paint fumes in the residence during pregnancy and fetal growth.

  3. Early placental insulin-like protein (INSL4 or EPIL) in placental and fetal membrane growth.

    PubMed

    Millar, Lynnae; Streiner, Nicole; Webster, Lisa; Yamamoto, Sandra; Okabe, Rachel; Kawamata, Tasha; Shimoda, Jacqueline; Büllesbach, Erika; Schwabe, Christian; Bryant-Greenwood, Gillian

    2005-10-01

    Early placental insulin-like protein (INSL4 or EPIL) is a member of the insulin superfamily of hormones, which is highly expressed in the placenta. We have confirmed this at term and shown it to be expressed by the maternal decidua. Although an abundance of locally acting growth factors are produced within the uterus during pregnancy, we hypothesized that INSL4 plays an important role in fetal and placental growth. We have demonstrated with cell lines and primary cells that it has a growth-inhibitory effect by causing apoptosis and loss of cell viability. We used primary amniotic epithelial cells for flow cytometry to show that INSL4 caused apoptosis, which was dose-related and significant (P < 0.05) at 50 ng/ml. This was confirmed by measurement of the nuclear matrix protein in the media. In comparison, relaxin treatment (up to 200 ng/ml) had no effect on apoptosis. The addition of INSL4 (3-30 ng/ml) also caused a loss of cell viability, although it had no effect on the numbers of cells at different phases of the cell cycle. Placental apoptosis is an important process in both normal placental development and in fetal growth restriction. Therefore, an in vivo clinical correlate was sought in fraternal twins exhibiting discordant growth. Expression of the INSL4 gene was doubled in the placenta of the growth-restricted twin compared to the normally grown sibling, suggesting that it may be linked to a higher level of apoptosis and loss of cell viability and, therefore, that it may contribute to fetal growth restriction.

  4. Fetal alcohol exposure and mammary tumorigenesis in offspring: role of the estrogen and insulin-like growth factor systems.

    PubMed

    Cohick, Wendie S; Crismale-Gann, Catina; Stires, Hillary; Katz, Tiffany A

    2015-01-01

    Fetal alcohol spectrum disorders affect a significant number of live births each year, indicating that alcohol consumption during pregnancy is an important public health issue. Environmental exposures and lifestyle choices during pregnancy may affect the offspring's risk of disease in adulthood, leading to the idea that a woman's risk of breast cancer may be pre-programmed prior to birth. Exposure of pregnant rats to alcohol increases tumorigenesis in the adult offspring in response to mammary carcinogens. The estrogen and insulin-like growth factor (IGF-I) axes occupy central roles in normal mammary gland development and breast cancer. 17-β estradiol (E2) and IGF-I synergize to regulate formation of terminal end buds and ductal elongation during pubertal development. The intracellular signaling pathways mediated by the estrogen and IGF-I receptors cross-talk at multiple levels through both genomic and non-genomic mechanisms. Several components of the E2 and IGF-I systems are altered in early development in rat offspring exposed to alcohol in utero, therefore, these changes may play a role in the enhanced susceptibility to mammary carcinogens observed in adulthood. Alcohol exposure in utero induces a number of epigenetic alterations in non-mammary tissues in the offspring and other adverse in utero exposures induce epigenetic modifications in the mammary gland. Future studies will determine if fetal alcohol exposure can induce epigenetic modifications in genes that regulate E2/IGF action at key phases of mammary development, ultimately leading to changes in susceptibility to carcinogens.

  5. Brachmann-de Lange syndrome: a cause of early symmetric fetal growth delay.

    PubMed

    Boog, G; Sagot, F; Winer, N; David, A; Nomballais, M F

    1999-08-01

    Brachmann-de Lange syndrome is characterized by pre- and postnatal growth retardation, microbrachycephaly, hirsutism, various visceral and limb anomalies and a typical face. A sonographic prenatal diagnosis at mid-trimester is reported in a case of severe, symmetrical fetal growth delay at 20 weeks gestation, with a thickened skin on the forehead, a small nose and a marked depressed nasal bridge, a long philtrum, micrognathia and a persistently flexed right forearm, with a single bone associated to oligodactyly. Due to the severe mental impairment with a commonly estimated intelligence quotient under 60, the pregnancy was terminated after parental consent. PMID:10584631

  6. Influence of progesterone supplementation during the first third of pregnancy on fetal and placental growth in overnourished adolescent ewes.

    PubMed

    Wallace, J M; Bourke, D A; Da Silva, P; Aitken, R P

    2003-10-01

    intake plus progesterone group (4150+/-389 g) was intermediate between the high intake (P<0.02) and moderate intake (P<0.05) groups, but this change in birth weight was not associated with corresponding changes in fetal cotyledon mass (76+/-10.3 g). Moreover, the number of fetal cotyledons was similar in all three groups. Thus, progesterone did not directly affect the growth of the fetal cotyledon but may have influenced placental vascularity, blood flow or nutrient transfer capacity or alternatively the development of the embryonic inner cell mass.

  7. Maternal cadmium exposure reduces placental zinc transport and induces fetal growth restriction in mice.

    PubMed

    Wang, Hua; Wang, Ying; Bo, Qing-Li; Ji, Yan-Li; Liu, Lu; Hu, Yong-Fang; Chen, Yuan-Hua; Zhang, Jun; Zhao, Ling-Li; Xu, De-Xiang

    2016-08-01

    Cadmium (Cd) is linked with increased risk of fetal growth restriction (FGR). Nevertheless, the mechanism remains unknown. This study established a mouse model of Cd-induced FGR through two exposure methods. Pregnant mice were either administered with CdCl2 (5, 50 and 250ppm) throughout pregnancy through drinking water or intraperitoneally injected with CdCl2 (4.5mg/kg) on GD9. As expected, fetal weight and crown-rump length were reduced in a gender-independent manner. Interestingly, Mt1 and Mt2, two metallothionein genes, were up-regulated in maternal liver. Correspondingly, Cd accumulated mainly in maternal liver and kidney, and only trace amounts of Cd could pass from dam to placentas and fetuses. Further analysis showed that placental Zn concentration was elevated. Conversely, embryonic Zn concentration was reduced. Moreover, placental Znt1 and Znt2, two zinc transporters, were down-regulated in Cd-exposed mice. These results suggest that maternal Cd exposure during pregnancy reduces placental Zn transport and induces fetal growth restriction. PMID:27319394

  8. Fetal growth according to different reference ranges in twin pregnancies with placental insufficiency

    PubMed Central

    Nakano, Julianny Cavalheiro Nery; Liao, Adolfo Wenjaw; de Lourdes Brizot, Maria; Miyadahira, Mariana; Francisco, Rossana Pulcineli Vieira; Zugaib, Marcelo

    2015-01-01

    The aim of this study was to compare different fetal growth curves in twin pregnancies with severe placental insufficiency. A retrospective cross-sectional analysis of 47 twin pregnancies with absent or reverse end diastolic flow in the umbilical artery of one fetus was performed. Pregnancies with major fetal abnormalities, twin-twin transfusion or three or more fetuses were not included. The estimated fetal weight zeta-scores were calculated for both fetuses (abnormal Doppler and co-twin) according to the following criteria: Hadlock, Liao and Araújo. The abdominal circumference zeta-scores were calculated according to Hadlock, Liao, Araújo, Ong and Stirrup. The mean estimates of the zeta-score values were calculated using generalized estimating equation regression analysis. The mean gestational age at inclusion was 27.4±4.7 weeks. The fetal sex and the interaction Doppler findings × criteria correlated significantly with the zeta-score values (p<0.001 for both variables). The estimated fetal weight mean zeta-scores (standard error) according to each criteria were as follows: Hadlock - abnormal Doppler: -2.98 (0.18), co-twin: -1.16 (0.15); Liao - abnormal Doppler: -2.89 (0.24), co-twin: -0.58 (0.19); and Araújo - abnormal Doppler: -3.05 (0.29), co-twin: -0.75 (0.18). Values for abdominal circumference were as follows: Hadlock - abnormal Doppler: -3.14 (0.26), co-twin: -1.13 (0.19); Liao - abnormal Doppler: -2.63 (0.27), co-twin: -0.42 (0.19); Araújo - abnormal Doppler: -2.44 (0.22), co-twin: -0.71 (0.14); Ong - abnormal Doppler: -3.36 (0.34), co-twin: -1.48 (0.23); and Stirrup AD -- -2.36 (0.14), co-twin: -1.18 (0.10). Sex- and plurality-specific charts should be used in the evaluation of fetal growth in twin pregnancies with placental insufficiency. PMID:26735222

  9. Allometric studies on growth and development of the human placenta: growth of tissue compartments and diffusive conductances in relation to placental volume and fetal mass.

    PubMed

    Mayhew, Terry M

    2006-06-01

    Correlations between placental size and fetal mass during gestation fail to account for changes in composition that accompany placental growth and maturation. This study uses stereological data on the sizes of different tissue compartments in human placentas from 10 weeks of gestation to term and relates them to placental volume and to fetal mass by means of allometric analysis. In addition, tissue dimensions are used to calculate a physiological transport measure (diffusive conductance) for the villous membrane. Histological sections randomly sampled from placentas and analysed stereologically provided estimates of structural quantities (volumes, exchange surface areas, lengths, numbers of nuclei, diffusion distances). These data were combined with a physicochemical quantity (Krogh's diffusion coefficient) in order to estimate oxygen diffusive conductances for the villous membrane and its two components (trophoblast and stroma). Allometric relationships between these quantities and placental volume or fetal mass were obtained by linear regression analyses after log-transformation. Placental tissues had different growth trajectories: most grew more rapidly than placental volume and all grew more slowly than fetal mass. Diffusion distances were inversely related to placental and fetal size. Differential growth impacted on diffusive conductances, which, again, did not improve commensurately with placental volume but did match exactly growth of the fetus. Findings show that successful integration between supply and demand can be achieved by differential tissue growth. Allometric analysis of results from recent studies on the murine placenta suggest further that diffusive conductances may also be matched to fetal mass during gestation and to fetal mass at term across species.

  10. Fetal PCB syndrome: clinical features, intrauterine growth retardation and possible alteration in calcium metabolism

    SciTech Connect

    Yamashita, F.; Hayashi, M.

    1985-02-01

    Pregnant mothers with Yusho in Fukuoka, Nagasaki and Kochi Prefectures delivered babies with a peculiar clinical manifestation which will be called fetal PCB syndrome (FPS). The birth rate incidences were 3.6% (Fukuoka Prefecture), 4% (Nagasaki Prefecture), 2.9% (Kochi Prefecture) and 3.9% (total). The manifestations consisted of dark brown pigmentation of the skin and the mucous membrane, gingival hyperplasia, exophthalmic edematous eye, dentition at birth, abnormal calcification of the skull as demonstrated by X-ray, rocker bottom heel and high incidence of light for date (low birth weight) babies. The authors suggest that there may be a possible alteration in calcium metabolism in these babies, related to the fragile egg shells observed in PCB-contaminated birds and to the female hormone-enhancing effect of PCB. The high incidence of low birth weight among these newborns and two other similar studies indicated that PCBs suppress fetal growth.

  11. Ethnic/racial disparities in the fetal growth outcomes of Ecuadorian newborns.

    PubMed

    Margaret Weigel, M; Sanchez, Maria Elena Caiza

    2013-02-01

    Size at birth is an important indicator of future infant morbidity and mortality. Ethnic/racial disparities in birth weight and other fetal growth outcomes are well documented for US and Canadian minority groups but not for those in Latin America. The study compared the growth outcomes of 1,227 full-term Ecuadorian newborns delivered by Afro-descendant and indigenous minority women with those of ethnic majority (mestizo) women. Minority newborns had higher risk for congenital microcephaly but no excess risk for low birth weight or stunted linear growth compared to mestizos. However, minority newborns were significantly heavier at birth, weighing an average of 3-5% more than mestizos. Afro-Ecuadorians newborns also were fatter. The risk profile of Ecuadorian ethnic groups for certain fetal growth outcomes differs from some of those reported for North American minorities. Further studies are needed to investigate the origins of these between-group differences and to develop ethnic specific interventions for adverse growth outcomes.

  12. Postnatal growth restriction and gene expression changes in a mouse model of fetal alcohol syndrome.

    PubMed

    Kaminen-Ahola, Nina; Ahola, Arttu; Flatscher-Bader, Traute; Wilkins, Sarah J; Anderson, Greg J; Whitelaw, Emma; Chong, Suyinn

    2010-10-01

    Growth restriction, craniofacial dysmorphology, and central nervous system defects are the main diagnostic features of fetal alcohol syndrome. Studies in humans and mice have reported that the growth restriction can be prenatal or postnatal, but the underlying mechanisms remain unknown.We recently described a mouse model of moderate gestational ethanol exposure that produces measurable phenotypes in line with fetal alcohol syndrome (e.g., craniofacial changes and growth restriction in adolescent mice). In this study, we characterize in detail the growth restriction phenotype by measuring body weight at gestational day 16.5, cross-fostering from birth to weaning, and by extending our observations into adulthood. Furthermore, in an attempt to unravel the molecular events contributing to the growth phenotype, we have compared gene expression patterns in the liver and kidney of nonfostered, ethanol-exposed and control mice at postnatal day 28.We find that the ethanol-induced growth phenotype is not detectable prior to birth, but is present at weaning, even in mice that have been cross-fostered to unexposed dams. This finding suggests a postnatal growth restriction phenotype that is not due to deficient postpartum care by dams that drank ethanol, but rather a physiologic result of ethanol exposure in utero. We also find that, despite some catch-up growth after 5 weeks of age, the effect extends into adulthood, which is consistent with longitudinal studies in humans.Genome-wide gene expression analysis revealed interesting ethanol-induced changes in the liver, including genes involved in the metabolism of exogenous and endogenous compounds, iron homeostasis, and lipid metabolism.

  13. Prostaglandin E2 regulation of amnion cell vascular endothelial growth factor expression: relationship with intramembranous absorption rate in fetal sheep.

    PubMed

    Cheung, Cecilia Y; Beardall, Michael K; Anderson, Debra F; Brace, Robert A

    2014-08-01

    We hypothesized that prostaglandin E2 (PGE2) stimulates amniotic fluid transport across the amnion by upregulating vascular endothelial growth factor (VEGF) expression in amnion cells and that amniotic PGE2 concentration correlates positively with intramembranous (IM) absorption rate in fetal sheep. The effects of PGE2 at a range of concentrations on VEGF 164 and caveolin-1 gene expressions were analyzed in cultured ovine amnion cells. IM absorption rate, amniotic fluid (AF) volume, and PGE2 concentration in AF were determined in late-gestation fetal sheep during control conditions, isovolumic fetal urine replacement (low IM absorption rate), or intra-amniotic fluid infusion (high IM absorption rate). In ovine amnion cells, PGE2 induced dose- and time-dependent increases in VEGF 164 mRNA levels and reduced caveolin-1 mRNA and protein levels. VEGF receptor blockade abolished the caveolin-1 response, while minimally affecting the VEGF response to PGE2. In sheep fetuses, urine replacement reduced amniotic PGE2 concentration by 58%, decreased IM absorption rate by half, and doubled AF volume (P < 0.01). Intra-amniotic fluid infusion increased IM absorption rate and AF volume (P < 0.01), while amniotic PGE2 concentration was unchanged. Neither IM absorption rate nor AF volume correlated with amniotic PGE2 concentration under each experimental condition. Although PGE2 at micromolar concentrations induced dose-dependent responses in VEGF and caveolin-1 gene expression in cultured amnion cells consistent with a role of PGE2 in activating VEGF to mediate AF transport across the amnion, amniotic PGE2 at physiological nanomolar concentrations does not appear to regulate IM absorption rate or AF volume.

  14. Antenatal taurine supplementation increases taurine content in intrauterine growth restricted fetal rat brain tissue.

    PubMed

    Li, Fang; Teng, Hui-Yun; Liu, Jing; Wang, Hua-Wei; Zeng, Li; Zhao, Li-Fang

    2014-09-01

    This study aimed to determine the influence of antenatal taurine supplementation on taurine content in the brains of fetal rats with intrauterine growth restriction (IUGR). Experiments were performed at the Central Laboratory of Bayi Children's Hospital Affiliated to Beijing Military General Hospital in China from January to June 2013. Fifteen pregnant rats were randomly divided into three groups: normal controls, an IUGR group and an IUGR + antenatal taurine supplement group (Taurine group) (n = 5). The IUGR model was induced using a low-protein diet throughout gestation. Rats in the taurine group were fed a diet supplemented with 300 mg/kg/day taurine for 12 days after conception until natural delivery. Two fetal rats were randomly selected in every litter, and taurine levels in the brains of rats were detected using high-performance liquid chromatography-mass spectrometry. Results showed that (1) the mean body weight of the fetal rats in the normal control, IUGR and IUGR + antenatal taurine supplement groups was 6.619 ± 0.4132, 4.509 ± 0.454, and 5.176 ± 0.436 g (F = 429.818, P < 0.01), respectively, and (2) that taurine levels in the brains of the fetal rats in the normal control, IUGR and taurine groups were (2.399 ± 0.134) × 10(5), (1.881 ± 0.166) × 10(5) and (2.170 ± 0.191) × 10(5) μg/g (F = 24.828, P < 0.01), respectively. Overall, our results indicated that taurine levels in IUGR fetal rat brains were lower than in the control animals, and that antenatal taurine supplementation could significantly increase taurine levels in the brains of fetal rats with IUGR.

  15. Antenatal taurine supplementation increases taurine content in intrauterine growth restricted fetal rat brain tissue.

    PubMed

    Li, Fang; Teng, Hui-Yun; Liu, Jing; Wang, Hua-Wei; Zeng, Li; Zhao, Li-Fang

    2014-09-01

    This study aimed to determine the influence of antenatal taurine supplementation on taurine content in the brains of fetal rats with intrauterine growth restriction (IUGR). Experiments were performed at the Central Laboratory of Bayi Children's Hospital Affiliated to Beijing Military General Hospital in China from January to June 2013. Fifteen pregnant rats were randomly divided into three groups: normal controls, an IUGR group and an IUGR + antenatal taurine supplement group (Taurine group) (n = 5). The IUGR model was induced using a low-protein diet throughout gestation. Rats in the taurine group were fed a diet supplemented with 300 mg/kg/day taurine for 12 days after conception until natural delivery. Two fetal rats were randomly selected in every litter, and taurine levels in the brains of rats were detected using high-performance liquid chromatography-mass spectrometry. Results showed that (1) the mean body weight of the fetal rats in the normal control, IUGR and IUGR + antenatal taurine supplement groups was 6.619 ± 0.4132, 4.509 ± 0.454, and 5.176 ± 0.436 g (F = 429.818, P < 0.01), respectively, and (2) that taurine levels in the brains of the fetal rats in the normal control, IUGR and taurine groups were (2.399 ± 0.134) × 10(5), (1.881 ± 0.166) × 10(5) and (2.170 ± 0.191) × 10(5) μg/g (F = 24.828, P < 0.01), respectively. Overall, our results indicated that taurine levels in IUGR fetal rat brains were lower than in the control animals, and that antenatal taurine supplementation could significantly increase taurine levels in the brains of fetal rats with IUGR. PMID:24676564

  16. Fetal growth and birth size is associated with maternal anthropometry and body composition.

    PubMed

    Thame, Minerva; Osmond, Clive; Trotman, Helen

    2015-10-01

    The objective was to investigate the association of maternal weight, height and body composition with fetal growth. We recruited 425 women at the University Hospital of the West Indies, Jamaica, who had singleton pregnancies, were less than 15 weeks gestation and had no systemic illness. Maternal weight, height and skinfold thicknesses were measured at the first antenatal visit and lean mass was calculated. Sonographic measurements of the fetus were made at 15, 25 and 35 weeks gestation. Weight, crown-heel length and head circumference were measured at birth. Analyses were confined to 360 (85%) women; 65 women did not complete the study. Maternal height was positively associated with femoral length at 25 and 35 weeks gestation and with head circumference at 35 weeks (all P < 0.02). Maternal weight was positively associated with abdominal circumference and femoral length at 25 weeks, and with larger head and abdominal circumference and longer femur at 35 weeks (all P < 0.02). Maternal lean mass had similar associations to maternal weight and they were both positively associated with estimated fetal weight (all P < 0.02). All three maternal measurements were positively associated with birthweight, length and head circumference. Maternal size was associated with fetal size as early as 25 weeks gestation, with height strongly associated with femoral length, and with weight and lean mass strongly associated with abdominal circumference.

  17. Effect of fetal growth on maternal protein metabolism in postabsorptive rat

    SciTech Connect

    Ling, P.R.; Bistrian, B.R.; Blackburn, G.L.; Istfan, N.

    1987-03-01

    Rates of protein synthesis were measured in whole fetuses and maternal tissues at 17 and 20 days of gestation in postabsorptive rats using continuous infusion of L-(1-/sup 14/C)leucine. Fetal protein degradation rates were derived from the fractional rates of synthesis and growth. Whole-body (plasma) leucine kinetics in the mother showed a significant reduction of the fraction of plasma leucine oxidized in the mothers bearing older fetuses, a slight increase in the plasma flux, with total leucine oxidation and incorporation into protein remaining similar at the two gestational ages. Estimates of fractional protein synthesis in maternal tissues revealed an increase in placental and hepatic rates at 20 days of gestation, whereas the fractional synthetic rate in muscle remained unchanged. A model for estimation of the redistribution of leucine between plasma and tissues is described in detail. This model revealed a more efficient utilization of leucine in fetal protein synthesis in comparison with other maternal tissues, a greater dependency of the fetus on plasma supply of leucine, and a significant increase (2-fold) in the release of leucine from maternal muscle as the fetal requirements increased proportionately with its size. The latter conclusion, supported by nitrogen analysis and the ratio of bound-to-free leucine in maternal tissues, confirms the importance of maternal stores in maintaining the homeostasis of essential amino acids during late pregnancy.

  18. Invited commentary: the incremental value of customization in defining abnormal fetal growth status.

    PubMed

    Zhang, Jun; Sun, Kun

    2013-10-15

    Reference tools based on birth weight percentiles at a given gestational week have long been used to define fetuses or infants that are small or large for their gestational ages. However, important deficiencies of the birth weight reference are being increasingly recognized. Overwhelming evidence indicates that an ultrasonography-based fetal weight reference should be used to classify fetal and newborn sizes during pregnancy and at birth, respectively. Questions have been raised as to whether further adjustments for race/ethnicity, parity, sex, and maternal height and weight are helpful to improve the accuracy of the classification. In this issue of the Journal, Carberry et al. (Am J Epidemiol. 2013;178(8):1301-1308) show that adjustment for race/ethnicity is useful, but that additional fine tuning for other factors (i.e., full customization) in the classification may not further improve the ability to predict infant morbidity, mortality, and other fetal growth indicators. Thus, the theoretical advantage of full customization may have limited incremental value for pediatric outcomes, particularly in term births. Literature on the prediction of short-term maternal outcomes and very long-term outcomes (adult diseases) is too scarce to draw any conclusions. Given that each additional variable being incorporated in the classification scheme increases complexity and costs in practice, the clinical utility of full customization in obstetric practice requires further testing.

  19. Transfusion effects on cardiomyocyte growth and proliferation in fetal sheep following chronic anemia

    PubMed Central

    Jonker, Sonnet S.; Scholz, Thomas D.; Segar, Jeffrey L.

    2011-01-01

    Chronic fetal anemia results in significant cardiac remodeling. The capacity to reverse these effects is unknown. We examined the effects of transfusion on cardiomyocyte adaptations following chronic anemia in fetal sheep subjected to daily hemorrhage beginning at 109d gestation age (GA; term ∼145d). Following 10 days of anemia, one group was euthanized for comparison to age-matched controls. A separate group of anemic fetuses was transfused with red blood cells at 119d GA for comparison to controls at 129d GA. Anemia significantly increased the heart-to-body weight ratio, an effect partially ameliorated following transfusion. Cardiomyocyte dimensions were similar among all groups, suggesting an absence of hypertrophy. The percentages of mono- and binucleated cardiomyocytes were similar between groups at 119d GA, though the percentage of binucleated cells was significantly less in transfused fetuses compared to controls at 129d GA. Protein levels of mitogen activated protein kinases and protein kinase B were similar between controls and their respective intervention groups, except for a significant increase in phosphorylated c-Jun N-terminal kinase 1/2 (JNK1/2) in transfused fetuses. Thus, cardiomyocyte proliferation but not hypertrophy contributes to cardiac enlargement during fetal anemia. Transfusion results in slowing but not cessation of cardiac growth following anemia. PMID:21386752

  20. Stillbirth classification in population-based data and role of fetal growth restriction: the example of RECODE

    PubMed Central

    2013-01-01

    Background Stillbirth classifications use various strategies to synthesise information associated with fetal demise with the aim of identifying key causes for the death. RECODE is a hierarchical classification of death-related conditions, which grants a major place to fetal growth restriction (FGR). Our objective was to explore how placement of FGR in the hierarchy affected results from the classification. Methods In the Rhône-Alpes region, all stillbirths were recorded in a local registry from 2000 to 2010 in three districts (N = 969). Small for gestational age (SGA) was defined as a birthweight below the 10th percentile. We applied RECODE and then modified the hierarchy, including FGR as the penultimate category (RECODE-R). Results 49.0% of stillbirths were SGA. From RECODE to RECODE-R, stillbirths attributable to FGR decreased from 38% to 14%, in favour of other related conditions. Nearly half of SGA stillbirths (49%) were reclassified. There was a non-significant tendency toward moderate SGA, singletons and full-term stillbirths to older mothers being reclassified. Conclusions The position of FGR in hierarchical stillbirth classification has a major impact on the first condition associated with stillbirth. RECODE-R calls less attention to monitoring SGA fetuses but illustrates the diversity of death-related conditions for small fetuses. PMID:24090495

  1. Ex Vivo Expansion and Differentiation of Human and Mouse Fetal Pancreatic Progenitors Are Modulated by Epidermal Growth Factor.

    PubMed

    Bonfanti, Paola; Nobecourt, Estelle; Oshima, Masaya; Albagli-Curiel, Olivier; Laurysens, Veerle; Stangé, Geert; Sojoodi, Mozhdeh; Heremans, Yves; Heimberg, Harry; Scharfmann, Raphael

    2015-08-01

    A comparative analysis of mouse and human pancreatic development may reveal common mechanisms that control key steps as organ morphogenesis and cell proliferation and differentiation. More specifically, understanding beta cell development remains an issue, despite recent progress related to their generation from human embryonic and induced pluripotent stem cells. In this study, we use an integrated approach, including prospective isolation, organ culture, and characterization of intermediate stages, and report that cells from human and mouse fetal pancreas can be expanded in the long term and give rise to hollow duct-like structures in 3D cultures. The expanded cells express a combination of markers (E-cadherin, PDX1, NKX6-1, SOX9, and HNF1β) that reveals pancreatic progenitor identity. Proliferation of embryonic progenitors was stimulated by the Wnt agonist R-spondin1 (RSPO1), FGF10, and EGF. This combination of growth factors allowed maintaining human fetal pancreatic progenitors in culture for many passages, a finding not reported previously. Importantly, in the absence of EGF, proliferation was reduced, while endocrine differentiation was significantly enhanced. We conclude that modulation of EGF signaling affects in vitro expansion and differentiation of progenitors from embryonic pancreas of both mice and man.

  2. The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Systematic Review of Nonhuman Evidence for PFOA Effects on Fetal Growth

    PubMed Central

    Lam, Juleen; Sutton, Patrice; Johnson, Paula I.; Atchley, Dylan S.; Sen, Saunak; Robinson, Karen A.; Axelrad, Daniel A.; Woodruff, Tracey J.

    2014-01-01

    Background: In contrast to current methods of expert-based narrative review, the Navigation Guide is a systematic and transparent method for synthesizing environmental health research from multiple evidence streams. The Navigation Guide was developed to effectively and efficiently translate the available scientific evidence into timely prevention-oriented action. Objectives: We applied the Navigation Guide systematic review method to answer the question “Does fetal developmental exposure to perfluorooctanoic acid (PFOA) or its salts affect fetal growth in animals ?” and to rate the strength of the experimental animal evidence. Methods: We conducted a comprehensive search of the literature, applied prespecified criteria to the search results to identify relevant studies, extracted data from studies, obtained additional information from study authors, conducted meta-analyses, and rated the overall quality and strength of the evidence. Results: Twenty-one studies met the inclusion criteria. From the meta-analysis of eight mouse gavage data sets, we estimated that exposure of pregnant mice to increasing concentrations of PFOA was associated with a change in mean pup birth weight of –0.023 g (95% CI: –0.029, –0.016) per 1-unit increase in dose (milligrams per kilogram body weight per day). The evidence, consisting of 15 mammalian and 6 nonmammalian studies, was rated as “moderate” and “low” quality, respectively. Conclusion: Based on this first application of the Navigation Guide methodology, we found sufficient evidence that fetal developmental exposure to PFOA reduces fetal growth in animals. Citation: Koustas E, Lam J, Sutton P, Johnson PI, Atchley DS, Sen S, Robinson KA, Axelrad DA, Woodruff TJ. 2014. The Navigation Guide—evidence-based medicine meets environmental health: systematic review of nonhuman evidence for PFOA effects on fetal growth. Environ Health Perspect 122:1015–1027; http://dx.doi.org/10.1289/ehp.1307177 PMID:24968374

  3. Antenatal taurine supplementation for improving brain ultrastructure in fetal rats with intrauterine growth restriction.

    PubMed

    Liu, J; Liu, L; Chen, H

    2011-05-01

    Changes in brain ultrastructure of fetal rats with intrauterine growth restriction (IUGR) were explored and the effects of antenatal taurine supplementation on their brain ultrastructure were determined. Fifteen pregnant rats were randomly divided into three groups: control group, IUGR model group and IUGR group given antenatal taurine supplements. Taurine was added to the diet of the taurine group at a dose of 300 mg/kg/d from 12 days after conception until natural delivery. Transmission electron microscopy was used to observe ultrastructural changes in the brains of the newborn rats. At the same time, brain cellular apoptosis was detected using TUNEL, and the changes in protein expression of neuron specific enolase and glial fibrillary acidic protein were analyzed using immunohistochemistry. The results showed that: 1) The average body weight and cerebral weight were significantly lower in the IUGR group than in the control group (p<0.01) and both of them were less so after taurine was supplemented (p<0.01). 2) Transmission electron microscopy revealed that brain cortex structures were sparse IUGR rats, showing many scattered apoptotic cells, decreased numbers of synapses, lower glial cell proliferation, and fewer neurons, more sparsely arranged, while these factors were significantly improved with taurine supplementation. 3) The results of TUNEL showed that the counts of apoptotic brain cells in IUGR groups were significantly increased from those in control groups and that taurine could significantly decrease brain cell apoptosis (p<0.001). 4) The results of immunohistochemistry showed that antenatal taurine-supplementation could significantly increase the counts of neuron specific enolase and glial fibrillary acidic protein immunoreactive cells in fetal rats with IUGR (p<0.001). It can be concluded that it IUGR has a significant detrimental influence on the development of fetal rat brains, and antenatal supplement of taurine can significantly improve the IUGR

  4. High Dosage Folic Acid Supplementation, Oral Cleft Recurrence and Fetal Growth

    PubMed Central

    Wehby, George L.; Félix, Têmis Maria; Goco, Norman; Richieri-Costa, Antonio; Chakraborty, Hrishikesh; Souza, Josiane; Pereira, Rui; Padovani, Carla; Moretti-Ferreira, Danilo; Murray, Jeffrey C.

    2013-01-01

    Objectives: To evaluate the effects of folic acid supplementation on isolated oral cleft recurrence and fetal growth. Patients and Methods: The study included 2,508 women who were at-risk for oral cleft recurrence and randomized into two folic acid supplementation groups: 0.4 and 4 mg per day before pregnancy and throughout the first trimester. The infant outcome data were based on 234 live births. In addition to oral cleft recurrence, several secondary outcomes were compared between the two folic acid groups. Cleft recurrence rates were also compared to historic recurrence rates. Results: The oral cleft recurrence rates were 2.9% and 2.5% in the 0.4 and 4 mg groups, respectively. The recurrence rates in the two folic acid groups both separately and combined were significantly different from the 6.3% historic recurrence rate post the folic acid fortification program for this population (p = 0.0009 when combining the two folic acid groups). The rate of cleft lip with palate recurrence was 2.9% in the 0.4 mg group and 0.8% in the 4 mg group. There were no elevated fetal growth complications in the 4 mg group compared to the 0.4 mg group. Conclusions: The study is the first double-blinded randomized clinical trial (RCT) to study the effect of high dosage folic acid supplementation on isolated oral cleft recurrence. The recurrence rates were similar between the two folic acid groups. However, the results are suggestive of a decrease in oral cleft recurrence compared to the historic recurrence rate. A RCT is still needed to identify the effect of folic acid on oral cleft recurrence given these suggestive results and the supportive results from previous interventional and observational studies, and the study offers suggestions for such future studies. The results also suggest that high dosage folic acid does not compromise fetal growth. PMID:23380913

  5. Serial measurements of serum human placental lactogen (hPL) and serial ultrasound examinations in the evaluation of fetal growth.

    PubMed

    Sørensen, S; von Tabouillot, D; Schioler, V; Greisen, G; Petersen, S; Larsen, T

    2000-11-01

    Serial serum hPL measurements and serial ultrasound fetometry were compared in the evaluation of fetal growth by relating these two parameters to size at birth and to clinical factors known to influence size at birth. The data were from a prospective study of 1000 consecutive pregnant women considered to be at risk for fetal growth retardation with retrospective analysis. Serum hPL was measured by radioimmunoassay and fetal weight estimated by ultrasound every 3 weeks during the last trimester. hPL values were expressed as multiples of the median (MoM) and linear regression analysis of the hPL MoM values was carried out for each pregnancy to find the slope of the line (hPL-slope); at least 3 serum hPL values were required. The estimated fetal weight and weight-for-age at birth was expressed in Z-scores. The individual intrauterine growth velocity was calculated by regression analysis and expressed as change in Z-score for 12 weeks. At least two ultrasound measurements over an interval of at least 42 days were used to estimate the fetal growth velocity. In 588 women the file was complete. The main outcome measures were the individual mean hPL, hPL-slope, fetal growth velocity, birth weight deviation, smoking in pregnancy and diagnosis of preeclampsia. A significant correlation was found between the hPL-slope and the intrauterine fetal growth velocity (r=0.34), and between hPL-slope and birth weight deviation (r=0.32). Mean hPL was correlated to birth weight deviation (r=0.27), but only very weakly to intrauterine growth velocity (r=0.08). hPL-slope and intrauterine growth velocity independently predicted birth weight deviation. Heavy smoking which was stopped before the third trimester was not associated with low intrauterine growth velocity, but with a low hPL-slope. Preeclampsia was associated with a trend towards low and decreasing hPL and with an increasing intrauterine growth velocity and birth weight deviation. In conclusion the rate of change of serial h

  6. Child abuse registration, fetal growth, and preterm birth: a population based study

    PubMed Central

    Spencer, Nick; Wallace, Ann; Sundrum, Ratna; Bacchus, Claire; Logan, Stuart

    2006-01-01

    Objectives To study the relation of intra‐uterine growth and gestational age with child protection registration in a 20 year whole population birth cohort. Setting West Sussex area of England. Study design Retrospective whole population birth cohort. Outcomes Child protection registration; individual categories of registration—sexual abuse, physical abuse, emotional abuse, and neglect. Population and participants 119 771 infants born in West Sussex between January 1983 and December 2001 with complete data including birth weight, gestational age, maternal age, and postcode. Results In all categories of registration a linear trend was noted such that the lower the birth weight z score the higher the likelihood of child protection registration. Similar trends were noted for gestational age. All these trends were robust to adjustment for maternal age and socioeconomic status. Conclusions The results of this study suggest that lower levels of fetal growth and shorter gestational duration are associated with increased likelihood of child protection registration in all categories including sexual abuse independent of maternal age or socioeconomic status. This study does not permit comment on whether poor fetal growth or preterm birth predispose to child abuse and neglect or the association arises because they share a common pathway. PMID:16537351

  7. Maternal oxygen delivery is not related to altitude- and ancestry-associated differences in human fetal growth

    PubMed Central

    Zamudio, Stacy; Postigo, Lucrecia; Illsley, Nicholas P; Rodriguez, Carmelo; Heredia, Gladys; Brimacombe, Michael; Echalar, Lourdes; Torricos, Tatiana; Tellez, Wilma; Maldonado, Ivan; Balanza, Elfride; Alvarez, Tatiana; Ameller, Julio; Vargas, Enrique

    2007-01-01

    Fetal growth is reduced at high altitude, but the decrease is less among long-resident populations. We hypothesized that greater maternal uteroplacental O2 delivery would explain increased fetal growth in Andean natives versus European migrants to high altitude. O2 delivery was measured with ultrasound, Doppler and haematological techniques. Participants (n= 180) were pregnant women of self-professed European or Andean ancestry living at 3600 m or 400 m in Bolivia. Ancestry was quantified using ancestry-informative single nucleotide polymorphims. The altitude-associated decrement in birth weight was 418 g in European versus 236 g in Andean women (P < 0.005). Altitude was associated with decreased uterine artery diameter, volumetric blood flow and O2 delivery regardless of ancestry. But the hypothesis was rejected as O2 delivery was similar between ancestry groups at their respective altitudes of residence. Instead, Andean neonates were larger and heavier per unit of O2 delivery, regardless of altitude (P < 0.001). European admixture among Andeans was negatively correlated with birth weight at both altitudes (P < 0.01), but admixture was not related to any of the O2 transport variables. Genetically mediated differences in maternal O2 delivery are thus unlikely to explain the Andean advantage in fetal growth. Of the other independent variables, only placental weight and gestational age explained significant variation in birth weight. Thus greater placental efficiency in O2 and nutrient transport, and/or greater fetal efficiency in substrate utilization may contribute to ancestry- and altitude-related differences in fetal growth. Uterine artery O2 delivery in these pregnancies was 99 ± 3 ml min−1, ∼5-fold greater than near-term fetal O2 consumption. Deficits in maternal O2 transport in third trimester normal pregnancy are unlikely to be causally associated with variation in fetal growth. PMID:17510190

  8. Is There Hope for Renal Growth on Imaging Studies Following Ureteral Reimplant for Boys With Fetal Hydronephrosis and Urinary Reflux?

    PubMed Central

    Wang, Ming-Hsien

    2015-01-01

    Reflux nephropathy is thought to be the etiology for renal maldevelopment. We present two boys with fetal hydronephrosis and sterile vesicoureteral reflux (VUR). There was lack of renal growth of the refluxing renal units on surveillance renal ultrasound. Parents elected to undergo open ureteral reimplants. Post-surgical ultrasounds demonstrated improved renal growth. PMID:26793522

  9. Protein restriction during pregnancy affects postnatal growth in swine progeny.

    PubMed

    Schoknecht, P A; Pond, W G; Mersmann, H J; Maurer, R R

    1993-11-01

    Protein deficiency during pregnancy affects fetal development. The critical period, when the fetus is most susceptible to maternal protein deficiency and its effect on neonatal growth, is unknown. Therefore, we studied the effect of a protein-restricted diet during early and late pregnancy and throughout pregnancy on growth of pigs from birth to market weight. Sows were fed a control (13% protein) or protein-restricted (0.5% protein) diet throughout pregnancy or protein-restricted diet from d 1 to 44, then control diet to term or control diet from d 1 to 81, then the protein-restricted diet to term. In Experiment 1, birth weights were measured, and 12 pigs/diet group were weaned at 4 wk and raised to market weight. Feeding the protein-restricted diet throughout pregnancy reduced birth and slaughter weights, whereas the control followed by protein-restricted and protein-restricted followed by control diets reduced only birth weight relative to controls. Indices of carcass lean were reduced in the protein-restricted piglets, with carcass fat not affected. In Experiment 2, control and control-protein-restricted litters were reduced to six piglets and 3/litter cross-fostered to a sow of the other treatment group. After weaning at 4 wk, 4 piglets/group were individually fed to 8 wk. The control and control followed by protein-restricted diet fed piglets had similar weights at birth, but piglets raised by a control-protein-restricted sow tended to weight less at weaning than their littermates raised by a control sow. After weaning, these piglets had greater feed intakes relative to other groups and there were no weight differences by 8 wk.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Relationships among Polycyclic Aromatic Hydrocarbon–DNA Adducts, Proximity to the World Trade Center, and Effects on Fetal Growth

    PubMed Central

    Perera, Frederica P.; Tang, Deliang; Rauh, Virginia; Lester, Kristin; Tsai, Wei Yann; Tu, Yi Hsuan; Weiss, Lisa; Hoepner, Lori; King, Jeffrey; Del Priore, Giuseppe; Lederman, Sally Ann

    2005-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are toxic pollutants released by the World Trade Center (WTC) fires and various urban combustion sources. Benzo[a]pyrene (BaP) is a representative member of the class of PAHs. PAH–DNA adducts, or BaP–DNA adducts as their proxy, provide a measure of chemical-specific genetic damage that has been associated with increased risk of adverse birth outcomes and cancer. To learn whether PAHs from the WTC disaster increased levels of genetic damage in pregnant women and their newborns, we analyzed BaP–DNA adducts in maternal (n = 170) and umbilical cord blood (n = 203) obtained at delivery from nonsmoking women who were pregnant on 11 September 2001 and were enrolled at delivery at three downtown Manhattan hospitals. The mean adduct levels in cord and maternal blood were highest among newborns and mothers who resided within 1 mi of the WTC site during the month after 11 September, intermediate among those who worked but did not live within this area, and lowest in those who neither worked nor lived within 1 mi (reference group). Among newborns of mothers living within 1 mi of the WTC site during this period, levels of cord blood adducts were inversely correlated with linear distance from the WTC site (p = 0.02). To learn whether PAHs from the WTC disaster may have affected birth outcomes, we analyzed the relationship between these outcomes and DNA adducts in umbilical cord blood, excluding preterm births to reduce variability. There were no independent fetal growth effects of either PAH–DNA adducts or environmental tobacco smoke (ETS), but adducts in combination with in utero exposure to ETS were associated with decreased fetal growth. Specifically, a doubling of adducts among ETS-exposed subjects corresponded to an estimated average 276-g (8%) reduction in birth weight (p = 0.03) and a 1.3-cm (3%) reduction in head circumference (p = 0.04). The findings suggest that exposure to elevated levels of PAHs, indicated by PAH

  11. The Role of Mucosal Defense in Intestinal Injury of Infants With Fetal Growth Retardation

    PubMed Central

    Panakhova, Nushaba F.

    2016-01-01

    Background: Infants with fetal growth retardation (FGR) are prone to intestinal disorders. Objectives: Aim of the study was to determine the role of mucosal defense ability in formation of gut injury in infants with FGR. Materials and Methods: 44 premature infants who were admitted to the Neonatal Intensive Care Unit were divided into two groups: 20 infants with FGR (FGR group) and 24 appropriate-for-gestational age newborns (AGA group). Control group consisted of 22 premature infants who were delivered after uncomplicated pregnancy. Gut barrier function was evaluated by detecting serum intestinal trefoil factor (ITF) and intestinal fatty acid binding protein (IFABP). The level of serum IFABP and ITF was measured by using ELISA method. Results: FGR group showed significantly higher ITF concentration than AGA group on the first days of life (P ˂ 0.01). High level of ITF in the FGR group significantly declines up to 7th - 10th day of life (P ˂ 0.01). This reduction was accompanied by increase of IFABP which is a marker of ischemic intestinal mucosal injury. Correlation analyses showed that ITF had a negative correlation with IFABP. Conclusions: Infants with fetal growth retardation are characterized by a high level of ITF on the first days of life. This protects intestinal mucosa under hypoxic conditions. Its subsequent decline accompanied by an increase of IFABP reflects the depletion of Goblet cells to secret ITF causing damage to the integrity of intestinal mucosal barrier. PMID:26848381

  12. Maternal and fetal influences on uterine and conceptus development in the cow: I. Growth of tissues of the gravid uterus.

    PubMed

    Ferrell, C L

    1991-05-01

    Objectives of this study were to evaluate maternal and fetal influences on development of gravid uterine tissues of cows. Brahman cows with Brahman or Charolais fetuses and Charolais cows with Brahman or Charolais fetuses were used. Cows were killed 232 +/- .5 or 271 +/- .7 d after mating. The gravid uterus of each cow was weighed and dissected into its component parts. Weights of the fetus, fetal membranes, cotyledons, caruncles, and uterus were recorded as were weights of the fetal liver, heart, kidneys, spleen, lungs, stomach complex, intestines, and semitendinosus muscle. Ribonucleic acid, DNA, and protein concentrations in caruncles, cotyledons, liver, heart, kidney, and semitendinosus muscle were determined. Data were analyzed by analysis of variance; breed of cow (C), breed of fetus (F), day of gestation (D), and all interactions were included in the model as fixed effects. Fetal weights were influenced (P less than .003) by C, F, D, and C x D and tended (P = .07) to be influenced by C X F X D. Weight, RNA, DNA, and protein contents of selected fetal tissues followed similar patterns of significance. Thus, both maternal and fetal genotype influenced fetal growth. Greater influences of the maternal system and interrelationships between maternal and fetal systems were observed at the latter stage of gestation. Placentomal (caruncle + cotyledon) weights were greater for Charolais than for Brahman cows (P less than .02) or fetuses (P less than .001) and were greater (P less than .01) at 271 than at 232 d. Caruncular weights followed similar patterns; however, fetal genotype was the only significant source of variation in cotyledonary weight, RNA, DNA, or protein content.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Fetal, but not postnatal, deletion of semaphorin-neuropilin-1 signaling affects murine alveolar development.

    PubMed

    Joza, Stephen; Wang, Jinxia; Tseu, Irene; Ackerley, Cameron; Post, Martin

    2013-10-01

    The disruption of angiogenic pathways, whether through genetic predisposition or as a consequence of life-saving interventions, may underlie many pulmonary diseases of infancy, including bronchopulmonary dysplasia. Neuropilin-1 (Nrp1) is a transmembrane receptor that plays essential roles in normal and pathological vascular development and binds two distinct ligand families: vascular endothelial growth factor (Vegf) and class 3 semaphorins (Sema3). Although Nrp1 is critical for systemic vascular development, the importance of Nrp1 in pulmonary vascular morphogenesis is uncertain. We hypothesized that Sema3-Nrp1 and Vegf-Nrp1 interactions are important pathways in the orchestration of pulmonary vascular development during alveolarization. Complete ablation of Nrp1 signaling would therefore lead to interruption of normal angiogenic and vascular maturation processes that are relevant to the pathogenesis of bronchopulmonary dysplasia. We have previously shown that congenital loss of Sema3-Nrp1 signaling in transgenic Nrp1(Sema-) mice resulted in disrupted alveolar-capillary interface formation and high neonatal mortality. Here, pathohistological examination of Nrp1(Sema-) survivors in the alveolar period revealed moderate to severe respiratory distress, alveolar hemorrhaging, abnormally dilated capillaries, and disintegrating alveolar septa, demonstrating continued instability of the alveolar-capillary interface. Moreover, consistent with a reduced capillary density and consequent increases in vascular resistance, hypertensive remodeling was observed. In contrast, conditional Nrp1 deletion beginning at postnatal day 5 had only a transient effect upon alveolar and vascular development or pneumocyte differentiation despite an increase in mortality. Our results demonstrate that although Sema3-Nrp1 signaling is critical during fetal pulmonary development, Nrp1 signaling does not appear to be essential for alveolar development or vascular function in the postnatal period.

  14. Prenatal acetaminophen affects maternal immune and endocrine adaptation to pregnancy, induces placental damage, and impairs fetal development in mice.

    PubMed

    Thiele, Kristin; Solano, M Emilia; Huber, Samuel; Flavell, Richard A; Kessler, Timo; Barikbin, Roja; Jung, Roman; Karimi, Khalil; Tiegs, Gisa; Arck, Petra C

    2015-10-01

    Acetaminophen (APAP; ie, Paracetamol or Tylenol) is generally self-medicated to treat fever or pain and recommended to pregnant women by their physicians. Recent epidemiological studies reveal an association between prenatal APAP use and an increased risk for asthma. Our aim was to identify the effects of APAP in pregnancy using a mouse model. Allogeneically mated C57Bl/6J females were injected i.p. with 50 or 250 mg/kg APAP or phosphate-buffered saline on gestation day 12.5; nonpregnant females served as controls. Tissue samples were obtained 1 or 4 days after injection. APAP-induced liver toxicity was mirrored by significantly increased plasma alanine aminotransferase levels. In uterus-draining lymph nodes of pregnant dams, the frequencies of mature dendritic cells and regulatory T cells significantly increased on 250 mg/kg APAP. Plasma progesterone levels significantly decreased in dams injected with APAP, accompanied by a morphologically altered placenta. Although overall litter sizes and number of fetal loss remained unaltered, a reduced fetal weight and a lower frequency of hematopoietic stem cells in the fetal liver were observed on APAP treatment. Our data provide strong evidence that prenatal APAP interferes with maternal immune and endocrine adaptation to pregnancy, affects placental function, and impairs fetal maturation and immune development. The latter may have long-lasting consequences on children's immunity and account for the increased risk for asthma observed in humans. PMID:26254283

  15. Prenatal acetaminophen affects maternal immune and endocrine adaptation to pregnancy, induces placental damage, and impairs fetal development in mice.

    PubMed

    Thiele, Kristin; Solano, M Emilia; Huber, Samuel; Flavell, Richard A; Kessler, Timo; Barikbin, Roja; Jung, Roman; Karimi, Khalil; Tiegs, Gisa; Arck, Petra C

    2015-10-01

    Acetaminophen (APAP; ie, Paracetamol or Tylenol) is generally self-medicated to treat fever or pain and recommended to pregnant women by their physicians. Recent epidemiological studies reveal an association between prenatal APAP use and an increased risk for asthma. Our aim was to identify the effects of APAP in pregnancy using a mouse model. Allogeneically mated C57Bl/6J females were injected i.p. with 50 or 250 mg/kg APAP or phosphate-buffered saline on gestation day 12.5; nonpregnant females served as controls. Tissue samples were obtained 1 or 4 days after injection. APAP-induced liver toxicity was mirrored by significantly increased plasma alanine aminotransferase levels. In uterus-draining lymph nodes of pregnant dams, the frequencies of mature dendritic cells and regulatory T cells significantly increased on 250 mg/kg APAP. Plasma progesterone levels significantly decreased in dams injected with APAP, accompanied by a morphologically altered placenta. Although overall litter sizes and number of fetal loss remained unaltered, a reduced fetal weight and a lower frequency of hematopoietic stem cells in the fetal liver were observed on APAP treatment. Our data provide strong evidence that prenatal APAP interferes with maternal immune and endocrine adaptation to pregnancy, affects placental function, and impairs fetal maturation and immune development. The latter may have long-lasting consequences on children's immunity and account for the increased risk for asthma observed in humans.

  16. Dysregulated flow-mediated vasodilatation in the human placenta in fetal growth restriction

    PubMed Central

    Jones, Sarah; Bischof, Helen; Lang, Ingrid; Desoye, Gernot; Greenwood, Sue L; Johnstone, Edward D; Wareing, Mark; Sibley, Colin P; Brownbill, Paul

    2015-01-01

    Increased vascular resistance and reduced fetoplacental blood flow are putative aetiologies in the pathogenesis of fetal growth restriction (FGR); however, the regulating sites and mechanisms remain unclear. We hypothesised that placental vessels dictate fetoplacental resistance and in FGR exhibit endothelial dysfunction and reduced flow-mediated vasodilatation (FMVD). Resistance was measured in normal pregnancies (n = 10) and FGR (n = 10) both in vivo by umbilical artery Doppler velocimetry and ex vivo by dual placental perfusion. Ex vivo FMVD is the reduction in fetal-side inflow hydrostatic pressure (FIHP) following increased flow rate. Results demonstrated a significant correlation between vascular resistance measured in vivo and ex vivo in normal pregnancy, but not in FGR. In perfused FGR placentas, vascular resistance was significantly elevated compared to normal placentas (58 ± 7.7 mmHg and 36.8 ± 4.5 mmHg, respectively; 8 ml min−1; means ± SEM; P < 0.0001) and FMVD was severely reduced (3.9 ± 1.3% and 9.1 ± 1.2%, respectively). In normal pregnancies only, the highest level of ex vivo FMVD was associated with the lowest in vivo resistance. Inhibition of NO synthesis during perfusion (100 μm l-NNA) moderately elevated FIHP in the normal group, but substantially in the FGR group. Human placenta artery endothelial cells from FGR groups exhibited increased shear stress-induced NO generation, iNOS expression and eNOS expression compared with normal groups. In conclusion, fetoplacental resistance is determined by placental vessels, and is increased in FGR. The latter also exhibit reduced FMVD, but with a partial compensatory increased NO generation capacity. The data support our hypothesis, which highlights the importance of FMVD regulation in normal and dysfunctional placentation. Key points A correlation was found between in vivo umbilical artery Doppler velocimetry and resistance to fetal-side flow in the human ex vivo dually

  17. Phenotypic and molecular characterization of intrauterine fetal growth restriction in interspecies sheep pregnancy.

    PubMed

    Chávez-García, A; Vázquez-Martínez, E R; Murcia, C; Rodríguez, A; Cerbón, M; Mejía, O

    2015-10-01

    Interspecies pregnancies between closely related species are usually performed in livestock to obtain improved and enriched offspring. Indeed, different hybrids have been obtained for research purposes since many years ago, and the maternal-fetal interactions have been studied as a possible strategy for species preservation. The aim of this study was to characterize by physiological and molecular approaches the interspecies pregnancy between bighorn sheep () and domestic sheep (). Hybrids were obtained by artificial insemination; the blood pressure and protein urine levels were measured during the last two-thirds of gestation. After parturition, offspring and placentas were weighed and measured and cotyledons were counted and weighed and their surface area determined. Plasma samples were obtained between wk 8 and 21 of gestation to assess progesterone (P4), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) levels and cell-free RNA was isolated during the same period to assess hypoxia-inducible factor-1 α (α) gene expression. Hybrid and normal pregnancies were analyzed using physiological and molecular parameters during the last two-thirds of gestation (wk 8-21). The results show that during the measurement period, ewes with a hybrid pregnancy presented normal blood pressure and no alteration in urinary protein content. However, compared with sheep with a normal pregnancy, those with a hybrid pregnancy had a decrease in fetal and placental growth as well as in the cotyledonary surface area. Furthermore, in the hybrid group, there was placental insufficiency, characterized by a decrease in P4 production, as well as indications of endothelial dysfunction, characterized an increase in plasma levels of VEGF and PlGF as well as in plasma gene expression of α. Overall, the results indicate that hybrids of and presented intrauterine growth restriction, essentially due to altered endothelial function and chronic placental insufficiency

  18. Statistical considerations for the development of prescriptive fetal and newborn growth standards in the INTERGROWTH-21st Project.

    PubMed

    Altman, D G; Ohuma, E O

    2013-09-01

    The INTERGROWTH-21(st) Project has in its mandate to develop prescriptive standards for fetal, neonatal and preterm post-neonatal growth. The project comprises three components: the Fetal Growth Longitudinal Study (FGLS), the Preterm Postnatal Follow-up Study (PPFS), and the Newborn Cross-Sectional Study (NCSS). We consider here the statistical aspects of the three components as they relate to the construction of these standards, in particular the sample size, and outline the principles that will guide the planned main analyses.

  19. Ultrasonographic fetal growth charts: an informatic approach by quantitative analysis of the impact of ethnicity on diagnoses based on a preliminary report on Salentinian population.

    PubMed

    Tinelli, Andrea; Bochicchio, Mario Alessandro; Vaira, Lucia; Malvasi, Antonio

    2014-01-01

    Clear guidance on fetal growth assessment is important because of the strong links between growth restriction or macrosomia and adverse perinatal outcome in order to reduce associated morbidity and mortality. Fetal growth curves are extensively adopted to track fetal sizes from the early phases of pregnancy up to delivery. In the literature, a large variety of reference charts are reported but they are mostly up to five decades old. Furthermore, they do not address several variables and factors (e.g., ethnicity, foods, lifestyle, smoke, and physiological and pathological variables), which are very important for a correct evaluation of the fetal well-being. Therefore, currently adopted fetal growth charts are inadequate to support the melting pot of ethnic groups and lifestyles of our society. Customized fetal growth charts are needed to provide an accurate fetal assessment and to avoid unnecessary obstetric interventions at the time of delivery. Starting from the development of a growth chart purposely built for a specific population, in the paper, authors quantify and analyse the impact of the adoption of wrong growth charts on fetal diagnoses. These results come from a preliminary evaluation of a new open service developed to produce personalized growth charts for specific ethnicity, lifestyle, and other parameters.

  20. Caffeine-induced fetal rat over-exposure to maternal glucocorticoid and histone methylation of liver IGF-1 might cause skeletal growth retardation.

    PubMed

    Tan, Yang; Liu, Jin; Deng, Yu; Cao, Hong; Xu, Dan; Cu, Fenglong; Lei, Youying; Magdalou, Jacques; Wu, Min; Chen, Liaobin; Wang, Hui

    2012-11-15

    Several epidemiological investigations, including previous work by our laboratory, indicate that maternal caffeine consumption is associated with intrauterine growth retardation and impaired fetal length growth. Skeletal development is critical for length growth. In the present study, our goals were to determine the effects of prenatal caffeine exposures on fetal skeletal growth and to investigate the mechanisms associated with such effects. Pregnant Wistar rats were injected intragastrically with 120mg/kg of caffeine intragastrically each day from gestational days 11-20. Maternal prenatal caffeine exposure was associated with decreased fetal femur lengths and inhibited of synthesis of extracellular matrices in fetal growth plates Moreover, caffeine exposure significantly increased the levels of fetal blood corticosterone and decreased IGF-1mRNA expression levels in the liver and growth plate. The expression levels of IGF-1 signaling pathway components (IGF-1R, IRS-1, AKT1/2 and Col2A1) were also reduced. In addition, the results of chromatin immunoprecipitation assays indicated that caffeine exposure down-regulated histone methylation of fetal IGF-1 in the liver. These results suggest that prenatal caffeine exposure may inhibit fetal skeletal growth through a mechanism that is associated with increased fetal exposure to maternal glucocorticoids and results in lower IGF-1 signaling pathway activity. Taken together, these results raise important concerns regarding the skeletal growth toxicity of caffeine and potentially indicate the intrauterine origins of adult osteoporosis and osteoarthritis.

  1. Extracellular vesicle–depleted fetal bovine and human sera have reduced capacity to support cell growth

    PubMed Central

    Eitan, Erez; Zhang, Shi; Witwer, Kenneth W.; Mattson, Mark P.

    2015-01-01

    Background Fetal bovine serum (FBS) is the most widely used serum supplement for mammalian cell culture. It supports cell growth by providing nutrients, growth signals, and protection from stress. Attempts to develop serum-free media that support cell expansion to the same extent as serum-supplemented media have not yet succeeded, suggesting that FBS contains one or more as-yet-undefined growth factors. One potential vehicle for the delivery of growth factors from serum to cultured cells is extracellular vesicles (EVs). Methods EV-depleted FBS and human serum were generated by 120,000g centrifugation, and its cell growth–supporting activity was measured. Isolated EVs from FBS were quantified and characterized by nanoparticle tracking analysis, electron microscopy, and protein assay. EV internalization into cells was quantified using fluorescent plate reader analysis and microscopy. Results Most cell types cultured with EV-depleted FBS showed a reduced growth rate but not an increased sensitivity to the DNA-damaging agent etoposide and the endoplasmic reticulum stress–inducing chemical tunicamycin. Supplying cells with isolated FBS-derived EVs enhanced their growth. FBS-derived EVs were internalized by mouse and human cells wherein 65±26% of them interacted with the lysosomes. EV-depleted human serum also exhibited reduced cell growth–promoting activity. Conclusions EVs play a role in the cell growth and survival-promoting effects of FBS and human serum. Thus, it is important to take the effect of EV depletion under consideration when planning EV extraction experiments and while attempting to develop serum-free media that support rapid cell expansion. In addition, these findings suggest roles for circulating EVs in supporting cell growth and survival in vivo. PMID:25819213

  2. Maternal choline modifies fetal liver copper, gene expression, DNA methylation, and neonatal growth in the tx-j mouse model of Wilson disease

    PubMed Central

    Medici, Valentina; Shibata, Noreene M; Kharbanda, Kusum K; Islam, Mohammad S; Keen, Carl L; Kim, Kyoungmi; Tillman, Brittany; French, Samuel W; Halsted, Charles H; LaSalle, Janine M

    2014-01-01

    Maternal diet can affect fetal gene expression through epigenetic mechanisms. Wilson disease (WD), which is caused by autosomal recessive mutations in ATP7B encoding a biliary copper transporter, is characterized by excessive hepatic copper accumulation, but variability in disease severity. We tested the hypothesis that gestational supply of dietary methyl groups modifies fetal DNA methylation and expression of genes involved in methionine and lipid metabolism that are impaired prior to hepatic steatosis in the toxic milk (tx-j) mouse model of WD. Female C3H control and tx-j mice were fed control (choline 8 mmol/Kg of diet) or choline-supplemented (choline 36 mmol/Kg of diet) diets for 2 weeks throughout mating and pregnancy to gestation day 17. A second group of C3H females, half of which were used to cross foster tx-j pups, received the same diet treatments that extended during lactation to 21 d postpartum. Compared with C3H, fetal tx-j livers had significantly lower copper concentrations and significantly lower transcript levels of Cyclin D1 and genes related to methionine and lipid metabolism. Maternal choline supplementation prevented the transcriptional deficits in fetal tx-j liver for multiple genes related to cell growth and metabolism. Global DNA methylation was increased by 17% in tx-j fetal livers after maternal choline treatment (P < 0.05). Maternal dietary choline rescued the lower body weight of 21 d tx-j mice. Our results suggest that WD pathogenesis is modified by maternal in utero factors, including dietary choline. PMID:24220304

  3. Maternal magnesium deficiency in mice leads to maternal metabolic dysfunction and altered lipid metabolism with fetal growth restriction.

    PubMed

    Gupta, Madhu; Solanki, Malvika H; Chatterjee, Prodyot K; Xue, Xiangying; Roman, Amanda; Desai, Neeraj; Rochelson, Burton; Metz, Christine N

    2014-08-14

    Inadequate magnesium (Mg) intake is a widespread problem, with over 50% of women of reproductive age consuming less than the Recommended Dietary Allowance (RDA). Because pregnancy increases the requirement for Mg and the beneficial effects of magnesium sulfate for preeclampsia/eclampsia and fetal neuroprotection are well described, we examined the outcomes of Mg deficiency during pregnancy. Briefly, pregnant Swiss Webster mice were fed either control or Mg-deficient diets starting on gestational day (GD) 6 through euthanasia on GD17. Mg-deficient dams had significantly reduced weight gain and higher plasma adipokines, in the absence of inflammation. Livers of Mg-deficient dams had significantly higher saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) and lower polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) (P < 0.0001) and arachidonic acid (AA) (P < 0.0001). Mechanistically, Mg deficiency was accompanied by enhanced desaturase and elongase mRNA expression in maternal livers along with higher circulating insulin and glucose concentrations (P < 0.05) and increased mRNA expression of Srebf1 and Chrebp, regulators of fatty acid synthesis (P < 0.05). Fetal pups exposed to Mg deficiency were growth-restricted and exhibited reduced survival. Mg-deficient fetal livers showed lower MUFAs and higher PUFAs, with lower desaturase and elongase mRNA expression than controls. In addition, DHA concentrations were lower in Mg-deficient fetal brains (P < 0.05). These results indicate that Mg deficiency during pregnancy influences both maternal and fetal fatty acid metabolism, fetal growth and fetal survival, and support better understanding maternal Mg status before and during pregnancy.

  4. Empowering Translational Research in Fetal Growth Restriction: Sheep and Swine Animal Models.

    PubMed

    Gonzalez-Bulnes, Antonio; Astiz, Susana; Parraguez, Victor H; Garcia-Contreras, Consolación; Vazquez-Gomez, Marta

    2016-01-01

    Fetal or intrauterine growth restriction (FGR or IUGR) is a concerning health issue not only due to its implications in mortality and morbidity of neonates but also because of its long-term consequences on health and disease risk of the individuals. Its main cause is an insufficient supply of nutrients and oxygen by maternal (malnutrition or hypobaric hypoxia) or placental factors (placental insufficiency) during late gestation, when the requirements of fetus are higher. The availability of reliable animal models would be highly useful for the future development of diagnostic, preventive and therapeutic strategies. Most of the studies using animal models have been performed in rodents, while the use of large animals (sheep and swine) has been scarce. The objective of the current review is to offer an overview on the possibilities of using large animals for conducting translational research on IUGR related to inadequate maternal conditions and/or placental dysfunction. PMID:27194361

  5. A comparative analysis of prenatal care and fetal growth in eight South American countries.

    PubMed

    Woodhouse, Cristina; Lopez Camelo, Jorge; Wehby, George L

    2014-01-01

    There has been little work that comprehensively compared the relationship between prenatal care and infant health across multiple countries using similar data sources and analytical models. Such comparative analyses are useful for understanding the background of differences in infant health between populations. We evaluated the association between prenatal care visits and fetal growth measured by birth weight (BW) in grams or low birth weight (<2500 grams; LBW) adjusted for gestational age in eight South American countries using similarly collected data across countries and the same analytical models. OLS and logistic regressions were estimated adjusting for a large set of relevant infant, maternal, and household characteristics and birth year and hospital fixed effects. Birth data were acquired from 140 hospitals that are part of the Latin American Collaborative Study of Congenital Malformations (ECLAMC) network. The analytical sample included 56,014 live-born infants (∼69% of total sample) with complete data born without congenital anomalies in the years 1996-2011 in Brazil, Argentina, Chile, Venezuela, Ecuador, Colombia, Bolivia, and Uruguay. Prenatal care visits were significantly (at p<.05) and positively associated with BW and negatively associated with LBW for all countries. The OLS coefficients ranged from 9 grams per visit in Bolivia to 36 grams in Uruguay. The association with LBW was strongest for Chile (OR = 0.87 per visit) and lowest for Argentina and Venezuela (OR = 0.95). The association decreased in the recent decade compared to earlier years. Our findings suggest that estimates of association between prenatal care and fetal growth are population-specific and may not be generalizable to other populations. Furthermore, as one of the indicators for a country's healthcare system for maternal and child health, prenatal care is a highly variable indicator between countries in South America. PMID:24625630

  6. A comparative analysis of prenatal care and fetal growth in eight South American countries.

    PubMed

    Woodhouse, Cristina; Lopez Camelo, Jorge; Wehby, George L

    2014-01-01

    There has been little work that comprehensively compared the relationship between prenatal care and infant health across multiple countries using similar data sources and analytical models. Such comparative analyses are useful for understanding the background of differences in infant health between populations. We evaluated the association between prenatal care visits and fetal growth measured by birth weight (BW) in grams or low birth weight (<2500 grams; LBW) adjusted for gestational age in eight South American countries using similarly collected data across countries and the same analytical models. OLS and logistic regressions were estimated adjusting for a large set of relevant infant, maternal, and household characteristics and birth year and hospital fixed effects. Birth data were acquired from 140 hospitals that are part of the Latin American Collaborative Study of Congenital Malformations (ECLAMC) network. The analytical sample included 56,014 live-born infants (∼69% of total sample) with complete data born without congenital anomalies in the years 1996-2011 in Brazil, Argentina, Chile, Venezuela, Ecuador, Colombia, Bolivia, and Uruguay. Prenatal care visits were significantly (at p<.05) and positively associated with BW and negatively associated with LBW for all countries. The OLS coefficients ranged from 9 grams per visit in Bolivia to 36 grams in Uruguay. The association with LBW was strongest for Chile (OR = 0.87 per visit) and lowest for Argentina and Venezuela (OR = 0.95). The association decreased in the recent decade compared to earlier years. Our findings suggest that estimates of association between prenatal care and fetal growth are population-specific and may not be generalizable to other populations. Furthermore, as one of the indicators for a country's healthcare system for maternal and child health, prenatal care is a highly variable indicator between countries in South America.

  7. Effortful Control Mediates Associations of Fetal Growth with Hyperactivity and Behavioural Problems in 7- to 9-Year-Old Children

    ERIC Educational Resources Information Center

    Schlotz, Wolff; Jones, Alexander; Godfrey, Keith M.; Phillips, David I. W.

    2008-01-01

    Background: Inverse associations of fetal growth with behavioural problems in childhood have been repeatedly reported, suggesting long-term effects of the prenatal developmental environment on behaviour later in life. However, no study so far has examined effects on temperament and potential developmental pathways. Temperamental traits may be…

  8. Ultrasonographic measurement of fetal growth parameters over three successive pregnancies in a captive Malayan tapir (Tapirus indicus).

    PubMed

    Hoyer, M J; van Engeldorp Gastelaars, H M D

    2014-01-01

    This study was conducted to establish representative curves that allow evaluation of fetal growth and estimation of gestational age from measurement of fetal structures by ultrasound in Malayan tapirs (Tapirus indicus). Three pregnancies (i.e. 3 fetuses) were examined in one female Malayan tapir. Transabdominal ultrasonographic examination was performed without anesthesia from 79 ± 8 days to 281 ± 48 days (mean ± S.D.) post mating. To assess fetal growth attempts were made to measure biparietal diameter (BPD), head length (HL), thorax diameter A (TDA), thorax height A (THA), thorax diameter B (TDB), thorax height B (THB), abdomen diameter (AD), abdomen height (AH), humerus length (HUL) and Crown rump length (CRL). The value of each parameter as an estimator of gestational age was assessed by ease of observation and the length of time the parameter was measurable throughout gestation. The most precise predictors for gestational age in this study were BPD and CRL (weeks 10-20 of gestation), as well as AD and AH (weeks 14-43 of gestation). The parameters TDB, THB and HUL (weeks 15-41 of gestation) gave almost as good predictions. Fetal viability was assessed by identifying a fetal heartbeat and movement. All pregnancies resulted in normal deliveries and healthy offspring. The ultrasound examination was well tolerated by the female. The gestation lengths (399 ± 3 days) were within reported ranges. The serial transabdominal ultrasound, without the need for anesthesia, was an effective method to evaluate fetal growth, development and well being in a Malayan tapir. PMID:25042428

  9. Ultrasonographic measurement of fetal growth parameters over three successive pregnancies in a captive Malayan tapir (Tapirus indicus).

    PubMed

    Hoyer, M J; van Engeldorp Gastelaars, H M D

    2014-01-01

    This study was conducted to establish representative curves that allow evaluation of fetal growth and estimation of gestational age from measurement of fetal structures by ultrasound in Malayan tapirs (Tapirus indicus). Three pregnancies (i.e. 3 fetuses) were examined in one female Malayan tapir. Transabdominal ultrasonographic examination was performed without anesthesia from 79 ± 8 days to 281 ± 48 days (mean ± S.D.) post mating. To assess fetal growth attempts were made to measure biparietal diameter (BPD), head length (HL), thorax diameter A (TDA), thorax height A (THA), thorax diameter B (TDB), thorax height B (THB), abdomen diameter (AD), abdomen height (AH), humerus length (HUL) and Crown rump length (CRL). The value of each parameter as an estimator of gestational age was assessed by ease of observation and the length of time the parameter was measurable throughout gestation. The most precise predictors for gestational age in this study were BPD and CRL (weeks 10-20 of gestation), as well as AD and AH (weeks 14-43 of gestation). The parameters TDB, THB and HUL (weeks 15-41 of gestation) gave almost as good predictions. Fetal viability was assessed by identifying a fetal heartbeat and movement. All pregnancies resulted in normal deliveries and healthy offspring. The ultrasound examination was well tolerated by the female. The gestation lengths (399 ± 3 days) were within reported ranges. The serial transabdominal ultrasound, without the need for anesthesia, was an effective method to evaluate fetal growth, development and well being in a Malayan tapir.

  10. PRETERM BIRTH AND FETAL GROWTH RESTRICTION IN HIV-INFECTED BRAZILIAN PREGNANT WOMEN

    PubMed Central

    dos REIS, Helena Lucia Barroso; ARAUJO, Karina da Silva; RIBEIRO, Lilian Paula; da ROCHA, Daniel Ribeiro; ROSATO, Drielli Petri; PASSOS, Mauro Romero Leal; de VARGAS, Paulo Roberto Merçon

    2015-01-01

    Introduction: Maternal HIV infection and related co-morbidities may have two outstanding consequences to fetal health: mother-to-child transmission (MTCT) and adverse perinatal outcomes. After Brazilian success in reducing MTCT, the attention must now be diverted to the potentially increased risk for preterm birth (PTB) and intrauterine fetal growth restriction (IUGR). Objective: To determine the prevalence of PTB and IUGR in low income, antiretroviral users, publicly assisted, HIV-infected women and to verify its relation to the HIV infection stage. Patients and Methods: Out of 250 deliveries from HIV-infected mothers that delivered at a tertiary public university hospital in the city of Vitória, state of Espírito Santo, Southeastern Brazil, from November 2001 to May 2012, 74 single pregnancies were selected for study, with ultrasound validated gestational age (GA) and data on birth dimensions: fetal weight (FW), birth length (BL), head and abdominal circumferences (HC, AC). The data were extracted from clinical and pathological records, and the outcomes summarized as proportions of preterm birth (PTB, < 37 weeks), low birth weight (LBW, < 2500g) and small (SGA), adequate (AGA) and large (LGA) for GA, defined as having a value below, between or beyond the ±1.28 z/GA score, the usual clinical cut-off to demarcate the 10th and 90th percentiles. Results: PTB was observed in 17.5%, LBW in 20.2% and SGA FW, BL, HC and AC in 16.2%, 19.1%, 13.8%, and 17.4% respectively. The proportions in HIV-only and AIDS cases were: PTB: 5.9 versus 27.5%, LBW: 14.7% versus 25.0%, SGA BW: 17.6% versus 15.0%, BL: 6.0% versus 30.0%, HC: 9.0% versus 17.9%, and AC: 13.3% versus 21.2%; only SGA BL attained a significant difference. Out of 15 cases of LBW, eight (53.3%) were preterm only, four (26.7%) were SGA only, and three (20.0%) were both PTB and SGA cases. A concomitant presence of, at least, two SGA dimensions in the same fetus was frequent. Conclusions: The proportions of preterm

  11. Growth and metabolism of fetal and maternal muscles of adolescent sheep on adequate or high feed intake: possible role of protein kinase C-alpha in fetal muscle growth.

    PubMed

    Palmer, R M; Thompson, M G; Meallet, C; Thom, A; Aitken, R P; Wallace, J M

    1998-04-01

    From days 4-104 of pregnancy, adolescent sheep, weighing 43.7 (SE 0.87) kg were offered a complete diet at two different intakes (approximately 5 or 15 kg/week) designed to meet slightly, or well above, maternal maintenance requirements. The fetal and maternal muscles were taken on day 104 of pregnancy and analysed for total DNA, RNA and protein. Ewes offered a high intake to promote rapid maternal weight gain, weighed more (76.5 (SE 4.5) v 50.0 (SE 1.7) kg) and had muscles with a greater fresh weight, whilst their fetuses had smaller muscles, than those fed at a lower intake. Plantaris muscle of the ewes fed at the high intake contained more RNA and protein; again the opposite situation was found in the fetal muscle. On the higher maternal intakes, the DNA, RNA and protein contents of the fetal plantaris muscle were less than in fetuses of ewes fed at the lower intake. To investigate the possible mechanisms involved in this decrease in fetal muscle mass, cytosolic and membrane-associated muscle proteins were subjected to Western immunoblotting with antibodies to nine isoforms of protein kinase C (PKC), a family of enzymes known to play an important role in cell growth. Five PKC isoforms (alpha, epsilon, theta, mu, zeta) were identified in fetal muscle. One of these, PKC-alpha was located predominantly in the cytosolic compartment in the smaller fetuses of the ewes fed at a high plane of nutrition, but was present to a greater extent in the membranes of the more rapidly growing fetuses of the ewes fed at the lower intake. This was the only isoform to demonstrate nutritionally related changes in it subcellular compartmentation suggesting that it may mediate some aspects of the change in fetal growth rate.

  12. Effects of dietary lead and zinc on fetal organ growth. [Rats

    SciTech Connect

    Dilts, P.V. Jr.; Ahokas, R.A.

    1980-04-01

    In order to further understand the effects of ingested lead (Pb) on the fetus and the possible interaction of the trace element zinc (Zn) with Pb, groups of rats with dated pregnancies were fed 0, 10, 50, 100, 200, or 500 mg/L of Pb in water throughout pregnancy. Diet was provided ad libitum. A group pair fed with the 200 mg/L of Pb group and a group fed both Zn and Pb, 200 mg/L, were also studied. Placental weight remained constant, but cell division and total protein level were decreased while cell size increased markedly. Fetal carcass and liver weight, cell division, and protein were decreased while cell growth was unchanged. Brain weight decreased while cell division, growth, and protein were unchanged. Kidney weight, cell division, and protein level were unchanged but cell growth was decreased. Organ dry weight varied with wet weight while the percentage of water was unchanged. Whether pair feeding and Zn supplements improve carcass and liver weight is questionable.

  13. Effect of fetal undernutrition and postnatal overfeeding on rat adipose tissue and organ growth at early stages of postnatal development.

    PubMed

    Munoz-Valverde, D; Rodríguez-Rodríguez, P; Gutierrez-Arzapalo, P Y; López de Pablo, A L; Carmen González, M; López-Giménez, R; Somoza, B; Arribas, S M

    2015-01-01

    Intrauterine and perinatal life are critical periods for programming of cardiometabolic diseases. However, their relative role remains controversial. We aimed to assess, at weaning, sex-dependent alterations induced by fetal or postnatal nutritional interventions on key organs for metabolic and cardiovascular control. Fetal undernutrition was induced by dam food restriction (50 % from mid-gestation to delivery) returning to ad libitum throughout lactation (Maternal Undernutrition, MUN, 12 pups/litter). Postnatal overfeeding (POF) was induced by litter size reduction from normally fed dams (4 pups/litter). Compared to control, female and male MUN offspring exhibited: 1) low birth weight and accelerated growth, reaching similar weight and tibial length by weaning, 2) increased glycemia, liver and white fat weights; 3) increased ventricular weight and tendency to reduced kidney weight (males only). Female and male POF offspring showed: 1) accelerated growth; 2) increased glycemia, liver and white fat weights; 3) unchanged heart and kidney weights. In conclusion, postnatal accelerated growth, with or without fetal undernutrition, induces early alterations relevant for metabolic disease programming, while fetal undernutrition is required for heart abnormalities. The progression of cardiac alterations and their role on hypertension development needs to be evaluated. The similarities between sexes in pre-pubertal rats suggest a role of sex-hormones in female protection against programming.

  14. Intrauterine growth restriction and the fetal programming of the hedonic response to sweet taste in newborn infants.

    PubMed

    Ayres, Caroline; Agranonik, Marilyn; Portella, André Krumel; Filion, Françoise; Johnston, Celeste C; Silveira, Patrícia Pelufo

    2012-01-01

    Intrauterine growth restriction is associated with increased risk for adult metabolic syndrome and cardiovascular disease, which seems to be related to altered food preferences in these individuals later in life. In this study, we sought to understand whether intrauterine growth leads to fetal programming of the hedonic responses to sweet. Sixteen 1-day-old preterm infants received 24% sucrose solution or water and the taste reactivity was filmed and analyzed. Spearman correlation demonstrated a positive correlation between fetal growth and the hedonic response to the sweet solution in the first 15 seconds after the offer (r = 0.864, P = 0.001), without correlation when the solution given is water (r = 0.314, P = 0.455). In fact, the more intense the intrauterine growth restriction, the lower the frequency of the hedonic response observed. IUGR is strongly correlated with the hedonic response to a sweet solution in the first day of life in preterm infants. This is the first evidence in humans to demonstrate that the hedonic response to sweet taste is programmed very early during the fetal life by the degree of intrauterine growth. The altered hedonic response at birth and subsequent differential food preference may contribute to the increased risk of obesity and related disorders in adulthood in intrauterine growth-restricted individuals.

  15. Fetal and infant growth patterns of the mandibular symphysis in modern humans and chimpanzees (Pan troglodytes).

    PubMed

    Coquerelle, Michael; Bookstein, Fred L; Braga, José; Halazonetis, Demetrios J; Weber, Gerhard W

    2010-11-01

    Comparison of the early development of the mandibular symphysis between primates and modern humans is of particular interest in human palaeontology. Using geometric morphometric methods, we explored and compared the ontogenetic shape changes of 14 chimpanzee mandibles (Pan troglodytes) against 66 human CT-scanned mandibles over the age range from fetal life to the complete emergence of the deciduous dentition in a visualization incorporating the deciduous tooth arrangement. The results reveal that the symphysis is anteriorly inclined in the youngest chimpanzee fetuses but develops an increasingly vertical orientation up until birth. At the same time, the anterior teeth reorient before a vertical emergence, and a symphyseal tuber appears on the labial side. When the deciduous canine emerges, the symphysis inclines anteriorly again, exhibiting the adult characteristic slope. These two phases are characterized by a repositioning of the simian shelf. Unlike chimpanzees, the human symphysis remains vertical throughout fetal development. However, the combination of morphological changes observed in chimpanzee fetuses is similar to that of modern humans after birth, as the mental region projects forward. By elongating the alveolar process, the inclination of the chimpanzee symphysis could be a key event for emergence of the deciduous canine, as space is lacking at the alveolar ridge in a vertical symphysis once the deciduous incisors and molars have emerged. The repositioning of the simian shelf suggests that the suprahyoid muscles have a significant influence on the anterior growth of the symphysis. The anteroposterior positioning of the basal symphysis in both species may be related to hyoid bone position during ontogeny.

  16. Fetal and infant growth patterns of the mandibular symphysis in modern humans and chimpanzees (Pan troglodytes)

    PubMed Central

    Coquerelle, Michael; Bookstein, Fred L; Braga, José; Halazonetis, Demetrios J; Weber, Gerhard W

    2010-01-01

    Comparison of the early development of the mandibular symphysis between primates and modern humans is of particular interest in human palaeontology. Using geometric morphometric methods, we explored and compared the ontogenetic shape changes of 14 chimpanzee mandibles (Pan troglodytes) against 66 human CT-scanned mandibles over the age range from fetal life to the complete emergence of the deciduous dentition in a visualization incorporating the deciduous tooth arrangement. The results reveal that the symphysis is anteriorly inclined in the youngest chimpanzee fetuses but develops an increasingly vertical orientation up until birth. At the same time, the anterior teeth reorient before a vertical emergence, and a symphyseal tuber appears on the labial side. When the deciduous canine emerges, the symphysis inclines anteriorly again, exhibiting the adult characteristic slope. These two phases are characterized by a repositioning of the simian shelf. Unlike chimpanzees, the human symphysis remains vertical throughout fetal development. However, the combination of morphological changes observed in chimpanzee fetuses is similar to that of modern humans after birth, as the mental region projects forward. By elongating the alveolar process, the inclination of the chimpanzee symphysis could be a key event for emergence of the deciduous canine, as space is lacking at the alveolar ridge in a vertical symphysis once the deciduous incisors and molars have emerged. The repositioning of the simian shelf suggests that the suprahyoid muscles have a significant influence on the anterior growth of the symphysis. The anteroposterior positioning of the basal symphysis in both species may be related to hyoid bone position during ontogeny. PMID:20807267

  17. Relation of fingerprints and shape of the palm to fetal growth and adult blood pressure.

    PubMed Central

    Godfrey, K M; Barker, D J; Peace, J; Cloke, J; Osmond, C

    1993-01-01

    OBJECTIVE--To examine how finger and palm prints are related to fetal growth and adult blood pressure. DESIGN--Follow up study of babies born around 50 years ago whose birth weight, placental weight, head circumference, and length at birth were recorded. SETTING--Preston, Lancashire. SUBJECTS--139 men and women born in Sharoe Green Hospital in Preston during 1935-43 and still living in Lancashire. MAIN OUTCOME MEASURES--Finger and palm prints and current blood pressure. RESULTS--People who were thin at birth had more whorl patterns on their fingers. People who were short at birth in relation to their head circumference had longer hands and a narrower palmer angle. Mean systolic blood pressure was 8 mmHg higher (95% confidence interval 2 to 13; p = 0.01) in the 93 men and women with a whorl pattern on one or more fingers compared with the 46 who had no whorls. The greater the number of fingers with whorls the higher the systolic blood pressure. Whorls on the right hand were more strongly associated with higher systolic pressure than whorls on the left, mean systolic pressure rising by 2.2 mmHg (0.2 to 4.1; p = 0.03) for each additional whorl on the right hand. People with long hands and a narrow palmar angle also had higher systolic pressure. Again, these associations were stronger for the right hand. Mean systolic pressure rose by 0.49 mmHg (-0.03 to 1.01; p = 0.03) for each degree decrease in palmar angle on the right hand. CONCLUSIONS--Fingertip whorls and a narrow palmar angle are indelible markers of impaired fetal development at different stages in pregnancy. Both are associated with raised blood pressure in adult life. PMID:8374451

  18. Maternal dietary omega-3 fatty acid supplementation reduces placental oxidative stress and increases fetal and placental growth in the rat.

    PubMed

    Jones, Megan L; Mark, Peter J; Mori, Trevor A; Keelan, Jeffrey A; Waddell, Brendan J

    2013-02-01

    Placental oxidative stress plays a key role in the pathophysiology of several placenta-related disorders including intrauterine growth restriction. Oxidative stress occurs when accumulation of reactive oxygen species damages DNA, proteins, and lipids, an outcome normally limited by antioxidant defenses. Dietary supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFAs) may limit oxidative stress by increasing antioxidant capacity, but n-3 PUFAs are also highly susceptible to lipid peroxidation; so n-3 PUFA supplementation is potentially harmful. Here we examined the effect of n-3 PUFAs on placental oxidative stress and on placental and fetal growth in the rat. We also investigated whether diet-induced changes in maternal plasma fatty acid profiles are associated with comparable changes in placental and fetal tissues. Rats were fed either standard or high n-3 PUFA diets from Day 1 of pregnancy, and tissues were collected on Day 17 or 22 (term = Day 23). Dietary supplementation with n-3 PUFAs increased fetal (6%) and placental (12%) weights at Day 22, the latter attributable primarily to growth of the labyrinth zone (LZ). Increased LZ weight was accompanied by reduced LZ F(2)-isoprostanes (by 31% and 11% at Days 17 and 22, respectively), a marker of oxidative damage. Maternal plasma PUFA profiles were altered by dietary fatty acid intake and were strongly predictive of corresponding profiles in placental and fetal tissues. Our data indicate that n-3 PUFA supplementation reduces placental oxidative stress and enhances placental and fetal growth. Moreover, fatty acid profiles in the mother, placenta, and fetus are highly dependent on dietary fatty acid intake.

  19. Decreased maternal and fetal cholesterol following maternal bococizumab (anti-PCSK9 monoclonal antibody) administration does not affect rat embryo-fetal development.

    PubMed

    Campion, Sarah N; Han, Bora; Cappon, Gregg D; Lewis, Elise M; Kraynov, Eugenia; Liang, Hong; Bowman, Christopher J

    2015-11-01

    Bococizumab is a humanized monoclonal IgG2Δa antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) for the treatment of hyperlipidemia. The evaluation of potential effects on embryo-fetal development was conducted in the rat. In a pharmacokinetic/pharmacodynamic study bococizumab was administered intravenously to pregnant Sprague-Dawley (SD) rats (n = 8/group) at 0, 10, 30, and 100 mg/kg during organogenesis. Maternal and fetal bococizumab, total cholesterol and HDL concentrations were determined. Bococizumab was well tolerated and there were no effects on ovarian or uterine parameters. Maternal and fetal bococizumab exposure increased with increasing dose, with a corresponding dose-dependent decrease in fetal cholesterol levels. Maternal cholesterol levels were decreased significantly, with reductions that were of a similar magnitude regardless of dose. In the definitive embryo-fetal development study bococizumab was administered to pregnant SD rats (n = 20/group) at 0, 10, 30, and 100 mg/kg and no adverse maternal or developmental effects were observed up to 100 mg/kg. These studies have provided an appropriate and relevant safety assessment of bococizumab in pregnant rats to inform human risk assessment, demonstrating no adverse effects on embryo-fetal development at magnitudes greater than anticipated clinical exposure and in the presence of maximal reductions in maternal cholesterol and dose-dependent reductions in fetal cholesterol.

  20. Non-imprinted epigenetics in fetal and postnatal development and growth.

    PubMed

    Godfrey, Keith M; Lillycrop, Karen A; Burdge, Graham C; Gluckman, Peter D; Hanson, Mark A

    2013-01-01

    Recent evidence demonstrates that the environment in early life can have important effects on fetal and postnatal growth, on development and on risk of developing common non-communicable diseases in later life. In animals, the environment during early life induces altered phenotypes in ways which are influenced or mediated by epigenetic mechanisms. The latter include DNA methylation, covalent modifications of histones and non-coding RNAs. Most is known about DNA methylation changes, which are gene specific, include effects on non-imprinted genes and function at the level of individual CpG dinucleotides to alter gene expression. Preliminary evidence from human studies suggests a similar important role for epigenetic processes. Tuning of phenotype by the developmental environment has adaptive value because it attempts to match an individual's responses to the environment predicted to be experienced later; hence, such processes have been selected during evolution as conferring fitness advantage. When the phenotype is mismatched, e.g. from inaccurate nutritional cues from the mother or placenta before birth, or from rapid environmental change through improved socioeconomic conditions, risk of non-communicable diseases increases. Evidence is accruing that endocrine or nutritional interventions during early postnatal life can reverse epigenetic and phenotypic changes induced, for example, by unbalanced maternal diet during pregnancy. Elucidation of epigenetic processes may enable early intervention strategies to improve early development and growth.

  1. Effect of maternal alcohol and nicotine intake, individually and in combination, on fetal growth in the rat

    SciTech Connect

    Leichter, J. )

    1991-03-15

    The effect of maternal ethanol and nicotine administration, separately and in combination, on fetal growth of rats was studied. Nicotine was administered by gavage for the entire gestational period. Alcohol was given in drinking water for 4 weeks prior to mating and 30% throughout gestation. Appropriate pair-fed and ad libitum control animals were included to separate the effect of ethanol and nicotine on the outcome of pregnancy from those produced by the confounding variables of malnutrition. Body weights of fetuses exposed to alcohol alone or in combination with nicotine were significantly lower than those of the pair-fed and ad libitum controls. However, the difference in fetal body weight between the alcohol plus nicotine and the alcohol alone group was not significant. Similarly, in the rats administered nicotine only, fetal weight was not significantly different compared to control animals. The results of this study indicate that maternal alcohol intake impairs fetal growth and nicotine does not, regardless whether it is administered separately or in combination with alcohol for the entire gestational period.

  2. Update on the diagnosis and classification of fetal growth restriction and proposal of a stage-based management protocol.

    PubMed

    Figueras, Francesc; Gratacós, Eduard

    2014-01-01

    Small fetuses are defined as those with an ultrasound estimated weight below a threshold, most commonly the 10th centile. The first clinically relevant step is the distinction of 'true' fetal growth restriction (FGR), associated with signs of abnormal fetoplacental function and poorer perinatal outcome, from constitutional small-for-gestational age, with a near-normal perinatal outcome. Nowadays such a distinction should not be based solely on umbilical artery Doppler, since this index detects only early-onset severe forms. FGR should be diagnosed in the presence of any of the factors associated with a poorer perinatal outcome, including Doppler cerebroplacental ratio, uterine artery Doppler, a growth centile below the 3rd centile, and, possibly in the near future, maternal angiogenic factors. Once the diagnosis is established, differentiating into early- and late-onset FGR is useful mainly for research purposes, because it distinguishes two clear phenotypes with differences in severity, association with preeclampsia, and the natural history of fetal deterioration. As a second clinically relevant step, management of FGR and the decision to deliver aims at an optimal balance between minimizing fetal injury or death versus the risks of iatrogenic preterm delivery. We propose a protocol that integrates current evidence to classify stages of fetal deterioration and establishes follow-up intervals and optimal delivery timings, which may facilitate decisions and reduce practice variability in this complex clinical condition.

  3. The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Integration of Animal and Human Evidence for PFOA Effects on Fetal Growth

    PubMed Central

    Koustas, Erica; Sutton, Patrice; Johnson, Paula I.; Atchley, Dylan S.; Sen, Saunak; Robinson, Karen A.; Axelrad, Daniel A.; Woodruff, Tracey J.

    2014-01-01

    Background: The Navigation Guide is a novel systematic review method to synthesize scientific evidence and reach strength of evidence conclusions for environmental health decision making. Objective: Our aim was to integrate scientific findings from human and nonhuman studies to determine the overall strength of evidence for the question “Does developmental exposure to perfluorooctanoic acid (PFOA) affect fetal growth in humans?” Methods: We developed and applied prespecified criteria to systematically and transparently a) rate the quality of the scientific evidence as “high,” “moderate,” or “low”; b) rate the strength of the human and nonhuman evidence separately as “sufficient,” “limited,” “moderate,” or “evidence of lack of toxicity”; and c) integrate the strength of the human and nonhuman evidence ratings into a strength of the evidence conclusion. Results: We identified 18 epidemiology studies and 21 animal toxicology studies relevant to our study question. We rated both the human and nonhuman mammalian evidence as “moderate” quality and “sufficient” strength. Integration of these evidence ratings produced a final strength of evidence rating in which review authors concluded that PFOA is “known to be toxic” to human reproduction and development based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species. Conclusion: We concluded that developmental exposure to PFOA adversely affects human health based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species. The results of this case study demonstrate the application of a systematic and transparent methodology, via the Navigation Guide, for reaching strength of evidence conclusions in environmental health. Citation: Lam J, Koustas E, Sutton P, Johnson PI, Atchley DS, Sen S, Robinson KA, Axelrad DA, Woodruff TJ. 2014. The Navigation Guide—evidence-based medicine meets environmental health

  4. Fine-mapping at three loci known to affect fetal hemoglobin levels explains additional genetic variation.

    PubMed

    Galarneau, Geneviève; Palmer, Cameron D; Sankaran, Vijay G; Orkin, Stuart H; Hirschhorn, Joel N; Lettre, Guillaume

    2010-12-01

    We used resequencing and genotyping in African Americans with sickle cell anemia (SCA) to characterize associations with fetal hemoglobin (HbF) levels at the BCL11A, HBS1L-MYB and β-globin loci. Fine-mapping of HbF association signals at these loci confirmed seven SNPs with independent effects and increased the explained heritable variation in HbF levels from 38.6% to 49.5%. We also identified rare missense variants that causally implicate MYB in HbF production.

  5. Prenatal Exposure to Organophosphorous Pesticides and Fetal Growth: Pooled Results from Four Longitudinal Birth Cohort Studies

    PubMed Central

    Harley, Kim G.; Engel, Stephanie M.; Vedar, Michelle G.; Eskenazi, Brenda; Whyatt, Robin M.; Lanphear, Bruce P.; Bradman, Asa; Rauh, Virginia A.; Yolton, Kimberly; Hornung, Richard W.; Wetmur, James G.; Chen, Jia; Holland, Nina T.; Barr, Dana Boyd; Perera, Frederica P.; Wolff, Mary S.

    2015-01-01

    Background: Organophosphorous (OP) pesticides are associated with reduced fetal growth in animals, but human studies are inconsistent. Objectives: We pooled data from four cohorts to examine associations of prenatal OP exposure with birth weight (n = 1,169), length (n = 1,152), and head circumference (n = 1,143). Methods: Data were from the CHAMACOS, HOME, Columbia, and Mount Sinai birth cohorts. Concentrations of three diethyl phosphate (ΣDEP) and three dimethyl phosphate (ΣDMP) metabolites of OP pesticides [summed to six dialkyl phosphates (ΣDAPs)] were measured in maternal urine. Linear regression and mixed-effects models were used to examine associations with birth outcomes. Results: We found no significant associations of ΣDEP, ΣDMP, or ΣDAPs with birth weight, length, or head circumference overall. However, among non-Hispanic black women, increasing urinary ΣDAP and ΣDMP concentrations were associated with decreased birth length (β = –0.4 cm; 95% CI: –0.9, 0.0 and β = –0.4 cm; 95% CI: –0.8, 0.0, respectively, for each 10-fold increase in metabolite concentration). Among infants with the PON1192RR genotype, ΣDAP and ΣDMP were negatively associated with length (β = –0.4 cm; 95% CI: –0.9, 0.0 and β = –0.5 cm; 95% CI: –0.9, –0.1). Conclusions: This study confirms previously reported associations of prenatal OP exposure among black women with decreased infant size at birth, but finds no evidence of smaller birth weight, length, or head circumference among whites or Hispanics. Contrary to our hypothesis, we found stronger inverse associations of DAPs and birth outcome in infants with the less susceptible PON1192RR genotype. The large pooled data set facilitated exploration of interactions by race/ethnicity and PON1 genotype, but was limited by differences in study populations. Citation: Harley KG, Engel SM, Vedar MG, Eskenazi B, Whyatt RM, Lanphear BP, Bradman A, Rauh VA, Yolton K, Hornung RW, Wetmur JG, Chen J, Holland NT, Barr DB

  6. Perfluoroalkyl Acids in Maternal Serum and Indices of Fetal Growth: The Aarhus Birth Cohort

    PubMed Central

    Bach, Cathrine Carlsen; Bech, Bodil Hammer; Nohr, Ellen Aagaard; Olsen, Jørn; Matthiesen, Niels Bjerregård; Bonefeld-Jørgensen, Eva Cecilie; Bossi, Rossana; Henriksen, Tine Brink

    2015-01-01

    Background: Previous studies indicated an association between intrauterine exposure to perfluorooctane sulfonate (PFOS) or perfluorooctanoate (PFOA) and lower birth weight. However, these perfluoroalkyl acids (PFAAs) have to some extent been substituted by other compounds on which little is known. Objectives: We investigated the association between specific PFAAs and birth weight, birth length, and head circumference at birth. Methods: We studied 1,507 mothers and their children from the Aarhus Birth Cohort (2008–2013). Nulliparous women were included during pregnancy, and serum levels of 16 PFAAs were measured between 9 and 20 completed gestational weeks (96% within 13 weeks). For compounds with quantifiable values in > 50% of samples (7 compounds), we report the associations with birth weight, birth length, and head circumference at birth determined by multivariable linear regression. Results: Estimated mean birth weights were lower among women with serum perfluorohexane sulfonate, perfluoroheptane sulfonate, and PFOS concentrations above the lowest exposure quartile, but we found no consistent monotonic dose–response patterns. These associations were stronger when the population was restricted to term births (n = 1,426). For PFOS, the birth weight estimates for the highest versus lowest quartile were –50 g (95% CI: –123, 23 g) in all births and –62 g (95% CI: –126, 3 g) in term births. For the other PFAAs, the direction of the associations was inconsistent, and no overall association with birth weight was apparent. No PFAAs were associated with birth length or head circumference at birth. Conclusions: Overall, we did not find strong or consistent associations between PFAAs and birth weight or other indices of fetal growth, though estimated mean birth weights were lower among those with exposures above the lowest quartile for some compounds. Citation: Bach CC, Bech BH, Nohr EA, Olsen J, Matthiesen NB, Bonefeld-Jørgensen EC, Bossi R, Henriksen TB

  7. Nicotine-induced retardation of chondrogenesis through down-regulation of IGF-1 signaling pathway to inhibit matrix synthesis of growth plate chondrocytes in fetal rats

    SciTech Connect

    Deng, Yu; Cao, Hong; Cu, Fenglong; Xu, Dan; Lei, Youying; Tan, Yang; Magdalou, Jacques; Wang, Hui; Chen, Liaobin

    2013-05-15

    Previous studies have confirmed that maternal tobacco smoking causes intrauterine growth retardation (IUGR) and skeletal growth retardation. Among a multitude of chemicals associated with cigarette smoking, nicotine is one of the leading candidates for causing low birth weights. However, the possible mechanism of delayed chondrogenesis by prenatal nicotine exposure remains unclear. We investigated the effects of nicotine on fetal growth plate chondrocytes in vivo and in vitro. Rats were given 2.0 mg/kg·d of nicotine subcutaneously from gestational days 11 to 20. Prenatal nicotine exposure increased the levels of fetal blood corticosterone and resulted in fetal skeletal growth retardation. Moreover, nicotine exposure induced the inhibition of matrix synthesis and down-regulation of insulin-like growth factor 1 (IGF-1) signaling in fetal growth plates. The effects of nicotine on growth plates were studied in vitro by exposing fetal growth plate chondrocytes to 0, 1, 10, or 100 μM of nicotine for 10 days. Nicotine inhibited matrix synthesis and down-regulated IGF-1 signaling in chondrocytes in a concentration-dependent manner. These results suggest that prenatal nicotine exposure induces delayed chondrogenesis and that the mechanism may involve the down-regulation of IGF-1 signaling and the inhibition of matrix synthesis by growth plate chondrocytes. The present study aids in the characterization of delayed chondrogenesis caused by prenatal nicotine exposure, which might suggest a candidate mechanism for intrauterine origins of osteoporosis and osteoarthritis. - Highlights: ► Prenatal nicotine-exposure could induce delayed chondrogenesis in fetal rats. ► Nicotine inhibits matrix synthesis of fetal growth plate chondrocytes. ► Nicotine inhibits IGF-1 signaling pathway in fetal growth plate chondrocytes.

  8. Placental restriction of fetal growth reduces cutaneous responses to antigen after sensitization in sheep.

    PubMed

    Wooldridge, Amy L; Bischof, Robert J; Meeusen, Els N; Liu, Hong; Heinemann, Gary K; Hunter, Damien S; Giles, Lynne C; Kind, Karen L; Owens, Julie A; Clifton, Vicki L; Gatford, Kathryn L

    2014-04-01

    Prenatal and early childhood exposures are implicated as causes of allergy, but the effects of intrauterine growth restriction on immune function and allergy are poorly defined. We therefore evaluated effects of experimental restriction of fetal growth on immune function and allergic sensitization in adolescent sheep. Immune function (circulating total red and white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, and the antibody response to Clostridial vaccination) and responses to house dust mite (HDM) allergen and ovalbumin (OVA) antigen sensitization (specific total Ig, IgG1, and IgE antibodies, and cutaneous hypersensitivity) were investigated in adolescent sheep from placentally restricted (PR, n = 23) and control (n = 40) pregnancies. Increases in circulating HDM-specific IgE (P = 0.007) and OVA-specific IgE (P = 0.038) were greater in PR than control progeny. PR did not alter total Ig, IgG1, or IgM responses to either antigen. PR increased OVA-specific but not HDM-specific IgA responses in females only (P = 0.023). Multiple birth increased Ig responses to OVA in a sex-specific manner. PR decreased the proportion of positive cutaneous hypersensitivity responders to OVA at 24 h (P = 0.030) but had no effect on cutaneous responses to HDM. Acute wheal responses to intradermal histamine correlated positively with birth weight in singletons (P = 0.023). Intrauterine growth restriction may suppress inflammatory responses in skin downstream of IgE induction, without impairment in antibody responses to a nonpolysaccharide vaccine. Discord between cutaneous and IgE responses following sensitization suggests new mechanisms for prenatal allergy programming.

  9. The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Systematic Review of Human Evidence for PFOA Effects on Fetal Growth

    PubMed Central

    Sutton, Patrice; Atchley, Dylan S.; Koustas, Erica; Lam, Juleen; Sen, Saunak; Robinson, Karen A.; Axelrad, Daniel A.; Woodruff, Tracey J.

    2014-01-01

    Background: The Navigation Guide methodology was developed to meet the need for a robust method of systematic and transparent research synthesis in environmental health science. We conducted a case study systematic review to support proof of concept of the method. Objective: We applied the Navigation Guide systematic review methodology to determine whether developmental exposure to perfluorooctanoic acid (PFOA) affects fetal growth in humans. Methods: We applied the first 3 steps of the Navigation Guide methodology to human epidemiological data: 1) specify the study question, 2) select the evidence, and 3) rate the quality and strength of the evidence. We developed a protocol, conducted a comprehensive search of the literature, and identified relevant studies using prespecified criteria. We evaluated each study for risk of bias and conducted meta-analyses on a subset of studies. We rated quality and strength of the entire body of human evidence. Results: We identified 18 human studies that met our inclusion criteria, and 9 of these were combined through meta-analysis. Through meta-analysis, we estimated that a 1-ng/mL increase in serum or plasma PFOA was associated with a –18.9 g (95% CI: –29.8, –7.9) difference in birth weight. We concluded that the risk of bias across studies was low, and we assigned a “moderate” quality rating to the overall body of human evidence. Conclusion: On the basis of this first application of the Navigation Guide systematic review methodology, we concluded that there is “sufficient” human evidence that developmental exposure to PFOA reduces fetal growth. Citation: Johnson PI, Sutton P, Atchley DS, Koustas E, Lam J, Sen S, Robinson KA, Axelrad DA, Woodruff TJ. 2014. The Navigation Guide—evidence-based medicine meets environmental health: systematic review of human evidence for PFOA effects on fetal growth. Environ Health Perspect 122:1028–1039; http://dx.doi.org/10.1289/ehp.1307893 PMID:24968388

  10. Somatomedin-C/insulin-like growth factor-I and Insulin-like growth factor-II mRNAs in rate fetal and adult tissues

    SciTech Connect

    Lund, P.K.; Moats-Staats, B.M.; Hynes, M.A.; Simmons, J.G.; Jansen, M.; D'ercole, A.J.; Van Wyk, J.J.

    1986-11-05

    Somatomedin-C or insulin-like growth factor I (Sm-C/IGF-I) and insulin-like growth factor II (IGF-II) have been implicated in the regulation of fetal growth and development. In the present study /sup 32/P-labeled complementary DNA probes encoding human and mouse Sm-C/IGF-I and human IGF-II were used in Northern blot hybridizations to analyze rat Sm-C/IGF-I and IGF-II mRNAs in poly(A/sup +/) RNAs from intestine, liver, lung, and brain of adult rats and fetal rats between day 14 and 17 of gestation. In fetal rats, all four tissues contained a major mRNA of 1.7 kilobase (kb) that hybridized with the human Sm-C/IGF-I cDNA and mRNAs of 7.5, 4.7, 1.7, and 1.2 kb that hybridized with the mouse Sm-C/IGF-I cDNA. Adult rat intestine, liver, and lung also contained these mRNAs but Sm-C/IGF-I mRNAs were not detected in adult rat brain. These findings provide direct support for prior observations that multiple tissues in the fetus synthesize immunoreactive Sm-C/IGF-I and imply a role for Sm-C/IGF-I in fetal development as well as postnatally. Multiple IGF-II mRNAs of estimated sizes 4.7, 3.9, 2.2, 1.75, and 1.2 kb were observed in fetal rat intestine, liver, lung, and brain. The 4.7- and 3.9-kb mRNAs were the major hybridizing IGF-II mRNAs in all fetal tissues. Higher abundance of IGF-II mRNAs in rat fetal tissues compared with adult tissues supports prior hypotheses, based on serum IGF-II concentrations, that IGF-II is predominantly a fetal somatomedin. IGF-II mRNAs are present, however, in some poly(A/sup +/) RNAs from adult rat tissues. The brain was the only tissue in the adult rat where the 4.7- and 3.9-kb IGF-II mRNAs were consistently detected. These findings suggest that a role for IGF-II in the adult rat, particularly in the central nervous system, cannot be excluded.

  11. Genomic Alterations Are Enhanced in Placentas from Pregnancies with Fetal Growth Restriction and Preeclampsia: Preliminary Results

    PubMed Central

    Biron-Shental, Tal; Sharony, Reuven; Shtorch-Asor, Atalia; Keiser, Meirav; Sadeh-Mestechkin, Dana; Laish, Ido; Amiel, Aliza

    2016-01-01

    Fetal growth restriction (FGR) secondary to placental insufficiency and preeclampsia (PE) are associated with substantially increased childhood and adult morbidity and mortality. The long-term outcomes are related to placental aberrations and intrauterine programming. Advances in microarray technology allow high-resolution, genome-wide evaluation for DNA copy number variations - deletions and duplications. The aim of our study was to demonstrate the usefulness of microarray testing in FGR placentas. Using Affymetrix GeneChip for chromosomal microarray (CMA), we analyzed 10 placentas from pregnancies with FGR attributed to placental insufficiency; 5 with FGR below the 5th percentile and 5 from the 5th to <10th percentiles. All fetuses had normal anomaly scans and karyotypes. We also analyzed 5 third-trimester placentas from pregnancies complicated by PE with severe features and 5 from PE without severe features, all with appropriately grown fetuses. The results were compared to 10 placentas from uncomplicated pregnancies with healthy neonates. CMA analysis identified more genomic alterations in FGR (p < 0.05) and in PE (p < 0.05) placentas than in healthy controls. There was a correlation to the severity of FGR and PE. The genomic alterations were below the resolution of normal karyotyping. The altered genes are related to adult human height, stress reactions and to cellular migration, differentiation and adhesion. Though very preliminary, our data support evaluating FGR and PE placentas using CMA. Larger data sets are needed for further evaluation of the findings and their clinical implications. PMID:27022328

  12. Craniofacial growth in fetal Tarsius bancanus: brains, eyes and nasal septa

    PubMed Central

    Jeffery, Nathan; Davies, Karen; Köckenberger, Walter; Williams, Steve

    2007-01-01

    The tarsier skull has been of particular interest in studies of primate taxonomy and functional morphology for several decades. Despite this, there remains no comprehensive data on how the tarsier skull develops, especially in relation to the soft-tissues of the head. Here we have documented for the first time fetal development of the skull and brain as well as the nasal septum and eyes in T. bancanus. We have also tested for the possible influence of these tissues in shaping skull architecture. Nineteen post-mortem specimens were imaged using high-resolution magnetic resonance imaging and magnetic resonance microscopy. Landmarks and volume data were collected and analysed. Findings demonstrated massive increases of brain size and eye size as well as flattening of the midline cranial base, facial projection and orbital margin frontation. Little evidence was found to support the notion that growth of the brain or nasal septum physically drives the observed changes of the skull. However, increases in the size of the eyes relative to skull size were associated with orbital margin frontation. With the possible exception of the results for eye size, the findings indicate that rather than forcing change the soft-tissues form a framework that physically constrains the morphogenetic template of the skeletal elements. This suggests, for example, that the degree of cranial base angulation seen in adulthood is not directly determined by brain expansion bending the basicranium, but by brain enlargement limiting the extent of cranial base flattening (retroflexion) in the fetus. PMID:17451471

  13. Cord Blood 25-hydroxyvitamin D and Fetal Growth in the China-Anhui Birth Cohort Study.

    PubMed

    Zhu, Peng; Tong, Shi-lu; Hu, Wen-biao; Hao, Jia-hu; Tao, Rui-xue; Huang, Kun; Mou, Zhe; Zhou, Qi-fan; Jiang, Xiao-min; Tao, Fang-biao

    2015-01-01

    We determined the association of cord blood 25-hydroxyvitamin D [25(OH)D] with birth weight and the risk of small for gestational age (SGA). As part of the China-Anhui Birth Cohort (C-ABC) study, we measured cord blood levels of 25(OH)D in 1491 neonates in Hefei, China. The data on maternal sociodemographic characteristics, health status, lifestyle, birth outcomes were prospectively collected. Multiple regression models were used to estimate the association of 25(OH)D levels with birth weight and the risk of SGA. Compared with neonates in the lowest decile of cord blood 25(OH)D levels, neonates in four deciles (the fourth, fifth, sixth and seventh deciles) had significantly increased birth weight and decreased risk of SGA. Multiple linear regression models showed that per 10 nmol/L increase in cord blood 25(OH)D, birth weight increased by 61.0 g (95% CI: 31.9, 89.9) at concentrations less than 40 nmol/L, and then decreased by 68.5 g (95% CI: -110.5, -26.6) at concentrations from 40 to 70 nmol/L. This study provides the first epidemiological evidence that there was an inverted U shaped relationship between neonatal vitamin D status and fetal growth, and the risk of SGA reduced at moderate concentration. PMID:26450157

  14. Growth characteristics of the fetal ligament of the head of femur: significance in congenital hip disease.

    PubMed Central

    Walker, J. M.

    1980-01-01

    Measurement of the length and width of the ligament of the head of femur (ligamentum teres) in 140 normal human fetuses between 12 weeks and term provides limits for growth changes in this structure. These observations provide no morphological evidence of a significant difference between males and females, or between the right and left sides, to explain the female and left hip preponderance reported in congenital hip disease. The ligament is shown to be variable in length, width, and shape, and it is not a distinctly linear structure through linearity may increase with age. Tests of femoral head mobility support the opinion that this ligament must play a role in fetal and neonatal hip joint stability. Weak correlation only was demonstrated between the ligament variables and acetabular depth, which suggests that ligament shape and socket shape are not closely related. Comparison of measurements from normal and 12 dysplastic or subluxated joints provides no evidence to support previous observations that this structure is unusually long in abnormal hip joints which are not frankly dislocated. Images FIG. 1 PMID:7445537

  15. Blood Biomarkers of Late Pregnancy Exposure to Trihalomethanes in Drinking Water and Fetal Growth Measures and Gestational Age in a Chinese Cohort

    PubMed Central

    Cao, Wen-Cheng; Zeng, Qiang; Luo, Yan; Chen, Hai-Xia; Miao, Dong-Yue; Li, Li; Cheng, Ying-Hui; Li, Min; Wang, Fan; You, Ling; Wang, Yi-Xin; Yang, Pan; Lu, Wen-Qing

    2015-01-01

    Background: Previous studies have suggested that elevated exposure to disinfection by-products (DBPs) in drinking water during gestation may result in adverse birth outcomes. However, the findings of these studies remain inconclusive. Objective: The purpose of our study was to examine the association between blood biomarkers of late pregnancy exposure to trihalomethanes (THMs) in drinking water and fetal growth and gestational age. Methods: We recruited 1,184 pregnant women between 2011 and 2013 in Wuhan and Xiaogan City, Hubei, China. Maternal blood THM concentrations, including chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM), were measured as exposure biomarkers during late pregnancy. We estimated associations with gestational age and fetal growth indicators [birth weight, birth length, and small for gestational age (SGA)]. Results: Total THMs (TTHMs; sum of TCM, BDCM, DBCM, and TBM) were associated with lower mean birth weight (–60.9 g; 95% CI: –116.2, –5.6 for the highest vs. lowest tertile; p for trend = 0.03), and BDCM and DBCM exposures were associated with smaller birth length (e.g., –0.20 cm; 95% CI: –0.37, –0.04 for the highest vs. lowest tertile of DBCM; p for trend = 0.02). SGA was increased in association with the second and third tertiles of TTHMs (OR = 2.91; 95% CI: 1.32, 6.42 and OR = 2.25; 95% CI: 1.01, 5.03; p for trend = 0.08). Conclusions: Our results suggested that elevated maternal THM exposure may adversely affect fetal growth. Citation: Cao WC, Zeng Q, Luo Y, Chen HX, Miao DY, Li L, Cheng YH, Li M, Wang F, You L, Wang YX, Yang P, Lu WQ. 2016. Blood biomarkers of late pregnancy exposure to trihalomethanes in drinking water and fetal growth measures and gestational age in a Chinese cohort. Environ Health Perspect 124:536–541; http://dx.doi.org/10.1289/ehp.1409234 PMID:26340795

  16. Effects of hyperthyroidism on expression of vascular endothelial growth factor (VEGF) and apoptosis in fetal adrenal glands.

    PubMed

    Karaca, T; Hulya Uz, Y; Karabacak, R; Karaboga, I; Demirtas, S; Cagatay Cicek, A

    2015-11-26

    This study investigated the expression of vascular endothelial growth factor (VEGF), vascular density, and apoptosis in fetal rat adrenal glands with hyperthyroidism in late gestation. Twelve mature female Wistar albino rats with the same biological and physiological features were used for this study. Rats were divided into two groups: control and hyperthyroidism. Hyperthyroidism was induced by daily subcutaneous injections of L-thyroxine (250 μg/kg) before pregnancy for 21 days and during pregnancy. Rats in the control and hyperthyroidism groups were caged according to the number of male rats. Zero day of pregnancy (Day 0) was indicated when the animals were observed to have microscopic sperm in vaginal smears. Pregnant rats were sacrificed on the 20th day of pregnancy; blood from each animal was collected to determine the concentrations of maternal adrenocorticotropic hormone and thyroxine. Rat fetuses were then quickly removed from the uterus, and the adrenal glands of the fetuses were dissected. VEGF expression, vascular density, and apoptosis were analyzed in fetal rat adrenal glands. Maternal serum levels of the adrenocorticotropic hormone and free thyroxine were significantly higher in the hyperthyroidism group than in the control group. Immunohistochemistry revealed that the number of VEGF positive cells and vessel density significantly increased in the hyperthyroidism rat fetal adrenal group compared with the control group. Hyperthyroidism did not change the fetal and placental weights and the number of fetuses. This study demonstrates that hyperthyroidism may have an effect on the development of rat adrenal glands mediated by VEGF expression, angiogenesis, and apoptosis.

  17. Effects of Hyperthyroidism on Expression of Vascular Endothelial Growth Factor (VEGF) and Apoptosis in Fetal Adrenal Glands

    PubMed Central

    Hulya Uz, Y.; Karabacak, R.; Karaboga, I.; Demirtas, S.; Cagatay Cicek, A.

    2015-01-01

    This study investigated the expression of vascular endothelial growth factor (VEGF), vascular density, and apoptosis in fetal rat adrenal glands with hyperthyroidism in late gestation. Twelve mature female Wistar albino rats with the same biological and physiological features were used for this study. Rats were divided into two groups: control and hyperthyroidism. Hyperthyroidism was induced by daily subcutaneous injections of L-thyroxine (250 µg/kg) before pregnancy for 21 days and during pregnancy. Rats in the control and hyperthyroidism groups were caged according to the number of male rats. Zero day of pregnancy (Day 0) was indicated when the animals were observed to have microscopic sperm in vaginal smears. Pregnant rats were sacrificed on the 20th day of pregnancy; blood from each animal was collected to determine the concentrations of maternal adrenocorticotropic hormone and thyroxine. Rat fetuses were then quickly removed from the uterus, and the adrenal glands of the fetuses were dissected. VEGF expression, vascular density, and apoptosis were analyzed in fetal rat adrenal glands. Maternal serum levels of the ACTH and free thyroxine were significantly higher in the hyperthyroidism group than in the control group. Immunohistochemistry revealed that the number of VEGF positive cells and vessel density significantly increased in the hyperthyroidism rat fetal adrenal group compared with the control group. Hyperthyroidism did not change the fetal and placental weights and the number of fetuses. This study demonstrates that hyperthyroidism may have an effect on the development of rat adrenal glands mediated by VEGF expression, angiogenesis, and apoptosis. PMID:26708182

  18. Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts.

    PubMed

    Beck, Michaël; Moreels, Marjan; Quintens, Roel; Abou-El-Ardat, Khalil; El-Saghire, Hussein; Tabury, Kevin; Michaux, Arlette; Janssen, Ann; Neefs, Mieke; Van Oostveldt, Patrick; De Vos, Winnok H; Baatout, Sarah

    2014-08-01

    Microgravity and cosmic rays as found in space are difficult to recreate on earth. However, ground-based models exist to simulate space flight experiments. In the present study, an experimental model was utilized to monitor gene expression changes in fetal skin fibroblasts of murine origin. Cells were continuously subjected for 65 h to a low dose (55 mSv) of ionizing radiation (IR), comprising a mixture of high‑linear energy transfer (LET) neutrons and low-LET gamma-rays, and/or simulated microgravity using the random positioning machine (RPM), after which microarrays were performed. The data were analyzed both by gene set enrichment analysis (GSEA) and single gene analysis (SGA). Simulated microgravity affected fetal murine fibroblasts by inducing oxidative stress responsive genes. Three of these genes are targets of the nuclear factor‑erythroid 2 p45-related factor 2 (Nrf2), which may play a role in the cell response to simulated microgravity. In addition, simulated gravity decreased the expression of genes involved in cytoskeleton remodeling, which may have been caused by the downregulation of the serum response factor (SRF), possibly through the Rho signaling pathway. Similarly, chronic exposure to low-dose IR caused the downregulation of genes involved in cytoskeleton remodeling, as well as in cell cycle regulation and DNA damage response pathways. Many of the genes or gene sets that were altered in the individual treatments (RPM or IR) were not altered in the combined treatment (RPM and IR), indicating a complex interaction between RPM and IR.

  19. [Fetal magnetocardiography].

    PubMed

    van Leeuwen, P

    1997-09-01

    demonstrate the potential of the method in the examination of the fetal conductive system, arrhythmias, congential defects, growth, development of the autonomic system, acidosis and distress. Furthermore, first results in pathological cases indicate that it may become a valuable tool in prenatal diagnostics. Improvements in instrumentation as well as prospective multicenter studies with larger numbers of appropriate subjects are required to determine whether magnetocardiography will establish itself as a new tool in clinical fetal, surveillance.

  20. How population growth affects linkage disequilibrium.

    PubMed

    Rogers, Alan R

    2014-08-01

    The "LD curve" relates the linkage disequilibrium (LD) between pairs of nucleotide sites to the distance that separates them along the chromosome. The shape of this curve reflects natural selection, admixture between populations, and the history of population size. This article derives new results about the last of these effects. When a population expands in size, the LD curve grows steeper, and this effect is especially pronounced following a bottleneck in population size. When a population shrinks, the LD curve rises but remains relatively flat. As LD converges toward a new equilibrium, its time path may not be monotonic. Following an episode of growth, for example, it declines to a low value before rising toward the new equilibrium. These changes happen at different rates for different LD statistics. They are especially slow for estimates of [Formula: see text], which therefore allow inferences about ancient population history. For the human population of Europe, these results suggest a history of population growth.

  1. Hyperglycemia Differentially Affects Maternal and Fetal DNA Integrity and DNA Damage Response

    PubMed Central

    Moreli, Jusciele B.; Santos, Janine H.; Lorenzon-Ojea, Aline Rodrigues; Corrêa-Silva, Simone; Fortunato, Rodrigo S.; Rocha, Clarissa Ribeiro; Rudge, Marilza V.; Damasceno, Débora C.; Bevilacqua, Estela; Calderon, Iracema M.

    2016-01-01

    Objective: Investigate the DNA damage and its cellular response in blood samples from both mother and the umbilical cord of pregnancies complicated by hyperglycemia. Methods: A total of 144 subjects were divided into 4 groups: normoglycemia (ND; 46 cases), mild gestational hyperglycemia (MGH; 30 cases), gestational diabetes mellitus (GDM; 45 cases) and type-2 diabetes mellitus (DM2; 23 cases). Peripheral blood mononuclear cell (PBMC) isolation and/or leukocytes from whole maternal and umbilical cord blood were obtained from all groups at delivery. Nuclear and mitochondrial DNA damage were measured by gene-specific quantitative PCR, and the expression of mRNA and proteins involved in the base excision repair (BER) pathway were assessed by real-time qPCR and Western blot, respectively. Apoptosis was measured in vitro experiments by caspase 3/7 activity and ATP levels. Results: GDM and DM2 groups were characterized by an increase in oxidative stress biomarkers, an increase in nuclear and mitochondrial DNA damage, and decreased expression of mRNA (APE1, POLβ and FEN1) and proteins (hOGG1, APE1) involved in BER. The levels of hyperglycemia were associated with the in vitro apoptosis pathway. Blood levels of DNA damage in umbilical cord were similar among the groups. Newborns of diabetic mothers had increased expression of BER mRNA (APE1, POLβ and FEN1) and proteins (hOGG1, APE1, POLβ and FEN1). A diabetes-like environment was unable to induce apoptosis in the umbilical cord blood cells. Conclusions: Our data show relevant asymmetry between maternal and fetal blood cell susceptibility to DNA damage and apoptosis induction. Maternal cells seem to be more predisposed to changes in an adverse glucose environment. This may be due to differential ability in upregulating multiple genes involved in the activation of DNA repair response, especially the BER mechanism. However if this study shows a more effective adaptive response by the fetal organism, it also calls for

  2. Lack of Thromboxane Synthase Prevents Hypertension and Fetal Growth Restriction after High Salt Treatment during Pregnancy

    PubMed Central

    Pai, Chen-Hsueh; Yen, Ching-Tzu; Chen, Chie-Pein; Yu, I-Shing

    2016-01-01

    Preeclampsia (PE) is a potentially fatal pregnancy-related hypertensive disorder characterized by poor placenta development that can cause fetal growth restriction. PE-associated pathologies, including thrombosis, hypertension, and impaired placental development, may result from imbalances between thromboxane A2 (TXA2) and prostacyclin. Low-dose aspirin, which selectively inhibits TXA2 production, is used to prevent high-risk PE. However, the role of TXA2 in aspirin-mediated protective effects in women with PE is not understood fully. In this study, we examined the role of prostanoids in PE using human samples and an induced PE mouse model. We demonstrated that the administration of salted drinking water (2.7% NaCl) to wild-type mice resulted in elevated placental TXA2 synthase (TXAS) and plasma TXA2, but not prostacyclin, levels, which was also found in our clinical PE placenta samples. The high salt-treated wild-type pregnant mice had shown unchanged maternal body weight, hypertension (MAP increase 15 mmHg), and decreased pup weight (~50%) and size (~24%), but these adverse effects were ameliorated in TXAS knockout (KO) mice. Moreover, increased expression of interleukin-1β and downstream phosphorylated-p38-mitogen-activated protein kinase were concordant with apoptosis induction in the placentas of salt water-treated wild-type mice. These alterations were not observed in TXAS KO mice. Together, our data suggest that TXA2 depletion has anti-PE effects due to the prevention of hypertension and placental damage through downregulation of the interleukin-1β pathway. PMID:26974824

  3. Lack of Thromboxane Synthase Prevents Hypertension and Fetal Growth Restriction after High Salt Treatment during Pregnancy.

    PubMed

    Pai, Chen-Hsueh; Yen, Ching-Tzu; Chen, Chie-Pein; Yu, I-Shing; Lin, Shu-Wha; Lin, Shu-Rung

    2016-01-01

    Preeclampsia (PE) is a potentially fatal pregnancy-related hypertensive disorder characterized by poor placenta development that can cause fetal growth restriction. PE-associated pathologies, including thrombosis, hypertension, and impaired placental development, may result from imbalances between thromboxane A2 (TXA2) and prostacyclin. Low-dose aspirin, which selectively inhibits TXA2 production, is used to prevent high-risk PE. However, the role of TXA2 in aspirin-mediated protective effects in women with PE is not understood fully. In this study, we examined the role of prostanoids in PE using human samples and an induced PE mouse model. We demonstrated that the administration of salted drinking water (2.7% NaCl) to wild-type mice resulted in elevated placental TXA2 synthase (TXAS) and plasma TXA2, but not prostacyclin, levels, which was also found in our clinical PE placenta samples. The high salt-treated wild-type pregnant mice had shown unchanged maternal body weight, hypertension (MAP increase 15 mmHg), and decreased pup weight (~50%) and size (~24%), but these adverse effects were ameliorated in TXAS knockout (KO) mice. Moreover, increased expression of interleukin-1β and downstream phosphorylated-p38-mitogen-activated protein kinase were concordant with apoptosis induction in the placentas of salt water-treated wild-type mice. These alterations were not observed in TXAS KO mice. Together, our data suggest that TXA2 depletion has anti-PE effects due to the prevention of hypertension and placental damage through downregulation of the interleukin-1β pathway. PMID:26974824

  4. Lack of Thromboxane Synthase Prevents Hypertension and Fetal Growth Restriction after High Salt Treatment during Pregnancy.

    PubMed

    Pai, Chen-Hsueh; Yen, Ching-Tzu; Chen, Chie-Pein; Yu, I-Shing; Lin, Shu-Wha; Lin, Shu-Rung

    2016-01-01

    Preeclampsia (PE) is a potentially fatal pregnancy-related hypertensive disorder characterized by poor placenta development that can cause fetal growth restriction. PE-associated pathologies, including thrombosis, hypertension, and impaired placental development, may result from imbalances between thromboxane A2 (TXA2) and prostacyclin. Low-dose aspirin, which selectively inhibits TXA2 production, is used to prevent high-risk PE. However, the role of TXA2 in aspirin-mediated protective effects in women with PE is not understood fully. In this study, we examined the role of prostanoids in PE using human samples and an induced PE mouse model. We demonstrated that the administration of salted drinking water (2.7% NaCl) to wild-type mice resulted in elevated placental TXA2 synthase (TXAS) and plasma TXA2, but not prostacyclin, levels, which was also found in our clinical PE placenta samples. The high salt-treated wild-type pregnant mice had shown unchanged maternal body weight, hypertension (MAP increase 15 mmHg), and decreased pup weight (~50%) and size (~24%), but these adverse effects were ameliorated in TXAS knockout (KO) mice. Moreover, increased expression of interleukin-1β and downstream phosphorylated-p38-mitogen-activated protein kinase were concordant with apoptosis induction in the placentas of salt water-treated wild-type mice. These alterations were not observed in TXAS KO mice. Together, our data suggest that TXA2 depletion has anti-PE effects due to the prevention of hypertension and placental damage through downregulation of the interleukin-1β pathway.

  5. Maternal Dietary Patterns and Fetal Growth: A Large Prospective Cohort Study in China

    PubMed Central

    Lu, Min-Shan; Chen, Qiao-Zhu; He, Jian-Rong; Wei, Xue-Ling; Lu, Jin-Hua; Li, Sheng-Hui; Wen, Xing-Xuan; Chan, Fan-Fan; Chen, Nian-Nian; Qiu, Lan; Mai, Wei-Bi; Zhang, Rui-Fang; Hu, Cui-Yue; Xia, Hui-Min; Qiu, Xiu

    2016-01-01

    There was limited evidence revealing the association of Chinese maternal dietary patterns with fetal growth. We aimed to examine the relationship of maternal dietary patterns during pregnancy to neonatal birth weight and birth weight for gestational age in a Chinese population. A total of 6954 mother-child pairs were included from the Born in Guangzhou Cohort Study. Maternal diet during pregnancy was assessed using a self-administered food frequency questionnaire. Cluster analysis was used to identify dietary patterns. The following six dietary patterns were identified: “Cereals, eggs, and Cantonese soups” (n 1026, 14.8%), “Dairy” (n 1020, 14.7%), “Fruits, nuts, and Cantonese desserts” (n 799, 11.5%), “Meats” (n 1066, 15.3%), “Vegetables” (n 1383, 19.9%), and “Varied” (n 1224, 17.6%). The mean neonatal birth weight Z scores of women in the above patterns were 0.02, 0.07, 0.20, 0.01, 0.06, and 0.14, respectively. Women in the “Fruits, nuts, and Cantonese desserts” and “Varied” groups had significantly heavier infants compared with those in the “Cereals, eggs, and Cantonese soups” group. Compared with women in the “Cereals, eggs, and Cantonese soups” group, those in the “Varied” group had marginally significantly lower odds of having a small-for-gestational age (SGA) infant after adjustment for other confounders (OR 0.77, 95% CI 0.57, 1.04, p = 0.08). These findings suggest that compared to a traditional Cantonese diet high in cereals, eggs, and Cantonese soups, a diet high in fruits, nuts, and Cantonese desserts might be associated with a higher birth weight, while a varied diet might be associated with a greater birth weight and also a decreased risk of having a SGA baby. PMID:27136584

  6. Spiral artery remodeling and trophoblast invasion in preeclampsia and fetal growth restriction: relationship to clinical outcome.

    PubMed

    Lyall, Fiona; Robson, Stephen C; Bulmer, Judith N

    2013-12-01

    Failure to transform uteroplacental spiral arteries is thought to underpin disorders of pregnancy, including preeclampsia and fetal growth restriction (FGR). In this study, spiral artery remodeling and extravillous-cytotrophoblast were examined in placental bed biopsies from normal pregnancy (n = 25), preeclampsia (n = 22), and severe FGR (n = 10) and then compared with clinical parameters. Biopsies were immunostained to determine vessel wall integrity, extravillous-cytotrophoblast location/density, periarterial fibrinoid, and endothelium. Muscle disruption was reduced in myometrial spiral arteries in preeclampsia (P = 0.0001) and FGR (P = 0.0001) compared with controls. Myometrial vessels from cases with birth weight <5th percentile (P<0.001), abnormal uterine Doppler (P<0.01), abnormal umbilical artery Doppler (P<0.001), and preterm delivery (P<0.001) had less muscle destruction compared with >5th percentile. Fewer extravillous-cytotrophoblast surrounded both decidual and myometrial vessels in the normal group and preeclampsia group compared with the FGR group (P = 0.001). For myometrial vessels, the normal group contained more intramural extravillous-cytotrophoblast than in preeclampsia (P = 0.015). Decidual vessels in the FGR group had less fibrinoid deposition compared with controls (P = 0.013). For myometrial vessels, less fibrinoid was deposited in both the preeclampsia group (P = 0.0001) and the FGR group (P = 0.01) when compared with controls, and less fibrinoid was deposited in the preeclampsia group when compared with FGR group (P<0.001). Myometrial vessels obtained from birth weights <5th percentile had less periarterial fibrinoid than those with >5th percentile (P<0.02). A major defect in myometrial spiral artery remodeling occurs in preeclampsia and FGR that is linked to clinical parameters. Interstitial extravillous-cytotrophoblast is not reduced in preeclampsia but is increased in FGR. PMID:24060885

  7. Embryo development, fetal growth and postnatal phenotype of eGFP lambs generated by lentiviral transgenesis.

    PubMed

    Crispo, M; Vilariño, M; dos Santos-Neto, P C; Núñez-Olivera, R; Cuadro, F; Barrera, N; Mulet, A P; Nguyen, T H; Anegón, I; Menchaca, A

    2015-02-01

    Lentiviral technology has been recently proposed to generate transgenic farm animals more efficiently and easier than traditional techniques. The objective was to evaluate several parameters of lambs obtained by lentiviral transgenesis in comparison with non-transgenic counterparts. In vitro produced embryos were microinjected (TG group) at two-cell stage with a lentiviral construct containing enhanced green fluorescent protein (eGFP) gene, while embryos produced by in vitro fertilization (IVF group) or intrauterine insemination (IUI group) were not microinjected. Microinjection technique efficiently generated eight-cell transgenic embryos (97.4%; 114/117). Development rate on day 5 after fertilization was similar for TG (39.3%, 46/117) and IVF embryos (39.6%, 44/111). Pregnancy rate was detected in 50.0% (6/12) of recipient ewes with TG embryos, in 46.7% (7/15) with IVF embryos, and in 65.0% (13/20) of IUI ewes (P = NS). Nine lambs were born in TG group, six lambs in IVF group, and 16 lambs in IUI group. All TG lambs (9/9) were GFP positive to real-time PCR and eight (88.9%) showed a strong and evident GFP expression in mucosae, eyes and keratin tissues. Fetal growth monitored every 15 day by ultrasonography did not show significant differences. Transgenic lambs neither differ in morphometric variables in comparison with non transgenic IVF lambs within 3 months after birth. Transmission of the transgene to the progeny was observed in green fluorescent embryos produced by IVF using semen from the TG founder lambs. In conclusion, this study demonstrates the high efficiency of lentiviral technology to produce transgenic sheep, with no clinic differences in comparison with non transgenic lambs.

  8. The Effect of Fetal and Childhood Growth over Depression in Early Adulthood in a Southern Brazilian Birth Cohort

    PubMed Central

    Loret de Mola, Christian; Quevedo, Luciana de Avila; Pinheiro, Ricardo Tavares; Gonçalves, Helen; Gigante, Denise Petrucci; Motta, Janaína Vieira dos Santos; Barros, Fernando C.; Horta, Bernardo Lessa

    2015-01-01

    Background Poor nutrition and growth during fetal life and childhood might be associated with depression in adulthood; however, studies evaluating these associations present controversial results, especially when comparing studies using different proxies for fetal growth. We evaluated the association of fetal and childhood growth/nutrition with depression, in adulthood, using different approaches and measurement methods. Method In 1982, hospital births (n = 5914) in Pelotas, southern Brazil, were examined and have been prospectively followed. At 30 years, the presence of major depression and depressive symptoms severity was evaluated using the Mini International Neuropsychiatric Interview (MINI) and Beck Depression Inventory (BDI-II). The present study assessed their association with birth weight, premature birth, small for gestational age (SGA), stunting and conditional growth during childhood. Results At 30 years, 3576 individuals were evaluated and 7.9% had major depression. Low birth weight (PR = 1.01 95%CI [0.64–1.60]), having been born SGA (PR = 0.87 95%CI [0.64–1.19]) and premature birth (PR = 1.22 95%CI [0.72–2.07]) were not associated with major depression in multivariable models. However, those born SGA who were also stunted in childhood had a higher prevalence of major depression (PR = 1.87 95%CI [1.06–3.29]) and greater odds of scoring a higher level of depression in the BDI-II (OR = 2.18 95%CI [1.34–3.53]). Conclusion In this Brazilian cohort of young adults, those born SGA who were also stunted during childhood had a higher risk of depression in adulthood. Our results show that the effect of growth impairment on depression is cumulative. PMID:26469192

  9. Low and high dietary protein:carbohydrate ratios during pregnancy affect materno-fetal glucose metabolism in pigs.

    PubMed

    Metges, Cornelia C; Görs, Solvig; Lang, Iris S; Hammon, Harald M; Brüssow, Klaus-Peter; Weitzel, Joachim M; Nürnberg, Gerd; Rehfeldt, Charlotte; Otten, Winfried

    2014-02-01

    Inadequate dietary protein during pregnancy causes intrauterine growth retardation. Whether this is related to altered maternal and fetal glucose metabolism was examined in pregnant sows comparing a high-protein:low-carbohydrate diet (HP-LC; 30% protein, 39% carbohydrates) with a moderately low-protein:high-carbohydrate diet (LP-HC; 6.5% protein, 68% carbohydrates) and the isoenergetic standard diet (ST; 12.1% protein, 60% carbohydrates). During late pregnancy, maternal and umbilical glucose metabolism and fetal hepatic mRNA expression of gluconeogenic enzymes were examined. During an i.v. glucose tolerance test (IVGTT), the LP-HC-fed sows had lower insulin concentrations and area under the curve (AUC), and higher glucose:insulin ratios than the ST- and the HP-LC-fed sows (P < 0.05). Insulin sensitivity and glucose clearance were higher in the LP-HC sows compared with ST sows (P < 0.05). Glucagon concentrations during postabsorptive conditions and IVGTT, and glucose AUC during IVGTT, were higher in the HP-LC group compared with the other groups (P < 0.001). (13)C glucose oxidation was lower in the HP-LC sows than in the ST and LP-HC sows (P < 0.05). The HP-LC fetuses were lighter and had a higher brain:liver ratio than the ST group (P < 0.05). The umbilical arterial inositol concentration was greater in the HP-LC group (P < 0.05) and overall small fetuses (230-572 g) had higher values than medium and heavy fetuses (≥573 g) (P < 0.05). Placental lactate release was lower in the LP-HC group than in the ST group (P < 0.05). Fetal glucose extraction tended to be lower in the LP-HC group than in the ST group (P = 0.07). In the HP-LC and LP-HC fetuses, hepatic mRNA expression of cytosolic phosphoenolpyruvate carboxykinase (PCK1) and glucose-6-phosphatase (G6PC) was higher than in the ST fetuses (P < 0.05). In conclusion, the HP-LC and LP-HC sows adapted by reducing glucose turnover and oxidation and having higher glucose utilization, respectively. The HP-LC and LP

  10. Utilizing Longitudinal Measures of Fetal Growth to Create a Standard Method to Assess the Impacts of Maternal Disease and Environmental Exposure.

    PubMed

    Cantonwine, David E; Ferguson, Kelly K; Mukherjee, Bhramar; Chen, Yin-Hsiu; Smith, Nicole A; Robinson, Julian N; Doubilet, Peter M; Meeker, John D; McElrath, Thomas F

    2016-01-01

    Impaired or suboptimal fetal growth is associated with an increased risk of perinatal morbidity and mortality. By utilizing readily available clinical data on the relative size of the fetus at multiple points in pregnancy, including delivery, future epidemiological research can improve our understanding of the impacts of maternal, fetal, and environmental factors on fetal growth at different windows during pregnancy. This study presents mean and standard deviation ultrasound measurements from a clinically representative US population that can be utilized for creating Z-scores to this end. Between 2006 and 2012, 18, 904 non-anomalous pregnancies that received prenatal care, first and second trimester ultrasound evaluations, and ultimately delivered singleton newborns at Brigham and Women's hospital in Boston were used to create the standard population. To illustrate the utility of this standard, we created Z-scores for ultrasound and delivery measurements for a cohort study population and examined associations with factors known to be associated with fetal growth. In addition to cross-sectional regression models, we created linear mixed models and generalized additive mixed models to illustrate how these scores can be utilized longitudinally and for the identification of windows of susceptibility. After adjustment for a priori confounders, maternal BMI was positively associated with increased fetal size beginning in the second trimester in cross-sectional models. Female infants and maternal smoking were associated with consistently reduced fetal size in the longitudinal models. Maternal age had a non-significant association with increased size in the first trimester that was attenuated as gestation progressed. As the growth measurements examined here are widely available in contemporary obstetrical practice, these data may be abstracted from medical records by investigators and standardized with the population means presented here. This will enable easy extension of

  11. Utilizing Longitudinal Measures of Fetal Growth to Create a Standard Method to Assess the Impacts of Maternal Disease and Environmental Exposure

    PubMed Central

    Cantonwine, David E.; Ferguson, Kelly K.; Mukherjee, Bhramar; Chen, Yin-Hsiu; Smith, Nicole A.; Robinson, Julian N.; Doubilet, Peter M.; Meeker, John D.; McElrath, Thomas F.

    2016-01-01

    Impaired or suboptimal fetal growth is associated with an increased risk of perinatal morbidity and mortality. By utilizing readily available clinical data on the relative size of the fetus at multiple points in pregnancy, including delivery, future epidemiological research can improve our understanding of the impacts of maternal, fetal, and environmental factors on fetal growth at different windows during pregnancy. This study presents mean and standard deviation ultrasound measurements from a clinically representative US population that can be utilized for creating Z-scores to this end. Between 2006 and 2012, 18, 904 non-anomalous pregnancies that received prenatal care, first and second trimester ultrasound evaluations, and ultimately delivered singleton newborns at Brigham and Women’s hospital in Boston were used to create the standard population. To illustrate the utility of this standard, we created Z-scores for ultrasound and delivery measurements for a cohort study population and examined associations with factors known to be associated with fetal growth. In addition to cross-sectional regression models, we created linear mixed models and generalized additive mixed models to illustrate how these scores can be utilized longitudinally and for the identification of windows of susceptibility. After adjustment for a priori confounders, maternal BMI was positively associated with increased fetal size beginning in the second trimester in cross-sectional models. Female infants and maternal smoking were associated with consistently reduced fetal size in the longitudinal models. Maternal age had a non-significant association with increased size in the first trimester that was attenuated as gestation progressed. As the growth measurements examined here are widely available in contemporary obstetrical practice, these data may be abstracted from medical records by investigators and standardized with the population means presented here. This will enable easy extension

  12. Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts.

    PubMed

    Beck, Michaël; Moreels, Marjan; Quintens, Roel; Abou-El-Ardat, Khalil; El-Saghire, Hussein; Tabury, Kevin; Michaux, Arlette; Janssen, Ann; Neefs, Mieke; Van Oostveldt, Patrick; De Vos, Winnok H; Baatout, Sarah

    2014-08-01

    Microgravity and cosmic rays as found in space are difficult to recreate on earth. However, ground-based models exist to simulate space flight experiments. In the present study, an experimental model was utilized to monitor gene expression changes in fetal skin fibroblasts of murine origin. Cells were continuously subjected for 65 h to a low dose (55 mSv) of ionizing radiation (IR), comprising a mixture of high‑linear energy transfer (LET) neutrons and low-LET gamma-rays, and/or simulated microgravity using the random positioning machine (RPM), after which microarrays were performed. The data were analyzed both by gene set enrichment analysis (GSEA) and single gene analysis (SGA). Simulated microgravity affected fetal murine fibroblasts by inducing oxidative stress responsive genes. Three of these genes are targets of the nuclear factor‑erythroid 2 p45-related factor 2 (Nrf2), which may play a role in the cell response to simulated microgravity. In addition, simulated gravity decreased the expression of genes involved in cytoskeleton remodeling, which may have been caused by the downregulation of the serum response factor (SRF), possibly through the Rho signaling pathway. Similarly, chronic exposure to low-dose IR caused the downregulation of genes involved in cytoskeleton remodeling, as well as in cell cycle regulation and DNA damage response pathways. Many of the genes or gene sets that were altered in the individual treatments (RPM or IR) were not altered in the combined treatment (RPM and IR), indicating a complex interaction between RPM and IR. PMID:24859186

  13. Enhancing Learning Environments for Students Affected by Fetal Alcohol Spectrum Disorders: An Exploratory Study of Canadian Pre-Service Teacher Knowledge and Conceptions

    ERIC Educational Resources Information Center

    Pei, Jacqueline; Job, Jenelle; Poth, Cheryl; O'Brien-Langer, Anna; Tang, Wei

    2015-01-01

    There is a pressing need for enhancing the learning environment for students affected by Fetal Alcohol Spectrum Disorders (FASDs). To develop relevant professional learning opportunities for teachers, a logical initial step is to explore the extent to which pre-service teachers accurately understand the unique neuropsychological functioning…

  14. Environmental and urinary markers of prenatal exposure to drinking water disinfection by-products, fetal growth, and duration of gestation in the PELAGIE birth cohort (Brittany, France, 2002-2006).

    PubMed

    Costet, Nathalie; Garlantézec, Ronan; Monfort, Christine; Rouget, Florence; Gagnière, Bertrand; Chevrier, Cécile; Cordier, Sylvaine

    2012-02-15

    Although prenatal exposure to water disinfection by-products does not appear to affect the duration of gestation, its impact on fetal growth remains an open question. The authors studied the associations between prenatal exposure to disinfection by-products and fetal growth restriction (FGR) and preterm birth in the PELAGIE cohort, a French birth cohort comprising 3,421 pregnant women recruited between 2002 and 2006. Exposure was assessed by estimating levels of trihalomethanes (THMs) in tap water during pregnancy and maternal water use and by measuring maternal urinary levels of trichloroacetic acid (TCAA) during early pregnancy in a nested case-control design that compared 174 FGR cases, 114 preterm births, and 399 controls. Higher uptake of THMs (especially brominated THMs) was associated with a higher risk of FGR. Women with TCAA detected in their urine (>0.01 mg/L) had a higher risk of FGR than those with TCAA levels below the detection limit (adjusted odds ratio = 1.8, 95% confidence interval: 0.9, 3.7) and had an odds ratio for preterm birth below 1 (adjusted odds ratio = 0.8, 95% confidence interval: 0.3, 2.6). Results from this prospective study, the first to use a biomarker of disinfection by-product exposure, suggest that prenatal exposure affects fetal growth, but the causal agent or agents remain to be identified.

  15. Prenatal Exposure to Perfluorocarboxylic Acids (PFCAs) and Fetal and Postnatal Growth in the Taiwan Maternal and Infant Cohort Study

    PubMed Central

    Wang, Yan; Adgent, Margaret; Su, Pen-Hua; Chen, Hsiao-Yen; Chen, Pau-Chung; Hsiung, Chao A.; Wang, Shu-Li

    2016-01-01

    Background: Perfluorocarboxylic acids (PFCAs) are environmentally and biologically persistent synthetic chemicals. PFCAs include perfluorooctanoic acid (PFOA; C8) and long-chain PFCAs (C9–C20). Studies examining long-chain PFCAs and fetal and postnatal growth are limited. Objectives: We investigated the associations of prenatal exposure to long-chain PFCAs with fetal and postnatal growth. Methods: For 223 Taiwanese mothers and their term infants, we measured PFOA and four long-chain PFCAs (ng/mL) in third-trimester maternal serum; infant weight (kg), length and head circumference (cm) at birth; and childhood weight and height at approximately 2, 5, 8, and 11 years of age. For each sex, we used multivariable linear regression to examine associations between ln-transformed prenatal PFCAs and continuous infant measures, and logistic regression to examine small for gestational age (SGA). Linear mixed models were applied to prenatal PFCAs and childhood weight and height z-scores. Results: In girls, prenatal perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) concentrations were inversely associated with birth weight [e.g., βbirth weight (kg) = –0.06, 95% CI: –0.11, –0.01 per 1 ln-unit PFUnDA increase]; prenatal PFDeA and PFUnDA were associated with elevated odds of SGA; and PFDeA, PFUnDA, and PFDoDA were associated with lower average childhood height z-score. In boys, prenatal PFNA, and PFDoDA were associated with reductions in height at certain ages in childhood, but not with size at birth. Conclusions: Prenatal exposure to long-chain PFCAs may interfere with fetal and childhood growth in girls, and childhood growth in boys. Citation: Wang Y, Adgent M, Su PH, Chen HY, Chen PC, Hsiung CA, Wang SL. 2016. Prenatal exposure to perfluorocarboxylic acids (PFCAs) and fetal and postnatal growth in the Taiwan Maternal and Infant Cohort Study. Environ Health Perspect 124:1794–1800;

  16. Insulin-like growth factor I receptors of fetal brain are enriched in nerve growth cones and contain a beta-subunit variant.

    PubMed Central

    Quiroga, S; Garofalo, R S; Pfenninger, K H

    1995-01-01

    Nerve growth cones isolated from fetal rat brain are highly enriched in a 97-kDa glycoprotein, termed beta gc, that comigrates with the beta subunit of the IGF-I receptor upon two-dimensional PAGE and is disulfide-linked to this receptor's alpha subunit. Antibodies prepared to a conserved domain shared by the insulin and IGF-I receptor beta subunits (AbP2) or to beta gc were used to study receptor distribution further. Subcellular fractionation of the fetal brain segregated most AbP2 immunoreactivity away from growth cones, whereas most beta gc immunoreactivity copurified with growth cones. Experiments involving ligand-activated receptor autophosphorylation confirmed the concentration of IGF-I but not of insulin receptors in growth cone fractions. These results indicate the enrichment of IGF-I receptors in (presumably axonal) growth cones of the differentiating neuron. Furthermore, the segregation of beta gc from AbP2 immunoreactivity suggests that such neurons express an immunochemically distinct variant of the IGF-I receptor beta subunit at the growth cone. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7753803

  17. Fetal malnutrition: a possible cause of the fetal alcohol syndrome.

    PubMed

    Lin, G W

    1981-01-01

    The effects of ethanol ingestion during pregnancy on total folate levels in fetal tissues and on the concentrations of free amino acids in fetal and maternal plasma were examined in the rat. No differences were observed between the ethanol-fed and the control groups in total folates in fetal brain and liver. However, the concentration of fetal plasma histidine was reduced by 50% as a result of maternal ethanol consumption; the maternal plasma histidine level was not affected. It is suggested that fetal malnutrition in an essential amino acid, histidine, could impair fetal protein synthesis producing the fetal alcohol syndrome. PMID:7312865

  18. Overexpression of transforming growth factor-beta1 in fetal monkey lung results in prenatal pulmonary fibrosis.

    PubMed

    Tarantal, A F; Chen, H; Shi, T T; Lu, C-H; Fang, A B; Buckley, S; Kolb, M; Gauldie, J; Warburton, D; Shi, W

    2010-10-01

    Altered transforming growth factor (TGF)-β expression levels have been linked to a variety of human respiratory diseases, including bronchopulmonary dysplasia and pulmonary fibrosis. However, a causative role for aberrant TGF-β in neonatal lung diseases has not been defined in primates. Exogenous and transient TGF-β1 overexpression in fetal monkey lung was achieved by transabdominal ultrasound-guided fetal intrapulmonary injection of adenoviral vector expressing TGF-β1 at the second or third trimester of pregnancy. The lungs were then harvested near term, and fixed for histology and immunohistochemistry. Lung hypoplasia was observed where TGF-β1 was overexpressed during the second trimester. The most clearly marked phenotype consisted of severe pulmonary and pleural fibrosis, which was independent of the gestational time point when TGF-β1 was overexpressed. Increased cell proliferation, particularly in α-smooth muscle actin-positive myofibroblasts, was detected within the fibrotic foci. But epithelium to mesenchyme transdifferentiation was not detected. Massive collagen fibres were deposited on the inner and outer sides of the pleural membrane, with an intact elastin layer in the middle. This induced fibrotic pathology persisted even after adenoviral-mediated TGF-β1 overexpression was no longer evident. Therefore, overexpression of TGF-β1 within developing fetal monkey lung results in severe and progressive fibrosis in lung parenchyma and pleural membrane, in addition to pulmonary hypoplasia.

  19. Cadmium-induced neural tube defects and fetal growth restriction: Association with disturbance of placental folate transport.

    PubMed

    Zhang, Gui-Bin; Wang, Hua; Hu, Jun; Guo, Min-Yin; Wang, Ying; Zhou, Yan; Yu, Zhen; Fu, Lin; Chen, Yuan-Hua; Xu, De-Xiang

    2016-09-01

    Previous studies found that maternal Cd exposure on gestational day (GD)9 caused forelimb ectrodactyly and tail deformity, the characteristic malformations. The aim of the present study was to investigate whether maternal Cd exposure on GD8 induces fetal neural tube defects (NTDs). Pregnant mice were intraperitoneally injected with CdCl2 (2.5 or 5.0mg/kg) on GD8. Neither forelimb ectrodactyly nor tail deformity was observed in mice injected with CdCl2 on GD8. Instead, maternal Cd exposure on GD8 resulted in the incidence of NTDs. Moreover, maternal Cd exposure on GD8 resulted in fetal growth restriction. In addition, maternal Cd exposure on GD8 reduced placental weight and diameter. The internal space of maternal and fetal blood vessels in the labyrinth layer was decreased in the placentas of mice treated with CdCl2. Additional experiment showed that placental PCFT protein and mRNA, a critical folate transporter, was persistently decreased when dams were injected with CdCl2 on GD8. Correspondingly, embryonic folate content was markedly decreased in mice injected with CdCl2 on GD8, whereas Cd had little effect on folate content in maternal serum. Taken together, these results suggest that maternal Cd exposure during organogenesis disturbs transport of folate from maternal circulation to the fetuses through down-regulating placental folate transporters. PMID:27417525

  20. Relationship between fetal growth and the development of asthma and atopy in childhood

    PubMed Central

    Leadbitter, P.; Pearce, N.; Cheng, S.; Sears, M.; Holdaway, M; Flannery, E.; Herbison, G; Beasley, R.

    1999-01-01

    BACKGROUND—A study was undertaken to investigate the relationship between birth anthropometric measures and the subsequent development of asthma, airway hyperresponsiveness, and atopy in later childhood.
METHODS—A longitudinal study was performed on 734 subjects (71%) from a cohort of children born in Dunedin, New Zealand in 1972-73. The birth anthropometric measures were available from hospital records and the main outcome measures of reported asthma, skin prick tests, and methacholine hyperresponsiveness were measured at the age of 13 years, while the serum total IgE was measured at 11years.
RESULTS—After adjustment for other factors, infants with a larger head circumference at birth tended to have higher serum total IgE at 11 years of age (p = 0.02) but IgE was not associated significantly with birth length or birth weight. The adjusted odds ratio for raised serum IgE (>150 IU/ml) in infants with a head circumference of 37 cm or more was 3.4 (95% CI 1.4 to 7.9). In contrast, recent asthma symptoms were positively associated with birth length (p= 0.04) but not with head circumference. The adjusted odds ratio for asthma in the previous two years in infants with a birth length of 56 cm or more was 6.4 (95% CI 2.0 to 19.8). Infants with a birth weight of less than 3.0 kg had an odds ratio for reported asthma of 0.2 (95% CI 0.0-0.6). There were no significant associations of any of the birth parameters with skin prick positivity, reported hay fever, or eczema.
CONCLUSIONS—These results suggest that increased fetal growth is related to an increased risk of asthma and atopy in childhood. The precision of the findings is limited by the small numbers in the extreme categories of each birth parameter, but the results are consistent with intrauterine programming of the developing respiratory and immune systems.

 PMID:10491453

  1. Association between reduced stillbirth rates in England and regional uptake of accreditation training in customised fetal growth assessment

    PubMed Central

    Gardosi, Jason; Giddings, Sally; Clifford, Sally; Wood, Lynne; Francis, André

    2013-01-01

    Objective To assess the effect that accreditation training in fetal growth surveillance and evidence-based protocols had on stillbirth rates in England and Wales. Design Analysis of mortality data from Office of National Statistics. Setting England and Wales, including three National Health Service (NHS) regions (West Midlands, North East and Yorkshire and the Humber) which between 2008 and 2011 implemented training programmes in customised fetal growth assessment. Population Live births and stillbirths in England and Wales between 2007 and 2012. Main outcome measure Stillbirth. Results There was a significant downward trend (p=0.03) in stillbirth rates between 2007 and 2012 in England to 4.81/1000, the lowest rate recorded since adoption of the current stillbirth definition in 1992. This drop was due to downward trends in each of the three English regions with high uptake of accreditation training, and led in turn to the lowest stillbirth rates on record in each of these regions. In contrast, there was no significant change in stillbirth rates in the remaining English regions and Wales, where uptake of training had been low. The three regions responsible for the record drop in national stillbirth rates made up less than a quarter (24.7%) of all births in England. The fall in stillbirth rate was most pronounced in the West Midlands, which had the most intensive training programme, from the preceding average baseline of 5.73/1000 in 2000–2007 to 4.47/1000 in 2012, a 22% drop which is equivalent to 92 fewer deaths a year. Extrapolated to the whole of the UK, this would amount to over 1000 fewer stillbirths each year. Conclusions A training and accreditation programme in customised fetal growth assessment with evidence-based protocols was associated with a reduction in stillbirths in high-uptake areas and resulted in a national drop in stillbirth rates to their lowest level in 20 years. PMID:24345900

  2. Metabolomic analysis reveals differences in umbilical vein plasma metabolites between normal and growth-restricted fetal pigs during late gestation.

    PubMed

    Lin, Gang; Liu, Chuang; Feng, Cuiping; Fan, Zhiyong; Dai, Zhaolai; Lai, Changhua; Li, Zhen; Wu, Guoyao; Wang, Junjun

    2012-06-01

    Intrauterine growth restriction (IUGR) remains a major problem for both human health and animal production due to its association with high rates of neonatal morbidity and mortality, low efficiency of food utilization, permanent adverse effects on postnatal growth and development, and long-term health and productivity of the offspring. However, the underlying mechanisms for IUGR are largely unknown. In this study, one IUGR fetus and one normal body weight (NBW) fetus were obtained from each of 9 gilts at each of 2 gestational ages (d 90 and 110). Metabolomes of umbilical vein plasma in IUGR and NBW fetuses were determined by MS, while hormones, amino acids, and related metabolites in maternal and fetal plasma were measured using assay kits and chromatographic methods. Metabolites (including glucose, urea, ammonia, amino acids, and lipids) in umbilical vein plasma exhibited a cluster of differences between IUGR and NBW fetuses on d 90 and 110 of gestation. These changes in the IUGR group are associated with disorders of nutrient and energy metabolism as well as endocrine imbalances, which may contribute to the retardation of fetal growth and development. The findings help provide information regarding potential mechanisms responsible for IUGR in swine and also have important implications for the design of effective strategies to prevent, diagnose, and treat IUGR in other mammalian species, including humans.

  3. Fetal, infant, and childhood growth are predictors of coronary heart disease, diabetes, and hypertension in adult men and women.

    PubMed Central

    Osmond, C; Barker, D J

    2000-01-01

    Many human fetuses have to adapt to a limited supply of nutrients. In doing so they permanently change their structure and metabolism. These programmed changes may be the origins of a number of diseases in later life, including coronary heart disease, hypertension, and noninsulin- dependent diabetes. We review epidemiologic studies in which the incidence of these diseases has been related to the recorded, early growth of individuals, while considering factors in the adult lifestyle, such as obesity and socioeconomic status. We discuss possible mechanisms. For hypertension these mechanisms include placentation, maternal blood pressure, fetal undernutrition; childhood growth, activation of the renin-angiotensin system, renal structure, programming of the hypothalamic-pituitary-adrenal axis, vascular structure, and sympathetic nervous activity. For noninsulin-dependent diabetes we discuss mechanisms concerning both insulin resistance and insulin deficiency. We include a review of evidence for the programming of serum cholesterol and clotting factor concentrations. We address the timing of critical windows for coronary heart disease, reviewing studies that allow assessment of the relative importance of fetal, infant, and childhood growth. We argue for a research strategy that combines clinical, animal, and epidemiological studies. PMID:10852853

  4. Effect of nebivolol treatment during pregnancy on the genital circulation, fetal growth and postnatal development in the Wistar rat.

    PubMed

    Altoama, Kassem; Yassine Mallem, Mohamed; Thorin, Chantal; Betti, Eric; Desfontis, Jean-Claude

    2015-07-01

    The aim of study was to evaluate the effects of nebivolol, a cardioselective beta-1 adrenergic receptor blocker of the third generation with vasodilatory properties, vs. bisoprolol on the genital circulation, uterine vasculature, fetal growth and postnatal development in pregnant Wistar rats. Non invasive measurements of systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR), and invasive measurement of genital blood flow (GBF) were taken in pregnant rats, by tail cuff and transonic probe methods respectively, after an oral treatment by gastric gavage with nebivolol (8mg/kg/day) or bisoprolol (10mg/kg/day) from day 11 to day 18 of pregnancy. Other morphometrical and histological measurements were performed on the ovarian and uterine arteries to evaluate the effect of nebivolol on the uterine vasculature. Furthermore, postnatal mortality and pup growth were recorded. The data demonstrated that nebivolol (compared with bisoprolol) induced a significant decrease in SBP, HR and GBF while DBP remained unchanged. Moreover, nebivolol increased the diameter and the length of ovarian and uterine arteries and the number of uterine artery segmental branches. The results also showed that the body weight gain of newborns in the nebivolol group was significantly lower vs. bisoprolol and vs. control with a higher mortality rate. The nebivolol action is not only limited to its favorable hemodynamic effects represented by a decrease in blood pressure, but it also produces adverse effects on fetal growth and postnatal development that may limit its therapeutic use in females during pregnancy.

  5. Role of Insulinlike Growth Factor 1 in Fetal Development and in the Early Postnatal Life of Premature Infants.

    PubMed

    Hellström, Ann; Ley, David; Hansen-Pupp, Ingrid; Hallberg, Boubou; Ramenghi, Luca A; Löfqvist, Chatarina; Smith, Lois E H; Hård, Anna-Lena

    2016-09-01

    The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and development of most organs especially the central nervous system including the retina. Glucose metabolism in the developing brain is controlled by IGF-1 which also stimulates differentiation and prevents apoptosis. Serum concentrations of IGF-1 decrease to very low levels after very preterm birth and remain low for most of the perinatal development. Strong correlations have been found between low neonatal serum concentrations of IGF-1 and poor brain and retinal growth as well as poor general growth with multiorgan morbidities, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. Experimental and clinical studies indicate that early supplementation with IGF-1 can improve growth in catabolic states and reduce brain injury after hypoxic/ischemic events. A multicenter phase II study is currently underway to determine whether intravenous replacement of human recombinant IGF-1 up to normal intrauterine serum concentrations can improve growth and development and reduce prematurity-associated morbidities.

  6. Role of Insulinlike Growth Factor 1 in Fetal Development and in the Early Postnatal Life of Premature Infants.

    PubMed

    Hellström, Ann; Ley, David; Hansen-Pupp, Ingrid; Hallberg, Boubou; Ramenghi, Luca A; Löfqvist, Chatarina; Smith, Lois E H; Hård, Anna-Lena

    2016-09-01

    The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and development of most organs especially the central nervous system including the retina. Glucose metabolism in the developing brain is controlled by IGF-1 which also stimulates differentiation and prevents apoptosis. Serum concentrations of IGF-1 decrease to very low levels after very preterm birth and remain low for most of the perinatal development. Strong correlations have been found between low neonatal serum concentrations of IGF-1 and poor brain and retinal growth as well as poor general growth with multiorgan morbidities, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. Experimental and clinical studies indicate that early supplementation with IGF-1 can improve growth in catabolic states and reduce brain injury after hypoxic/ischemic events. A multicenter phase II study is currently underway to determine whether intravenous replacement of human recombinant IGF-1 up to normal intrauterine serum concentrations can improve growth and development and reduce prematurity-associated morbidities. PMID:27603537

  7. Amino acid transport systems beta and A in fetal T lymphocytes in intrauterine growth restriction and with tumor necrosis factor-alpha treatment.

    PubMed

    Iruloh, Chibuike G; D'Souza, Stephen W; Fergusson, William D; Baker, Philip N; Sibley, Colin P; Glazier, Jocelyn D

    2009-01-01

    Intrauterine growth restriction (IUGR) is associated with reduced activity of placental amino acid transport systems beta and A. Whether this phenotype is maintained in fetal cells outside the placenta is unknown. In IUGR, cord blood tumor necrosis factor (TNF)-alpha concentrations are raised, potentially influencing amino acid transport in fetal cells. We used fetal T lymphocytes as a model to study systems beta and A amino acid transporters in IUGR compared with normal pregnancy. We also studied the effect of TNF-alpha on amino acid transporter activity. In fetal lymphocytes from IUGR pregnancies, taurine transporter mRNA expression encoding system beta transporter was reduced, but there was no change in system beta activity. No significant differences were observed in system A mRNA expression (encoding SNAT1 and SNAT2) or system A activity between the two groups. After 24 or 48 h TNF-alpha treatment, fetal T lymphocytes from normal pregnancies showed no significant change in system A or system beta activity, although cell viability was compromised. This study represents the first characterization of amino acid transport in a fetal cell outside the placenta in IUGR. We conclude that the reduced amino acid transporter activity found in placenta in IUGR is not a feature of all fetal cells.

  8. Growth and fertilization of porcine fetal oocytes grafted under the renal capsules of nude mice.

    PubMed

    Kaneko, Hiroyuki; Kikuchi, Kazuhiro; Noguchi, Junko

    2016-10-15

    The fetal ovary contains a larger pool of oocytes than the adult ovary, but utilization of the fetal oocytes of large animals has hardly been examined. In this study, we investigated the developmental competence of oocytes grown in host mice harboring ovarian grafts obtained from fetal pigs. Ovarian fragments from fetuses at 55, 70, and 90 days postartificial insemination (dpi) were grafted into ovariectomized nude mice (Crlj:CD1-Foxn1(nu); 55-, 70- and 90-dpi groups, respectively). For comparison, ovarian fragments from 20-day postpartum (dpp) piglets were also grafted (20-dpp group). About 60 days after detection of vaginal opening, the mice were given 62.5 U/mL porcine FSH for 13 days by infusion to enhance their follicular development. In the fetal ovaries before grafting, the percentage of germ cells in primordial follicles (termed primordial oocytes) relative to the total number of germ cells was 0.06% at 55 dpi, 2.4% at 70 dpi, and 7.2% at 90 dpi, but the majority was contained within egg nests. At 20 dpp, primordial oocytes accounted for 91.7% of the total number of germ cells and the rest were mostly in primary follicles. After FSH stimulation of host mice, formation of antral follicles was promoted in the grafts of the 70- and 90-dpi groups as well as the 20-dpp group, but a very small number of antral follicles developed in the 55-dpi group consistent with the lowest (P < 0.05) levels of circulating inhibin in that group. The mean number of full-sized oocytes with meiotic competence recovered per mouse was 6.0 in the 70-dpi, 18.0 in the 90-dpi, and 21.2 in the 20-dpp groups, whereas virtually no oocytes were recovered from mice in the 55-dpi group. Moreover, the mature oocytes in the 70- and 90-dpi groups were fertilized in vitro, as shown by formation of male and female pronuclei, but the percentage of oocytes penetrated by sperm was low in the 70- (49%) and 90-dpi (29%) groups as compared with the 20-dpp group (88%). These results clearly

  9. [Fetal nutrition and future health].

    PubMed

    Henriksen, Tore; Haugen, Guttorm; Bollerslev, Jens; Kolset, Svein Olav; Drevon, Christian A; Iversen, Per Ole; Clausen, Torun

    2005-02-17

    Fetal nutrition may permanently affect physiological properties of the new individual and hence the risk of future disease. Epidemiological studies indicate that fetal nutrition may significantly influence the risk of diabetes, cardiovascular disease, and cancer. Controlled animal studies show that even properties traditionally considered as exclusively genetic, like fur colour, may be modified by altered maternal nutrition. The expression "fetal programming" has been introduced to describe permanent effects of environmental conditions in fetal life. An important mechanism of fetal programming seems to be epigenetic regulation. One example of epigenetic regulation is methylation of the DNA base cytosine in promoter regions of some genes. DNA methylation will lead to decreased gene expression. Over the last two decades, marked changes in dietary habits and other life style features have taken place among young Norwegian women. This is particularly reflected in the increasing prevalence of obesity. Maternal weight and metabolic status is closely associated with the growth and development of the fetus. Thus, diet and physical activity become particularly important aspects of the health of young women.

  10. Intrauterine growth restriction affects the preterm infant's hippocampus.

    PubMed

    Lodygensky, Gregory A; Seghier, Mohammed L; Warfield, Simon K; Tolsa, Cristina Borradori; Sizonenko, Stephane; Lazeyras, François; Hüppi, Petra S

    2008-04-01

    The hippocampus is known to be vulnerable to hypoxia, stress, and undernutrition, all likely to be present in fetal intrauterine growth restriction (IUGR). The effect of IUGR in preterm infants on the hippocampus was studied using 3D magnetic resonance imaging at term-equivalent age Thirteen preterm infants born with IUGR after placental insufficiency were compared with 13 infants with normal intrauterine growth age matched for gestational age. The hippocampal structural differences were defined using voxel-based morphometry and manual segmentation. The specific neurobehavioral function was evaluated by the Assessment of Preterm Infants' Behavior at term and at 24 mo of corrected age by a Bayley Scales of Infant and Toddler Development. Voxel-based morphometry detected significant gray matter volume differences in the hippocampus between the two groups. This finding was confirmed by manual segmentation of the hippocampus with a reduction of hippocampal volume after IUGR. The hippocampal volume reduction was further associated with functional behavioral differences at term-equivalent age in all six subdomains of the Assessment of Preterm Infants' Behavior but not at 24 mo of corrected age. We conclude that hippocampal development in IUGR is altered and might result from a combination of maternal corticosteroid hormone exposure, hypoxemia, and micronutrient deficiency. PMID:18356754

  11. Proto-oncogene c-fos expression in growth regions of fetal bone and mesodermal web tissue.

    PubMed

    Dony, C; Gruss, P

    The phylogenic conservation of the proto-oncogene c-fos suggests that this gene product is required for normal metabolic processes. Investigations into the transcription pattern of c-fos in normal tissues and cells have revealed expression during development, differentiation and growth which is dependent to a large extent on external signals transferred by growth factors. The complex pattern of stage and tissue-specific expression has raised the hypothesis that the c-fos gene product might function in the control of either proliferation or differentiation. However, no detailed analysis is yet available concerning the normal expression of c-fos during embryonic and fetal development. Interestingly, recent data derived from studies in transgenic mice reveal that the biological effect of overexpression of exogenous fos is restricted to the developing bone tissue and T-cell development of the mice, perhaps signifying that these cells represent a physiological target tissue of the proto-oncogene fos. Thus, to gain deeper insight into the functional role of the c-fos gene product during physiological processes, it is a requirement to carry out a detailed analysis of the localization and cell-type specificity of c-fos expression in normal mouse embryos. Using the technique of in situ hybridization, we demonstrate here that stage-specific expression of the proto-oncogene c-fos in mouse embryos is restricted to the perichondrial growth regions of the cartilaginous skeleton. Moreover, we found strong c-fos transcription in web-forming mesodermal cells, which are also characterized by a stage-specific high growth capacity. Our results suggest a tissue-specific regulatory role of c-fos during differentiation-dependent growth processes of fetal bone and mesodermal web tissue.

  12. Affective decision-making on the Iowa gambling task in children and adolescents with fetal alcohol spectrum disorders.

    PubMed

    Kully-Martens, Katrina; Treit, Sarah; Pei, Jacqueline; Rasmussen, Carmen

    2013-02-01

    Individuals with fetal alcohol spectrum disorders (FASD) have difficulties with cognitive-based executive function (EF) tasks. The goal of the present study was to determine if children with FASD have impairments on the Iowa Gambling Task (IGT), which measures affective EF (i.e., decision-making and risk-taking). Individuals with FASD (n = 31) and healthy controls (n = 31), aged 8-17 completed the IGT. Children with FASD were significantly impaired on the IGT compared to controls. Over the course of the task, control scores improved, whereas children with FASD exhibited an overall decrease in scores. Scores increased significantly with age in the control group but did not differ significantly with age for FASD participants. Children with FASD exhibited decision-making and risk-taking impairments on a hot EF task. Children with FASD did not appear to learn from negative experiences and shift to making more positive decisions over time and their performance did not improve with age. The implications of poor task performance and a lack of age-related findings in children with FASD are discussed.

  13. Fetal programming of overweight through the microbiome: boys are disproportionately affected.

    PubMed

    Kozyrskyj, A L; Kalu, R; Koleva, P T; Bridgman, S L

    2016-02-01

    Maternal and childhood obesity in pregnancy are worrisome public health issues facing our world today. New gene sequencing methods have advanced our knowledge of the disruptive effect of birth interventions and postnatal exposures on the maturation of gut microbiota and immunity during infancy. Yet, little is known about the impact of maternal pregnancy overweight on gut microbes and related processes, and how this may affect overweight risk in offspring. To address this gap in knowledge, we surveyed human studies for evidence in children, infants and pregnant women to piece together the limited literature and generate hypotheses for future investigation. From this literature, we learned that higher Lactobacillus yet lower Bacteroides spp. colonization of gut microbiota within 3 months of birth predicted risk for infant and child overweight. The abundance of bifidobacteria and staphylococci also appeared to play a role in the association with overweight, as did infant fecal immunoglobulin A levels, glycoproteins of the gut immune system that are acquired from breast milk and produced by the infant. We proposed that pregnancy overweight influences the compositional structure of gut microbiota in infants through vertical transfer of microbiota and/or their metabolites during pregnancy, delivery and breastfeeding. Finally, we brought forward emerging evidence on sex dimorphism, as well as ethnic and geographic variation, in reported associations between maternal overweight-induced gut microbiota dysbiosis and overweight risk.

  14. Roles of Melatonin in Fetal Programming in Compromised Pregnancies

    PubMed Central

    Chen, Yu-Chieh; Sheen, Jiunn-Ming; Tiao, Miao-Meng; Tain, You-Lin; Huang, Li-Tung

    2013-01-01

    Compromised pregnancies such as those associated with gestational diabetes mellitus, intrauterine growth retardation, preeclampsia, maternal undernutrition, and maternal stress may negatively affect fetal development. Such pregnancies may induce oxidative stress to the fetus and alter fetal development through the epigenetic process that may affect development at a later stage. Melatonin is an oxidant scavenger that reverses oxidative stress during the prenatal period. Moreover, the role of melatonin in epigenetic modifications in the field of developmental programming has been studied extensively. Here, we describe the physiological function of melatonin in pregnancy and discuss the roles of melatonin in fetal programming in compromised pregnancies, focusing on its involvement in redox and epigenetic mechanisms. PMID:23466884

  15. Hypoxia and fetal heart development.

    PubMed

    Patterson, A J; Zhang, L

    2010-10-01

    Fetal hearts show a remarkable ability to develop under hypoxic conditions. The metabolic flexibility of fetal hearts allows sustained development under low oxygen conditions. In fact, hypoxia is critical for proper myocardial formation. Particularly, hypoxia inducible factor 1 (HIF-1) and vascular endothelial growth factor play central roles in hypoxia-dependent signaling in fetal heart formation, impacting embryonic outflow track remodeling and coronary vessel growth. Although HIF is not the only gene involved in adaptation to hypoxia, its role places it as a central figure in orchestrating events needed for adaptation to hypoxic stress. Although "normal" hypoxia (lower oxygen tension in the fetus as compared with the adult) is essential in heart formation, further abnormal hypoxia in utero adversely affects cardiogenesis. Prenatal hypoxia alters myocardial structure and causes a decline in cardiac performance. Not only are the effects of hypoxia apparent during the perinatal period, but prolonged hypoxia in utero also causes fetal programming of abnormality in the heart's development. The altered expression pattern of cardioprotective genes such as protein kinase c epsilon, heat shock protein 70, and endothelial nitric oxide synthase, likely predispose the developing heart to increased vulnerability to ischemia and reperfusion injury later in life. The events underlying the long-term changes in gene expression are not clear, but likely involve variation in epigenetic regulation.

  16. [Nutrition of pregnant women: consequences for fetal growth and adult diseases].

    PubMed

    Weber, M; Ayoubi, J-M; Picone, O

    2015-01-01

    The developmental origins of human adult disease are thought to be secondary to a perturbation of the embryonic or fetal development, which leads to metabolic disorders such as diabetes or hypertension at adulthood. Maternal undernutrition or overnutrition, repeated glucocorticosteroids administered to the mother, or placental dysfunction are the most frequently considered causal factors. Therefore, it is necessary that the pediatrician is aware of these phenomena, as this knowledge may contribute to the prevention of adult diseases. Little is known yet, however, on the pathophysiological or epigenetic mechanisms that lead to theses observations, and more studies are needed both in humans and animal models. PMID:25440770

  17. Fetal programming in meat production.

    PubMed

    Du, Min; Wang, Bo; Fu, Xing; Yang, Qiyuan; Zhu, Mei-Jun

    2015-11-01

    Nutrient fluctuations during the fetal stage affects fetal development, which has long-term impacts on the production efficiency and quality of meat. During the early development, a pool of mesenchymal progenitor cells proliferate and then diverge into either myogenic or adipogenic/fibrogenic lineages. Myogenic progenitor cells further develop into muscle fibers and satellite cells, while adipogenic/fibrogenic lineage cells develop into adipocytes, fibroblasts and resident fibro-adipogenic progenitor cells. Enhancing the proliferation and myogenic commitment of progenitor cells during fetal development enhances muscle growth and lean production in offspring. On the other hand, promoting the adipogenic differentiation of adipogenic/fibrogenic progenitor cells inside the muscle increases intramuscular adipocytes and reduces connective tissue, which improves meat marbling and tenderness. Available studies in mammalian livestock, including cattle, sheep and pigs, clearly show the link between maternal nutrition and the quantity and quality of meat production. Similarly, chicken muscle fibers develop before hatching and, thus, egg and yolk sizes and hatching temperature affect long-term growth performance and meat production of chicken. On the contrary, because fishes are able to generate new muscle fibers lifelong, the impact of early nutrition on fish growth performance is expected to be minor, which requires further studies.

  18. Expression of Nerve Growth Factor (NGF), TrkA, and p75(NTR) in Developing Human Fetal Teeth.

    PubMed

    Mitsiadis, Thimios A; Pagella, Pierfrancesco

    2016-01-01

    Nerve growth factor (NGF) is important for the development and the differentiation of neuronal and non-neuronal cells. NGF binds to specific low- and high-affinity cell surface receptors, respectively, p75(NTR) and TrkA. In the present study, we examined by immunohistochemistry the expression patterns of the NGF, p75(NTR), and TrkA proteins during human fetal tooth development, in order to better understand the mode of NGF signaling action in dental tissues. The results obtained show that these molecules are expressed in a wide range of dental cells of both epithelial and mesenchymal origin during early stages of odontogenesis, as well as in nerve fibers that surround the developing tooth germs. At more advanced developmental stages, NGF and TrkA are localized in differentiated cells with secretory capacities such as preameloblasts/ameloblasts secreting enamel matrix and odontoblasts secreting dentine matrix. In contrast, p75(NTR) expression is absent from these secretory cells and restricted in proliferating cells of the dental epithelium. The temporospatial distribution of NGF and p75(NTR) in fetal human teeth is similar, but not identical, with that observed previously in the developing rodent teeth, thus indicating that the genetic information is well-conserved during evolution. The expression patterns of NGF, p75(NTR), and TrkA during odontogenesis suggest regulatory roles for NGF signaling in proliferation and differentiation of epithelial and mesenchymal cells, as well as in attraction and sprouting of nerve fibers within dental tissues. PMID:27536251

  19. Expression of Nerve Growth Factor (NGF), TrkA, and p75(NTR) in Developing Human Fetal Teeth.

    PubMed

    Mitsiadis, Thimios A; Pagella, Pierfrancesco

    2016-01-01

    Nerve growth factor (NGF) is important for the development and the differentiation of neuronal and non-neuronal cells. NGF binds to specific low- and high-affinity cell surface receptors, respectively, p75(NTR) and TrkA. In the present study, we examined by immunohistochemistry the expression patterns of the NGF, p75(NTR), and TrkA proteins during human fetal tooth development, in order to better understand the mode of NGF signaling action in dental tissues. The results obtained show that these molecules are expressed in a wide range of dental cells of both epithelial and mesenchymal origin during early stages of odontogenesis, as well as in nerve fibers that surround the developing tooth germs. At more advanced developmental stages, NGF and TrkA are localized in differentiated cells with secretory capacities such as preameloblasts/ameloblasts secreting enamel matrix and odontoblasts secreting dentine matrix. In contrast, p75(NTR) expression is absent from these secretory cells and restricted in proliferating cells of the dental epithelium. The temporospatial distribution of NGF and p75(NTR) in fetal human teeth is similar, but not identical, with that observed previously in the developing rodent teeth, thus indicating that the genetic information is well-conserved during evolution. The expression patterns of NGF, p75(NTR), and TrkA during odontogenesis suggest regulatory roles for NGF signaling in proliferation and differentiation of epithelial and mesenchymal cells, as well as in attraction and sprouting of nerve fibers within dental tissues.

  20. Expression of Nerve Growth Factor (NGF), TrkA, and p75NTR in Developing Human Fetal Teeth

    PubMed Central

    Mitsiadis, Thimios A.; Pagella, Pierfrancesco

    2016-01-01

    Nerve growth factor (NGF) is important for the development and the differentiation of neuronal and non-neuronal cells. NGF binds to specific low- and high-affinity cell surface receptors, respectively, p75NTR and TrkA. In the present study, we examined by immunohistochemistry the expression patterns of the NGF, p75NTR, and TrkA proteins during human fetal tooth development, in order to better understand the mode of NGF signaling action in dental tissues. The results obtained show that these molecules are expressed in a wide range of dental cells of both epithelial and mesenchymal origin during early stages of odontogenesis, as well as in nerve fibers that surround the developing tooth germs. At more advanced developmental stages, NGF and TrkA are localized in differentiated cells with secretory capacities such as preameloblasts/ameloblasts secreting enamel matrix and odontoblasts secreting dentine matrix. In contrast, p75NTR expression is absent from these secretory cells and restricted in proliferating cells of the dental epithelium. The temporospatial distribution of NGF and p75NTR in fetal human teeth is similar, but not identical, with that observed previously in the developing rodent teeth, thus indicating that the genetic information is well-conserved during evolution. The expression patterns of NGF, p75NTR, and TrkA during odontogenesis suggest regulatory roles for NGF signaling in proliferation and differentiation of epithelial and mesenchymal cells, as well as in attraction and sprouting of nerve fibers within dental tissues. PMID:27536251

  1. Fetal Alcohol Spectrum Disorder

    ERIC Educational Resources Information Center

    Caley, Linda M.; Kramer, Charlotte; Robinson, Luther K.

    2005-01-01

    Fetal alcohol spectrum disorder (FASD) is a serious and widespread problem in this country. Positioned within the community with links to children, families, and healthcare systems, school nurses are a critical element in the prevention and treatment of those affected by fetal alcohol spectrum disorder. Although most school nurses are familiar…

  2. Folate ameliorates dexamethasone-induced fetal and placental growth restriction potentially via improvement of trophoblast migration.

    PubMed

    Zhou, Linfang; Zhang, Ai; Wang, Kai; Zhou, Qian; Duan, Tao

    2015-01-01

    Overexposure to prenatal dexamethasone (Dex) leads to small placental and fetal size and the alteration of fetal programming. Folate plays important roles in processes associated with successful pregnancy, including angiogenesis and trophoblast invasion. Placental folate transport is altered with prenatal Dex administration. The purpose of this study was to investigate the protective role of maternal folate administration in placentas exposed to Dex. In vitro, four groups of C57BL/6J pregnant mice were utilized: 1) normal drinking water+Saline injection group (NN); 2) normal drinking water+Dex injection group (ND); 3) drinking water with folate+Saline injection group (FN); and 4) drinking water with folate+Dex injection group (FD). In vivo, four treatment groups of the human extravillous trophoblast HTR-8/SVneo cells were classified: 1) control (NN); 2) Dex treatment (ND); 3) folate treatment (FN); and 4) folate and Dex treatment (FD). The results showed the maternal folate increases the placental size, birth weight, and expression of matrix metalloproteinases 9 (MMP9) in a mice model of Dex overexposure. In human extravillous trophoblast HTR8/SVneo, folate ameliorated the Dex-induced supress of cell migration and improved the expression/activity of MMP2 and MMP9. In conclusion, folate might be a potential therapy intervention to reduce the adverse effects of prenatal Dex exposure partially via improved trophoblast migration.

  3. Fetal growth restriction and intra-uterine growth restriction: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians.

    PubMed

    Vayssière, C; Sentilhes, L; Ego, A; Bernard, C; Cambourieu, D; Flamant, C; Gascoin, G; Gaudineau, A; Grangé, G; Houfflin-Debarge, V; Langer, B; Malan, V; Marcorelles, P; Nizard, J; Perrotin, F; Salomon, L; Senat, M-V; Serry, A; Tessier, V; Truffert, P; Tsatsaris, V; Arnaud, C; Carbonne, B

    2015-10-01

    Small for gestational age (SGA) is defined by weight (in utero estimated fetal weight or birth weight) below the 10th percentile (professional consensus). Severe SGA is SGA below the third percentile (professional consensus). Fetal growth restriction (FGR) or intra-uterine growth restriction (IUGR) usually correspond with SGA associated with evidence indicating abnormal growth (with or without abnormal uterine and/or umbilical Doppler): arrest of growth or a shift in its rate measured longitudinally (at least two measurements, 3 weeks apart) (professional consensus). More rarely, they may correspond with inadequate growth, with weight near the 10th percentile without being SGA (LE2). Birthweight curves are not appropriate for the identification of SGA at early gestational ages because of the disorders associated with preterm delivery. In utero curves represent physiological growth more reliably (LE2). In diagnostic (or reference) ultrasound, the use of growth curves adjusted for maternal height and weight, parity and fetal sex is recommended (professional consensus). In screening, the use of adjusted curves must be assessed in pilot regions to determine the schedule for their subsequent introduction at national level. This choice is based on evidence of feasibility and the absence of any proven benefits for individualized curves for perinatal health in the general population (professional consensus). Children born with FGR or SGA have a higher risk of minor cognitive deficits, school problems and metabolic syndrome in adulthood. The role of preterm delivery in these complications is linked. The measurement of fundal height remains relevant to screening after 22 weeks of gestation (Grade C). The biometric ultrasound indicators recommended are: head circumference (HC), abdominal circumference (AC) and femur length (FL) (professional consensus). They allow calculation of estimated fetal weight (EFW), which, with AC, is the most relevant indicator for screening

  4. [The imbalance of metal-containing proteins and free metal ions in the amniotic fluid during fetal growth].

    PubMed

    Pogorelova, T N; Linde, V A; Gunko, V O; Selyutina, S N

    2016-01-01

    The levels of zinc, copper, iron, and magnesium ions, and some of their binding proteins have been investigated in an amniotic fluid under the fetal growth retardation (FGR). FGR, developed under conditions of placental insufficiency, is characterized by a decrease in the content of zinc, iron, and magnesium ions and by an increase in the copper content in the amniotic fluid in the II and III trimesters of pregnancy. During these trimesters the levels of ceruloplasmin, ferritin, and Ca2+,Mg2+-ATPase were lower in FGR, while the level of zinc-a-2-glycoprotein was higher than during the same periods of normal pregnancy. Changes in the parameters studied in the amniotic fluid were associated with developmental disorders of the newborns. These changes obviously have a pathogenetic importance in the development of FGR, and the levels of metal ions and their ratio in the amniotic fluid can be used as markers of the pre- and postnatal pathology.

  5. Effect of a milk-based food supplement on maternal nutritional status and fetal growth in underweight Chilean women.

    PubMed

    Mardones-Santander, F; Rosso, P; Stekel, A; Ahumada, E; Llaguno, S; Pizarro, F; Salinas, J; Vial, I; Walter, T

    1988-03-01

    The effects on pregnancy outcome and maternal iron status of powdered milk (PUR) and a milk-based fortified product (V-N) were compared in a group of underweight gravidas. These take-home products were distributed during regular prenatal visits. Women in the V-N group had greater weight gain (12.29 vs 11.31 kg, p less than 0.05) and mean birth weights (3178 vs 3105 g, p less than 0.05) than those in the PUR group. Values for various indicators of maternal Fe status were also higher in the V-N group. Compared with self-selected noncompliers, similar in all control variables to compliers, children of women who consumed powdered milk or the milk-based fortified product had mean birth weights that were higher by 258 and 335 g, respectively. Data indicate a beneficial effect of the fortified product on both maternal nutritional status and fetal growth. PMID:3279745

  6. Fetal Research

    NASA Astrophysics Data System (ADS)

    Hansen, John T.; Sladek, John R.

    1989-11-01

    This article reviews some of the significant contributions of fetal research and fetal tissue research over the past 20 years. The benefits of fetal research include the development of vaccines, advances in prenatal diagnosis, detection of malformations, assessment of safe and effective medications, and the development of in utero surgical therapies. Fetal tissue research benefits vaccine development, assessment of risk factors and toxicity levels in drug production, development of cell lines, and provides a source of fetal cells for ongoing transplantation trials. Together, fetal research and fetal tissue research offer tremendous potential for the treatment of the fetus, neonate, and adult.

  7. Sildenafil Therapy Normalizes the Aberrant Metabolomic Profile in the Comt−/− Mouse Model of Preeclampsia/Fetal Growth Restriction

    PubMed Central

    Stanley, Joanna L.; Sulek, Karolina; Andersson, Irene J.; Davidge, Sandra T.; Kenny, Louise C.; Sibley, Colin P.; Mandal, Rupasri; Wishart, David S.; Broadhurst, David I.; Baker, Philip N.

    2015-01-01

    Preeclampsia (PE) and fetal growth restriction (FGR) are serious complications of pregnancy, associated with greatly increased risk of maternal and perinatal morbidity and mortality. These complications are difficult to diagnose and no curative treatments are available. We hypothesized that the metabolomic signature of two models of disease, catechol-O-methyl transferase (COMT−/−) and endothelial nitric oxide synthase (Nos3−/−) knockout mice, would be significantly different from control C57BL/6J mice. Further, we hypothesised that any differences in COMT−/− mice would be resolved following treatment with Sildenafil, a treatment which rescues fetal growth. Targeted, quantitative comparisons of serum metabolic profiles of pregnant Nos3−/−, COMT−/− and C57BL/6J mice were made using a kit from BIOCRATES. Significant differences in 4 metabolites were observed between Nos3−/− and C57BL/6J mice (p < 0.05) and in 18 metabolites between C57BL/6J and COMT−/− mice (p < 0.05). Following treatment with Sildenafil, only 5 of the 18 previously identified differences in metabolites (p < 0.05) remained in COMT−/− mice. Metabolomic profiling of mouse models is possible, producing signatures that are clearly different from control animals. A potential new treatment, Sildenafil, is able to normalize the aberrant metabolomic profile in COMT−/− mice; as this treatment moves into clinical trials, this information may assist in assessing possible mechanisms of action. PMID:26667607

  8. Association of in Utero Organophosphate Pesticide Exposure and Fetal Growth and Length of Gestation in an Agricultural Population

    PubMed Central

    Eskenazi, Brenda; Harley, Kim; Bradman, Asa; Weltzien, Erin; Jewell, Nicholas P.; Barr, Dana B.; Furlong, Clement E.; Holland, Nina T.

    2004-01-01

    Although pesticide use is widespread, little is known about potential adverse health effects of in utero exposure. We investigated the effects of organophosphate pesticide exposure during pregnancy on fetal growth and gestational duration in a cohort of low-income, Latina women living in an agricultural community in the Salinas Valley, California. We measured nonspecific metabolites of organophosphate pesticides (dimethyl and diethyl phosphates) and metabolites specific to malathion (malathion dicarboxylic acid), chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridinyl) phosphoro-thioate], and parathion (4-nitrophenol) in maternal urine collected twice during pregnancy. We also measured levels of cholinesterase in whole blood and butyryl cholinesterase in plasma in maternal and umbilical cord blood. We failed to demonstrate an adverse relationship between fetal growth and any measure of in utero organophosphate pesticide exposure. In fact, we found increases in body length and head circumference associated with some exposure measures. However, we did find decreases in gestational duration associated with two measures of in utero pesticide exposure: urinary dimethyl phosphate metabolites [βadjusted = −0.41 weeks per log10 unit increase; 95% confidence interval (CI), −0.75–−0.02; p = 0.02], which reflect exposure to dimethyl organophosphate compounds such as malathion, and umbilical cord cholinesterase (βadjusted = 0.34 weeks per unit increase; 95% CI, 0.13–0.55; p = 0.001). Shortened gestational duration was most clearly related to increasing exposure levels in the latter part of pregnancy. These associations with gestational age may be biologically plausible given that organophosphate pesticides depress cholinesterase and acetylcholine stimulates contraction of the uterus. However, despite these observed associations, the rate of preterm delivery in this population (6.4%) was lower than in a U.S. reference population. PMID:15238287

  9. Platelet-activating factor induces ovine fetal pulmonary venous smooth muscle cell proliferation: role of epidermal growth factor receptor transactivation.

    PubMed

    Zhou, Weilin; Ibe, Basil O; Raj, J Usha

    2007-06-01

    We have previously reported that platelet-activating factor (PAF) is present in very high levels in the ovine fetal lung and circulation and that PAF serves as an important physiological vasoconstrictor of the pulmonary circulation in utero. However, it is not known whether PAF stimulates pulmonary vascular smooth muscle cell (SMC) proliferation. In this study, we used ovine fetal pulmonary venous SMCs as our model system to study the effects and mechanisms of action of PAF on SMC proliferation. We found that PAF induced SMC proliferation in a dose-dependent manner. PAF also stimulated activation of both ERK and p38 but not c-Jun NH(2) terminal kinase (JNK) mitogen-activated protein (MAP) kinase pathways. PAF (10 nM) induced phosphorylation of epidermal growth factor receptor (EGFR). Specific inhibition of EGFR by AG-1478 and by the expression of a dominant-negative EGFR mutant in SMCs attenuated PAF-stimulated cell proliferation. Inhibition of heparin-binding EGF-like growth factor (HB-EGF) release by CRM-197 and inhibition of matrix metalloproteinases (MMP) by GM-6001 abolished PAF-induced MAP kinase activation and cell proliferation. Increased alkaline phosphatase (AP) activity after PAF treatment in AP-HB-EGF fusion construct-transfected SMCs indicated that PAF induced the release of HB-EGF within 1 min. Gelatin zymography data showed that PAF stimulated MMP-2 activity and MMP-9 activity within 1 min. These results suggest that PAF promotes pulmonary vascular SMC proliferation via transactivation of EGFR through MMP activation and HB-EGF, resulting in p38 and ERK activation and that EGFR transactivation is essential for the mitogenic effect of PAF in pulmonary venous SMC. PMID:17322418

  10. Spaceflight and age affect tibial epiphyseal growth plate histomorphometry

    NASA Technical Reports Server (NTRS)

    Montufar-Solis, Dina; Duke, Pauline J.; Durnova, G.

    1992-01-01

    Growth plate histomorphometry of rats flown aboard the Soviet biosatellite Cosmos 2044, a 14-day spaceflight, was compared with that of control groups. In growth plates of flight animals, there was a significant increase in cell number per column and height of the proliferative zone and a reduction in height and cell number in the hypertrophy/calcification zone. No significant differences were found in matrix organization at the ultrastructural level of flight animals, indicating that although spacefligfht continues to affect bone growth of 15-wk-old rats, extracellular matrix is not altered in the same manner as seen previously in younger animals. All groups showed growth plate characteristics attributed to aging: lack of calcification zone, reduced hypertrophy zone, and unraveling of collagen fibrils. Tail-suspended controls did not differ from other controls in any of the parameters measured. The results suggest that growth plates of older rats are less responsive to unloading by spaceflight or suspension than those of younger rats and provide new evidence about the modifying effect of spaceflight on the growth plate.

  11. Fetal alcohol spectrum disorders.

    PubMed

    Dörrie, Nora; Föcker, Manuel; Freunscht, Inga; Hebebrand, Johannes

    2014-10-01

    Prenatal alcohol exposure (PAE) is one of the most prevalent and modifiable risk factors for somatic, behavioral, and neurological abnormalities. Affected individuals exhibit a wide range of such features referred to as fetal alcohol spectrum disorders (FASD). These are characterized by a more or less specific pattern of minor facial dysmorphic features, growth deficiency and central nervous system symptoms. Nevertheless, whereas the diagnosis of the full-blown fetal alcohol syndrome does not pose a major challenge, only a tentative diagnosis of FASD can be reached if only mild features are present and/or maternal alcohol consumption during pregnancy cannot be verified. The respective disorders have lifelong implications. The teratogenic mechanisms induced by PAE can lead to various additional somatic findings and structural abnormalities of cerebrum and cerebellum. At the functional level, cognition, motor coordination, attention, language development, executive functions, memory, social perception and emotion processing are impaired to a variable extent. The long-term development is characterized by disruption and failure in many domains; an age-adequate independency is frequently not achieved. In addition to primary prevention, individual therapeutic interventions and tertiary prevention are warranted; provision of extensive education to affected subjects and their caregivers is crucial. Protective environments are often required to prevent negative consequences such as delinquency, indebtedness or experience of physical/sexual abuse.

  12. Fetal alcohol spectrum disorders.

    PubMed

    Dörrie, Nora; Föcker, Manuel; Freunscht, Inga; Hebebrand, Johannes

    2014-10-01

    Prenatal alcohol exposure (PAE) is one of the most prevalent and modifiable risk factors for somatic, behavioral, and neurological abnormalities. Affected individuals exhibit a wide range of such features referred to as fetal alcohol spectrum disorders (FASD). These are characterized by a more or less specific pattern of minor facial dysmorphic features, growth deficiency and central nervous system symptoms. Nevertheless, whereas the diagnosis of the full-blown fetal alcohol syndrome does not pose a major challenge, only a tentative diagnosis of FASD can be reached if only mild features are present and/or maternal alcohol consumption during pregnancy cannot be verified. The respective disorders have lifelong implications. The teratogenic mechanisms induced by PAE can lead to various additional somatic findings and structural abnormalities of cerebrum and cerebellum. At the functional level, cognition, motor coordination, attention, language development, executive functions, memory, social perception and emotion processing are impaired to a variable extent. The long-term development is characterized by disruption and failure in many domains; an age-adequate independency is frequently not achieved. In addition to primary prevention, individual therapeutic interventions and tertiary prevention are warranted; provision of extensive education to affected subjects and their caregivers is crucial. Protective environments are often required to prevent negative consequences such as delinquency, indebtedness or experience of physical/sexual abuse. PMID:24965796

  13. Sonar biparietal diameter. II. Predictive of three fetal growth patterns leading to a closer assessment of gestational age and neonatal weight.

    PubMed

    Sabbagha, R E; Barton, B A; Barton, F B; Kingas, E; Turner, J H

    1976-10-15

    Serial BPD readings were obtained from 142 normal parturients, with established dates, between 20 to 40 weeks of pregnancy. It is noted that fetal BPD's can be separated into one of three percentile rankings: large (i.e. above the seventy-fifth percentile), average (i.e. twenty-fifth to seventy-fifth percentile), and small (i.e. below the twenty-fifth percentile). In addition, it is shown that, under normal conditions, fetuses intially placed in any one of these cephalic levels will continue to grow within the confines of the same percentile range. This biologic phenomenon has not been previously reported in human fetal growth. It is important because it leads to a closer prediction of fetal age and a better assessment of neonatal weight and outcome.

  14. Maternal blood and hair manganese concentrations, fetal growth, and length of gestation in the ISA cohort in Costa Rica

    PubMed Central

    Mora, Ana M.; van Wendel de Joode, Berna; Mergler, Donna; Córdoba, Leonel; Cano, Camilo; Quesada, Rosario; Smith, Donald R.; Menezes-Filho, José A.; Eskenazi, Brenda

    2014-01-01

    Background Animal studies have shown that both deficiency and excess manganese (Mn) may result in decreased fetal size and weight, but human studies have reported inconsistent results. Methods We examined the association of blood and hair Mn concentrations measured at different times during pregnancy with fetal growth among term births and length of gestation in a cohort of 380 mother-infant pairs living near banana plantations aerially sprayed with Mn-containing fungicides in Costa Rica. We used linear regression and generalized additive models to test for linear and nonlinear associations. Results Mean (± SD) blood Mn concentration was 24.4 ± 6.6 μg/L and geometric mean (geometric SD) hair Mn concentration was 1.8 (3.2) μg/g. Hair Mn concentrations during the second and third trimesters of gestation were positively related to infant chest circumference (β for 10-fold increase = 0.62 cm; 95% CI: 0.16, 1.08; and β = 0.55 cm; 95% CI: −0.16, 1.26, respectively). Similarly, average maternal hair Mn concentrations during pregnancy were associated with increased chest circumference (β for 10-fold increase = 1.19 cm; 95% CI: 0.43, 1.95) in infants whose mothers did not have gestational anemia, but not in infants of mothers who had gestational anemia (β = 0.39 cm; 95% CI: −0.32, 1.10; pINT = 0.14). All these associations were linear. Blood Mn concentrations did not show consistent linear nor nonlinear relationships with any of the birth outcomes. Conclusions Mn plays an important role in fetal development, but the extent to which environmental exposures may cause adverse health effects to the developing fetus is not well understood. Among women living near banana plantations in Costa Rica, we did not observe linear or nonlinear associations of Mn concentrations with lowered birth weight or head circumference, as reported in previous studies. However, we did find positive linear associations between maternal hair Mn concentrations during pregnancy and infant

  15. Estrogen Receptor-β and Fetoplacental Endothelial Prostanoid Biosynthesis: A Link to Clinically Demonstrated Fetal Growth Restriction

    PubMed Central

    Ernst, Linda; Abdallah, Nadine; Chatterton, Robert; Xin, Hong; Monsivais, Diana; Coon, John; Bulun, Serdar E.

    2011-01-01

    Context: Fetal growth restriction (FGR) due to placental dysfunction impacts short- and long-term neonatal outcomes. Abnormal umbilical artery Doppler velocimetry indicating elevated fetoplacental vascular resistance has been associated with fetal morbidity and mortality. Estrogen receptors are regulators of vasomotor tone, and fetoplacental endothelium expresses estrogen receptor-β (ESR2) as its sole estrogen receptor. Objective: Our objective was to elucidate the mechanism whereby ESR2 regulates placental villous endothelial cell prostanoid biosynthesis. Design and Participants: We conducted immunohistochemical analysis of human placental specimens and studies of primary fetoplacental endothelial cells isolated from subjects with uncomplicated pregnancies. Main Outcome Measures: We evaluated in vivo levels of ESR2 and cyclooxygenase-2 (PTGS2) in villous endothelial cells from fetuses with or without FGR and/or abnormal umbilical artery Doppler indices and in vitro effects of ESR2 on prostanoid biosynthetic gene expression. Results: ESR2 and PTGS2 expression were significantly higher within subjects with FGR with abnormal umbilical artery Doppler indices in comparison with controls (P < 0.01). ESR2 knockdown led to decreased cyclooxygenase-1 (PTGS1), PTGS2, prostaglandin F synthase (AKR1C3), and increased prostacyclin synthase (PTGIS), with opposing results found after ESR2 overexpression (P < 0.05). ESR2 mediates prostaglandin H2 substrate availability and, in the setting of differential regulation of AKR1C3 and PTGIS, altered the balance between vasodilatory and vasoconstricting prostanoid production. Conclusions: Higher ESR2 expression in the placental vasculature of FGR subjects with abnormal blood flow is associated with an endothelial cell phenotype that preferentially produces vasoconstrictive prostanoids. Endothelial ESR2 appears to be a master regulator of prostanoid biosynthesis and contributes to high-resistance fetoplacental blood flow, thereby

  16. Cortisol augments synthesis of growth hormone, but does not alter synthesis of prolactin and proopiomelanocortin, in the 120- to 125-day fetal ovine pituitary.

    PubMed

    Miller, W L; Leisti, S

    1984-07-01

    In adult animal pituitaries or in cultured pituitary tumor cells, glucocorticoids are regulators of GH, PRL, and proopiomelancortin (POMC) synthesis. However, ovine fetal plasma cortisol concentrations are low until shortly before parturition, suggesting that cortisol may not normally regulate hormone synthesis in the fetal pituitary. To investigate whether cortisol could affect fetal synthesis of GH, PRL, and POMC, we obtained fetal pituitary tissue from normal fetuses and from fetuses which had received cortisol infusion for 48 h. Tissues were labeled in short term organ culture and the newly synthesized proteins were displayed by two-dimensional gel electrophoresis and autoradiography. Results were quantified by computerized integration of the area and density of the autoradiographic spots after high resolution television scanning. Cortisol infusion augmented synthesis of GH in comparison to controls (P = 0.01), but did not alter PRL synthesis. Cortisol also did not inhibit POMC synthesis in either the anterior pituitary or the neurointermediate lobe. These data suggest that the pituitary-adrenocortical slow feedback inhibition of POMC synthesis is not functional in the ovine fetus at 120 to 125-days gestation, but that pituitary somatotropes are responsive to glucocorticoids at this stage of fetal development. PMID:6734516

  17. Improving metabolic health in obese male mice via diet and exercise restores embryo development and fetal growth.

    PubMed

    McPherson, Nicole O; Bakos, Hassan W; Owens, Julie A; Setchell, Brian P; Lane, Michelle

    2013-01-01

    Paternal obesity is now clearly associated with or causal of impaired embryo and fetal development and reduced pregnancy rates in humans and rodents. This appears to be a result of reduced blastocyst potential. Whether these adverse embryo and fetal outcomes can be ameliorated by interventions to reduce paternal obesity has not been established. Here, male mice fed a high fat diet (HFD) to induce obesity were used, to determine if early embryo and fetal development is improved by interventions of diet (CD) and/or exercise to reduce adiposity and improve metabolism. Exercise and to a lesser extent CD in obese males improved embryo development rates, with increased cell to cell contacts in the compacting embryo measured by E-cadherin in exercise interventions and subsequently, increased blastocyst trophectoderm (TE), inner cell mass (ICM) and epiblast cell numbers. Implantation rates and fetal development from resulting blastocysts were also improved by exercise in obese males. Additionally, all interventions to obese males increased fetal weight, with CD alone and exercise alone, also increasing fetal crown-rump length. Measures of embryo and fetal development correlated with paternal measures of glycaemia, insulin action and serum lipids regardless of paternal adiposity or intervention, suggesting a link between paternal metabolic health and subsequent embryo and fetal development. This is the first study to show that improvements to metabolic health of obese males through diet and exercise can improve embryo and fetal development, suggesting such interventions are likely to improve offspring health.

  18. Indoor exposure and adverse birth outcomes related to fetal growth, miscarriage and prematurity-a systematic review.

    PubMed

    Patelarou, Evridiki; Kelly, Frank J

    2014-06-01

    The purpose of this review was to summarize existing epidemiological evidence of the association between quantitative estimates of indoor air pollution and all-day personal exposure with adverse birth outcomes including fetal growth, prematurity and miscarriage. We carried out a systematic literature search of MEDLINE and EMBASE databases with the aim of summarizing and evaluating the results of peer-reviewed epidemiological studies undertaken in "westernized" countries that have assessed indoor air pollution and all-day personal exposure with specific quantitative methods. This comprehensive literature search identified 16 independent studies which were deemed relevant for further review and two additional studies were added through searching the reference lists of all included studies. Two reviewers independently and critically appraised all eligible articles using the Critical Appraisal Skills Programme (CASP) tool. Of the 18 selected studies, 14 adopted a prospective cohort design, three were case-controls and one was a retrospective cohort study. In terms of pollutants of interest, seven studies assessed exposure to electro-magnetic fields, four studies assessed exposure to polycyclic aromatic hydrocarbons, four studies assessed PM2.5 exposure and three studies assessed benzene, phthalates and noise exposure respectively. Furthermore, 12 studies examined infant growth as the main birth outcome of interest, six examined spontaneous abortion and three studies assessed gestational age at birth and preterm delivery. This survey demonstrates that there is insufficient research on the possible association of indoor exposure and early life effects and that further research is needed. PMID:24896737

  19. For debate: Fetal and early postnatal growth restriction lead to diabetes, the metabolic syndrome and renal failure.

    PubMed

    Hales, C N; Ozanne, S E

    2003-07-01

    We review the progress in testing the thrifty phenotype hypothesis. Many human epidemiological studies both by ourselves and others have confirmed and extended the original observations on which the hypothesis was based. We are not aware of any contradictory findings and we emphasise the strength of the association between birth weight and the subsequent development of the metabolic syndrome. We have worked extensively experimentally to test the hypothesis in a rat model in which pregnant and/or lactating dams are fed a diet moderately restricted in proteins. The range of programming effects that we have discovered in this example of fetal and early postnatal growth restriction is listed and includes changes in hormone receptors, signalling molecules and regulatory enzymes. We have shown the model to develop diabetes, the metabolic syndrome and signs of premature renal failure. We summarise these and other similarities between the phenotype of this model and human Type 2 diabetes and the metabolic syndrome. The number of insults during early development which can lead to a similar outcome is discussed and the suggestion is made that the early life response to stress is limited in its flexibility with outcomes including ageing and decreased longevity. Our preliminary results indicate that some MODY genes could suggest pathways whereby the changes occur and that epigenetic changes during development are involved. We conclude that the way is now clear to discover early human markers of programming by early life growth restriction and to use these to devise strategies for the prevention of Type 2 diabetes.

  20. Indoor Exposure and Adverse Birth Outcomes Related to Fetal Growth, Miscarriage and Prematurity—A Systematic Review

    PubMed Central

    Patelarou, Evridiki; Kelly, Frank J.

    2014-01-01

    The purpose of this review was to summarize existing epidemiological evidence of the association between quantitative estimates of indoor air pollution and all-day personal exposure with adverse birth outcomes including fetal growth, prematurity and miscarriage. We carried out a systematic literature search of MEDLINE and EMBASE databases with the aim of summarizing and evaluating the results of peer-reviewed epidemiological studies undertaken in “westernized” countries that have assessed indoor air pollution and all-day personal exposure with specific quantitative methods. This comprehensive literature search identified 16 independent studies which were deemed relevant for further review and two additional studies were added through searching the reference lists of all included studies. Two reviewers independently and critically appraised all eligible articles using the Critical Appraisal Skills Programme (CASP) tool. Of the 18 selected studies, 14 adopted a prospective cohort design, three were case-controls and one was a retrospective cohort study. In terms of pollutants of interest, seven studies assessed exposure to electro-magnetic fields, four studies assessed exposure to polycyclic aromatic hydrocarbons, four studies assessed PM2.5 exposure and three studies assessed benzene, phthalates and noise exposure respectively. Furthermore, 12 studies examined infant growth as the main birth outcome of interest, six examined spontaneous abortion and three studies assessed gestational age at birth and preterm delivery. This survey demonstrates that there is insufficient research on the possible association of indoor exposure and early life effects and that further research is needed. PMID:24896737

  1. How maternal malnutrition affects linear growth and development in the offspring.

    PubMed

    Papathakis, Peggy C; Singh, Lauren N; Manary, Mark J

    2016-11-01

    Maternal malnutrition is common in the developing world and has detrimental effects on both the mother and infant. Pre-pregnancy nutritional status and weight gain during pregnancy are positively related to fetal growth and development. Internationally, there is no agreement on the method of diagnosis or treatment of moderate or severe malnutrition during pregnancy. Establishing clear guidelines for diagnosis and treatment will be essential in elevating the problem. Possible anthropometric measurements used to detect and monitor maternal malnutrition include pre-pregnancy BMI, weight gain, and mid upper arm circumference. Food supplements have the potential to increase gestational weight gain and energy intake which are positively associated with fetal growth and development. Overall more studies are needed to conclude the impact of food/nutrient supplements on infant growth in undernourished pregnant women in developing countries. Currently, a study underway may provide much needed documentation of the benefits of treating malnutrition in pregnancy.

  2. Studies in Fetal Behavior: Revisited, Renewed, and Reimagined

    PubMed Central

    DiPietro, Janet A.; Costigan, Kathleen A.; Voegtline, Kristin M.

    2016-01-01

    Among the earliest volumes of this Monograph series was a report by Lester Sontag and colleagues, of the esteemed Fels Institute, on the heart rate of the human fetus as an expression of the developing nervous system. Here, some 75 years later, we commemorate this work and provide historical and contemporary context on knowledge regarding fetal development, as well as results from our own research. These are based on synchronized monitoring of maternal and fetal parameters assessed between 24 and 36 weeks gestation on 740 maternal-fetal pairs compiled from eight separate longitudinal studies, which commenced in the early 1990s. Data include maternal heart rate, respiratory sinus arrhythmia, and electrodermal activity and fetal heart rate, motor activity, and their integration. Hierarchical linear modeling of developmental trajectories reveals that the fetus develops in predictable ways consistent with advancing parasympathetic regulation. Findings also include: within-fetus stability (i.e., preservation of rank ordering over time) for heart rate, motor, and coupling measures; a transitional period of decelerating development near 30 weeks gestation; sex differences in fetal heart rate measures but not in most fetal motor activity measures; modest correspondence in fetal neurodevelopment among siblings as compared to unrelated fetuses; and deviations from normative fetal development in fetuses affected by intrauterine growth restriction and other conditions. Maternal parameters also change during this period of gestation and there is evidence that fetal sex and individual variation in fetal neurobehavior influence maternal physiological processes and the local intrauterine context. Results are discussed within the framework of neuromaturation, the emergence of individual differences, and the bidirectional nature of the maternal-fetal relationship. We pose a number of open questions for future research. Although the human fetus remains just out of reach, new

  3. STUDIES IN FETAL BEHAVIOR: REVISITED, RENEWED, AND REIMAGINED.

    PubMed

    DiPietro, Janet A; Costigan, Kathleen A; Voegtline, Kristin M

    2015-09-01

    Among the earliest volumes of this monograph series was a report by Lester Sontag and colleagues, of the esteemed Fels Institute, on the heart rate of the human fetus as an expression of the developing nervous system. Here, some 75 years later, we commemorate this work and provide historical and contemporary context on knowledge regarding fetal development, as well as results from our own research. These are based on synchronized monitoring of maternal and fetal parameters assessed between 24 and 36 weeks gestation on 740 maternal-fetal pairs compiled from eight separate longitudinal studies, which commenced in the early 1990s. Data include maternal heart rate, respiratory sinus arrhythmia, and electrodrmal activity and fetal heartrate, motor activity, and their integration. Hierarchical linear modeling of developmental trajectories reveals that the fetus develops in predictable ways consistent with advancing parasympathetic regulation. Findings also include:within-fetus stability (i.e., preservation of rank ordering over time) for heart rate, motor, and coupling measures; a transitional period of decelerating development near 30 weeks gestation; sex differences in fetal heart rate measures but not in most fetal motor activity measures; modest correspondence in fetal neurodevelopment among siblings as compared to unrelated fetuses; and deviations from normative fetal development in fetuses affected by intrauterine growth restriction and other conditions. Maternal parameters also change during this period of gestation and there is evidence that fetal sex and individual variation in fetal neurobehavior influence maternal physio-logical processes and the local intrauterine context. Results are discussed within the framework of neuromaturation, the emergence of individual differences, and the bidirectional nature of the maternal-fetal relationship.We pose a number of open questions for future research. Although the human fetus remains just out of reach, new

  4. Influence of gestational salt restriction in fetal growth and in development of diseases in adulthood.

    PubMed

    Sakuyama, Hiroe; Katoh, Minami; Wakabayashi, Honoka; Zulli, Anthony; Kruzliak, Peter; Uehara, Yoshio

    2016-01-20

    Recent studies reported the critical role of the intrauterine environment of a fetus in growth or the development of disease in adulthood. In this article we discussed the implications of salt restriction in growth of a fetus and the development of growth-related disease in adulthood. Salt restriction causes retardation of fatal growth or intrauterine death thereby leading to low birth weight or decreased birth rate. Such retardation of growth along with the upregulation of the renin angiotensin system due to salt restriction results in the underdevelopment of cardiovascular organs or decreases the number of the nephron in the kidney and is responsible for onset of hypertension in adulthood. In addition, gestational salt restriction is associated with salt craving after weaning. Moreover, salt restriction is associated with a decrease in insulin sensitivity. A series of alterations in metabolism due to salt restriction are probably mediated by the upregulation of the renin angiotensin system and an epigenetic mechanism including proinflammatory substances or histone methylation. Part of the metabolic disease in adulthood may be programmed through such epigenetic changes. The modification of gene in a fetus may be switched on through environment factors or life style after birth. The benefits of salt restriction have been assumed thus far; however, more precise investigation is required of its influence on the health of fetuses and the onset of various diseases in adulthood.

  5. Growth, nitrogen uptake and flow in maize plants affected by root growth restriction.

    PubMed

    Xu, Liangzheng; Niu, Junfang; Li, Chunjian; Zhang, Fusuo

    2009-07-01

    The objective of the present study was to investigate the influence of a reduced maize root-system size on root growth and nitrogen (N) uptake and flow within plants. Restriction of shoot-borne root growth caused a strong decrease in the absorption of root: shoot dry weight ratio and a reduction in shoot growth. On the other hand, compensatory growth and an increased N uptake rate in the remaining roots were observed. Despite the limited long-distance transport pathway in the mesocotyl with restriction of shoot-borne root growth, N cycling within these plants was higher than those in control plants, implying that xylem and phloem flow velocities via the mesocotyl were considerably higher than in plants with an intact root system. The removal of the seminal roots in addition to restricting shoot-borne root development did not affect whole plant growth and N uptake, except for the stronger compensatory growth of the primary roots. Our results suggest that an adequate N supply to maize plant is maintained by compensatory growth of the remaining roots, increased N uptake rate and flow velocities within the xylem and phloem via the mesocotyl, and reduction in the shoot growth rate.

  6. Increasing fetal ovine number per gestation alters fetal plasma clinical chemistry values.

    PubMed

    Zywicki, Micaela; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

    2016-08-01

    Intrauterine growth restriction (IUGR) is interconnected with developmental programming of lifelong pathophysiology. IUGR is seen in human multifetal pregnancies, with stepwise rises in fetal numbers interfering with placental nutrient delivery. It remains unknown whether fetal blood analyses would reflect fetal nutrition, liver, and excretory function in the last trimester of human or ovine IUGR In an ovine model, we hypothesized that fetal plasma biochemical values would reflect progressive placental, fetal liver, and fetal kidney dysfunction as the number of fetuses per gestation rose. To determine fetal plasma biochemical values in singleton, twin, triplet, and quadruplet/quintuplet ovine gestation, we investigated morphometric measures and comprehensive metabolic panels with nutritional measures, liver enzymes, and placental and fetal kidney excretory measures at gestational day (GD) 130 (90% gestation). As anticipated, placental dysfunction was supported by a stepwise fall in fetal weight, fetal plasma glucose, and triglyceride levels as fetal number per ewe rose. Fetal glucose and triglycerides were directly related to fetal weight. Plasma creatinine, reflecting fetal renal excretory function, and plasma cholesterol, reflecting placental excretory function, were inversely correlated with fetal weight. Progressive biochemical disturbances and growth restriction accompanied the rise in fetal number. Understanding the compensatory and adaptive responses of growth-restricted fetuses at the biochemical level may help explain how metabolic pathways in growth restriction can be predetermined at birth. This physiological understanding is important for clinical care and generating interventional strategies to prevent altered developmental programming in multifetal gestation. PMID:27565903

  7. Increasing fetal ovine number per gestation alters fetal plasma clinical chemistry values.

    PubMed

    Zywicki, Micaela; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

    2016-08-01

    Intrauterine growth restriction (IUGR) is interconnected with developmental programming of lifelong pathophysiology. IUGR is seen in human multifetal pregnancies, with stepwise rises in fetal numbers interfering with placental nutrient delivery. It remains unknown whether fetal blood analyses would reflect fetal nutrition, liver, and excretory function in the last trimester of human or ovine IUGR In an ovine model, we hypothesized that fetal plasma biochemical values would reflect progressive placental, fetal liver, and fetal kidney dysfunction as the number of fetuses per gestation rose. To determine fetal plasma biochemical values in singleton, twin, triplet, and quadruplet/quintuplet ovine gestation, we investigated morphometric measures and comprehensive metabolic panels with nutritional measures, liver enzymes, and placental and fetal kidney excretory measures at gestational day (GD) 130 (90% gestation). As anticipated, placental dysfunction was supported by a stepwise fall in fetal weight, fetal plasma glucose, and triglyceride levels as fetal number per ewe rose. Fetal glucose and triglycerides were directly related to fetal weight. Plasma creatinine, reflecting fetal renal excretory function, and plasma cholesterol, reflecting placental excretory function, were inversely correlated with fetal weight. Progressive biochemical disturbances and growth restriction accompanied the rise in fetal number. Understanding the compensatory and adaptive responses of growth-restricted fetuses at the biochemical level may help explain how metabolic pathways in growth restriction can be predetermined at birth. This physiological understanding is important for clinical care and generating interventional strategies to prevent altered developmental programming in multifetal gestation.

  8. Fetal endocrinology

    PubMed Central

    Kota, Sunil Kumar; Gayatri, Kotni; Jammula, Sruti; Meher, Lalit Kumar; Kota, Siva Krishna; Krishna, S. V. S.; Modi, Kirtikumar D.

    2013-01-01

    Successful outcome of pregnancy depends upon genetic, cellular, and hormonal interactions, which lead to implantation, placentation, embryonic, and fetal development, parturition and fetal adaptation to extrauterine life. The fetal endocrine system commences development early in gestation and plays a modulating role on the various physiological organ systems and prepares the fetus for life after birth. Our current article provides an overview of the current knowledge of several aspects of this vast field of fetal endocrinology and the role of endocrine system on transition to extrauterine life. We also provide an insight into fetal endocrine adaptations pertinent to various clinically important situations like placental insufficiency and maternal malnutrition. PMID:23961471

  9. Fetal thyroid function: diagnosis and management of fetal thyroid disorders.

    PubMed

    Fisher, D A

    1997-03-01

    The fetal hypothalamic-pituitary-thyroid axis develops independently of the maternal axis, but it is dependent on the maternal-placental system for adequate supply of iodide substrate. This iodide is supplied by direct transfer of maternal plasma iodide and by placental deiodination of T4. In addition, although placental transport of iodothyronines is limited, significant maternal-fetal transfer of T4 occurs, accounting for approximately 30% of the average 10 ug/dL serum-T4 concentration in fetal-cord blood at term. Current information suggests that this maternal contribution to the fetal-T4 levels is important for normal fetal maturation, particularly of the central nervous system. Combined maternal-fetal hypothyroxinemia can lead to irreversible fetal central nervous system damage. The timing of this fetal T4 dependency is not clear. It may be important in the first half of gestation, before the fetal thyroid gland is capable of T4 production, as well as the latter half of gestation when thyroid hormone effects on multiple organ systems are developing. Management of fetal thyroid dysfunction requires normalization of maternal serum T4 concentrations, avoidance or careful monitoring of potentially goitrogenic drug effects in the fetus, and in some instances, direct or indirect fetal therapy. In most cases fetal hypothyroidism is sporadic and undetected, and prognosis for normal growth and development is excellent if the mother is euthyroid and the hypothyroid state is detected and adequately treated at birth. Fetal treatment by intraamniotic thyroxine injection has been provided in cases of inadvertent maternal radioiodine treatment of Graves' disease between 10 and 20 weeks gestation and for fetal goiter detected by ultrasound. Effective treatment of fetal hyperthyroidism in pregnant women with high titers of thyroid stimulating autoantibody is possible by judicious administration of antithyroid drugs to the mother. Management of the hyperthyroid state in the

  10. Effects of Low-Dose Drinking Water Arsenic on Mouse Fetal and Postnatal Growth and Development

    PubMed Central

    Kozul-Horvath, Courtney D.; Zandbergen, Fokko; Jackson, Brian P.; Enelow, Richard I.; Hamilton, Joshua W.

    2012-01-01

    Background Arsenic (As) exposure is a significant worldwide environmental health concern. Chronic exposure via contaminated drinking water has been associated with an increased incidence of a number of diseases, including reproductive and developmental effects. The goal of this study was to identify adverse outcomes in a mouse model of early life exposure to low-dose drinking water As (10 ppb, current U.S. EPA Maximum Contaminant Level). Methodology and Findings C57B6/J pups were exposed to 10 ppb As, via the dam in her drinking water, either in utero and/or during the postnatal period. Birth outcomes, the growth of the F1 offspring, and health of the dams were assessed by a variety of measurements. Birth outcomes including litter weight, number of pups, and gestational length were unaffected. However, exposure during the in utero and postnatal period resulted in significant growth deficits in the offspring after birth, which was principally a result of decreased nutrients in the dam's breast milk. Cross-fostering of the pups reversed the growth deficit. Arsenic exposed dams displayed altered liver and breast milk triglyceride levels and serum profiles during pregnancy and lactation. The growth deficits in the F1 offspring resolved following separation from the dam and cessation of exposure in male mice, but did not resolve in female mice up to six weeks of age. Conclusions/Significance Exposure to As at the current U.S. drinking water standard during critical windows of development induces a number of adverse health outcomes for both the dam and offspring. Such effects may contribute to the increased disease risks observed in human populations. PMID:22693606

  11. Strength of Rocks Affected by Deformation Enhanced Grain Growth

    NASA Astrophysics Data System (ADS)

    Kellermann Slotemaker, A.; de Bresser, H.; Spiers, C.

    2005-12-01

    One way of looking into the possibility of long-term strength changes in the lithosphere is to study transient effects resulting from modifications of the microstructure of rocks. It is generally accepted that mechanical weakening may occur due to progressive grain size refinement resulting from dynamic recrystallization. A decrease in grain size may induce a switch from creep controlled by grain size insensitive dislocation mechanisms to creep governed by grain size sensitive (GSS) mechanisms involving diffusion and grain boundary sliding processes. This switch forms a well-known scenario to explain localization in the lithosphere. However, fine-grained rocks in localized deformation zones are prone to grain coarsening due to surface energy driven grain boundary migration (SED-GBM). This might harden the rock, affecting its role in localizing strain in the long term. The question has arisen if grain growth by SED-GBM in a rock deforming in the GSS creep field can be significantly affected by strain. The broad aim of this study is to shed more light onto this. We have experimentally investigated the microstructural and strength evolution of fine-grained (~0.6 μm) synthetic forsterite and Fe-bearing olivine aggregates that coarsen in grain size while deforming by GSS creep at elevated pressure (600 MPa) and temperature (850-1000 °C). The materials were prepared by `sol-gel' method and contained 0.3-0.5 wt% water and 5-10 vol% enstatite. We performed i) static heat treatment tests of various time durations involving hot isostatic pressing (HIP), and ii) heat treatment tests starting with HIP and continuing with deformation up to 45% axial strain at strain rates in the range 4x10-7 - 1x10-4 s-1. Microstructures were characterized by analyzing full grain size distributions and textures using SEM/EBSD. In addition to the experiments, we studied microstructural evolution in simple two-dimensional numerical models, combining deformation and SED-GBM by means of the

  12. Similar photoperiod-related birth seasonalities among professional baseball players and lesbian women with an opposite seasonality among gay men: Maternal melatonin may affect fetal sexual dimorphism.

    PubMed

    Marzullo, Giovanni

    2014-05-30

    Based on pre-mid-20th-century data, the same photoperiod-related birth seasonality previously observed in schizophrenia was also recently found in neural-tube defects and in extreme left-handedness among professional baseball players. This led to a hypothesis implicating maternal melatonin and other mediators of sunlight actions capable of affecting 4th-embryonic-week developments including neural-tube closure and left-right differentiation of the brain. Here, new studies of baseball players suggest that the same sunlight actions could also affect testosterone-dependent male-female differentiation in the 4-month-old fetus. Independently of hand-preferences, baseball players (n=6829), and particularly the stronger hitters among them, showed a unique birth seasonality with an excess around early-November and an equally significant deficit 6 months later around early-May. In two smaller studies, north-American and other northern-hemisphere born lesbians showed the same strong-hitter birth seasonality while gay men showed the opposite seasonality. The sexual dimorphism-critical 4th-fetal-month testosterone surge coincides with the summer-solstice in early-November births and the winter-solstice in early-May births. These coincidences are discussed and a "melatonin mechanism" is proposed based on evidence that in seasonal breeders maternal melatonin imparts "photoperiodic history" to the newborn by direct inhibition of fetal testicular testosterone synthesis. The present effects could represent a vestige of this same phenomenon in man.

  13. Similar photoperiod-related birth seasonalities among professional baseball players and lesbian women with an opposite seasonality among gay men: Maternal melatonin may affect fetal sexual dimorphism.

    PubMed

    Marzullo, Giovanni

    2014-05-30

    Based on pre-mid-20th-century data, the same photoperiod-related birth seasonality previously observed in schizophrenia was also recently found in neural-tube defects and in extreme left-handedness among professional baseball players. This led to a hypothesis implicating maternal melatonin and other mediators of sunlight actions capable of affecting 4th-embryonic-week developments including neural-tube closure and left-right differentiation of the brain. Here, new studies of baseball players suggest that the same sunlight actions could also affect testosterone-dependent male-female differentiation in the 4-month-old fetus. Independently of hand-preferences, baseball players (n=6829), and particularly the stronger hitters among them, showed a unique birth seasonality with an excess around early-November and an equally significant deficit 6 months later around early-May. In two smaller studies, north-American and other northern-hemisphere born lesbians showed the same strong-hitter birth seasonality while gay men showed the opposite seasonality. The sexual dimorphism-critical 4th-fetal-month testosterone surge coincides with the summer-solstice in early-November births and the winter-solstice in early-May births. These coincidences are discussed and a "melatonin mechanism" is proposed based on evidence that in seasonal breeders maternal melatonin imparts "photoperiodic history" to the newborn by direct inhibition of fetal testicular testosterone synthesis. The present effects could represent a vestige of this same phenomenon in man. PMID:24612972

  14. Myosin helical pitch angle as a quantitative imaging biomarker for characterization of cardiac programming in fetal growth restriction measured by polarization second harmonic microscopy

    NASA Astrophysics Data System (ADS)

    Amat-Roldan, I.; Psilodimitrakopoulos, S.,; Eixarch, E.,; Torre, I.; Wotjas, B.; Crispi, F.; Figueras, F.; Artigas, D.,; Loza-Alvarez, P.; Gratacos, E.,

    2009-07-01

    Fetal growth restriction (FGR) has recently shown a strong association with cardiac programming which predisposes to cardiovascular mortality in adulthood. Polarization Second Harmonic Microscopy can quantify molecular architecture changes with high sensitivity in cardiac myofibrils. In this work, we use myosin helical pitch angle as an example to quantify such alterations related to this high risk population. Importantly, this shows a potential use of the technique as an early diagnostic tool and an alternative method to understand pathophysiological processes.

  15. Factors Affecting Growth of Pinus radiata in Chile

    NASA Astrophysics Data System (ADS)

    Alvarez-Munoz, Jose Santos

    The Chilean forestry industry is based on hundreds of thousands of hectares of Pinus radiata plantations that have been established in a variety of soil and climate conditions. This approach has resulted in highly variable plantation productivity even when the best available technology was used. Little information is known about the ecophysiology basis for this variability. We explored the spatial and temporal variation of stand growth in Chile using a network of permanent sample plots from Modelo Nacional de Simulacion de Pino radiata. We hypothesized that the climate would play an important role in the annual variations in productivity. To answer these questions we developed the following projects: (1) Determination of site resource availability from historical data from automatic weather stations (rainfall, temperatures) and a geophysical model for solar irradiation, (2) Determination of peak annual leaf area index (LAI) for selected permanent sample plots using remote sensing technologies, (3) Analysis of soil, climate, canopy and stand factors affecting the Pinus radiata plantation growth and the use efficiency of site resources. For project 1, we estimated solar irradiation using the r.sun , Hargreaves-Samani (HS), and Bristow-Campbell (BC) models and validated model estimates with observations from weather stations. Estimations from a calibrated r.sun model accounted for 94% of the variance (r2=0.94) in monthly mean measured values. The r.sun model performed quite well for a wide range of Chilean conditions when compared with the HS and BC models. Our estimates of global irradiation may be improved with better estimates of cloudiness as they become available. Our model was able to provide spatial estimates of daily, weekly, monthly and yearly solar irradiation. For project 2, we estimated the inter-annual variation of LAI (Leaf Area Index), using remote sensing technologies. We determined LAI using Landsat Thematic Mapper (TM) data covering a 5 year period

  16. Spontaneous intra-uterine growth restriction modulates the endocrine status and the developmental expression of genes in porcine fetal and neonatal adipose tissue.

    PubMed

    Gondret, Florence; Père, Marie-Christine; Tacher, Sandrine; Daré, Sophie; Trefeu, Christine; Le Huërou-Luron, Isabelle; Louveau, Isabelle

    2013-12-01

    Low birth weight is correlated with low adiposity at birth, a phenotype that influences neonatal survival and later adiposity. A better understanding of events affecting the fetal adipose tissue development and its functionality around birth is thus needed. This study was undertaken to examine the impact of spontaneous intra-uterine growth restriction (IUGR) on circulating concentrations of hormones and nutrients together with the developmental expression patterns of various genes in subcutaneous adipose tissue of pig fetus during the last third of pregnancy and just after birth. At 71 and 112 days post-conception and 2 days postnatal, pairs of same-sex piglets were chosen within litters to have either a medium (MBW) or a low (LBW) weight (n=6 pairs at each stage). The results indicate that IUGR counteracts the temporal fall of DLK1 gene expression in developing adipose tissue across gestation. It also attenuates the time-dependent increase in expression levels of many genes promoting adipocyte differentiation (PPARG, CEBPA) and lipogenesis (LPL, SREBF1, FASN, FABP4). Opposite responses to IUGR were observed for the IGF system, so that IGF1 mRNA levels were lower (P<0.001) but IGF2 mRNA levels were greater in adipose tissue of LBW piglets compared with MBW piglets. The plasma insulin concentration and the mRNA levels of insulin receptor (INSR) and insulin-responsive glucose transporter (GLUT4) in adipose tissue were also greater in LBW piglets at day 2 postnatal. The data indicate that IUGR delays the normal ontogeny of adipose tissue across gestation and affects the insulin and IGF axes around birth.

  17. Programming of maternal and offspring disease: impact of growth restriction, fetal sex and transmission across generations.

    PubMed

    Cheong, Jean N; Wlodek, Mary E; Moritz, Karen M; Cuffe, James S M

    2016-09-01

    Babies born small are at an increased risk of developing myriad adult diseases. While growth restriction increases disease risk in all individuals, often a second hit is required to unmask 'programmed' impairments in physiology. Programmed disease outcomes are demonstrated more commonly in male offspring compared with females, with these sex-specific outcomes partly attributed to different placenta-regulated growth strategies of the male and female fetus. Pregnancy is known to be a major risk factor for unmasking a number of conditions and can be considered a 'second hit' for women who were born small. As such, female offspring often develop impairments of physiology for the first time during pregnancy that present as pregnancy complications. Numerous maternal stressors can further increase the risk of developing a maternal complication during pregnancy. Importantly, these maternal complications can have long-term consequences for both the mother after pregnancy and the developing fetus. Conditions such as preeclampsia, gestational diabetes and hypertension as well as thyroid, liver and kidney diseases are all conditions that can complicate pregnancy and have long-term consequences for maternal and offspring health. Babies born to mothers who develop these conditions are often at a greater risk of developing disease in adulthood. This has implications as a mechanism for transmission of disease across generations. In this review, we discuss the evidence surrounding long-term intergenerational implications of being born small and/or experiencing stress during pregnancy on programming outcomes.

  18. Variables that affect the middle cerebral artery peak systolic velocity in fetuses with anemia and intrauterine growth restriction.

    PubMed

    Hanif, Farhan; Drennan, Kathrin; Mari, Giancarlo

    2007-09-01

    We have previously reported that the fetal middle cerebral artery (MCA) peak systolic velocity (PSV) increases in anemic fetuses and in fetuses with intrauterine growth restriction (IUGR). We hypothesized that the pathophysiology for the increased MCA PSV is different in anemic and IUGR fetuses. Thus the aim of this study was to determine the factor(s) among fetal umbilical vein blood pH, Po2, Pco2, and hemoglobin that might affect the MCA PSV in fetuses with anemia and IUGR. This study included two groups of fetuses. The first group included fetuses at risk for anemia because of red cell alloimmunization, whereas the second group included IUGR fetuses. For both groups of fetuses, we determined hemoglobin, umbilical vein blood gases -- at cordocentesis in anemic fetuses and immediately after cesarean delivery in IUGR fetuses -- and MCA PSV before cordocentesis, or before delivery. The relationship between MCA PSV and the hemoglobin, Po2, Pco2, and pH values for the anemic and the IUGR fetuses were assessed by regression analysis using multiples of the mean. There were 14 fetuses in the first group and 22 fetuses in the second group. In the first group, the only parameter that was related to MCA PSV was the fetal hemoglobin (R2 = 0.34; p < 0.05); in fetuses with IUGR, the Pco2 (R2 = 0.36; p < 0.01) and the PO2 (R2 = 0.30; p < 0.01) correlated well with the MCA PSV, whereas no relationship was found between the MCA PSV and the hemoglobin. The data indicate that the mechanism of high MCA PSV is different in anemic and nonanemic IUGR fetuses, and suggest that the process of cerebral autoregulation is present in the preterm IUGR fetus.

  19. Do plastic particles affect microalgal photosynthesis and growth?

    PubMed

    Sjollema, Sascha B; Redondo-Hasselerharm, Paula; Leslie, Heather A; Kraak, Michiel H S; Vethaak, A Dick

    2016-01-01

    The unbridled increase in plastic pollution of the world's oceans raises concerns about potential effects these materials may have on microalgae, which are primary producers at the basis of the food chain and a major global source of oxygen. Our current understanding about the potential modes and mechanisms of toxic action that plastic particles exert on microalgae is extremely limited. How effects might vary with particle size and the physico-chemical properties of the specific plastic material in question are equally unelucidated, but may hold clues to how toxicity, if observed, is exerted. In this study we selected polystyrene particles, both negatively charged and uncharged, and three different sizes (0.05, 0.5 and 6μm) for testing the effects of size and material properties. Microalgae were exposed to different polystyrene particle sizes and surface charges for 72h. Effects on microalgal photosynthesis and growth were determined by pulse amplitude modulation fluorometry and flow cytometry, respectively. None of the treatments tested in these experiments had an effect on microalgal photosynthesis. Microalgal growth was negatively affected (up to 45%) by uncharged polystyrene particles, but only at high concentrations (250mg/L). Additionally, these adverse effects were demonstrated to increase with decreasing particle size.

  20. Do plastic particles affect microalgal photosynthesis and growth?

    PubMed

    Sjollema, Sascha B; Redondo-Hasselerharm, Paula; Leslie, Heather A; Kraak, Michiel H S; Vethaak, A Dick

    2016-01-01

    The unbridled increase in plastic pollution of the world's oceans raises concerns about potential effects these materials may have on microalgae, which are primary producers at the basis of the food chain and a major global source of oxygen. Our current understanding about the potential modes and mechanisms of toxic action that plastic particles exert on microalgae is extremely limited. How effects might vary with particle size and the physico-chemical properties of the specific plastic material in question are equally unelucidated, but may hold clues to how toxicity, if observed, is exerted. In this study we selected polystyrene particles, both negatively charged and uncharged, and three different sizes (0.05, 0.5 and 6μm) for testing the effects of size and material properties. Microalgae were exposed to different polystyrene particle sizes and surface charges for 72h. Effects on microalgal photosynthesis and growth were determined by pulse amplitude modulation fluorometry and flow cytometry, respectively. None of the treatments tested in these experiments had an effect on microalgal photosynthesis. Microalgal growth was negatively affected (up to 45%) by uncharged polystyrene particles, but only at high concentrations (250mg/L). Additionally, these adverse effects were demonstrated to increase with decreasing particle size. PMID:26675372

  1. Family Poverty Affects the Rate of Human Infant Brain Growth

    PubMed Central

    Hanson, Jamie L.; Hair, Nicole; Shen, Dinggang G.; Shi, Feng; Gilmore, John H.; Wolfe, Barbara L.; Pollak, Seth D.

    2013-01-01

    Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems. PMID:24349025

  2. Artificial Polychromatic Light Affects Growth and Physiology in Chicks

    PubMed Central

    Yang, Bo; Yu, Yonghua

    2014-01-01

    Despite the overwhelming use of artificial light on captive animals, its effect on those animals has rarely been studied experimentally. Housing animals in controlled light conditions is useful for assessing the effects of light. The chicken is one of the best-studied animals in artificial light experiments, and here, we evaluate the effect of polychromatic light with various green and blue components on the growth and physiology in chicks. The results indicate that green-blue dual light has two side-effects on chick body mass, depending on the various green to blue ratios. Green-blue dual light with depleted and medium blue component decreased body mass, whereas enriched blue component promoted body mass in chicks compared with monochromatic green- or blue spectra-treated chicks. Moreover, progressive changes in the green to blue ratios of green-blue dual light could give rise to consistent progressive changes in body mass, as suggested by polychromatic light with higher blue component resulting in higher body mass. Correlation analysis confirmed that food intake was positively correlated with final body mass in chicks (R2 = 0.7664, P = 0.0001), suggesting that increased food intake contributed to the increased body mass in chicks exposed to higher blue component. We also found that chicks exposed to higher blue component exhibited higher blood glucose levels. Furthermore, the glucose level was positively related to the final body mass (R2 = 0.6406, P = 0.0001) and food intake (R2 = 0.784, P = 0.0001). These results demonstrate that spectral composition plays a crucial role in affecting growth and physiology in chicks. Moreover, consistent changes in spectral components might cause the synchronous response of growth and physiology. PMID:25469877

  3. Family poverty affects the rate of human infant brain growth.

    PubMed

    Hanson, Jamie L; Hair, Nicole; Shen, Dinggang G; Shi, Feng; Gilmore, John H; Wolfe, Barbara L; Pollak, Seth D

    2013-01-01

    Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems.

  4. Biomonitoring of human fetal exposure to environmental chemicals in early pregnancy.

    PubMed

    Cooke, Gerard M

    2014-01-01

    The first trimester of human fetal life, a period of extremely rapid development of physiological systems, represents the most rapid growth phase in human life. Interference in the establishment of organ systems may result in abnormal development that may be manifest immediately or programmed for later abnormal function. Exposure to environmental chemicals may be affecting development at these early stages, and yet there is limited knowledge of the quantities and identities of the chemicals to which the fetus is exposed during early pregnancy. Clearly, opportunities for assessing fetal chemical exposure directly are extremely limited. Hence, this review describes indirect means of assessing fetal exposure in early pregnancy to chemicals that are considered disrupters of development. Consideration is given to such matrices as maternal hair, fingernails, urine, saliva, sweat, breast milk, amniotic fluid and blood, and fetal matrices such as cord blood, cord tissue, meconium, placenta, and fetal liver. More than 150 articles that presented data from chemical analysis of human maternal and fetal tissues and fluids were reviewed. Priority was given to articles where chemical analysis was conducted in more than one matrix. Where correlations between maternal and fetal matrices were determined, these articles were included and are highlighted, as these may provide the basis for future investigations of early fetal exposure. The determination of fetal chemical exposure, at the time of rapid human growth and development, will greatly assist regulatory agencies in risk assessments and establishment of advisories for risk management concerning environmental chemicals.

  5. Exposure to an environmentally relevant mixture of brominated flame retardants affects fetal development in Sprague-Dawley rats.

    PubMed

    Berger, Robert G; Lefèvre, Pavine L C; Ernest, Sheila R; Wade, Michael G; Ma, Yi-Qian; Rawn, Dorothea F K; Gaertner, Dean W; Robaire, Bernard; Hales, Barbara F

    2014-06-01

    Brominated flame retardants are incorporated into a wide variety of consumer products and are known to enter into the surrounding environment, leading to human exposure. There is accumulating evidence that these compounds have adverse effects on reproduction and development in humans and animal models. Animal studies have generally characterized the outcome of exposure to a single technical mixture or congener. Here, we determined the impact of exposure of rats prior to mating and during gestation to a mixture representative of congener levels found in North American household dust. Adult female Sprague-Dawley rats were fed a diet containing 0, 0.75, 250 or 750mg/kg of a mixture of flame retardants (polybrominated diphenyl ethers, hexabromocyclododecane) from two weeks prior to mating to gestation day 20. This formulation delivered nominal doses of 0, 0.06, 20 and 60mg/kg body weight/day. The lowest dose approximates high human exposures based on house dust levels and the dust ingestion rates of toddlers. Litter size and resorption sites were counted and fetal development evaluated. No effects on maternal health, litter size, fetal viability, weights, crown rump lengths or sex ratios were detected. The proportion of litters with fetuses with anomalies of the digits (soft tissue syndactyly or malposition of the distal phalanges) was increased significantly in the low (0.06mg/kg/day) dose group. Skeletal analysis revealed a decreased ossification of the sixth sternebra at all exposure levels. Thus, exposure to an environmentally relevant mixture of brominated flame retardants results in developmental abnormalities in the absence of apparent maternal toxicity. The relevance of these findings for predicting human risk is yet to be determined.

  6. Maternal high-fat diet is associated with impaired fetal lung development.

    PubMed

    Mayor, Reina S; Finch, Katelyn E; Zehr, Jordan; Morselli, Eugenia; Neinast, Michael D; Frank, Aaron P; Hahner, Lisa D; Wang, Jason; Rakheja, Dinesh; Palmer, Biff F; Rosenfeld, Charles R; Savani, Rashmin C; Clegg, Deborah J

    2015-08-15

    Maternal nutrition has a profound long-term impact on infant health. Poor maternal nutrition influences placental development and fetal growth, resulting in low birth weight, which is strongly associated with the risk of developing chronic diseases, including heart disease, hypertension, asthma, and type 2 diabetes, later in life. Few studies have delineated the mechanisms by which maternal nutrition affects fetal lung development. Here, we report that maternal exposure to a diet high in fat (HFD) causes placental inflammation, resulting in placental insufficiency, fetal growth restriction (FGR), and inhibition of fetal lung development. Notably, pre- and postnatal exposure to maternal HFD also results in persistent alveolar simplification in the postnatal period. Our novel findings provide a strong association between maternal diet and fetal lung development.

  7. Effects of transforming growth factor beta and epidermal growth factor on cell proliferation and the formation of bone nodules in isolated fetal rat calvaria cells.

    PubMed

    Antosz, M E; Bellows, C G; Aubin, J E

    1989-08-01

    When cells enzymatically isolated from fetal rat calvaria (RC cells) are cultured in vitro in the presence of ascorbic acid and Na beta-glycerophosphate, discrete three-dimensional nodules form with the histologic, immunohistochemical, and ultrastructural characteristics of bone (Bellows et al; Calcified Tissue International 38:143-154, 1986; Bhargava et al., Bone, 9:155-163, 1988). Quantitation of the number of bone nodules that forms provides a colony assay for osteoprogenitor cells present in the RC population (Bellows and Aubin, Develop. Biol., 133:8-13, 1989). Continuous culture with either epidermal growth factor (EGF) or transforming growth factor beta (TGF-beta) results in dose-dependent inhibition of bone nodule formation; however, the former causes increased proliferation and saturation density, while the latter reduces both parameters. Addition of EGF (48 h pulse, 2-200 ng/ml) to RC cells at day 1 after plating results in increased proliferation and population saturation density and an increased number of bone nodules formed. Similar pulses at confluence and in postconfluent multilayered cultures when nodules first begin forming (approx. day 11) inhibited bone nodule formation and resulted in a smaller stimulation of cell proliferation. Forty-eight hour pulses of TGF-beta (0.01-1 ng/ml) reduced bone nodule formation and proliferation at all times examined, with pulses on day 1 causing maximum inhibition. The effects of pulses with TGF-beta and EGF on inhibition of nodule formation are independent of the presence of serum in the culture medium during the pulse. The data suggest that whereas EGF can either stimulate or inhibit the formation of bone nodules depending upon the time and duration of exposure, TGF-B inhibits bone nodule formation under all conditions tested. Moreover, these effects on osteoprogenitor cell differentiation do not always correlate with the effects of the growth factors on RC cell proliferation. PMID:2787326

  8. Fetal Alcohol Syndrome and Fetal Alcohol Effects in Child Development.

    ERIC Educational Resources Information Center

    Pancratz, Diane R.

    This literature review defines Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) and considers their causes, diagnoses, prevalence, and educational ramifications. Effects of alcohol during each of the trimesters of pregnancy are summarized. Specific diagnostic characteristics of FAS are listed: (1) growth deficiency, (2) a…

  9. Placental hormones, nutrition, and fetal development.

    PubMed

    Mulay, S; Browne, C A; Varma, D R; Solomon, S

    1980-02-01

    Fetal growth retardation due to maternal malnutrition is widespread especially in the Third World. Little is known about the mechanisms that regulate the growth of the fetus and placenta during protein malnutrition. It is known that the placental size and levels of circulating placental hormones such as human chorionic gonadotrophins (hCG), human placental lactogen (hPL), and estrogens are affected by the nutritional status of the mother. There is suggestive evidence that during malnutrition, hPL may increase lipolysis and exert a glucose sparing effect in the mother, thereby promoting glucose availability to the fetus. We have studied the influence of dietary protein deficiency on the binding of dexamethasone to the specific cytosol receptors in adult and fetal tissues. A low protein diet in adult male rats is associated with a decrease in dexamethasone binding to liver cytosol receptors. On the other hand, protein deprivation in pregnant female rats leads to an increase in dexamethasone binding to liver cytosol receptors of both the mother and fetus. However, the influences of maternal protein deprivation on dexamethasone receptors in the fetal liver and lungs are not similar. At 21 days gestation the binding of dexamethasone to fetal lung receptors of protein-deficient mothers is lower than that in the controls. These differences at a critical time in the fetal lung development indicate that a fall in receptors for dexamethasone may lead to impaired phospholipid synthesis in fetuses of protein-deficient mothers and point to the importance of nutritional factors in the biochemistry of fetal development. PMID:7353684

  10. Levels of Adipokines in Amniotic Fluid and Cord Blood Collected from Dichorionic-Diamniotic Twins Discordant for Fetal Growth

    PubMed Central

    Park, Joong Shin; Norwitz, Errol R.; Panyavatthanasinh, Sitthysack; Kim, Sun Min; Lee, JoonHo; Park, Chan-Wook; Kim, Byoung Jae; Jun, Jong Kwan

    2016-01-01

    Objective To compare the concentrations of adipokines in amniotic fluid (AF) and cord blood collected from discordant dichorionic-diamniotic (DCDA) twin fetuses. Study Design The study population included DCDA twins discordant for fetal growth (birth weight difference >10%) who either underwent mid-trimester amniocentesis for routine clinical indication (Cohort 1) or whose amniotic fluid was collected at the time of delivery (Cohort 2). In both cohorts, cord blood was collected at delivery. Results A total of 92 twin pairs were enrolled (n = 49 in Cohort 1; n = 43 in Cohort 2). In Cohort 1, the concentrations of adiponectin (median, 68.5 ng/mL vs 61.4 ng/mL; p<0.05) and leptin (median, 13.9 ng/mL vs 11.2 ng/mL; p<0.1) in mid-trimester AF were significantly higher in smaller compared with larger twins. In Cohort 2, the concentration of serpin E1 (median, 246.0 ng/mL vs 182.8 ng/mL; p<0.01) in AF at delivery was significantly higher in smaller twins, but no difference was noted in adiponectin and leptin concentrations. Levels of adiponectin (median, 10425.5 ng/mL vs 11552.0 ng/mL; p<0.005) and leptin (median, 2.1 ng/mL vs 2.6 ng/mL; p<0.005) were significantly lower in the cord blood of smaller twins whereas cord blood concentrations of serpin E1 (median, 15.5 ng/mL vs 13.3 ng/mL; p<0.05) was higher in the smaller twins. Conclusion In discordant DCDA twin pairs, concentrations of adiponectin, leptin, and serpin E1 in mid-trimester AF, AF at delivery, and cord blood at birth vary significantly but predictably between the smaller and larger twins. PMID:27135745

  11. Assessed occupational exposure to chlorinated, aromatic and Stoddard solvents during pregnancy and risk of fetal growth restriction

    PubMed Central

    Desrosiers, Tania A; Lawson, Christina C; Meyer, Robert E; Stewart, Patricia A; Waters, Martha A; Correa, Adolfo; Olshan, Andrew F

    2015-01-01

    Objectives Previous experimental and epidemiological research suggests that maternal exposure to some organic solvents during pregnancy may increase the risk of fetal growth restriction (FGR). We evaluated the association between expert-assessed occupational solvent exposure and risk of small for gestational age (SGA) infants in a population-based sample of women in the National Birth Defects Prevention Study. Methods We analysed data from 2886 mothers and their infants born between 1997 and 2002. Job histories were self-reported. Probability of exposure to six chlorinated, three aromatic and one petroleum solvent was assessed by industrial hygienists. SGA was defined as birthweight<10th centile of birthweight-by-gestational age in a national reference. Logistic regression was used to estimate ORs and 95% CIs to assess the association between SGA and exposure to any solvent(s) or specific solvent classes, adjusting for maternal age and education. Results Approximately 8% of infants were SGA. Exposure prevalence to any solvent was 10% and 8% among mothers of SGA and non-SGA infants, respectively. Among women with ≥50% probability of exposure, we observed elevated but imprecise associations between SGA and exposure to any solvent(s) (1.71; 0.86 to 3.40), chlorinated solvents (1.70; 0.69 to 4.01) and aromatic solvents (1.87; 0.78 to 4.50). Conclusions This is the first population-based study in the USA to investigate the potential association between FGR and assessed maternal occupational exposure to distinct classes of organic solvents during pregnancy. The potential associations observed between SGA and exposure to chlorinated and aromatic solvents are based on small numbers and merit further investigation. PMID:26076683

  12. Adequacy of maternal iron status protects against behavioral, neuroanatomical, and growth deficits in fetal alcohol spectrum disorders.

    PubMed

    Rufer, Echoleah S; Tran, Tuan D; Attridge, Megan M; Andrzejewski, Matthew E; Flentke, George R; Smith, Susan M

    2012-01-01

    Fetal alcohol spectrum disorders (FASD) are the leading non-genetic cause of neurodevelopmental disability in children. Although alcohol is clearly teratogenic, environmental factors such as gravidity and socioeconomic status significantly modify individual FASD risk despite equivalent alcohol intake. An explanation for this variability could inform FASD prevention. Here we show that the most common nutritional deficiency of pregnancy, iron deficiency without anemia (ID), is a potent and synergistic modifier of FASD risk. Using an established rat model of third trimester-equivalent binge drinking, we show that ID significantly interacts with alcohol to impair postnatal somatic growth, associative learning, and white matter formation, as compared with either insult separately. For the associative learning and myelination deficits, the ID-alcohol interaction was synergistic and the deficits persisted even after the offsprings' iron status had normalized. Importantly, the observed deficits in the ID-alcohol animals comprise key diagnostic criteria of FASD. Other neurobehaviors were normal, showing the ID-alcohol interaction was selective and did not reflect a generalized malnutrition. Importantly ID worsened FASD outcome even though the mothers lacked overt anemia; thus diagnostics that emphasize hematological markers will not identify pregnancies at-risk. This is the first direct demonstration that, as suggested by clinical studies, maternal iron status has a unique influence upon FASD outcome. While alcohol is unquestionably teratogenic, this ID-alcohol interaction likely represents a significant portion of FASD diagnoses because ID is more common in alcohol-abusing pregnancies than generally appreciated. Iron status may also underlie the associations between FASD and parity or socioeconomic status. We propose that increased attention to normalizing maternal iron status will substantially improve FASD outcome, even if maternal alcohol abuse continues. These findings

  13. Diagnosis of twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anaemia-polycythaemia sequence, and twin reversed arterial perfusion sequence.

    PubMed

    Sueters, Marieke; Oepkes, Dick

    2014-02-01

    Monochorionic twin pregnancies are well known to be at risk for a variety of severe complications, a true challenge for the maternal-fetal medicine specialist. With current standards of care, monochorionicity should be established in the first trimester. Subsequently, frequent monitoring using the appropriate diagnostic tools, and in-depth knowledge about the pathophysiology of all possible clinical presentations of monochorionic twin abnormalities, should lead to timely recognition, and appropriate management. Virtually all unique diseases found in monochorionic twins are directly related to placental angio-architecture. This, however, cannot be established reliably before birth. The clinician needs to be aware of the definitions and symptoms of twin-to twin transfusion syndrome, selective fetal growth restriction, twin anaemia-polycythaemia sequence, and twin reversed arterial perfusion sequence, to be able to recognise each disease and take the required action. In this chapter, we address current standards on correct and timely diagnoses of severe complications of monochorionic twin pregnancies.

  14. Management of fetal endocrine disorders.

    PubMed

    Hughes, I A

    2003-08-01

    A number of maternal endocrine disorders, when active during pregnancy, can have adverse effects on the newborn. Frequently, these affects can be anticipated as in Graves' disease, or the adverse effect can be prevented as in macrosomia in the infant of the diabetic mother. Occasionally, there are opportunities for prenatal treatment of a fetal endocrine disorder. For instance, a large goitre that may cause problems during delivery can be treated with thyroid hormones administered intra-amniotically or as analogues that cross the placenta. A uniquely effective form of treatment for prevention of a major birth defect is administration of dexamethasone to the mother to avoid virilisation of a female fetus with congenital adrenal hyperplasia (CAH). However, such treatment should only be conducted within the framework of a clinical trial as the long-term effects of exposure to potent glucocorticoids in utero are unknown. Intrauterine growth retardation, which affects about 5% of newborns, is currently not amenable to direct pharmacological treatment before birth. However, there are more practical options for managing this condition, including improved maternal nutrition and avoidance of toxins injurious to fetal growth.

  15. Doppler Impedance Changes at the Fetal Brain Vessels in a Pregnancy Affected with a Multiple Combination of Uteroplacental Anomalies

    PubMed Central

    Morales-Roselló, José; Peralta Llorens, Núria

    2012-01-01

    A fetus with a very rare five-fold combination of uteroplacental anomalies, bicornuate uterus, short cervix with cervical incompetence, multilobed placenta succenturiata, accessory cotyledon within the cervical funneling, and umbilical cord insertion into the anomalous cervical cotyledon, presented an early and marked decrease at the vertebral and middle cerebral arteries Doppler resistances. This cerebral low-impedance state, usually found before labor, and considered an adaptive mechanism developed to protect the fetus at term from labor asphyxia, was present for an unknown reason at 20 weeks. After the patient was treated with vaginal progesterone, the cervix shortening improved and markedly, at the same time, the cerebral vascular resistances increased and maintained an adequate for gestational age impedance until delivery at 34 weeks. As the described uteroplacental anomalies determined a high risk of preterm delivery, due to cervical dilation, cord compresion, and placental haemorrhage, these fluctuating brain vascular changes might be the result of the fetal adaptation to the changes preceding an imminent delivery. PMID:22481947

  16. PRENATAL NICOTINE EXPOSURE SELECTIVELY AFFECTS NICOTINIC RECEPTOR EXPRESSION IN PRIMARY AND ASSOCIATIVE VISUAL CORTICES OF THE FETAL BABOON

    PubMed Central

    Duncan, Jhodie R.; Garland, Marianne; Stark, Raymond I.; Myers, Michael M.; Fifer, William P.; Mokler, David J.; Kinney, Hannah C.

    2014-01-01

    Exposure to nicotine during pregnancy via maternal cigarette smoking is associated with visual deficits in children. This is possibly due to activation of nicotinic acetylcholine receptors (nAChRs) in the occipital cortex which are important in the development of visual mapping. Using a baboon model we explored the effects of prenatal nicotine on parameters in the primary and associated visual cortices. Pregnant baboons were infused with nicotine (0.5 mg/hr, i.v.) or saline from 86 days gestation. At 161 days gestation fetal brains were collected (n=5/group) and the occipital lobe assessed for nAChRs and markers of the serotonergic and catecholaminergic systems using tissue autoradiography and/or high performance liquid chromatography. Neuronal nAChRs and serotonergic markers were expressed in a region and subunit dependent manner. Prenatal nicotine exposure was associated with increased binding for 3H-epibatidine sensitive nAChRs in the primary visual cortex (BA 17) and BA 18, but not BA 19, of the associative visual cortex (p<0.05). Markers of the serotonergic or catecholaminergic systems were not significantly altered. Thus, prenatal nicotine exposure is associated with alterations in the cholinergic system in the occipital lobe which may aid in the explanation of the appearance of visual deficits in children from mothers who smoke during pregnancy. PMID:24903536

  17. Genetic ablation of androgen receptor signaling in fetal Leydig cell lineage affects Leydig cell functions in adult testis.

    PubMed

    Kaftanovskaya, Elena M; Lopez, Carolina; Ferguson, Lydia; Myhr, Courtney; Agoulnik, Alexander I

    2015-06-01

    It is commonly accepted that androgen-producing fetal Leydig cells (FLC) are substituted by adult Leydig cells (ALC) during perinatal testis development. The mechanisms influencing this process are unclear. We used mice with a retinoid acid receptor 2 promoter-Cre recombinase transgene (Rarb-cre) expressed in embryonic FLC precursors, but not in postnatal testis, and a dual fluorescent Cre recombinase reporter to label FLC and ALC in vivo. All FLC in newborn testis had the recombinant, whereas the majority of LC in adult testis had the nonrecombinant reporter. Primary LC cultures from adult testis had either recombinant (20%) or nonrecombinant (80%) cells, demonstrating that the FLC survive in adult testis and their ontogeny is distinct from ALC. Conditional inactivation of androgen receptor (AR) allele using the Rarb-cre transgene resulted in a 50% increase of AR-negative LC in adult testis. The mutant males became infertile with age, with all LC in older testis showing signs of incomplete differentiation, such as a large number of big lipid droplets, an increase of finger-like protrusions, and a misexpression of steroidogenic or FLC- and ALC-specific genes. We propose that the antiandrogenic exposure during early development may similarly result in an increase of FLC in adult testis, leading to abnormal LC differentiation.

  18. Fetal Abuse.

    ERIC Educational Resources Information Center

    Kent, Lindsey; And Others

    1997-01-01

    Five cases of fetal abuse by mothers suffering from depression are discussed. Four of the women had unplanned pregnancies and had considered termination of the pregnancy. Other factors associated with fetal abuse include pregnancy denial, pregnancy ambivalence, previous postpartum depression, and difficulties in relationships. Vigilance for…

  19. The effects of alcohol on fetal development.

    PubMed

    Jones, Kenneth Lyons

    2011-03-01

    Prenatal exposure to alcohol has profound effects on many aspects of fetal development. Although alterations of somatic growth and specific minor malformations of facial structure are most characteristic, the effects of alcohol on brain development are most significant in that they lead to substantial problems with neurobehavioral development. Since the initial recognition of the fetal alcohol syndrome (FAS), a number of important observations have been made from studies involving both humans and animals. Of particular importance, a number of maternal risk factors have been identified, which may well be of relevance relative to the development of strategies for prevention of the FAS as well as intervention for those who have been affected. These include maternal age >30 years, ethnic group, lower socioeconomic status, having had a previously affected child, maternal under-nutrition, and genetic background. The purpose of this review is to discuss these issues as well as to set forth a number of questions that have not adequately been addressed relative to alcohol's effect on fetal development. Of particular importance is the critical need to identify the full spectrum of structural defects associated with the prenatal effects of alcohol as well as to establish a neurobehavioral phenotype. Appreciation of both of these issues is necessary to understand the full impact of alcohol on fetal development.

  20. Fetal biomodelling.

    PubMed

    D'Urso, P S; Thompson, R G

    1998-05-01

    A study has been performed to determine if a stereolithographic (SL) biomodel of a fetal face could be created from 3 dimensional (3D) ultrasound (US). 3D ultrasound images were acquired by Diasonics Gateway 2D Array ultrasound systems (Diasonics Ultrasound, San Jose, CA, USA) using an electromagnetic localizer (Tomtec Free Hand Scanning Device, Tomtec Imaging Systems, Middle Cove, Australia). 3D volumetric reconstruction of the fetal face was performed and the data was prepared to guide the construction of an exact solid biomodel by stereolithography (SLA 250 3D Systems, Valencia, CA, USA). A faithful solid representation of the fetal face was produced within 12 hours of the US scan. The fetal biomodel seemed to improve the display of the 3D data. The user-friendly nature of biomodelling may have clinical utility for fetal morphological assessment and as an aid when counselling parents.

  1. Fetal and neonatal thyrotoxicosis

    PubMed Central

    Batra, Chandar Mohan

    2013-01-01

    Fetal thyrotoxicosis is a rare disease occurring in 1 out of 70 pregnancies with Grave's disease or in 1 out of 4000-50,000 deliveries. The mortality is 12-20%, usually from heart failure, but other complications are tracheal compression, infections and thrombocytopenia. It results from transfer of thyroid stimulating immunoglobulins from mother to fetus through the placenta. This transplacental transfer begins around 20th week of pregnancy and reaches its maximum by 30th week. These autoantibodies bind to the fetal thyroid stimulating hormone (TSH) receptors and increase the secretion of the thyroid hormones. The mother has an active autoimmune thyroid disease or has been treated for it in the past. She may be absolutely euthyroid due to past treatment by drugs, surgery or radioiodine ablation, but still have active TSH receptor stimulating autoantibodies, which can cause fetal thyrotoxicosis. The other features of this disease are fetal tachycardia, fetal goiter and history of spontaneous abortions and findings of goiter, ascites, craniosyntosis, fetal growth retardation, maceration and hydrops at fetal autopsy. If untreated, this disease can result in intrauterine death. The treatment for this disease consists of giving carbimazole to the mother, which is transferred through the placenta to the fetus. The dose of carbimazole is titrated with the fetal heart rate. If the mother becomes hypothyroid due to carbimazole, thyroxine is added taking advantage of the fact that very little of thyroxine is transferred across the placenta. Neonatal thyrotoxicosis patients are very sick and require emergency treatment. The goal of the treatment is to normalize thyroid functions as quickly as possible, to avoid iatrogenic hypothyroidism while providing management and supportive therapy for the infant's specific signs and symptoms. PMID:24251220

  2. Fetal and neonatal thyrotoxicosis.

    PubMed

    Batra, Chandar Mohan

    2013-10-01

    Fetal thyrotoxicosis is a rare disease occurring in 1 out of 70 pregnancies with Grave's disease or in 1 out of 4000-50,000 deliveries. The mortality is 12-20%, usually from heart failure, but other complications are tracheal compression, infections and thrombocytopenia. It results from transfer of thyroid stimulating immunoglobulins from mother to fetus through the placenta. This transplacental transfer begins around 20(th) week of pregnancy and reaches its maximum by 30(th) week. These autoantibodies bind to the fetal thyroid stimulating hormone (TSH) receptors and increase the secretion of the thyroid hormones. The mother has an active autoimmune thyroid disease or has been treated for it in the past. She may be absolutely euthyroid due to past treatment by drugs, surgery or radioiodine ablation, but still have active TSH receptor stimulating autoantibodies, which can cause fetal thyrotoxicosis. The other features of this disease are fetal tachycardia, fetal goiter and history of spontaneous abortions and findings of goiter, ascites, craniosyntosis, fetal growth retardation, maceration and hydrops at fetal autopsy. If untreated, this disease can result in intrauterine death. The treatment for this disease consists of giving carbimazole to the mother, which is transferred through the placenta to the fetus. The dose of carbimazole is titrated with the fetal heart rate. If the mother becomes hypothyroid due to carbimazole, thyroxine is added taking advantage of the fact that very little of thyroxine is transferred across the placenta. Neonatal thyrotoxicosis patients are very sick and require emergency treatment. The goal of the treatment is to normalize thyroid functions as quickly as possible, to avoid iatrogenic hypothyroidism while providing management and supportive therapy for the infant's specific signs and symptoms. PMID:24251220

  3. Effects of L-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol.

    PubMed

    Sawant, Onkar B; Ramadoss, Jayanth; Hankins, Gary D; Wu, Guoyao; Washburn, Shannon E

    2014-08-01

    Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and L-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75-2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal L-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. L-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid-base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, L-glutamine supplementation mitigates alcohol-induced acid-base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy.

  4. Rhizobacterial volatiles affect the growth of fungi and Arabidopsis thaliana.

    PubMed

    Vespermann, Anja; Kai, Marco; Piechulla, Birgit

    2007-09-01

    Volatiles of Stenotrophomonas, Serratia, and Bacillus species inhibited mycelial growth of many fungi and Arabidopsis thaliana (40 to 98%), and volatiles of Pseudomonas species and Burkholderia cepacia retarded the growth to lesser extents. Aspergillus niger and Fusarium species were resistant, and B. cepacia and Staphylococcus epidermidis promoted the growth of Rhizoctonia solani and A. thaliana. Bacterial volatiles provide a new source of compounds with antibiotic and growth-promoting features.

  5. Maternal–Fetal Nutrient Transport in Pregnancy Pathologies: The Role of the Placenta

    PubMed Central

    Brett, Kendra Elizabeth; Ferraro, Zachary Michael; Yockell-Lelievre, Julien; Gruslin, Andrée; Adamo, Kristi Bree

    2014-01-01

    Appropriate in utero growth is essential for offspring development and is a critical contributor to long-term health. Fetal growth is largely dictated by the availability of nutrients in maternal circulation and the ability of these nutrients to be transported into fetal circulation via the placenta. Substrate flux across placental gradients is dependent on the accessibility and activity of nutrient-specific transporters. Changes in the expression and activity of these transporters is implicated in cases of restricted and excessive fetal growth, and may represent a control mechanism by which fetal growth rate attempts to match availability of nutrients in maternal circulation. This review provides an overview of placenta nutrient transport with an emphasis on macro-nutrient transporters. It highlights the changes in expression and activity of these transporters associated with common pregnancy pathologies, including intrauterine growth restriction, macrosomia, diabetes and obesity, as well as the potential impact of maternal diet. Molecular signaling pathways linking maternal nutrient availability and placenta nutrient transport are discussed. How sexual dimorphism affects fetal growth strategies and the placenta’s response to an altered intrauterine environment is considered. Further knowledge in this area may be the first step in the development of targeted interventions to help optimize fetal growth. PMID:25222554

  6. Spontaneous pre-existing hypoxia does not affect brain damage after global cerebral ischaemia in late-gestation fetal sheep.

    PubMed

    Davidson, Joanne O; Yuill, Caroline A; Wassink, Guido; Bennet, Laura; Gunn, Alistair J

    2015-01-01

    There is considerable evidence that a mild, non-injurious insult can protect (precondition) against a subsequent injurious insult. Typically, protection is seen when the gap between insults is several days to a week. However, the effect of mild but persistent hypoxia is unknown. In this study we examined the hypothesis that mild pre-existing hypoxia (PaO2<17 mm Hg) would reduce neural injury in chronically instrumented late-gestation (0.85 gestation) fetal sheep exposed to 30 min of global cerebral ischaemia induced by bilateral carotid artery occlusion (normoxia: n=9 vs. pre-existing hypoxia: n=9) or normoxia plus sham ischaemia (sham controls: n=9). Histopathology was assessed after 7 days of recovery. Fetuses with pre-existing hypoxia had lower PaO2 values (16.1±0.6 vs. 26.0±1.1 mm Hg) and were lighter at post-mortem (4,033±412 vs. 5,261±238 g) compared to normoxic fetuses. Cerebral ischaemia was associated with secondary cortical oedema and seizures, reduced final EEG power, loss of sleep state cycling, and significant loss of neurons and oligodendrocytes, with no significant effect of pre-existing hypoxia. Pre-existing hypoxia was associated with a significantly attenuated rise in mean arterial pressure between 18 and 36 h and slower resolution of cortical oedema between 96 and 150 h after ischaemia. These data suggest that chronic hypoxia is not associated with a significant preconditioning effect.

  7. Prenatal Intestinal Obstruction Affects the Myenteric Plexus and Causes Functional Bowel Impairment in Fetal Rat Experimental Model of Intestinal Atresia

    PubMed Central

    Khen-Dunlop, Naziha; Sarnacki, Sabine; Victor, Anais; Grosos, Celine; Menard, Sandrine; Soret, Rodolphe; Goudin, Nicolas; Pousset, Maud; Sauvat, Frederique; Revillon, Yann; Cerf-Bensussan, Nadine; Neunlist, Michel

    2013-01-01

    Background Intestinal atresia is a rare congenital disorder with an incidence of 3/10 000 birth. About one-third of patients have severe intestinal dysfunction after surgical repair. We examined whether prenatal gastrointestinal obstruction might effect on the myenteric plexus and account for subsequent functional disorders. Methodology/Principal Findings We studied a rat model of surgically induced antenatal atresia, comparing intestinal samples from both sides of the obstruction and with healthy rat pups controls. Whole-mount preparations of the myenteric plexus were stained for choline acetyltransferase (ChAT) and nitric oxide synthase (nNOS). Quantitative reverse transcription PCR was used to analyze mRNAs for inflammatory markers. Functional motility and permeability analyses were performed in vitro. Phenotypic studies were also performed in 8 newborns with intestinal atresia. In the experimental model, the proportion of nNOS-immunoreactive neurons was similar in proximal and distal segments (6.7±4.6% vs 5.6±4.2%, p = 0.25), but proximal segments contained a higher proportion of ChAT-immunoreactive neurons (13.2±6.2% vs 7.5±4.3%, p = 0.005). Phenotypic changes were associated with a 100-fold lower concentration-dependent contractile response to carbachol and a 1.6-fold higher EFS-induced contractile response in proximal compared to distal segments. Transcellular (p = 0.002) but not paracellular permeability was increased. Comparison with controls showed that modifications involved not only proximal but also distal segments. Phenotypic studies in human atresia confirmed the changes in ChAT expression. Conclusion Experimental atresia in fetal rat induces differential myenteric plexus phenotypical as well as functional changes (motility and permeability) between the two sides of the obstruction. Delineating these changes might help to identify markers predictive of motility dysfunction and to define guidelines for post-surgical care. PMID:23667464

  8. Sulfate in fetal development.

    PubMed

    Dawson, Paul A

    2011-08-01

    Sulfate (SO(4)(2-)) is an important nutrient for human growth and development, and is obtained from the diet and the intra-cellular metabolism of sulfur-containing amino acids, including methionine and cysteine. During pregnancy, fetal tissues have a limited capacity to produce sulfate, and rely on sulfate obtained from the maternal circulation. Sulfate enters and exits placental and fetal cells via transporters on the plasma membrane, which maintain a sufficient intracellular supply of sulfate and its universal sulfonate donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) for sulfate conjugation (sulfonation) reactions to function effectively. Sulfotransferases mediate sulfonation of numerous endogenous compounds, including proteins and steroids, which biotransforms their biological activities. In addition, sulfonation of proteoglycans is important for maintaining normal structure and development of tissues, as shown for reduced sulfonation of cartilage proteoglycans that leads to developmental dwarfism disorders and four different osteochondrodysplasias (diastrophic dysplasia, atelosteogenesis type II, achondrogenesis type IB and multiple epiphyseal dysplasia). The removal of sulfate via sulfatases is an important step in proteoglycan degradation, and defects in several sulfatases are linked to perturbed fetal bone development, including mesomelia-synostoses syndrome and chondrodysplasia punctata 1. In recent years, interest in sulfate and its role in developmental biology has expanded following the characterisation of sulfate transporters, sulfotransferases and sulfatases and their involvement in fetal growth. This review will focus on the physiological roles of sulfate in fetal development, with links to human and animal pathophysiologies.

  9. Sulfate in fetal development.

    PubMed

    Dawson, Paul A

    2011-08-01

    Sulfate (SO(4)(2-)) is an important nutrient for human growth and development, and is obtained from the diet and the intra-cellular metabolism of sulfur-containing amino acids, including methionine and cysteine. During pregnancy, fetal tissues have a limited capacity to produce sulfate, and rely on sulfate obtained from the maternal circulation. Sulfate enters and exits placental and fetal cells via transporters on the plasma membrane, which maintain a sufficient intracellular supply of sulfate and its universal sulfonate donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) for sulfate conjugation (sulfonation) reactions to function effectively. Sulfotransferases mediate sulfonation of numerous endogenous compounds, including proteins and steroids, which biotransforms their biological activities. In addition, sulfonation of proteoglycans is important for maintaining normal structure and development of tissues, as shown for reduced sulfonation of cartilage proteoglycans that leads to developmental dwarfism disorders and four different osteochondrodysplasias (diastrophic dysplasia, atelosteogenesis type II, achondrogenesis type IB and multiple epiphyseal dysplasia). The removal of sulfate via sulfatases is an important step in proteoglycan degradation, and defects in several sulfatases are linked to perturbed fetal bone development, including mesomelia-synostoses syndrome and chondrodysplasia punctata 1. In recent years, interest in sulfate and its role in developmental biology has expanded following the characterisation of sulfate transporters, sulfotransferases and sulfatases and their involvement in fetal growth. This review will focus on the physiological roles of sulfate in fetal development, with links to human and animal pathophysiologies. PMID:21419855

  10. Fetal Surgery

    PubMed Central

    Laberge, Jean-Martin

    1986-01-01

    Fetal surgery has come of age. For decades experimental fetal surgery proved essential in studying normal fetal physiology and development, and pathophysiology of congenital defects. Clinical fetal surgery started in the 1960s with intrauterine transfusions. In the 1970s, the advent of ultrasonography revolutionized fetal diagnosis and created a therapeutic vacuum. Fetal treatment, medical and surgical, is slowly trying to fill the gap. Most defects detected are best treated after birth, some requiring a modification in the time, mode and place of delivery for optimal obstetrical and neonatal care. Surgical intervention in utero should be considered for malformations that cause progressive damage to the fetus, leading to death or severe morbidity; that can be corrected or palliated in utero with a reasonable expectation of normal postnatal development; that cannot wait to be corrected after birth, even considering pre-term delivery; that are not accompanied by chromosomal or other major anomalies. At present, congenital hydronephrosis is the most common indication for fetal surgery, followed by obstructive hydrocephalus. Congenital diaphragmatic hernia also fulfills the criteria, but its correction poses more problems, and no clinical attempts have been reported so far. In the future many other malformations or diseases may become best treated in utero. The ethical and moral issues are complex and need to be discussed as clinical and experimental progress is made. PMID:21267309

  11. Elsevier Trophoblast Research Award Lecture: Searching for an early pregnancy 3-D morphometric ultrasound marker to predict fetal growth restriction.

    PubMed

    Collins, S L; Stevenson, G N; Noble, J A; Impey, L

    2013-03-01

    Fetal growth restriction (FGR) is a major cause of perinatal morbidity and mortality, even in term babies. An effective screening test to identify pregnancies at risk of FGR, leading to increased antenatal surveillance with timely delivery, could decrease perinatal mortality and morbidity. Placental volume, measured with commercially available packages and a novel, semi-automated technique, has been shown to predict small for gestational age babies. Placental morphology measured in 2-D in the second trimester and ex-vivo post delivery, correlates with FGR. This has also been investigated using 2-D estimates of diameter and site of cord insertion obtained using the Virtual Organ Computer-aided AnaLysis (VOCAL) software. Data is presented describing a pilot study of a novel 3-D method for defining compactness of placental shape. We prospectively recruited women with a singleton pregnancy and BMI of <35. A 3-D ultrasound scan was performed between 11 and 13 + 6 weeks' gestation. The placental volume, total placental surface area and the area of the utero-placental interface were calculated using our validated technique. From these we generated dimensionless indices including sphericity (ψ), standardised placental volume (sPlaV) and standardised functional area (sFA) using Buckingham π theorem. The marker for FGR used was small for gestational age, defined as <10th customised birth weight centile (cSGA). Regression analysis examined which of the morphometric indices were independent predictors of cSGA. Data were collected for 143 women, 20 had cSGA babies. Only sPlaV and sFA were significantly correlated to birth weight (p < 0.001). Regression demonstrated all dimensionless indices were inter-dependent co-factors. ROC curves showed no advantage for using sFA over the simpler sPlaV. The generated placental indices are not independent of placental volume this early in gestation. It is hoped that another placental ultrasound marker based on vascularity can improve the

  12. Arginine nutrition and fetal brown adipose tissue development in nutrient-restricted sheep.

    PubMed

    Satterfield, M Carey; Dunlap, Kathrin A; Keisler, Duane H; Bazer, Fuller W; Wu, Guoyao

    2013-09-01

    Intrauterine growth restriction is a significant problem worldwide, resulting in increased rates of neonatal morbidity and mortality, as well as increased risks for metabolic and cardiovascular disease. The present study investigated the role of maternal undernutrition and L-arginine administration on fetal growth and development. Embryo transfer was utilized to generate genetically similar singleton pregnancies. On Day 35 of gestation, ewes were assigned to receive either 50 or 100% of their nutritional requirements. Ewes received i.v. injections of either saline or L-arginine three times daily from Day 100 to Day 125. Fetal growth was assessed at necropsy on Day 125. Maternal dietary manipulation altered circulating concentrations of leptin, progesterone, and amino acids in maternal plasma. Fetal weight was reduced in nutrient-restricted ewes on Day 125 compared with 100% fed ewes. Compared with saline-treated underfed ewes, maternal L-arginine administration did not affect fetal weight but increased weight of the fetal pancreas by 32% and fetal peri-renal brown adipose tissue mass by 48%. These results indicate that L-arginine administration enhanced fetal pancreatic and brown adipose tissue development. The postnatal effects of increased pancreatic and brown adipose tissue growth warrant further study.

  13. Fetal Alcohol Syndrome.

    ERIC Educational Resources Information Center

    Zerrer, Peggy

    The paper reviews Fetal Alcohol Syndrome (FAS), a series of effects seen in children whose mothers drink alcohol to excess during pregnancy. The identification of FAS and its recognition as a major health problem in need of prevention are traced. Characteristics of children with FAS are described and resultant growth retardation, abnormal physical…

  14. The Fetal Alcohol Syndrome.

    ERIC Educational Resources Information Center

    Umbreit, John; Ostrow, Lisa S.

    1980-01-01

    Fetal alcohol syndrome is a pattern of altered growth and morphogenesis found in about half the offspring of severely and chronically alcoholic women who continue drinking throughout their pregnancy. Of children studied, mild to moderate mental retardation was the most common disorder, occurring in 44 percent of the cases. (PHR)

  15. Factors affecting spontaneous reduction of corpora lutea and twin embryos during the late embryonic/early fetal period in multiple-ovulating dairy cows.

    PubMed

    López-Gatius, F; García-Ispierto, I; Hunter, R H F

    2010-02-01

    Spontaneous reduction of advanced twin embryos has been described in high-producing, Holstein-Fresian (Bos taurus) dairy herds. The first objective of the current study was to determine whether management and cow factors could have an effect on such a reduction in twin pregnancies during the early fetal period. Because loss of a corpus luteum was noted in cows suffering twin reduction, we expanded our study to include multiple-ovulating cows carrying singletons. Pregnancy was diagnosed and confirmed from Days 28 to 34 and 56 to 62 postinsemination. Sixty-nine (23.5%) of 293 pregnant cows with two corpora lutea carrying singletons and 132 (28.4%) of 464 twin pregnancies recorded on first pregnancy diagnosis subsequently lost one of the corpora lutea or one of the embryos, respectively. Thirty-four (25.8%) of the 132 twin pregnancies suffering embryo reduction lost one corpus luteum along with the embryo. Corpus luteum reduction always occurred in the ovary ipsilateral to the gravid horn suffering embryo reduction. Binary logistic regressions were performed considering corpus luteum and embryo reduction as dependent variables in single and twin pregnancies, respectively, and several management- and cow-related factors as independent variables. In cows carrying singletons, the risk of corpus luteum reduction was 14.3 (1/0.07) times lower for a given herd, whereas the interaction season by laterality significantly affected corpus luteum reduction such that in cows with two corpora lutea ipsilateral to the horn of pregnancy, the risk of reduction decreased during the winter period. In cows carrying twins, ipsilateral twin pregnancies were 3.45 (1/0.29) times more likely to undergo the loss of one embryo than bilateral twin pregnancies. As an overall conclusion, both corpora lutea and embryos were vulnerable to the effects of stress factors during the early fetal period in cows maintaining their pregnancies. A strong unilateral relationship between the corpus luteum and

  16. PPARγ stimulates expression of L-type amino acid and taurine transporters in human placentas: the evidence of PPARγ regulating fetal growth

    PubMed Central

    Chen, Zhaoguang; He, Ping; Ding, Xiaoying; Huang, Ying; Gu, Hang; Ni, Xin

    2015-01-01

    Placental amino acid transporters and peroxisome proliferator-activated receptors (PPARs) have been implicated to placental development and therefore regulation of fetal growth. We analyzed the correlation between the expression of amino acid transporters and PPARs and investigated whether PPARs control the expression of amino acid transporters in placentas. It was found that protein expression of PPARγ and L-type amino acid transporter 1(LAT1) and 2 (LAT2) was decreased in small-for-gestational-age (SGA) placentas. LAT1, LAT2 and taurine transporter (TAUT) expression correlated to PPARγ level and birth weight. In cultured placental cells, PPARγ agonist stimulated LAT1 and LAT2 and TAUT, which was reversed by PPARγ siRNA. PPARγ up-regulation of LAT1 and TAUT was through specificity protein 1 (Sp-1) while stimulation of LAT2 expression was via induction of gene transcription. Our data suggest that PPARγ, SP-1, LAT1 and LAT2 in placentas are involved in control of fetal growth. PPARγ signaling pathway may be the therapeutic target for intrauterine growth restriction. PMID:26227476

  17. PPARγ stimulates expression of L-type amino acid and taurine transporters in human placentas: the evidence of PPARγ regulating fetal growth.

    PubMed

    Chen, Zhaoguang; He, Ping; Ding, Xiaoying; Huang, Ying; Gu, Hang; Ni, Xin

    2015-07-31

    Placental amino acid transporters and peroxisome proliferator-activated receptors (PPARs) have been implicated to placental development and therefore regulation of fetal growth. We analyzed the correlation between the expression of amino acid transporters and PPARs and investigated whether PPARs control the expression of amino acid transporters in placentas. It was found that protein expression of PPARγ and L-type amino acid transporter 1(LAT1) and 2 (LAT2) was decreased in small-for-gestational-age (SGA) placentas. LAT1, LAT2 and taurine transporter (TAUT) expression correlated to PPARγ level and birth weight. In cultured placental cells, PPARγ agonist stimulated LAT1 and LAT2 and TAUT, which was reversed by PPARγ siRNA. PPARγ up-regulation of LAT1 and TAUT was through specificity protein 1 (Sp-1) while stimulation of LAT2 expression was via induction of gene transcription. Our data suggest that PPARγ, SP-1, LAT1 and LAT2 in placentas are involved in control of fetal growth. PPARγ signaling pathway may be the therapeutic target for intrauterine growth restriction.

  18. Factors affecting Staphylococcus epidermidis growth in peritoneal dialysis solutions.

    PubMed Central

    McDonald, W A; Watts, J; Bowmer, M I

    1986-01-01

    Staphylococcus epidermidis is the most frequent cause of peritonitis complicating continuous ambulatory peritoneal dialysis. We studied factors that might influence the growth of S. epidermidis in commercially available peritoneal dialysis solution (PDS). Test strains were inoculated into PDS and incubated overnight at 37 degrees C. Samples were removed at appropriate intervals, bacterial counts were performed, and growth curves were constructed. We studied the effects of various osmolarities, the neutralization and acidification of fresh and spent PDS, and the effect of intraperitoneal dwell time on the ability PDS to support growth of S. epidermidis. In fresh PDS, numbers of bacteria remained constant after 24 h. No significant differences in growth were observed among PDS with 0.5, 1.5, 2.5, and 4.25% glucose. Neutralizing acidic fresh PDS had no effect on bacterial growth. However, growth did occur in spent PDS. PDS which was recovered after only 2 h in the peritoneal cavity supported growth to the same extent as did PDS recovered after 4 to 6 h. Mean log10 changes after 24 h of incubation were as follows: for fresh PDS, -1.3; after 2 h dwell time, 2.9; after 4 h dwell time, 1.9; and after 6 h dwell time, 1.3. Acidification of spent PDS to less than pH 6.35 produced less rapid growth; mean log10 increases after 24 h of incubation were 1.9 for pH 7.75, 1.6 for pH 6.35, 0.6 for pH 5.75, and 0.7 for pH 4.95. Fresh PDS of all available osmolarities neither supported the growth of S. epidermidis nor was bactericidal. Spent PDS supported bacterial growth, and this growth was partly independent of the neutralization which occurred during the dialysis. PMID:3722356

  19. Organizational Career Growth, Affective Occupational Commitment and Turnover Intentions

    ERIC Educational Resources Information Center

    Weng, Qingxiong; McElroy, James C.

    2012-01-01

    Survey data, collected from the People's Republic of China, were used to test Weng's (2010) four facet model of career growth and to examine its effect on occupational commitment and turnover intentions. Weng conceptualized career growth as consisting of four factors: career goal progress, professional ability development, promotion speed, and…

  20. Environmental Crack Growth Behavior Affected by Thickness/Geometry Constraint

    NASA Astrophysics Data System (ADS)

    Kujawski, Daniel

    2013-03-01

    This article gives a short review on the effects of thickness/constraint and environment on crack growth behavior under cyclic and static loadings. Fatigue crack growth data taken from the literature, corresponding to different environments, ranging from vacuum to air and NaCl solution for a number of alloys and different specimens geometries are presented and analyzed. Reported results indicate that for relatively inert material/environment systems, there is a weak thickness/constraint effect on fatigue crack growth behavior. On the other hand, for corrosive material/environment systems, there is a significant thickness/constraint effect on crack growth rate behavior under both cyclic and static loadings. Some implications related to crack growth modeling are suggested.

  1. Slower Economic Growth Affects the 1995 Labor Market.

    ERIC Educational Resources Information Center

    Gardner, Jennifer M.; Hayghe, Howard V.

    1996-01-01

    Shows how job growth slowed dramatically in 1995, but the unemployment rate remained little changed. Discusses trends in nonfarm payroll employment by industry and changes in employment status of people in various demographic and occupational groups. (Author)

  2. Artificial oxygen carriers rescue placental hypoxia and improve fetal development in the rat pre-eclampsia model.

    PubMed

    Li, Heng; Ohta, Hidenobu; Tahara, Yu; Nakamura, Sakiko; Taguchi, Kazuaki; Nakagawa, Machiko; Oishi, Yoshihisa; Goto, Yu-Ichi; Wada, Keiji; Kaga, Makiko; Inagaki, Masumi; Otagiri, Masaki; Yokota, Hideo; Shibata, Shigenobu; Sakai, Hiromi; Okamura, Kunihiro; Yaegashi, Nobuo

    2015-10-16

    Pre-eclampsia affects approximately 5% of all pregnant women and remains a major cause of maternal and fetal morbidity and mortality. The hypertension associated with pre-eclampsia develops during pregnancy and remits after delivery, suggesting that the placenta is the most likely origin of this disease. The pathophysiology involves insufficient trophoblast invasion, resulting in incomplete narrow placental spiral artery remodeling. Placental insufficiency, which limits the maternal-fetal exchange of gas and nutrients, leads to fetal intrauterine growth restriction. In this study, in our attempt to develop a new therapy for pre-eclampsia, we directly rescued placental and fetal hypoxia with nano-scale size artificial oxygen carriers (hemoglobin vesicles). The present study is the first to demonstrate that artificial oxygen carriers successfully treat placental hypoxia, decrease maternal plasma levels of anti-angiogenic proteins and ameliorate fetal growth restriction in the pre-eclampsia rat model.

  3. Artificial oxygen carriers rescue placental hypoxia and improve fetal development in the rat pre-eclampsia model

    PubMed Central

    Li, Heng; Ohta, Hidenobu; Tahara, Yu; Nakamura, Sakiko; Taguchi, Kazuaki; Nakagawa, Machiko; Oishi, Yoshihisa; Goto, Yu-ichi; Wada, Keiji; Kaga, Makiko; Inagaki, Masumi; Otagiri, Masaki; Yokota, Hideo; Shibata, Shigenobu; Sakai, Hiromi; Okamura, Kunihiro; Yaegashi, Nobuo

    2015-01-01

    Pre-eclampsia affects approximately 5% of all pregnant women and remains a major cause of maternal and fetal morbidity and mortality. The hypertension associated with pre-eclampsia develops during pregnancy and remits after delivery, suggesting that the placenta is the most likely origin of this disease. The pathophysiology involves insufficient trophoblast invasion, resulting in incomplete narrow placental spiral artery remodeling. Placental insufficiency, which limits the maternal-fetal exchange of gas and nutrients, leads to fetal intrauterine growth restriction. In this study, in our attempt to develop a new therapy for pre-eclampsia, we directly rescued placental and fetal hypoxia with nano-scale size artificial oxygen carriers (hemoglobin vesicles). The present study is the first to demonstrate that artificial oxygen carriers successfully treat placental hypoxia, decrease maternal plasma levels of anti-angiogenic proteins and ameliorate fetal growth restriction in the pre-eclampsia rat model. PMID:26471339

  4. Endotoxin-induced nitric oxide production rescues airway growth and maturation in atrophic fetal rat lung explants

    SciTech Connect

    Rae, C.; Cherry, J.I.; Land, F.M.; Land, S.C. . E-mail: s.c.land@dundee.ac.uk

    2006-10-13

    Inflammation induces premature maturation of the fetal lung but the signals causing this effect remain unclear. We determined if nitric oxide (NO) synthesis, evoked by Escherichia coli lipopolysaccharide (LPS, 2 {mu}g ml{sup -1}), participated in this process. Fetal rat lung airway surface complexity rose 2.5-fold over 96 h in response to LPS and was associated with increased iNOS protein expression and activity. iNOS inhibition by N6-(1-iminoethyl)-L-lysine-2HCl (L-NIL) abolished this and induced airway atrophy similar to untreated explants. Surfactant protein-C (SP-C) expression was also induced by LPS and abolished by L-NIL. As TGF{beta} suppresses iNOS activity, we determined if feedback regulation modulated NO-dependent maturation. LPS induced TGF{beta}1 release and SMAD4 nuclear translocation 96 h after treatment. Treatment of explants with a blocking antibody against TGF{beta}1 sustained NO production and airway morphogenesis whereas recombinant TGF{beta}1 antagonized these effects. Feedback regulation of NO synthesis by TGF{beta} may, thus, modulate airway branching and maturation of the fetal lung.

  5. Some factors affecting the growth and decay of plages

    NASA Astrophysics Data System (ADS)

    Howard, Robert F.

    1993-09-01

    The Mount Wilson coarse array magnetograph data set is analyzed to examine the dependence of growth and decay rates on the tilt angles of the magnetic axes of the regions. It is found that there is a relationship between these quantities which is similar to that found earlier for sunspot groups. Regions near the average tilt angle show larger average (absolute) growth and decay rates. The percentage growth and decay rates show minima (in absolute values) at the average tilt angles because the average areas of regions are largest near this angle. This result is similar to that derived earlier for sunspot groups. As in the case of spot groups, this suggests that, for decay, the effect results from the fact that the average tilt angle may represent the simplest subsurface configuration of the flux loop or loops that make up the region. In the case of region growth, it was suggested that the more complicated loop configuration should result in increased magnetic tension in the flux loop, and thus in a slower ascent of the loop to the surface, and thus a slower growth rate.

  6. Corn metabolites affect growth and virulence of Agrobacterium tumefaciens.

    PubMed Central

    Sahi, S V; Chilton, M D; Chilton, W S

    1990-01-01

    Homogenates of corn seedlings inhibit both growth of Agrobacterium tumefaciens and induction of its Ti plasmid virulence (vir) genes by acetosyringone (AS). The heat-labile inhibitor has been identified as 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA), present in 2-week-old seedlings (B73) at a concentration of 1.5 mM or greater. A concentration of 0.3 mM DIMBOA is sufficient to block growth of A. tumefaciens completely for 220 hr. DIMBOA at 0.1 mM concentration completely inhibited vir gene induction by 100 microM AS and reduced growth rate by 50%. Thus, DIMBOA can be expected to have a significant effect on attempts to transform corn by using A. tumefaciens as a vector. Images PMID:11607078

  7. Factors affecting plant growth in membrane nutrient delivery

    NASA Technical Reports Server (NTRS)

    Dreschel, T. W.; Wheeler, R. M.; Sager, J. C.; Knott, W. M.

    1990-01-01

    The development of the tubular membrane plant growth unit for the delivery of water and nutrients to roots in microgravity has recently focused on measuring the effects of changes in physical variables controlling solution availability to the plants. Significant effects of membrane pore size and the negative pressure used to contain the solution were demonstrated. Generally, wheat grew better in units with a larger pore size but equal negative pressure and in units with the same pore size but less negative pressure. Lettuce also exhibited better plant growth at less negative pressure.

  8. Shade periodicity affects growth of container grown dogwoods

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Container-grown dogwoods rank third in the US in nursery sales of ornamental trees. However, Dogwoods are a challenging crop to produce in container culture, especially when bare root liners are used as the initial transplant into containers due unacceptable levels of mortality and poor growth. This...

  9. Dissolved oxygen concentration affects hybrid striped bass growth

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Management of dissolved oxygen (DO) concentration in ponds at night during the growing season is important because fish growth and yield are greater in ponds with higher nightly DO concentrations. Three studies were conducted to quantify performance traits and metabolic responses of hybrid striped b...

  10. A Comparative Study of Growth Kinetics, In Vitro Differentiation Potential and Molecular Characterization of Fetal Adnexa Derived Caprine Mesenchymal Stem Cells

    PubMed Central

    Somal, Anjali; Bhat, Irfan A.; B., Indu; Pandey, Sriti; Panda, Bibhudatta S. K.; Thakur, Nipuna; Sarkar, Mihir; Chandra, Vikash; Saikumar, G.; Sharma, G. Taru

    2016-01-01

    The present study was conducted with an objective of isolation, in vitro expansion, growth kinetics, molecular characterization and in vitro differentiation of fetal adnexa derived caprine mesenchymal stem cells. Mid-gestation gravid caprine uteri (2–3 months) were collected from abattoir to derive mesenchymal stem cells (MSCs) from fetal adnexa {amniotic fluid (cAF), amniotic sac (cAS), Wharton’s jelly (cWJ) and cord blood (cCB)} and expanded in vitro. These cultured MSCs were used at the 3rd passage (P3) to study growth kinetics, localization as well as molecular expression of specific surface antigens, pluripotency markers and mesenchymal tri-lineage differentiation. In comparison to cAF and cAS MSCs, cWJ and cCB MSCs showed significantly (P<0.05) higher clonogenic potency, faster growth rate and low population doubling (PDT) time. All the four types of MSCs were positive for alkaline phosphatase (AP) and differentiated into chondrogenic, osteogenic, and adipogenic lineages. These stem cells expressed MSC surface antigens (CD73, CD90 and CD105) and pluripotency markers (Oct4, Sox2, Nanog, KLF, cMyc, FoxD3) but did not express CD34, a hematopoietic stem cell marker (HSC) as confirmed by RT-PCR, immunocytochemistry and flow cytometric analysis. The relative mRNA expression of MSC surface antigens (CD73, CD90 and CD105) was significantly (P<0.05) higher in cWJ MSCs compared to the other cell lines. The mRNA expression of Oct4 was significantly (P<0.05) higher in cWJ, whereas mRNA expression of KLF and cMyc was significantly (P<0.05) higher in cWJ and cAF than that of cAS and cCB. The comparative assessment revealed that cWJ MSCs outperformed MSCs from other sources of fetal adnexa in terms of growth kinetics, relative mRNA expression of surface antigens, pluripotency markers and tri-lineage differentiation potential, hence, these MSCs could be used as a preferred source for regenerative medicine. PMID:27257959

  11. Phasic temperature change patterns affect growth and tuberization in potatoes

    SciTech Connect

    Cao, W.; Tibbitts, T.W. . Dept. of Horticulture)

    1994-07-01

    This study determined the response of potato (Solanum tuberosum L., cv. Norland) plants to various patterns of air temperature changes over different growth periods. In each of two experiments under controlled environments, eight treatments of temperature changes were carried out in two growth rooms maintained at 17 and 22 C and a constant vapor pressure deficit of 0.60 kPa and 14-hour photoperiod. Plants were grown for 63 days after transplanting of tissue culture plantlets in 20-liter pots containing peat-vermiculite mix. Temperature changes were imposed on days 21 and 42, which were essentially at the beginning of tuber initiation and tuber enlargement, respectively, for this cultivar. Plants were moved between two temperature rooms to obtain eight temperature change patterns: 17-17-17, 17-17-22, 17-22-17, 22-17-17, 17-22-22, 22-17-22, 22-22-17, and 22-22-22C over three 21-day growth periods. At harvest on day 63, total plant dry weight was higher for the treatments beginning with 22 C than for those beginning with 17C, with highest biomass obtained at 22-22-17 and 22-17-17C. Shoot dry weight increased with temperature increased from 17-17-17 to 22-22-22C during the three growth periods. Tuber dry weight was highest with 22-17-17C, and lowest with 17-17-22 and 17-22-22C. With 22-17-17C, both dry weights of stolons and roots were lowest. Total tuber number and number of small tubers were highest with 17-17-17 and 17-17-22C, and lowest with 17-22-22 and 22-22-22C, whereas number of medium tubers was highest with 22-17-22C, and number of large tubers was highest with 22-17-17C. This study indicates that tuber development of potatoes is optimized with a phasic pattern of high temperature during early growth and low temperature during later growth.

  12. Effects of maternal subtotal nephrectomy on the development of the fetal kidney: A morphometric study.

    PubMed

    Kondo, Tomohiro; Kitano-Amahori, Yoko; Nagai, Hiroaki; Mino, Masaki; Takeshita, Ai; Kusakabe, Ken Takeshi; Okada, Toshiya

    2015-11-01

    The present study was designed to explore if maternal subtotal (5/6) nephrectomy affects the development of fetal rat kidneys using morphometric methods and examining whether there are any apoptotic changes in the fetal kidney. To generate 5/6 nephrectomized model rats, animals underwent 2/3 left nephrectomy on gestation day (GD) 5 and total right nephrectomy on GD 12. The fetal kidneys were examined on GDs 16 and 22. A significant decrease in fetal body weight resulting from maternal 5/6 nephrectomy was observed on GD 16, and a significant decrease in fetal renal weight and fetal body weight caused by maternal nephrectomy was observed on GD 22. Maternal 5/6 nephrectomy induced a significant increase in glomerular number, proximal tubular length, and total proximal tubular volume of fetuses on GD 22. Maternal 5/6 nephrectomy resulted in an increase in the number of apoptotic cells in the metanephric mesenchyme of the kidney on GD 16, and in the collecting tubules on GD 22. These findings suggest that maternal 5/6 nephrectomy stimulates the development of the fetal kidney while suppressing fetal growth.

  13. Growth and aggressiveness factors affecting Monilinia spp. survival peaches.

    PubMed

    Villarino, M; Melgarejo, P; De Cal, A

    2016-05-01

    Brown rot of stone fruit is caused by three species of Monilinia, Monilinia laxa, M. fructigena, and M. fructicola. Eleven components of 20 different isolates of each of the three Monilinia species were analysed to determine distinct aggressiveness and growth characteristics among the three fungi. M. fructicola showed the greatest lesion diameter, and the lowest incubation and latency period on fruit postharvest, however isolates of M. fructigena exhibited less aggressiveness components. Five growth characteristics of M. fructicola could be used to distinguish M. fructicola from the other two species. The dendrogram generated from only the presence of sclerotia and lesion length on infected fruit separated the 60 isolates into two clusters (r=0.93). One cluster was composed of the M. laxa and M. fructigena isolates and the other cluster comprised the M. fructicola isolates. However, the dendrogram generated based on the presence of stromata and sclerotia in the same colony of the three species when they were grown on potato dextrose agar, and the lesion diameter on fruit infected with each species separated the 60 isolates into three clusters (r=0.81). Each cluster comprised the isolates of each of three Monilinia spp. We discussed the effect of M. fructicola growth and aggressiveness differences on the displacement of M. laxa and M. fructigena by M. fructicola recorded in Spanish peach orchards and their effect on brown rot at postharvest.

  14. Organic Matter Loading Affects Lodgepole Pine Seedling Growth

    NASA Astrophysics Data System (ADS)

    Wei, Xiaohua; Li, Qinglin; Waterhouse, M. J.; Armleder, H. M.

    2012-06-01

    Organic matter plays important roles in returning nutrients to the soil, maintaining forest productivity and creating habitats in forest ecosystems. Forest biomass is in increasing demand for energy production, and organic matter has been considered as a potential supply. Thus, an important management question is how much organic matter should be retained after forest harvesting to maintain forest productivity. To address this question, an experimental trial was established in 1996 to evaluate the responses of lodgepole pine seedling growth to organic matter loading treatments. Four organic matter loading treatments were randomly assigned to each of four homogeneous pine sites: removal of all organic matter on the forest floor, organic matter loading quantity similar to whole-tree-harvesting residuals left on site, organic matter loading quantity similar to stem-only-harvesting residuals, and organic matter loading quantity more similar to what would be found in disease- or insect-killed stands. Our 10-year data showed that height and diameter had 29 and 35 % increase, respectively, comparing the treatment with the most organic matter loading to the treatment with the least organic matter loading. The positive response of seedling growth to organic matter loading may be associated with nutrients and/or microclimate change caused by organic matter, and requires further study. The dynamic response of seedling growth to organic matter loading treatments highlights the importance of long-term studies. Implications of those results on organic matter management are discussed in the context of forest productivity sustainability.

  15. Growth and aggressiveness factors affecting Monilinia spp. survival peaches.

    PubMed

    Villarino, M; Melgarejo, P; De Cal, A

    2016-06-16

    Brown rot of stone fruit is caused by three species of Monilinia, Monilinia laxa, M. fructigena, and M. fructicola. Eleven components of 20 different isolates of each of the three Monilinia species were analyzed to determine distinct aggressiveness and growth characteristics among the three fungi. M. fructicola showed the greatest lesion diameter, and the lowest incubation and latency period on fruit postharvest, however isolates of M. fructigena exhibited less aggressiveness components. Five growth characteristics of M. fructicola could be used to distinguish M. fructicola from the other two species. The dendrogram generated from only the presence of sclerotia and lesion length on infected fruit separated the 60 isolates into two clusters (r=0.93). One cluster was composed of the M. laxa and M. fructigena isolates and the other cluster comprised the M. fructicola isolates. However, the dendrogram generated based on the presence of stromata and sclerotia in the same colony of the three species when they were grown on potato dextrose agar, and the lesion diameter on fruit infected with each species separated the 60 isolates into three clusters (r=0.81). Each cluster comprised the isolates of each of three Monilinia spp. We discussed the effect of M. fructicola growth and aggressiveness differences on the displacement of M. laxa and M. fructigena by M. fructicola recorded in Spanish peach orchards and their effect on brown rot at postharvest. PMID:27043383

  16. Growth in body size affects rotational performance in women's gymnastics.

    PubMed

    Ackland, Timothy; Elliott, Bruce; Richards, Joanne

    2003-07-01

    National and state representative female gymnasts (n = 37), aged initially between 10 and 12 years, completed a mixed longitudinal study over 3.3 years, to investigate the effect of body size on gymnastic performance. Subjects were tested at four-monthly intervals on a battery of measures including structural growth, strength and gymnastic performance. The group were divided into 'high growers' and 'low growers' based on height (> 18 cm or < 14 cm/37 months, respectively) and body mass (> 15 kg or < 12 kg/37 months, respectively) for comparative purposes. Development of gymnastic performance was assessed through generic skills (front and back rotations, a twisting jump and a V-sit action) and a vertical jump for maximum height. The results show that the smaller gymnast, with a high strength to mass ratio, has greater potential for performing skills involving whole-body rotations. Larger gymnasts, while able to produce more power and greater angular momentum, could not match the performance of the smaller ones. The magnitude of growth experienced by the gymnast over this period has a varying effect on performance. While some activities were greatly influenced by rapid increases in whole-body moment of inertia (e.g. back rotation), performance on others like the front rotation and vertical jump, appeared partly immune to the physical and mechanical changes associated with growth. PMID:14737925

  17. Growth and aggressiveness factors affecting Monilinia spp. survival peaches.

    PubMed

    Villarino, M; Melgarejo, P; De Cal, A

    2016-05-01

    Brown rot of stone fruit is caused by three species of Monilinia, Monilinia laxa, M. fructigena, and M. fructicola. Eleven components of 20 different isolates of each of the three Monilinia species were analysed to determine distinct aggressiveness and growth characteristics among the three fungi. M. fructicola showed the greatest lesion diameter, and the lowest incubation and latency period on fruit postharvest, however isolates of M. fructigena exhibited less aggressiveness components. Five growth characteristics of M. fructicola could be used to distinguish M. fructicola from the other two species. The dendrogram generated from only the presence of sclerotia and lesion length on infected fruit separated the 60 isolates into two clusters (r=0.93). One cluster was composed of the M. laxa and M. fructigena isolates and the other cluster comprised the M. fructicola isolates. However, the dendrogram generated based on the presence of stromata and sclerotia in the same colony of the three species when they were grown on potato dextrose agar, and the lesion diameter on fruit infected with each species separated the 60 isolates into three clusters (r=0.81). Each cluster comprised the isolates of each of three Monilinia spp. We discussed the effect of M. fructicola growth and aggressiveness differences on the displacement of M. laxa and M. fructigena by M. fructicola recorded in Spanish peach orchards and their effect on brown rot at postharvest. PMID:26918325

  18. Regulation by glucocorticoids of cell differentiation and insulin-like growth factor binding protein production in cultured fetal rat nasal chondrocytes.

    PubMed

    Nadra, Reem; Menuelle, Pierrette; Chevallier, Sylviana; Berdal, Ariane

    2003-04-01

    Glucocorticoids (GCs) modulate insulin-like growth factor action in cartilage through mechanisms that are complex and insufficiently defined, especially in the context of cranio-facial growth. Because the family of IGF-binding proteins (IGFBP-1 to -6) is important in the regulation of IGF availability and bioactivity, we examined the effect of GCs on chondrocyte differentiation in correlation with IGFBP production in cultured fetal rat chondrocytes isolated from nasal septum cartilage of fetal rat. Dexamethasone (DEX) effects were tested before and at the onset of extracellular matrix maturation. DEX induced a dose-dependent increase in the size of cartilage nodule formed, (45)Ca incorporation into extracellular matrix, alkaline phosphatase activity, and sulfatation of glycosaminoglycans, maximal effects being obtained with a 10-mM DEX concentration. The IGFBPs produced by cultured chondrocytes were characterized in culture medium which had been conditioned for 24 h under serum-free conditions by these cells. Western ligand blotting with a mixture of [(125)I]IGF-I and -II revealed bands of 20, 24, 29, a 31-32 kDa doublet and a 39-41 kDa triplet which were differently regulated by DEX. Immunoblotting showed that following DEX exposure, IGFBP-3 and -6 were up-regulated whereas IGFBP-2, -5, and the 24 kDa band were down-regulated. The effect of DEX on both differentiation and IGFBP production showed a same dependence, and developed when extracellular matrix maturation had been just induced. The results obtained in this chondrocyte culture system show that production of IGFBPs is modulated by DEX at physiological concentrations thus regulating IGF availability and action, a control which could promote the primordial role of the rat nasal septum in craniofacial growth.

  19. Evaluation methods for intrauterine growth using neonatal fat stores instead of birth weight as outcome measures: fetal and neonatal measurements correlated with neonatal skinfold thicknesses.

    PubMed

    Sumners, J E; Findley, G M; Ferguson, K A

    1990-01-01

    Neonatal anthropometry, including timed skinfold measurements, was performed on 55 products of selected pregnancies. These skinfold measurements were compared with published standards of measurements obtained by similar techniques. Values outside the 3rd percentile to 97th percentile range were overlaid on the birth weight/menstrual age relationship of these subjects. Seven of 10 subjects with the lowest midtriceps skinfolds weighed more than 2500 g at birth (2 more than 3500 g) and 2 of 4 with the largest midtriceps skinfold had birth weights less than 4000 g. This comparison emphasizes the imprecision of birth weight as a measure of quality of fetal growth. Since skinfold thickness measurement is cumbersome for clinical use, other neonatal measures that may be more readily available to the clinician were examined for correlation with skinfolds. Simple birth weight/crown-heel length ratio was found to have the closest relationship of the parameters examined. Although estimated fetal weight was found to be the ultrasonography-derived parameter best correlated with skinfold thickness, ultrasonography discriminated poorly between babies with normal and low skinfolds. Low skinfold thickness predicted thermal vulnerability in the nursery better than did birth weight.

  20. Gestational dexamethasone alters fetal neuroendocrine axis.

    PubMed

    Ahmed, R G

    2016-09-01

    This study tested whether the maternal transport of dexamethasone (DEXA) may affect the development of the neuroendocrine system. DEXA (0.2mg/kg b.w., subcutaneous injection) was administered to pregnant rats from gestation day (GD) 1-20. In the DEXA-treated group, a decrease in maternal serum thyroxine (T4), triiodothyronine (T3), and increase in thyrotropin (TSH) levels (hypothyroid status) were observed at GDs 15 & 20 with respect to control group. The reverse pattern (hyperthyroid status) was observed in their fetuses at embryonic days (EDs) 15 & 20. Although the maternal body weight was diminished, the weight of the thyroid gland was increased at studied GDs as compared to the control group. The fetal growth retardation, hyperleptinemia, hyperinsulinism, and cytokines distortions (transforming growth factor-beta; TGF-β, tumor necrosis factor-alpha; TNF-α, and interferon-γ; IFN-γ) were noticed at examined EDs if compared to the control group. Alternatively, the maternofetal thyroid dysfunctions due to the maternal DEXA administration attenuated the levels of fetal cerebral norepinephrine (NE) and epinephrine (E), and elevated the levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) at considered days. These alterations were age-dependent and might damage the nerve transmission. Finally, maternal DEXA might act as neuroendocrine disruptor causing dyshormonogenesis and fetal cerebral dysfunction. PMID:27220267

  1. Formaldehyde exposure affects growth and metabolism of common bean

    SciTech Connect

    Mutters, R.G.; Madore, M. ); Bytnerowicz, A. )

    1993-01-01

    Recent state and federal directives have slated a substantial increase in the use of methanol as an alternative to gasoline in both fleet and private vehicles in the coming decade. The incomplete combustion of methanol produces formaldehyde vapor, and catalytic converter technology that completely oxidizes formaldehyde has yet to be developed. The approach of this study was to use a range of methanol concentrations encompassing levels currently found or that may occur in the future in the ambient air of some heavily polluted areas to test the potential phytotoxicity of formaldehyde. The study had the following objectives: (1) design and build a formaldehyde vapor generator with sufficient capacity for long-term plant fumigations; (2) determine growth response of common bean to formaldehyde; (3) evaluate physiological and biochemical changes of bean plants associated with formaldehyde exposures. 20 refs., 2 figs., 2 tabs.

  2. Fetal MRI: A pictorial essay.

    PubMed

    Rathee, Sapna; Joshi, Priscilla; Kelkar, Abhimanyu; Seth, Nagesh

    2016-01-01

    Ultrasonography (USG) is the primary method for antenatal fetal evaluation. However, fetal magnetic resonance imaging (MRI) has now become a valuable adjunct to USG in confirming/excluding suspected abnormalities and in the detection of additional abnormalities, thus changing the outcome of pregnancy and optimizing perinatal management. With the development of ultrafast sequences, fetal MRI has made remarkable progress in recent times. In this pictorial essay, we illustrate a spectrum of structural abnormalities affecting the central nervous system, thorax, genitourinary and gastrointestinal tract, as well as miscellaneous anomalies. Anomalies in twin gestations and placental abnormalities have also been included.

  3. Fetal MRI: A pictorial essay

    PubMed Central

    Rathee, Sapna; Joshi, Priscilla; Kelkar, Abhimanyu; Seth, Nagesh

    2016-01-01

    Ultrasonography (USG) is the primary method for antenatal fetal evaluation. However, fetal magnetic resonance imaging (MRI) has now become a valuable adjunct to USG in confirming/excluding suspected abnormalities and in the detection of additional abnormalities, thus changing the outcome of pregnancy and optimizing perinatal management. With the development of ultrafast sequences, fetal MRI has made remarkable progress in recent times. In this pictorial essay, we illustrate a spectrum of structural abnormalities affecting the central nervous system, thorax, genitourinary and gastrointestinal tract, as well as miscellaneous anomalies. Anomalies in twin gestations and placental abnormalities have also been included. PMID:27081224

  4. Effects of stage of gestation and nutrient restriction during early to mid-gestation on maternal and fetal visceral organ mass and indices of jejunal growth and vascularity in beef cows.

    PubMed

    Meyer, A M; Reed, J J; Vonnahme, K A; Soto-Navarro, S A; Reynolds, L P; Ford, S P; Hess, B W; Caton, J S

    2010-07-01

    The objectives were to evaluate effects of maternal nutrient restriction and stage of gestation on maternal and fetal visceral organ mass and indices of jejunal growth and vascularity in beef cows. Thirty multiparous beef cows (BW = 571 +/- 63 kg; BCS = 5.4 +/- 0.7) carrying female fetuses (d 30 of gestation) were allocated to receive a diet of native grass hay (CON; 12.1% CP, 70.7% IVDMD, DM basis) to meet NRC recommendations for BW gain during early gestation or a nutrient-restricted diet of millet straw (NR; 9.9% CP, 54.5% IVDMD, DM basis) to provide 68.1% of NE(m) and 86.7% of MP estimated requirements. On d 125 of gestation, 10 CON and 10 NR cows were killed and necropsied. Five remaining CON cows received the CON diet, and 5 NR cows were realimented with a concentrate supplement (13.2% CP, 77.6% IVDMD, DM basis) and the CON hay to achieve a BCS similar to CON cows by d 220 of gestation. Remaining cows were necropsied on d 245 of gestation. Cow BW and eviscerated BW (EBW) were less (P < 0.01) for NR than CON at d 125 but did not differ (P > 0.63) at d 245. Cows fed the CON diet had greater (P < 0.09) total gastrointestinal (GI) tract, omasal, and pancreatic weights. Stomach complex, ruminal, and liver weights were greater for CON than NR cows (P < 0.09) on d 125. Total GI, stomach complex, and pancreatic weights increased (P < 0.001) with day of gestation. Restricted cows had decreased (P = 0.09) duodenal RNA:DNA compared with CON. Duodenal DNA was less (P = 0.01) and jejunal RNA:DNA (P = 0.09) was greater for cows at d 125 vs. 245. Cow jejunal capillary area density increased with day of gestation (P = 0.02). Fetal BW and EBW were unaffected by dietary treatment (P > or = 0.32). Total GI tract and all components increased in mass with day of gestation (P < 0.001). Fetuses from NR dams had greater (P = 0.003) reticular mass at d 245 than CON fetuses. Fetuses from NR cows had greater (P = 0.02) percent jejunal proliferation at d 125 and greater (P = 0.03) total

  5. Progestin treatment does not affect expression of cytokines, steroid receptors, oxytocin receptor, and cyclooxygenase 2 in fetal membranes and endometrium from pony mares at parturition.

    PubMed

    Palm, F; Walter, I; Nowotny, N; Budik, S; Helmreich, M; Aurich, C

    2013-01-01

    In most mammalian species, progestins have a major function in maintaining pregnancy. In humans, the physiologic initiation of parturition bears similarities with inflammatory processes and anti-inflammatory effects of progestins have been suggested to postpone birth until term. To examine if comparable effects exist in the horse, mares were treated with the synthetic progestin altrenogest from day 280 of gestation until parturition (N = 5) or were left untreated as controls (N = 7). Tissue from the amnion (AMN), allantochorion (AC), and endometrium (EM) was collected at foaling and mRNA expression of interleukin (IL)-6 and -8, cyclooxygenase 2 (COX2), estrogen receptor (ER) α, progesterone receptor, and oxytocin receptor (OTR) was analyzed. Leukocytes, steroid receptors, COX2, and OTR were also investigated by histology and immunohistochemistry. Expression of mRNA for IL-6 was higher in AMN and EM versus AC (P < 0.01). Expression of IL-8 was higher in AMN than AC and EM (P < 0.001). Steroid receptors and OTR were highly expressed in EM but not in AMN and AC (P < 0.001). Expression of COX2 was most pronounced in AC whereas IL expression was not upregulated in AC. No differences in mRNA expression existed between altrenogest-treated and control animals. Endometrial polymorphonuclear leukocytes were increased in altrenogest-treated mares. Epithelial cells of all tissues, except AC chorionic villi stained progesterone receptor-positive. Staining for ER was more pronounced in the amnion facing epithelium of the AC in altrenogest-treated versus control animals (P < 0.01). In conclusion, COX2 is highly expressed in the AC. The fetal membranes thus might play a role in the onset of labor in the horse. Altrenogest did not affect gene expression in the AMN, AC, and EM but had localized effects on inflammatory cells and ER expression. No anti-inflammatory effects of altrenogest in healthy, late pregnant pony mares could be detected.

  6. IFPA meeting 2014 workshop report: Animal models to study pregnancy pathologies; new approaches to study human placental exposure to xenobiotics; biomarkers of pregnancy pathologies; placental genetics and epigenetics; the placenta and stillbirth and fetal growth restriction.

    PubMed

    Barbaux, S; Erwich, J J H M; Favaron, P O; Gil, S; Gallot, D; Golos, T G; Gonzalez-Bulnes, A; Guibourdenche, J; Heazell, A E P; Jansson, T; Laprévote, O; Lewis, R M; Miller, R K; Monk, D; Novakovic, B; Oudejans, C; Parast, M; Peugnet, P; Pfarrer, C; Pinar, H; Roberts, C T; Robinson, W; Saffery, R; Salomon, C; Sexton, A; Staff, A C; Suter, M; Tarrade, A; Wallace, J; Vaillancourt, C; Vaiman, D; Worton, S A; Lash, G E

    2015-04-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2014 there were six themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of animal models, xenobiotics, pathological biomarkers, genetics and epigenetics, and stillbirth and fetal growth restriction.

  7. Ethanol-induced impairment of polyamine homeostasis – A potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome

    SciTech Connect

    Haghighi Poodeh, Saeid; Alhonen, Leena; Salonurmi, Tuire; Savolainen, Markku J.

    2014-03-28

    Highlights: • Polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. • Alcohol administration perturbs polyamine levels in the tissues with various patterns. • Total absence of polyamines in the embryo head at 9.5 dpc is critical for development. • The deficiency is associated with reduction in endothelial cell sprouting in the head. • Retarded migration of neural crest cells may cause development of neural tube defect. - Abstract: Introduction: Polyamines play a fundamental role during embryogenesis by regulating cell growth and proliferation and by interacting with RNA, DNA and protein. The polyamine pools are regulated by metabolism and uptake from exogenous sources. The use of certain inhibitors of polyamine synthesis causes similar defects to those seen in alcohol exposure e.g. retarded embryo growth and endothelial cell sprouting. Methods: CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals 8.75 days post coitum (dpc). The fetal head, trunk, yolk sac and placenta were collected at 9.5 and 12.5 dpc and polyamine concentrations were determined. Results: No measurable quantity of polyamines could be detected in the embryo head at 9.5 dpc, 12 h after ethanol exposure. Putrescine was not detectable in the trunk of the embryo at that time, whereas polyamines in yolk sac and placenta were at control level. Polyamine deficiency was associated with slow cell growth, reduction in endothelial cell sprouting, an altered pattern of blood vessel network formation and consequently retarded migration of neural crest cells and growth restriction. Discussion: Our results indicate that the polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. Alcohol administration, at the critical stage, perturbs polyamine levels with various patterns, depending on the tissue and its developmental stage. The total absence of polyamines in the embryo head at 9.5 dpc may explain why this

  8. Growth of ponderosa pine seedlings as affected by air pollution

    NASA Astrophysics Data System (ADS)

    Momen, B.; Anderson, P. D.; Houpis, J. L. J.; Helms, J. A.

    The effect of air pollution on seedling survival and competitive ability is important to natural and artificial regeneration of forest trees. Although biochemical and physiological processes are sensitive indicators of pollution stress, the cumulative effects of air pollutants on seedling vigor and competitive ability may be assessed directly from whole-plant growth characteristics such as diameter, height, and photosynthetic area. A few studies that have examined intraspecific variation in seedling response to air pollution indicate that genotypic differences are important in assessing potential effects of air pollution on forest regeneration. Here, we studied the effects of acid rain (no-rain, pH 5.1 rain, pH 3.0 rain) and ozone (filtered, ambient, twice-ambient) in the field on height, diameter, volume, the height:diameter ratio, maximum needle length, and time to reach maximum needle length in seedlings of three families of ponderosa pine ( Pinus ponderosa Dougl. ex Laws). Seedling diameter, height, volume, and height:diameter ratio related significantly to their pre-treatment values. Twice-ambient ozone decreased seedling diameter compared with ozone-filtered air. A significant family-by-ozone interaction was detected for seedling height, as the height of only one of the three families was decreased by twice-ambient ozone compared with the ambient level. Seedling diameter was larger and the height:diameter ratio was smaller under pH 3.0 rain compared to either the no-rain or the pH 5.1-rain treatment. This suggests greater seedling vigor, perhaps due to a foliar fertilization effect of the pH 3.0 rain.

  9. Alteration of proteoglycan sulfation affects bone growth and remodeling

    PubMed Central

    Gualeni, Benedetta; de Vernejoul, Marie-Christine; Marty-Morieux, Caroline; De Leonardis, Fabio; Franchi, Marco; Monti, Luca; Forlino, Antonella; Houillier, Pascal; Rossi, Antonio; Geoffroy, Valerie

    2013-01-01

    Diastrophic dysplasia (DTD) is a chondrodysplasia caused by mutations in the SLC26A2 gene, leading to reduced intracellular sulfate pool in chondrocytes, osteoblasts and fibroblasts. Hence, proteoglycans are undersulfated in the cartilage and bone of DTD patients. To characterize the bone phenotype of this skeletal dysplasia we used the Slc26a2 knock-in mouse (dtd mouse), that was previously validated as an animal model of DTD in humans. X-rays, bone densitometry, static and dynamic histomorphometry, and in vitro studies revealed a primary bone defect in the dtd mouse model. We showed in vivo that this primary bone defect in dtd mice is due to decreased bone accrual associated with a decreased trabecular and periosteal appositional rate at the cell level in one month-old mice. Although the osteoclast number evaluated by histomorphometry was not different in dtd compared to wild-type mice, urine analysis of deoxypyridinoline cross-links and serum levels of type I collagen C-terminal telopeptides showed a higher resorption rate in dtd mice compared to wild-type littermates. Electron microscopy studies showed that collagen fibrils in bone were thinner and less organized in dtd compared to wild-type mice. These data suggest that the low bone mass observed in mutant mice could possibly be linked to the different bone matrix compositions/organizations in dtd mice triggering changes in osteoblast and osteoclast activities. Overall, these results suggest that proteoglycan undersulfation not only affects the properties of hyaline cartilage, but can also lead to unbalanced bone modeling and remodeling activities, demonstrating the importance of proteoglycan sulfation in bone homeostasis. PMID:23369989

  10. The effect of repeated acute hypoxaemia on fetal cardiovascular development in the sheep.

    PubMed

    Steyn, C; Hanson, M A

    1998-10-01

    1. Hypoxaemia during intrauterine life may be important in the development of cardiovascular diseases in later life. Thus it was the aim of this study to investigate the effect of repeated acute hypoxia on the cardiovascular development and growth of the fetus. 2. Fourteen fetal sheep (105-109 days gestational age) were instrumented with amniotic and vascular catheters, an electrocardiogram (ECG) electrode and a flow probe around the femoral artery. Seven animals were given repeated acute isocapnic hypoxaemia (Pa,O2 reduced to ca. 13 mmHg) for 1 h every day for 14 days and they were compared to seven animals which remained normoxic throughout with respect to fetal mean arterial blood pressure (MAP), fetal heart rate (FHR), and fetal baro- and chemoreflexes. 3. No differences were found between the two groups of fetuses in FHR, MAP, baro- or chemoreflexes, femoral blood flow, femoral vascular resistance or fetal growth. 4. Repeated acute hypoxaemia of a moderate degree over a period of 2 weeks in late gestation does not affect cardiovascular development or growth in the fetal sheep.

  11. Reproducibility and reliability of fetal cardiac time intervals using magnetocardiography.

    PubMed

    van Leeuwen, P; Lange, S; Klein, A; Geue, D; Zhang, Y; Krause, H J; Grönemeyer, D

    2004-04-01

    We investigated several factors which may affect the accuracy of fetal cardiac time intervals (CTI) determined in magnetocardiographic (MCG) recordings: observer differences, the number of available recording sites and the type of sensor used in acquisition. In 253 fetal MCG recordings, acquired using different biomagnetometer devices between the 15th and 42nd weeks of gestation, P-wave, QRS complex and T-wave onsets and ends were identified in signal averaged data sets independently by different observers. Using a defined procedure for setting signal events, interobserver reliability was high. Increasing the number of registration sites led to more accurate identification of the events. The differences in wave morphology between magnetometer and gradiometer configurations led to deviations in timing whereas the differences between low and high temperature devices seemed to be primarily due to noise. Signal-to-noise ratio played an important overall role in the accurate determination of CTI and changes in signal amplitude associated with fetal maturation may largely explain the effects of gestational age on reproducibility. As fetal CTI may be of value in the identification of pathologies such as intrauterine growth retardation or fetal cardiac hypertrophy, their reliable estimation will be enhanced by strategies which take these factors into account.

  12. Physiologic assessment of fetal compromise: biomarkers of toxic exposure

    SciTech Connect

    Longo, L.D.

    1987-10-01

    Understanding the physiologic and endocrinologic basis of fetal development is a major goal of perinatal biology. During the past decade a number of technological developments have allowed more precise evaluation of the fetus in utero and diagnosis of abnormalities. Despite these methodological achievements, however, there are no specific biological markers currently available to indicate that exposure to a given xenobiotic is associated with a cellular, subcellular, or pharmacodynamic event. This paper evaluates the following issues: what are some of the unique physiologic and endocrinologic features of the fetal milieu interieur. What problems are peculiar to fetal assessment. What are some examples of validated biomarkers and their applicability. What promising biomarkers are on the horizon. How may molecular probes be of value as biological markers of fetal compromise. What are some of the major research gaps and needs, and how should research priorities be set. Some of these topics are addressed. Moreover, the more general role(s) that various diagnostic methods and biological markers can have in an understanding of the regulation of fetal growth and differentiation and the role of xenobiotics in affecting the normal course of events are discussed.

  13. Fetal electrocardiograph

    NASA Astrophysics Data System (ADS)

    Rios, Heriberto; Andrade, Armando; Puente, Ernestina; Lizana, Pablo R.; Mendoza, Diego

    2002-11-01

    The high intra-uterine death rate is due to failure in appropriately diagnosing some problems in the cardiobreathing system of the fetus during pregnancy. The electrocardiograph is one apparatus which might detect problems at an early stage. With electrodes located near the womb and uterus, in a way similar to the normal technique, the detection of so-called biopotential differences, caused by concentrations of ions, can be achieved. The fetal electrocardiograph is based on an ultrasound technique aimed at detecting intrauterine problems in pregnant women, because it is a noninvasive technique due to the very low level of ultrasound power used. With this system, the following tests can be done: Heart movements from the ninth week onwards; Rapid and safe diagnosis of intrauterine fetal death; Location and size of the placenta. The construction of the fetal electrocardiograph requires instrument level components directly mounted on the printed circuit board, in order to avoid stray capacitance in the cabling which prevents the detection of the E.C.G. activity. The low cost of the system makes it affordable to low budget institutions; in contrast, available commercial systems are priced in U.S. Dollars. (To be presented in Spanish.)

  14. Complete Biallelic Insulation at the H19/Igf2 Imprinting Control Region Position Results in Fetal Growth Retardation and Perinatal Lethality

    PubMed Central

    Lee, Dong-Hoon; Singh, Purnima; Tsark, Walter M. K.; Szabó, Piroska E.

    2010-01-01

    Background The H19/Igf2 imprinting control region (ICR) functions as an insulator exclusively in the unmethylated maternal allele, where enhancer-blocking by CTCF protein prevents the interaction between the Igf2 promoter and the distant enhancers. DNA methylation inhibits CTCF binding in the paternal ICR allele. Two copies of the chicken β-globin insulator (ChβGI)2 are capable of substituting for the enhancer blocking function of the ICR. Insulation, however, now also occurs upon paternal inheritance, because unlike the H19 ICR, the (ChβGI)2 does not become methylated in fetal male germ cells. The (ChβGI)2 is a composite insulator, exhibiting enhancer blocking by CTCF and chromatin barrier functions by USF1 and VEZF1. We asked the question whether these barrier proteins protected the (ChβGI)2 sequences from methylation in the male germ line. Methodology/Principal Findings We genetically dissected the ChβGI in the mouse by deleting the binding sites USF1 and VEZF1. The methylation of the mutant versus normal (ChβGI)2 significantly increased from 11% to 32% in perinatal male germ cells, suggesting that the barrier proteins did have a role in protecting the (ChβGI)2 from methylation in the male germ line. Contrary to the H19 ICR, however, the mutant (mChβGI)2 lacked the potential to attain full de novo methylation in the germ line and to maintain methylation in the paternal allele in the soma, where it consequently functioned as a biallelic insulator. Unexpectedly, a stricter enhancer blocking was achieved by CTCF alone than by a combination of the CTCF, USF1 and VEZF1 sites, illustrated by undetectable Igf2 expression upon paternal transmission. Conclusions/Significance In this in vivo model, hypomethylation at the ICR position together with fetal growth retardation mimicked the human Silver-Russell syndrome. Importantly, late fetal/perinatal death occurred arguing that strict biallelic insulation at the H19/Igf2 ICR position is not tolerated in development

  15. Cloned cattle fetuses with the same nuclear genetics are more variable than contemporary half-siblings resulting from artificial insemination and exhibit fetal and placental growth deregulation even in the first trimester.

    PubMed

    Lee, Rita S F; Peterson, A James; Donnison, Martyn J; Ravelich, Susan; Ledgard, Anita M; Li, Ning; Oliver, Jan E; Miller, Andria L; Tucker, Fleur C; Breier, Bernhard; Wells, David N

    2004-01-01

    The cloning of cattle by somatic cell nuclear transfer (NT) is associated with a high incidence of abnormal placentation, excessive fluid accumulation in the fetal sacs (hydrops syndrome), and fetal overgrowth. Fetal and placental development was investigated at Day 50, during placentome formation; at Day 100, when placentation was completed; and at Day 150, when the hydrops syndrome frequently develops. The NT fetuses were compared with contemporary half-siblings generated from in vitro-produced embryos or by artificial insemination (AI). Fetal cotyledon formation and vascularization of the chorioallantoic membranes was initiated normally in NT conceptuses, but fewer cotyledons successfully formed placentomes. By Day 100, the mean number of placentomes was significantly lower in surviving NT fetuses. Only those with normal placentome numbers were represented in surviving NT pregnancies at Day 150. The mean total caruncle tissue weight of the placentomes was significantly higher in the surviving NT groups at Days 100 and 150, irrespective of the placentome numbers, indicating that increased NT placental weight was caused by excessive uterine tissue growth. By Day 100, NT fetuses exhibited growth deregulation, and those that survived to Day 150 were 17% heavier than contemporary AI controls. Placentome, liver, and kidney overgrowth accompanied the hydrops syndrome at Day 150. The NT fetal overgrowth was not a consequence of in vitro embryo culture and showed no correlation with placental overgrowth. However, in vitro culture and incomplete reprogramming of the donor genome are epigenetic effects that may override genetic traits and contribute to the greater variability in placental and fetal development in the NT group compared with AI half-siblings.

  16. Evaluation of a synthetic serum substitute to replace fetal cord serum for human oocyte fertilization and embryo growth in vitro.

    PubMed

    Psalti, I; Loumaye, E; Pensis, M; Depreester, S; Thomas, K

    1989-11-01

    A comparison was made between a serum substitute. UltroSer G (Gibco, Ghent, Belgium) (2%) (medium B) and 10% human fetal cord serum (medium A), as regards their ability to support 1-cell and 2-cell mice embryo development in vitro. Sixty percent and 56% of the 1-cell embryos reached the expanded blastocyst stage when cultured in media A and B, respectively. Eighty-four percent and 88% of 2-cell embryos reached the expanded blastocyst stage when cultured in media A and B, respectively. A prospective randomized study was then performed to evaluate this synthetic serum substitute in human in vitro fertilization. Among 141 ovum pick-up (OPU), oocytes retrieved in 74 cases were processed in medium A and oocytes retrieved in 67 others in medium B. In media A and B, the fertilization rate was 67% and 44.3% respectively, and the pregnancy rate/OPU 23% and 9%, respectively. The pregnancy rate/transfer was 28.8% and 12.2% respectively, and the implantation rate/transferred embryo 9.5% and 4.2%. In the human sperm survival assay, the vitality and residual motility after 24 hours of incubation were significantly lower in medium B. In conclusion, UltroSer G successfully sustained the development in vitro of mouse embyros. However in human, it reduced sperm survival, oocyte fertilization, and embryo viability. PMID:2806622

  17. Root pressurization affects growth-induced water potentials and growth in dehydrated maize leaves.

    PubMed

    Tang, An-Ching; Boyer, John S

    2003-11-01

    Profiles of water potential (Psi w) were measured from the soil to the tips of growing leaves of maize (Zea mays L.) when pressure (P) was applied to the soil/root system. At moderately low soil Psi w, leaf elongation was somewhat inhibited, large tensions existed in the xylem, and Psi w were slightly lower in the elongating leaf tissues than in the xylem, i.e. a growth-induced Psi w was present but small. With P, the tension was relieved, enlarging the difference in Psi w between the xylem and the elongating tissues, i.e. enlarging the growth-induced Psi w, which is critical for growth. Guttation occurred, confirming the high Psi w of the xylem, and the mature leaf tissue rehydrated. Water uptake increased and met the requirements of transpiration. Leaf elongation recovered to control rates. Under more severe conditions at lower soil Psi w, P induced only a brief elongation and the growth-induced Psi w responded only slightly. Guttation did not occur, water flow did not meet the requirements of transpiration, and the mature leaf tissues did not rehydrate. A rewatering experiment indicated that a low conductance existed in the severely dehydrated soil, which limited water delivery to the root and shoot. Therefore, the initial growth inhibition appeared to be hydraulic because the enlargement of the growth-induced Psi w by P together with rehydration of the mature leaf tissue were essential for growth recovery. In more severe conditions, P was ineffective because the soil could not supply water at the required rate, and metabolic factors began to contribute to the inhibition. PMID:14512379

  18. Sonography in Fetal Birth Weight Estimation

    ERIC Educational Resources Information Center

    Akinola, R. A.; Akinola, O. I.; Oyekan, O. O.

    2009-01-01

    The estimation of fetal birth weight is an important factor in the management of high risk pregnancies. The information and knowledge gained through this study, comparing a combination of various fetal parameters using computer assisted analysis, will help the obstetrician to screen the high risk pregnancies, monitor the growth and development,…

  19. Uteroplacental circulation and fetal vascular function and development.

    PubMed

    Thornburg, Kent L; Louey, Samantha

    2013-09-01

    Although blood flow in the placental vasculature is governed by the same physiological forces of shear, pressure and resistance as in other organs, it is also uniquely specialized on the maternal and fetal sides. At the materno-fetal interface, the independent uteroplacental and umbilicoplacental circulations must coordinate sufficiently to supply the fetus with the nutrients and substrates it needs to grow and develop. Uterine arterial flow must increase dramatically to accommodate the growing fetus. Recent evidence delineates the hormonal and endothelial mechanisms by which maternal vessels dilate and remodel during pregnancy. The umbilical circulation is established de novo during embryonic development but blood does not flow through the placenta until late in the first trimester. The umbilical circulation operates in the interest of maintaining fetal oxygenation over the course of pregnancy, and is affected differently by mechanical and chemical regulators of vascular tone compared to other organs. The processes that match placental vascular growth and fetal tissue growth are not understood, but studies of compromised pregnancies provide clues. The subtle changes that cause the failure of the normally regulated vascular processes during pregnancy have not been thoroughly identified. Likewise, practical and effective therapeutic strategies to reverse detrimental placental perfusion patterns have yet to be investigated.

  20. Fetal movements as a predictor of health.

    PubMed

    Lai, Jonathan; Nowlan, Niamh C; Vaidyanathan, Ravi; Shaw, Caroline J; Lees, Christoph C

    2016-09-01

    The key determinant to a fetus maintaining its health is through adequate perfusion and oxygen transfer mediated by the functioning placenta. When this equilibrium is distorted, a number of physiological changes, including reduced fetal growth, occur to favor survival. Technologies have been developed to monitor these changes with a view to prolong intrauterine maturity while reducing the risks of stillbirth. Many of these strategies involve complex interpretation, for example Doppler ultrasound for fetal blood flow and computerized analysis of fetal heart rate changes. However, even with these modalities of fetal assessment to determine the optimal timing of delivery, fetal movements remain integral to clinical decision-making. In high-risk cohorts with fetal growth restriction, the manifestation of a reduction in perceived movements may warrant an expedited delivery. Despite this, there has been little evolution in the development of technologies to objectively evaluate fetal movement behavior for clinical application. This review explores the available literature on the value of fetal movement analysis as a method of assessing fetal wellbeing, and demonstrates how interdisciplinary developments in this area may aid in the improvement of clinical outcomes. PMID:27374723

  1. Fetal alloimmune thrombocytopenia and maternal intravenous immunoglobulin infusion

    PubMed Central

    Giers, Günther; Wenzel, Folker; Stockschläder, Markus; Riethmacher, Regina; Lorenz, Horst; Tutschek, Boris

    2010-01-01

    Background Different therapeutic approaches have been used in fetal-neonatal alloimmune thrombocytopenia, but many centers administer immunoglobulin G infusions to the pregnant woman. We studied the effect of maternal antenatal immunoglobulin infusions on fetal platelet counts in pregnancies with fetal alloimmune thrombocytopenia. Design and Methods We retrospectively analyzed the clinical courses of fetuses with fetal alloimmune thrombocytopenia whose mothers were treated with immunoglobulin G infusions in a single center between 1999 and 2005. In a center-specific protocol, weekly maternal immunoglobulin G infusions were given to 25 pregnant women with previously affected neonates and four women with strong platelet antibodies, but no previous history of fetal alloimmune thrombocytopenia; before each infusion diagnostic fetal blood sampling was performed to determine fetal platelet counts and immunoglobulin G levels. Results There were 30 fetuses with fetal alloimmune thrombocytopenia, confirmed by initial fetal blood sampling showing fetal platelet counts between 4×109/L and 130×109/L and antibody-coated fetal platelets using a glycoprotein specific assay. Despite weekly antenatal maternal immunoglobulin G infusions fetal platelet counts did not change significantly. Maternal and fetal immunoglobulin G levels, measured before every infusion, increased significantly with the number of maternal immunoglobulin G infusions. Conclusions In this group of fetuses with fetal alloimmune thrombocytopenia no consistent increase of fetal platelets was achieved as a result of regular maternal immunoglobulin G infusions. PMID:20534698

  2. Perinatal protein restriction affects milk free amino acid and fatty acid profile in lactating rats: potential role on pup growth and metabolic status.

    PubMed

    Martin Agnoux, Aurore; Antignac, Jean-Philippe; Boquien, Clair-Yves; David, Agnes; Desnots, Emmanuelle; Ferchaud-Roucher, Veronique; Darmaun, Dominique; Parnet, Patricia; Alexandre-Gouabau, Marie-Cécile

    2015-07-01

    Perinatal undernutrition affects not only fetal and neonatal growth but also adult health outcome, as suggested by the metabolic imprinting concept. Although maternal milk is the only channel through which nutrients are transferred from mother to offspring during the postnatal period, the impact of maternal undernutrition on milk composition is poorly understood. The present study investigates, in a rat model of nutritional programming, the effects of feeding an isocaloric, low-protein diet throughout gestation and lactation on milk composition and its possible consequences on offspring's growth and metabolic status. We used an integrated methodological approach that combined targeted analyses of macronutrients, free amino acid and fatty acid content throughout lactation, with an untargeted mass-spectrometric-based metabolomic phenotyping. Whereas perinatal dietary protein restriction failed to alter milk protein content, it dramatically decreased the concentration of most free amino acids at the end of lactation. Interestingly, a decrease of several amino acids involved in insulin secretion or gluconeogenesis was observed, suggesting that maternal protein restriction during the perinatal period may impact the insulinotrophic effect of milk, which may, in turn, account for the slower growth of the suckled male offspring. Besides, the decrease in sulfur amino acids may alter redox status in the offspring. Maternal undernutrition was also associated with an increase in milk total fatty acid content, with modifications in their pattern. Altogether, our results show that milk composition is clearly influenced by maternal diet and suggest that alterations in milk composition may play a role in offspring growth and metabolic programming. PMID:25935308

  3. Cryopreserved mouse fetal liver stromal cells treated with mitomycin C are able to support the growth of human embryonic stem cells

    PubMed Central

    ZHANG, WEI; HU, JIABO; MA, QUANHUI; HU, SANQIANG; WANG, YANYAN; WEN, XIANGMEI; MA, YONGBIN; XU, HONG; QIAN, HUI; XU, WENRONG

    2014-01-01

    An immortalized mouse fetal liver stromal cell line, named KM3, has demonstrated the potential to support the growth and maintenance of human embryonic stem cells (hESCs). In this study, the characteristics of KM3 cells were examined following cryopreservation at −70°C and in liquid nitrogen for 15, 30 and 60 days following treatment with 10 μg/ml mitomycin C. In addition, whether the KM3 cells were suitable for use as feeder cells to support the growth of hESCs was evaluated. The inhibition of mitosis without cell death was observed when the KM3 cells were treated with 10 μg/ml mitomycin C for 2 h. The morphology of the KM3 cells cryopreserved in liquid nitrogen for 60 days was not markedly changed, and the cell survival rate was 84.60±1.14%. By contrast, the survival rate of the KM3 cells was 66.40±2.88% following cryopreservation at −70°C for 60 days; the cells readily detached, were maintained for a shorter time, and had a reduced expression level of basic fibroblast growth factor. hESCs cultured on KM3 cells cryopreserved in liquid nitrogen for 60 days showed the typical bird’s nest structure, with clear boundaries and a differentiation rate of 16.33±2.08%. The differentiation rate of hESCs cultured on KM3 cells cryopreserved at −70°C for 60 days was 37.67±3.51%. These results indicate that the cryopreserved KM3 cells treated with mitomycin C may be directly used in the subculture of hESCs, and the effect is relatively good with −70°C short-term or liquid nitrogen cryopreservation. PMID:25120627

  4. Maternal omega-3 fatty acid intake increases placental labyrinthine antioxidant capacity but does not protect against fetal growth restriction induced by placental ischaemia-reperfusion injury.

    PubMed

    Jones, Megan L; Mark, Peter J; Waddell, Brendan J

    2013-12-01

    Placental oxidative stress plays a key role in the pathophysiology of several placenta-related disorders. Oxidative stress occurs when excess reactive oxygen species (ROS) damages cellular components, an outcome limited by antioxidant enzymes; mitochondrial uncoupling protein 2 (UCP2) also limits ROS production. We recently reported that maternal dietary omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation reduced placental oxidative damage and enhanced fetal and placental growth in the rats. Here, we examined the effect of n-3 PUFAs on placental antioxidant defences and whether n-3 PUFA supplementation could prevent growth restriction induced by placental ischaemia-reperfusion (IR), a known inducer of oxidative stress. Rats were fed either standard or high-n-3 PUFA diets from day 1 of pregnancy. Placentas were collected on days 17 and 22 in untreated pregnancies (term=day 23) and at day 22 following IR treatment on day 17. Expression of several antioxidant enzyme genes (Sod1, Sod2, Sod3, Cat, Txn1 and Gpx3) and Ucp2 was measured by quantitative RT-PCR in the placental labyrinth zone (LZ) and junctional zone (JZ). Cytosolic superoxide dismutase (SOD), mitochondrial SOD and catalase (CAT) activities were also analyzed. Maternal n-3 PUFA supplementation increased LZ mRNA expression of Cat at both gestational days (2- and 1.5-fold respectively; P<0.01) and female Sod2 at day 22 (1.4-fold, P<0.01). Cytosolic SOD activity increased with n-3 PUFA supplementation at day 22 (1.3-fold, P<0.05). Sod1 and Txn1 expression decreased marginally (30 and 22%, P<0.05). JZ antioxidant defences were largely unaffected by diet. Despite increased LZ antioxidant defences, maternal n-3 PUFA supplementation did not protect against placental IR-induced growth restriction of the fetus and placental LZ.

  5. Segmented independent component analysis for improved separation of fetal cardiac signals from nonstationary fetal magnetocardiograms

    PubMed Central

    Murta, Luiz O.; Guzo, Mauro G.; Moraes, Eder R.; Baffa, Oswaldo; Wakai, Ronald T.; Comani, Silvia

    2015-01-01

    Fetal magnetocardiograms (fMCGs) have been successfully processed with independent component analysis (ICA) to separate the fetal cardiac signals, but ICA effectiveness can be limited by signal nonstation-arities due to fetal movements. We propose an ICA-based method to improve the quality of fetal signals separated from fMCG affected by fetal movements. This technique (SegICA) includes a procedure to detect signal nonstationarities, according to which the fMCG recordings are divided in stationary segments that are then processed with ICA. The first and second statistical moments and the signal polarity reversal were used at different threshold levels to detect signal transients. SegICA effectiveness was assessed in two fMCG datasets (with and without fetal movements) by comparing the signal-to-noise ratio (SNR) of the signals extracted with ICA and with SegICA. Results showed that the SNR of fetal signals affected by fetal movements improved with SegICA, whereas the SNR gain was negligible elsewhere. The best measure to detect signal nonstationarities of physiological origin was signal polarity reversal at threshold level 0.9. The first statistical moment also provided good results at threshold level 0.6. SegICA seems a promising method to separate fetal cardiac signals of improved quality from nonstationary fMCG recordings affected by fetal movements. PMID:25781658

  6. Fetal alcohol exposure: consequences, diagnosis, and treatment.

    PubMed

    Pruett, Dawn; Waterman, Emily Hubbard; Caughey, Aaron B

    2013-01-01

    Maternal alcohol use during pregnancy is prevalent, with as many as 12% of pregnant women consuming alcohol. Alcohol intake may vary from an occasional drink, to weekly binge drinking, to chronic alcohol use throughout pregnancy. Whereas there are certain known consequences from fetal alcohol exposure, such as fetal alcohol syndrome, other effects are less well defined. Craniofacial dysmorphologies, abnormalities of organ systems, behavioral and intellectual deficits, and fetal death have all been attributed to maternal alcohol consumption. This review article considers the theoretical mechanisms of how alcohol affects the fetus, including the variable susceptibility to fetal alcohol exposure and the implications of ethanol dose and timing of exposure. Criteria for diagnosis of fetal alcohol syndrome are discussed, as well as new methods for early detection of maternal alcohol use and fetal alcohol exposure, such as the use of fatty acid ethyl esters. Finally, current and novel treatment strategies, both in utero and post utero, are reviewed.

  7. Cloning the promoter for transforming growth factor-beta type III receptor. Basal and conditional expression in fetal rat osteoblasts

    NASA Technical Reports Server (NTRS)

    Ji, C.; Chen, Y.; McCarthy, T. L.; Centrella, M.

    1999-01-01

    Transforming growth factor-beta binds to three high affinity cell surface molecules that directly or indirectly regulate its biological effects. The type III receptor (TRIII) is a proteoglycan that lacks significant intracellular signaling or enzymatic motifs but may facilitate transforming growth factor-beta binding to other receptors, stabilize multimeric receptor complexes, or segregate growth factor from activating receptors. Because various agents or events that regulate osteoblast function rapidly modulate TRIII expression, we cloned the 5' region of the rat TRIII gene to assess possible control elements. DNA fragments from this region directed high reporter gene expression in osteoblasts. Sequencing showed no consensus TATA or CCAAT boxes, whereas several nuclear factors binding sequences within the 3' region of the promoter co-mapped with multiple transcription initiation sites, DNase I footprints, gel mobility shift analysis, or loss of activity by deletion or mutation. An upstream enhancer was evident 5' proximal to nucleotide -979, and a silencer region occurred between nucleotides -2014 and -2194. Glucocorticoid sensitivity mapped between nucleotides -687 and -253, whereas bone morphogenetic protein 2 sensitivity co-mapped within the silencer region. Thus, the TRIII promoter contains cooperative basal elements and dispersed growth factor- and hormone-sensitive regulatory regions that can control TRIII expression by osteoblasts.

  8. Postnatal nutritional restriction affects growth and immune function of piglets with intra-uterine growth restriction.

    PubMed

    Hu, Liang; Liu, Yan; Yan, Chuan; Peng, Xie; Xu, Qin; Xuan, Yue; Han, Fei; Tian, Gang; Fang, Zhengfeng; Lin, Yan; Xu, Shengyu; Zhang, Keying; Chen, Daiwen; Wu, De; Che, Lianqiang

    2015-07-14

    Postnatal rapid growth by excess intake of nutrients has been associated with an increased susceptibility to diseases in neonates with intra-uterine growth restricted (IUGR). The aim of the present study was to determine whether postnatal nutritional restriction could improve intestinal development and immune function of neonates with IUGR using piglets as model. A total of twelve pairs of normal-birth weight (NBW) and IUGR piglets (7 d old) were randomly assigned to receive adequate nutrient intake or restricted nutrient intake (RNI) by artificially liquid feeding for a period of 21 d. Blood samples and intestinal tissues were collected at necropsy and were analysed for morphology, digestive enzyme activities, immune cells and expression of innate immunity-related genes. The results indicated that both IUGR and postnatal nutritional restriction delayed the growth rate during the sucking period. Irrespective of nutrient intake, piglets with IUGR had a significantly lower villous height and crypt depth in the ileum than the NBW piglets. Moreover, IUGR decreased alkaline phosphatase activity while enhanced lactase activity in the jejunum and mRNA expressions of Toll-like receptor 9 (TLR-9) and DNA methyltransferase 1 (DNMT1) in the ileum of piglets. Irrespective of body weight, RNI significantly decreased the number and/or percentage of peripheral leucocytes, lymphocytes and monocytes of piglets, whereas the percentage of neutrophils and the ratio of CD4+ to CD8+ were increased. Furthermore, RNI markedly enhanced the mRNA expression of TLR-9 and DNMT1, but decreased the expression of NOD2 and TRAF-6 in the ileum of piglets. In summary, postnatal nutritional restriction led to abnormal cellular and innate immune response, as well as delayed the growth and intestinal development of IUGR piglets. PMID:26059215

  9. Placental restriction of fetal growth reduces size at birth and alters postnatal growth, feeding activity, and adiposity in the young lamb.

    PubMed

    De Blasio, Miles J; Gatford, Kathryn L; Robinson, Jeffrey S; Owens, Julie A

    2007-02-01

    Intrauterine growth restriction (IUGR) is associated with accelerated growth after birth. Together, IUGR and accelerated growth after birth predict reduced lean tissue mass and increased obesity in later life. Although placental insufficiency is a major cause of IUGR, whether it alters growth and adiposity in early postnatal life is not known. We hypothesized that placental restriction (PR) in the sheep would reduce size at birth and increase postnatal growth rate, fat mass, and feeding activity in the young lamb. PR reduced survival rate and size at birth, with soft tissues reduced to a greater extent than skeletal tissues and relative sparing of head width (P < 0.05 for all). PR did not alter absolute growth rates (i.e., the slope of the line of best fit for age vs. parameter size from birth to 45 days of age) but increased neonatal fractional growth rates (absolute growth rate relative to size at birth) for body weight (+24%), tibia (+15%) and metatarsal (+18%) lengths, hindlimb (+23%) and abdominal (+19%) circumferences, and fractional growth rates for current weight (P < 0.05) weekly throughout the first 45 days of life. PR and small size at birth reduced individual skeletal muscle weights and increased visceral adiposity in absolute and relative terms. PR also altered feeding activity, which increased with decreasing size at birth and was predictive of increased postnatal growth and adiposity. In conclusion, PR reduced size at birth and induced catch-up growth postnatally, normalizing weight and length but increasing adiposity in early postnatal life. Increased feeding activity may contribute to these alterations in growth and body composition following prenatal restraint and, if they persist, may lead to adverse metabolic and cardiovascular outcomes in later life. PMID:17023666

  10. IFPA Meeting 2012 Workshop Report II: epigenetics and imprinting in the placenta, growth factors and villous trophoblast differentiation, role of the placenta in regulating fetal exposure to xenobiotics during pregnancy, infection and the placenta.

    PubMed

    Ahmed, M S; Aleksunes, L M; Boeuf, P; Chung, M K; Daoud, G; Desoye, G; Díaz, P; Golos, T G; Illsley, N P; Kikuchi, K; Komatsu, R; Lao, T; Morales-Prieto, D M; Nanovskaya, T; Nobuzane, T; Roberts, C T; Saffery, R; Tamura, I; Tamura, K; Than, N G; Tomi, M; Umbers, A; Wang, B; Weedon-Fekjaer, M S; Yamada, S; Yamazaki, K; Yoshie, M; Lash, G E

    2013-03-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2012 there were twelve themed workshops, four of which are summarized in this report. These workshops related to various aspects of placental biology: 1) epigenetics and imprinting in the placenta; 2) growth factors and villous trophoblast differentiation; 3) role of the placenta in regulating fetal exposure to xenobiotics during pregnancy; 4) infection and the placenta.

  11. IFPA meeting 2014 workshop report: Animal models to study pregnancy pathologies; new approaches to study human placental exposure to xenobiotics; biomarkers of pregnancy pathologies; placental genetics and epigenetics; the placenta and stillbirth and fetal growth restriction.

    PubMed

    Barbaux, S; Erwich, J J H M; Favaron, P O; Gil, S; Gallot, D; Golos, T G; Gonzalez-Bulnes, A; Guibourdenche, J; Heazell, A E P; Jansson, T; Laprévote, O; Lewis, R M; Miller, R K; Monk, D; Novakovic, B; Oudejans, C; Parast, M; Peugnet, P; Pfarrer, C; Pinar, H; Roberts, C T; Robinson, W; Saffery, R; Salomon, C; Sexton, A; Staff, A C; Suter, M; Tarrade, A; Wallace, J; Vaillancourt, C; Vaiman, D; Worton, S A; Lash, G E

    2015-04-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2014 there were six themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of animal models, xenobiotics, pathological biomarkers, genetics and epigenetics, and stillbirth and fetal growth restriction. PMID:25703592

  12. Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells

    PubMed Central

    Kilcoyne, Karen R.; Smith, Lee B.; Atanassova, Nina; Macpherson, Sheila; McKinnell, Chris; van den Driesche, Sander; Jobling, Matthew S.; Chambers, Thomas J. G.; De Gendt, Karel; Verhoeven, Guido; O’Hara, Laura; Platts, Sophie; Renato de Franca, Luiz; Lara, Nathália L. M.; Anderson, Richard A.; Sharpe, Richard M.

    2014-01-01

    Fetal growth plays a role in programming of adult cardiometabolic disorders, which in men, are associated with lowered testosterone levels. Fetal growth and fetal androgen exposure can also predetermine testosterone levels in men, although how is unknown, because the adult Leydig cells (ALCs) that produce testosterone do not differentiate until puberty. To explain this conundrum, we hypothesized that stem cells for ALCs must be present in the fetal testis and might be susceptible to programming by fetal androgen exposure during masculinization. To address this hypothesis, we used ALC ablation/regeneration to identify that, in rats, ALCs derive from stem/progenitor cells that express chicken ovalbumin upstream promoter transcription factor II. These stem cells are abundant in the fetal testis of humans and rodents, and lineage tracing in mice shows that they develop into ALCs. The stem cells also express androgen receptors (ARs). Reduction in fetal androgen action through AR KO in mice or dibutyl phthalate (DBP) -induced reduction in intratesticular testosterone in rats reduced ALC stem cell number by ∼40% at birth to adulthood and induced compensated ALC failure (low/normal testosterone and elevated luteinizing hormone). In DBP-exposed males, this failure was probably explained by reduced testicular steroidogenic acute regulatory protein expression, which is associated with increased histone methylation (H3K27me3) in the proximal promoter. Accordingly, ALCs and ALC stem cells immunoexpressed increased H3K27me3, a change that was also evident in ALC stem cells in fetal testes. These studies highlight how a key component of male reproductive development can fundamentally reprogram adult hormone production (through an epigenetic change), which might affect lifetime disease risk. PMID:24753613

  13. Effects of ambient oxygen concentration on the growth and antioxidant defenses of of human cell cultures established from fetal and postnatal skin.

    PubMed

    Balin, Arthur K; Pratt, Loretta; Allen, R G

    2002-02-01

    Oxygen toxicity is believed to arise from changes in the rates at which cells generate reactive oxygen species (ROS). Sensitivity to hyperoxia has been postulated to depend on levels of antioxidant defense. Human cells obtained from fetal tissues have lower antioxidant defenses than those obtained from adult tissue. The present study was performed to determine whether the differences in fetal and adult antioxidant defense levels modulated their responses to changes in the ambient oxygen concentration. Our results demonstrate that oxygen modulates the proliferation of human fetal and adult skin fibroblasts in a similar fashion. In general, skin fibroblasts grew better at approximately 31 mm Hg, regardless of donor age. Manganese superoxide dismutase, catalase, and glutathione peroxidase activities were lower in fetal cells than in adult fibroblasts. Copper/zinc superoxide dismutase and glucose-6-phosphate dehydrogenase were similar in fetal and postnatal tissues and were unaltered appreciably by hyperoxic exposure. Glutathione concentration increased at higher oxygen tensions; however, the increase was much greater in fetal cells than in cultures derived from adult skin. These observations demonstrate that the capacity of fetal and adult cells to cope with oxidative stress, while similar, result from distinct mechanisms. PMID:11827751

  14. Disruption of the lower food web in Lake Ontario: Did it affect alewife growth or condition?

    USGS Publications Warehouse

    O'Gorman, R.; Prindle, S.E.; Lantry, J.R.; Lantry, B.F.

    2008-01-01

    From the early 1980s to the late 1990s, a succession of non-native invertebrates colonized Lake Ontario and the suite of consequences caused by their colonization became known as "food web disruption". For example, the native burrowing amphipod Diporeia spp., a key link in the profundal food web, declined to near absence, exotic predaceous cladocerans with long spines proliferated, altering the zooplankton community, and depth distributions of fishes shifted. These changes had the potential to affect growth and condition of planktivorous alewife Alosa pseudoharengus, the most abundant fish in the lake. To determine if food web disruption affected alewife, we used change-point analysis to examine alewife growth and adult alewife condition during 1976-2006 and analysis-of-variance to determine if values between change points differed significantly. There were no change points in growth during the first year of life. Of three change points in growth during the second year of life, one coincided with the shift in springtime distribution of alewife to deeper water but it was not associated with a significant change in growth. After the second year of life, no change points in growth were evident, although growth in the third year of life spiked in those years when Bythotrephes, the largest of the exotic cladocerans, was abundant suggesting that it was a profitable prey item for age-2 fish. We detected two change points in condition of adult alewife in fall, but the first occurred in 1981, well before disruption began. A second change point occurred in 2003, well after disruption began. After the springtime distribution of alewife shifted deeper during 1992-1994, growth in the first two years of life became more variable, and growth in years of life two and older became correlated (P < 0.05). In conclusion, food web disruption had no negative affect on growth and condition of alewife in Lake Ontario although it appears to have resulted in growth in the first two years of

  15. Placental and fetal growth restriction, size at birth and neonatal growth alter cognitive function and behaviour in sheep in an age- and sex-specific manner.

    PubMed

    Hunter, Damien S; Hazel, Susan J; Kind, Karen L; Liu, Hong; Marini, Danila; Giles, Lynne C; De Blasio, Miles J; Owens, Julie A; Pitcher, Julia B; Gatford, Kathryn L

    2015-12-01

    Intrauterine growth restriction and slow neonatal growth in humans are each associated with poorer learning, memory and cognitive flexibility in childhood and adulthood. The relative contributions of pre- and post-natal growth to cognitive outcomes are unclear, however. We therefore compared performance in learning, memory and reversal tasks using a modified Y-maze at 18 and 40 weeks of age in offspring of placentally-restricted (PR: 10 M, 13 F) and control (23 M, 17 F) ovine pregnancies. We also investigated relationships between size at birth, neonatal growth rates and cognitive outcomes. PR had limited effects on cognitive outcomes, with PR males requiring more trials to solve the initial learning task than controls (P=0.037) but faster completion of reversal tasks in both sexes at 18 weeks of age. In males, neonatal growth rate correlated inversely with numbers of trials and total time required to solve memory tasks at 40 weeks of age. In females, bleat frequency in the first reversal task at 18 weeks of age correlated positively with birth weight (r=0.734, P<0.05) and neonatal growth rate (r=0.563, P<0.05). We conclude that PR induces limited effects on cognitive outcomes in sheep, with some evidence of impaired learning in males, but little effect on memory or cognitive flexibility in either sex. Rapid neonatal growth predicted improved memory task performance in males, suggesting that strategies to optimize neonatal growth may have long-term cognitive benefits but that these may be sex-specific.

  16. Fetal Alcohol Syndrome "Chemical Genocide."

    ERIC Educational Resources Information Center

    Asetoyer, Charon

    In the Northern Plains of the United States, 100% of Indian reservations are affected by alcohol related problems. Approximately 90% of Native American adults are currently alcohol users or abusers or are recovering from alcohol abuse. Alcohol consumption has a devastating effect on the unborn. Fetal Alcohol Syndrome (FAS) is an irreversible birth…

  17. Salinity fluctuation of the brine discharge affects growth and survival of the seagrass Cymodocea nodosa.

    PubMed

    Garrote-Moreno, A; Fernández-Torquemada, Y; Sánchez-Lizaso, J L

    2014-04-15

    The increase of seawater desalination plants may affect seagrasses as a result of its hypersaline effluents. There are some studies on the salinity tolerance of seagrasses under controlled laboratory conditions, but few have been done in situ. To this end, Cymodocea nodosa shoots were placed during one month at four localities: two close to a brine discharge; and the other two not affected by the discharge, and this experiment was repeated four times. The results obtained showed a decrease in growth and an increased mortality at the localities affected by the brine discharge. An increase was detected in the percentage of horizontal shoots in respect to vertical shoots at the impacted localities. It is probably that not only the average salinity, but also the constant salinity fluctuations and slightly higher temperatures associated with the brine that may have caused physiological stress thus reducing C. nodosa growth and survival.

  18. Ketamine affects the neurogenesis of rat fetal neural stem progenitor cells via the PI3K/Akt-p27 signaling pathway

    PubMed Central

    Dong, Chaoxuan; Rovnaghi, Cynthia R.; Anand, KJS

    2014-01-01

    Ketamine is widely used as an anesthetic, analgesic, or sedative in pediatric patients. We reported that ketamine alters the normal neurogenesis of rat fetal neural stem progenitor cells (NSPCs) in the developing brain, but the underlying mechanisms remain unknown. The PI3K-PKB/Akt (Phosphatidylinositide 3-kinases/protein kinase B) signaling pathway plays many important roles in cell survival, apoptosis, and proliferation. We hypothesized that PI3K-PKB/Akt signaling may be involved in ketamine-altered neurogenesis of cultured NSPCs in vitro. NSPCs were isolated from Sprague-Dawley rat fetuses on gestational day 17. BrdU (bromodeoxyuridine) incorporation, Ki67 staining, and differentiation tests were utilized to identify primary cultured NSPCs. Immunofluorescent staining was used to detect Akt expression, whereas, Western blots measured phosphorylated Akt and p27 expression in NSPCs exposed to different treatments. We report that cultured NSPCs had properties of neurogenesis: proliferation and neural differentiation. PKB/Akt was expressed in cultured rat fetal cortical NSPCs. Ketamine inhibited the phosphorylation of Akt and further enhanced p27 expression in cultured NSPCs. All ketamine-induced PI3K/Akt signaling changes could be recovered by NMDA (N-Methyl-D-aspartate) receptor agonist, NMDA. These data suggest that inhibition of PI3K/Akt-p27 signaling may be involved in ketamine-induced neurotoxicity in the developing brain, whereas excitatory NMDA receptor activation may reverse these effects. PMID:25231110

  19. MicroRNA-26a modulates transforming growth factor beta-1-induced proliferation in human fetal lung fibroblasts

    SciTech Connect

    Li, Xiaoou; Liu, Lian; Shen, Yongchun; Wang, Tao; Chen, Lei; Xu, Dan; Wen, Fuqiang

    2014-11-28

    Highlights: • Endogenous miR-26a inhibits TGF-beta 1 induced proliferation of lung fibroblasts. • miR-26a induces G1 arrest through directly targeting 3′-UTR of CCND2. • TGF indispensable receptor, TGF-beta R I, is regulated by miR-26a. • miR-26a acts through inhibiting TGF-beta 2 feedback loop to reduce TGF-beta 1. • Collagen type I and connective tissue growth factor are suppressed by miR-26a. - Abstract: MicroRNA-26a is a newly discovered microRNA that has a strong anti-tumorigenic capacity and is capable of suppressing cell proliferation and activating tumor-specific apoptosis. However, whether miR-26a can inhibit the over-growth of lung fibroblasts remains unclear. The relationship between miR-26a and lung fibrosis was explored in the current study. We first investigated the effect of miR-26a on the proliferative activity of human lung fibroblasts with or without TGF-beta1 treatment. We found that the inhibition of endogenous miR-26a promoted proliferation and restoration of mature miR-26a inhibited the proliferation of human lung fibroblasts. We also examined that miR-26a can block the G1/S phase transition via directly targeting 3′-UTR of CCND2, degrading mRNA and decreasing protein expression of Cyclin D2. Furthermore, we showed that miR-26a mediated a TGF-beta 2-TGF-beta 1 feedback loop and inhibited TGF-beta R I activation. In addition, the overexpression of miR-26a also significantly suppressed the TGF-beta 1-interacting-CTGF–collagen fibrotic pathway. In summary, our studies indicated an essential role of miR-26a in the anti-fibrotic mechanism in TGF-beta1-induced proliferation in human lung fibroblasts, by directly targeting Cyclin D2, regulating TGF-beta R I as well as TGF-beta 2, and suggested the therapeutic potential of miR-26a in ameliorating lung fibrosis.

  20. Dietary fish oil affects food intake, growth and hematologic values of weanling rats.

    PubMed

    Domínguez, Z; Bosch, V

    1994-06-01

    The object of this study was to evaluate the effect of increasing amounts of dietary fish oil on growth and hematological variables of the weanling male Sprague-Dawley rat. Animals were fed diets containing either fish oil (FO) or sesame oil (SO) at 5, 10 or 15% (w/w) for 31 d. Growth retardation and reduced food intake was noted in groups fed FO. Hemoglobin (Hb) concentration diminished when the dietary FO was above 5% (w/w). FO is a poor source of (n-6) fatty acids. We postulate that a partial deficiency in (n-6) polyenic family, is a consequence of the increasing amounts of FO in the diets, that may affect growth and erytropoiesis. In this report we show evidence supporting the hypothesis that diets enriched with fish oil can alter normal growth and induced hematological changes in the male weanling rat.

  1. The ability of Salmonella to enter mammalian cells is affected by bacterial growth state.

    PubMed Central

    Lee, C A; Falkow, S

    1990-01-01

    We have examined the effect of different growth conditions on the ability of Salmonella to interact with Madin-Darby canine kidney cells. Two growth conditions that affect the expression of Salmonella adherence and invasiveness have been identified. First, bacteria lose their invasiveness in the stationary phase of growth. Second, bacteria growing in oxygen-limited growth conditions are induced for adherence and invasiveness, whereas those growing aerobically are relatively nonadherent and noninvasive. Salmonella from cultures aerated with gas mixtures containing 0% or 1% oxygen were 6- to 70-fold more adherent and invasive than those from cultures aerated with a gas mixture containing 20% oxygen. The Salmonella typhimurium oxrA gene that is required for the anaerobic induction of many proteins is not involved in the regulation of Salmonella invasiveness. We speculate that oxygen limitation might be an environmental cue that triggers the expression of Salmonella invasiveness within the intestinal lumen and other tissues. Images PMID:2349239

  2. Dietary zinc affects concentrations of insulin, insulin-like growth factor-I and growth hormone in lambs

    SciTech Connect

    Droke, E.A.; Spears, J.W.; Armstrong, J.D. )

    1991-03-15

    Glucose tolerance and concentrations of insulin, growth hormone (GH) and insulin-like growth factor-I (IGF-I) were evaluated in lambs deficient, marginal or adequate in zinc (Zn). Lambs were fed a semipurified diet that contained either 3.7, 8.7, or 43.7 mg Zn/kg. Zinc deficiency resulted in lower serum insulin levels 1 h after feeding while levels in marginal lambs were not different from that of adequate lambs. Dietary Zn did not affect plasma glucose post feeding. One h after IV glucose administration plasma glucose concentrations were lower in deficient lambs compared to adequate lambs; marginal lambs had intermediate glucose levels. Concentration of GH before and after feeding or glucose challenge were not affected by Zn status; however, serum IGF-I was lower in deficient than in marginal or adequate lambs. A GH releasing factor (GRF) analog was given to evaluate the release of GH. Serum GH in response to GRF challenge was higher in deficient lambs and tended to be higher in marginal lambs when compared to adequate lambs. Impaired growth observed with Zn deficiency may be mediated in part by its effect on insulin, GH and IGF-I concentrations.

  3. Oxidative Stress in Mouse Sperm Impairs Embryo Development, Fetal Growth and Alters Adiposity and Glucose Regulation in Female Offspring

    PubMed Central

    Lane, Michelle; McPherson, Nicole O.; Fullston, Tod; Spillane, Marni; Sandeman, Lauren; Kang, Wan Xian; Zander-Fox, Deirdre L.

    2014-01-01

    Paternal health cues are able to program the health of the next generation however the mechanism for this transmission is unknown. Reactive oxygen species (ROS) are increased in many paternal pathologies, some of which program offspring health, and are known to induce DNA damage and alter the methylation pattern of chromatin. We therefore investigated whether a chemically induced increase of ROS in sperm impairs embryo, pregnancy and offspring health. Mouse sperm was exposed to 1500 µM of hydrogen peroxide (H2O2), which induced oxidative damage, however did not affect sperm motility or the ability to bind and fertilize an oocyte. Sperm treated with H2O2 delayed on-time development of subsequent embryos, decreased the ratio of inner cell mass cells (ICM) in the resulting blastocyst and reduced implantation rates. Crown-rump length at day 18 of gestation was also reduced in offspring produced by H2O2 treated sperm. Female offspring from H2O2 treated sperm were smaller, became glucose intolerant and accumulated increased levels of adipose tissue compared to control female offspring. Interestingly male offspring phenotype was less severe with increases in fat depots only seen at 4 weeks of age, which was restored to that of control offspring later in life, demonstrating sex-specific impacts on offspring. This study implicates elevated sperm ROS concentrations, which are common to many paternal health pathologies, as a mediator of programming offspring for metabolic syndrome and obesity. PMID:25006800

  4. Fusarium Oxysporum Volatiles Enhance Plant Growth Via Affecting Auxin Transport and Signaling.

    PubMed

    Bitas, Vasileios; McCartney, Nathaniel; Li, Ningxiao; Demers, Jill; Kim, Jung-Eun; Kim, Hye-Seon; Brown, Kathleen M; Kang, Seogchan

    2015-01-01

    Volatile organic compounds (VOCs) have well-documented roles in plant-plant communication and directing animal behavior. In this study, we examine the less understood roles of VOCs in plant-fungal relationships. Phylogenetically and ecologically diverse strains of Fusarium oxysporum, a fungal species complex that often resides in the rhizosphere of assorted plants, produce volatile compounds that augment shoot and root growth of Arabidopsis thaliana and tobacco. Growth responses of A. thaliana hormone signaling mutants and expression patterns of a GUS reporter gene under the auxin-responsive DR5 promoter supported the involvement of auxin signaling in F. oxysporum volatile-mediated growth enhancement. In addition, 1-naphthylthalamic acid, an inhibitor of auxin efflux, negated F. oxysporum volatile-mediated growth enhancement in both plants. Comparison of the profiles of volatile compounds produced by F. oxysporum strains that differentially affected plant growth suggests that the relative compositions of both growth inhibitory and stimulatory compounds may determine the degree of plant growth enhancement. Volatile-mediated signaling between fungi and plants may represent a potentially conserved, yet mostly overlooked, mechanism underpinning plant-fungus interactions and fungal niche adaption. PMID:26617587

  5. Fusarium Oxysporum Volatiles Enhance Plant Growth Via Affecting Auxin Transport and Signaling

    PubMed Central

    Bitas, Vasileios; McCartney, Nathaniel; Li, Ningxiao; Demers, Jill; Kim, Jung-Eun; Kim, Hye-Seon; Brown, Kathleen M.; Kang, Seogchan

    2015-01-01

    Volatile organic compounds (VOCs) have well-documented roles in plant-plant communication and directing animal behavior. In this study, we examine the less understood roles of VOCs in plant-fungal relationships. Phylogenetically and ecologically diverse strains of Fusarium oxysporum, a fungal species complex that often resides in the rhizosphere of assorted plants, produce volatile compounds that augment shoot and root growth of Arabidopsis thaliana and tobacco. Growth responses of A. thaliana hormone signaling mutants and expression patterns of a GUS reporter gene under the auxin-responsive DR5 promoter supported the involvement of auxin signaling in F. oxysporum volatile-mediated growth enhancement. In addition, 1-naphthylthalamic acid, an inhibitor of auxin efflux, negated F. oxysporum volatile-mediated growth enhancement in both plants. Comparison of the profiles of volatile compounds produced by F. oxysporum strains that differentially affected plant growth suggests that the relative compositions of both growth inhibitory and stimulatory compounds may determine the degree of plant growth enhancement. Volatile-mediated signaling between fungi and plants may represent a potentially conserved, yet mostly overlooked, mechanism underpinning plant-fungus interactions and fungal niche adaption. PMID:26617587

  6. Relative binding and biochemical effects of heterodimeric and homodimeric isoforms of platelet-derived growth factor in osteoblast-enriched cultures from fetal rat bone

    SciTech Connect

    Centrella, M.; McCarthy, T.L.; Kusmik, W.F.; Canalis, E. )

    1991-06-01

    Platelet-derived growth factor (PDGF) exists as a homodimer or a heterodimer comprising either PDGF-A or PDGF-B subunits, and each isoform occurs in various tissues, including bone. Although the stimulatory effects of PDGF-BB have been studied in cultures of bone cells and intact bone fragments, the influence of other isoforms that may arise locally or systematically in vivo, has not been reported. Therefore recombinant human PDGF-BB, PDGF-AB, and PDGF-AA were evaluated in osteoblast-enriched cultures from fetal rat bone. Within 24 hours these factors produced a graded response in bone cell DNA and protein synthesis, with half-maximal effects at approximately 0.6, 2.1, and 4.8 nM PDGF-BB, PDGF-AB, and PDGF-AA, respectively. Increases in collagen and noncollagen protein synthesis were abrogated when DNA synthesis was blocked with hydroxyurea. Furthermore, each factor reduced alkaline phosphatase activity, PDGF-BB being the most inhibitory. Binding studies with 125I-PDGF-BB or 125I-PDGF-AA and each unlabeled PDGF isoform produced discrete ligand binding and displacement patterns: 125I-PDGF-BB binding was preferentially displaced by PDGF-BB (Ki approximately 0.7 nM), less by PDGF-AB (Ki approximately 2.3 nM) and poorly by PDGF-AA. In contrast, 125I-PDGF-AA binding was measurably reduced by PDGF-AA (Ki approximately 4.0 nM), but was more effectively displaced by PDGF-BB or PDGF-AB (each with Ki approximately 0.7 nM). These studies indicate that each PDGF isoform produces biochemical effects proportional to binding site occupancy and suggest that receptors that favor PDGF-B subunit binding preferentially mediate these results in osteoblast-enriched bone cell cultures.

  7. Controlled Cu nanoparticle growth on wrinkle affecting deposition of large scale graphene

    NASA Astrophysics Data System (ADS)

    Ahmed, Mohsin; Uddin, Md Jasim; Rahman, Muhammad Anisur; Kishi, Naoki; Soga, Tetsuo

    2016-09-01

    For Chemical Vapor Deposition (CVD) grown graphene on Cu substrate, deviation from atomic orientation in crystals may be resulted from diffusion of abnormalities in the form of Cu nanoparticle (NP) formation or defects and affects graphene quality and properties drastically. However, for the uniform graphene deposition, mechanism of nanoparticle formation and its suppression procedure need to be better understood. We report growth of graphene, affected by Cu nanoparticles (NPs) emergence on Cu substrates. In the current study, growth of these nanoparticles has been suppressed by fine tuning of carrier gas by two-fold gas insertion mechanism and hence, quality and uniformity of graphene is significantly improved. It has been also observed that during the deposition by CVD, Cu nanoparticles cluster preferentially on wrinkles or terrace of the Cu surface. Composition of NP is extensively studied and found to be the oxide nanoparticle of Cu. Our result, controlled NP growth affecting deposition of graphene layer would provide useful insight on the growth of uniform and high quality Single layer or bilayer graphene for numerous electronics applications.

  8. Fetal and maternal manifestations of tuberous sclerosis complex: Value of fetal MRI.

    PubMed

    Goel, Reema; Aggarwal, Nishant; Lemmon, Monica E; Bosemani, Thangamadhan

    2016-02-01

    Tuberous sclerosis complex (TSC) is a genetic disorder characterized by benign hamartomas in various organ systems of the body. Prenatal screening of fetuses of mothers affected with TSC using ultrasonography (US) may detect cardiac lesions. Fetal US is not sensitive for evaluation of the brain. We describe brain MRI findings in a fetus with cardiac rhabdomyomas identified on prenatal screening US. Postnatal brain MRI at 5 days of age demonstrated fetal MRI findings without significant added information. Fetal MRI is the imaging modality of choice for evaluation of cerebral manifestations of TSC. Maternal manifestations of TSC in the abdomen or pelvis may also be demonstrated on fetal MRI. PMID:26838171

  9. Timing of cotyledon damage affects growth and flowering in mature plants.

    PubMed

    Hanley, M E; Fegan, E L

    2007-07-01

    Although the effects of herbivory on plant fitness are strongly linked to age, we understand little about how the timing of herbivory at the seedling stage affects growth and reproduction for plants that survive attack. In this study, we subjected six north-western European, dicotyledonous grassland species (Leontodon autumnalis, Leontodon hispidus, Plantago lanceolata, Plantago major, Trifolium pratense and Trifolium repens) to cotyledon removal at 7, 14 and 21 d old. We monitored subsequent growth and flowering (number of inflorescences recorded, and time taken for first flowers to open) over a 107 d period. Cotyledon removal reduced growth during establishment (35 d) for all species, and a further three exhibited reduced growth at maturity. Four species developed fewer inflorescences, or had delayed flowering after cotyledon removal. Although early damage (7 d old) had the greatest long-term effect on plant performance, responses varied according to the age at which the damage occurred and the species involved. Our results illustrate how growth and flowering into the mature phase is affected by cotyledon damage during different stages of seedling ontogeny, and we highlight the ways in which ontogenetic variation in seedling tolerance of tissue loss might impact upon plant fitness in mature plant communities. PMID:17547653

  10. Correlation of maternal-fetal attachment and health practices during pregnancy with neonatal outcomes

    PubMed Central

    Maddahi, Maryam Sadat; Dolatian, Mahrokh; khoramabadi, Monirsadat; Talebi, Atefeh

    2016-01-01

    Introduction Low birth weight due to preterm delivery or intrauterine growth restriction (IUGR) is the strongest factor contributing to prenatal, neonatal, and postnatal mortality. Maternal–fetal attachment plays a significant role in maternal and fetal health. Health practices performed by the mother during pregnancy constitute one of the factors that may affect neonatal outcomes. The present study was conducted to identify the relationship between maternal–fetal attachment and health practices during pregnancy with neonatal outcomes. Methods This cross-sectional study was conducted on 315 pregnant women with a gestational age of 33–41 weeks who presented to hospitals in Sirjan (Iran) between December 2014 and February 2015. The data collection tools used included the Health Practices in Pregnancy Questionnaire and the Maternal Fetal Attachment Scale. Data were analyzed using IBM-SPSS version 20, focusing on the Pearson product–moment correlation and the logistic regression model. Statistical significance was set to p<0.05. Results The mean score of maternal–fetal attachment was 60.34, and the mean score of health practices was 123.57. The mean birth weight of the neonates was 3052.38 g. Health practices (p<0.05, r=0.11) and maternal-fetal attachment (p<0.01, r=0.23) were positively and significantly correlated with neonatal outcomes. A significant positive relationship was also observed between maternal–fetal attachment and neonatal outcomes. No significant relationships were observed between health practices during pregnancy and neonatal outcomes. Conclusion Maternal-fetal attachment and health practices during pregnancy are positively and significantly correlated with neonatal outcomes. PMID:27648191

  11. Estimation of fetal gestational age from ultrasound images

    NASA Astrophysics Data System (ADS)

    Salari, Valiollah

    1992-06-01

    Estimation of fetal gestational age, weight, and determination of fetal growth from the measurements of certain parameters of fetal head, abdomen, and femur have been well established in prenatal sonography. The measurements are made from the two dimensional, B- mode, ultrasound images of the fetus. The most common parameters measured are, biparietal diameter, occipital frontal diameter, head circumference, femur diaphysis length, and abdominal circumference. Since the fetal head has an elliptical shape and the femur has a linear shape, fitting the ellipse on the image of the fetal head, a line on the image of the femur are the tasks of image processing which are discussed in this paper.

  12. Effects of proposed adipogenic factors in fetal swine sera upon preadipocyte development

    SciTech Connect

    Ramsay, T.G.; Hausman, G.J.; Martin, R.J.

    1986-03-01

    Genetic obesity has been detected in fetal pigs which suggests primary factors that cause the obesity develop prenatally. Growth hormone and thyroid hormones have been implicated as regulatory factors in fetal serum for preadipocyte differentiation. This experiment examined effects of growth hormone (GH) and thyroxine (T4) addition upon preadipocyte proliferation and differentiation when supplemented to deficient fetal pig sea. Hormones were added to decapitated fetal pig (Decap) sera to concentrations present in intact littermate (Reference) sera. Primary stromal-vascular cell cultures were prepared from rat inguinal adipose tissue. Cells were incubated with 5% decap or reference sera and hormones in media 199 during: days 1 to 5 for a /sup 3/H-thymidine incorporation assay; days 1 to 15 for assay of ..cap alpha..-glycerol phosphate dehydrogenase; days 5 to 14 for a complete differentiation assay. Decap sera promoted less proliferation and enzyme differentiation than reference sera with no effect of GH addition. GH reduced detection of lipid accumulating cells on percol density gradients by 81%. T4 addition stimulated preadipocyte multiplication and produced a 30% increase in completely differentiated preadipocytes. These results indicate thyroid hormones are important components of fetal sera for regulation of preadipocyte development, whereas GH may only affect cellular metabolism.

  13. Pleiotropic Genes Affecting Carcass Traits in Bos indicus (Nellore) Cattle Are Modulators of Growth.

    PubMed

    G T Pereira, Anirene; Utsunomiya, Yuri T; Milanesi, Marco; Torrecilha, Rafaela B P; Carmo, Adriana S; Neves, Haroldo H R; Carvalheiro, Roberto; Ajmone-Marsan, Paolo; Sonstegard, Tad S; Sölkner, Johann; Contreras-Castillo, Carmen J; Garcia, José F

    2016-01-01

    Two complementary methods, namely Multi-Trait Meta-Analysis and Versatile Gene-Based Test for Genome-wide Association Studies (VEGAS), were used to identify putative pleiotropic genes affecting carcass traits in Bos indicus (Nellore) cattle. The genotypic data comprised over 777,000 single-nucleotide polymorphism markers scored in 995 bulls, and the phenotypic data included deregressed breeding values (dEBV) for weight measurements at birth, weaning and yearling, as well visual scores taken at weaning and yearling for carcass finishing precocity, conformation and muscling. Both analyses pointed to the pleomorphic adenoma gene 1 (PLAG1) as a major pleiotropic gene. VEGAS analysis revealed 224 additional candidates. From these, 57 participated, together with PLAG1, in a network involved in the modulation of the function and expression of IGF1 (insulin like growth factor 1), IGF2 (insulin like growth factor 2), GH1 (growth hormone 1), IGF1R (insulin like growth factor 1 receptor) and GHR (growth hormone receptor), suggesting that those pleiotropic genes operate as satellite regulators of the growth pathway. PMID:27410030

  14. Pleiotropic Genes Affecting Carcass Traits in Bos indicus (Nellore) Cattle Are Modulators of Growth

    PubMed Central

    Milanesi, Marco; Torrecilha, Rafaela B. P.; Carmo, Adriana S.; Neves, Haroldo H. R.; Carvalheiro, Roberto; Ajmone-Marsan, Paolo; Sonstegard, Tad S.; Sölkner, Johann; Contreras-Castillo, Carmen J.; Garcia, José F.

    2016-01-01

    Two complementary methods, namely Multi-Trait Meta-Analysis and Versatile Gene-Based Test for Genome-wide Association Studies (VEGAS), were used to identify putative pleiotropic genes affecting carcass traits in Bos indicus (Nellore) cattle. The genotypic data comprised over 777,000 single-nucleotide polymorphism markers scored in 995 bulls, and the phenotypic data included deregressed breeding values (dEBV) for weight measurements at birth, weaning and yearling, as well visual scores taken at weaning and yearling for carcass finishing precocity, conformation and muscling. Both analyses pointed to the pleomorphic adenoma gene 1 (PLAG1) as a major pleiotropic gene. VEGAS analysis revealed 224 additional candidates. From these, 57 participated, together with PLAG1, in a network involved in the modulation of the function and expression of IGF1 (insulin like growth factor 1), IGF2 (insulin like growth factor 2), GH1 (growth hormone 1), IGF1R (insulin like growth factor 1 receptor) and GHR (growth hormone receptor), suggesting that those pleiotropic genes operate as satellite regulators of the growth pathway. PMID:27410030

  15. Dietary nucleotides affect hepatic growth and composition in the weanling mouse.

    PubMed

    Novak, D A; Carver, J D; Barness, L A

    1994-01-01

    The effect of dietary nucleotides upon hepatic growth and composition was examined in weanling mice. For 5 weeks, mice were fed either Purina Rat Chow, a nucleotide-free diet (NT-), a nucleotide-free diet supplemented with a mixture of five nucleotides (0.21% w/w), (NT+) or a nucleotide-free diet supplemented with adenosine 5'-monophosphate (0.0425% w/w) (NTA). Hepatic cholesterol and lipid phosphorous were significantly higher, whereas liver weight (expressed as a percentage of body weight), and glycogen were lower in animals fed NT- vs all other groups. NTA-fed animals presented a greater contrast to the NT- group than did animals fed the mixture of nucleotides. Liver fatty acid composition and distribution of phospholipid subclasses were not affected by dietary nucleotide supplementation. Dietary nucleotide supplementation in weanling mice affects hepatic growth and composition; adenosine 5'-monophosphate may play a unique role in these effects.

  16. Color of illumination during growth affects LHCII chiral macroaggregates in pea plant leaves.

    PubMed

    Gussakovsky, Eugene E; Shahak, Yosepha; Schroeder, Dana F

    2007-02-01

    To determine whether the color of illumination under which plants are grown, affects the structure of photosynthetic antennae, pea plants were grown under either blue-enriched, red-enriched, or white light. Carotenoid content of isolated chloroplasts was found to be insensitive to the color of illumination during growth, while chlorophyll a/b ratio in chloroplasts isolated from young illuminated leaves showed susceptibility to color. Color of illumination affects the LHCII chiral macroaggregates in intact leaves and isolated chloroplasts, providing light-induced alteration of the handedness of the LHCII chiral macroaggregate, as measured with circular dichroism and circularly polarized luminescence. The susceptibility of handedness to current illumination (red light excitation of chlorophyll fluorescence) is dependent on the color under which the plants were grown, and was maximal for the red-enriched illumination. We propose the existence of a long-term (growth period) color memory, which influences the susceptibility of the handedness of LHCII chiral macroaggregates to current light.

  17. A murine model for the assessment of placental and fetal development in teratogenicity studies.

    PubMed

    Hau, J; Basse, A; Wolstrup, C

    1987-01-01

    During normal pregnancy in the mouse, maternal serum levels of the analogues to human schwangerschaftsprotein-1 and alpha-fetoprotein correlate significantly with the growth of the placenta and fetus respectively. This relationship has been utilized in the analysis of the effect of sodium selenite on placental and fetal growth in mice. Moderate doses of sodium selenite did not affect the growth of the placenta and fetus significantly, whereas high doses of selenite resulted in a large percentage of abortions. The protein markers were found to be useful in the prediction of placental and fetal growth, and they are suggested to be of general use in the study of the impact of teratogenic substances, since they reflect the status of the fetoplacental mass during gestation.

  18. Challenge of Fetal Mortality

    MedlinePlus

    ... Death Data File and Linked Birth/Infant Death Data Set, National Vital Statistics System The magnitude of fetal ... Death Data File and Linked Birth/Infant Death Data Set, NVSS. The vital statistics Fetal Death Data File ...

  19. Fetal alcohol syndrome

    MedlinePlus

    Alcohol in pregnancy; Alcohol-related birth defects; Fetal alcohol effects; FAS ... varies. Almost none of these babies have normal brain development. Infants and children with fetal alcohol syndrome have many different problems, which can be ...

  20. Fetal Alcohol Spectrum Disorders

    MedlinePlus

    ... alcohol can cause a group of conditions called fetal alcohol spectrum disorders (FASDs). Effects can include physical and behavioral problems such ... alcohol syndrome is the most serious type of FASD. People with fetal alcohol syndrome have facial abnormalities, ...

  1. Macronutrient content of plant-based food affects growth of a carnivorous arthropod.

    PubMed

    Wilder, Shawn M; Holway, David A; Suarez, Andrew V; Eubanks, Micky D

    2011-02-01

    Many arthropods engage in mutualisms in which they consume plant-based foods including nectar, extrafloral nectar, and honeydew. However, relatively little is known about the manner in which the specific macronutrients in these plant-based resources affect growth, especially for carnivorous arthropods. Using a combination of laboratory and field experiments, we tested (1) how plant-based foods, together with ad libitum insect prey, affect the growth of a carnivorous ant, Solenopsis invicta, and (2) which macronutrients in these resources (i.e., carbohydrates, amino acids, or both) contribute to higher colony growth. Access to honeydew increased the production of workers and brood in experimental colonies. This growth effect appeared to be due to carbohydrates alone as colonies provided with the carbohydrate component of artificial extrafloral nectar had greater worker and brood production compared to colonies deprived of carbohydrates. Surprisingly, amino acids only had a slight interactive effect on the proportion of a colony composed of brood and negatively affected worker survival. Diet choice in the laboratory and field matched performance in the laboratory with high recruitment to carbohydrate baits and only slight recruitment to amino acids. The strong, positive effects of carbohydrates on colony growth and the low cost of producing this macronutrient for plants and hemipterans may have aided the evolution of food-for-protection mutualisms and help explain why these interactions are so common in ants. In addition, greater access to plant-based resources in the introduced range of S. invicta may help to explain the high densities achieved by this species throughout the southeastern United States.

  2. Macronutrient content of plant-based food affects growth of a carnivorous arthropod.

    PubMed

    Wilder, Shawn M; Holway, David A; Suarez, Andrew V; Eubanks, Micky D

    2011-02-01

    Many arthropods engage in mutualisms in which they consume plant-based foods including nectar, extrafloral nectar, and honeydew. However, relatively little is known about the manner in which the specific macronutrients in these plant-based resources affect growth, especially for carnivorous arthropods. Using a combination of laboratory and field experiments, we tested (1) how plant-based foods, together with ad libitum insect prey, affect the growth of a carnivorous ant, Solenopsis invicta, and (2) which macronutrients in these resources (i.e., carbohydrates, amino acids, or both) contribute to higher colony growth. Access to honeydew increased the production of workers and brood in experimental colonies. This growth effect appeared to be due to carbohydrates alone as colonies provided with the carbohydrate component of artificial extrafloral nectar had greater worker and brood production compared to colonies deprived of carbohydrates. Surprisingly, amino acids only had a slight interactive effect on the proportion of a colony composed of brood and negatively affected worker survival. Diet choice in the laboratory and field matched performance in the laboratory with high recruitment to carbohydrate baits and only slight recruitment to amino acids. The strong, positive effects of carbohydrates on colony growth and the low cost of producing this macronutrient for plants and hemipterans may have aided the evolution of food-for-protection mutualisms and help explain why these interactions are so common in ants. In addition, greater access to plant-based resources in the introduced range of S. invicta may help to explain the high densities achieved by this species throughout the southeastern United States. PMID:21618912

  3. Fetal behavioral teratology.

    PubMed

    Visser, Gerard H A; Mulder, Eduard J H; Tessa Ververs, F F

    2010-10-01

    Ultrasound studies of fetal motor behavior provide direct – in vivo – insight in the functioning of the motor component of the fetal central nervous system. In this article, studies are reviewed showing changes in the first timetable of appearance of fetal movements, changes in quality and/or quantity of movements and disturbances in the development of fetal behavioral states in case of endogenous malfunctions, maternal diseases and exogenous behavioral teratogens.

  4. Soil Particle Heterogeneity Affects the Growth of a Rhizomatous Wetland Plant

    PubMed Central

    Xue, Wei; Peng, Yi-Ke; Zhang, Ming-Xiang; Yu, Fei-Hai

    2013-01-01

    Soil is commonly composed of particles of different sizes, and soil particle size may greatly affect the growth of plants because it affects soil physical and chemical properties. However, no study has tested the effects of soil particle heterogeneity on the growth of clonal plants. We conducted a greenhouse experiment in which individual ramets of the wetland plant Bolboschoenus planiculmis were grown in three homogeneous soil treatments with uniformly sized quartz particles (small: 0.75 mm, medium: 1.5 mm, or large: 3 mm), one homogeneous treatment with an even mixture of large and medium particles, and two heterogeneous treatments consisting of 16 or 4 patches of large and medium particles. Biomass, ramet number, rhizome length and spacer length were significantly greater in the treatment with only medium particles than in the one with only large particles. Biomass, ramet number, rhizome length and tuber number in the patchy treatments were greater in patches of medium than of large particles; this difference was more pronounced when patches were small than when they were large. Soil particle size and soil particle heterogeneity can greatly affect the growth of clonal plants. Thus, studies to test the effects of soil heterogeneity on clonal plants should distinguish the effects of nutrient heterogeneity from those of particle heterogeneity. PMID:23936110

  5. Gonadotropin ratio affects the in vitro growth of rhesus ovarian preantral follicles.

    PubMed

    Kim, Yoon Young; Yun, Jun-Won; Kim, Jong Min; Park, Chung Gyu; Rosenwaks, Zev; Liu, Hung Ching; Kang, Byeong-Cheol; Ku, Seung-Yup

    2016-04-01

    In vitro follicle growth (IVFG) strategy is critical in the fertility preservation of cancer survivors; however, its optima