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Sample records for lactating rat dams

  1. Effects of Hypergravity Exposure On Plasma Oxytocin Concentrations In Pregnant and Lactating Rat Dams

    NASA Technical Reports Server (NTRS)

    Baer, Lisa A.; Wade, Charles E.; Ronca, April E.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    Rat dams and offspring were exposed to 1.5-g, 1.75-g or 2.0-g hypergravity (hg) from Gestational day (G) 11 until Postnatal day (P) 10. To ascertain the role of maternal factors in reduced postnatal body weights of offspring developed in hg, the dams' lactational hormones were measured. Oxytocin (OT), the major hormone responsible for milk ejection, was reduced in hg dams whereas prolactin (Prl), involved in milk production, was unchanged. Video analyses of nursing behavior revealed that hg dams spent more time nursing relative to 1-g controls. We hypothesized impaired milk transfer from dam to pup, however pup body weight gains following a discrete suckling episode were comparable across conditions. Changes in lactational hormones and nursing behavior by dams exposed to hg do not account for reduced body masses of their offspring.

  2. Effects of Hypergravity Exposure on Prolactin Levels in Pre-parturient , Parturient and Lactating Rat Dams

    NASA Technical Reports Server (NTRS)

    Baer. Lisa A.; Wade, Charles E.; Ronca, April E.; Sun, Sid (Technical Monitor)

    2001-01-01

    We analyzed the effects of 2.0-g, 1.75-g and 1.5-g hypergravity exposure on plasma concentrations of the lactotrophic hormone, prolactin (PRL), in female rats on pre-parturient (Gestation Day 20), parturient (Post-natal day 0) and lactating (P10) days. PRL levels have been found to be reduced in rat dams around the time of birth following exposure to gravitational loads varying from 2.16 to 3.14-g (Megory et. al., Aviation, Space and Environs 1129-1135, 1984). It has also been reported that at these high gravitational loads, neonatal mortality has been extremely high, suggesting a possible interaction between dam PRL concentration and neonatal outcome. We have previously reported no significant differences in PRL levels of parturient (PO) and lactating (P6 & P 15) dams when exposed to 1.5-g hypergravity, but did observe a slight elevation of PRL on PO and P 15, with a decrease on P6. In the present study, time-bred pregnant dams were exposed to either continuous 2.0-g, 1.75-g or 1.5-g centrifugation, beginning on Gestational day (G) 11 of the rats' 22-day pregnancy. We observed no significant differences in PRL concentrations between SC and any of the HG conditions. On G20 and PO, PRL concentrations of the 2.0-g and 1.5-g groups were slightly elevated as compared to SC. Similar to what we previously reported. PRL secretion was elevated in both HG and SC conditions on the day of birth relative to later during lactation, but on P10 it appeared to be reduced in HG relative to SC dams. These findings suggests that hypergravity slightly elevates plasma concentration of PRL in pre-parturient and lactating rat dams, with effects most pronounced during the periparturitional period and in a direction opposite to that observed following microgravity exposure.

  3. Effects of Hypergravity Exposure on Prolactin Levels in Pre-parturient , Parturient and Lactating Rat Dams

    NASA Technical Reports Server (NTRS)

    Baer. Lisa A.; Wade, Charles E.; Ronca, April E.; Sun, Sid (Technical Monitor)

    2001-01-01

    We analyzed the effects of 2.0-g, 1.75-g and 1.5-g hypergravity exposure on plasma concentrations of the lactotrophic hormone, prolactin (PRL), in female rats on pre-parturient (Gestation Day 20), parturient (Post-natal day 0) and lactating (P10) days. PRL levels have been found to be reduced in rat dams around the time of birth following exposure to gravitational loads varying from 2.16 to 3.14-g (Megory et. al., Aviation, Space and Environs 1129-1135, 1984). It has also been reported that at these high gravitational loads, neonatal mortality has been extremely high, suggesting a possible interaction between dam PRL concentration and neonatal outcome. We have previously reported no significant differences in PRL levels of parturient (PO) and lactating (P6 & P 15) dams when exposed to 1.5-g hypergravity, but did observe a slight elevation of PRL on PO and P 15, with a decrease on P6. In the present study, time-bred pregnant dams were exposed to either continuous 2.0-g, 1.75-g or 1.5-g centrifugation, beginning on Gestational day (G) 11 of the rats' 22-day pregnancy. We observed no significant differences in PRL concentrations between SC and any of the HG conditions. On G20 and PO, PRL concentrations of the 2.0-g and 1.5-g groups were slightly elevated as compared to SC. Similar to what we previously reported. PRL secretion was elevated in both HG and SC conditions on the day of birth relative to later during lactation, but on P10 it appeared to be reduced in HG relative to SC dams. These findings suggests that hypergravity slightly elevates plasma concentration of PRL in pre-parturient and lactating rat dams, with effects most pronounced during the periparturitional period and in a direction opposite to that observed following microgravity exposure.

  4. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring.

    PubMed

    Axelstad, Marta; Boberg, Julie; Vinggaard, Anne Marie; Christiansen, Sofie; Hass, Ulla

    2013-09-01

    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T₄) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout gestation and lactation. Total T₄ serum levels were measured in dams and offspring, and all doses of triclosan significantly lowered T₄ in dams, but no significant effects on T₄ levels were seen in the offspring at the end of the lactation period. Since this lack of effect could be due to minimal exposure through maternal milk, a second study using direct per oral pup exposure from postnatal day 3-16 to 50 or 150 mg triclosan/kg bw/day was performed. This exposure pointed to significant T₄ reductions in 16 day old offspring in both dose groups. These results corroborate previous studies showing that in rats lactational transfer of triclosan seems limited. Since an optimal study design for testing potential developmental neurotoxicants in rats, should include exposure during both the pre- and postnatal periods of brain development, we suggest that in the case of triclosan, direct dosing of pups may be the best way to obtain that goal.

  5. Effects of Hypergravity Exposure on Plasma Oxytocin (OT) Concentrations in Pregnant and Lactating Rat Dams

    NASA Technical Reports Server (NTRS)

    Baer, Lisa A.; Wade, Charles E.; Plaut, Karen; Ronca, April E.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    From pregnancy to weaning there is a progressive elevation of plasma oxytocin (OT) levels associated with nursing activity, irrespective of litter size. In the present study, we analyzed the effects of continuous 1.5G, 1.75G and 2.0G hypergravity exposure on OT plasma concentration in prepartum (Gestation Day 20) (G20) and lactating (Postnatal day) (P10) rat dams. For this study, litter size was controlled with a yoking procedure established in our lab where individual control litters were yoked-matched to individual hypergravity litters. We reviewed all data at hypergravity irrespective of gravitational level and compared the values with the controls in both G20 (HG, n=15;SC, n=9) and P10 (HG, n=21;SC, n=16). Results showed that over time, we did observe the expected OT increase in both groups. In G20 dams, measurement of OT concentrations showed no significance. However, at P10, measurements of OT concentrations suggest a reduction of about 20% compared to established controls in our laboratory, 0.9+/-0.09 ng/ml for the controls and 0.7+/-0.06 ng/ml for centrifuged animals (p<0.02). These data suggest that exposure to centrifugation may reduce OT levels during lactation. When these plasma samples were obtained, the dams were removed from the litters, and values were not adjusted for the size of the litters. The reduction in OT with centrifugation may reflect a decrease in nursing activity or a decreased responsiveness of the mammary hypothalamic axis. In addition, we have analyzed data on plasma prolactin concentrations and mammary gland development, which may give additional insight to the results of our OT measurements.

  6. Effects of Hypergravity Exposure on Plasma Oxytocin (OT) Concentrations in Pregnant and Lactating Rat Dams

    NASA Technical Reports Server (NTRS)

    Baer, Lisa A.; Wade, Charles E.; Plaut, Karen; Ronca, April E.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    From pregnancy to weaning there is a progressive elevation of plasma oxytocin (OT) levels associated with nursing activity, irrespective of litter size. In the present study, we analyzed the effects of continuous 1.5G, 1.75G and 2.0G hypergravity exposure on OT plasma concentration in prepartum (Gestation Day 20) (G20) and lactating (Postnatal day) (P10) rat dams. For this study, litter size was controlled with a yoking procedure established in our lab where individual control litters were yoked-matched to individual hypergravity litters. We reviewed all data at hypergravity irrespective of gravitational level and compared the values with the controls in both G20 (HG, n=15;SC, n=9) and P10 (HG, n=21;SC, n=16). Results showed that over time, we did observe the expected OT increase in both groups. In G20 dams, measurement of OT concentrations showed no significance. However, at P10, measurements of OT concentrations suggest a reduction of about 20% compared to established controls in our laboratory, 0.9+/-0.09 ng/ml for the controls and 0.7+/-0.06 ng/ml for centrifuged animals (p<0.02). These data suggest that exposure to centrifugation may reduce OT levels during lactation. When these plasma samples were obtained, the dams were removed from the litters, and values were not adjusted for the size of the litters. The reduction in OT with centrifugation may reflect a decrease in nursing activity or a decreased responsiveness of the mammary hypothalamic axis. In addition, we have analyzed data on plasma prolactin concentrations and mammary gland development, which may give additional insight to the results of our OT measurements.

  7. Effects of zinc depletion and repletion during lactation on rat dams and their offspring

    SciTech Connect

    Dibi, K.

    1985-01-01

    The effects of feeding 5 mg Zn/kg, 12 mg Zn/kg, 50 mg Zn/kg in egg white diets and 50 mg Zn/kg in defatted glandless cottonseed diet on postnatal growth and tissue zinc concentrations of dams and neonates were investigated. One or more of the following tissues were obtained on days 7, 14, 21, and 56 for analyses: femur, liver, brain, testes, spleen, and/or blood. Dams fed the cottonseed diet weighted more than dams fed the egg white diets. Dams fed zinc in cottonseed diet had higher blood zinc concentrations than dams fed zinc in the egg white diets. Dams and the offspring fed 50 mg zn/kg egg white diet had higher femur zinc levels than dams and the offspring fed 50 mg Zn/kg in the cottonseed diet. There was no difference in the weight gain/loss of dams fed 50 mg Zn/kg or 12 mg Zn/kg egg white diets. Femur zinc concentrations of pups suckling dams fed 50 mg Zn/kg egg white were higher than femur zinc concentrations of pups suckling dams fed 12 mg Zn/kg egg white diet. Body weights and tissue zinc concentrations of the neonates suckling dams fed 5 mg Zn/kg egg white diet and then repleted with zinc in either egg white or cottonseed diet were similar. There was complete recovery when rats were fed 5 mg Zn/kg and then repleted with zinc at 50 mg Zn/kg level. Therefore, the protein source did not have statistically significantly different effects on zinc availability to the rats.

  8. Impairment of male rat reproductive function in F1 offspring from dams exposed to 2-bromopropane during gestation and lactation.

    PubMed

    Kang, Kyung-Sun; Li, Guang-Xun; Che, Jeong-Hwan; Lee, Yong-Soon

    2002-01-01

    The toxic effects of 2-bromopropane (2-BP) on the reproductive tracts of male F1 offspring from dams exposed to 2-BP during gestation and lactation were investigated. Ten pregnant (sperm-positive) Sprague-Dawley rats per group were exposed sc to 2-BP at 135, 405, and 1215 mg/kg/day from gestation day (GD) 6 to postnatal day (PND) 20. 2-BP decreased the proportion of dams littering at the two highest doses. At the highest dose, the rate of delivery and surviving pups were significantly lower than in the controls (P < or = 0.05). The relative weights of testes vs. brain were significantly lower than the controls (P < or = 0.05) on PND 33 and 63 at 405 mg/kg/day, and on PND 90 at 1215 mg/kg/day in the F1 rats. Seminiferous tubule atrophy, germ cell loss, and increased Leydig cell proliferation were observed at the highest dose by histopathologic examination. Female offspring has a decrease in all follicle types at the high dose. These results suggest that gestational and lactational exposure to 2-BP at a high maternally toxic dose impairs the development of the reproductive organs of the offspring.

  9. Exposure to nicotine increases dopamine receptor content in the mesocorticolimbic pathway of rat dams and offspring during lactation.

    PubMed

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

    2015-09-01

    Nicotine exposure causes the release of dopamine from the ventral tegmental area (VTA) to the nucleus accumbens (NAc). We have previously shown that maternal exposure to nicotine during lactation causes hyperleptinemia in dams and pups, and leptin is known to decrease dopamine release from the VTA. Here we evaluated whether maternal exposure to nicotine during lactation causes changes in dopamine and leptin signaling pathways at the end of exposure and after 5days of withdrawal in the: VTA, NAc, arcuate nucleus (ARC) and dorsal striatum (DS). On postnatal day (PN) 2, lactating Wistar rats were implanted with minipumps releasing nicotine (NIC; 6mg/kg/day, s.c.) or saline (C) for 14days. Offspring were tested in the elevated plus maze (EPM) and open field on PN14 or PN20, and euthanized on PN15 or PN21. Entries into the open arms and head dips in the EPM were reduced in NIC pups at P20. At weaning (PN21), NIC dams had: lower tyrosine hydroxylase (TH), higher OBRb and SOCS3 contents in VTA; lower TH, higher D1R, D2R and DAT contents in NAc; higher TH content in DS; and higher D2R and SOCS3 contents in ARC. On PN15, NIC offspring had higher D1R, D2R and lower DAT contents in NAc, while on PN21, they had lower DAT in DS, and lower pSTAT3 content in ARC. We evidenced that postnatal nicotine exposure induces relevant changes in the brain reward system of dams and pups, possibly associated with changes in leptinemia and increased offspring anxiety-like behavior.

  10. Maternal High-Fat Diet during Pregnancy and Lactation Influences Obestatin and Ghrelin Concentrations in Milk and Plasma of Wistar Rat Dams and Their Offspring

    PubMed Central

    Słupecka, Monika; Romanowicz, Katarzyna; Woliński, Jarosław

    2016-01-01

    The study aims to establish the effect of a maternal high-fat diet on obestatin concentration, total ghrelin, and ghrelin/obestatin ratio during pregnancy and lactation of Wistar rats and their offspring in the first 21 days of life. On the mating day, females were randomly allocated and fed either a high-fat diet (30% of fat; HF) or breeding diet (5% fat; BD) till the 21st day of lactation. Hormones were analyzed in the blood plasma and milk of rat dams as well as in the blood plasma of their offspring. HF resulted in a significant decrease in obestatin level on the 14th day of lactation and elevation on the 21st day. Plasma obestatin in HFD offspring was significantly higher than in BD ones. HF diet did not significantly affect dam plasma ghrelin until the 21st day of lactation. The ghrelin concentrations in milk after both diets were significantly lower than in blood plasma. Milk ghrelin in HF dams was significantly higher than in the BD ones. Plasma ghrelin from HF offspring was significantly higher than that from BD dams. Our results demonstrate that a maternal HF diet during pregnancy and lactation influences ghrelin and obestatin level in both dams and their offspring. PMID:27127509

  11. Maternal High-Fat Diet during Pregnancy and Lactation Influences Obestatin and Ghrelin Concentrations in Milk and Plasma of Wistar Rat Dams and Their Offspring.

    PubMed

    Słupecka, Monika; Romanowicz, Katarzyna; Woliński, Jarosław

    2016-01-01

    The study aims to establish the effect of a maternal high-fat diet on obestatin concentration, total ghrelin, and ghrelin/obestatin ratio during pregnancy and lactation of Wistar rats and their offspring in the first 21 days of life. On the mating day, females were randomly allocated and fed either a high-fat diet (30% of fat; HF) or breeding diet (5% fat; BD) till the 21st day of lactation. Hormones were analyzed in the blood plasma and milk of rat dams as well as in the blood plasma of their offspring. HF resulted in a significant decrease in obestatin level on the 14th day of lactation and elevation on the 21st day. Plasma obestatin in HFD offspring was significantly higher than in BD ones. HF diet did not significantly affect dam plasma ghrelin until the 21st day of lactation. The ghrelin concentrations in milk after both diets were significantly lower than in blood plasma. Milk ghrelin in HF dams was significantly higher than in the BD ones. Plasma ghrelin from HF offspring was significantly higher than that from BD dams. Our results demonstrate that a maternal HF diet during pregnancy and lactation influences ghrelin and obestatin level in both dams and their offspring.

  12. Effects of a maternal diet supplemented with chocolate and fructose beverage during gestation and lactation on rat dams and their offspring.

    PubMed

    Zhang, Zhi-Yun; Zeng, Jin-Jing; Kjaergaard, Marina; Guan, Ni; Raun, Kirsten; Nilsson, Cecilia; Wang, Ming-Wei

    2011-09-01

    1. Consumption of a high-fat and high-energy diet during pregnancy leads to a risk of long-term consequences on fetal development, as well as on the postnatal health of offspring. To investigate the effects of such a diet on fetal programming, we established a high-energy intake pregnant rat model using chocolate and fructose beverage as supplements to a normal chow diet. 2. Pregnant Sprague-Dawley rats were assigned to either chow (control) or a diet supplemented with chocolate and fructose beverage throughout gestation and lactation. The male F(1) pups received normal chow diet after weaning. Physiological or pathological changes in dams and pups (e.g. glucose and lipid metabolism) were evaluated. 3. The results showed that dams offered the high-fat (mainly from chocolate) and high-calorie diet during gestation consumed more energy and gained more weight than chow-fed dams. Over-consumption of chocolate reduced chow intake in dams, leading to low maternal protein supply. As a result, pups from these dams exhibited reduced birth weight that lasted until adulthood. The high-energy diet during lactation led to increased total body fat, as well as impaired liver function, in offspring; thus, the lactational diet is suggested to be a stronger determinant of offspring fat metabolism than gestational diet. 4. The results of the study suggest that over-supply of carbohydrates, such as chocolate and fructose, either during gestation or lactation has a negative impact on the well-being of offspring.

  13. Large Litter Rearing Improves Leptin Sensitivity and Hypothalamic Appetite Markers in Offspring of Rat Dams Fed High-Fat Diet During Pregnancy and Lactation

    PubMed Central

    Sun, Bo; Song, Lin; Tamashiro, Kellie L. K.; Moran, Timothy H.

    2014-01-01

    Maternal high-fat (HF) diet has long-term consequences on the offspring's metabolic phenotype. Here, we determined the effects of large litter (LL) rearing in offspring of rat dams fed HF diet during gestation and lactation. Pregnant Sprague-Dawley rats were maintained on standard chow (CHOW) or HF diet throughout gestation and lactation. Pups were raised in normal litters (NLs) (10 pups/dam) or LLs (16 pups/dam) during lactation, resulting in 4 groups: CHOW-NL, CHOW-LL, HF-NL, and HF-LL. The offspring were weaned onto to either CHOW or HF diet on postnatal day 21. Male and female pups with maternal HF diet (HF-NL) had greater body weight and adiposity, higher plasma leptin levels, impaired glucose tolerance, abnormal hypothalamic leptin signaling pathways (lower leptin receptor-b [OB-Rb] and signal transducer and activator of transcription 3, higher suppressor of cytokine signaling 3 mRNA expression) and appetite markers (lower neuropeptide Y and Agouti-related peptide mRNA expression), and reduced phospho-signal transducer and activator of transcription 3 level in response to leptin in the arcuate nucleus at weaning, whereas LL rearing normalized these differences. When weaned onto CHOW diet, adult male offspring from HF diet-fed dams continued to have greater adiposity, higher leptin levels, and lower hypothalamic OB-Rb, and LL rearing improved them. When weaned onto HF diet, both adult male and female offspring with maternal HF diet had greater body weight and adiposity, higher leptin levels, impaired glucose tolerance, lower OB-Rb, and higher suppressor of cytokine signaling 3 in hypothalamus compared with those of CHOW dams, whereas LL rearing improved most of them except male OB-Rb expression. Our data suggest that LL rearing improves hypothalamic leptin signaling pathways and appetite markers in an age- and sex-specific manner in this model. PMID:24926823

  14. Large litter rearing improves leptin sensitivity and hypothalamic appetite markers in offspring of rat dams fed high-fat diet during pregnancy and lactation.

    PubMed

    Sun, Bo; Song, Lin; Tamashiro, Kellie L K; Moran, Timothy H; Yan, Jianqun

    2014-09-01

    Maternal high-fat (HF) diet has long-term consequences on the offspring's metabolic phenotype. Here, we determined the effects of large litter (LL) rearing in offspring of rat dams fed HF diet during gestation and lactation. Pregnant Sprague-Dawley rats were maintained on standard chow (CHOW) or HF diet throughout gestation and lactation. Pups were raised in normal litters (NLs) (10 pups/dam) or LLs (16 pups/dam) during lactation, resulting in 4 groups: CHOW-NL, CHOW-LL, HF-NL, and HF-LL. The offspring were weaned onto to either CHOW or HF diet on postnatal day 21. Male and female pups with maternal HF diet (HF-NL) had greater body weight and adiposity, higher plasma leptin levels, impaired glucose tolerance, abnormal hypothalamic leptin signaling pathways (lower leptin receptor-b [OB-Rb] and signal transducer and activator of transcription 3, higher suppressor of cytokine signaling 3 mRNA expression) and appetite markers (lower neuropeptide Y and Agouti-related peptide mRNA expression), and reduced phospho-signal transducer and activator of transcription 3 level in response to leptin in the arcuate nucleus at weaning, whereas LL rearing normalized these differences. When weaned onto CHOW diet, adult male offspring from HF diet-fed dams continued to have greater adiposity, higher leptin levels, and lower hypothalamic OB-Rb, and LL rearing improved them. When weaned onto HF diet, both adult male and female offspring with maternal HF diet had greater body weight and adiposity, higher leptin levels, impaired glucose tolerance, lower OB-Rb, and higher suppressor of cytokine signaling 3 in hypothalamus compared with those of CHOW dams, whereas LL rearing improved most of them except male OB-Rb expression. Our data suggest that LL rearing improves hypothalamic leptin signaling pathways and appetite markers in an age- and sex-specific manner in this model.

  15. Placental and lactational transfer of decabromodiphenyl ether and 2,2',4,4'-tetrabromodiphenyl ether in dam-offspring pairs of Sprague-Dawley rats.

    PubMed

    Shin, Mi-Yeon; Lee, Sunggyu; Choi, Hyeyoung; Jeong, Da-In; Moon, Hyo-Bang; Kim, Sungkyoon

    2017-01-31

    Although several studies have conducted maternal transfer of individual PBDE congener in experimental animals, there is a paucity of research on differences in maternal transfer of PBDE congeners. The purpose of the study was to investigate and compare placental and lactational transfer of BDE 47, -209 and its metabolites in rat dam-offspring pairs following repeated administration of BDE 47 and -209. (13)C-BDE 47, BDE 209 and its debrominated congeners were detected both in dam serum and offspring body, which indicates that PBDEs can be maternally transferred. In addition, BDE 196 and -197 appeared in offspring body earlier than in maternal serum, which suggests that debromination can be occur in offspring body. BDE 209 increased in both dam and offspring while levels of (13)C-BDE 47 was not increased in dam serum. 13C-BDE 47 seems to be stored in breast milk rather than in maternal serum, which can be assumed through the drastic increase of the congener in suckling pups. The magnitude of lactational transfer of the administered congeners was greater than that of placental transfer. And (13)C-BDE 47 was relatively more transferred to suckling pups than BDE 209 through breastfeeding.

  16. Early postweaning exercise improves central leptin sensitivity in offspring of rat dams fed high-fat diet during pregnancy and lactation.

    PubMed

    Sun, Bo; Liang, Nu-Chu; Ewald, Erin R; Purcell, Ryan H; Boersma, Gretha J; Yan, Jianqun; Moran, Timothy H; Tamashiro, Kellie L K

    2013-11-01

    Maternal high-fat (HF) diet has long-term consequences on the metabolic phenotype of the offspring. Here, we determined the effects of postweaning exercise in offspring of rat dams fed HF diet during gestation and lactation. Pregnant Sprague-Dawley rats were maintained on chow or HF diet throughout gestation and lactation. All pups were weaned onto chow diet on postnatal day (PND) 21. At 4 wk of age, male pups were given free access to running wheels (RW) or remained sedentary (SED) for 3 wk, after which all rats remained sedentary, resulting in four groups: CHOW-SED, CHOW-RW, HF-SED, and HF-RW. Male HF offspring gained more body weight by PND7 compared with CHOW pups and maintained this weight difference through the entire experiment. Three weeks of postweaning exercise did not affect body weight gain in either CHOW or HF offspring, but reduced adiposity in HF offspring. Plasma leptin was decreased at the end of the 3-wk running period in HF-RW rats but was not different from HF-SED 9 wk after the exercise period ended. At 14 wk of age, intracerebroventricular injection of leptin suppressed food intake in CHOW-SED, CHOW-RW, and HF-RW, while it did not affect food intake in HF-SED group. At death, HF-RW rats also had higher leptin-induced phospho-STAT3 level in the arcuate nucleus than HF-SED rats. Both maternal HF diet and postweaning exercise had effects on hypothalamic neuropeptide and receptor mRNA expression in adult offspring. Our data suggest that postweaning exercise improves central leptin sensitivity and signaling in this model.

  17. Phenobarbital (PB)-induced changes in blood coagulationrelated parameters in pregnant rats, lactating rats and pups.

    PubMed

    Mochizuki, Masahiro; Shimizu, Satomi; Kidokoro, Yuri; Kamata, Takashi; Kitazawa, Takahiro; Kishi, Daisuke; Okazaki, Emi; Nishihata, Yoshito; Ohishi, Takumi

    2009-12-01

    Effects of repeated administration of phenobarbital (PB) on blood coagulation-related parameters were examined in non-pregnant, pregnant and lactating rats, and also in pups born to PB-treated lactating dams. PB was orally administered at a dose level of 80 mg/kg/day to pregnant (from gestation day (GD) 13), postpartum (from postpartum day (PPD) 7) and non-pregnant rats (from 13 weeks of age) for 7 days. Blood was collected on GD20 or PPD14 to perform blood coagulation examination. Concurrently, the blood coagulation parameters were examined in the pups. Increases in liver weight and/or hepatic cytochrome P450 content were observed in the PB-treated non-pregnant, pregnant and lactating rats. Activated partial thromboplastin time (APTT) was prolonged and anti-thrombin III (ATIII) concentration was increased in the lactating rats, while there were no changes in prothrombin time (PT) or APTT in the non-pregnant and pregnant rats. Moreover, prolongation of PT and APTT and decreases in factors VII and IX activities were observed in their pups. Thus, prolongation of blood coagulation time was confirmed in both dams and their pups following PB-administration to lactating dams. Effects of vitamin K(2) (VK(2)) on PB-induced changes in blood coagulation-related parameters of both dams and their pups were examined by co-administration with PB and VK(2) to lactating dams. PT and APTT were comparable to the control and PB-induced prolongation of blood coagulation time was improved in the pups while APTT was prolonged in dams, suggesting that VK(2) was beneficial to pups but not to dams.

  18. Acute cocaine alters oxytocin levels in the medial preoptic area and amygdala in lactating rat dams: implications for cocaine-induced changes in maternal behavior and maternal aggression.

    PubMed

    Elliott, J C; Lubin, D A; Walker, C H; Johns, J M

    2001-04-01

    Acute cocaine administration has been correlated with disruptions in the onset and maintenance of maternal behavior as well as decreases in maternal aggressive behavior in rat dams. A growing body of evidence suggests that cocaine may alter oxytocin levels leading to impairments in maternal behavior and aggression. The current study assessed whether acute cocaine injections alter oxytocin (OT) levels in the medial preoptic area (MPOA), ventral tegmental area (VTA), amygdala (AMY), and hippocampus (HIP) on postpartum day (PPD) 1 or PPD 6. On PPD 1, 30 mg/kg cocaine reduced OT levels by approximately 26.9% (picograms/milligram) in the MPOA (t (18) = 3.44, P<.01) compared to saline. On PPD 6, 30 mg/kg cocaine significantly increased OT levels by approximately 20.9% (picograms/brain area) in the AMY (F (2,25) = 3.44, P=.05) relative to saline. These findings suggest that acute cocaine may disrupt maternal behavior and maternal aggression at least in part through its action on the oxytocinergic system. Copyright 2001 Harcourt Publishers Ltd.

  19. Choline is required in the diet of lactating dams to maintain maternal immune function.

    PubMed

    Dellschaft, Neele S; Ruth, Megan R; Goruk, Susan; Lewis, Erin D; Richard, Caroline; Jacobs, René L; Curtis, Jonathan M; Field, Catherine J

    2015-06-14

    Choline demands during lactation are high; however, detailed knowledge is lacking regarding the optimal dietary intake during this critical period. The present study was designed to determine the effects of varying intakes of choline on maternal immune function during lactation. Primiparous Sprague-Dawley rats (n 42) were randomised 24-48 h before birth and fed the following diets for 21 d: choline-devoid (0 g choline/kg diet; D, n 10); 1·0 g choline/kg diet (C1, n 11); 2·5 g choline/kg diet (C2·5, n 10); 6·2 g choline/kg diet (C6, n 11). Splenocytes were isolated and stimulated ex vivo with concanavalin A, lipopolysaccharide (LPS) or CD3/CD28. D and C6 dams had lower final body weight, spleen weight and average pup weight than C1 dams (P< 0·05). There was a linear relationship between free choline concentration in pup stomach contents with maternal dietary choline content (P< 0·001, r² 0·415). Compared with C1 and C2·5, D spleens had a lower proportion of mature T cells and activated suppressor cells, and this resulted in reduced cytokine production after stimulation (P< 0·05). Feeding 6·2 g choline/kg diet resulted in a higher cytokine production after stimulation with CD3/CD28 (P< 0·05). Except for a higher IL-6 production after LPS stimulation with cells from the C2·5 dams (P< 0·05), there were no differences between the C1 and C2·5 dams. For the first time, we show that feeding lactating mothers a diet free of choline has substantial effects on their immune function and on offspring growth. Additionally, excess dietary choline had adverse effects on maternal and offspring body weight but only minimal effects on maternal immune function.

  20. Effects of dietary sialic acid in n-3 fatty acid-deficient dams during pregnancy and lactation on the learning abilities of their pups after weaning.

    PubMed

    Hiratsuka, Seiichi; Honma, Hiroyuki; Saitoh, Yoichi; Yasuda, Yuki; Yokogoshi, Hidehiko

    2013-01-01

    The effects of dietary sialic acid in dams on the learning abilities of their pups after weaning were investigated using rats deficient in n-3 fatty acids. Nine-week-old female Wistar rats were fed an n-3 fatty acid-deficient diet for 3 wk and were mated at 12 wk of age. During pregnancy and lactation, the female rats were fed the n-3 fatty acid-deficient diet, and were given water or water containing 1% N-acetylneuraminic acid (NANA) ad libitum. After weaning, the learning abilities of the pups were evaluated using a novel object recognition test. The recognition index of pups nursed by dams fed on water containing 1% NANA (NANA-intake dams) was significantly higher than that of pups nursed by dams fed only on water (NANA non-intake dams). There were no significant differences in the total sialic acid or docosahexaenoic acid contents in the cerebral cortex or hippocampus of pups nursed by dams fed on either type of water. The total dimethylacetal (DMA, from plasmalogen) level in the cerebral cortex of pups nursed by NANA-intake dams was significantly higher than that of pups nursed by NANA non-intake dams. These results suggest that dietary sialic acid in dams during pregnancy and lactation might be beneficial for the learning abilities of pups after weaning, which may be related to the plasmalogen level in the brain of pups.

  1. Early life triclocarban exposure during lactation affects neonate rat survival.

    PubMed

    Kennedy, Rebekah C M; Menn, Fu-Min; Healy, Laura; Fecteau, Kellie A; Hu, Pan; Bae, Jiyoung; Gee, Nancy A; Lasley, Bill L; Zhao, Ling; Chen, Jiangang

    2015-01-01

    Triclocarban (3,4,4'-trichlorocarbanilide; TCC), an antimicrobial used in bar soaps, affects endocrine function in vitro and in vivo. This study investigates whether TCC exposure during early life affects the trajectory of fetal and/or neonatal development. Sprague Dawley rats were provided control, 0.2% weight/weight (w/w), or 0.5% w/w TCC-supplemented chow through a series of 3 experiments that limited exposure to critical growth periods: gestation, gestation and lactation, or lactation only (cross-fostering) to determine the susceptible windows of exposure for developmental consequences. Reduced offspring survival occurred when offspring were exposed to TCC at concentrations of 0.2% w/w and 0.5% w/w during lactation, in which only 13% of offspring raised by 0.2% w/w TCC dams survived beyond weaning and no offspring raised by 0.5% w/w TCC dams survived to this period. In utero exposure status had no effect on survival, as all pups nursed by control dams survived regardless of their in utero exposure status. Microscopic evaluation of dam mammary tissue revealed involution to be a secondary outcome of TCC exposure rather than a primary effect of compound administration. The average concentration of TCC in the milk was almost 4 times that of the corresponding maternal serum levels. The results demonstrate that gestational TCC exposure does not affect the ability of dams to carry offspring to term but TCC exposure during lactation has adverse consequences on the survival of offspring although the mechanism of reduced survival is currently unknown. This information highlights the importance of evaluating the safety of TCC application in personal care products and the impacts during early life exposure.

  2. Early Life Triclocarban Exposure During Lactation Affects Neonate Rat Survival

    PubMed Central

    Kennedy, Rebekah C. M.; Menn, Fu-Min; Healy, Laura; Fecteau, Kellie A.; Hu, Pan; Bae, Jiyoung; Gee, Nancy A.; Lasley, Bill L.; Zhao, Ling

    2015-01-01

    Triclocarban (3,4,4′-trichlorocarbanilide; TCC), an antimicrobial used in bar soaps, affects endocrine function in vitro and in vivo. This study investigates whether TCC exposure during early life affects the trajectory of fetal and/or neonatal development. Sprague Dawley rats were provided control, 0.2% weight/weight (w/w), or 0.5% w/w TCC-supplemented chow through a series of 3 experiments that limited exposure to critical growth periods: gestation, gestation and lactation, or lactation only (cross-fostering) to determine the susceptible windows of exposure for developmental consequences. Reduced offspring survival occurred when offspring were exposed to TCC at concentrations of 0.2% w/w and 0.5% w/w during lactation, in which only 13% of offspring raised by 0.2% w/w TCC dams survived beyond weaning and no offspring raised by 0.5% w/w TCC dams survived to this period. In utero exposure status had no effect on survival, as all pups nursed by control dams survived regardless of their in utero exposure status. Microscopic evaluation of dam mammary tissue revealed involution to be a secondary outcome of TCC exposure rather than a primary effect of compound administration. The average concentration of TCC in the milk was almost 4 times that of the corresponding maternal serum levels. The results demonstrate that gestational TCC exposure does not affect the ability of dams to carry offspring to term but TCC exposure during lactation has adverse consequences on the survival of offspring although the mechanism of reduced survival is currently unknown. This information highlights the importance of evaluating the safety of TCC application in personal care products and the impacts during early life exposure. PMID:24803507

  3. Maternal use of flaxseed oil during pregnancy and lactation prevents morphological alterations in pancreas of female offspring from rat dams with experimental diabetes.

    PubMed

    Correia-Santos, André Manoel; Vicente, Gabriela C; Suzuki, Akemi; Pereira, Aline D; dos Anjos, Juliana S; Lenzi-Almeida, Kátia C; Boaventura, Gilson T

    2015-04-01

    Nutritional recommendations have promoted the increased need to consume n-3 polyunsaturated fatty acids. Flaxseed is the richest dietary source of n-3 fatty acids among plant sources and is widely used for its edible oil. This study aimed to investigate whether maternal use of flaxseed oil has effects on pancreas morphology in the female offspring of diabetic mothers. Female Wistar rats (n = 12) were induced into diabetes by a high-fat diet and low dose of streptozotocin. After confirmation of the diabetes, rats were mated, and once pregnancy was confirmed, they were allocated into three groups (n = 6): high-fat group (HG); flaxseed oil group (FOG); and control group (CG) (non-diabetic rats). At weaning, female offspring (n = 6/group) received standard chow diet. The animals were euthanized at 180 days. Pancreas was collected for histomorphometric and immunohistochemistry analysis. HG showed hypertrophy of pancreatic islets (P < 0.0001), whereas FOG offspring had islets with smaller diameters compared to HG (P < 0.0001). HG offspring showed higher percentage of larger (P = 0.0061) and lower percentage of smaller islets (P = 0.0036). HG showed lower islet insulin immunodensity at 180 days (P < 0.0001), whereas FOG was similar to CG (P < 0.0001). Flaxseed oil reduced the damage caused by maternal hyperglycaemia, promoting normal pancreas histomorphometry and β-cell mass in female offspring.

  4. Maternal use of flaxseed oil during pregnancy and lactation prevents morphological alterations in pancreas of female offspring from rat dams with experimental diabetes

    PubMed Central

    Correia-Santos, André Manoel; Vicente, Gabriela C; Suzuki, Akemi; Pereira, Aline D; dos Anjos, Juliana S; Lenzi-Almeida, Kátia C; Boaventura, Gilson T

    2015-01-01

    Nutritional recommendations have promoted the increased need to consume n-3 polyunsaturated fatty acids. Flaxseed is the richest dietary source of n-3 fatty acids among plant sources and is widely used for its edible oil. This study aimed to investigate whether maternal use of flaxseed oil has effects on pancreas morphology in the female offspring of diabetic mothers. Female Wistar rats (n = 12) were induced into diabetes by a high-fat diet and low dose of streptozotocin. After confirmation of the diabetes, rats were mated, and once pregnancy was confirmed, they were allocated into three groups (n = 6): high-fat group (HG); flaxseed oil group (FOG); and control group (CG) (non-diabetic rats). At weaning, female offspring (n = 6/group) received standard chow diet. The animals were euthanized at 180 days. Pancreas was collected for histomorphometric and immunohistochemistry analysis. HG showed hypertrophy of pancreatic islets (P < 0.0001), whereas FOG offspring had islets with smaller diameters compared to HG (P < 0.0001). HG offspring showed higher percentage of larger (P = 0.0061) and lower percentage of smaller islets (P = 0.0036). HG showed lower islet insulin immunodensity at 180 days (P < 0.0001), whereas FOG was similar to CG (P < 0.0001). Flaxseed oil reduced the damage caused by maternal hyperglycaemia, promoting normal pancreas histomorphometry and β-cell mass in female offspring. PMID:25808815

  5. Effects of perinatal undernutrition on the basilar dendritic arbor of the anterior cingulate pyramidal neurons in lactating dams.

    PubMed

    Salas, Manuel; Torrero, Carmen; Regalado, Mirelta; Rubio, Lorena

    2015-01-01

    In altricial species, early pre- and neonatal undernutrition interferes with the neuronal organization of several brain structures that have critical time windows for synaptic organization, including the prefrontal cortex. In Golgi-Cox stained tissue the basilar dendritic arbor of pyramidal neurons in the anterior cingulate cortex of early underfed adult lactating dams was evaluated. The anterior cingulate of the rat plays a major role in the execution of sexual, maternal and visual attentional control and other cognitive responses. The effects of neonatal undernutrition on the basilar dendritic tree and perikaryon measurements in layer II/III pyramidal neurons of the anterior cingulate were examined in lactating dams at postpartum days 8 and 12. In the underfed dams the distal portions of the basilar dendrites had fewer branches and a lower dendritic density of dendrites, and neurons had perikarya with reduced perimeter and cross-sectional area. Thus, the neuronal alterations may interfere the plastic synaptic activity and with maternal cognitive performance of rats subjected to early underfeeding. These anatomical alterations of the anterior cingulate may help to understand the disruption of long-term cognitive processes associated with perinatal food restriction.

  6. Blunted HPA axis response in lactating, vasopressin-deficient Brattleboro rats.

    PubMed

    Fodor, Anna; Pintér, Ottó; Domokos, Agnes; Langnaese, Kristina; Barna, István; Engelmann, Mario; Zelena, Dóra

    2013-11-01

    Adaptation to stress is a basic phenomenon in mammalian life that is mandatorily associated with the activity of the hypothalamic-pituitary-adrenal (HPA) axis. An increased resting activity of the HPA axis can be measured during pregnancy and lactation, suggesting that these reproductive states lead to chronic load in females. In this study, we examined the consequences of the congenital lack of vasopressin on the activity of the HPA axis during lactation using vasopressin-deficient Brattleboro rats. Virgin and lactating, homozygous vasopressin-deficient rats were compared with control, heterozygous rats. In control dams compared with virgins, physiological changes similar to those observed in a chronic stress state (thymus involution, adrenal gland hyperplasia, elevation of proopiomelanocortin mRNA levels in the adenohypophysis, and resting plasma corticosterone levels) were observed. In vasopressin-deficient dams, adrenal gland hyperplasia and resting corticosterone level elevations were not observed. Corticotropin-releasing hormone (Crh) mRNA levels in the hypothalamic paraventricular nucleus were elevated in only the control dams, while oxytocin (OT) mRNA levels were higher in vasopressin-deficient virgins and lactation induced a further increase in both the genotypes. Suckling-induced ACTH and corticosterone level elevations were blunted in vasopressin-deficient dams. Anaphylactoid reaction (i.v. egg white) and insulin-induced hypoglycemia stimulated the HPA axis, which were blunted in lactating rats compared with the virgins and in vasopressin-deficient rats compared with the controls without interaction of the two factors. Vasopressin seems to contribute to the physiological changes observed during lactation mimicking a chronic stress state, but its role in acute HPA axis regulation during lactation seems to be similar to that observed in virgins. If vasopressin is congenitally absent, OT, but not the CRH, compensates for the missing vasopressin; however

  7. Low-Protein Diet during Lactation and Maternal Metabolism in Rats

    PubMed Central

    Moretto, Vera L.; Ballen, Marcia O.; Gonçalves, Talita S. S.; Kawashita, Nair H.; Stoppiglia, Luiz F.; Veloso, Roberto V.; Latorraca, Márcia Q.; Martins, Maria Salete F.; Gomes-da-Silva, Maria Helena G.

    2011-01-01

    Some metabolic alterations were evaluated in Wistar rats which received control or low-protein (17%; 6%) diets, from the pregnancy until the end of lactation: control non-lactating (CNL), lactating (CL), low-protein non-lactating (LPNL) and lactating (LPL) groups. Despite the increased food intake by LPL dams, both LP groups reduced protein intake and final body mass was lower in LPL. Higher serum glucose occurred in both LP groups. Lactation induced lower insulin and glucagon levels, but these were reduced by LP diet. Prolactin levels rose in lactating, but were impaired in LPL, followed by losses of mammary gland (MAG) mass and, a fall in serum leptin in lactating dams. Lipid content also reduced in MAG and gonadal white adipose tissue of lactating and, in LPL, contributed to a decreased daily milk production, and consequent impairment of body mass gain by LPL pups. Liver mass, lipid content and ATP-citrate enzyme activity were increased by lactation, but malic enzyme and lipid: glycogen ratio elevated only in LPL. Conclusion. LP diet reduced the development of MAG and prolactin secretion which compromised milk production and pups growth. Moreover, this diet enhanced the store of lipid to glycogen ratio and suggests a higher risk of fatty liver development. PMID:21637364

  8. Nicotine exposure affects mother's and pup's nutritional, biochemical, and hormonal profiles during lactation in rats.

    PubMed

    Oliveira, E; Pinheiro, C R; Santos-Silva, A P; Trevenzoli, I H; Abreu-Villaça, Y; Nogueira Neto, J F; Reis, A M; Passos, M C F; Moura, E G; Lisboa, P C

    2010-05-01

    We have shown that maternal nicotine exposure during lactation has long-lasting effects on body adiposity and hormonal status of rat offspring. Here, we studied the nutritional and hormonal profiles in this experimental model. Two days after birth, osmotic minipumps were implanted in lactating rats divided into two groups: NIC - continuous s.c. infusions of nicotine (6 mg/kg per day) for 14 days and C - saline. Dams and pups were killed at 15 and 21 days of lactation. Body weight and food intake were evaluated. Milk, blood, visceral fat, carcass, and adrenal gland were collected. All the significant data were P<0.05. At the end of nicotine exposure (15 days), dams presented higher milk production, hyperprolactinemia, and higher serum high-density lipoprotein cholesterol (HDL-C). Milk from NIC dams had higher lactose concentration and energy content. After nicotine withdrawal (21 days), dams showed lower food intake and hyperleptinemia. The 15-day-old NIC pups presented higher total body fat, higher HDL-C, serum leptin, serum corticosterone, and adrenal catecholamine content, but lower tyrosine hydroxylase protein levels. The 21-day-old NIC pups had higher body protein content and serum globulin. Thus, maternal nicotine exposure during lactation results in important changes in nutritional, biochemical, and hormonal parameters in dams and offspring. The pattern of these effects is clearly distinct when comparing the nicotine-exposed group to the withdrawal group, which could be important for the programming effects observed previously.

  9. Comparison of the "nursing" and other parental behaviors of nulliparous and lactating female rats.

    PubMed

    Lonstein, J S; Wagner, C K; De Vries, G J

    1999-12-01

    Virgin female rats display maternal behaviors after continuous exposure to pups (sensitization) that are in some respects similar to those of postpartum females. We herein provide a detailed comparison of the "nursing" and other parental behaviors of maternally sensitized virgin females and postpartum lactating dams. Ovariectomized and intact virgin females were exposed to pups until displaying maternal behavior. On the females' fourth day of maternal responsiveness, the pups were removed for 3 h and then returned, and subject-litter interactions were observed for 45 min. Behavior of maternal virgins was compared with that of lactating dams observed on day 4 postpartum interacting with either suckling pups or pups unable to suckle due to perioral anesthesia. Ovariectomy had no effect on behavior of virgins. Retrieval and licking of pups were deficient in virgins compared with lactating dams. Suckled dams showed prolonged kyphosis (upright crouched nursing), whereas nonsuckled dams displayed little kyphosis but rather were often in a hunched position over pups. Some aspects of quiescent "nursing" behaviors of virgins were surprisingly similar to those of suckled dams, including the latency to and duration of quiescence. Nonsuckling pup stimulation elicited more kyphosis in virgins than in lactating dams, which was still much less than in suckled dams. Virgins also "nursed" pups in hunched and prone postures. Differences between sensitized and postpartum females in their maternal behaviors likely reflect differences in motivation as well as sensory inputs they receive from pups. In particular, sensory regulation of "nursing" behaviors is influenced by reproductive state because nonsuckling pups elicit different postural responses in sensitized and lactating mothers. Copyright 1999 Academic Press.

  10. Maternal cinnamon extract intake during lactation leads to sex-specific endocrine modifications in rat offspring.

    PubMed

    Bento-Bernardes, Thais; Toste, Fernanda P; Pazos-Moura, Carmen C; Oliveira, Karen J

    2017-08-01

    Cinnamon supplementation has been associated with an improvement in glucose disposal and a reduction in fat mass in type 2 diabetes. Maternal nutrition during lactation impacts the health of the offspring throughout life. We hypothesize that cinnamon intake by lactating rats affects maternal physiology, leading to hormonal and metabolic changes in their offspring. To investigate this hypothesis, dams received aqueous cinnamon extract (400 mg cinnamon kg(-1)  body mass day(-1) ) or water orally, during lactation. Maternal cinnamon intake did not affect the body mass gain or food intake of dams or their offspring, although it decreased visceral white adipose tissue mass in dams and in their adult offspring of both sexes. Cinnamon-treated dams exhibited no differences in serum insulin, adiponectin, leptin or estradiol levels, although they presented higher serum progesterone. At weaning, cinnamon male pups exhibited lower insulinemia, whereas cinnamon female pups exhibited lower glycemia. Interestingly, in adulthood, only the female offspring exhibited an altered hormonal profile, with reduced serum leptin, adiponectin and insulin levels accompanied by lower glycemia. The present study demonstrates that maternal cinnamon intake during lactation promotes mild changes in dams and can trigger sex-specific metabolic programming in pups that lasts into adulthood. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  11. Positive long-term outcomes from presuckling calcium supplementation in lactating rats and the offspring.

    PubMed

    Suntornsaratoon, Panan; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2015-06-01

    Adequate dietary calcium intake and the enhanced intestinal calcium absorption in lactating mothers have long been postulated to prevent maternal bone loss and benefit neonatal bone growth. We recently showed that calcium supplementation just before breastfeeding efficiently alleviated lactation-induced bone loss in dams as well as increased milk calcium concentration, which led to higher bone mineral density (BMD) in the newborns. Herein, we further elaborated in detail how presuckling calcium supplements worked in lactating rats and how they benefited bone growth in the offspring. As revealed by bone histomorphometry, presuckling supplement with calcium alone reduced the osteoclast surface and active erosion surface, leading to an increase in trabecular thickness without changes in trabecular separation or number in dams. The beneficial effects of presuckling calcium supplements, particularly the regimen containing glucose and galactose that enhanced intestinal calcium absorption, were found to last for 3 mo postweaning, although it could not restore estrogen-deficient osteopenia induced by ovariectomy. Regarding the neonatal benefits, pups nursed by calcium-supplemented dams exhibited increases in trabecular BMD, which could be observed even at the age of 27 wk. Bone elongation was also greater in pups of calcium-supplemented dams, which was due possibly to accelerated growth plate chondrocyte turnover. It could be concluded that calcium supplements markedly diminished the lactation-induced osteopenia in dams and positively affected BMD and bone elongation in growing rats. Therefore, presuckling calcium supplementation in lactating mothers is an effective strategy for promoting a long-lasting high bone density for both mother and the offspring.

  12. A nest box to facilitate excreta collection from mouse dams through pregnancy, parturition, and lactation.

    SciTech Connect

    Blum, C. A.; Wilson, A. K.; Bhattacharyya, M. H.; Center for Mechanistic Biology and Biotechnology; Oregon State Univ.; Benedictine Univ.

    1999-05-01

    Standard metabolism cages are inadequate for collecting excreta from dams during parturition because newborn pups can fall through the grating into the excreta collection area and out of reach of the dam. A nest box was designed that facilitates excreta collection from mouse dams continuously housed in metabolism cages from conception, through parturition, and into lactation and provides a safe, warm environment for pups during their first week of life. The nest box was tested by using pregnant and lactating mice of two varieties of strain 129/SvJ, metallothionein-normal and metallothionein-knockout; non-pregnant mice were used as controls. Pregnant mice (with nest box) and non-pregnant mice (without nest box) each twice received a solution of 109CdCl2 by gavage. Dams with nest boxes fastidiously urinated and defecated outside the nest box. The percentage of gavage 109Cd dose recovered in dam feces was the same after the first gavage (mean6SE, with nest box through parturition, 95%66%; n=5) as after the second gavage (mean6SE, without nest box, 95%66%; n=5). Weights and percentage weight gain of mouse dams were independent of housing conditions (metabolic cage with next box vs. conventional polycarbonate caging). Furthermore, pup growth and survival were unaffected by the inclusion of the nest box or by its removal at 1 week after birth. Therefore, the described nest box provides for the first time a way to quantitatively collect excreta from mouse dams through pregnancy, parturition, and the early postnatal period. Additional experiments are needed to test its application to other animal species and strains of mice, including those with poor mothering behavior.

  13. Perinatal thiamine deficiency-induced spontaneous abortion and pup-killing responses in rat dams.

    PubMed

    Bâ, Abdoulaye

    2013-03-01

    The current study attempts to determine whether thiamine (B1 vitamin) deficiency and chronic alcohol-related thiamine-deficient (TD) status, disturb maternal behavior towards pups. During gestation and lactation, Wistar rat dams were exposed to the following treatments: (i) prenatal TD dams; (ii) perinatal TD dams; (iii) postnatal TD dams; (iv) 12% alcohol/water drinking mothers; (v) ad libitum control dams. Pair-feeding treatments controlled malnutrition related to thiamine deficiency; (vi) prenatal pair-fed (PF) dams; (vii) perinatal PF dams; (viii) postnatal PF dams and included also the control of alcohol consummation: (ix) PF saccharose dams. Dams were observed for gestation outcome and for apparent disorders of the maternal behavior related to the pups at parturition. From the nine experimental groups studied, only pre- and perinatal TD dams exhibited spontaneous abortion (33.36 and 41.66%, respectively) followed by pups-killing responses where, respectively, 4 dams/7 (57.14%) and 5 dams/7 (71.43%) showed disruption of maternal behavior and appearance of cannibalism towards pups which all were killed within 48 hours after parturition. Spontaneous abortion and pup-killing responses were not observed in the dams of any other experimental group, suggesting that perinatal disturbances of hormonal factors underlay these maternal disorders. Previous studies reported that thiamine deficiency-induced degeneration of dopamine neurons may be related to mouse-killing aggression in rats. The present study suggests that perinatal thiamine deficiency-induced alteration of dopaminergic neurons in maternal brain could be a trigger factor of pup-killing responses. Central dopamine and oxytocin have been strongly associated with both the onset and maintenance of maternal behavior and the regulation of maternal aggressiveness as well. Our studies suggest that estrogen control oxytocin levels in brain structures of pregnancy-terminated rats via dopamine transmission. Thiamine

  14. Fructose consumption during pregnancy and lactation induces fatty liver and glucose intolerance in rats.

    PubMed

    Zou, Mi; Arentson, Emily J; Teegarden, Dorothy; Koser, Stephanie L; Onyskow, Laurie; Donkin, Shawn S

    2012-08-01

    Nutritional insults during pregnancy and lactation are health risks for mother and offspring. Both fructose (FR) and low-protein (LP) diets are linked to hepatic steatosis and insulin resistance in nonpregnant animals. We hypothesized that dietary FR or LP intake during pregnancy may exacerbate the already compromised glucose homeostasis to induce gestational diabetes and fatty liver. Therefore, we investigated and compared the effects of LP or FR intake on hepatic steatosis and insulin resistance in unmated controls (CTs) and pregnant and lactating rats. Sprague-Dawley rats were fed a CT, or a 63% FR, or an 8% LP diet. Glucose tolerance test at day 17 of the study revealed greater (P < .05) blood glucose at 10 (75.6 mg/dL vs 64.0 ± 4.8 mg/dL) minutes and 20 (72.4 mg/dL vs 58.6 ± 4.0 mg/dL) minutes after glucose dose and greater area under the curve (4302.3 mg∙dL(-1)∙min(-1) vs 3763.4 ± 263.6 mg∙dL(-1)∙min(-1)) for FR-fed dams compared with CT-fed dams. The rats were euthanized at 21 days postpartum. Both the FR- and LP-fed dams had enlarged (P < .05) livers (9.3%, 7.1% body weight vs 4.8% ± 0.2% body weight) and elevated (P < .05) liver triacylglycerol (216.0, 130.0 mg/g vs 19.9 ± 12.6 mg/g liver weight) compared with CT-fed dams. Fructose induced fatty liver and glucose intolerance in pregnant and lactating rats, but not unmated CT rats. The data demonstrate a unique physiological status response to diet resulting in the development of gestational diabetes coupled with hepatic steatosis in FR-fed dams, which is more severe than an LP diet.

  15. Iodine excess exposure during pregnancy and lactation impairs maternal thyroid function in rats.

    PubMed

    Serrano-Nascimento, Caroline; Salgueiro, Rafael Barrera; Vitzel, Kaio Fernando; Pantaleão, Thiago; Corrêa da Costa, Vânia Maria; Nunes, Maria Tereza

    2017-10-01

    Adequate maternal iodine consumption during pregnancy and lactation guarantees normal thyroid hormones (TH) production, which is crucial to the development of the fetus. Indeed, iodine deficiency is clearly related to maternal hypothyroidism and deleterious effects in the fetal development. Conversely, the effects of iodine excess (IE) consumption on maternal thyroid function are still controversial. Therefore, this study aimed to investigate the impact of IE exposure during pregnancy and lactation periods on maternal hypothalamus-pituitary-thyroid axis. IE-exposed dams presented reduced serum TH concentration and increased serum thyrotropin (TSH) levels. Moreover, maternal IE exposure increased the hypothalamic expression of Trh and the pituitary expression of Trhr, Dio2, Tsha and Tshb mRNA, while reduced the Gh mRNA content. Additionally, IE-exposed dams presented thyroid morphological alterations, increased thyroid oxidative stress and decreased expression of thyroid genes/proteins involved in TH synthesis, secretion and metabolism. Furthermore, Dio1 mRNA expression and D1 activity were reduced in the liver and the kidney of IE-treated animals. Finally, the mRNA expression of Slc5a5 and Slc26a4 were reduced in the mammary gland of IE-exposed rats. The latter results are in accordance with the reduction of prolactin expression and serum levels in IE-treated dams. In summary, our study indicates that the exposure to IE during pregnancy and lactation induces primary hypothyroidism in rat dams and impairs iodide transfer to the milk. © 2017 The authors.

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

    PubMed

    Karbaschi, Roxana; Sadeghimahalli, Forouzan; Zardooz, Homeira

    2016-09-01

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

  17. Cross-fostering inhalation toxicity study with HCFC-123 in lactating Sprague-Dawley rats.

    PubMed

    Buschmann, J; Bartsch, W; Dasenbrock, C; Fuhst, R; Pohlmann, G; Preiss, A; Berger-Preiss, E

    2001-08-01

    A study was performed in Sprague-Dawley rats (Crl:CD BR) to differentiate between effects of hydrofluorocarbon 123 (HCFC-123) on the lactating dam or on the fetus using fostering and cross-fostering of the offspring. Pregnant and/or lactating dams without the pups present were exposed to the test substance (1000 ppm) or clean air by whole-body inhalation for 6 h/day from day 6 to 19 post conceptionem (p.c.) and from day 5 to 21 post partum (p.p.). Pups were cross-fostered to new dams within the first 2 days after birth. Treatment of the mothers with HCFC-123 led to decreases in serum glucose, cholesterol, and triglycerides and increases in absolute and relative maternal liver weights. Decreased litter and individual pup weight and decreased serum triglycerides were observed in the pups of treated foster mothers. Treatment of the mothers with HCFC-123 did not influence milk production based on the body weight difference of the dam before suckling and 60 min after beginning of suckling using 12-pup "standard litters" of untreated dams. Total fat, glucose, and protein contents in the milk were also not influenced by the treatment. Trifluoroacetic acid (TFA), a main metabolite of HCFC-123, was observed in urine samples of standard litters that had been nursed by treated dams. In conclusion, the effects on offspring due to HCFC-123 treatment consisted of decreased pup weight and decreased serum triglycerides at weaning. All effects were due to treatment of the lactating dams, as no prenatally induced effects were found. Since milk production and nutritional constituents of the milk were not influenced, but significant amounts of the main metabolite were found in pup urine, an effect of HCFC-123 or its metabolite on the pups via maternal milk is considered to be a possible cause for their decreased weight gain.

  18. Adverse effects of lactational exposure to chlorpyrifos in suckling rats.

    PubMed

    Mansour, S A; Mossa, A H

    2010-02-01

    The present study was undertaken to evaluate the oxidative damage, biochemical and histopathological alterations in sucking rats whose mothers were exposed to the insecticide chlorpyrifos (CPF). Dams were administered CPF, via oral route. Doses equalled 0.01 mg kg(-1) body weight (b.wt.; acceptable daily intake, ADI), 1.00 mg kg(-1) b.wt. (no observed adverse effects level, NOAEL) and 1.35 mg kg(-1) b.wt. (1/100 lethal dose [LD(50)]) from postnatal day 1 until day 20 after delivery. At two high doses of CPF, the body weight gain and relative liver and kidney weight of suckling pups were significantly decreased. Exposure of the mothers to CPF caused increase in lipid peroxidation (LPO) and decrease in superoxide dismutase (SOD) and glutathione-s-transferase (GST) in lactating pups. CPF altered the level of the marker parameters related to the liver and kidneys. Consistent histological changes were found in the liver and kidneys of the subjected pups, especially at the higher doses. The results suggested that the transfer of CPF intoxication through the mother's milk has resulted in oxidative stress and biochemical and histopathological alterations in the suckling pups. The data of this study may be considered as a contribution to the problem of lactational transfer of the relatively less persistent OP pesticides, such as CPF.

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

    PubMed

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

    2015-10-14

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

  20. Flaxseed bioactive compounds change milk, hormonal and biochemical parameters of dams and offspring during lactation.

    PubMed

    Troina, A A; Figueiredo, M S; Passos, M C F; Reis, A M; Oliveira, E; Lisboa, P C; Moura, E G

    2012-07-01

    We evaluated maternal intake of SDG (secoisolariciresinol diglucoside), a compound from flaxseed, and flaxseed oil+SDG on biochemical and hormonal parameters of dams and male and female offspring during lactation. Dams were fed a standard diet (C); diet added 40 mg of SDG/100g diet (SDG) or diet added 40 mg of SDG/100g diet and 7% of flaxseed oil (OLSDG). SDG and OLSDG dams showed hyperprolactinemia. The OLSDG milk had lower lactose and protein, while the SDG milk had lower protein on the 14th day of lactation. At 14 days, OLSDG male and female pups showed lower body mass, SDG and OLSDG male pups had hypoprolactinemia and lower body fat mass, but higher visceral fat mass (VFM) and hypertriglyceridemia. At 21 days, male SDG and OLSDG presented hypotriglyceridemia. At 14 days, SDG and OLSDG female offspring showed higher serum 17-β estradiol (E2); OLSDG presented hypercholesterolemia and SDG presented hypertriglyceridemia. At 21 days, SDG and OLSDG female pups showed hypotriglyceridemia and OLSDG shower lower E2. Both maternal treatments changes maternal metabolism as well as hormonal and biochemical parameters of the offspring, which are gender-dependent. Maternal hyperprolactinemia may act as an imprint factor responsible for the hormonal and metabolic changes observed in the pups.

  1. Cadmium, iron and zinc interaction and hematological parameters in rat dams and their offspring.

    PubMed

    Mikolić, Anja; Schönwald, Neala; Piasek, Martina

    2016-12-01

    The effects of cadmium (Cd) were evaluated in offspring exposed from birth until weaning (neonatal day 0-21) and 4 weeks after exposure cessation focusing on iron (Fe) and zinc (Zn) levels in organs and hematological parameters. Wistar female rats were administered 50mg Cd/L in drinking water (Cd-exposed) for 4 weeks before mating and during 3 weeks of gestation plus 3 weeks of lactation. Controls were supplied drinking water. At birth, part of Cd-exposed dams' litters was cross-fostered to control dams (CCd group) and their control litters were cross-fostered to Cd-exposed dams (CdC group). This procedure enabled to discern the effects of gestational, lactational and gestational plus lactational Cd exposure until weaning in F1 offspring. Elements were analyzed by atomic absorption spectrometry; hematological parameters manually; and histopathological changes by light microscopy. Gestational plus lactational exposure in Cd-exposed dams and their offspring increased Cd and decreased Fe levels, increased Zn in dams and decreased Zn and body weights in 11- and 21-day pups. In 21-day weanling pups, decreased red blood cell (RBC) count, hemoglobin and hematocrit values and increased reticulocytes in peripheral blood were also found with concomitant histopathological finding of extramedullary hematopoiesis in the liver. In cross-fostered pups with gestational exposure (CCd pups), Fe in the liver decreased on day 11 and Zn increased in the kidney on day 21 whereas in pups with lactational exposure (CdC pups) Zn in the brain decreased on day 11 and Fe decreased in the liver and brain on day 21. Regardless of exposure cessation at weaning, in offspring with gestational plus lactational exposure (Cd-exposed) body weights, kidney and brain Fe levels and RBC and hemoglobin remained decreased in blood until puberty. Furthermore Zn levels increased in the liver, kidney and brain. It was concluded that gestational plus lactational Cd exposure caused decreases in Fe and Zn levels

  2. Reproductive experience alters corticosterone and CBG levels in the rat dam.

    PubMed

    Pawluski, Jodi L; Charlier, Thierry D; Lieblich, Stephanie E; Hammond, Geoffrey L; Galea, Liisa A M

    2009-01-08

    Reproductive experience has significant effects on the brain, behavior and hormone profiles of the mother. Recent work has demonstrated that primiparous rats exhibit decreased dendritic arborizations in the hippocampus, and enhanced hippocampus-dependent spatial memory performance at the time of weaning compared to nulliparous and, to a lesser degree, multiparous rats. Interestingly, enhanced spatial learning and reduced dendritic arbors are seen in nulliparous female rats exposed to chronic stress or repeated corticosterone administration. Based on these observations, we hypothesized that corticosterone may be altered in primiparous rats compared to multiparous and nulliparous rats. The present study investigated whether the levels of circulating corticosterone and its binding protein, corticosteroid binding globulin (CBG), are altered with reproductive experience and pup-exposure during late pregnancy and the postpartum. Total serum corticosterone and CBG were assayed from five groups; multiparous, primiparous, nulliparous, primip-no-pups, and sensitized rats during gestation (days 14 and 19) and the postpartum period (days 1, 5, 14, 21, and 35). Results show that primiparous rats had significantly elevated total corticosterone on postpartum day 1. In addition, primiparous and multiparous rats had significantly lower CBG throughout the postpartum period than all other groups, with primiparous rats exhibiting lower levels than multiparous rats during mid-lactation. These data suggest that free corticosterone is elevated in both primiparous and multiparous dams and is elevated to a greater degree in primiparous compared to multiparous dams during lactation. Corticosterone and CBG levels were positively correlated with specific maternal behaviors during the first week postpartum in parturient rats, but not in sensitized rats, suggesting a role for corticosterone in the modulation of maternal behavior in parturient rats alone.

  3. Effect of high-fat diet during gestation, lactation, or postweaning on physiological and behavioral indexes in borderline hypertensive rats

    PubMed Central

    Mitra, Anaya; Alvers, Kristin M.; Crump, Erica M.; Rowland, Neil E.

    2009-01-01

    Maternal obesity is becoming more prevalent. We used borderline hypertensive rats (BHR) to investigate whether a high-fat diet at different stages of development has adverse programming consequences on metabolic parameters and blood pressure. Wistar dams were fed a high- or low-fat diet for 6 wk before mating with spontaneously hypertensive males and during the ensuing pregnancy. At birth, litters were fostered to a dam from the same diet group as during gestation or to the alternate diet condition. Female offspring were weaned on either control or “junk food” diets until about 6 mo of age. Rats fed the high-fat junk food diet were hyperphagic relative to their chow-fed controls. The junk food-fed rats were significantly heavier and had greater fat pad mass than those rats maintained on chow alone. Importantly, those rats suckled by high-fat dams had heavier fat pads than those suckled by control diet dams. Fasting serum leptin and insulin levels differed as a function of the gestational, lactational, and postweaning diet histories. Rats gestated in, or suckled by high-fat dams, or maintained on the junk food diet were hyperleptinemic compared with their respective controls. Indirect blood pressure did not differ as a function of postweaning diet, but rats gestated in the high-fat dams had lower mean arterial blood pressures than those gestated in the control diet dams. The postweaning dietary history affected food-motivated behavior; junk food-fed rats earned less food pellets on fixed (FR) and progressive (PR) ratio cost schedules than chow-fed controls. In conclusion, the effects of maternal high-fat diet during gestation or lactation were mostly small and transient. The postweaning effects of junk food diet were evident on the majority of the parameters measured, including body weight, fat pad mass, serum leptin and insulin levels, and operant performance. PMID:18971351

  4. Effect of high-fat diet during gestation, lactation, or postweaning on physiological and behavioral indexes in borderline hypertensive rats.

    PubMed

    Mitra, Anaya; Alvers, Kristin M; Crump, Erica M; Rowland, Neil E

    2009-01-01

    Maternal obesity is becoming more prevalent. We used borderline hypertensive rats (BHR) to investigate whether a high-fat diet at different stages of development has adverse programming consequences on metabolic parameters and blood pressure. Wistar dams were fed a high- or low-fat diet for 6 wk before mating with spontaneously hypertensive males and during the ensuing pregnancy. At birth, litters were fostered to a dam from the same diet group as during gestation or to the alternate diet condition. Female offspring were weaned on either control or "junk food" diets until about 6 mo of age. Rats fed the high-fat junk food diet were hyperphagic relative to their chow-fed controls. The junk food-fed rats were significantly heavier and had greater fat pad mass than those rats maintained on chow alone. Importantly, those rats suckled by high-fat dams had heavier fat pads than those suckled by control diet dams. Fasting serum leptin and insulin levels differed as a function of the gestational, lactational, and postweaning diet histories. Rats gestated in, or suckled by high-fat dams, or maintained on the junk food diet were hyperleptinemic compared with their respective controls. Indirect blood pressure did not differ as a function of postweaning diet, but rats gestated in the high-fat dams had lower mean arterial blood pressures than those gestated in the control diet dams. The postweaning dietary history affected food-motivated behavior; junk food-fed rats earned less food pellets on fixed (FR) and progressive (PR) ratio cost schedules than chow-fed controls. In conclusion, the effects of maternal high-fat diet during gestation or lactation were mostly small and transient. The postweaning effects of junk food diet were evident on the majority of the parameters measured, including body weight, fat pad mass, serum leptin and insulin levels, and operant performance.

  5. Leptin and prolactin, but not corticosterone, modulate body weight and thyroid function in protein-malnourished lactating rats.

    PubMed

    Lisboa, P C; Passos, M C; Dutra, S C; Bonomo, I T; Denolato, A T; Reis, A M; Moura, E G

    2006-05-01

    To understand the role of hormonal changes in the lower food ingestion and body weight in protein-restricted lactating rats as well as the higher serum T (3), higher deiodination, iodide and T (3) milk transfer, we measured maternal serum prolactin, leptin, TSH and corticosterone, which are hormones that could influence those parameters. After birth, dams were separated into: control-fed with a 23 % protein diet (n = 12) and PR (protein-restricted)-fed with an 8 % protein diet (n = 12). At the 4 (th) and 21 (st) day of lactation, half of the animals in each group were sacrificed. PR dams presented hyperleptinemia (day 4: + 20 %; day 21: + 19 %; p < 0.05) and hypoprolactinemia (day 4: - 85 %; day 21: - 92 %; p < 0.05), which could help explain the lower food consumption and body weight in lactating PR rats since leptin is anorexigenic and prolactin is orexigenic. Also, this hyperleptinemia could contribute for the increase in serum T (3) of PR dams, since leptin stimulates T (3) production, especially acting on deiodinases. Serum corticosterone was not different between PR and C groups, and TSH was lower only at the end of lactation. Thus, we suggest that both leptin and prolactin could play an important role in the body weight and thyroid hormone changes observed in protein-malnourished lactating rats.

  6. Effects of oral exposure to arsenobetaine during pregnancy and lactation in Sprague-Dawley rats.

    PubMed

    Taylor, Marnie; Lau, Ben P; Feng, Sherry Y; Bourque, Christine; Buick, Julie K; Bondy, Genevieve S; Cooke, Gerard M

    2013-01-01

    Arsenobetaine (ASB) is the major form of arsenic (As) in seafood sources such as molluscs and fish. Limited data demonstrated that ASB toxicity in mammals is minimal; however, data on possible reproductive effects are lacking. This study investigated the tissue distribution and developmental effects of ASB during pregnancy, early postnatal life, and development to adulthood. Pregnant rats were randomly assigned to 3 cohorts and gavaged daily from gestational day 8 (GD8) with ASB in deionized water at 0, 0.1, 1, or 10 mg/kg body weight (bw)/d. Cohort 1 dams were sacrificed on GD20 (n = 6 per dose group), cohort 2 dams and pups were sacrificed on postnatal day 13 (PND13; n = 4 dams per dose group), and cohort 3 pups (n = 2 dams per dose group) were sacrificed on PND90. Residue analysis detected significant levels of ASB in livers of cohort 1 dams and lower levels in cohort 1 GD20 fetuses, as well as in cohort 2 male and female offspring, indicating placental transfer from the maternal circulation in utero. Trace amounts of ASB in dams' milk were found only in the 10-mg/kg bw/d dose cohort 2 (PND13), demonstrating that lactational transfer was limited. ASB levels in liver varied during pregnancy, lactation, and postweaning, with levels falling rapidly as these physiological states progress. Although transfer of ASB through the placenta to the fetuses and to a limited extent through milk was confirmed, ASB exposure during pregnancy and lactation appeared to produce no teratogenic or deleterious effects on reproductive development.

  7. In utero and lactation exposure of mice to pan masala: effect on dams and pregnancy outcome.

    PubMed

    Archana, K; Gautam, A K; Lakkad, B C; Kumar, Sunil

    2011-01-01

    Pan masala, a chewing mixture, is a popular alternate of areca nut/tobacco/betal quid in various parts of the world. In view of embryotoxic effects of areca nut and tobacco, it is hypothesized that in utero and lactational exposure to pan masala plain (PMP, containing areca nut as major ingredient), and pan masala with tobacco (PMT) can also have similar effects. To investigate this, pregnant female Swiss albino mice were treated with 3 and 6% of PMP and PMT from gestation day (GD) 0, 6, and 14 until lactation. They were weighed during pregnancy and lactation. At parturition, pups were counted, weighed, and measured. At weaning, dams were sacrificed for implantation count. Three percent and 6% PMT considerably reduced female fertility. Gestation length was lower in all the pan masala–treated mice, which was significant at 3 and 6% PMT treatment from GD 0. Pups born to pan masala–treated dams had significantly low birth weight at 3 and 6% PMT in GD 0 and GD 6, and 6% PMT in the GD 14 group. Sex ratio declined in the GD 0 pan masala–treated group. Neonatal death was observed in all the pan masala–treated groups from GD 0 and 6% of both PMP- and PMT-treated groups from GD 14 with respect to control. Weaning index was considerably altered in GD 0 and 14 pan masala–treated groups. Postimplantation loss was considerably high in all the pan masala–treated groups. The data points toward the in utero and lactational fetotoxic effects of pan masala treatment, mainly PMT.

  8. Effect of vitamin B6 status of the lactating rat on taurine biosynthesis and availability to the pup

    SciTech Connect

    Trumbo, P. )

    1990-02-26

    Cysteinesulfinate decarboxylase (CD), a pyridoxal 5{prime}-phosphate-dependent enzyme, is believed to be rate-limiting for taurine biosynthesis in the rat. Although taurine is synthesized by the pup, it is abundant in milk of the lactating rat. CD activity has been shown to be reduced in vitamin B6-deficient, lactating rats and their pups, without much change in taurine concentration of certain tissues. To further understand the effect of B6 status of lactating rats on taurine biosynthesis and availability to their pups, pregnant dams were fed either a B6-deficient or B6-adequate (20 mg/kg) diet during gestation and 10 days postpartum. After this time period, all dams were gavaged {sup 35}S cysteine and {sup 3}H taurine, milk and tissues of the dams and pups collected, and taurine isolated by ion-exchange chromatography. There was no difference in the {sup 35}S/{sup 3}H ratio in the heart or liver for the adequate and deficient dams. The {sup 35}S/{sup 3}H ratio was slightly but significantly greater in the liver of the B6-adequate pups compared to the B6-deficient pups without a difference in the level of {sup 3}H taurine (pmol/gram protein) in the milk or pup's liver. Results indicate that a B6 deficiency can influence taurine biosynthesis in the pup without impairing secretion of taurine in milk.

  9. Female offspring of rat dams fed low boron diets during pregnancy and lactation exhibit signs of the metabolic syndrome during early adulthood: increased body weight, & serum triglycerides and total cholesterol concentrations

    USDA-ARS?s Scientific Manuscript database

    To expand on reports from this laboratory that low dietary boron may affect energy substrate utilization, we determined whether low dietary boron during early development promotes manifestation of the metabolic syndrome in adult offspring. Sprague-Dawley dams were fed either a boron-low (BL; ~0.1 mg...

  10. Methylprednisolone improves lactate metabolism through reduction of elevated serum lactate in rat model of multiple sclerosis.

    PubMed

    Ghareghani, Majid; Ghanbari, Amir; Dokoohaki, Shima; Farhadi, Naser; Hosseini, Seyed Mojtaba; Mohammadi, Reza; Sadeghi, Heibatollah

    2016-12-01

    Some studies have demonstrated elevated concentrations of lactate both in the cerebrospinal fluid (CSF) and blood samples of multiple sclerosis (MS) patients as a pathological condition. We designed an experimental study first to investigate the serum level of lactate as a biomarker of MS progression and also to investigate the effect of methylprednisolone on serum lactate. Experimental autoimmune encephalomyelitis (EAE) was inducted in Lewis rats, and then rats were treated intraperitoneally with methylprednisolone (30mg/kg/d), at the disease onset, and the clinical scores were recorded. After seven days of treatment, the serum levels of lactate were determined using high performance liquid chromatography (HPLC). Moreover, lymphocyte infiltration and the demyelinated area was analysed in spinal cord. Compared to the untreated-EAE rats, methylprednisolone remarkably improved the clinical score of EAE and ameliorated the spinal cord inflammation and demyelination. In addition, the marked decline in IFN-γ and the increase in IL-4 confirmed improvement in the rats treated with methylprednisolone. Measurement of lactate using HPLC indicated enhancement in the serum level of lactate in the untreated-EAE rats; the lactate level significantly decreased after methylprednisolone therapy. Moreover, serum lactates and disease severity were correlated positively and significantly. These data confirmed for the first time, that methylprednisolone can decreases the enhanced level of serum lactate in EAE model. In addition, it was shown that measurement of serum lactate could be an inexpensive and accurate laboratory test to determine the response to treatment and to assess disease severity in MS patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. Effect of dam weight and pregnancy nutrition on average lactation performance of ewe offspring over 5 years.

    PubMed

    Paten, A M; Pain, S J; Peterson, S W; Lopez-Villalobos, N; Kenyon, P R; Blair, H T

    2016-11-21

    The foetal mammary gland is sensitive to maternal weight and nutrition during gestation, which could affect offspring milk production. It has previously been shown that ewes born to dams offered maintenance nutrition during pregnancy (day 21 to 140 of gestation) produced greater milk, lactose and CP yields in their first lactation when compared with ewes born to dams offered ad libitum nutrition. In addition, ewes born to heavier dams produced greater milk and lactose yields when compared with ewes born to lighter dams. The objective of this study was to analyse and compare the 5-year lactation performance of the previously mentioned ewes, born to heavy or light dams that were offered maintenance or ad libitum pregnancy nutrition. Ewes were milked once per week, for the first 6 weeks of their lactation, for 5 years. Using milk yield and composition data, accumulated yields were calculated over a 42-day period for each year for milk, milk fat, CP, true protein, casein and lactose using a Legendre orthogonal polynomial model. Over the 5-year period, ewes born to heavy dams produced greater average milk (P=0.04), lactose (P=0.01) and CP (P=0.04) yields than offspring born to light dams. In contrast, over the 5-year period dam nutrition during pregnancy did not affect average (P>0.05) offspring milk yields or composition, but did increase milk and lactose accumulated yield (P=0.03 and 0.01, respectively) in the first lactation. These results indicate that maternal gestational nutrition appears to only affect the first lactational performance of ewe offspring. Neither dam nutrition nor size affected grand-offspring live weight gain to, or live weight at weaning (P>0.05). Combined these data indicate that under the conditions of the present study, manipulating dam weight or nutrition in pregnancy can have some effects of offspring lactational performance, however, these effects are not large enough to alter grand-offspring growth to weaning. Therefore, such manipulations

  12. Estimation of placental and lactational transfer and tissue distribution of atrazine and its main metabolites in rodent dams, fetuses, and neonates with physiologically based pharmacokinetic modeling

    SciTech Connect

    Lin, Zhoumeng; Fisher, Jeffrey W.; Wang, Ran; Ross, Matthew K.; Filipov, Nikolay M.

    2013-11-15

    Atrazine (ATR) is a widely used chlorotriazine herbicide, a ubiquitous environmental contaminant, and a potential developmental toxicant. To quantitatively evaluate placental/lactational transfer and fetal/neonatal tissue dosimetry of ATR and its major metabolites, physiologically based pharmacokinetic models were developed for rat dams, fetuses and neonates. These models were calibrated using pharmacokinetic data from rat dams repeatedly exposed (oral gavage; 5 mg/kg) to ATR followed by model evaluation against other available rat data. Model simulations corresponded well to the majority of available experimental data and suggest that: (1) the fetus is exposed to both ATR and its major metabolite didealkylatrazine (DACT) at levels similar to maternal plasma levels, (2) the neonate is exposed mostly to DACT at levels two-thirds lower than maternal plasma or fetal levels, while lactational exposure to ATR is minimal, and (3) gestational carryover of DACT greatly affects its neonatal dosimetry up until mid-lactation. To test the model's cross-species extrapolation capability, a pharmacokinetic study was conducted with pregnant C57BL/6 mice exposed (oral gavage; 5 mg/kg) to ATR from gestational day 12 to 18. By using mouse-specific parameters, the model predictions fitted well with the measured data, including placental ATR/DACT levels. However, fetal concentrations of DACT were overestimated by the model (10-fold). This overestimation suggests that only around 10% of the DACT that reaches the fetus is tissue-bound. These rodent models could be used in fetal/neonatal tissue dosimetry predictions to help design/interpret early life toxicity/pharmacokinetic studies with ATR and as a foundation for scaling to humans. - Highlights: • We developed PBPK models for atrazine in rat dams, fetuses, and neonates. • We conducted pharmacokinetic (PK) study with atrazine in pregnant mice. • Model predictions were in good agreement with experimental rat and mouse PK data.

  13. Late reproductive analysis in rat male offspring exposed to nicotine during pregnancy and lactation.

    PubMed

    Miranda-Spooner, M; Paccola, C C; Neves, F M O; de Oliva, S U; Miraglia, S M

    2016-03-01

    We previously observed that nicotine, administered to rats (Wistar) during pregnancy and lactation periods, provokes, in the progeny, late morphofunctional alterations in Leydig cell, body weight increase in adulthood (90 days post partum, dpp) as well as seminiferous epithelium injury. Aiming to investigate whether the spermatogenic damage previously observed in adult progenies from pregnant and lactating nicotine-exposed rat dams are maintained or whether it is worsened in older rats, we analyzed the morphological testicular alterations after up to two complete periods of spermatogenesis (53 days each), spermatic parameters, and sperm DNA fragmentation. Pregnant and lactating rats were nicotine-exposed (2 mg/kg/day) through an osmotic minipump implanted on the first day of pregnancy and replaced after birth. Absolute Control (no minipump) and Sham Control (minipump without nicotine) groups were established. The offspring were killed at 90, 143, and 196 dpp. Significant alterations in morphometric and stereological testicular parameters, such as concentration of sperm number, daily sperm production, and plasma and intratesticular levels of cholesterol and testosterone were not observed in nicotine-exposed rats. Testicular histopathological analysis showed small intraepithelial vacuolization and an accentuated germ cell desquamation in exposed rats. However, the offspring from nicotine-exposed dams exhibited higher frequency of morphologically abnormal spermatozoa and lower sperm motility in comparison with control groups. In addition, nicotine-exposed groups showed a significant reduction in sperm mitochondrial activity and an increased sperm DNA fragmentation (Comet assay). These results indicate a late reproductive damage in the male progeny caused by maternal nicotine exposure, related to the decrease in sperm quality.

  14. Influence of maternal ethanol ingestion on copper utilization during gestation and lactation in the rat

    SciTech Connect

    Baek, J.H.; Cerklewski, F.L.

    1986-03-05

    A factorial experiment was conducted to determine the influence of ethanol intake (30% of Kcal) on the utilization of copper (Cu) at two dietary levels of Cu during gestation and lactation in the rat. Cu levels in the liquid diet were adjusted to provide either 60% of the minimum requirement or a more than adequate intake. Both ethanol and low Cu depressed dam liver Cu, but the lowest concentration was produced when ethanol and low Cu were combined. Although only ethanol depressed pup liver Cu concentration, the effects observed in dams were reflected in pup Cu content of the metallothionein fraction eluted from a Sephadex G-75 column. Otherwise, neither the metallothionein content of maternal intestinal cells nor that of pup liver affected the outcome of ethanol-antagonized Cu utilization. Effects of ethanol on Cu status of dams and pups cannot be defined as a simple C deficiency even though liver iron was elevated because the ferroxidase activity of dam ceruloplasmin was enhanced rather than inhibited by ethanol which is in agreement with observations made in alcoholics. The authors results are more consistent with a possible enhancing effect of ethanol on biliary excretion of Cu. Exactly why ethanol would have this effect in dams is not defined by available data. In pups, however, maternal ethanol ingestion caused a 30% increase in pup plasma corticosterone, a steroid known to enhance loss of neonatal liver Cu by way of biliary excretion.

  15. Suppressed hepcidin expression correlates with hypotransferrinemia in copper-deficient rat pups but not dams.

    PubMed

    Broderius, Margaret; Mostad, Elise; Prohaska, Joseph R

    2012-07-01

    Copper deficiency leads to anemia but the mechanism is unknown. Copper deficiency also leads to hypoferremia, which may limit erythropoiesis. The hypoferremia may be due to limited function of multicopper oxidases (MCO) hephaestin in enterocytes or GPI-ceruloplasmin in macrophages of liver and spleen whose function as a ferroxidase is thought essential for iron transfer out of cells. Iron release may also be limited by ferroportin (Fpn), the iron efflux transporter. Fpn may be lower following copper deficiency because of impaired ferroxidase activity of MCO. Fpn is also dependent on the liver hormone hepcidin as Fpn is degraded when hepcidin binds to Fpn. Anemia and hypoferremia both down regulate hepcidin by separate mechanisms. Current studies confirmed and extended earlier studies with copper-deficient (CuD) rats that suggested low hepicidin resulted in augmented Fpn. However, current studies in CuD dams failed to confirm a correlation that hepcidin expression was associated with low transferrin receptor 2 (TfR2) levels and also challenged the dogma that holotransferrin can explain the correlation with hepcidin. CuD dams exhibited hypoferremia, low liver TfR2, anemia in some rats, yet no depression in Hamp expression, the hepcidin gene. Normal levels of GDF-15, the putative erythroid cytokine that suppresses hepcidin, were detected in plasma of CuD and iron-deficient (FeD) dams. Importantly, FeD dams did display greatly lower Hamp expression. Normal hepcidin in these CuD dams is puzzling since these rats may need extra iron to meet needs of lactation and the impaired iron transfer noted previously.

  16. Exposure to toluene and stress during pregnancy impairs pups' growth and dams' lactation.

    PubMed

    Soberanes-Chávez, Paulina; López-Rubalcava, Carolina; de Gortari, Patricia; Cruz, Silvia L

    2013-01-01

    Inhalant misuse starts at an early age, and a large number of users are women in reproductive age. This study investigates whether exposure to toluene, a commonly misused solvent, alone or combined with restraint stress during pregnancy, produces adverse effects in pregnant mice and their offspring during lactation and adulthood. Pregnant animals were exposed to either 8000ppm toluene (30min/twice daily from gestational days 7-19), restraint stress (three times/day during the same gestation period) or both; control mice were only exposed to air. Our results show that toluene, stress and their combination reduced body weight gain in pregnant females without changing food consumption. In the offspring, all treatments resulted in low body weight at weaning, but with the toluene and stress combination this effect was seen from birth. Weight deficiency could not be attributed to poor maternal behavior during the first 3weeks of age, but to a reduction in pro-TRH mRNA expression in the hypothalamic paraventricular nucleus and serum prolactin levels in dams. After weaning, pups that were subjected to toluene and stress during gestation had lower body weight and ate less than control animals. In conclusion, the combined exposure to toluene and stress during pregnancy lead to more pronounced effects in dams and longer-lasting actions in pups than exposure to either toluene or stress. © 2013 Elsevier Inc. All rights reserved.

  17. Chemically Contaminated Eel Fed to Pregnant and Lactating Mouse Dams Causes Hyperactivity in Their Offspring.

    PubMed

    Dridi, Imen; Soualeh, Nidhal; Bohn, Torsten; Soulimani, Rachid; Bouyaed, Jaouad

    2017-08-15

    This study examined whether perinatal exposure to polluted eels (Anguilla anguilla L.) induces changes in the locomotor activity of offspring mice across lifespan (post-natal days (PNDs) 47 - 329), using the open field and the home cage activity tests. Dams were exposed during gestation and lactation, through diets enriched in eels naturally contaminated with pollutants including PCBs. Analysis of the eel muscle focused on the six non-dioxin-like (NDL) indicator PCBs (Σ6 NDL-PCBs: 28, 52, 101, 138, 153 and 180). Four groups of dams (n = 10 per group) received either a standard diet without eels or eels (0.8 mg/kg/day) containing 85, 216, or 400 ng/kg/day of ϵ6 NDL-PCBs. The open field test showed that early-life exposure to polluted eels increased locomotion in female offspring of exposed dams but not in males, compared to controls. This hyperlocomotion appeared later in life, at PNDs 195 and 329 (up to 32 % increase, p < 0.05). In addition, overactivity was observed in the home cage test at PND 305: exposed offspring females showed a faster overall locomotion speed (3.6 - 4.2 cm/s) than controls (2.9 cm/s, p <0.05); again, males remained unaffected. Covered distances in the home cage test were only elevated significantly in offspring females exposed to highest PCB concentrations (3411 ± 590 cm vs. 1377 ± 114 cm, p < 0.001). These results suggest that early-life exposure to polluted eels containing dietary contaminants including PCBs caused late, persistent and gender-dependent neurobehavioral hyperactive effects in offspring mice. Furthermore, female hyperactivity was associated with a significant inhibition of acetylcholinesterase activity in the hippocampus and the prefrontal cortex.

  18. Prenatal copper deficiency in rat dams causes persistent reduction in nuclear-encoded cytochrome c oxidase subunits in cardiac mitochrondria of the first generation

    USDA-ARS?s Scientific Manuscript database

    Previous studies have shown that the offspring of rat dams having low copper (Cu) intake during pregnancy and lactation experience a deficiency in cardiac cytochrome c oxidase (CCO) after postnatal day 10. The present study was undertaken to determine the relative influences of pre-and postnatal Cu ...

  19. Cardiac Cytochrome c Oxidase Activity and Contents of Submits 1 and 4 are Altered in Offspring by Low Prenatal Intake by Rat Dams

    USDA-ARS?s Scientific Manuscript database

    It has been reported previously that the offspring of rat dams consuming low dietary copper (Cu) during pregnancy and lactation experience a deficiency in cardiac cytochrome c oxidase (CCO) characterized by reduced catalytic activity and mitochondrial- and nuclear-subunit content after postnatal day...

  20. Placental Transfer of Lactate, Glucose and 2-deoxyglucose in Control and Diabetic Wistar Rats

    PubMed Central

    Oon, Beryl B.; Lowy, Clara

    2001-01-01

    Placental transfer of lactate, glucose and 2-deoxyglucose was examined employing the in situ perfused placenta. Control and streptozotocin induced diabetic Wistar rats were infused with [U14C]-glucose and [3H]-2-deoxyglucose (2DG). The fetal side of the placenta was perfuseci with a cell free medium and glucose uptake was calculated in the adjacent fetuses. Despite the 5-fold higher maternal plasma glucose concentration in the diabetic dams the calculated fetal glucose metabolic index was not significantly different between the 2 groups. Placental blood flow was reduced in the diabetic animals compared with controls but reduction of transfer of [U14C]-glucose and [3H]-2-deoxyglucose and endogenously derived [14C]-Lactate to the fetal compartment, could not be accounted for by reduced placental blood flow alone. There was no significant net production or uptake of lactate into the perfusion medium that had perfused the fetal side of the placenta in either group. The plasma lactate levels in the fetuses adjacent to the perfused placenta were found to be higher than in the maternal plasma and significantly higher in the fetuses of the diabetic group compared with control group. In this model the in situ perfused placenta does not secrete significant quantities of lactate into the fetal compartment in either the control or diabetic group. PMID:12369714

  1. Fructose intake during gestation and lactation differentially affects the expression of hippocampal neurosteroidogenic enzymes in rat offspring.

    PubMed

    Mizuno, Genki; Munetsuna, Eiji; Yamada, Hiroya; Ando, Yoshitaka; Yamazaki, Mirai; Murase, Yuri; Kondo, Kanako; Ishikawa, Hiroaki; Teradaira, Ryoji; Suzuki, Koji; Ohashi, Koji

    2017-02-01

    Neurosteroids, steroidal hormones synthesized de novo from cholesterol within the brain, stimulate hippocampal functions such as neuron protection and synapse formation. Previously, we examined the effect of maternal fructose on the transcriptional regulation of neurosteroidogenic enzymes. We found that the mRNA expression level of the steroidogenic acute regulatory protein (StAR), peripheral benzodiazepine receptor (PBR), cytochrome P450(11β), 11β-hydroxysteroid dehydrogenase (HSD), and 17β-HSD was altered. However, we could not determine whether maternal fructose intake played a role in the gestation or lactation period because the dam rats were fed fructose solution during both periods. Thus, in this study, we analyzed the hippocampi of the offspring of dams fed fructose during the gestation or lactation period. Maternal fructose consumption during either the gestation or lactation period did not affect the mRNA levels of StAR, P450(17α), 11β-HSD-2, and 17β-HSD-1. PBR expression was down-regulated, even when rats consumed fructose during the lactation period only, while fructose consumption during gestation tended to activate the expression of P450(11β)-2. We found that maternal fructose intake during gestation and lactation differentially affected the expression of hippocampal neurosteroidogenic enzymes in the offspring.

  2. Cardiac cytochrome C oxidase activity and contents of subunits 1 and 4 are altered in offspring by low prenatal copper intake by rat dams.

    PubMed

    Johnson, W Thomas; Anderson, Cindy M

    2008-07-01

    It has been reported previously that the offspring of rat dams consuming low dietary copper (Cu) during pregnancy and lactation experience a deficiency in cardiac cytochrome c oxidase (CCO) characterized by reduced catalytic activity and mitochondrial and nuclear subunit content after postnatal d 10. The present study was undertaken to determine whether the cardiac CCO deficiency was caused directly by low postnatal Cu intake or whether it was a prenatal effect of low Cu intake by the dams that became manifest postnatally. Dams were fed either a Cu-adequate diet (6 mg Cu/kg) or Cu-deficient diet (1 mg Cu/kg) beginning 3 wk before conception and throughout gestation and lactation. One day following parturition, several litters from Cu-adequate dams were cross fostered to Cu-deficient dams and several litters from Cu-deficient dams were cross fostered to Cu-adequate dams. Litters that remained with their birth dams served as controls. CCO activity, the content of the mitochondrial-encoded CCO subunit 1 (COX1), and the content of the nuclear-encoded subunit COX4 in cardiac mitochondria were reduced in the 21-d-old offspring of Cu-deficient dams. COX1 content was normal in the 21-d-old cross-fostered offspring of Cu-deficient dams, but CCO activity and COX4 were reduced. Cross fostering the offspring of Cu-adequate dams to Cu-deficient dams did not significantly affect CCO activity, COX1 content, or COX4 content in cardiac mitochondria of 21-d-old offspring. These data indicate that low prenatal Cu intake by dams was the determinant of CCO activity in cardiac mitochondria of the 21-d-old offspring and may have led to the assembly of a less-than-fully active holoenzyme.

  3. Dietary l-leucine supplementation of lactating rats results in a tendency to increase lean/fat ratio associated to lower orexigenic neuropeptide expression in hypothalamus.

    PubMed

    López, N; Sánchez, J; Picó, C; Palou, A; Serra, F

    2010-07-01

    The aim of this study was to assess the effects of dietary leucine supplementation in lactating dams, particularly on energy homeostasis through signaling mechanisms in the central nervous system. Dams were fed ad libitum with standard diet during pregnancy (control dams) or supplemented with 2% leucine (leucine-supplemented dams) from delivery onwards. Food intake, body weight and composition were periodically recorded. Hypothalamus was collected at the end of lactation, and the expression of neuropeptide Y (NPY), agouti-related protein (AgRP) pro-opiomelanocortin (POMC), cocaine and amphetamine regulated transcript (CART), insulin receptor (InsR), ghrelin receptor (GSHR), melanocortin receptor (MCR4), leptin receptor (Ob-Rb) and suppressor of cytokine signaling 3 (SOCS3) were analyzed. Dietary leucine supplementation to lactating rats increased plasma leucine by 56%, modulated body composition and contributed to a tendency of higher ratio of lean/fat mass content of dams during lactation, without affecting food intake, thermogenesis capacity or body or tissue/organs weights. No differences in body weight of offspring from control and leucine-supplemented dams were found. The expression of orexigenic peptides (NPY and AgRP) decreased in leucine-dams, whereas the expression of anorexigenic peptides (POMC and CART), the hypothalamic receptors of insulin, ghrelin, melanocortin and leptin and SOCS3 did not change by leucine supplementation. In conclusion, increased leucine intake during lactation may contribute to a healthier profile of body composition in dams, without compromising the growth and development of the progeny by a mechanism associated with lower expression of orexigenic neuropeptides in hypothalamus.

  4. ATRAZINE DISPOSITION IN PREGNANT AND LACTATING LONG-EVANS RATS

    EPA Science Inventory

    Atrazine (ATR) is a widely used herbicide shown to delay early mammary development in female offspring of gestationally exposed rats. The effects of ATR can be induced by in utero exposure and/or suckling from a dam exposed during late pregnancy, but ATR is reported to have a hal...

  5. Carbon tetrachloride-induced hepatotoxicity in pregnant and lactating rats.

    PubMed

    Mochizuki, Masahiro; Shimizu, Satomi; Urasoko, Yoshinaka; Umeshita, Kazuhiko; Kamata, Takashi; Kitazawa, Takahiro; Nakamura, Daichi; Nishihata, Yoshito; Ohishi, Takumi; Edamoto, Hiroshi

    2009-04-01

    Carbon tetrachloride (CCl4) is well known to induce hepatotoxicity after being metabolized to trichloromethyl free radical ((.)CCl3) by CYP2E1. In the present study, the hepatotoxicity induced by a single oral dose (2,000 mg/kg) of CCl4 was compared between pregnant (gestation days (GD) 13 and 19) or postpartum (postpartum days (PPD) 1, 13 and 27) and non-pregnant rats. Hepatotoxicity in CCl4-treated pregnant rats evaluated by blood chemistry (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities) and histopathological finding (area of damaged hepatocytes) was minimal on GD19, being weaker than that in non-pregnant rats. CYP2E1 expression in non-treated pregnant rats decreased as pregnancy progressed and reached minimum level on GD19. Thus, the degree of CCl4-induced hepatotoxicity roughly corresponded to CYP2E1 levels during pregnancy. After delivery, hepatotoxicity in CCl4-treated lactating rats was maximal on PPD13, being stronger than that in non-pregnant rats, and then it decreased slightly on PPD27. The CYP2E1 level in the non-treated lactating rats tended to increase but remained at lower levels until PPD13 compared with that in non-pregnant rats. Thus, the degree of CCl4-induced hepatotoxicity did not correspond to CYP2E1 levels during lactation. This suggests that during lactation, there may be certain factors other than CYP2E1 expression responsible for the degree of CCl4-induced hepatotoxicity.

  6. Conjugated linoleic acid influences the metabolism of tocopherol in lactating rats but has little effect on tissue tocopherol concentrations in pups.

    PubMed

    Zeitz, Johanna O; Most, Erika; Eder, Klaus

    2016-05-31

    Conjugated linoleic acid (CLA) is known to affect the lipid metabolism in growing and lactating animals. However, potential effects on the metabolism of fat-soluble vitamins in lactating animals and co-occurring effects on their offspring are unknown. We aimed to investigate the effects of dietary CLA on concentrations of tocopherol in various tissues of lactating rats and their offspring and expression of genes involved in tocopherol metabolism. Twenty-eight Wistar Han rats were allocated to 2 groups and fed either a control diet (control group) or a diet containing 0.9 % of cis-9, trans-11 and trans-10, cis-12 (1:1) CLA (CLA group) during pregnancy and lactation. Feed intake of dams and body weight of dams and their pups were recorded weekly. Tocopherol concentrations in various body tissues were determined at day 14 of lactation in dams and 1, 7 and 14 days after birth in pups. Expression of selected genes involved in metabolism of tocopherol was determined in dams and pups. The data were statistically analysed by analysis of variance. Feed intake and body weight development of nursing rats and their pups was similar in both groups. In livers of CLA-fed dams, tocopherol concentrations decreased by 24 % but expression of TTPA and CYP3A1, involved in tocopherol transport and metabolism, were not influenced. In the dams' adipose tissue, gene expression of receptors involved in tissue tocopherol uptake, LDLR and SCARB1, but not of LPL, increased by 30 to 50 % and tocopherol concentrations increased by 47 % in CLA-fed compared to control dams. Expression of LPL, LDLR and SCARB1 in mammary gland was not influenced by CLA-feeding. Tocopherol concentrations in the pup's livers and lungs were similar in both groups, but at 14 days of age, adipose tissue tocopherol concentrations, and LDLR and SCARB1 expression, were higher in the CLA-exposed pups. We show that dietary CLA affects tissue concentrations of tocopherol in lactating rats and tocopherol metabolism in

  7. Catecholamine regulation of lactate dehydrogenase in rat brain cell culture

    SciTech Connect

    Kumar, S.; McGinnis, J.F.; de Vellis, J.

    1980-03-25

    The mechanism of catecholamine induction of the soluble cytoplasmic enzyme lactate dehydrogenase (EC 1.1.1.27) was studied in the rat glial tumor cell line, C6. Lactate dehydrogenase was partially purified from extracts of (/sup 3/H)leucine-labeled cells by affinity gel chromatography and quantitatively immunoprecipitated with anti-lactate dehydrogenase-5 IgG and with antilactate dehydrogenase-1 IgG. The immunoprecipitates were dissociated and electrophoresed on sodium dodecyl sulfate polyacrylamide gels. Using this methodology, the increased enzyme activity of lactate dehydrogenase in norepinephrine-treated C6 cells was observed to be concomitant with the increased synthesis of enzyme molecules. Despite the continued presence of norepinephrine, the specific increase in the rate of synthesis of lactate dehydrogenase was transient. It was first detected at 4 h, was maximum at 9 h, and returned to basal levels by 24 h. The half-life of lactate dehydrogenase enzyme activity was 36 h during the induction and 40 h during deinduction. The half-life for decay of /sup 3/H-labeled lactate dehydrogenase was 41 h. These observations suggest that the increase in lactate dehydrogenase activity in norepinephrine-treated cells does not involve any change in the rate of degradation. Norepinephrine increased the specific rate of synthesis of both lactate dehydrogenase-5 (a tetramer of four M subunits) and lactate dehydrogenase-1 (a tetramer of four H subunits), although to different extents. Since these subunits are coded for by two separate genes on separate chromosomes, it suggests that the regulatory mechanism involves at least two separate sites of action.

  8. Effect of hypothyroidism on hormone profiles in virgin, pregnant and lactating rats, and on lactation.

    PubMed

    Hapon, M B; Simoncini, M; Via, G; Jahn, G A

    2003-09-01

    Thyroid dysfunctions can produce reproductive problems. Untreated maternal hypothyroidism has serious consequences on development of offspring, resulting in stunted growth and mental retardation. The effects of propylthiouracyl-induced hypothyroidism (0.1 g l(-1) in drinking water starting 8 days before mating, or given to virgin rats for 30 or 50 days) on the serum profiles of hormones related to reproduction and mammary function (prolactin, growth hormone (GH), progesterone, corticosterone, oestradiol, insulin-like growth factor I (IGF-I), thyroid-stimulating hormone (TSH), triiodothyronine and tetraiodothyronine), and on mammary function in virgin, pregnant and lactating rats, were investigated. Propylthiouracyl treatment severely decreased circulating triiodothyronine and tetraiodothyronine concentrations, and increased serum TSH concentrations. Virgin rats showed prolonged periods of vaginal dioestrus, increased circulating progesterone concentrations and afternoon peaks of prolactin concentration, which are indicative of prolactin-induced pseudopregnancy. Propylthiouracyl-treated virgin rats had mammary development comparable to that of midpregnancy, and half of these rats had increased mammary casein and lactose concentrations. Serum prolactin concentrations were decreased on the afternoon of day 5 of pregnancy, increased during late pregnancy (days 15-21) and were normal during lactation. Circulating GH concentrations decreased on days 15-21 of pregnancy, whereas progesterone concentrations increased during late pregnancy and early lactation. Circulating oestradiol (measured in late pregnancy and in virgin rats), IGF-I and corticosterone concentrations were decreased. Although assessment of mammary histology showed no differences in extent of development, casein content was increased in propylthiouracyl-treated rats on day 21 of pregnancy; litter growth was severely reduced and at day 20 of age the pups were hypothyroid, with decreased GH serum

  9. Prenatal and lactation nicotine exposure affects morphology and function of brown adipose tissue in male rat offspring.

    PubMed

    Fan, Jie; Ping, Jie; Zhang, Wan-Xia; Rao, Yi-Song; Liu, Han-Xiao; Zhang, Jing; Yan, You-E

    2016-01-01

    The aim of this study was to investigate the effects of prenatal and lactation nicotine exposure on the morphology and function of brown adipose tissue (BAT) in male rat offspring. We conducted a morphological assay and gene expression study of interscapular BAT (iBAT) in male rat offspring. The male offspring from nicotine-exposed dams exhibited higher body weight and iBAT weight. Hematoxylin and eosin staining and transmission electron microscopy showed that iBAT from nicotine-exposed male offspring presented a "whitening" phenotype characterized by lipid droplet accumulation and impaired mitochondria with a randomly oriented and fractured cristae. The expression of the iBAT structure and function-related genes all decreased in nicotine-exposed male offspring. These data indicate that prenatal and lactation nicotine exposure affects morphology and function of iBAT in male rat offspring.

  10. Effects of venlafaxine and chronic unpredictable stress on behavior and hippocampal neurogenesis of rat dams.

    PubMed

    Belovicova, Kristina; Bogi, Eszter; Koprdova, Romana; Ujhazy, Eduard; Mach, Mojmir; Dubovicky, Michal

    2017-02-01

    Epidemiological studies strongly support the theory that stressful life events play an important role in the etiology of depression. The mechanism of chronic stress induced depression involves a number of systems. Chronic stress represents a serious health issue especially during pregnancy and lactation. In this sensitive period, stress can lead to changes in emotion and cognitive behavior both of the mothers and the offspring. It is thus necessary to properly manage stress events during gestation. Venlafaxine belongs to the group of serotonin and noradrenaline re-uptake inhibitor drugs. It is used for the treatment of depression, anxiety disorders and other mood disorders. During pregnancy, however, the use of venlafaxine is questionable due to the lack of experimental and clinical studies. Therefore the aim of this study was to evaluate the effect of chronic unpredictable stress and/or venlafaxine treatment on maternal and open field behavior of dams. Moreover, hippocampal neurogenesis was investigated either. Female Wistar rats were subjected to 2-week chronic unpredictable stress induced by random stressors and treated with venlafaxine orally at a dose of 5 mg/kg twice a day. Maternal behavior was evaluated within 5-min observations twice a day. Mothers were also tested in the open field 8 weeks after chronic unpredictable stress procedure in a single 15-min session. Hippocampal neurogenesis was investigated by immunohistochemistry essay using DCX staining. Results of the present study showed altered maternal and open field behavior of the dams. Stressed dams had lowered hippocampal neurogenesis, while venlafaxine treatment reversed this lowering. These results suggest that stress and antidepressant therapy can have significant impact on behavior and hippocampal neurogenesis in rat dams.

  11. Amino acid metabolism and protein synthesis in lactating rats fed on a liquid diet.

    PubMed Central

    Barber, T; García de la Asunción, J; Puertes, I R; Viña, J R

    1990-01-01

    1. Amino acid metabolism was studied in control virgin rats, lactating rats and virgin rats protein-pair-fed with the lactating rats (high-protein virgin rats). 2. Urinary excretion of nitrogen and urea was higher in lactating than in control virgin rats, and in high-protein virgin rats it was higher than in lactating rats. 3. The activities of urea-cycle enzymes (units/g) were higher in high-protein virgin than in lactating rats, except for arginase. In lactating rats the activities of carbamoyl-phosphate synthase, ornithine carbamoyltransferase and argininosuccinate synthase were lower than in control virgin rats. When the liver size is considered, the activities in lactating rats were similar to those in high-protein virgin rats, except for arginase. 4. N-Acetylglutamate content was higher in high-protein virgin rats than in the other two groups. 5. The rate of urea synthesis from precursors by isolated hepatocytes was higher in high-protein virgin rats than in the other two groups. 6. The flooding-dose method (L-[4-3H]phenylalanine) for measuring protein synthesis was used. The absolute synthesis rates of mammary gland, liver and small-intestinal mucosa were higher in lactating rats than in the other two groups, and in high-protein virgin rats than in control virgin rats 7. These results show that the increased needs for amino acids during lactation are met by hyperphagia and by a nitrogen-sparing mechanism. PMID:2396994

  12. Non-targeted plasma metabolomic profile at early and late lactation in parity 1 dams with diverging body composition at weaning

    USDA-ARS?s Scientific Manuscript database

    Lactation is an extremely energy demanding event, impacting naïve dams to a greater extent as they are still physiologically immature. The objective of the current study was to determine if a unique plasma metabolome exists at early and late lactation from first parity gilts having similar body meas...

  13. Inhibition of lactate removal by ketone bodies in rat liver. Evidence for a quantitatively important role of the plasma membrane lactate transporter in lactate metabolism.

    PubMed Central

    Metcalfe, H K; Monson, J P; Welch, S G; Cohen, R D

    1986-01-01

    We studied the effect of DL-3-hydroxybutyrate and acetoacetate on lactate transport into isolated hepatocytes and on lactate removal in the isolated perfused rat liver. Ketone bodies inhibited lactate transport into isolated hepatocytes (maximum, 35% at concentrations of 10-20 mM). Lactate removal and glucose production by perfused livers were examined before and after the introduction of a constant infusion of hydroxybutyrate, acetoacetate, or appropriate control into the portal venous limb. Lactate removal was significantly inhibited within 10 s of the appearance of increasing concentrations of ketone bodies in the effluent. Corresponding decreases in glucose production were observed. The dependence of inhibition on D-3-hydroxybutyrate concentration was documented in isolated perfused livers (maximum inhibition of lactate removal, 58% at 14 mM). This phenomenon could be a factor in the development of lactic acidosis accompanying ketoacidosis, and indicates that plasma membrane lactate transport may determine the rate of hepatic lactate removal. PMID:3745435

  14. Oxytocin modulates unconditioned fear response in lactating dams: an fMRI study

    PubMed Central

    Febo, Marcelo; Shields, Jessica; Ferris, Craig F.; King, Jean A.

    2009-01-01

    Oxytocinergic neurotransmission during lactation contributes to reduction of anxiety levels and fear. However, our knowledge of where oxytocin acts in the brain to achieve this effect, particularly to an unconditioned fear stimulus, is incomplete. We used blood oxygenation level dependent (BOLD) fMRI to test whether central administration of oxytocin 45–60 minutes before fMRI scanning alters maternal brain activation in response to a predator scent (TMT, trimethylthiazoline). Comparison behavioral experiments that examined maternal responses to this unconditioned fear -inducing odor were carried out in a separate cohort of lactating rats given similar treatments. Behavioral experiments confirmed the effectiveness of oxytocin at reducing freezing behavior as compared to vehicle controls. Our fMRI findings indicate that oxytocin modulated both positive and negative BOLD responses across several olfactory and forebrain nuclei. Significantly greater percent increases in BOLD signal in response to TMT were observed in the anterior cingulate, bed nucleus of stria terminalis and perirhinal area of oxytocin pretreated rats. These animals also showed significantly larger percent decreases in BOLD in mammillary bodies, secondary motor cortex, gustatory cortex, prelimbic prefrontal cortex, orbital cortex, and the anterior olfactory nucleus. The observed pattern of brain activity suggests that oxytocin enhances neural processing in emotion and cognition driven brain areas such as the cingulate cortex, while dramatically reducing activity in areas also controlling autonomic, visceromotor and skeletomotor responses. The present data contribute to the growing literature suggesting the oxytocin modulate the integration of emotional and cognitive information through myriad brain regions to facilitate decreases in anxiety (even to an unconditioned stimulus) while potentially promoting pair-bonding, social memory and parental care. PMID:19766607

  15. Green tea extract intake during lactation modified cardiac macrophage infiltration and AMP-activated protein kinase phosphorylation in weanling rats from undernourished mother during gestation and lactation.

    PubMed

    Matsumoto, E; Kataoka, S; Mukai, Y; Sato, M; Sato, S

    2017-04-01

    Maternal dietary restriction is often associated with cardiovascular disease in offspring. The aim of this study was to investigate the effect of green tea extract (GTE) intake during lactation on macrophage infiltration, and activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and serine-threonine kinase Akt (Akt) in the hearts of weanlings exposed to maternal dietary protein restriction. Pregnant Wistar rats were fed control (C) or low-protein diets (LP) throughout gestation. Following delivery, the dams received a control or a GTE-containing control diet during lactation: control diet during gestation and lactation (CC), low-protein diet during gestation and lactation (LPC), low-protein diet during gestation and 0.12% GTE-containing low-protein diet during lactation (LPL), and low-protein diet during gestation and 0.24% GTE-containing low-protein diet during lactation (LPH). The female offspring were sacrificed at day 22. Biochemical parameters in the plasma, macrophage infiltration, degree of fibrosis and expression levels of AMPK and Akt were examined. The plasma insulin level increased in LPH compared with LPC. Percentage of the fibrotic areas and the number of macrophages in LPC were higher than those in CC. Conversely, the fibrotic areas and the macrophage number in LPH were smaller (21 and 56%, respectively) than those in LPC. The levels of phosphorylated AMPK in LPL and LPH, and Akt in LPH were greater than those in LPC. In conclusion, maternal protein restriction may induce macrophage infiltration and the decrease of insulin levels. However, GTE intake during lactation may suppress macrophage infiltration and restore insulin secretion function via upregulation of AMPK and insulin signaling in weanlings.

  16. Lactational Vitamin E Protects Against the Histotoxic Effects of Systemically Administered Vanadium in Neonatal Rats.

    PubMed

    Olaolorun, F A; Obasa, A A; Balogun, H A; Aina, O O; Olopade, J O

    2014-12-29

    The work investigated the protective role of lactational vitamin E administration on vanadium-induced histotoxicity. Three groups of Wistar rats, with each group comprising of two dams and their pups, were used in this study. Group I pups were administered intraperitoneal injection of sterile water at volumes corresponding to the dose rate of the vanadium (sodium metavanadate) treated group from postnatal day (PND) 1-14 while those in Group II were administered intraperitoneal injection of 3mg/kg vanadium from PND 1-14. Group III pups were administered intraperitoneal injection of 3mg/kg vanadium while the dam received oral vitamin E (500 mg) concurrently every 72 hours. The results showed that group II pups exhibited histopathological changes which included seminiferous tubule disruption of the testes characterised by vacuolar degeneration and coagulative necrosis of spermatogonia and Sertoli cells with reduction in mitosis, and areas of interstitial thickening with fibroblast proliferation. In addition, the lungs showed disruption of the bronchiolar wall and denudation of the bronchiolar respiratory epithelium while the liver showed hydropic degeneration and coagulative necrosis of the centrilobular hepatocytes. These histotoxic changes were ameliorated in the vanadium + vitamin E group. We conclude that lactational vitamin E protects against the histotoxic effects of vanadium and could be a consideration for supplementation in the occupationally and environmentally exposed neonates. However, caution should be taken in vitamin E supplementation because there is still equivocal evidence surrounding its benefits as a supplement at the moment.

  17. Lactating Rats Retain Nursing Behavior and Maternal Care in Space

    NASA Technical Reports Server (NTRS)

    Daly, Megan E.; Ronca, April E.; Dalton, Bonnie (Technical Monitor)

    2001-01-01

    In 1997, suckling mammals were flown in space for the first time as part of the NIH.R3 experiment sponsored jointly by NIH (National Institutes of Health) and NASA. Six rat dams and litters (Rattus norvegicus) were launched on an eight-day Space Shuttle mission at each of three postnatal ages (P5, P8, and P15). Dams and litters (N = 10 pups/litter) were housed within modified Animal Enclosure Modules (AEMs). Comparisons were made to ground controls. Dams and litters were videotaped daily in flight. The P8 and P15 flight litters showed excellent survival (99%) and weight gain relative to AEM ground controls, whereas P5 litters showed reduced survival (0% and 60%, respectively) and weight gain (less than 40% AEM). To examine the possibility that failures of maternal care contributed to P5 results, we analyzed the dams' in-flight nursing, licking and retrieving from four video segments ranging from twelve to fifteen minutes in length with control data derived from multiple ground segments. Video analyses revealed clear evidence of maternal care in flight. For P5 dams, frequency and duration of nursing and licking bouts fell within or above one standard deviation of control values. Retrieving was noted in the P5 and P8 groups only. The observed results suggest that factors other than maternal care contributed to the low survival rates and body weight gains of the P5 flight offspring.

  18. Induction of drug metabolizing enzymes in polybrominated biphenyl-fed lactating rats and their pups.

    PubMed

    Moore, R W; Dannan, G A; Aust, S D

    1978-04-01

    Polybrominated biphenyls (PBBs) cause a mixed-type (phenobarbital- plus 3-methylcholanthrene-like) induction of liver microsomal drug metabolizing enzymes in rats. However, 2,2',4,4',5,5'-hexabromobiphenyl and 2,2',3,4,4',5,5'-heptabromobiphenyl, which together comprise less than 80% of PBBs (FireMaster), were shown to be strictly phenobarbital-type inducers. Other components (unidentified) must therefore cause the 3-methylcholanthrene-like effects. The potential for PBBs to exert effects on neonates through milk was examined. Lactating rats were fed 0, 0.1, 1.0, or 10 ppm FireMaster for the 18 days following delivery, at which time mothers and most pups were sacrificed. Pups nursing from mothers fed 10 ppm PBBs showed significant increases in liver weights and microsomal protein, and both mothers and pups had increased cytochrome P-450, aminopyrine demethylation, benzo[a]pyrene hydroxylation, and UDP-glucuronyltransferase. Pups nursing from rats fed 1.0 ppm had increases in microsomal protein, cytochrome P-450, aminopyrine demethylation, and benzo[a]pyrene hydroxylation, while their mothers were unaffected. Several pups from the 0, 0.1, and 1.0 ppm groups were maintained on their mother's diets, raised, and allowed to mate. Their pups showed much the same responses to PBBs as did the original group of pups. The effects on both generations of adult female rats were also comparable. PBBs cause a mixed-type induction in both lactating rats and their nursing pups; PBB components responsible for both aspects of this induction must be transmitted through milk. Nursing rats are approximately tenfold more sensitive to the effects of PBBs in their mother's diets than are the dams. The approximate no-effect level for microsomal induction in nursing rats is 0.1 ppm PBBs in the diet of the adult.

  19. Differential effects of habitual chow-based and semi-purified diets on lipid metabolism in lactating rats and their offspring.

    PubMed

    Del Bas, Josep Maria; Caimari, Antoni; Ceresi, Enzo; Arola-Arnal, Anna; Palou, Andreu; Arola, Lluís; Crescenti, Anna

    2015-03-14

    Diet during pregnancy and lactation is a critical factor in relation to the health of dams and their offspring. Currently, control diets used in metabolic imprinting studies differ in composition and type, i.e. semi-purified diets (SD) or chow-based diets (ND). The aim of the present study was to determine whether two widely used control diets, a SD and a ND, that mainly differ in fat content (5·08 and 3·26 %, respectively) and its sources (soyabean oil for the SD and cereals and fish for the ND), fibre (6 and 15 %, respectively), and cholesterol (26 and 69 mg/kg diet, respectively) can influence the lipid metabolism of dams and their offspring. Wistar rats were fed either the SD or the ND during pregnancy and lactation. At weaning, SD-fed dams presented severe hepatic steatosis and increased levels of circulating TAG, NEFA and insulin. Importantly, the offspring presented an altered plasma lipid profile. In contrast, the ND allowed for a normal gestation and lactation process, and did not affect the metabolism of offspring. In parallel, virgin rats fed the SD showed no metabolic alterations. A higher intake of SFA and MUFA and a lower consumption of PUFA observed in SD-fed dams during the lactation period could contribute to explaining the observed effects. In conclusion, two different control diets produced very different outcomes in the lipid metabolism of lactating rats and their offspring. The present results highlight the importance of the assessment of the metabolic state of dams when interpreting the results of metabolic programming studies.

  20. Effects of Pregnancy and Lactation on Iron Metabolism in Rats

    PubMed Central

    Gao, Guofen; Liu, Shang-Yuan; Wang, Hui-Jie; Zhang, Tian-Wei; Yu, Peng; Duan, Xiang-Lin; Zhao, Shu-E; Chang, Yan-Zhong

    2015-01-01

    In female, inadequate iron supply is a highly prevalent problem that often leads to iron-deficiency anemia. This study aimed to understand the effects of pregnancy and lactation on iron metabolism. Rats with different days of gestation and lactation were used to determine the variations in iron stores and serum iron level and the changes in expression of iron metabolism-related proteins, including ferritin, ferroportin 1 (FPN1), ceruloplasmin (Cp), divalent metal transporter 1 (DMT1), transferrin receptor 1 (TfR1), and the major iron-regulatory molecule—hepcidin. We found that iron stores decline dramatically at late-pregnancy period, and the low iron store status persists throughout the lactation period. The significantly increased FPN1 level in small intestine facilitates digestive iron absorption, which maintains the serum iron concentration at a near-normal level to meet the increase of iron requirements. Moreover, a significant decrease of hepcidin expression is observed during late-pregnancy and early-lactation stages, suggesting the important regulatory role that hepcidin plays in iron metabolism during pregnancy and lactation. These results are fundamental to the understanding of iron homeostasis during pregnancy and lactation and may provide experimental bases for future studies to identify key molecules expressed during these special periods that regulate the expression of hepcidin, to eventually improve the iron-deficiency status. PMID:26788496

  1. DISTRIBUTION OF 14C-ATRAZINE FOLLOWING AN ACUTE LACTATIONAL EXPOSURE IN THE WISTAR RAT.

    EPA Science Inventory

    The purpose of the present study was to examine the distribution of atrazine in the lactating dam and suckling neonate following an acute exposure to either 2 or 4 mg/kg 14C-atrazine (14C-ATR) by gavage. 14C-ATR was administered to the nursing dam on postnatal day 3 by oral gavag...

  2. DISTRIBUTION OF 14C-ATRAZINE FOLLOWING AN ACUTE LACTATIONAL EXPOSURE IN THE WISTAR RAT.

    EPA Science Inventory

    The purpose of the present study was to examine the distribution of atrazine in the lactating dam and suckling neonate following an acute exposure to either 2 or 4 mg/kg 14C-atrazine (14C-ATR) by gavage. 14C-ATR was administered to the nursing dam on postnatal day 3 by oral gavag...

  3. Dietary fructose inhibits lactation-induced adaptations in rat 1,25-(OH)2D3 synthesis and calcium transport

    PubMed Central

    Douard, Veronique; Suzuki, Takuji; Sabbagh, Yves; Lee, Jacklyn; Shapses, Sue; Lin, Sheldon; Ferraris, Ronaldo P.

    2012-01-01

    We recently showed that excessive fructose consumption, already associated with numerous metabolic abnormalities, reduces rates of intestinal Ca2+ transport. Using a rat lactation model with increased Ca2+ requirements, we tested the hypothesis that mechanisms underlying these inhibitory effects of fructose involve reductions in renal synthesis of 1,25-(OH)2D3. Pregnant and virgin (control) rats were fed isocaloric fructose or, as controls, glucose, and starch diets from d 2 of gestation to the end of lactation. Compared to virgins, lactating dams fed glucose or starch had higher rates of intestinal transcellular Ca2+ transport, elevated intestinal and renal expression of Ca2+ channels, Ca2+-binding proteins, and CaATPases, as well as increased levels of 25-(OH)D3 and 1,25-(OH)2D3. Fructose consumption prevented almost all of these lactation-induced increases, and reduced vitamin D receptor binding to promoter regions of Ca2+ channels and binding proteins. Changes in 1,25-(OH)2D3 level were tightly correlated with alterations in expression of 1α-hydroxylase but not with levels of parathyroid hormone and of 24-hydroxylase. Bone mineral density, content, and mechanical strength each decreased with lactation, but then fructose exacerbated these effects. When Ca2+ requirements increase during lactation or similar physiologically challenging conditions, excessive fructose consumption may perturb Ca2+ homeostasis because of fructose-induced reductions in synthesis of 1,25-(OH)2D3.—Douard, V., Suzuki, T., Sabbagh, Y., Lee, J., Shapses, S., Lin, S., Ferraris, R. P. Dietary fructose inhibits lactation-induced adaptations in rat 1,25-(OH)2D3 synthesis and calcium transport. PMID:22038050

  4. Characterization of maternal motivation in the lactating rat: Contrasts between early and late postpartum responses

    PubMed Central

    Wansaw, Michael P.; Pereira, Mariana; Morrell, Joan I.

    2008-01-01

    We previously assessed the motivational properties of pups relative to those of cocaine in parturient female rats (dams) across the postpartum period and demonstrated that the larger subset of dams in early postpartum (PPD8) preferred the pup-associated chamber, whereas the majority of dams tested in late postpartum (PPD16) preferred the cocaine-associated chamber [Mattson, B.J., Williams, S., Rosenblatt, J.S., Morrell, J.I. 2001. Comparison of two positive reinforcing stimuli: pups and cocaine throughout the postpartum period. Behav. Neurosci., 115, 683-694; Seip, K.M., Morrell, J.I. 2007. Increasing the incentive salience of cocaine challenges preference for pup- over cocaine-associated stimuli during early postpartum: place preference and locomotor analyses in the lactating female rat. Psychopharmacology 194, 309-319]. The present study uses a dual-choice conditioned place preference to ask how the progression of the postpartum period, including natural pup development, influences maternal motivation for pups. Preferences for cued chambers associated with pups that were age-matched to the postpartum stage of the dam in contrast to a stimulus with little incentive salience were higher during the early than the late postpartum, suggesting that the incentive salience of pups diminishes as the postpartum period progresses. Preferences of the early postpartum dams deprived of pups for 15 min, 2, 6, 12 or 22 hrs prior to conditioning and testing did not differ statistically but there was a trend of more pup preference after 22 hr deprivation; pup age was not an important factor in early postpartum. In marked contrast, late postpartum dams only exhibited robust pup-associated place preference when they were conditioned with young (4-7 day-old) pups or after a 22 hr period of deprivation from contemporaneous pups. Together these results suggest that both forces are at work in the mother-pup dyad, changes in the pups as they develop and changes in the physiological and

  5. Characterization of maternal motivation in the lactating rat: Contrasts between early and late postpartum responses.

    PubMed

    Wansaw, Michael P; Pereira, Mariana; Morrell, Joan I

    2008-08-01

    We previously assessed the motivational properties of pups relative to those of cocaine in parturient female rats (dams) across the postpartum period and demonstrated that the larger subset of dams in early postpartum (PPD8) preferred the pup-associated chamber, whereas the majority of dams tested in late postpartum (PPD16) preferred the cocaine-associated chamber [Mattson, B.J., Williams, S., Rosenblatt, J.S., Morrell, J.I. 2001. Comparison of two positive reinforcing stimuli: pups and cocaine throughout the postpartum period. Behav. Neurosci., 115, 683-694; Seip, K.M., Morrell, J.I. 2007. Increasing the incentive salience of cocaine challenges preference for pup- over cocaine-associated stimuli during early postpartum: place preference and locomotor analyses in the lactating female rat. Psychopharmacology 194, 309-319]. The present study uses a dual-choice conditioned place preference to ask how the progression of the postpartum period, including natural pup development, influences maternal motivation for pups. Preferences for cued chambers associated with pups that were age-matched to the postpartum stage of the dam in contrast to a stimulus with little incentive salience were higher during the early than the late postpartum, suggesting that the incentive salience of pups diminishes as the postpartum period progresses. Preferences of the early postpartum dams deprived of pups for 15 min, 2, 6, 12 or 22 hrs prior to conditioning and testing did not differ statistically but there was a trend of more pup preference after 22 hr deprivation; pup age was not an important factor in early postpartum. In marked contrast, late postpartum dams only exhibited robust pup-associated place preference when they were conditioned with young (4-7 day-old) pups or after a 22 hr period of deprivation from contemporaneous pups. Together these results suggest that both forces are at work in the mother-pup dyad, changes in the pups as they develop and changes in the physiological and

  6. Effects on the reproductive parameters of two generations of Rattus norvegicus offspring from dams exposed to heptachlor during gestation and lactation.

    PubMed

    Martínez-Ibarra, Alejandra; Morimoto, Sumiko; Cerbón, Marco; Prado-Flores, Guadalupe

    2017-03-01

    Heptachlor has been targeted for global elimination because of its toxicity and environmental persistence, in accordance with the Stockholm Convention on Persistent Organic Pollutants (POPs). However, there is no regulation of heptachlor use in Mexico, where relatively high levels have been found in maternal breast milk. The aim of this study was to determine the effects of heptachlor on the reproductive system of offspring of two consecutive generations of rats (F1 and F2) from dams orally administered heptachlor during midgestation and lactation. Female offspring were analyzed for different phenotypic, reproductive, and molecular parameters. In the F1 generation, heptachlor treatment induced decreased body weight at weaning, increased female anogenital distance, and delayed vaginal opening. In both generations, serum progesterone levels decreased and estradiol levels remained unchanged, while overexpression of the progesterone receptor was observed in uterine epithelial cells on estrus day. In the F2 generation, expression of the estrogen receptor α increased in the glandular epithelium. Finally, heptachlor treatment did not affect apoptosis in the uterine epithelial cells. Overall, the results indicate that heptachlor induced female reproductive alterations when administered to dams during the perinatal period. Accordingly, exposure to heptachlor may represent a risk for the reproductive health of humans. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 856-868, 2017.

  7. Impact of cafeteria feeding during lactation in the rat on novel object discrimination in the offspring.

    PubMed

    Wright, Thomas M; King, Madeleine V; Davey, William G; Langley-Evans, Simon C; Voigt, Jörg-Peter W

    2014-12-28

    There is increasing evidence that hyperenergetic diets have an impact on memory in rodents. However, it is largely unknown how diets, such as a cafeteria diet (CD), that mimic a Western-type diet act on learning and memory, in particular when fed during early stages of development. Here, we fed lactating dams a CD and exposed both male and female offspring to a novel object discrimination (NOD) task, a two-trial test of recognition memory in which rats exposed to two identical objects during a training/familiarisation trial can discriminate a novel from a familiar object during the subsequent choice trial. The choice trial was performed following inter-trial interval (ITI) delays of up to 4 h. Maternal diet did not have an impact on exploration of the objects by either sex during the familiarisation trial. Control males discriminated the novel from the familiar object, indicating intact memory with an ITI of 1 h, but not 2 or 4 h. The CD delayed this natural forgetting in male rats such that discrimination was also evident after a 2 h ITI. In contrast, control females exhibited discrimination following both 1 and 2 h ITI, but the CD impaired performance. In summary, the present study shows that maternal exposure to the CD programmes NOD in the adult. In better-performing females, dietary programming interferes with NOD, whereas NOD was improved in males after lactational CD feeding.

  8. Distribution and biomarker of carbon-14 labeled fullerene C60 ([(14) C(U)]C60 ) in pregnant and lactating rats and their offspring after maternal intravenous exposure.

    PubMed

    Snyder, Rodney W; Fennell, Timothy R; Wingard, Christopher J; Mortensen, Ninell P; Holland, Nathan A; Shannahan, Jonathan H; Pathmasiri, Wimal; Lewin, Anita H; Sumner, Susan C J

    2015-12-01

    A comprehensive distribution study was conducted in pregnant and lactating rats exposed to a suspension of uniformly carbon-14 labeled C60 ([(14) C(U)]C60 ). Rats were administered [(14) C(U)]C60 (~0.2 mg [(14) C(U)]C60 kg(-1) body weight) or 5% polyvinylpyrrolidone (PVP)-saline vehicle via a single tail vein injection. Pregnant rats were injected on gestation day (GD) 11 (terminated with fetuses after either 24 h or 8 days), GD15 (terminated after 24 h or 4 days), or GD18 (terminated after 24 h). Lactating rats were injected on postnatal day 8 and terminated after 24 h, 3 or 11 days. The distribution of radioactivity in pregnant dams was influenced by both the state of pregnancy and time of termination after exposure. The percentage of recovered radioactivity in pregnant and lactating rats was highest in the liver and lungs. Radioactivity was quantitated in over 20 tissues. Radioactivity was found in the placenta and in fetuses of pregnant dams, and in the milk of lactating rats and in pups. Elimination of radioactivity was < 2% in urine and feces at each time point. Radioactivity remained in blood circulation up to 11 days after [(14) C(U)]C60 exposure. Biomarkers of inflammation, cardiovascular injury and oxidative stress were measured to study the biological impacts of [(14) C(U)]C60 exposure. Oxidative stress was elevated in female pups of exposed dams. Metabolomics analysis of urine showed that [(14) C(U)]C60 exposure to pregnant rats impacted the pathways of vitamin B, regulation of lipid and sugar metabolism and aminoacyl-tRNA biosynthesis. This study demonstrated that [(14) C(U)]C60 crosses the placenta at all stages of pregnancy examined, and is transferred to pups via milk.

  9. Distribution and Biomarker of Carbon-14 Labeled Fullerene C60 ([14C(U)]C60) in Pregnant and Lactating Rats and their Offspring after Maternal Intravenous Exposure

    PubMed Central

    Snyder, Rodney W.; Fennell, Timothy R.; Wingard, Christopher J.; Mortensen, Ninell P.; Holland, Nathan A.; Shannahan, Jonathan H.; Pathmasiri, Wimal; Lewin, Anita H.; Sumner, Susan C. J.

    2015-01-01

    A comprehensive distribution study was conducted in pregnant and lactating rats exposed to a suspension of uniformly carbon-14 labeled C60 ([14C(U)]C60). Rats were administered [14C(U)]C60 (~0.2 mg [14C(U)]C60/kg body weight) or 5% polyvinylpyrrolidone (PVP)-saline vehicle via a single tail vein injection. Pregnant rats were injected on gestation day (GD) 11 (terminated with fetuses after either 24h or 8d), GD15 (terminated after 24h or 4d), or GD18 (terminated after 24h). Lactating rats were injected on postnatal day 8 and terminated after 24h, 3d or 11d. The distribution of radioactivity in pregnant dams was influenced by both the state of pregnancy and time of termination after exposure. The percentage of recovered radioactivity in pregnant and lactating rats was highest in liver and lungs. Radioactivity was quantitated in over 20 tissues. Radioactivity was found in placenta and in fetuses of pregnant dams, and in the milk of lactating rats and in pups. Elimination of radioactivity was <2% in urine and feces at each time point. Radioactivity remained in blood circulation up to 11 days after [14C(U)]C60 exposure. Biomarkers of inflammation, cardiovascular injury and oxidative stress were measured to study the biological impacts of [14C(U)]C60 exposure. Oxidative stress were elevated in female pups of exposed dams. Metabolomics analysis of urine showed that [14C(U)]C60 exposure to pregnant rats impacted the pathways of vitamin B, regulation of lipid and sugar metabolism and aminoacyl-tRNA biosynthesis. This study demonstrated that [14C(U)]C60 crosses the placenta at all stages of pregnancy examined, and is transferred to pups via milk. PMID:26081520

  10. [Behavioural studies during the gestational-lactation period in morphine treated rats].

    PubMed

    Sobor, Melinda; Timár, Júlia; Riba, Pál; Király, Kornél P; Al-Khrasani, Mahmoud; Gyarmati, Zsuzsanna; Fürst, Zsuzsanna

    2013-12-01

    Opioids impair the maternal behaviour of experimental animals. The effect of morphine on maternal behaviour in rat dams treated chronically with morphine during the whole pregnancy and lactation has not been yet analysed systematically. The aim of our work was to investigate the behavioural effects of moderate dose morphine administered constantly in the whole perinatal period in rats. Nulliparous female rats were treated with 10 mg/kg morphine s.c. once daily, from the day of mating. Maternal behaviour was observed, the effects of acute morphine treatment on the maternal behaviour and whether this effect could be antagonised by naloxone were also investigated. Physical and other behavioural (anxiety-like signals in elevated plus maze, changes in locomotor activity) withdrawal signs precipitated by naloxone were registered. After weaning sensitivity to the rewarding effect of morphine was measured by conditioned place preference and to the aversive effect of naloxone by conditioned place aversion tests. Antinociceptive test on tail-flick apparatus was performed to investigate the changes in morphine antinociceptive effects due to chronic morphine treatment. Maternal behaviour was significantly impaired in morphine-treated dams. This effect of morphine lasted c.a. 2-3 hours a day, it showed dose-dependency and was enhanced in MO-treated group (sensitisation). Only weak physical and no other behavioural (anxiety-like behaviour or hypolocomotion) withdrawal signs were precipitated by naloxone. The positive reinforcing effect of morphine and aversive effect of naloxone were markedly increased on conditioned place paradigm. Significant antinociceptive tolerance was not seen. Although human drug abuse can be hardly modelling under experimental circumstances, our constant, relatively moderate dose morphine treatment administered once daily during the whole pregnancy and lactation resulted in several subtle behavioural changes in dams. In perinatally opioid

  11. Maternal high-fat diet during pregnancy and lactation had gender difference effect on adiponectin in rat offspring.

    PubMed

    Gregoraszczuk, E; Slupecka, M; Wolinski, J; Hejmej, A; Bilinska, B; Fiedor, E; Piwnicka, N; Rak, A

    2016-08-01

    This study investigated the effect of a high-fat (HF) diet on plasma adiponectin and steroid hormones levels, and the protein expression of adiponectin and its receptors, in the gonads and gonadal (periovarian and epididymal) white adipose tissue (WAT) of dams and their offspring. Female Wistar rats were fed a HF diet (30% fat) or a standard breeding (BD) diet (5% fat) during pregnancy and lactation. At 21 days of lactation, mothers and both sexes of prepubertal offspring were killed by decapitation. Plasma adiponectin, testosterone (T) and oestradiol (E2) levels were analyzed by ELISA. The protein expression of adiponectin and its receptors 1 (AdipoR1) and 2 (AdipoR2) was assayed by Western blot and immunohistochemistry. Plasma adiponectin levels in HF dams were lower compared to BD dams, and correlated with protein expression of adiponectin and its receptors, but not with steroid hormone levels. Female HF offspring had lower plasma adiponectin levels, reduced intensity of adiponectin and AdipoR1 in the ovary, and decreased E2 in parallel with increased T. In contrast, male HF offspring had higher plasma adiponectin levels, increased intensity of adiponectin and AdipoR1 in the testis, and decreased T in parallel with increased E2. In conclusion, feeding a HF diet to dams during pregnancy and lactation disturbs plasma adiponectin levels and protein expression, both in female and male offspring; it lowers adiponectin secretion and protein expression in the female whereas in male it is increased. As a consequence, there is disruption of steroid secretion in offspring, towards T in females, and E2 in males.

  12. Preferential fat intake of pups nursed by dams fed low fat diet during pregnancy and lactation is higher than that of pups nursed by dams fed control diet and high fat diet.

    PubMed

    Nakashima, Yoko; Tsukita, Yoko; Yokoyama, Meiko

    2008-06-01

    To investigate the effect of dams' dietary fat type during pregnancy and lactation on fat choice of pups, three groups of dams were fed one of three diets: a low fat diet (LFD), a control diet (CTD) or a high fat diet (HFD). After weaning their pups were offered a self-selection regimen of both a fat protein diet (FPD) and a carbohydrate protein diet (CPD) for 3 wk. Although the ratio of FPD intake [FPD intake (g)/total intake (g)] by pups nursed by dams fed LFD during the self-selection period was higher than that by pups nursed by dams fed CTD and HFD, no significant difference in the ratio was observed between pups nursed by dams fed CTD and HFD. It was considered that pups nursed by dams fed CTD and HFD self-selected FPD and CPD in an adequate fat energy ratio (F ratio) compared to that of AIN-93G and AIN-93M. The ratio of FPD intake by pups of these three groups was 16-21% within the first week after weaning. Although pups nursed by dams fed CTD continued to consume the same ratio of FPD during the self-selection period, the ratio of pups nursed by dams fed LFD increased and that of pups nursed by dams fed HFD decreased. These findings indicate that: [1] pups nursed by dams fed CTD and HFD have the ability to consume FPD and CPD in an adequate F ratio, and [2] preferential fat intake of pups nursed by dams fed LFD is stronger than that of pups nursed by dams fed CTD and HFD.

  13. Recovery of motor coordination after exercise is correlated to enhancement of brain-derived neurotrophic factor in lactational vanadium-exposed rats.

    PubMed

    Wang, Dean-Chuan; Lin, Yu-Yi; Lin, Hwai-Ting

    2015-07-23

    Lactational exposure to vanadium can reduce the locomotor activity in adult animals. In this study, we investigated whether lactational vanadium exposure impairs the motor coordination and whether exercise ameliorates this dysfunction. Sprague-Dawley dams were treated with or without vanadium during lactation. The weaned male offspring were trained to treadmill running for 5 weeks and then examined their motor coordination on a rotarod. The neuroprotective effect of exercise was evaluated by the brain-derived neurotrophic factor (BDNF) in plasma and cerebellum. The results demonstrated that vanadium-exposed rats exhibited impaired motor coordination and reduced plasma and cerebellar BDNF levels. Treadmill running during childhood-adolescence prevented the impaired motor coordination in the lactational vanadium-exposed rats. The beneficial effect of treadmill running on motor coordination in the vanadium-exposed rats was correlated to the normalization of plasma and cerebellar BDNF levels, as well as the increased TrkB phosphorylation in the cerebellum. The result suggests that exercise may prevent the impairment of motor coordination in the lactational vanadium-exposed rats.

  14. Hypothyroidism following developmental iodine deficiency reduces hippocampal neurogranin, CaMK II and calmodulin and elevates calcineurin in lactational rats.

    PubMed

    Dong, Jing; Liu, Wanyang; Wang, Yi; Xi, Qi; Chen, Jie

    2010-11-01

    Developmental iodine deficiency (ID) leads to inadequate thyroid hormone that impairs learning and memory with an unclear mechanism. Here, we show that hippocampal neurogranin, calcium/calmodulin dependent protein kinase II (CaMKII), calmodulin (CaM) and calcineurin (CaN) are implicated in the brain impairment in lactational rat hippocampus following developmental ID and hypothyroidism. Three developmental rat models were created by administrating dam rats with either iodine-deficient diet or propylthiouracil (PTU, 5 ppm or 15 ppm)-added drinking water from gestational day (GD) 6 till postnatal day (PN) 21. Then, the neurogranin, CaMKII, CaM and CaN in the hippocampus were detected with immunohistochemistry and western blotting on PN14 and PN21. The iodine-deficient and hypothyroid pups showed significantly lower level of neurogranin, CaMKII and CaM and significantly increased CaN in hippocampal CA1 and CA3 regions than the controls on PN14 and PN21 (P<0.05, respectively). Data indicate that, in lactational rats, hippocampal neurogranin, CaMKII, CaM and CaN are involved in the brain impairment by developmental ID and hypothyroidism. Copyright © 2010 ISDN. Published by Elsevier Ltd. All rights reserved.

  15. Maternal Dietary Supplementation with Oligofructose-Enriched Inulin in Gestating/Lactating Rats Preserves Maternal Bone and Improves Bone Microarchitecture in Their Offspring

    PubMed Central

    Diaz-Castro, Javier; López-Aliaga, Inmaculada; Rueda, Ricardo

    2016-01-01

    Nutrition during pregnancy and lactation could exert a key role not only on maternal bone, but also could influence the skeletal development of the offspring. This study was performed in rats to assess the relationship between maternal dietary intake of prebiotic oligofructose-enriched inulin and its role in bone turnover during gestation and lactation, as well as its effect on offspring peak bone mass/architecture during early adulthood. Rat dams were fed either with standard rodent diet (CC group), calcium-fortified diet (Ca group), or prebiotic oligofructose-enriched inulin supplemented diet (Pre group), during the second half of gestation and lactation. Bone mineral density (BMD) and content (BMC), as well as micro-structure of dams and offspring at different stages were analysed. Dams in the Pre group had significantly higher trabecular thickness (Tb.Th), trabecular bone volume fraction (BV/TV) and smaller specific bone surface (BS/BV) of the tibia in comparison with CC dams. The Pre group offspring during early adulthood had an increase of the lumbar vertebra BMD when compared with offspring of CC and Ca groups. The Pre group offspring also showed significant increase versus CC in cancellous and cortical structural parameters of the lumbar vertebra 4 such as Tb.Th, cortical BMD and decreased BS/BV. The results indicate that oligofructose-enriched inulin supplementation can be considered as a plausible nutritional option for protecting against maternal bone loss during gestation and lactation preventing bone fragility and for optimizing peak bone mass and architecture of the offspring in order to increase bone strength. PMID:27115490

  16. Maternal Dietary Supplementation with Oligofructose-Enriched Inulin in Gestating/Lactating Rats Preserves Maternal Bone and Improves Bone Microarchitecture in Their Offspring.

    PubMed

    Bueno-Vargas, Pilar; Manzano, Manuel; Diaz-Castro, Javier; López-Aliaga, Inmaculada; Rueda, Ricardo; López-Pedrosa, Jose María

    2016-01-01

    Nutrition during pregnancy and lactation could exert a key role not only on maternal bone, but also could influence the skeletal development of the offspring. This study was performed in rats to assess the relationship between maternal dietary intake of prebiotic oligofructose-enriched inulin and its role in bone turnover during gestation and lactation, as well as its effect on offspring peak bone mass/architecture during early adulthood. Rat dams were fed either with standard rodent diet (CC group), calcium-fortified diet (Ca group), or prebiotic oligofructose-enriched inulin supplemented diet (Pre group), during the second half of gestation and lactation. Bone mineral density (BMD) and content (BMC), as well as micro-structure of dams and offspring at different stages were analysed. Dams in the Pre group had significantly higher trabecular thickness (Tb.Th), trabecular bone volume fraction (BV/TV) and smaller specific bone surface (BS/BV) of the tibia in comparison with CC dams. The Pre group offspring during early adulthood had an increase of the lumbar vertebra BMD when compared with offspring of CC and Ca groups. The Pre group offspring also showed significant increase versus CC in cancellous and cortical structural parameters of the lumbar vertebra 4 such as Tb.Th, cortical BMD and decreased BS/BV. The results indicate that oligofructose-enriched inulin supplementation can be considered as a plausible nutritional option for protecting against maternal bone loss during gestation and lactation preventing bone fragility and for optimizing peak bone mass and architecture of the offspring in order to increase bone strength.

  17. Delayed physical and neurobehavioral development and increased aggressive and depression-like behaviors in the rat offspring of dams fed a high-fat diet.

    PubMed

    Giriko, Catherine Ássuka; Andreoli, Carla Albuquerque; Mennitti, Laís Vales; Hosoume, Lilian Fazion; Souto, Tayane Dos Santos; Silva, Alexandre Valotta da; Mendes-da-Silva, Cristiano

    2013-12-01

    Early maternal exposure to a high-fat diet (HFD) may influence the brain development of rat offspring and consequently affect physiology and behavior. Thus, in the present study, we investigated the somatic, physical, sensory-motor and neurobehavioral development of the offspring of dams fed an HFD (52% calories from fat, mainly saturated) and the offspring of dams fed a control diet (CD - 14.7% fat) during lactation from the 1st to the 21st postnatal day (P). Maternal body weights were evaluated during lactation. In the progeny, somatic (body weight, head and lengths axes) and physical (ear unfolding, auditory conduit opening, eruption of the incisors and eye opening) development and the consolidation of reflex responses (palm grasp, righting, vibrissa placing, cliff avoidance, negative geotaxis, auditory startle response and free-fall righting) were determined during suckling. Depressive and aggressive behaviors were tested with the forced swimming test (FST) and the "foot-shock" test on days 60 and 110, respectively. The open field test was used to assess motor function. Compared to controls, the HFD-pups exhibited decreases in body weight (P7-P21) and body length (P4-P18), but by days P71 and P95, these pups were overweight. All indicators of physical maturation and the consolidation of the following reflexes, vibrissa placing, auditory startle responses, free-fall righting and negative geotaxis, were delayed in HFD-progeny. In addition, the pups from HFD dam rats also exhibited reduced swimming and climbing times in the FST and increased aggressive behavior. No changes in locomotion were observed. These findings show developmental and neurobehavioral changes in the rat offspring of dams fed the HFD during lactation and suggest possible disruption of physical and sensory-motor maturation and increased susceptibility to depressive and aggressive-like behavior.

  18. Body adiposity and bone parameters of male rats from mothers fed diet containing flaxseed flour during lactation.

    PubMed

    da Costa, C A S; da Silva, P C A; Ribeiro, D C; Pereira, A D D; Santos, A D S D; Maia, L D A; Ruffoni, L D G; de Santana, F C; de Abreu, M D C; Boueri, B F D C; Pessanha, C R; Nonaka, K O; Mancini-Filho, J; do Nascimento-Saba, C C A; Boaventura, G T

    2015-12-07

    Obesity and osteoporosis may have their origins in early postnatal life. This study was designed to evaluate whether flaxseed flour use during lactation period bears effect on body adiposity and skeletal structure of male rat pups at weaning. At birth, male Wistar rats were randomly assigned to control and experimental (FF) groups, whose dams were treated with control or flaxseed flour diet, respectively, during lactation. At 21 days of age, pups were weaned to assess body mass, length and composition by dual-energy X-ray absorptiometry. The animals were then sacrificed to carry out analysis of serum profile, intra-abdominal adipocyte morphology and femur characteristics. Differences were considered significant when P<0.05. The FF group displayed the following characteristics (P<0.05): higher body mass, length, bone mineral content, bone area and concentrations of osteoprotegerin, osteocalcin and high-density lipoprotein cholesterol; higher levels of stearic, α-linolenic, eicosapentaenoic and docosapentaenoic acids and lower levels of arachidonic acid and cholesterol; smaller adipocyte area; and higher mass, epiphysis distance, diaphysis width, maximal load, break load, resilience and stiffness of femur. Flaxseed flour intake during lactation period promoted adipocyte hypertrophy down-regulation and contributed to pup bone quality at weaning.

  19. Effects of in utero and lactational exposure to SbV on rat neurobehavioral development and fertility.

    PubMed

    Coelho, Deise R; De-Carvalho, Rosangela R; Rocha, Rafael C C; Saint'Pierre, Tatiana D; Paumgartten, Francisco J R

    2014-12-01

    Meglumine antimoniate (MA) is a pentavalent antimony drug used to treat leishmaniases. We investigated the neurobehavioral development, sexual maturation and fertility of the offspring of MA-treated rats. Dams were administered MA (0, 75, 150, 300 mg Sb(V)/kg body wt/d, sc) from gestation day 0, throughout parturition and lactation, until weaning. At the highest dose, MA reduced the birth weight and the number of viable newborns. In the male offspring, MA did not impair development (somatic, reflex maturation, weight gain, puberty onset, open field test), sperm count, or reproductive performance. Except for a minor effect on body weight gain and vertical exploration in the open field, MA also did not affect the development of female offspring. Measurements of the Sb levels (ICP-MS) in the blood of MA-treated female rats and their offspring demonstrated that Sb is transferred to the fetuses via the placenta and to the suckling pups via milk.

  20. Altered lipid metabolism in rat offspring of dams fed a low-protein diet containing soy protein isolate.

    PubMed

    Yoon, Mi; Won, Sae Bom; Kwon, Young Hye

    2017-04-01

    Substantial studies have reported that maternal protein restriction may induce later development of cardiovascular disease in offspring by impairing antioxidant system and lipid metabolism. Because a unique amino acid composition of soy protein isolate has been shown to provide health benefits, including hypolipidemic effects, we investigated effects of maternal low-protein diet composed of low-isoflavone soy protein isolate (SPI) on oxidative stress and lipid metabolism in offspring. Sprague-Dawley dams were fed 20% or 10% SPI diet throughout pregnancy and lactation. On postnatal day 21, male offspring and their dams were studied. Maternal consumption of low-protein diet composed of SPI did not induce hepatic oxidative stress in offspring. Although serum triacylglycerol and cholesterol levels in dams were not different between groups, serum triacylglycerol levels were lower in offspring of dams fed a 10% SPI diet (10% SPI group) compared to offspring of dams fed a 20% SPI diet (20% SPI group). Maternal protein restriction also reduced serum HDL/total cholesterol levels. The mRNA levels of apolipoprotein A1, which is required for HDL formation, were lower in 10% SPI group compared to 20% SPI group and were positively correlated with serum HDL-cholesterol levels. Although maternal consumption of low-protein diet containing SPI did not induce oxidative stress and hypertriglyceridemia, the present study indicates that it may disturb cholesterol metabolism of rat offspring on postnatal day 21. Further studies are warranted to investigate the effect of maternal diet composed of soy protein isolate on later development of cardiovascular disease in offspring. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Fish-oil high-fat diet intake of dams after day 5 of pregnancy and during lactation guards against excessive fat consumption of their weaning pups.

    PubMed

    Nakashima, Yoko

    2008-02-01

    To investigate the influence of parental fat intake on preferential fat intake by pups after weaning, two groups of dams in study 1 were fed either a low-fat diet (LFD) or a lard high-fat diet (HFD) and those in study 2 were fed either a LFD or a fish-oil HFD after day 5 of pregnancy and during lactation. In study 1, when pups were placed on a self-selection regimen of the LFD and the lard HFD within the first week after weaning, the ratio of the lard HFD intake [lard HFD intake (g)/total intake (g)] by pups of both groups was about 70%. Although pups nursed by dams fed the lard HFD continued to eat the same ratio of the lard HFD, the ratio for pups nursed by dams fed the LFD gradually decreased to 20% in week 3 after weaning. In study 2, when pups were placed on a self-selection regimen of the LFD and the fish-oil HFD after weaning, the ratio of the fish-oil HFD intake in both groups of pups nursed by dams fed the LFD and the fish-oil HFD was about 20% for 3 wk after weaning. In studies 1 and 2, although no significant difference in dietary intake or body weight of dams and pups was observed among all groups through the experimental period, perirenal fat tissue weight of dams fed the lard HFD was higher than that of dams fed the LFD. These findings indicate that (1) fat preference of weaning pups nursed by dams fed the lard HFD is higher than that of weaning pups nursed by dams fed the LFD, and (2) intake of dam's fish-oil HFD diet guards against pups' intake of excessive fat.

  2. Effects of ethanol and folic acid consumption during pregnancy and lactation on basal enzymatic secretion in the duodenal juice of offspring rats.

    PubMed

    Cano, Ma José; Murillo, Ma Luisa; Delgado, Ma José; Carreras, Olimpia

    2003-09-01

    Studies on duodenal juice enzyme activities were carried out on suckling Wistar rats born to dams given ethanol during gestation and suckling. The results were compared with offspring of dams given diets containing no ethanol. Comparisons were also made with offspring of dams given ethanol and folic acid supplementation to observe whether a folate supplement could sufficiently reverse the negative effect of ethanol consumption. The dams were fed increased amounts of ethanol (5% to 20%, vol/vol) in tap water for 4 wk. The maximum quantity, 20% ethanol, was given to the dams during pregnancy and lactation. Offspring animals were randomized into three groups: control (CG), ethanol treated (EG), and ethanol plus folic acid (EFG). Body weight at birth and at 21 d after birth and pancreatic weight were lower in offspring after ethanol treatment. Folic acid supplement increased these parameters in the EFG. Under basal conditions, decreases in amylase, lipase, and chymotrypsin activities in the duodenal juice after ethanol treatment were detected. Serum and urine amylase activities also decreased in the EG and EFG. These changes were different in the ethanol-treated progenitors. In these progenitors, ethanol treatment increased serum amylase levels. In the offspring, amylase activities in the EFG decreased with respect to the CG; however, an increase in the EG was observed. In dams the folic acid supplement did not significantly alter the serum amylase activities. Lipase and chymotrypsin activities in the EFG were similar to those in the EG. An increase of serum and urine amylase in the EFG with respect to the EG was found. Our findings indicated that, under basal conditions, ethanol treatment during gestation and lactation negatively affects the digestive function in offspring. The effects of ethanol were slightly attenuated in rats supplemented with folic acid for amylase activities. Although extrapolation from animal studies can be tenuous, the present findings may

  3. Effects of indirect exposure of mice pups to endosulfan via their dams during gestation and lactation periods and the ameliorative effect of vitamin E.

    PubMed

    Mansour, S A; Mohamed, D A; Gamet-Payrastre, L

    2014-09-01

    During gestation and lactation, the experimental mice dams received one of the following treatments: (a) diet free of pesticide; (b) diet enriched with endosulfan (END); 30.0 µg kg(-1); (c) diet free of pesticide + oral vitamin E (α-tocopherol; 200 mg kg(-1) per mouse); and (d) diet enriched with END (30.0 µg kg(-1)) + oral vitamin E (200 mg kg(-1) per mouse). At weaning, pups and dams were killed, and selected organs as well as blood samples were collected for analyses. Compared with the control results, END induced alteration in a number of biochemical and histopathological parameters either in the dams or their offspring. The ameliorative effect of vitamin E to superoxide dismutase based on the "ameliorative index (AI)" for mothers and pups was 0.84 and 0.72, respectively. The AI for malondialdehyde reached a maximum value of nearly equal to 1.0 for dams or pups. For butyryl cholinesterase, the AI was 0.90 and 0.94 for dams and pups, respectively. In conclusion, a dietary exposure during gestation and lactation to low dose of END caused significant changes in the mother but also in the weaned animals that had not been directly exposed to this pesticide. These biological and histological alterations could be reversed to a great extent by oral supplementation of vitamin E.

  4. Hypercholesterolemic diet applied to rat dams protects their offspring against cognitive deficits. Simulated neonatal anoxia model.

    PubMed

    Bohr, Iwo

    2004-09-30

    There is accumulating data suggesting a neuroprotective activity of cholesterol, especially in stroke and Alzheimer's disease (AD). In the present study, a protective activity of this lipid in simulated neonatal anoxia was investigated. Rats were subjected to high cholesterol by feeding their dams with a diet enriched with cholesterol. Half of these rats were subjected to anoxia. One and a half months later, the rats were tested for their ability to acquire a spatial memory, one group on the linear maze and the other on the Morris water maze. After these assessments, the level of total plasma cholesterol was measured. Rats from dams subjected to neonatal anoxia on standard diet performed worse than control rats in both types of behavioral experiments, whereas anoxic rats from dams were housed on hypercholesterolemic diet performed as control animals. It suggests that dietetic cholesterol applied by their dams protected rats against cognitive deficits elicited by neonatal anoxia. Furthermore, offspring of anoxic rats housed on standard diet had elevated levels of blood cholesterol in relation to control animals. Generally, anoxia affected the concentration of this lipid much stronger than hypercholesterolemic diet of their dams. It might mean that the anoxia-related rise of cholesterol could be involved in physiological phenomenon being an adaptive response to neurotoxic processes. This concept is discussed in relation to pathological mechanisms in AD. Copyright 2004 Elsevier Inc.

  5. THE CONSUMPTION OF RED PUPUNHA (BACTRIS GASIPAES KUNTH) INCREASES HDL CHOLESTEROL AND REDUCES WEIGHT GAIN OF LACTATING AND POST-LACTATING WISTAR RATS

    PubMed Central

    Carvalho, R. Piccolotto; Lemos, J.R. Gonzaga; de Aquino Sales, R. Souza; Martins, M. Gassen; Nascimento, C.H.; Bayona, M.; Marcon, J.L.; Monteiro, J. Barros

    2014-01-01

    Introduction The lactating and post-lactating periods are marked by large metabolic change. Production of milk is 60% lipid dependent. We reported in a recent scientific meeting that Red pupunha palm tree fruit increases HDL cholesterol in lactating rats. This study evaluated if consumption of Red Pupunha by adult female rats has a beneficial impact on the lipid metabolism of lacting and post-lacting adult rats. Objective Evaluate if consumption of red pupunha has a beneficial effect in the lipid metabolism of lacting and post-lacting adult Wistar rats. Research Methods Four groups including two for control; (1) control adult lactating rats, (2) control adults post-lactating rats; and two experimental groups; (3) pupunha adults lactating rats and (4) pupunha adult post-lactating rats were evaluated and compared regarding: weight gain, food consumption, plasma total protein, glucose, total lipid, triglycerides, total cholesterol and HDL-cholesterol levels. The mean difference and its 95% confidence intervals were used for group comparisons. Group comparisons were evaluated by using analysis of variance (one-way ANOVA). The statistical significance of the pairwise differences among groups was assessed by using the two-sided Tukey test. Results There were no important differences in food consumption, plasma glucose, total lipids and triglycerides among groups. The red pupunha lactating group gain less weight showing lower body mass index (BMI) than controls (p < 0.05). Total cholesterol was lower in red pupunha lactating than in controls but not in the red pupunha post-lactating group as compared to controls. Triglycerides were lower in the post-lactating red pupunha group as compared to the control group (p = 0.039) but not for the lactating groups. Red pupunha lactating and post-lactating groups had higher HDL-cholesterol than their corresponding control groups (p ≤ 0.01). Conclusion Original findings include the beneficial effect of red pupunha in post-lactating

  6. Simulation of the pentose cycle in lactating rat mammary gland

    PubMed Central

    Haut, Michael J.; London, Jack W.; Garfinkel, David

    1974-01-01

    A computer model representing the pentose cycle, the tricarboxylic acid cycle and glycolysis in slices of lactating rat mammary glands has been constructed. This model is based primarily on the studies, with radioactive chemicals, of Abraham & Chaikoff (1959) [although some of the discrepant data of Katz & Wals (1972) could be accommodated by changing one enzyme activity]. Data obtained by using [1-14C]-, [6-14C]- and [3,4-14C]-glucose were simulated, as well as data obtained by using unlabelled glucose (for which some new experimental data are presented). Much past work on the pentose cycle has been mainly concerned with the division of glucose flow between the pentose cycle and glycolysis, and has relied on the assumption that the system is in steady state (both labelled and unlabelled). This assumption may not apply to lactating rat mammary glands, since the model shows that the percentage flow through the shunt progressively decreased for the first 2h of a 3h experiment, and we were unable to construct a completely steady-state model. The model allows examination of many quantitative features of the system, especially the amount of material passing through key enzymes, some of which appear to be regulated by NADP+ concentrations as proposed by McLean (1960). Supplementary information for this paper has been deposited as Supplementary Publication SUP 50023 at the British Museum (Lending Division) (formerly the National Lending Library for Science and Technology), Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1973) 131, 5. PMID:4154746

  7. Effect of insulin on in vivo glucose utilization in individual tissues of anesthetized lactating rats

    SciTech Connect

    Burnol, A.F.; Ferre, P.; Leturque, A.; Girard, J.

    1987-02-01

    Glucose utilization rate has been measured in skeletal muscles, white adipose tissue, and mammary gland of anesthetized nonlactating and lactating rats. During lactation, basal (1-TH) glucose utilization is decreased by 40% in periovarian white adipose tissue and by 65% in epitrochlearis and extensor digitorum longus but not in soleus muscle. This may be related to the lower blood glucose and plasma insulin concentrations observed during lactation. Basal glucose utilization rate in the mammary gland was, respectively, 18 +/- 2 and 350 +/- 50 g/min in nonlactating and lactating rats. During the euglycemic hyperinsulinemic clamp, a physiological increment in plasma insulin concentration induces a similar increase in glucose utilization rate in skeletal muscles and white adipose tissue in the two groups of rats. Furthermore this low increase in plasma insulin concentration does not alter mammary glucose utilization rate in nonlactating rats but induces the same increase as a maximal insulin concentration in lactating rats. These data show that the active mammary gland is the most insulin-sensitive tissue of the lactating rat that has been tested. The overall increase in insulin sensitivity and responsiveness that has been described in lactating rats can then mainly be attributed to the presence of the active mammary gland. Plasma insulin was determined by radioimmunoassay.

  8. Lactation

    PubMed Central

    1989-01-01

    Lactation is the most energy-efficient way to provide for the dietary needs of young mammals, their mother's milk being actively protective, immunomodulatory, and ideal for their needs. Intrauterine mammary gland development in the human female is already apparent by the end of the sixth week of gestation. During puberty and adolescence secretions of the anterior pituitary stimulate the maturation of the graafian follicles in the ovaries and stimulate the secretion of follicular estrogens, which stimulate development of the mammary ducts. Pregnancy has the most dramatic effect on the breast, but development of the glandular breast tissue and deposition of fat and connective tissue continue under the influence of cyclic sex-hormone stimulation. Many changes occur in the nipple and breast during pregnancy and at delivery as a prelude to lactation. Preparation of the breasts is so effective that lactation could commence even if pregnancy were discontinued at 16 weeks. Following birth, placental inhibition of milk synthesis is removed, and a woman's progesterone blood levels decline rapidly. The breasts fill with milk, which is a high-density, low-volume feed called colostrum until about 30 hours after birth. Because it is not the level of maternal hormones, but the efficiency of infant suckling and/or milk removal that governs the volume of milk produced in each breast, mothers who permit their infants to feed ad libitum commonly observe that they have large volumes of milk 24-48 hours after birth. The two maternal reflexes involved in lactation are the milk-production and milk-ejection reflex. A number of complementary reflexes are involved when the infant feeds: the rooting reflex (which programmes the infant to search for the nipple), the sucking reflex (rhythmic jaw action creating negative pressure and a peristaltic action of the tongue), and the swallowing reflex. The infant's instinctive actions need to be consolidated into learned behaviour in the postpartum

  9. Different effects by sex on hypothalamic-pituitary axis of prepubertal offspring rats produced by in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP).

    PubMed

    Carbone, S; Samaniego, Y A; Cutrera, R; Reynoso, R; Cardoso, N; Scacchi, P; Moguilevsky, J A; Ponzo, O J

    2012-01-01

    This study investigated the effect of pre and perinatal exposure to di-(2-ethylhexyl) phthalate (DEHP) on the neuroendocrine parameters that regulate reproduction in prepubertal male and female rats. DEHP at doses of 3 and 30mg/kgbw/day was administered orally in the drinking water to dam rats since pregnancy onset until the moment of pups sacrifice at 15 days of age. In these animals gonadotropin serum level and the hypothalamic contents of the amino acids aspartate, glutamate and gamma-aminobutyric acid were determined. No changes in gonadotropin levels and amino acid neurotransmitters were detected at the low dose in both sexes. However, DEHP administered at high dose (30mg/kgbw/day) to dams produced a significant decrease in the inhibitory neurotransmitter GABA and an increase in the stimulatory neurotransmitter aspartate in prepubertal male offspring rats. These modifications were accompanied by gonadotropin serum levels increase. On the contrary, in treated female rats this chemical increased both, aspartate and GABA, which exert a characteristic stimulatory action on gonadotropin in 15-day-old normal females. This study provides new data about changes produced by DEHP on the hypothalamic amino acid neurotransmitters involved in the neuroendocrine reproductive regulation, in prepubertal male and female rat offspring from dams exposed during gestational and lactational periods. These alterations induced by DEHP exposure could be related to the gonadotropin modifications also described in this work, and with changes in the production of sexual hormones previously reported by other authors. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. The effects of changes in nutritional demand on gastrointestinal parasitism in lactating rats.

    PubMed

    Normanton, Heidi; Houdijk, Jos G M; Jessop, Neil S; Knox, Dave P; Kyriazakis, Ilias

    2007-01-01

    Lactating rats experience a breakdown of immunity to parasites, i.e. they carry larger worm burdens after re-infection compared to their non-lactating counterparts. Feeding high-protein foods to lactating rats results in reduced worm burdens. This could be attributed to changes in gastrointestinal environment or to overcoming effects of nutrient scarcity on host immunity. The latter hypothesis was addressed through a manipulation of nutrient demand by manipulating litter size. Twenty-three rats were immunized prior to mating and re-infected on day 2 of lactation with 1600 infective Nippostrongylus brasiliensis larvae. From parturition onwards, rats received ad libitum low-protein food (100 g crude protein/kg). Litter size were standardised to nine (LS9), six (LS6) or three (LS3) pups, by day 2 of lactation. After a further 10 d, LS9 and LS6 rats carried more worms than LS3 rats. However, feeding treatment did not affect concentrations of mucosal inflammatory cells. Achieved feed intake did not differ consistently between the treatment groups. However, LS9 and LS6 rats lost weight, whilst LS3 rats gained weight during lactation. The results support the view that resistance to N. brasiliensis is sensitive to changes in nutrient demand, and the improved resistance to N. brasiliensis is likely due to effects of overcoming nutrient scarcity on host immunity.

  11. Acute mercury exposition of virgin, pregnant, and lactating rats: Histopathological kidney and liver evaluations.

    PubMed

    Oliveira, Vitor Antunes; Favero, Gaia; Stacchiotti, Alessandra; Giugno, Lorena; Buffoli, Barbara; de Oliveira, Claudia Sirlene; Lavazza, Antonio; Albanese, Massimo; Rodella, Luigi Fabrizio; Pereira, Maria Ester; Rezzani, Rita

    2017-05-01

    This work investigated the effects of mercury chloride (HgCl2 ) acute exposure on virgin, pregnant and lactating rats by determination of renal and hepatic morphological and ultrastructural parameters and the expression of oxidative stress and stress tolerance markers, due to kidney and liver are the organs that more accumulate inorganic mercury. Adult Wistar rats virgin (90 days old), pregnant (18(th) gestation day) and lactating (7(th) lactation day) were injected once with HgCl2 (5 mg/kg) or saline (controls). We observed that HgCl2 exposure of virgin rats caused significant inflammatory infiltration and severe morphological variations, like glomeruli atrophy, dilatation of Bowman's capsule, tubular degeneration and hepatocytes alteration. Moreover, virgin rats presented mitochondrial modification, important oxidative stress and increase in stress tolerance proteins at both kidney and liver level, compared with virgin controls. In detail, virgin rats exposed to HgCl2 presented significantly elevated level of inducible nitric oxide synthase, heat shock protein 27 and glucose regulated proteins 75 expressions at both renal tubular and hepatocytes level, respect untreated virgin rats. Interestingly, pregnant and lactating rats exposed to HgCl2 presented weak renal and liver morphological alterations, showing weak inflammatory infiltration and no significant difference in structural mitochondrial transmembrane protein, oxidative stress markers and stress tolerance proteins expressions respect controls (virgin, pregnant and lactating rats). Although, both control and HgCl2 -exposed pregnant and lactating rats showed renal glomeruli greater in diameter respect virgin rats. In conclusion, we believe that virgin rats are more sensitive to HgCl2 toxicity respect pregnant and lactating rats. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1500-1512, 2017. © 2016 Wiley Periodicals, Inc.

  12. ABCG5/ABCG8-independent biliary cholesterol excretion in lactating rats

    PubMed Central

    Coy, Donna J.; Wooton-Kee, Clavia R.; Yan, Baoxiang; Sabeva, Nadezhda; Su, Kai; Graf, Gregory

    2010-01-01

    Lactation is associated with increased expression of bile acid transporters and an increased size and hydrophobicity of the bile acid pool in rats. ATP-binding cassette (ABC) transporters multidrug resistance protein 2 (Mdr2), Abcb11 [bile salt export pump (Bsep)], and Abcg5/Abcg8 heterodimers are essential for the biliary secretion of phospholipids, bile acids, and cholesterol, respectively. We investigated the expression of these transporters and secretion of their substrates in female control and lactating Sprague Dawley rats and C57BL/6 mice. Expression of Abcg5/Abcg8 mRNA was decreased by 97 and 60% by midlactation in rats and mice, respectively; protein levels of Abcg8 were below detection limits in lactating rats. Mdr2 mRNA expression was decreased in lactating rats and mice by 47 and 59%, respectively. Despite these changes in transporter expression, basal concentrations of cholesterol and phospholipid in bile were unchanged in rats and mice, whereas increased Bsep mRNA expression in early lactation coincided with an increased basal biliary bile acid concentration in lactating mice. Following taurocholate infusion, coupling of phospholipid and taurocholate secretion in bile of lactating mice was significantly impaired relative to control mice, with no significant changes in maximal secretion of cholesterol or bile acids. In rats, taurocholate infusion revealed a significantly impaired coupling of cholesterol to taurocholate secretion in bile in lactating vs. control animals. These data reveal marked utilization of an Abcg5/Abcg8-independent mechanism for basal biliary cholesterol secretion in rats during lactation, but a dependence on Abcg5/g8 for maximal biliary cholesterol secretion. PMID:20413720

  13. Perfluorooctanoate: Placental and lactational transport pharmacokinetics in rats.

    SciTech Connect

    Hinderliter, Paul M.; Mylchreest, E.; Gannon, S. A.; Butenhoff, J. L.; Kennedy, G.L., Jr.

    2005-07-01

    This study was conducted to develop a quantitative understanding of the potential for gestational and lactational transfer of perfluorooctanoate (PFOA) in the rat. Time-mated female rats were dosed by oral gavage once daily at concentrations of 3, 10, or 30 mg/kg/day of the ammonium salt of PFOA (APFO) starting on gestation (G) day 4 and continuing until sacrifice. On days 10, 15, and 21G, five rats per dose level were sacrificed and blood samples were collected 2h post-dose. Embryos were collected on day 10G, amniotic fluid, placentas, and embryos/fetuses were collected on days 15 and 21G, and fetal blood samples were collected on day 21G. Five rats per dose level were allowed to deliver and nurse their litters, and on days 3, 7, 14, and 21 post-partum (PP) milk and blood samples of maternal and pup were collected 2h post-dose. All samples were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) for PFOA concentration. Concentrations of PFOA in maternal plasma and milk attained steady state during the sampling interval. The steady-state concentrations in maternal plasma were 10-15, 25-30, and 60-75 microg/mL in rats receiving 3, 10, and 30 mg/kg, respectively. Steady-state concentrations in milk were approximately 10 times less than those in maternal plasma. The concentration of PFOA in fetal plasma on day 21G was approximately half the steady-state concentration in maternal plasma. The milk concentrations appeared to be generally comparable to the concentrations in pup plasma. Pup plasma concentrations decreased from day 3PP to day 7PP, and were similar on days 7, 14, and 21PP at all dose levels. PFOA was detected in placenta (days 15 and 21G), amniotic fluid (days 15 and 21G), embryo (days 10 and 15G), and fetus (day 21G). These pharmacokinetics allow estimation of the dose to developing and nursing rat offspring following maternal exposure.

  14. Microbial manipulation of the rat dam changes bacterial colonization and alters properties of the gut in her offspring.

    PubMed

    Fåk, Frida; Ahrné, Siv; Molin, Göran; Jeppsson, Bengt; Weström, Björn

    2008-01-01

    The impact of an altered bacterial colonization on gut development has not been thoroughly studied, despite the increased risk of certain diseases with a disturbed microbiota after birth. This study was conducted to determine the effect of microbial manipulation, i.e., antibiotic treatment or Escherichia coli exposure, of the dam on bacterial colonization and gut development in the offspring. Pregnant rats were administered either broad-spectrum antibiotics 3 days before parturition or live nonpathogenic E. coli Culture Collection of University of Göteborg, Sweden type strain (CCUG 29300(T)) 1 wk before parturition and up to 14 days of lactation in the drinking water. Cecal bacterial levels, gut growth, intestinal permeability, digestive enzyme levels, and intestinal inflammation were studied in 2-wk-old rats. Pups from dams that were antibiotic-treated had higher densities of Enterobacteriaceae, which correlated with a decreased stomach growth and function, lower pancreatic protein levels, higher intestinal permeability, and increased plasma levels of the acute phase protein, haptoglobin, compared with pups from untreated mothers. Exposure of pregnant/lactating mothers to E. coli CCUG 29300(T), also resulting in increased Enterobacteriaceae levels, gave in the offspring similar results on the stomach and an increased small intestinal growth compared with the control pups. Furthermore, E. coli pups showed increased mucosal disaccharidase activities, increased liver, spleen, and adrenal weights, as well as increased plasma concentrations of haptoglobin. These findings indicate that disturbing the normal bacterial colonization after birth, by increasing the densities of cecal Enterobacteriaceae, appears to have lasting effects on the postnatal microflora, which affects gut growth and function.

  15. The distribution of atrazine (ATR) and ATR metabolites in the Wistar rat following gestational/lactational exposures

    EPA Science Inventory

    Gestational/lactational exposure to ATR is reported to alter reproductive/developmental function, yet our understanding of the transfer of ATR and/or its metabolites from the dam to the fetus/offspring is limited. Previously we examined the lactational transfer of CI4-ATR, but sp...

  16. The distribution of atrazine (ATR) and ATR metabolites in the Wistar rat following gestational/lactational exposures

    EPA Science Inventory

    Gestational/lactational exposure to ATR is reported to alter reproductive/developmental function, yet our understanding of the transfer of ATR and/or its metabolites from the dam to the fetus/offspring is limited. Previously we examined the lactational transfer of CI4-ATR, but sp...

  17. Gluconeogenesis, glucose handling, and structural changes in livers of the adult offspring of rats partially deprived of protein during pregnancy and lactation.

    PubMed Central

    Burns, S P; Desai, M; Cohen, R D; Hales, C N; Iles, R A; Germain, J P; Going, T C; Bailey, R A

    1997-01-01

    Maternal protein restriction is a model of fetal programming of adult glucose intolerance. Perfused livers of 48-h- starved adult offspring of rat dams fed 8% protein diets during pregnancy and lactation produced more glucose from 6 mM lactate than did control livers from rats whose dams were fed 20% protein. In control livers, a mean of 24% of the glucose formed from lactate in the periportal region of the lobule was taken up by the most distal perivenous cells; this distal perivenous uptake was greatly diminished in maternal low protein (MLP) livers, accounting for a major fraction of the increased glucose output of MLP livers. In control livers, the distal perivenous cells contained 40% of the total glucokinase of the liver; this perivenous concentration of glucokinase was greatly reduced in MLP livers. Intralobular distribution of phosphenolpyruvate carboxykinase was unaltered, though overall increased activity could have contributed to the elevated glucose output. Hepatic lobular volume in MLP livers was twice that in control livers, indicating that MLP livers had half the normal number of lobules. Fetal programming of adult glucose metabolism may operate partly through structural alterations and changes in glucokinase expression in the immediate perivenous region. PMID:9312176

  18. Developmental iodine deficiency resulting in hypothyroidism reduces hippocampal ERK1/2 and CREB in lactational and adolescent rats

    PubMed Central

    2009-01-01

    Background Developmental iodine deficiency (ID) leads to inadequate thyroid hormone that impairs learning and memory with an unclear mechanism. Here, we show that hippocampal extracellular signal-regulated kinase (ERK1/2) and cAMP response element-binding protein (CREB) are implicated in the impaired learning and memory in lactational and adolescent rat hippocampus following developmental ID and hypothyroidism. Methods Three developmental rat models were created by administrating dam rats with either iodine-deficient diet or propylthiouracil (PTU, 5 ppm or 15 ppm)-added drinking water from gestational day (GD) 6 till postnatal day (PN) 28. Then, the total and phorsporylated ERK1/2 and total and phorsporylated CREB in the hippocampus were detected with western blot on PN14, PN21, PN28 and PN42. Results The iodine-deficient and hypothyroid pups showed lower serum FT3 and FT4 levels, smaller body size, and delayed eyes opening. The mean number of surviving cells in the hippocampus of the iodine-deficient and 15 ppm PTU-treated rats was significantly reduced compared to controls (P < 0.05). Iodine-deficient and 15 ppm PTU-treatment groups demonstrated significantly lower level of total and phosphorylated ERK1/2 and CREB than the controls on PN14, PN21 and PN28 (P < 0.05, respectively). The reduction of ERK1/2 and CREB was not reversible with the restoration of serum thyroid hormone concentrations on PN42. Conclusions Developmental ID and hypothyroidism down-regulate hippocampal ERK1/2 and CREB in lactational and adolescent rats. PMID:20021662

  19. Developmental iodine deficiency resulting in hypothyroidism reduces hippocampal ERK1/2 and CREB in lactational and adolescent rats.

    PubMed

    Dong, Jing; Liu, Wanyang; Wang, Yi; Hou, Yi; Xi, Qi; Chen, Jie

    2009-12-18

    Developmental iodine deficiency (ID) leads to inadequate thyroid hormone that impairs learning and memory with an unclear mechanism. Here, we show that hippocampal extracellular signal-regulated kinase (ERK1/2) and cAMP response element-binding protein (CREB) are implicated in the impaired learning and memory in lactational and adolescent rat hippocampus following developmental ID and hypothyroidism. Three developmental rat models were created by administrating dam rats with either iodine-deficient diet or propylthiouracil (PTU, 5 ppm or 15 ppm)-added drinking water from gestational day (GD) 6 till postnatal day (PN) 28. Then, the total and phorsporylated ERK1/2 and total and phorsporylated CREB in the hippocampus were detected with western blot on PN14, PN21, PN28 and PN42. The iodine-deficient and hypothyroid pups showed lower serum FT3 and FT4 levels, smaller body size, and delayed eyes opening. The mean number of surviving cells in the hippocampus of the iodine-deficient and 15 ppm PTU-treated rats was significantly reduced compared to controls (P < 0.05). Iodine-deficient and 15 ppm PTU-treatment groups demonstrated significantly lower level of total and phosphorylated ERK1/2 and CREB than the controls on PN14, PN21 and PN28 (P < 0.05, respectively). The reduction of ERK1/2 and CREB was not reversible with the restoration of serum thyroid hormone concentrations on PN42. Developmental ID and hypothyroidism down-regulate hippocampal ERK1/2 and CREB in lactational and adolescent rats.

  20. Maternal methyl donors supplementation during lactation prevents the hyperhomocysteinemia induced by a high-fat-sucrose intake by dams.

    PubMed

    Cordero, Paul; Milagro, Fermin I; Campion, Javier; Martinez, J Alfredo

    2013-12-16

    Maternal perinatal nutrition may program offspring metabolic features. Epigenetic regulation is one of the candidate mechanisms that may be affected by maternal dietary methyl donors intake as potential controllers of plasma homocysteine levels. Thirty-two Wistar pregnant rats were randomly assigned into four dietary groups during lactation: control, control supplemented with methyl donors, high-fat-sucrose and high-fat-sucrose supplemented with methyl donors. Physiological outcomes in the offspring were measured, including hepatic mRNA expression and global DNA methylation after weaning. The newborns whose mothers were fed the obesogenic diet were heavier longer and with a higher adiposity and intrahepatic fat content. Interestingly, increased levels of plasma homocysteine induced by the maternal high-fat-sucrose dietary intake were prevented in both sexes by maternal methyl donors supplementation. Total hepatic DNA methylation decreased in females due to maternal methyl donors administration, while Dnmt3a hepatic mRNA levels decreased accompanying the high-fat-sucrose consumption. Furthermore, a negative association between Dnmt3a liver mRNA levels and plasma homocysteine concentrations was found. Maternal high-fat-sucrose diet during lactation could program offspring obesity features, while methyl donors supplementation prevented the onset of high hyperhomocysteinemia. Maternal dietary intake also affected hepatic DNA methylation metabolism, which could be linked with the regulation of the methionine-homocysteine cycle.

  1. Maternal Methyl Donors Supplementation during Lactation Prevents the Hyperhomocysteinemia Induced by a High-Fat-Sucrose Intake by Dams

    PubMed Central

    Cordero, Paul; Milagro, Fermin I.; Campion, Javier; Martinez, J. Alfredo

    2013-01-01

    Maternal perinatal nutrition may program offspring metabolic features. Epigenetic regulation is one of the candidate mechanisms that may be affected by maternal dietary methyl donors intake as potential controllers of plasma homocysteine levels. Thirty-two Wistar pregnant rats were randomly assigned into four dietary groups during lactation: control, control supplemented with methyl donors, high-fat-sucrose and high-fat-sucrose supplemented with methyl donors. Physiological outcomes in the offspring were measured, including hepatic mRNA expression and global DNA methylation after weaning. The newborns whose mothers were fed the obesogenic diet were heavier longer and with a higher adiposity and intrahepatic fat content. Interestingly, increased levels of plasma homocysteine induced by the maternal high-fat-sucrose dietary intake were prevented in both sexes by maternal methyl donors supplementation. Total hepatic DNA methylation decreased in females due to maternal methyl donors administration, while Dnmt3a hepatic mRNA levels decreased accompanying the high-fat-sucrose consumption. Furthermore, a negative association between Dnmt3a liver mRNA levels and plasma homocysteine concentrations was found. Maternal high-fat-sucrose diet during lactation could program offspring obesity features, while methyl donors supplementation prevented the onset of high hyperhomocysteinemia. Maternal dietary intake also affected hepatic DNA methylation metabolism, which could be linked with the regulation of the methionine-homocysteine cycle. PMID:24351826

  2. Monosaccharide transport into lactating-rat mammary acini.

    PubMed Central

    Threadgold, L C; Coore, H G; Kuhn, N J

    1982-01-01

    The uptake and release of 3-O-methyl-D-[3H]glucose at 37 degrees C by acini, prepared from lactating-rat mammary gland with collagenase, was inhibited by glucose, phloretin, cytochalasin B, HgCl2 and low temperature. Uptake and phosphorylation of 2-deoxy-D-[3H]glucose, studied in greater detail, could be ascribed to a specific, saturable, inhibitable, process of apparent Km 16 mM and Vmax. approx. 56 nmol/min per mg of protein, plus a non-specific, non-inhibitable process that was monitored with [14C]fructose. The mean rate of uptake of 5 mM-2-deoxyglucose (16 nmol/min per mg of protein) was similar to the rate of consumption of 5 mM-glucose, suggesting that transport was a rate-limiting step in the overall metabolism of glucose. This accords with evidence for a glucose gradient across the plasma membrane. PMID:6214256

  3. Hormonal profile and reproductive performance in lactation deficient (OFA hr/hr) and normal (Sprague-Dawley) female rats.

    PubMed

    Valdez, Susana R; Penissi, Alicia B; Deis, Ricardo P; Jahn, Graciela A

    2007-04-01

    Lactation deficiency may have important consequences on infant health, particularly in populations of low socioeconomic status. The OFA hr/hr (OFA) strain of rats, derived from Sprague-Dawley (SD) rats, has deficient lactation and is a good model of lactation failure. We examined the reproductive performance and hormonal profiles in OFA and SD strains to determine the cause(s) of the lactation failure of the OFA strain. We measured hormonal (PRL, GH, gonadotropins, oxytocin, and progesterone) levels by RIA in cycling, pregnant, and lactating rats and in response to suckling. Dopaminergic metabolism was assessed by determination of mediobasal hypothalamic dopamine and dihydroxyphenylacetic acid (DOPAC) concentrations by HPLC and tyrosine hydroxylase expression by immunocytochemistry and western blot. OFA rats have normal fertility but 50% of the litters die of malnutrition on early lactation; only 6% of the mothers show normal lactation. The OFA rats showed lower circulating PRL during lactation, increased hypothalamic dopamine and DOPAC, and impaired milk ejection with decreased PRL and oxytocin response to suckling. Before parturition, PRL release and lactogenesis were normal, but dopaminergic metabolism was altered, suggesting activation of the dopaminergic system in OFA but not in SD rats. The number of arcuate and periventricular neurons expressing tyrosine hydroxylase was higher in SD rats, but hypothalamic expression of TH was higher in OFA rats at the end of pregnancy and early lactation. These results suggest that the OFA rats have impaired PRL release linked with an augmented dopaminergic tone which could be partially responsible for the lactational failure.

  4. Effect of inclusion or non-inclusion of short lactations and cow and/or dam genetic group on genetic evaluation of Girolando dairy cattle.

    PubMed

    Canaza-Cayo, A W; Silva, M V G B; Cobuci, J A; Martins, M F; Lopes, P S

    2016-04-04

    The objective of this study was to evaluate the effects of inclusion or non-inclusion of short lactations and cow (CGG) and/or dam (DGG) genetic group on the genetic evaluation of 305-day milk yield (MY305), age at first calving (AFC), and first calving interval (FCI) of Girolando cows. Covariance components were estimated by the restricted maximum likelihood method in an animal model of single trait analyses. The heritability estimates for MY305, AFC, and FCI ranged from 0.23 to 0.29, 0.40 to 0.44, and 0.13 to 0.14, respectively, when short lactations were not included, and from 0.23 to 0.28, 0.39 to 0.43, and 0.13 to 0.14, respectively, when short lactations were included. The inclusion of short lactations caused little variation in the variance components and heritability estimates of traits, but their non-inclusion resulted in the re-ranking of animals. Models with CGG or DGG fixed effects had higher heritability estimates for all traits compared with models that consider these two effects simultaneously. We recommend using the model with fixed effects of CGG and inclusion of short lactations for the genetic evaluation of Girolando cattle.

  5. Ameliorative effect of vitamin E to mouse dams and their pups following exposure of mothers to chlorpyrifos during gestation and lactation periods.

    PubMed

    Mansour, Sameeh Abdel-Kader; Gamet-Payrastre, Laurence

    2016-07-01

    Pesticides are omnipresent in environment, water, fruits, and vegetables and are considered as risk factors for human health. Consumers are mainly exposed to pesticides through diet, and the main question to be answered concerns the impact of such exposure on health. In this study, we developed a mouse model to mimic consumer exposure. During gestation and lactation periods, the experimental mouse dams (M) received one of the following treatments: (a) diet-free of pesticides; (b) diet enriched with chlorpyrifos (CPF; 44.0 μg kg(-1)); c) diet + oral vitamin E (vit. E; α-tocopherol; 200 mg/kg/mouse); and (d) diet enriched with CPF (44.0 μg/kg + oral vit. E (200 mg/kg/mouse). At weaning, pups (P) and dams were killed, and organs as well as blood samples were collected. Compared with control results, CPF induced alteration of measured parameters (e.g. organ weight, alkaline phosphatase, urea, malondialdehyde, superoxide dismutase, and cholinesterase) either in mouse dams or in their offspring. Also, CPF induced histological impairment in kidney, liver, and ovary. Administration of vit. E in conjunction with CPF clearly alleviated deviation of these parameters than those of control ones. In conclusion, a dietary exposure of mice during gestation and lactation to low dose of CPF led to significant changes in the mother but also in the weaned animals that have not been directly exposed to this pesticide. These biological and histological modifications could be reversed by an oral supplementation of vit. E.

  6. Consumption of sucrose, but not high fructose corn syrup, leads to increased adiposity and dyslipidaemia in the pregnant and lactating rat.

    PubMed

    Toop, C R; Muhlhausler, B S; O'Dea, K; Gentili, S

    2015-02-01

    Excess consumption of added sugars, including sucrose and high fructose corn syrup (HFCS-55), have been implicated in the global epidemics of obesity and type 2 diabetes. This study aimed to investigate and compare the impact of maternal consumption of sucrose or HFCS-55 during pregnancy and lactation on the metabolic health of the dam and her offspring at birth. Female Albino Wistar rats were given access to chow and water, in addition to a sucrose or HFCS-55 beverage (10% w/v) before, and during pregnancy and lactation. Maternal glucose tolerance was determined throughout the study, and a postmortem was conducted on dams following lactation, and on offspring within 24 h of birth. Sucrose and HFCS-55 consumption resulted in increased total energy intake compared with controls, however the increase from sucrose consumption was accompanied by a compensatory decrease in chow consumption. There was no effect of sucrose or HFCS-55 consumption on body weight, however sucrose consumption resulted in increased adiposity and elevated total plasma cholesterol in the dam, while HFCS-55 consumption resulted in increased plasma insulin and decreased plasma non-esterified fatty acids (NEFA). Maternal HFCS-55 consumption was associated with decreased relative liver weight and plasma NEFA in the offspring at birth. There was no effect of either treatment on pup weight at birth. These findings suggest that both sucrose and HFCS-55 consumption during pregnancy and lactation have the potential to impact negatively on maternal metabolic health, which may have adverse consequences for the long-term health of the offspring.

  7. Fluoxetine induces changes in the testicle and testosterone in adult male rats exposed via placenta and lactation.

    PubMed

    Monteiro Filho, Waldo Oliveira; de Torres, Sandra Maria; Amorim, Marleyne José Afonso Accioly Lins; Andrade, Anderson Joel Martino; de Morais, Rosana Nogueira; Tenorio, Bruno Mendes; da Silva Junior, Valdemiro Amaro

    2014-10-01

    Fluoxetine is a selective serotonin reuptake inhibitor used to treat depression in pregnant and nursing women. However, recent studies have shown adverse effects in the male reproductive system after fluoxetine treatment. Aiming to analyze the extent of damage caused by fluoxetine in the testicle and safe doses for treatment during the perinatal period, the present study analyzed the effects of in utero exposure and exposure during lactation to fluoxetine in spermatogenesis of male rat offspring in adulthood. Wistar rat dams were orally treated with fluoxetine (5, 10, and 20 mg/kg) from 13 days of gestation to lactation day 21 and their offspring were analyzed at 90 days old. Results showed a reduction in the weight of testes (16%), epididymis (28%), and seminal glands (18%) in animals exposed to fluoxetine 20 mg/kg compared to the control. Seminal gland weight was also reduced 25% and 30% in animals exposed to 5 mg/kg and 10 mg/kg fluoxetine, respectively. Body weight of animals exposed to 20 mg/kg fluoxetine was reduced from post-natal day 9 to 36 compared to controls but from the post-natal day 9 to 36 there was no statistical difference. The volume of seminiferous epithelium reduced 17% and the total volume of Leydig cells reduced 30% in the group exposed to fluoxetine at 20 mg/kg. Furthermore, Leydig cells volume reduced 29% in the 5 mg/kg group. The length of the seminiferous tubules reduced 17% and daily sperm production per testicle also reduced 18% in animals exposed to the highest dose of fluoxetine compared to controls. The individual area of Leydig cells increased 7% and plasma testosterone increased 49% in animals exposed to fluoxetine at 20 mg/kg. In conclusion, exposure to 20 mg/kg fluoxetine via the placenta and during lactation may change testosterone and testicular parameters important for sperm production and male fertility in adulthood.

  8. Developmental plasticity in adrenal function and leptin production primed by nicotine exposure during lactation: gender differences in rats.

    PubMed

    Pinheiro, C R; Oliveira, E; Trevenzoli, I H; Manhães, A C; Santos-Silva, A P; Younes-Rapozo, V; Claudio-Neto, S; Santana, A C; Nascimento-Saba, C C A; Moura, E G; Lisboa, P C

    2011-09-01

    Neonate male rats whose mothers were nicotine-treated during lactation have higher adiposity, hyperleptinemia, and adrenal dysfunction. At adulthood, they still present higher adiposity and hyperleptinemia, but there was no report about their adrenal function. Also, there was no report of this developmental plasticity on females. Here, we evaluated the adrenal function and leptin content in adipocytes and muscle of male and female adult offspring whose mothers were nicotine-treated during lactation. On the 2nd postnatal day (PN2), dams were subcutaneously implanted with osmotic minipumps releasing nicotine (NIC-6 mg/kg/day) or saline for 14 days (12 litters/group and 2 rats/litter). Male and female offspring were killed on PN180. Significant data were p<0.05. Male NIC offspring presented higher adrenal catecholamine content (+ 89%) and TH expression (+ 38%), lower "in vitro" catecholamine release (- 19%), and higher adrenergic β3 receptor (ADRB3, + 59%) content in visceral adipose tissue (VAT). Serum corticosterone was higher (+ 77%) in male NIC group, coherent with the increase of both CRH and ACTH immunostaining in hypothalamus and pituitary, respectively. Leptin content was higher in VAT (+ 23%), which may justify the observed hyperleptinemia. Female NIC offspring presented lower ADRB3 content in VAT (- 39%) and lower leptin content in subcutaneous adipose tissue (SAT) (- 46%), but higher leptin content in soleus muscle (+ 22%), although leptinemia was normal. We evidenced a sex dimorphism in the model of maternal nicotine exposure during lactation. The adrenal function in adult offspring was primed only in male offspring while the female offspring displayed relevant alterations in leptin content on muscle and adipocytes. Georg Thieme Verlag KG Stuttgart · New York.

  9. Maternal prolactin inhibition at the end of lactation affects learning/memory and anxiety-like behaviors but not novelty-seeking in adult rat progeny.

    PubMed

    Fraga, Mabel C; Moura, Egberto G; Silva, Juliana Oliveira; Bonomo, Isabela Teixeira; Filgueiras, Cláudio C; Abreu-Villaça, Yael; Passos, Magna C F; Lisboa, Patrícia C; Manhães, Alex C

    2011-11-01

    Maternal hypoprolactinemia at the end of lactation in rats reduces milk production and is associated with offspring's malnutrition. Since malnutrition during development is also known to have long lasting effects on cognition and emotion, in the present study we tested the hypothesis that maternal hypoprolactinemia, induced by bromocriptine treatment, at the end of the lactating period affects memory/learning, novelty-seeking and anxiety-like behaviors in adult male Wistar rats using, respectively, the radial arm water maze (RAWM), the hole board (HB) arena and the elevated plus-maze (EPM). We also analyzed serum corticosterone and thyroid hormone levels at postnatal day (PN) 21. Lactating dams were treated with bromocriptine (BRO, 1mg twice a day, inhibiting prolactin) or saline from PN19 to 21 (the last 3 days of lactation). BRO offspring had hypercorticosteronemia and hypothyroidism at PN21. In the RAWM, reductions in latency observed in CON rats were initially more accentuated than in BRO ones. By the end of the testing period, latencies became similar between groups. No difference was observed between groups regarding the number of nose-pokes in the HB. In the EPM, BRO rats stayed less time in and had fewer entries into the open-arms than CON ones. This pattern of results indicates that maternal bromocriptine treatment at the end of the lactating period results in poorer memory/learning performance and in higher levels of anxiety-like behavior in the adult offspring, demonstrating that even a relatively short period of malnutrition during development can have long lasting detrimental effects regarding cognition and emotion.

  10. The effect of exposure to hypergravity on pregnant rat dams, pregnancy outcome and early neonatal development

    NASA Astrophysics Data System (ADS)

    Ladd, B.; Nguon, K.; Sajdel-Sulkowska, E. M.

    2006-01-01

    We previously reported that hypergravity exposure affects food intake and mass gain during pregnancy. In the present study, we explored the hypothesis that changes in maternal body mass in hypergravity-exposed pregnant rat dams affect pregnancy outcome and early offspring development. Furthermore, we hypothesized that the changes observed at 1.5G will be magnified at higher gravity and by exposure during critical developmental periods. To test this hypothesis, we compared maternal body mass gain, food consumption, birth outcome and early offspring development between Sprague Dawley rat dams exposed to graded (1.5 1.75G) chronic hypergravity (HG) or rotation (rotational control, RC) on a 24-ft centrifuge for 22.5 h starting on gestational day (G) 10 with dams housed under identical conditions but not exposed to hypergravity (SC). We also compared maternal body mass, food consumption, birth outcome and early offspring development between rat dams exposed to 1.65G during different stages of pregnancy and nursing. Exposure to hypergravity resulted in transient loss in body mass and prolonged decrease in food consumption in HG dams, but the changes observed at 1.5G were not magnified at 1.65G or 1.75G. On the other hand RC dams gained more mass and consumed more food than SC dams. Exposure to hypergravity also affected pregnancy outcome as evidenced by decreased litter size, lowered neonatal mass at birth, and higher neonatal mortality; pregnancy outcome was not affected in RC dams. Neonatal changes evidenced by impaired righting response observed at 1.5G was magnified at higher gravity and was dependent on the period of hypergravity exposure. On the other hand, righting response was improved in RC neonates. Hypergravity exposure during early postpartum affected the food consumption of nursing mothers and affected early survival of their offspring. The changes observed in dams and neonates appear to be due to hypergravity exposure since animals exposed to the rotation

  11. Polybrominated diphenyl ether (PBDE)-induced alterations in vitamin A and thyroid hormone concentrations in the rat during lactation and early postnatal development

    SciTech Connect

    Ellis-Hutchings, Robert G.; Cherr, Gary N.; Hanna, Lynn A.; Keen, Carl L. . E-mail: clkeen@ucdavis.edu

    2006-09-01

    In experimental animals fed standard laboratory diets, penta-BDE mixtures can decrease circulating thyroid hormone and liver vitamin A concentrations. A substantial number of pregnant women and their children have marginal vitamin A status, potentially increasing their risk of adverse effects to penta-BDE exposure. The current study investigated the effects of maternal gestational and lactational penta-BDE exposure on thyroid hormone and vitamin A homeostasis in rats of sufficient vitamin A (VAS) or marginal vitamin A (VAM) status and their offspring. Dams were administered daily oral doses of 18 mg/kg DE-71 (a penta-BDE mixture) or a corn oil vehicle from gestation day 6 through lactation day (LD) 18. Thyroid hormone and vitamin A homeostasis were assessed in plasma and tissues of LD 19 dams and postnatal day (PND) 12, 18, and 31 pups. DE-71 exposure induced hepatomegaly in VAS and VAM pups at all timepoints and increased testes weights at PND 31. While liver vitamin A concentrations were low in DE-71 treated dams and pups, plasma retinol concentrations and plasma retinol binding protein levels were only low in VAM animals exposed to DE-71. DE-71 exposure lowered plasma thyroxine concentrations in VAS and VAM dams and pups. Plasma thyroid stimulating hormone concentrations were high in VAM dams exposed to DE-71, suggesting that marginal vitamin A status enhances the susceptibility to thyroid hormone axis disruption by DE-71. These results support the concept that marginal vitamin A status in pregnant women may increase the risk for PBDE-induced disruptions in vitamin A and thyroid hormone homeostasis.

  12. Interactive Effect of Corticosterone and Lactate on Regulation of Testosterone Production in Rat Leydig Cells.

    PubMed

    Chen, Chih-Chieh; Chen, Chien-Wei; Lin, Po-Han; Chou, Jou-Chun; Weng, Ting-Chun; Jian, Cai-Yun; Hu, Sindy; Lai, Wei-Ho; Lieu, Fu-Kong; Wang, Shyi-Wu; Wang, Paulus S

    2017-08-01

    The increasing intensity of exercise enhanced corticosterone and lactate production in both humans and rodents. Our previous studies also demonstrated that lactate could stimulate testosterone production in vivo and in vitro. However, the production of testosterone in response to combined corticosterone and lactate on Leydig cells, and underlying molecular mechanisms are remained unclear. This study investigated the changes in testosterone levels of Leydig cells upon exposure to lactate, corticosterone or combination of both, and revealed the detailed mechanisms. Leydig cells were isolated from rat testes, and treated with different concentrations of lactate (2.5-20 mM), cortiosterone (10(-9) -10(-4)  M) and lactate plus corticosterone. The production of testosterone were assayed by radioimmunoassay, and the key molecular proteins, including luteinizing hormone receptor (LHR), protein kinase A (PKA), steroidogenic acute regulatory protein (StAR), and cholesterol P450 side-chain cleavage enzyme (P450scc) involved in testosterone production were performed by Western blot. Results showed that testosterone levels were significantly increased with lactate, while decresed with corticosterone and lactate plus corticosterone treatment. Protein expressions of LHR and P450scc were upregulated with lactate treatment. However, PKA and P450scc were downregulated by lactate plus corticosterone treatment. This downregulation was followed by decreased testoterone levels in Leydig cells. Furthermore, acetylated cAMP, which activates testosterone production was increased with lactate, but not altered by conrtiosterone. Our findings conclude that corticosterone may interfere with lactate, and restrict lactate-stimulated testosterone production in Leydig cells. J. Cell. Physiol. 232: 2135-2144, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. The effects of lactation on impulsive behavior in vasopressin-deficient Brattleboro rats.

    PubMed

    Aliczki, Mano; Fodor, Anna; Balogh, Zoltan; Haller, Jozsef; Zelena, Dora

    2014-08-01

    Vasopressin (AVP)-deficient Brattleboro rats develop a specific behavioral profile, which-among other things-include altered cognitive performance. This profile is markedly affected by alterations in neuroendocrine state of the animal such as during lactation. Given the links between AVP and cognition we hypothesized that AVP deficiency may lead to changes in impulsivity that is under cognitive control and the changes might be altered by lactation. Comparing virgin and lactating AVP-deficient female Brattleboro rats to their respective controls, we assessed the putative lactation-dependent effects of AVP deficiency on impulsivity in the delay discounting paradigm. Furthermore, to investigate the basis of such effects, we assessed possible interactions of AVP deficiency with GABAergic and serotonergic signaling and stress axis activity, systems playing important roles in impulse control. Our results showed that impulsivity was unaltered by AVP deficiency in virgin rats. In contrast a lactation-induced increase in impulsivity was abolished by AVP deficiency in lactating females. We also found that chlordiazepoxide-induced facilitation of GABAergic and imipramine-induced enhancement of serotonergic activity in virgins led to increased and decreased impulsivity, respectively. In contrast, during lactation these effects were visible only in AVP-deficient rats. These rats also exhibited increased stress axis activity compared to virgin animals, an effect that was abolished by AVP deficiency. Taken together, AVP appears to play a role in the regulation of impulsivity exclusively during lactation: it has an impulsivity increasing effect which is potentially mediated via stress axis-dependent mechanisms and fine-tuning of GABAergic and serotonergic function.

  14. A Calcium-Deficient Diet in Rat Dams during Gestation and Nursing Affects Hepatic 11β-hydroxysteroid dehydrogenase-1 Expression in the Offspring

    PubMed Central

    Takaya, Junji; Yamanouchi, Sohsaku; Kaneko, Kazunari

    2014-01-01

    Background Prenatal malnutrition can affect the phenotype of offspring by changing epigenetic regulation of specific genes. Several lines of evidence demonstrate that calcium (Ca) plays an important role in the pathogenesis of insulin resistance syndrome. We hypothesized that pregnant female rats fed a Ca-deficient diet would have offspring with altered hepatic glucocorticoid-related gene expression and that lactation would modify these alterations. Methodology We determined the effects of Ca deficiency during pregnancy and/or lactation on hepatic 11β-hydroxysteroid dehydrogenase-1 (Hsd11b1) expression in offspring. Female Wistar rats consumed either a Ca-deficient (D: 0.008% Ca) or control (C: 0.90% Ca) diet ad libitum from 3 weeks preconception to 21 days postparturition. On postnatal day 1, pups were cross-fostered to the same or opposite dams and divided into the following four groups: CC, DD, CD, and DC (first letter: original mother's diet; second letter: nursing mother's diet). All offspring were fed a control diet beginning at weaning (day 21) and were killed on day 200±7. Serum insulin and adipokines in offspring were measured using ELISA kits. Principal Findings In males, mean levels of insulin, glucose, and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) were higher in the DD and DC groups than in the CC group. We found no difference in HOMA-IR between the CC and CD groups in either males or females. Expression of Hsd11b1 was lower in male DD rats than in CC rats. Hsd11b1 expression in male offspring nursed by cross-fostered dams was higher than that in those nursed by dams fed the same diet; CC vs. CD and DD vs. DC. In females, Hsd11b1 expression in DC rats was higher than that in CC rats. Conclusions These findings indicated that maternal Ca restriction during pregnancy and/or lactation alters postnatal growth, Hsd11b1 expression, and insulin resistance in a sex-specific manner. PMID:24427280

  15. Metabolic and Histopathological Effects of Fructose Intake During Pregestation, Gestation and Lactation in Rats and their Offspring

    PubMed Central

    Sarı, Erkan; Yeşilkaya, Ediz; Bolat, Ahmet; Topal, Turgut; Altan, Bilal; Fidancı, Kürşat; Saldır, Mehmet; Erdem, Galip; Gülgün, Mustafa; Gülcan Kurt, Yasemin; Güven, Ahmet

    2015-01-01

    Objective: Studies have demonstrated a significant relationship between maternal fructose intake and metabolic outcome in their offspring. However, there is a paucity of data about the long-term effects of fructose intake on the offspring of fructose-fed dams. Therefore, we planned a study to evaluate the long-term effects of fructose intake on the offspring of dam rats fed a high-fructose diet. Methods: Sixteen virgin female Sprague-Dawley rats were divided into two groups. Group 1 received a regular diet and Group 2 a high-fructose diet. Both groups received their experimental diets for 8 weeks before conception. They were mated and continued to feed with their experimental diet during mating and during their pregnancy and lactation periods. After weaning, the offspring from each group were divided into two groups. Group 1A received a regular diet, Group 1B - a fructose diet, Group 2A - a regular diet and Group 2B received a fructose diet. After weaning, the offspring were anesthetized and blood samples were collected for biochemical analysis. Liver, kidney and retroperitoneal adipose tissue were harvested for histopathological examination. Primary antibodies against inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were determined as early inflammation markers. Results: After weaning, while daily water consumption was found to be significantly higher in Groups 2B and 1B (p<0.01), daily laboratory chow consumption was significantly lower in Groups 1A and 2A (p<0.01). Body weight was significantly higher in Groups 1B and 2B (p<0.01). Serum glucose, triglyceride, low-density lipoprotein cholesterol and very low-density lipoprotein cholesterol levels were found to be increased and high-density lipoprotein cholesterol levels decreased in Group 2B (p<0.05). The intensities of iNOS staining in the retroperitoneal adipose tissue, COX-2 staining in the liver and both iNOS and COX-2 staining in the kidney were higher in Group 2B (p<0.05). Conclusion

  16. Microinjection of the dopamine D2-receptor antagonist Raclopride into the medial preoptic area reduces REM sleep in lactating rats.

    PubMed

    Benedetto, Luciana; Rivas, Mayda; Cavelli, Matias; Peña, Florencia; Monti, Jaime; Ferreira, Annabel; Torterolo, Pablo

    2017-10-17

    The medial preoptic area (mPOA) is a brain structure classically related to both non-REM (NREM) sleep and maternal behavior. Although the dopaminergic system is known to play a role in the control of the states of sleep and wakefulness, its effects within the mPOA on sleep are still not clear. Microinjection of the dopamine D2 receptor antagonist Raclopride into the mPOA has been shown to promote nursing postures in lactating dams with no effects on active maternal behavior. We hypothesized that the facilitation of nursing postures may be also associated with the promotion of NREM sleep. In order to test the hypothesis, Raclopride was microinjected into the mPOA and maternal behavior and sleep were assessed in lactating rats. The changes observed included a reduction of the latency to start nursing and an increase of the time to reunite the entire litter. Contrary to our hypothesis, NREM sleep was not affected by Raclopride. On the other hand, REM sleep and its transitional stage from NREM sleep, were significantly reduced by this pharmacological agent. These data suggest that dopamine D2 receptors within the mPOA are involved in the transition from NREM to REM sleep. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Bromocriptine treatment at the end of lactation prevents hyperphagia, higher visceral fat and liver triglycerides in early-weaned rats at adulthood.

    PubMed

    Peixoto-Silva, Nayara; Moura, Egberto G; Carvalho, Janaine C; Nobre, Jéssica L; Quitete, Fernanda T; Pinheiro, Cintia R; Santos-Silva, Ana Paula; de Oliveira, Elaine; Lisboa, Patricia C

    2017-04-01

    Non-pharmacological early weaning (NPEW) leads offspring to obesity, higher liver oxidative stress and microsteatosis in adulthood. Pharmacological EW (PEW) by maternal treatment with bromocriptine (BRO) causes obesity in the adult progeny but precludes hepatic injury. To test the hypothesis that BRO prevents the deleterious changes of NPEW, we injected BRO into the pups from the NPEW model in late lactation. Lactating rats were divided into two groups: dams with an adhesive bandage around the body to prevent breastfeeding on the last 3 days of lactation and dams whose pups had free suckling (C). Offspring from both groups were subdivided into two groups: pups treated with BRO (intraperitoneal (i.p.) 4 mg/kg per day) on the last 3 days of lactation (NPEW/BRO and C/BRO) or pups treated with the vehicle (NPEW and C). At PN120, offspring were challenged with a high fat diet (HFD), and food intake was recorded after 30 minutes and 12 hours. Rats were killed at PN120 and PN200. At PN120, adipocyte size was greater in the NPEW group but was normal in the NPEW/BRO group. At PN200, the NPEW group presented hyperphagia, higher adiposity, adipocyte hypertrophy, hyperleptinaemia, glucose intolerance and increased hepatic triglycerides. These parameters were normalized in the NPEW/BRO group. In the feeding test, BRO groups showed lower HFD intake at 30 minutes than did their controls; however, at 12 hours, the NPEW group ate more HFD. The treatment with BRO can preclude some deleterious effects of the NPEW model, which prevented the development of overweight and its comorbidities. © 2017 John Wiley & Sons Australia, Ltd.

  18. Effect of light during lactation on the phasic and tonic responses of the rat pacemaker.

    PubMed

    Canal-Corretger, M M; Cambras, T; Díez-Noguera, A

    2003-01-01

    The circadian system in mammals generates endogenous circadian rhythms and entrains them to external cycles. Here, we examine whether the lighting conditions under which rats are reared affect the properties of the circadian pacemaker. We maintained three groups of rats under constant darkness (DD-rats), constant bright light (LL-rats) or light-dark cycles of 24 hours (LD-rats) during lactation. We then studied motor activity rhythm under constant light of four intensities, and under seven light-dark cycles with periods ranging between 22 and 27 hours. Results show that neither the tau nor the phase angle to the external cycle differed between groups. Differences were found in the amplitude of the circadian rhythm and in the number of rats that became arrhythmic under LL. We conclude that the light received during lactation affects the strength of the circadian pacemaker and its sensitivity to light.

  19. Elevated blood lactate is not a primary cause of anorexia in tumor-bearing rats.

    PubMed

    Chance, William T; Dayal, Ramesh; Friend, Lou Ann; James, J Howard

    2004-01-01

    Tumor-bearing (TB) rats exhibit elevated concentrations of lactate in blood contiguous with the development of anorexia. Continuous intravenous infusion of lactate into non-TB rats reduced food intake at plasma concentrations lower than those observed in anorectic TB rats. Levels of neuropeptide Y (NPY) were elevated in the ventromedial (VMH) and dorsomedial hypothalamic regions of lactate-infused rats. The addition of the enhancer of pyruvate dehydrogenase activity, dichloroacetate (DCA), to the drinking water of TB rats (0.1-0.4%) normalized blood lactate concentration but had no significant effect on anorexia. However, the elevated concentration of NPY in the VMH of anorectic TB rats was also normalized by the DCA treatment. No alterations in regional hypothalamic levels of corticotropin-releasing factor were observed within any treatment conditions. These results suggest that, although hyperlactatemia may be involved in maintaining elevated NPY concentrations in anorectic TB rats, it does not appear to be a significant factor in the etiology of experimental cancer anorexia.

  20. [The toxicity of a prometryne/simazine combination in the lactation stage of rats].

    PubMed

    Messow, A; Benkwitz, F; Hellwig, A

    1990-03-01

    The postnatal effect of a combination of Prometryne and Simazine was analyzed in rats. Lactating rats were administered from 5 through 10 d pp. The effect on rat pups were characterized by reflex development, behavioural toxicological tests, and selected biochemical investigations. Distinct effects were observed on body weight, neuro-muscular maturation, and somatic development. There were also significant differences in the content of C-reactive protein and the number of white blood cells.

  1. Diazepam, but not buspirone, induces similar anxiolytic-like actions in lactating and ovariectomized Wistar rats.

    PubMed

    Fernández-Guasti, A; Ferreira, A; Picazo, O

    2001-09-01

    Previous reports indicate that the behavioural effects (including anxiolytic-like actions, hypothermia, "serotonergic syndrome," maternal behaviour and aggression and reduction in ambulation) of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), are completely blocked in lactating rats. The present study compares the behavioural effects of buspirone (1.25, 2.5 and 5.0 mg/kg) and diazepam (0.5, 1.0, 2.0 and 4.0 mg/kg) between ovariectomized and mid-lactating rats. The study was carried out on Wistar female rats under inverted light/dark cycle conditions, by using the burying behaviour paradigm, the elevated plus maze and a general activity test. In both ovariectomized and lactating rats, diazepam produced a dose-dependent reduction in burying behaviour and an increase in the time spent in open arms, responses interpreted as anxiolytic. Buspirone at all doses (1.25, 2.5 and 5.0 mg/kg) produced clear motor impairments in lactating, but not in ovariectomized animals, indicating that the effects of this drug on the anxiety paradigms are unspecific. Diazepam, by contrast, at the highest dose (4.0 mg/kg) similarly inhibited ambulation in both conditions. In the elevated plus maze, control lactating subjects spent more time in the open arms compared with saline-treated ovariectomized subjects, suggesting an anxiolytic-like effect of lactation per se. The present results support the idea that some behavioural actions of drugs acting at the serotonergic system vary between ovariectomized and lactating rats.

  2. Pups of dams fed low-fat diet during pregnancy and lactation showed strong preference for high-fat diet to achieve optimal growth.

    PubMed

    Nakashima, Yoko; Sato, Akie

    2011-01-01

    To investigate the causes why pups of dams fed a low-fat high-carbohydrate diet (LFD) showed a strong preference for fat, three groups of dams were fed one of three diets during pregnancy and lactation: the LFD, a control diet (CTD) or a high-fat low-carbohydrate diet (HFD). After weaning, pups of each of the three groups were divided into two equal subgroups (Pair 1 and Pair 2), for a total of six pup subgroups. Each subgroup was placed on a two-choice diet program of the LFD and the HFD (Pair 1), or the LFD and a HFDLE (with cellulose added to maintain the same energy concentration as the LFD) (Pair 2), for 3 wk. Although the energy intake of dams fed the LFD during the nursing period was lower than that of the HFD group, no significant difference in body weight was observed among the three groups. At weaning, the body weight of pups nursed by dams fed the LFD was lower than that of the other groups. In Pair 1, the HFD intake ratio of the LFD and the HFD groups during the self-selection period was higher than that of the CTD group. In Pair 2, the HFDLE intake ratio of the LFD and the CTD groups was lower than that of the HFD group. At the end of the self-selection period, no significant difference in body weight was observed among the three groups of Pair 1. However, in Pair 2, the body weight of the LFD group was lower than that of the other groups. Therefore, it was supposed that pups of dams fed the LFD showed strong preference for the HFD containing high energy in order to achieve optimal growth.

  3. Lanthanum damages learning and memory and suppresses astrocyte-neuron lactate shuttle in rat hippocampus.

    PubMed

    Jin, Cuihong; Gao, Liang; Li, Yingqi; Wu, Shengwen; Lu, Xiaobo; Yang, Jinghua; Cai, Yuan

    2017-10-09

    Rare-earth elements (REEs) are applied in various fields by virtue of their superior physical and chemical properties. Surveys have reported that REEs can impair learning and memory in children and induce neurobehavioral abnormalities in animals. However, the mechanism underlying this neurotoxicity is still unclear. Lanthanum (La) is often chosen to study the effects of REEs. Here, we investigated the role of astrocyte-neuron lactate shuttle (ANLS) in spatial learning and memory impairment induced by LaCl3 in hippocampus, an important spatial memory-related brain region. Pregnant Wistar rats were exposed to 0, 0.125, 0.25, 0.5, or 1% LaCl3 in drinking water during pregnancy and lactation. After weaning, young rats continued to receive 0, 0.125, 0.25, 0.5, and 1% LaCl3 in the drinking water for 1 month. The results showed that LaCl3 exposure impaired the spatial learning and memory of rats in Morris water maze test, significantly reduced the mRNA and protein levels of glycogen synthetase, glycogen phosphorylase, lactate dehydrogenase A, monocarboxylate transporter 4, MCT-1, and MCT-2, and decreased total LDH activity and lactate contents in rat hippocampus. These results indicate that LaCl3 impairs spatial learning and memory in rats probably by suppressing ANLS in rat hippocampus. The study provides a novel clue of energy supply for neurons to clarify the neurotoxicity of REEs.

  4. Role of maternal tissue in the synthesis of polyunsaturated fatty acids in response to a lipid-deficient diet during pregnancy and lactation in rats.

    PubMed

    González, Raúl Sánchez; Rodriguez-Cruz, Maricela; Maldonado, Jorge; Saavedra, Filiberto Jasso

    2014-10-01

    During pregnancy and lactation, metabolic adaptations involve changes in expression of desaturases and elongases (Elovl2 and Elovl5) in the mammary gland and liver for the synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic acid (AA) required for fetal and postnatal growth. Adipose tissue is a pool of LC-PUFAs. The response of adipose tissue for the synthesis of these fatty acids in a lipid-deficient diet of dams is unknown. The aim of this study was to explore the role of maternal tissue in the synthesis of LC-PUFAs in rats fed a low-lipid diet during pregnancy and lactation. Fatty acid composition (indicative of enzymatic activity) and gene expression of encoding enzymes for fatty acid synthesis were measured in liver, mammary gland and adipose tissue in rats fed a low-lipid diet. Gene expression of desaturases, elongases, fatty acid synthase (Fasn) and their regulator Srebf-1c was increased in the mammary gland, liver and adipose tissue of rats fed a low-lipid diet compared with rats from the adequate-lipid diet group throughout pregnancy and lactation. Genes with the highest (P<0.05) expression in the mammary gland, liver and adipose tissue were Elovl5 (1333%), Fads2 (490%) and Fasn (6608%), respectively, in a low-lipid diet than in adequate-lipid diet. The percentage of AA in the mammary gland was similar between the low-lipid diet and adequate-lipid diet groups during the second stage of pregnancy and during lactation. The percentage of monounsaturated and saturated fatty acids was significantly (P<0.05) increased throughout pregnancy and lactation in all tissues in rats fed a low-lipid diet than in rats fed an adequate-lipid diet. Results suggest that maternal metabolic adaptations used to compensate for lipid-deficient diet during pregnancy and lactation include increased expression of genes involved in LC-PUFAs synthesis in a stage- and tissue-specific manner and elevated lipogenic activity (saturated and monounsaturated

  5. Neurofunctional Evaluation of Young Male Offspring of Rat Dams with Diabetes Induced by Streptozotocin

    PubMed Central

    Delascio Lopes, Carla; Sinigaglia-Coimbra, Rita; Mazzola, Jacqueline; Camano, Luiz; Mattar, Rosiane

    2011-01-01

    Diabetes mellitus (DM) is a complex disease, being one of the most prevalent diseases worldwide. As a consequence, pregnancy-associated diabetes is increasingly common. Given the numerous studies about the influence of diabetes on offspring of diabetic rat dams, the neurological outcome is of outmost importance. This paper aimed at evaluating the neurofunctional performance of young male offspring of rat dams with diabetes induced by streptozotocin. Diabetes was induced in Wistar female rats by streptozotocin administration, while control groups received vehicle injection. At two-month survival period, male offspring from each group were randomized to the water maze Morris test, in order to assess their neurofunctional status. There was no significant difference between the groups as assessed by the Morris water maze test for spatial reference task. Our results point to the need of further investigation on the offspring neurofunctional performance. PMID:22363880

  6. Exercise during rat pregnancy and lactation: maternal effects and offspring growth.

    PubMed

    Courant, G T; Barr, S I

    1990-03-01

    Eighty Sprague-Dawley rats were divided into exercised (E) and sedentary (S) groups. E rats were trained to run on a treadmill (30 m/min, 2 hr/day). Within each group, two subgroups were mated and three served as virgin time controls. Of the mated subgroups, one was terminated within 24 hours of delivery and the other on day 14 of lactation. Subgroups of virgin S and E controls were terminated at times corresponding to the mating, delivery and lactation day 14 of mated rats. MANOVA revealed that exercise significantly affected food intake, body weight and body composition in both virgin and mated animals: generally, E rats ate more, gained more weight, and had less carcass fat than S controls. E rats did not store fat during pregnancy. At parturition, they were 7.0% fat, similar to both E (6.6%) and S (7.6%) controls prior to mating, and less than S rats at parturition (11.9%). Despite diminished fat stores at parturition in E rats, litter size and pup birthweight were similar in E and S rats, as was offspring growth during lactation (mean weights on day 14 of 28.9 g and 29.3 g, respectively). Remaining body fat and increased food intake were adequate to support normal pup growth.

  7. Changes in mRNA expression of arcuate nucleus appetite-regulating peptides during lactation in rats.

    PubMed

    Suzuki, Yoshihiro; Nakahara, Keiko; Maruyama, Keisuke; Okame, Rieko; Ensho, Takuya; Inoue, Yoshiyuki; Murakami, Noboru

    2014-04-01

    The contribution of hypothalamic appetite-regulating peptides to further hyperphagia accompanying the course of lactation in rats was investigated by using PCR array and real-time PCR. Furthermore, changes in the mRNA expression for appetite-regulating peptides in the hypothalamic arcuate nucleus (ARC) were analyzed at all stages of pregnancy and lactation, and also after weaning. Food intake was significantly higher during pregnancy, lactation, and after weaning than during non-lactation periods. During lactation, ARC expression of mRNAs for agouti-related protein (AgRP) and peptide YY was increased, whereas that of mRNAs for proopiomelanocortin (POMC) and cholecystokinin (CCK) was decreased, in comparison with non-lactation periods. The increase in AgRP mRNA expression during lactation was especially marked. The plasma level of leptin was significantly decreased during the course of lactation, whereas that of acyl-ghrelin was unchanged. In addition, food intake was negatively correlated with the plasma leptin level during lactation. This study has clarified synchronous changes in the expression of many appetite-regulating peptides in ARC of rats during lactation. Our results suggest that hyperphagia during lactation in rats is caused by decreases in POMC and CCK expression and increases in AgRP expression in ARC, the latter being most notable. Together with the decrease in the blood leptin level, such changes in mRNA expression may explain the further hyperphagia accompanying the course of lactation.

  8. Melinjo (Gnetum gnemon) extract intake during lactation stimulates hepatic AMP-activated protein kinase in offspring of excessive fructose-fed pregnant rats.

    PubMed

    Kataoka, Saori; Mukai, Yuuka; Takebayashi, Mihoko; Kudo, Megumi; Acuram, Uson Rachael; Kurasaki, Masaaki; Sato, Shin

    2016-06-01

    Excessive maternal fructose intake during pregnancy and in early postnatal life has metabolic consequences for the offspring. We investigated the effects of melinjo (Gnetum gnemon) extract (MeE) intake during lactation on the expression and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) in the liver of offspring from excessive fructose-fed pregnant dams. Pregnant Wistar rats received a normal diet and 100g/L fructose solution during gestation ad libitum. At delivery, dams were divided into two groups: a control diet (FC) or a 0.1% MeE-containing diet (FM) fed during lactation. The dams that were not treated with fructose were fed a control diet (CC). At postnatal week 3, some pups were sacrificed, while the remaining continued to receive a normal diet and were sacrificed at week 17. Blood chemistry and phosphorylation levels of AMPK and acetyl-coenzyme A carboxylase (ACC) were evaluated. Plasma glucose levels in FC female offspring increased compared to that receiving CC at weeks 3 and 17; however, the levels in FM female offspring decreased at week 17. The insulin levels in FM female offspring decreased significantly compared to that in FC female offspring at week 3. Hepatic AMPK phosphorylation was upregulated in FM offspring at week 3 and in female, but not male, offspring at week 17. ACC phosphorylation in FM female offspring was upregulated at week 17. Our results suggest that maternal MeE intake during lactation may modulate the hepatic AMPK pathways in female offspring. Copyright © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  9. Lactate per se improves the excitability of depolarized rat skeletal muscle by reducing the Cl− conductance

    PubMed Central

    de Paoli, Frank Vincenzo; Ørtenblad, Niels; Pedersen, Thomas Holm; Jørgensen, Rasmus; Nielsen, Ole Bækgaard

    2010-01-01

    Studies on rats have shown that lactic acid can improve excitability and function of depolarized muscles. The effect has been related to the ensuing reduction in intracellular pH causing inhibition of muscle fibre Cl− channels. However, since several carboxylic acids with structural similarities to lactate can inhibit muscle Cl− channels it is possible that lactate per se can increase muscle excitability by exerting a direct effect on these channels. We therefore examined the effects of lactate on the function of intact muscles and skinned fibres together with effects on pH and Cl− conductance (Gcl). In muscles where extracellular compound action potentials (M-waves) and tetanic force response to excitation were reduced by (mean ±s.e.m.) 82 ± 4% and 83 ± 2%, respectively, by depolarization with 11 mm extracellular K+, both M-waves and force exhibited an up to 4-fold increase when 20 mm lactate was added. This effect was present already at 5 mm and saturated at 15 mm lactate, and was associated with a 31% reduction in GCl. The effects of lactate were completely blocked by Cl− channel inhibition or use of Cl−-free solutions. Finally, both experiments where effects of lactate on intracellular pH in intact muscles were mimicked by increased CO2 tension and experiments with skinned fibres showed that the effects of lactate could not be related to reduced intracellular pH. It is concluded that addition of lactate can inhibit ClC-1 Cl− channels and increase the excitability and contractile function of depolarized rat muscles via mechanisms not related to a reduction in intracellular pH. PMID:20876199

  10. Relationship between plasma D(-)-lactate and intestinal damage after severe injuries in rats

    PubMed Central

    Sun, Xiao-Qing; Fu, Xiao-Bing; Rong-Zhang; Lü, Yi; Deng, Qun; Jiang, Xiao-Guo; Sheng, Zhi-Yong

    2001-01-01

    AIM: To explore the kinetic changes in plasma D(-)-lactate and lipopolysaccharide (LPS) levels, and investigate whether D(-)-lactate could be used as a marker of intestinal injury in rats following gut ischemia/reperfusion, burn, and acute necrotizing pancreatitis (ANP). METHODS: Three models were developed in rats: ① gut ischemia/reperfusion obtained by one hour of superior mesenteric artery occlusion followed by reperfusion; ② severe burn injury created by 30% of total body surface area (TBSA) full-thickness scald burn; and ③ ANP induced by continuous inverse infusion of sodium taurocholate and trypsin into main pancreatic duct. Plasma levels of D(-)-lactate in systemic circulation and LPS in portal circulation were measured by enzymatic-spectrophotometric method and limulus amebocyte lysate (LAL) test kit, respectively. Tissue samples of intestine were taken for histological analysis. RESULTS: One hour gut ischemia followed by reperfusion injuries resulted in a significant elevation in plasma D(-)-lactate and LPS levels, and there was a significant correlation between the plasma D(-)-lactate and LPS (r = 0.719, P < 0.05). The plasma concentrations of D(-)-lactate and LPS increased significantly at 6 h postburn, and there was also a remarkable correlation between them (r = 0.877, P < 0.01). D(-)-lactate and LPS levels elevated significantly at 2 h after ANP, with a similar significant correlation between the two levels (r = 0.798, P < 0.01). The desquamation of intestine villi and infiltration of inflammatory cells in the lamina propria were observed in all groups. CONCLUSION: The changes of plasma D(-)-lactate levels in systemic blood paralleled with LPS levels in the portal vein blood. The measurement of plasma D(-)-lactate level may be a useful marker to assess the intestinal injury and to monitor an increase of intestinal permeability and endotoxemia following severe injuries in early stage. PMID:11819828

  11. A BBDR-HPT Axis Model for the Lactating Rat and Nursing Pup: Evaluation of Iodide Deficiency

    EPA Science Inventory

    A biologically based dose response (BBDR) model for the lactating rat and pup hypothalamic-pituitary-thyroid (HPT) axis is being developed to advance understanding of thyroid hormone disruptions and developmental neurotoxicity (DNT). The model for the lactating rat and pup quanti...

  12. A BBDR-HPT Axis Model for the Lactating Rat and Nursing Pup: Evaluation of Iodide Deficiency

    EPA Science Inventory

    A biologically based dose response (BBDR) model for the lactating rat and pup hypothalamic-pituitary-thyroid (HPT) axis is being developed to advance understanding of thyroid hormone disruptions and developmental neurotoxicity (DNT). The model for the lactating rat and pup quanti...

  13. Fish oil diet in pregnancy and lactation reduces pup weight and modifies newborn hepatic metabolic adaptations in rats.

    PubMed

    Jiménez, Maria J; Bocos, Carlos; Panadero, Maribel; Herrera, Emilio

    2017-02-01

    To determine the effects of a diet containing fish oil (FD) during pregnancy and lactation in rats on the metabolic adaptations made by the offspring during early extrauterine life and to compare it to an olive oil diet (OD). Rats were mated and randomly allocated to OD or FD containing 10 % of the corresponding oil. During lactation, litters were adjusted to eight pups per dam. Fetuses of 20 days and pups of 0, 1, 10, 20 and 30 days of age were studied. Body weight and length were lower in pups of the FD group from birth. The diet, milk, pups' plasma and liver of FD group had higher proportions of n-3 LCPUFA, but the content of arachidonic acid (ARA) was lower. Plasma glucose was higher, but unesterified fatty acids, triacylglycerols (TAG), 3-hydroxybutyrate and liver TAG in 1-day-old pups were lower in the FD group, and differences in some of these variables were also found in pups up to 30 days old. Liver lipoprotein lipase activity and mRNA expression, and the expression of carnitine palmitoyl transferase I, acyl-CoA oxidase and 3-hydroxy 3-methyl glutaryl-CoA synthase increased more at birth in pups of the FD group, but the expression of sterol regulatory element binding protein-1c and Δ6-desaturase mRNA was lower in the FD group. Maternal intake of high n-3 LCPUFA retards postnatal development, which could be the result of impaired ARA synthesis, and affects hepatic metabolic adaptations to extrauterine life.

  14. Variations in the cellular proliferation of prolactin cells from late pregnancy to lactation in rats.

    PubMed

    Carretero, José; Rubio, Manuel; Blanco, Enrique; Burks, Deborah J; Torres, José L; Hernández, Elena; Bodego, Pilar; Riesco, José M; Juanes, Juan A; Vázquez, Ricardo

    2003-04-01

    Lactation is a physiological process associated with hyperactivity of hypophyseal prolactin-producing cells. It is known that the percentage of these cells is increased during lactation, although there are discrepancies in the reports regarding the mechanisms responsible for increasing the number of prolactin cells. In order to analyse whether this increase is a result of previous proliferation, variations in the proliferation rate of prolactin-positive cells were determined from late pregnancy to lactation in adult female rats by means of observation of the immunohistochemical expression of PCNA as a marker of cellular proliferation. During late pregnancy, a very significant increase in the percentage of proliferating prolactin cells was observed in comparison to non-pregnant females in the proestrus phase (p < 0.01). Although the percentage of prolactin-positive cells after one week of lactation was higher than in non-lactating or in pregnant females (p < 0.01), the proliferation rate was lower than in the other groups studied. In sum, our results suggest that late pregnancy constitutes a preliminary proliferative phase preparatory to the ensuing lactation phase and that endocrine changes in late pregnancy involve the cellular proliferation of hypophyseal prolactin cells in order to prepare the gland for later demands and to prevent proliferative changes from occurring during lactation.

  15. Analysis of glucose and lactate in dialysate from hypothalamus of rats after exhausting swimming using microdialysis.

    PubMed

    Wang, L; Dong, Y; Yu, X; Shangguan, D H; Zhao, R; Han, H W; Liu, G Q

    2002-10-01

    A microbore flow injection analysis-immobilized enzyme reactor-electrochemical detection (FIA-IMER-ECD) system for glucose and lactate detection was built up. The assays were precise, sensitive and practicable for determination of glucose and lactate levels in hypothalamic dialysate. The method had been used to detect the dynamic changes of glucose and lactate levels during rat exhausting swimming and recovery. The data showed that after exhausting swimming, the concentration of glucose in hypothalamic dialysate that reflected the concentration in the hypothalamic extracellular fluid decreased. The level fell to its nadir at day 1 after the exercise and then went back to the basal level at day 3 after the swimming. However, lactate levels increased to a maximum at day 3 and went back to the basal level at day 5 after the swimming. Copyright 2002 John Wiley & Sons, Ltd.

  16. Effects of protein level, methionine supplementation and carbohydrate type of the diet on liver lipid and plasma free threonine contents in the lactating rat.

    PubMed

    Leclerc, J; Chanussot, B; Miller, M L; Poisson, J P; Belleville, J

    1989-01-01

    Eight groups of 13-15 female rats were fed purified diets after littering. Four groups received a low protein (8% casein) diet (groups 8) and the others, a normal protein (20% casein) diet (groups 20). Carbohydrates were supplied either as starch (groups S) or as starch plus 40% fructose (groups F). Half the animals received a 0.4% methionine supplementation (groups M). Four or five dams per group were sacrificed on days 2, 7 and 14 after littering. The diet intake was increased by methionine supplementation, substitution of starch for fructose and increased protein content, mainly during the second week of lactation. This influenced weight variation of the dams and litter growth. On all days, the plasma levels of cholesterol esters, triglycerides and phospholipids were positively correlated with the dietary protein level. On days 7 and 14, the liver neutral lipid content was increased in rats fed the low protein diets supplemented with methionine (groups 8SM and 8FM) and the normal protein diets containing 40% fructose (groups 20F and 20FM). The plasma free threonine content was positively correlated with the protein level in the diet. On day 14, rats fed a low protein diet had a threonine deficiency, except those in groups 8S and 8F. The plasma free threonine content of these rats was not reduced, possibly due to an impaired utilization of this amino acid. The liver lipidosis observed during lactation, in contrast to that observed during growth with a low protein diet, was not due to a threonine deficiency.

  17. Prolactin inhibition at the end of lactation programs for a central hypothyroidism in adult rat.

    PubMed

    Bonomo, Isabela Teixeira; Lisboa, Patrícia Cristina; Passos, Magna Cottini Fonseca; Alves, Simone Bezerra; Reis, Adelina Martha; de Moura, Egberto Gaspar

    2008-08-01

    Malnutrition during lactation is associated with hypoprolactinemia and failure in milk production. Adult rats whose mothers were malnourished presented higher body weight and serum tri-iodothyronine (T(3)). Maternal hypoprolactinemia at the end of lactation caused higher body weight in adult life, suggesting an association between maternal prolactin (PRL) level and programming of the offspring's adult body weight. Here, we studied the consequences of the maternal PRL inhibition at the end of lactation by bromocriptine (BRO) injection, a dopaminergic agonist, upon serum TSH and thyroid hormones, thyroid iodide uptake, liver mitochondrial alpha-glycerophosphate dehydrogenase (mGPD), liver and pituitary de-iodinase activities (D1 and/or D2), and in vitro post-TRH TSH release in the adult offspring. Wistar lactating rats were divided into BRO - injected with 1 mg/twice a day, daily for the last 3 days of lactation, and C - control, saline-injected with the same frequency. At 180 days of age, the offspring were injected with (125)I i.p. and after 2 h, they were killed. Adult animals whose mothers were treated with BRO at the end of lactation presented lower serum TSH (-51%), T(3) (-23%), and thyroxine (-21%), lower thyroid (125)I uptake (-41%), liver mGPD (-55%), and pituitary D2 (-51%) activities, without changes in the in vitro post-TRH TSH release. We show that maternal PRL suppression at the end of lactation programs a hypometabolic state in adulthood, in part due to a thyroid hypofunction, caused by a central hypothyroidism, probably due to decreased TRH secretion. We suggest that PRL during lactation can regulate the hypothalamus-pituitary-thyroid axis and programs its function.

  18. Grape skin extract protects against programmed changes in the adult rat offspring caused by maternal high-fat diet during lactation.

    PubMed

    Resende, Angela C; Emiliano, Andréa F; Cordeiro, Viviane S C; de Bem, Graziele F; de Cavalho, Lenize C R M; de Oliveira, Paola Raquel B; Neto, Miguel L; Costa, Cristiane A; Boaventura, Gilson T; de Moura, Roberto S

    2013-12-01

    Maternal overnutrition during suckling period is associated with increased risk of metabolic disorders in the offspring. We aimed to assess the effect of Vitis vinifera L. grape skin extract (ACH09) on cardiovascular and metabolic disorders in adult male offspring of rats fed a high-fat (HF) diet during lactation. Four groups of female rats were fed: control diet (7% fat), ACH09 (7% fat plus 200 mg kg(-1) d(-1) ACH09 orally), HF (24% fat), and HF+ACH09 (24% fat plus 200 mg kg(-1) d(-1) ACH09 orally) during lactation. After weaning, all male offspring were fed a control diet and sacrificed at 90 or 180 days old. Systolic blood pressure was increased in adult offspring of HF-fed dams and ACH09 prevented the hypertension. Increased adiposity, plasma triglyceride, glucose levels and insulin resistance were observed in offspring from both ages, and those changes were reversed by ACH09. Expression of insulin cascade proteins IRS-1, AKT and GLUT4 in the soleus muscle was reduced in the HF group of both ages and increased by ACH09. The plasma oxidative damage assessed by malondialdehyde levels was increased, and nitrite levels decreased in the HF group of both ages, which were reversed by ACH09. In addition, ACH09 restored the decreased plasma and mesenteric arteries antioxidant activities of superoxide dismutase, catalase and glutathione peroxidase in the HF group. In conclusion, the treatment of HF-fed dams during lactation with ACH09 provides protection from later-life hypertension, body weight gain, insulin resistance and oxidative stress. The protective effect ACH09 may involve NO synthesis, antioxidant action and activation of insulin-signaling pathways. © 2013.

  19. Effects of repeated gestation and lactation on milk n-6 fatty acid composition in rats fed on a diet rich in 18:2n-6 or 18:3n-6.

    PubMed

    Huang, Y S; Redden, P R; Horrobin, D F; Churchill, S; Parker, B; Ward, R P; Mills, D E

    1992-09-01

    The present study examined the effect of repeated gestation and lactation on the levels of long-chain n-6 polyunsaturated fatty acids in rat milk fat, and examined whether such levels might be modulated by supplementing the diet of the lactating dams with either (g/kg) 50 safflower oil (SFO; containing 800 g 18:2n-6/kg), or 50 evening primrose oil (EPO; containing 720 g 18:2n-6 and 90 g 18:3n-6/kg). The milk was collected at three different times (days 1, 8 and 15) in each given lactation period from female Sprague-Dawley rats which were successively bred for four pregnancies and lactations. Results showed that dietary fat and breeding frequency had no significant effects on milk triacylglycerol content, but they modified the pattern of milk fatty acids in both triacylglycerol and phospholipid fractions. After three or four successive breedings rats fed on EPO produced milk containing less saturated but more monounsaturated and polyunsaturated fatty acids compared with those fed on SFO. During the course of lactation the levels of n-6 metabolites, e.g. 18:3n-6, 20:3n-6 and 20:4n-6, in milk fat declined progressively. However, they were consistently higher in the EPO group than in the SFO group. These findings suggest that the levels of long-chain n-6 metabolites in the milk fat may be increased through supplementing the maternal diet with 18:3n-6.

  20. Dichloroacetate increases glucose use and decreases lactate in developing rat brain

    SciTech Connect

    Miller, A.L.; Hatch, J.P.; Prihoda, T.J. )

    1990-12-01

    Dichloroacetate (DCA) activates pyruvate dehydrogenase (PDH) by inhibiting PDH kinase. Neutralized DCA (100 mg/kg) or saline was intravenously administered to 20 to 25-day-old rats (50-75g). Fifteen minutes later a mixture of {sup 6-14}C glucose and {sup 3}H fluorodeoxyglucose (FDG) was administered intravenously and the animals were sacrificed by microwave irradiation (2450 MHz, 8.0 kW, 0.6-0.8 sec) after 2 or 5 min. Brain regional rates of glucose use and metabolite levels were determined. DCA-treated rats had increased rates of glucose use in all regions studied (cortex, thalamus, striatum, and brain stem), with an average increase of 41%. Lactate levels were lower in all regions, by an average of 35%. There were no significant changes in levels of ATP, creatine phosphate, or glycogen in any brain region. Blood levels of lactate did not differ significantly between the DCA- and the saline-treated groups. Blood glucose levels were higher in the DCA group. In rats sacrificed by freeze-blowing, DCA treatment caused lower brain levels of both lactate and pyruvate. These results cannot be explained by any systemic effect of DCA. Rather, it appears that in the immature rat, DCA treatment results in activation of brain PDH, increased metabolism of brain pyruvate and lactate, and a resulting increase in brain glycolytic rate.

  1. Mechanism of lactate-induced relaxation of isolated rat mesenteric resistance arteries.

    PubMed Central

    McKinnon, W; Aaronson, P I; Knock, G; Graves, J; Poston, L

    1996-01-01

    1. The effects of the sodium salt of the weak acid lactate on tension and intracellular pH (pH1) were studied in rat mesenteric small arteries mounted on a wire myograph. Sodium lactate was substituted iso-osmotically for sodium chloride. 2. At a concentration of 50 mM, both L- and D-stereoisomers of lactate markedly relaxed arteries preconstricted with noradrenaline (NA) within 10 min. The concentration-response relationship for L-lactate showed that the NA contracture was relaxed by 50% at approximately 26 mM. L-Lactate did not, however, relax arteries preconstricted with high-K+(45 mM) solution. 3. L-Lactate did not alter extracellular pH (pHo) but caused a small but significant decrease in pH1, measured using the pH-sensitive fluorochrome, 2',7'-bis(carboxyethyl)-5-(6)-carboxyfluorescein (BCECF). Relaxation to L-lactate was unaffected when this change in pHi was offset by the simultaneous addition of NH4Cl to the solution. 4. Sodium pyruvate (50 mM) caused a significant intracellular acidosis but did not relax arteries preconstricted with NA. 5. L-Lactate-induced relaxations were unaffected by removal of the endothelium or when the synthesis of nitric oxide (NO) was inhibited by 10(-4) M N omega-nitro-L-arginine methyl ester (L-NAME). 6. The potassium channel blockers glibenclamide (10 microM), 4-aminopyridine (3 mM) and tetraethylammonium chloride (10 mM) did not affect L-lactate-induced relaxation in arteries preconstricted with NA. Inhibition of guanylate cyclase with Methylene Blue, or cyclooxgenase with indomethacin, also did not affect relaxation to L-lactate. 7. The Rp stereoisomer of adenosine-3',5'-cyclic monophosphothioate (Rp-cAMPS), an analogue of cAMP which inhibits competitively stimulation of protein kinase A, reduced significantly L-lactate-induced relaxation at a concentration of 25 microM. Rp-cAMPS also significantly reduced forskolin-induced relaxation of the NA contracture. 8. It is concluded that L-lactate-induced relaxation in this

  2. Trans fat intake across gestation and lactation increases morphine preference in females but not in male rats: Behavioral and biochemical parameters.

    PubMed

    Roversi, Karine; Pase, Camila Simonetti; Roversi, Katiane; Vey, Luciana Taschetto; Dias, Verônica Tironi; Metz, Vinícia Garzella; Burger, Marilise Escobar

    2016-10-05

    The abuse of morphine has risen considerably in recent years, mainly due to the increase of its prescription in clinical medicine. Also, increased consumption of processed foods, rich in trans fatty acids (TFA), has caused concerns about human health. Thus, the aim of our study was to determine whether trans fat consumption in the perinatal period may affect preference for morphine in adolescent female and male rats. Dams were orally supplemented with water (C-control) or hydrogenated vegetable fat (HVF-rich in TFA) during gestation and lactation periods. On post-natal day 43, pups were exposed to morphine (4mg/kg i.p., for 4 days) and assessed in the conditioned place preference paradigm. Anxiety-like symptoms were assessed, and oxidative status of the brain was estimated by reactive species (RS) generation. Female rats with HVF supplementation showed increased morphine preference and less anxiety-like symptoms. Additionally, both male and female rats from HVF-supplementation showed increased RS generation in the ventral tegmental area, whose level was similar in morphine-conditioned female rats. RS generation was increased in the hippocampus of morphine-conditioned female rats, regardless of the supplementation of their dams. We may infer that gender is a predictive factor to opioid preference, since adolescent female rats showed more susceptibility to addiction than males. Furthermore, trans fat consumption across the perinatal period is able to modify parameters of opioid preference in female rats, possibly due to TFA incorporation in phospholipid membranes, modifying the endogenous opioid system and the oxidative status in brain areas related to drug addiction.

  3. Maternal Food Restriction during Pregnancy and Lactation Adversely Affect Hepatic Growth and Lipid Metabolism in Three-Week-Old Rat Offspring

    PubMed Central

    Lee, Sangmi; You, Young-Ah; Kwon, Eun Jin; Jung, Sung-Chul; Jo, Inho; Kim, Young Ju

    2016-01-01

    Maternal malnutrition influences the early development of foetal adaptive changes for survival. We explored the effects of maternal undernutrition during gestation and lactation on hepatic growth and function. Sprague-Dawley rats were fed a normal or a food-restricted (FR) diet during gestation and/or lactation. We performed analyses of covariance (adjusting for the liver weight/body weight ratio) to compare hepatic growth and lipid metabolism among the offspring. Maternal FR during gestation triggered the development of wide spaces between hepatic cells and increased the expression of mammalian target of rapamycin (mTOR) in three-week-old male offspring compared with controls (both p < 0.05). Offspring nursed by FR dams exhibited wider spaces between hepatic cells and a lower liver weight/body weight ratio than control offspring, and increased mTOR expression (p < 0.05). Interestingly, the significant decrease in expression of lipogenic-related genes was dependent on carbohydrate-responsive element-binding protein, despite the increased expression of sterol regulatory element-binding protein 1 (SREBP1) (p < 0.05). This study demonstrated increased expression of key metabolic regulators (mTOR and SREBP1), alterations in lipid metabolism, and deficits in hepatic growth in the offspring of FR-treated dams. PMID:27983688

  4. Gestational and lactational exposure to the polychlorinated biphenyl mixture Aroclor 1254 modulates retinoid homeostasis in rat offspring.

    PubMed

    Esteban, Javier; Elabbas, Lubna E; Borg, Daniel; Herlin, Maria; Åkesson, Agneta; Barber, Xavier; Hamscher, Gerd; Nau, Heinz; Bowers, Wayne J; Nakai, Jamie S; Viluksela, Matti; Håkansson, Helen

    2014-08-17

    Polychlorinated biphenyls (PCBs) induce a broad spectrum of biochemical and toxic effects in mammals including alterations of the vital retinoid (vitamin A) system. The aim of this study was to characterize alterations of tissue retinoid levels in rat offspring and their dams following gestational and lactational exposure to the PCB mixture Aroclor 1254 (A1254) and to assess the interrelationship of these changes with other established sensitive biochemical and toxicological endpoints. Sprague-Dawley rat dams were exposed orally to 0 or 15 mg/kg body weight/day of A1254 from gestational day 1 to postnatal day (PND) 23. Livers, kidneys and serum were collected from the offspring on PNDs 35, 77 and 350. Tissue and serum retinoid levels, hepatic cytochrome P450 (CYP) enzymes and serum thyroid hormones were analyzed. A multivariate regression between A1254 treatment, hepatic retinoid levels, hepatic CYP enzymes activities, thyroid hormone levels and body/liver weights was performed using an orthogonal partial least-squares (PLS) analysis. The contribution of dioxin-like (DL) components of A1254 to the observed effects was also estimated using the toxic equivalency (TEQ) concept. In both male and female offspring short-term alterations in tissue retinoid levels occurred at PND35, i.e. decreased levels of hepatic retinol and retinoic acid (RA) metabolite 9-cis-4-oxo-13,14-dihydro-RA with concurrent increases in hepatic and renal all-trans-RA levels. Long-term changes consisted of decreased hepatic retinyl palmitate and increased renal retinol levels that were apparent until PND350. Retinoid system alterations were associated with altered CYP enzyme activities and serum thyroid hormone levels as well as body and liver weights in both offspring and dams. The estimated DL activity was within an order of magnitude of the theoretical TEQ for different endpoints, indicating significant involvement of DL congeners in the observed effects. This study shows that tissue retinoid

  5. Lactational exposure effect of polychlorinated biphenyl on rat Sertoli cell markers and functional regulators in prepuberal and puberal F1 offspring.

    PubMed

    Sugantha Priya, E; Sathish Kumar, T; Balaji, S; Bavithra, S; Raja Singh, P; Sakthivel, D; Ravi Sankar, B; Arunakaran, J

    2017-01-01

    Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental toxicants acting as endocrine disruptors. Many researches evidenced that PCBs affect the male reproductive system in adult rats and it can transfer from mother to offspring through milk. We investigated whether the lactational exposure to PCBs affects the Sertoli cell function in F1 offspring. Dams were orally treated with different doses of PCB-Aroclor 1254 (1, 2 and 5 mg/kg bw/day, respectively) from postpartum day 1-20. Male offspring rats were killed on PND 21 and PND 60. Testes were used both for histological study and to isolate Sertoli cell. Serum and testicular interstitial fluid (TIF) levels of testosterone, ABP and estradiol were analyzed by ELISA method. The mRNA and protein expressions of follicle-stimulating hormone (FSHR), androgen-binding protein (ABP), Inhibinβ, androgen receptor (AR) and estrogen receptor (ERβ) were studied using real-time PCR and immunoblotting, respectively. The testicular architecture was altered in PCB-treated groups of both prepuberal and puberal rats. Testosterone, estradiol and androgen-binding protein levels were altered in both serum and TIF in PCB treated groups. The gene expression level of FSHR, ABP, ERβ and AR was decreased in a dose-dependent manner, whereas Inhibinβ gene expression level was increased in PCB-treated groups. Lactational exposure to PCB affects both the histoarchitecture of testis, Sertoli cell maker and functional regulators in both prepuberal and puberal F1 male progeny.

  6. Compensatory nutrition-directed mammary cell proliferation and lactation in rats.

    PubMed

    Kim, S H; Moon, Y S; Keller, W L; Park, C S

    1998-02-01

    The proper use of a time-dependent and controlled nutrition regimen during the hormone-sensitive growth phase before first parturition can significantly affect mammary growth and subsequent lactation performance. The objective of the present study was to determine if a compensatory nutrition regimen improves lactation performance by affecting proliferation and apoptosis of mammary epithelial cells. Forty female rats (7 weeks of age, average weight 148 g) were assigned to either (1) control, free access to diet or (2) stair-step compensatory nutrition regimen, an alternating 3-4-week schedule beginning with an energy-restricted diet (31.2% restriction) for 3 weeks, followed by the control diet for 4 weeks. Estimated milk yield was greater (P < 0.05) on day 15 of lactation in the compensatory nutrition group than in the control group. Mammary cell proliferation values were 1.4- and 2.7-fold greater in mammary tissue from the compensatory group during pregnant and early lactating stages respectively, compared with those from the control group. Ornithine decarboxylase (EC 4.1.17) mRNA was 24% higher (P < 0.05) in mammary tissues of rats from the compensatory nutrition group during pregnancy than in those from the control group. These results indicate that the compensatory nutrition regimen imposed during the peripubertal growth phase stimulated mammary epithelial cell proliferation and improved lactation performance.

  7. Constant bright light (LL) during lactation in rats prevents arrhythmicity due to LL.

    PubMed

    Cambras, T; Vilaplana, J; Torres, A; Canal, M M; Casamitjana, N; Campuzano, A; Díez-Noguera, A

    1998-03-01

    Light has a strong effect on the circadian system. Light-dark (LD) cycles are the main zeitgebers for practically all organisms, and the exposure of animals to constant bright light (LL) alters the manifestation of circadian rhythms. In rats, exposure to LL in adulthood produces an arrhythmic pattern in their motor activity, with a large number of ultradian components. In previous experiments, we found that rats born and kept under LL during lactation develop, after weaning, a circadian rhythm which is maintained for at least a couple of months. Here, we examined motor activity rhythms under LL of two groups of rats which differed in the lighting conditions under which they were kept during lactation: 1) rats kept under LL during lactation (LL-rats), which manifested a circadian rhythm after weaning, and 2) rats kept under constant darkness (DD-rats), which were arrhythmic after weaning. We investigated whether the presence of rhythmicity under LL in LL-rats is a transitory effect or whether it persists throughout most of the life of the rat. Moreover, we examined motor activity rhythms of both groups of rats under different lighting conditions to find out other possible differences in the manifestation of their circadian rhythms. Results showed that there are no differences in the capacity of entrainment of both groups of rats to LD cycles or in the rhythm that rats show under DD. Most of the LL-rats maintained their circadian rhythms for the duration of the experiment (1 year), although we found differences in the rhythms manifested between males and females. We found that most of the LL-males became arrhythmic; consequently, at the end of the experiment, there were no differences in the number of males showing circadian rhythm in the LL- and DD-groups. Most of the females in the LL-group showed a clear circadian rhythm under LL during the entire experiment. Thus, LL during lactation has a protective effect against the disruptive effect of LL on the circadian

  8. Effect of 2,4-dichlorophenoxyacetic acid on milk transfer to the litter and prolactin release in lactating rats.

    PubMed

    Stürtz, Nelson; Jahn, Graciela A; Deis, Ricardo P; Rettori, Valeria; Duffard, Ricardo O; Evangelista de Duffard, Ana M

    2010-04-30

    The effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on brain monoamines and the serum level of hormones involved in milk synthesis and on the milk ejection reflex in rats were evaluated. Dams were treated with 2.5, 5, 15, 25, 50 or 70mg 2,4-D/kg bw according to two experimental designs: (a) through food from post partum day 1 (PPD 1) to PPD 16 and the respective control groups or (b) an unique i.p. injection on PPD 11. To measure milk ejection, the litter was separated from the mother at the 11th day of lactation during 8h, returned to their mothers and allowed to suckle for a period of 15min. The procedure was repeated on 3 consecutive days until the end of treatment. The change in litter weight during the suckling period was taken as a measure of the amount of milk ejected during this period. The dams' serum prolactin (PRL), oxytocin (OT) and growth hormone levels were determined by radioimmunoassay. Both treatment regimens produced a dose-dependent decrease in the amount of milk ejected and circulating PRL and OT secreted in response to the suckling stimulus. Administration of OT before returning the pups restored the milk ejection, indicating no impairment in the capacity of the mammary gland to produce and secrete milk. In addition, dopamine levels were increased by the 2,4-D treatments in arcuate nucleus (ArN) and anterior lobe of pituitary gland (AL), while serotonin level was drastically decreased in ArN. 2,4-D treatment increased both calcium-dependent and calcium-independent nitric oxide synthase (NOS) activities in ArN. These results suggest that 2,4-D inhibits the suckling-induced hormone release, milk transfer to the litter at the central level, through a stimulation of hypothalamic NOS and dopamine and by an inhibition of hypothalamic serotonin transmission.

  9. ACTIVITY AND ISOZYME CONTENT OF LACTATE DEHYDROGENASE UNDER LONG-TERM ORAL TAURINE ADMINISTRATION TO RATS.

    PubMed

    Ostapiv, R D; Humenyuk, S L; Manko, V V

    2015-01-01

    The effect of long-term oral taurine administration to rats on activity of lactate dehydrogenase (LDH), its isozyme content and activity in the whole blood, liver, thigh muscle, brain and testes tissues were studied in the present work. For this purpose male Wistar rats with body weight 190-220 g were randomly divided into three groups, they were orally administered drinking water (control group) or taurine solution 40 and 100 mg per kg of body weight ( groups I and II, respectively). The total lactate dehydrogenase activity was measured spectrophotometrically, the percentage content of isozymes was determined by electrophoresis in 7.5% poliacrylamide gel withfurther staining according to J. Garbus. It was found that the total lactate dehydrogenase activity increased in all studied tissues. In testes of animals of both groups and in brain of group I animals, the total percentage contents of isozymes that are responsible for lactate production (LDH4+LDH5) increased. In liver of animals of both groups and in whole blood of group II animals, the total percentage content of isozymes that produce pyruvate (LDH1+LDH2) increased. In thigh muscle of both groups and in brain of group II animals the balance between LDH1+LDH2 and LDH4+LDH5 content did not differ from control values, though total lactate dehydrogenase activity was significantly higher, than that in the control group. Thus, the increase in the lactate dehydrogenase activity under long-term oral taurine administration in different rat tissues was found to be tissue- and dose-dependent and was caused by the increase in the content of different isozymes. Such increase in group I animals might be explained by adaptive mechanisms to hypoxia caused by high doses of taurine. For group II animals high doses of taurine were toxic and directly affected metabolic processes in the animal bodies.

  10. [Effective method of isolating M4-lactate dehydrogenase from rat liver].

    PubMed

    Gorbach, Z V; Maglysh, S S; Konovalenko, O V

    1984-01-01

    Lactate dehydrogenase M4-isoform in the homogeneous state was isolated from the rat liver by successive application of sulphate-ammonium fractionation, phosphocellulose ion-exchange chromatography with high-affinity elution of 1 mM NADH and subsequent hydroxyl apatite fractionation. The method permits obtaining the preparation amounts of the enzymic protein with yield 37.5%, specific activity 386.8 units per 1 mg of protein. It is established that 1 mM NAD+, 10 mM pyruvate and 100 mM lactate are also effective as agents of the selective enzyme elution.

  11. Influence of low dietary calcium during pregnancy and lactation on zinc levels in maternal blood and bone in rats.

    PubMed

    Weisstaub, Adriana; de Ferrer, Patricia Ronayne; Zeni, Susana; de Portela, María Luz

    2003-01-01

    The effect of low dietary calcium on maternal zinc nutritional status was studied. Two groups of 6 adult female Wistar rats were fed during pregnancy and lactation with experimental diets containing either 0.2 g (LCa) or 0.6 g (NCa) of calcium/100 g. Both diets contained/100 g: 20.0 g protein (potassium caseinate), 3.5 mg Zn, 0.6 g P. A third group (n = 6) was fed a "stock diet" (SG), containing/100 g: 24.8 g protein, 1.5 g Ca, 0.6 g P, 11.6 mg Zn. Maternal blood samples were drawn from the tail before mating (To), at delivery (D) and at weaning (W); dams were sacrificed at weaning and the right femur was excised. Determinations (atomic absorption spectrometry) were: Zinc in red blood cells (RBC), Zn and Ca in ashed femur. The results (mean +/- SD) were: RBCZn (microg/mL) at To: 8.65 +/- 1.80, which did not change in the SG or in the NCa groups, but increased significantly in the LCa group (p < 0.001) (D: 18.20 +/- 4.63; W: 26.70 +/- 6.02), regarding To. Femur Zn (microg/100 mg) showed an increase (p < 0.001) in the LCa group (30.2 +/- 2.1) regarding both SG (25.3 +/- 0.7) and NCa groups (24.1 +/- 0.7). Femur Ca (mg/100 mg) decreased (p < 0.05) in the LCa group (19.2 +/- 0.9) regarding both SG (24.0 +/- 0.5) and NCa groups (21.4 +/- 0.7) and leading to a significant increase in Zn/Ca ratio (p < 0.001) in the LCa group. Therefore, dietary calcium deficiency during pregnancy and lactation would produce an increase of Zn utilization, reflected in the increase of maternal blood Zn levels and in femur Zn content.

  12. Effects of maternal vitamin B6 deficiency and over-supplementation on DNA damage and oxidative stress in rat dams and their offspring.

    PubMed

    Almeida, Mara Ribeiro; Venâncio, Vinícius Paula; Aissa, Alexandre Ferro; Darin, Joana Darc Castania; Pires Bianchi, Maria Lourdes; Antunes, Lusânia Maria Greggi

    2015-06-01

    Vitamin B6 is a cofactor for more than 140 essential enzymes and plays an important role in maternal health and fetal development. The goal of this study was to investigate the effects of maternal vitamin B6 on DNA damage and oxidative stress status in rat dams and their offspring. Female Wistar rats were randomly assigned to three dietary groups fed a standard diet (control diet), a diet supplemented with 30 mg/kg of vitamin B6, or a deficient diet (0 mg/kg of vitamin B6) for 10 weeks before and during mating, pregnancy and lactation. The dams were euthanized at weaning, and their male pups were euthanized either 10 days or 100 days after birth. We found that maternal vitamin B6 deficiency increased the micronucleus frequency in peripheral blood and bone marrow cells and also increased the concentration of hepatic TBARS (thiobarbituric acid reactive substances) in newborn pups (10 days old). In conclusion, maternal 5- to 6-fold over-supplementation of vitamin B6 had no adverse effects, however its deficiency may induce chromosomal damage and hepatic lipid peroxidation in the offspring.

  13. Diet-induced obesity accelerates blood lactate accumulation of rats in response to incremental exercise to maximum.

    PubMed

    Chen, Chiao-Nan Joyce; Liao, Yi-Hung; Lin, Shang-Ying; Yu, Jun-Xian; Li, Zhen-Jie; Lin, Yu-Chieh; Chang, Gwo-Jyh; Lin, Chung-Hao; Wong, Alice May-Kuen

    2017-08-30

    Blood lactate increases during incremental exercise at high-intensity workloads and limited exercise capacity is a characteristic of obese animals. This study examined whether blood lactate changes in response to incremental exercise is disrupted in obese animals. Muscular and hepatic proteins that are critical in lactate metabolism were also investigated. Rats were randomized to either standard chow (control) or high fat diet (HFD) groups. All animals underwent an incremental treadmill test after 14 weeks of diet intervention. Blood lactate levels were measured before and after the treadmill test. Activities of mitochondrial oxidative phosphorylation and glycolysis were examined in muscle tissues. Proteins in the liver and skeletal muscles that participate in the turnover of blood lactate were determined by Western blot. Running time in the incremental treadmill test decreased in the HFD group, and blood lactate accumulated faster in these animals than in the control group. Animals with HFD had a decreased level of hepatic monocarboxylate transporter 2, the protein responsible for blood lactate uptake in the liver. Skeletal muscles of animals with HFD showed greater glycolytic activity and decreased content of lactate dehydrogenase B, which converts lactate to pyruvate. Blood lactate accumulated faster during incremental exercise in obese animals and associated with their decreased exercise performance. Changes in the metabolic pattern of muscles and changes of liver and muscle proteins associated with lactate utilization likely contribute to the abnormal response of blood lactate to incremental exercise in obese animals. Copyright © 2017, American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.

  14. Lactation deficit in OFA hr/hr rats may be caused by differential sensitivity to stress compared with Wistar and Sprague Dawley rats.

    PubMed

    Valdez, Susana R; Bonafede, Melisa M; Carreño, Norma B; Deis, Ricardo P; Jahn, Graciela A

    2012-07-01

    OFA hr/hr (OFA) rats present a major lactation deficit that impairs offspring survival. To explore whether abnormal stress responsiveness causes this deficit, we compared their hormonal (prolactin, progesterone, and corticosterone) responses to stress (room change and 2-min ether exposure) with those of Wistar and Sprague Dawley (SD) rats. We tested responses during the estrous cycle, pregnancy, lactation, after ovariectomy, and ovarian steroid hormone priming, and responses to suckling. We evaluated hypothalamic expression of receptors for prolactin (PRLRlong) and the isoforms of receptors for progesterone (PRA and B) and estrogen (ERα and β) in late pregnancy. We tested whether administration of an anxiolytic (diazepam) improved lactation. Ether exposure increased circulating levels of the three hormones in the three strains of rats, cycling and ovariectomized, but was less effective in pregnancy and lactation. Elevated estrogen level (estrus and estradiol-treated ovariectomized rats) potentiated the prolactin response more in SD and OFA rats than in Wistar rats. Elevated progesterone level (late pregnancy, lactation, progesterone-treated ovariectomized rats) inhibited the prolactin response less in OFA than in SD or Wistar rats. Ether exposure inhibited the prolactin and oxytocin responses to suckling only in OFA rats. Diazepam treatment increased pup survival rate and the prolactin response to suckling. Hypothalamic total PR mRNA content, assayed by RT-PCR, was higher in pregnant OFA rats compared with SD and Wistar rats, but the PRB/PRA protein ratio determined by Western blot was lowest in Wistar rats, intermediate in OFA rats, and highest in SD rats. The heightened sensitivity to stress of lactating OFA rats may contribute to their lactational deficit and be caused by a combination of hypoprolactinemia and reduced inhibitory capacity of progesterone.

  15. Dopamine-Regulated Adrenocorticotropic Hormone Secretion in Lactating Rats: Functional Plasticity of Melanotropes

    PubMed Central

    Oláh, Márk; Fehér, Pálma; Ihm, Zsófia; Bácskay, Ildikó; Kiss, Timea; Freeman, Marc E.; Nagy, György M.; Vecsernyés, Miklós

    2009-01-01

    Pro-opiomelanocortin (POMC) is processed to adrenocorticotropic hormone (ACTH) and β-lipotropin in corticotropes of the anterior lobe, and to α-melanocyte-stimulating hormone (α-MSH) and β-endorphin in melanotropes of the intermediate lobe (IL) of the pituitary gland. While ACTH secretion is predominantly under the stimulatory influence of the hypothalamic factors, hormone secretion of the IL is tonically inhibited by neuroendocrine dopamine (NEDA) neurons. Lobe-specific POMC processing is not absolute. For example, D2 type DA receptor (D2R)-deficient mice have elevated plasma ACTH levels, although it is known that corticotropes do not express D2R(s). Moreover, observations that suckling does not influence α-MSH release, while it induces an increase in plasma ACTH is unexplained. The aim of the present study was to investigate the involvement of the NEDA system in the regulation of ACTH secretion and the participation of the IL in ACTH production in lactating rats. Untreated and estradiol (E2)-substituted ovariectomized (OVX) females were also studied. The concentration of ACTH in the IL was higher in lactating rats than in OVX rats, while the opposite change in α-MSH level of the IL was observed. DA levels in the IL and the neural lobe were lower in lactating rats than in OVX rats. Suckling-induced ACTH response was eliminated by pretreatment with the DA receptor agonist, bromocriptine (BRC). Inhibition of DA biosynthesis by α-methyl-p-tyrosine (αMpT) and blockade of D2R by domperidone (DOM) elevated plasma ACTH levels, but did not influence plasma α-MSH levels in lactating rats. The same drugs had opposite effects in OVX and OVX + E2 animals. In lactating mothers, BRC was able to block ACTH responses induced by both αMpT and DOM. Surgical denervation of the IL elevated basal plasma levels of ACTH. Taken together, these data indicate that melanotropes synthesize ACTH during lactation and its release from these cells is regulated by NEDA neurons. PMID

  16. Effect of zinc oxide nanoparticles on dams and embryo–fetal development in rats

    PubMed Central

    Hong, Jeong-Sup; Park, Myeong-Kyu; Kim, Min-Seok; Lim, Jeong-Hyeon; Park, Gil-Jong; Maeng, Eun-Ho; Shin, Jae-Ho; Kim, Yu-Ri; Kim, Meyoung-Kon; Lee, Jong-Kwon; Park, Jin-A; Kim, Jong-Choon; Shin, Ho-Chul

    2014-01-01

    This study investigated the potential adverse effects of zinc oxide nanoparticles (ZnOSM20[−] NPs; negatively charged, 20 nm) on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague Dawley rats. ZnOSM20(−) NPs were administered to pregnant rats by gavage at 0 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day. All dams were subjected to caesarean section on gestational day 20, and all the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight at 400 mg/kg/day and decreased liver weight, and increased adrenal glands weight at 200 mg/kg/day and 400 mg/kg/day. However, no treatment-related difference in the number of corpora lutea, the number of implantation sites, the implantation rate (%), resorption, dead fetuses, litter size, fetal deaths, fetal and placental weights, and sex ratio were observed between the groups. Morphological examinations of the fetuses demonstrated no significant difference in the incidences of abnormalities between the groups. No significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that a 15-day repeated oral dose of ZnOSM20(−) was minimally maternotoxic at dose of 200 mg/kg/day and 400 mg/kg/day. PMID:25565833

  17. Sampling of prenatal and postnatal offspring from individual rat dams enhances animal use without compromising development

    NASA Technical Reports Server (NTRS)

    Alberts, J. R.; Burden, H. W.; Hawes, N.; Ronca, A. E.

    1996-01-01

    To assess prenatal and postnatal developmental status in the offspring of a group of animals, it is typical to examine fetuses from some of the dams as well as infants born to the remaining dams. Statistical limitations often arise, particularly when the animals are rare or especially precious, because all offspring of the dam represent only a single statistical observation; littermates are not independent observations (biologically or statistically). We describe a study in which pregnant laboratory rats were laparotomized on day 7 of gestation (GD7) to ascertain the number and distribution of uterine implantation sites and were subjected to a simulated experience on a 10-day space shuttle flight. After the simulated landing on GD18, rats were unilaterally hysterectomized, thus providing a sample of fetuses from 10 independent uteruses, followed by successful vaginal delivery on GD22, yielding postnatal samples from 10 uteruses. A broad profile of maternal and offspring morphologic and physiologic measures indicated that these novel sampling procedures did not compromise maternal well-being and maintained normal offspring development and function. Measures included maternal organ weights and hormone concentrations, offspring body size, growth, organ weights, sexual differentiation, and catecholamine concentrations.

  18. Effect of zinc oxide nanoparticles on dams and embryo-fetal development in rats.

    PubMed

    Hong, Jeong-Sup; Park, Myeong-Kyu; Kim, Min-Seok; Lim, Jeong-Hyeon; Park, Gil-Jong; Maeng, Eun-Ho; Shin, Jae-Ho; Kim, Yu-Ri; Kim, Meyoung-Kon; Lee, Jong-Kwon; Park, Jin-A; Kim, Jong-Choon; Shin, Ho-Chul

    2014-01-01

    This study investigated the potential adverse effects of zinc oxide nanoparticles (ZnO(SM20[-]) NPs; negatively charged, 20 nm) on pregnant dams and embryo-fetal development after maternal exposure over the period of gestational days 5-19 with Sprague Dawley rats. ZnO(SM20(-)) NPs were administered to pregnant rats by gavage at 0 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day. All dams were subjected to caesarean section on gestational day 20, and all the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight at 400 mg/kg/day and decreased liver weight, and increased adrenal glands weight at 200 mg/kg/day and 400 mg/kg/day. However, no treatment-related difference in the number of corpora lutea, the number of implantation sites, the implantation rate (%), resorption, dead fetuses, litter size, fetal deaths, fetal and placental weights, and sex ratio were observed between the groups. Morphological examinations of the fetuses demonstrated no significant difference in the incidences of abnormalities between the groups. No significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that a 15-day repeated oral dose of ZnO(SM20(-)) was minimally maternotoxic at dose of 200 mg/kg/day and 400 mg/kg/day.

  19. Sampling of prenatal and postnatal offspring from individual rat dams enhances animal use without compromising development

    NASA Technical Reports Server (NTRS)

    Alberts, J. R.; Burden, H. W.; Hawes, N.; Ronca, A. E.

    1996-01-01

    To assess prenatal and postnatal developmental status in the offspring of a group of animals, it is typical to examine fetuses from some of the dams as well as infants born to the remaining dams. Statistical limitations often arise, particularly when the animals are rare or especially precious, because all offspring of the dam represent only a single statistical observation; littermates are not independent observations (biologically or statistically). We describe a study in which pregnant laboratory rats were laparotomized on day 7 of gestation (GD7) to ascertain the number and distribution of uterine implantation sites and were subjected to a simulated experience on a 10-day space shuttle flight. After the simulated landing on GD18, rats were unilaterally hysterectomized, thus providing a sample of fetuses from 10 independent uteruses, followed by successful vaginal delivery on GD22, yielding postnatal samples from 10 uteruses. A broad profile of maternal and offspring morphologic and physiologic measures indicated that these novel sampling procedures did not compromise maternal well-being and maintained normal offspring development and function. Measures included maternal organ weights and hormone concentrations, offspring body size, growth, organ weights, sexual differentiation, and catecholamine concentrations.

  20. Moderate caloric restriction in lactating rats programs their offspring for a better response to HF diet feeding in a sex-dependent manner.

    PubMed

    Palou, Mariona; Torrens, Juana María; Priego, Teresa; Sánchez, Juana; Palou, Andreu; Picó, Catalina

    2011-06-01

    We aimed to assess the lasting effects of moderate caloric restriction in lactating rats on the expression of key genes involved in energy balance of their adult offspring (CR) and their adaptations under high-fat (HF) diet. Dams were fed with either ad libitum normal-fat (NF) diet or a 30% caloric restricted diet throughout lactation. After weaning, the offspring were fed with NF diet until the age of 15 weeks and then with an NF or a HF diet until the age of 28 weeks, when they were sacrificed. Body weight and food intake were followed. Blood parameters and the expression of selected genes in hypothalamus and white adipose tissue (WAT) were analysed. CR ate fewer calories and showed lower body weight gain under HF diet than their controls. CR males were also resistant to the increase of insulin and leptin occurring in their controls under HF diet, and HF diet exposed CR females showed lower circulating fasting triglyceride levels than controls. In the hypothalamus, CR males had higher ObRb mRNA levels than controls, and CR females displayed greater InsR mRNA levels than controls and decreased neuropeptide Y mRNA levels when exposed to HF diet. CR males maintained WAT capacity of fat uptake and storage and of fatty-acid oxidation under HF diet, whereas these capacities were impaired in controls; female CR showed higher WAT ObRb mRNA levels than controls. These results suggest that 30% caloric restriction in lactating dams ameliorates diet-induced obesity in their offspring by enhancing their sensitivity to insulin and leptin signaling, but in a gender-dependent manner. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Increased ultrasonic vocalizations and risk-taking in rat pups of sleep-deprived dams.

    PubMed

    Gulia, Kamalesh K; Patel, Niraj; Kumar, Velayudhan Mohan

    2015-02-01

    Ultrasonic vocalizations (USVs) in rodent pups are analogous to cries in human babies. There is reduction in USVs in pups after experimental deprivation of rapid eye movement sleep of dams during pregnancy. However, the effects of total sleep deprivation on the USVs of newborns and their emotional development are not documented. Male pups born to the rats that underwent total sleep deprivation for 5h during the third trimester made higher vocalizations, when tested on early postnatal days (pnds) in an isolation-paradigm. Their anxiety-related behaviors during pnds 25-28, were tested using elevated plus maze (EPM). In comparison to the control pups, weanlings of sleep-deprived dams made increased entries into the open arms and higher mobility in the EPM. Enhanced distress calls during early pnds and reduction in risk assessment in weanlings indicate a link between the two behaviors. The USVs during ontogeny may provide early signals about altered emotional development.

  2. Inner capillary diameter of hypothalamic paraventricular nucleus of female rat increases during lactation

    PubMed Central

    2013-01-01

    Background The role of the endothelial cell (EC) in blood flow regulation within the central nervous system has been little studied. Here, we explored EC participation in morphological changes of the anterior hypothalamic paraventricular nucleus (PVN) microvasculature of female rats at two reproductive stages with different metabolic demand (virginity and lactation). We measured the inner capillary diameter (ICD) of 800 capillaries from either the magnocellular or parvocellular regions. The space occupied by neural (somas, dendrites and axons) and glial, but excluding vascular elements of the neurovascular compartment was also measured in 100-μm2 sample fields of both PVN subdivisions. Results The PVN of both groups of animals showed ICDs that ranged from 3 to 10 microns. The virgin group presented mostly capillaries with small ICD, whereas the lactating females exhibited a significant increment in the percentage of capillaries with larger ICD. The space occupied by the neural and glial elements of the neurovascular compartment did not show changes with lactation. Conclusions Our findings suggest that during lactation the microvasculature of the PVN of female rats undergoes dynamic, transitory changes in blood flow as represented by an increment in the ICD through a self-cytoplasmic volume modification reflected by EC changes. A model of this process is proposed. PMID:23302443

  3. Localisation of Lactate Transporters in Rat and Rabbit Placentae

    PubMed Central

    Picut, Catherine A.; Charlap, Jeffrey H.

    2016-01-01

    The distribution of monocarboxylate transporter (MCT) isoforms 1 and 4, which mediate the plasmalemmal transport of l-lactic and pyruvic acids, has been identified in the placentae of rats and rabbits at different ages of gestation. Groups of three pregnant Sprague-Dawley rats and New Zealand White rabbits were sacrificed on gestation days (GD) 11, 14, 18, or 20 and on GD 13, 18, or 28, respectively. Placentae were removed and processed for immunohistochemical detection of MCT1 and MCT4. In the rat, staining for MCT1 was associated with lakes and blood vessels containing enucleated red blood cells (maternal vessels) while staining for MCT4 was associated with vessels containing nucleated red blood cells (embryofoetal vessels). In the rabbit, staining for MCT1 was associated with blood vessels containing nucleated red blood cells while staining for MCT4 was associated with vessels containing enucleated red blood cells. Strength of staining for MCT1 decreased during gestation in both species, but that for MCT4 was stronger than that for MCT1 and was consistent between gestation days. The results imply an opposite polarity of MCT1 and MCT4 across the trophoblast between rat and rabbit. PMID:27843454

  4. Effect of aluminium on duodenal calcium transport in pregnant and lactating rats treated with bromocriptine.

    PubMed

    Orihuela, Daniel

    2007-09-01

    The aim of present work was to study the effect of oral aluminium (Al) overload on intestinal calcium (Ca) absorption in the critical stages of pregnancy and lactation of rats and to find out possible relationships with prolactin (PRL) and 17beta-estradiol (E2) circulating levels. Adult female Wistar rats were orally treated from day 1 of pregnancy with 0 (control), or 50 mg elemental Al (as chloride)/kg body weight per day. Ca transport was determined by everted duodenal sacs technique using 2 microCi of (45)CaCl(2) as flux marker (JCa(ms)). Al treatment reduced JCa(ms) either in late pregnancy (day 19) or in middle lactation (day 9 postpartum). Oral administration of bromocriptine (BrC), an inhibitor of PRL secretion, at dose of 10 mg/kg body weight given 18 h before JCa(ms) measurements were done, produced a significant decrease in the inhibitory effect of Al on JCa(ms), expressed as percent of control, at day 9 of nursing (vehicle: 51+/-7%, BrC: 28+/-4%, P <0.05). A positive correlation between Al effects on JCa(ms) and the physiological variations of E2 serum levels along pregnancy and lactation in BrC-treated rats was also found (r(2)=0.277, P =0.001). We conclude Al could reduce transcellular Ca absorption in the duodenum by interfering with physiological mechanisms of Ca transport partially mediated by serum level increments of E2 and PRL, observed in late pregnancy and mainly during middle lactation of rats.

  5. Enhanced inflammatory response to acute ozone exposure in rats during pregnancy and lactation

    SciTech Connect

    Gunnison, A.F.; Weideman, P.A.; Sobo, M. )

    1992-11-01

    Experimental evidence from several studies suggests that pregnant animals and women are more susceptible to oxidants than nonpregnant controls. In the study reported here, we sought to determine whether pregnant rats are more sensitive than age-matched virgin females to the inflammatory effects of ozone, a gaseous oxidant of considerable environmental significance. Rats at several stages of pregnancy and lactation, as well as age-matched virgin females, were exposed to 1 ppm ozone for 6 hr. Controls were sham-exposed to pure air for an identical period of time. Bronchoalveolar lavage was performed 24 hr after the beginning of exposure, and components of the lavage fluid considered to be indicators of inflammation were used to assess the severity of pulmonary inflammation. The results of this experiment showed that significantly enhanced sensitivity to ozone-induced pulmonary inflammation develops during pregnancy, is maintained during lactation, and disappears following lactation. Implicit in this pattern of differential sensitivity in rats is the possibility of a similar pattern of inflammatory response in analogous groups of humans as well as the potential for applicability to other oxidative pollutants.

  6. Morphological evaluation of rat incisor enamel and dentin induced by pregnancy and lactation using a scanning electron microscope.

    PubMed

    Ozbek, Murat; Dural, Sema; Kanli, Aydan; Tuncel, Murvet; Orhan, Kaan

    2009-10-01

    This study assessed the effects of pregnancy and lactation on the morphology of the dentine tubules and external enamel surface of rat incisor teeth using a scanning electron microscope (SEM) equipped with an energy dispersive x-ray (EDX) system. Twenty-four female Wistar rats were divided into three groups; group A rats were at the end of pregnancy, group B rats were in the post-lactation period and group C rats, the control group, were unmated. The outer enamel surface and openings of the dentine tubules at the neck regions of the incisors were observed under the SEM and photographed. Examination of the incisor teeth of pregnant and post-lactation rats revealed scratches on the enamel surface. There were few eroded areas and slight changes and the dentine tubules of the pregnant group were fully or partially occluded on the entire surface of the enamel in the lactating rats. Almost all dentine tubules of the rats in this group were open. During the study, EDX analysis of calcium, phosphate and magnesium was also performed at 20 kV and 0 degree tilt. The results of EDX analyses of magnesium were significantly lower in the pregnant group compared with the lactation and control groups for the dentine in the neck region (p<0.05). The calcium values increased in the lactation group compared with those of the rats in the other two groups (p<0.05). These results might indicate that changes during pregnancy and lactation affect the content and morphology of mineralized dental hard tissue.

  7. Effects of melamine on pregnant dams and embryo-fetal development in rats.

    PubMed

    Kim, Sung-Hwan; Lee, In-Chul; Lim, Jeong-Hyeon; Shin, In-Sik; Moon, Changjong; Kim, Sung-Ho; Park, Seung-Chun; Kim, Hyoung-Chin; Kim, Jong-Choon

    2011-08-01

    There are worldwide concerns regarding the potential adverse effect of melamine. This study investigated the potential effects of melamine on pregnant dams and embryo-fetal development in Sprague-Dawley rats following maternal exposure on gestational days (GD) 6-20. Melamine was administered to pregnant rats by gavage at doses of 0, 200, 400 and 800 mg kg⁻¹ per day (n = 8-10 for each group). All dams were subjected to a Caesarean section on GD 21 and their fetuses were examined for morphological abnormalities. With administration of melamine at 800 mg kg⁻¹ per day, maternal toxicity manifested as increased incidences of clinical signs and death, lower body weight gain and food intake, and increases in heart, adrenal gland and kidney weights. Histopathological examinations revealed an increase in incidences of congestion, tubular necrosis/degeneration, crystals, casts, inflammatory cells in tubules, tubular dilation and tubular hyaline droplets in the maternal kidneys, while fetal kidneys (one fetus/litter) did not show any histopathological changes. Developmental toxic effects included a decrease in fetal weight, an increase in the incidence of skeletal variations and a delay in fetal ossification. No treatment-related maternal or developmental effects were observed at doses ≤ 400 mg kg⁻¹ per day. These results show that 15-day repeated oral dosing of melamine is embryo-/fetotoxic at a maternotoxic dose, but not teratogenic in rats. The no-observed-adverse-effect level of melamine for pregnant dams and embryo-fetal development is considered to be 400 mg kg⁻¹ per day.

  8. Analysis of glucose and lactate in hippocampal dialysates of rats during the operant conditioned reflex using microdialysis.

    PubMed

    Dong, Yu; Wang, Lei; Shangguan, Dihua; Yu, Xiao; Zhao, Rui; Han, Huiwan; Liu, Guoquan

    2003-07-01

    Changes of extracellular glucose and lactate in hippocampus for freely moving rats during the operant conditioned reflex were examined simultaneously. Samples of the dialysate were assayed for both glucose and lactate using in vivo microdialysis and a microbore flow injection analysis-immobilized enzyme reactor-electrochemical detection (FIA-IMER-ECD) system. Microdialysis samplings were conducted in a Skinner box where lights were delivered as conditioned stimuli (CS) paired with foot shocks as unconditioned stimuli (US). In the treatment group the concentration of glucose and lactate showed no fluctuations during the whole process. However, in the control group in which the rats were exposed to many foot shocks, lactate levels decreased by 19% below baseline during the behavioral session and glucose showed a delayed decrease (by 18%). Compared with glucose, lactate can immediately indicate the dynamic changes in brain.

  9. Effects of Chronic Central Arginine Vasopressin (AVP) on Maternal Behavior in Chronically Stressed Rat Dams

    PubMed Central

    Coverdill, Alexander J.; McCarthy, Megan; Bridges, Robert S.; Nephew, Benjamin C.

    2012-01-01

    Exposure of mothers to chronic stressors during pregnancy or the postpartum period often leads to the development of depression, anxiety, or other related mood disorders. The adverse effects of mood disorders are often mediated through maternal behavior and recent work has identified arginine vasopressin (AVP) as a key neuropeptide hormone in the expression of maternal behavior in both rats and humans. Using an established rodent model that elicits behavioral and physiological responses similar to human mood disorders, this study tested the effectiveness of chronic AVP infusion as a novel treatment for the adverse effects of exposure to chronic social stress during lactation in rats. During early (day 3) and mid (day 10) lactation, AVP treatment significantly decreased the latency to initiate nursing and time spent retrieving pups, and increased pup grooming and total maternal care (sum of pup grooming and nursing). AVP treatment was also effective in decreasing maternal aggression and the average duration of aggressive bouts on day 3 of lactation. Central AVP may be an effective target for the development of treatments for enhancing maternal behavior in individuals exposed to chronic social stress. PMID:24349762

  10. Effects of Chronic Central Arginine Vasopressin (AVP) on Maternal Behavior in Chronically Stressed Rat Dams.

    PubMed

    Coverdill, Alexander J; McCarthy, Megan; Bridges, Robert S; Nephew, Benjamin C

    2012-12-01

    Exposure of mothers to chronic stressors during pregnancy or the postpartum period often leads to the development of depression, anxiety, or other related mood disorders. The adverse effects of mood disorders are often mediated through maternal behavior and recent work has identified arginine vasopressin (AVP) as a key neuropeptide hormone in the expression of maternal behavior in both rats and humans. Using an established rodent model that elicits behavioral and physiological responses similar to human mood disorders, this study tested the effectiveness of chronic AVP infusion as a novel treatment for the adverse effects of exposure to chronic social stress during lactation in rats. During early (day 3) and mid (day 10) lactation, AVP treatment significantly decreased the latency to initiate nursing and time spent retrieving pups, and increased pup grooming and total maternal care (sum of pup grooming and nursing). AVP treatment was also effective in decreasing maternal aggression and the average duration of aggressive bouts on day 3 of lactation. Central AVP may be an effective target for the development of treatments for enhancing maternal behavior in individuals exposed to chronic social stress.

  11. Effects of early life social stress on endocrinology, maternal behavior, and lactation in rats

    PubMed Central

    Carini, Lindsay M.; Nephew, Benjamin C.

    2013-01-01

    Exposure to early life stress is a predictor of mental health disorders, and two common forms of early life stress are social conflict and impaired maternal care, which are predominant features of postpartum mood disorders. Exposure of lactating female rats to a novel male intruder involves robust social conflict and induces deficits in maternal care towards the F1 offspring. This exposure is an early life social stressor for female F1 pups that induces inefficient lactation associated with central changes in oxytocin (OXT), prolactin (PRL), and arginine vasopressin (AVP) gene expression in adult F1 females. The mothers of the rats in the current study were either allowed to raise their pups without exposure to a social stressor (control), or presented with a novel male intruder for 1 hour each day on lactation days 2-16 (chronic social stress). The effects of this early life chronic social stress (CSS) exposure on subsequent peripheral endocrinology, maternal behavior, and physiology were assessed. Exposure of female pups to early life CSS resulted in persistent alterations in maternal endocrinology at the end of lactation (attenuated prolactin and elevated corticosterone), depressed maternal care and aggression, increased restlessness and anxiety-related behavior, impaired lactation, and decreased saccharin preference. The endocrine and behavioral data indicate that early life CSS has long-term effects which are similar to changes seen in clinical populations of depressed mothers, and provide support for the use of the chronic social stress paradigm as an ethologically relevant rodent model for maternal disorders such as postpartum depression and anxiety. PMID:24005186

  12. Behavioral effects of bidirectional selection for behavior towards human in virgin and lactate Norway rats.

    PubMed

    Konoshenko, Maria Yu; Plyusnina, Irina Z

    2012-06-01

    Although numerous studies have demonstrated strong differences in behavioral, hormonal and neurobiological characteristics between male rats selected for elimination (tame) and enhancement (aggressive) of aggressiveness towards humans, few studies have examined changes in female behavior under this selection. The objective of the current work was to evaluate the effects of bidirectional selection for aggressiveness towards humans on behavioral profiles of virgin and lactating rats compared with the behavior in tame, aggressive and unselected (wild-type) females. The behavior of virgin females was studied using the light-dark box, the startle response test and the modified glove test. Tame females were less anxious and more tolerant towards humans than unselected and aggressive rats. Principal component analysis of all behavioral parameters produced three independent factors, explaining 66.37% of the total variability. The measures of behavior towards humans and the measures of anxiety mainly loaded on PC1 (first principal component) which separated the tame females from the unselected and aggressive ones. These data suggest the genetic correlation between the selected behavior towards humans and anxiety-related behavior in virgin rats. No significant effect of line was found for PC2 scores, associated with risk assessment behavior. Measurements of freezing behavior mainly loaded on PC3, and this component separated rats of different genetic groups from each other. The behavior of lactating rats was studied in maternal defense and pup retrieval tests. Females of selected lines did not significantly differ in behavioral measurements of these tests and were characterized by higher maternal motivation than unselected rats. It is suggested that long-term breeding of tame and aggressive rats in captivity has reduced the threshold for maternal behavior. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Effect of Intramuscular Protons, Lactate, and ATP on Muscle Hyperalgesia in Rats

    PubMed Central

    Gregory, Nicholas S.; Whitley, Phillip E.; Sluka, Kathleen A.

    2015-01-01

    Chronic muscle pain is a significant health problem leading to disability[1]. Muscle fatigue can exacerbate muscle pain. Metabolites, including ATP, lactate, and protons, are released during fatiguing exercise and produce pain in humans. These substances directly activate purinergic (P2X) and acid sensing ion channels (ASICs) on muscle nociceptors, and when combined, produce a greater increase in neuron firing than when given alone. Whether the enhanced effect of combining protons, lactate, and ATP is the sum of individual effects (additive) or more than the sum of individual effects (synergistic) is unknown. Using a rat model of muscle nociceptive behavior, we tested each of these compounds individually over a range of physiologic and supra-physiologic concentrations. Further, we combined all three compounds in a series of dilutions and tested their effect on muscle nociceptive behavior. We also tested a non-hydrolyzable form of ATP (α,β-meATP) alone and in combination with lactate and acidic pH. Surprisingly, we found no dose-dependent effect on muscle nociceptive behavior for protons, lactate, or ATP when given alone. We similarly found no effect after application of each two-metabolite combination. Only pH 4 saline and α,β-meATP produced hyperalgesia when given alone. When all 3 substances were combined, however, ATP (2.4μm), lactate (10mM), and acidic pH (pH 6.0) produced an enhanced effect greater than the sum of the effects of the individual components, i.e. synergism. α,β me ATP (3nmol), on the other hand, showed no enhanced effects when combined with lactate (10mM) or acidic pH (pH 6.0), i.e. additive. These data suggest that combining fatigue metabolites in muscle produces a synergistic effect on muscle nociception. PMID:26378796

  14. Effect of Intramuscular Protons, Lactate, and ATP on Muscle Hyperalgesia in Rats.

    PubMed

    Gregory, Nicholas S; Whitley, Phillip E; Sluka, Kathleen A

    2015-01-01

    Chronic muscle pain is a significant health problem leading to disability[1]. Muscle fatigue can exacerbate muscle pain. Metabolites, including ATP, lactate, and protons, are released during fatiguing exercise and produce pain in humans. These substances directly activate purinergic (P2X) and acid sensing ion channels (ASICs) on muscle nociceptors, and when combined, produce a greater increase in neuron firing than when given alone. Whether the enhanced effect of combining protons, lactate, and ATP is the sum of individual effects (additive) or more than the sum of individual effects (synergistic) is unknown. Using a rat model of muscle nociceptive behavior, we tested each of these compounds individually over a range of physiologic and supra-physiologic concentrations. Further, we combined all three compounds in a series of dilutions and tested their effect on muscle nociceptive behavior. We also tested a non-hydrolyzable form of ATP (α,β-meATP) alone and in combination with lactate and acidic pH. Surprisingly, we found no dose-dependent effect on muscle nociceptive behavior for protons, lactate, or ATP when given alone. We similarly found no effect after application of each two-metabolite combination. Only pH 4 saline and α,β-meATP produced hyperalgesia when given alone. When all 3 substances were combined, however, ATP (2.4μm), lactate (10mM), and acidic pH (pH 6.0) produced an enhanced effect greater than the sum of the effects of the individual components, i.e. synergism. α,β me ATP (3nmol), on the other hand, showed no enhanced effects when combined with lactate (10mM) or acidic pH (pH 6.0), i.e. additive. These data suggest that combining fatigue metabolites in muscle produces a synergistic effect on muscle nociception.

  15. Periconceptional Heat Stress of Holstein Dams Is Associated with Differences in Daughter Milk Production during Their First Lactation

    PubMed Central

    Brown, Britni M.; Stallings, Jon W.; Clay, John S.; Rhoads, Michelle L.

    2016-01-01

    The fertility of lactating Holstein cows is severely reduced during periods of heat stress. Despite this reduction in fertility, however, some inseminations conducted during heat stress result in successful pregnancies from which heifer calves are born. Many of these heifer calves are retained and raised to enter the milking herd as replacement animals. Heat stress experienced by these females around the time they were conceived may confer long-lasting effects that alter subsequent milk production capacity. The objective of this study was to examine the relationship between periconceptional heat stress and subsequent milk production of primiparous cows. National Dairy Herd Improvement Association data was obtained from Dairy Records Management Systems. Records included Holstein cows that had completed at least one lactation in one of three states with large populations of dairy cattle and which are known for having hot, humid summers: Georgia, Florida or Texas. Dates of conception were calculated by subtracting 276 d from the recorded birth date of each individual cow. Records for cows conceived within the months of June, July, and August were retained as heat stress-conceived (HSC) cows (n = 94,440); cows conceived within the months of December, January, and February were retained as thermoneutral-conceived (TNC) contemporaries (n = 141,365). In order to account for the effects of environmental conditions on total milk production for a given lactation, cows were blocked by season of calving (winter, spring, summer or fall). Adjusted 305-day mature-equivalent milk production was evaluated with a mixed model ANOVA using SAS, in which random effects were used to account for variability between herds. Of the cows that calved in the summer, fall and winter, TNC cows had higher milk yield than the HSC cows in all states. Interestingly, the cows that calved in the spring presented a unique relationship, with HSC cows producing more milk. Overall however, heat stress at

  16. Periconceptional Heat Stress of Holstein Dams Is Associated with Differences in Daughter Milk Production during Their First Lactation.

    PubMed

    Brown, Britni M; Stallings, Jon W; Clay, John S; Rhoads, Michelle L

    2016-01-01

    The fertility of lactating Holstein cows is severely reduced during periods of heat stress. Despite this reduction in fertility, however, some inseminations conducted during heat stress result in successful pregnancies from which heifer calves are born. Many of these heifer calves are retained and raised to enter the milking herd as replacement animals. Heat stress experienced by these females around the time they were conceived may confer long-lasting effects that alter subsequent milk production capacity. The objective of this study was to examine the relationship between periconceptional heat stress and subsequent milk production of primiparous cows. National Dairy Herd Improvement Association data was obtained from Dairy Records Management Systems. Records included Holstein cows that had completed at least one lactation in one of three states with large populations of dairy cattle and which are known for having hot, humid summers: Georgia, Florida or Texas. Dates of conception were calculated by subtracting 276 d from the recorded birth date of each individual cow. Records for cows conceived within the months of June, July, and August were retained as heat stress-conceived (HSC) cows (n = 94,440); cows conceived within the months of December, January, and February were retained as thermoneutral-conceived (TNC) contemporaries (n = 141,365). In order to account for the effects of environmental conditions on total milk production for a given lactation, cows were blocked by season of calving (winter, spring, summer or fall). Adjusted 305-day mature-equivalent milk production was evaluated with a mixed model ANOVA using SAS, in which random effects were used to account for variability between herds. Of the cows that calved in the summer, fall and winter, TNC cows had higher milk yield than the HSC cows in all states. Interestingly, the cows that calved in the spring presented a unique relationship, with HSC cows producing more milk. Overall however, heat stress at

  17. Effects of L-Lactate and D-Mannitol on γ-Hydroxybutyrate Toxicokinetics and Toxicodynamics in Rats

    PubMed Central

    Wang, Qi; Wang, Xiaodong

    2008-01-01

    Overdoses of γ-hydroxybutyrate (GHB), a drug of abuse, result in coma, respiratory arrest, and death. The objective of this study was to evaluate a potential GHB detoxification strategy by inhibiting the monocarboxylate transporter (MCT)-mediated renal reabsorption of GHB in rats, using the MCT substrate L-Lactate. The use of the osmotic diuretic D-mannitol alone or combined with L-Lactate was also explored. GHB (208 mg/h/kg) was infused i.v. for 3 h in the absence or presence of L-Lactate (60.5, 121, and 302.5 mg h−1 kg−1), D-mannitol (0.5 g/kg), or L-Lactate (60.5 mg h−1 kg−1) combined with D-mannitol (0.5 g/kg). GHB in plasma and urine samples was determined along with blood pH, electrolytes, glucose, and L-Lactate. Administration of L-Lactate, or the combination of L-Lactate and D-mannitol, but not D-mannitol alone, significantly increased the renal and total clearances of GHB in rats. Blood pH and electrolyte concentrations exhibited small changes with GHB, GHB/lactate, and GHB/mannitol treatments, although most values remained within their normal range. The concomitant administration of lactated Ringer's solution (28 mM L-Lactate) at 300 µl/min with mannitol (0.5 g/kg) resulted in a significant increase in GHB clearance and a decrease in sleep time after an i.v. dose of 1 g/kg. Overall, our results indicated the following: 1) the use of the MCT inhibitor L-Lactate can increase the renal and total clearances of GHB, and 2) the combination of lactated Ringer's solution and D-mannitol significantly alters GHB toxicokinetics and toxicodynamics and represents a potential clinical detoxification strategy for the treatment of GHB overdoses. PMID:18719239

  18. Detection of intracellular lactate with localized diffusion { 1H- 13C}-spectroscopy in rat glioma in vivo

    NASA Astrophysics Data System (ADS)

    Pfeuffer, Josef; Lin, Joseph C.; DelaBarre, Lance; Ugurbil, Kamil; Garwood, Michael

    2005-11-01

    The aim of this study was to compare the diffusion characteristic of lactate and alanine in a brain tumor model to that of normal brain metabolites known to be mainly intracellular such as N-acetylaspartate or creatine. The diffusion of 13C-labeled metabolites was measured in vivo with localized NMR spectroscopy at 9.4 T (400 MHz) using a previously described localization and editing pulse sequence known as ACED-STEAM ('adiabatic carbon editing and decoupling'). 13C-labeled glucose was administered and the apparent diffusion coefficients of the glycolytic products, { 1H- 13C}-lactate and { 1H- 13C}-alanine, were determined in rat intracerebral 9L glioma. To obtain insights into { 1H- 13C}-lactate compartmentation (intra- versus extracellular), the pulse sequence used very large diffusion weighting (50 ms/μm 2). Multi-exponential diffusion attenuation of the lactate metabolite signals was observed. The persistence of a lactate signal at very large diffusion weighting provided direct experimental evidence of significant intracellular lactate concentration. To investigate the spatial distribution of lactate and other metabolites, 1H spectroscopic images were also acquired. Lactate and choline-containing compounds were consistently elevated in tumor tissue, but not in necrotic regions and surrounding normal-appearing brain. Overall, these findings suggest that lactate is mainly associated with tumor tissue and that within the time-frame of these experiments at least some of the glycolytic product ([ 13C] lactate) originates from an intracellular compartment.

  19. Differential Contribution of Hypothalamic MAPK Activity to Anxiety-Like Behaviour in Virgin and Lactating Rats

    PubMed Central

    Maloumby, Rodrigue; Hillerer, Katharina; Koszinowski, Sophie; Neumann, Inga D.; van den Burg, Erwin H.

    2012-01-01

    The c-Raf – MEK1/2 – ERK1/2 mitogen-activated protein kinase (MAPK) intracellular signalling cascade in neurons plays important roles in the control of a variety of behaviours, including social behaviours and anxiety. These roles partially overlap with those described for oxytocin (OXT), and it has been shown that OXT activates the MAPK pathway in the hypothalamus (of male), and hippocampus (of female) rats. Here, by combining behavioural (light/dark box) and biochemical analyses (western blotting), we tested two hypotheses: (i) that OXT is anxiolytic within the hypothalamus of females, and (ii) that this effect, as well as that of lactation-associated anxiolysis, depends on the recruitment of the MAPK pathway. We found that, when injected bilaterally into the hypothalamic paraventricular nucleus (PVN), OXT decreased anxiety-like behaviour in virgins, and that this effect depended on phosphorylation of MEK1/2. MAPK pathway activation in lactation was evident by high phosphorylated (p) MEK1/2 levels, and nuclear translocation of ERK1. The high pMEK1/2 levels were necessary for the anxiolytic phenotype typically observed during lactation. Interestingly, exogenous OXT in lactating rats reduced pMEK1/2 levels without a concomitant effect on anxiety, indicating that OXT receptor activation can lead to recruitment of additional intracellular pathways to modulate MEK activity. Still other pathways could include MEK, but without subsequent activation of ERK, as we did not observe any increase in OXT-induced ERK phosphorylation. Together the results demonstrate that the MAPK pathway, especially MEK1/2, is critically involved in the regulation of anxiety-like behaviour in female rats. PMID:22615888

  20. Differential contribution of hypothalamic MAPK activity to anxiety-like behaviour in virgin and lactating rats.

    PubMed

    Jurek, Benjamin; Slattery, David A; Maloumby, Rodrigue; Hillerer, Katharina; Koszinowski, Sophie; Neumann, Inga D; van den Burg, Erwin H

    2012-01-01

    The c-Raf - MEK1/2 - ERK1/2 mitogen-activated protein kinase (MAPK) intracellular signalling cascade in neurons plays important roles in the control of a variety of behaviours, including social behaviours and anxiety. These roles partially overlap with those described for oxytocin (OXT), and it has been shown that OXT activates the MAPK pathway in the hypothalamus (of male), and hippocampus (of female) rats. Here, by combining behavioural (light/dark box) and biochemical analyses (western blotting), we tested two hypotheses: (i) that OXT is anxiolytic within the hypothalamus of females, and (ii) that this effect, as well as that of lactation-associated anxiolysis, depends on the recruitment of the MAPK pathway. We found that, when injected bilaterally into the hypothalamic paraventricular nucleus (PVN), OXT decreased anxiety-like behaviour in virgins, and that this effect depended on phosphorylation of MEK1/2. MAPK pathway activation in lactation was evident by high phosphorylated (p) MEK1/2 levels, and nuclear translocation of ERK1. The high pMEK1/2 levels were necessary for the anxiolytic phenotype typically observed during lactation. Interestingly, exogenous OXT in lactating rats reduced pMEK1/2 levels without a concomitant effect on anxiety, indicating that OXT receptor activation can lead to recruitment of additional intracellular pathways to modulate MEK activity. Still other pathways could include MEK, but without subsequent activation of ERK, as we did not observe any increase in OXT-induced ERK phosphorylation. Together the results demonstrate that the MAPK pathway, especially MEK1/2, is critically involved in the regulation of anxiety-like behaviour in female rats.

  1. An Herbal Galactagogue Mixture Increases Milk Production and Aquaporin Protein Expression in the Mammary Glands of Lactating Rats

    PubMed Central

    Liu, Haibin; Hua, Ying; Luo, Hui; Shen, Zhaojun; Tao, Xuejiao

    2015-01-01

    Background. Herbal galactagogues have been increasingly used to treat postpartum hypogalactia. The mechanism of action of herbal galactagogues remains unclear. The purpose of this study was to investigate the effect of an herbal galactagogue mixture on milk production and aquaporin (AQP) expression in lactating rats. Methods. Thirty female Sprague Dawley rats were randomized into virgin, lactating + H2O, and lactating + galactagogue groups (n = 10 per group). Lactating rats were administered the decoction of an herbal galactagogue mixture by oral gavage or the same amount of distilled water. Results. The herbal decoction significantly increased milk production in lactating rats (P < 0.05). Both immunohistochemical staining and western blot showed that protein levels of AQP-3 and AQP-5 were significantly increased during lactation compared with virgin stage and the herbal decoction further elevated their expression (P < 0.05). AQP-1 was predominantly expressed in the capillaries whereas AQP-3 and AQP-5 were mainly detected in the epithelial cells and ducts of the mammary glands. Conclusion. The expression of AQPs in the mammary glands of rats was developmentally regulated. Herbal galactagogues might have increased milk secretion by regulating the expression and function of AQPs in the mammary glands. PMID:26075000

  2. Chronic fluoxetine treatment and maternal adversity differentially alter neurobehavioral outcomes in the rat dam.

    PubMed

    Pawluski, Jodi L; Charlier, Thierry D; Fillet, Marianne; Houbart, Virginie; Crispin, Hilda T; Steinbusch, Harry W; van den Hove, Daniël L

    2012-03-01

    The incidence of stress and stress-related disorders with the transition to motherhood, such as postpartum depression, is estimated to be 20%. Selective serotonin reuptake inhibitor (SSRI) medications are currently the antidepressant of choice to treat maternal mood disorders. However, little is known about the effects of these medications on the maternal brain and behavior. Therefore, the present study investigated how a commonly used SSRI, fluoxetine, affects neurobehavioral outcomes in the mother using a model of maternal adversity. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle. Dams were divided into four groups: (1) Control + Vehicle, (2) Control + Fluoxetine, (3) Stress + Vehicle and (4) Stress + Fluoxetine. Fluoxetine or vehicle was administered to the dam during the postpartum period via osmotic minipump implants (Alzet) for 28 days. Results show that chronic fluoxetine treatment, after exposure to gestational stress, significantly decreased serum levels of corticosteroid binding globulin and increased hippocampal neurogenesis. In the absence of maternal stress, fluoxetine treatment alone significantly increased maternal arched-back nursing of pups, increased anxiety-related behavior, and decreased serum levels of corticosterone and corticosteroid binding globulin in the dam. This research provides important information on how SSRIs may act on the behavior, physiology, and neural plasticity of the mother. Although this is a first step in investigating the role of antidepressant treatment on the mother, much more work is needed before we can understand and improve the efficacy of these medications to treat mood disorders in pregnant and postpartum women. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Estrogen receptor α and β expressions in hypothalamus-pituitary-ovary axis in rats exposed lactationally to soy isoflavones and bisphenol A.

    PubMed

    Yu, Bo; Chen, Qing-Feng; Liu, Zhao-Ping; Xu, He-Fei; Zhang, Xiao-Peng; Xiang, Qain; Zhang, Wen-Zhong; Cui, Wen-Ming; Zhang, Xin; Li, Ning

    2010-10-01

    This paper aims to investigate the uterotrophic activities of lactational exposure to combination of soy isoflavones (SIF) and bisphenol A (BPA) and to examine estrogen receptor α (ERα) and estrogen receptor β (ERβ) expressions in hypothalamus-pituitary-ovary axis and uterus. Maternal rats that were breeding about 8 litters were randomly divided into four groups with seven dams in each group. Dams in different treatment groups received corn oil (control), 150 mg/kg BW of SIF, 150 mg/kg BW of BPA or combination of 150 mg/kg BW of SIF and 150 mg/kg BW of BPA, respectively, from postnatal day 5 to 11 (PND5-11) by gavage. On PND12 and PND70, 10 female litters were killed and hypothalamus, pituitary, ovary and uterus were collected. ERα and ERβ expressions in these organs were detected with Western blotting assay. And vaginal opening time and estrus cycle were examined in animals fed for PND70. On PND12, the relative uterine weight of rats treated with ISF or BPA or their combination was significantly higher than that of untreated rats (P<0.05). But the relative uterine weight of rats in the co-exposure group was slightly lower than that in the group only exposed to SIF or BPA. On PND 70, however, the relative uterine weight in each treatment group was not statistically different from that in the control group (P>0.05). Vaginal opening time and estrus cycle in groups treated with SIF or BPA or their combination were similar to those in the control group (P>0.05). Exposure to SIF or BPA or their combination could up-regulate or down-regulate ERα and ERβ expressions in hypothalamus, pituitary, ovary and uterus on PND12 and PND70. These regulation patterns for ERα and ERβ were different in different organs at different time points. Lactational exposure to ISF or BPA or their combination could induce uterotrophic responses in neonate rats, which disappeared in later life. But these data fail to suggest a possibility for synergic actions between SIF and BPA. It was

  4. Dose-response effects of diphenylhydantoin on pregnant dams and embryo-fetal development in rats.

    PubMed

    Kim, Sung-Hwan; Lee, In-Chul; Baek, Hyung-Seon; Lim, Jeong-Hyeon; Moon, Changjong; Shin, Dong-Ho; Kim, Sung-Ho; Park, Seung-Chun; Kim, Jong-Choon

    2012-10-01

    Despite the widespread use of diphenylhydantoin (DPH), there is a lack of reliable information on the teratogenic effects, correlation with maternal and developmental toxicity, and dose-response relationship of DPH. This study investigated the dose-response effects of DPH on pregnant dams and embryo-fetal development as well as the relationship between maternal and developmental toxicity. DPH was orally administered to pregnant rats from gestational days 6 through 15 at 0, 50, 150, and 300 mg/kg/day. At 300 mg/kg, maternal toxicity including increased clinical signs, suppressed body weight, decreased food intake, and increased weights of adrenal glands, liver, kidneys, and brain were observed in dams. Developmental toxicity, including a decrease in fetal and placental weights, increased incidence of morphological alterations, and a delay in fetal ossification delay also occurred. At 150 mg/kg, maternal toxicity manifested as an increased incidence of clinical signs, reduced body weight gain and food intake, and increased weights of adrenal glands and brain. Only minimal developmental toxicity, including decreased placental weight and an increased incidence of visceral and skeletal variations, was observed. No treatment-related maternal or developmental effects were observed at 50 mg/kg. These results show that DPH is minimally embryotoxic at a minimal maternotoxic dose (150 mg/kg/day) but is embryotoxic and teratogenic at an overt maternotoxic dose (300 mg/kg/day). Under these experimental conditions, the no-observed-adverse-effect level of DPH for pregnant dams and embryo-fetal development is considered to be 50 mg/kg/day. These data indicate that DPH is not a selective developmental toxicant in the rat.

  5. Effects of silver nanoparticles on pregnant dams and embryo-fetal development in rats.

    PubMed

    Yu, Wook-Joon; Son, Jung-Mo; Lee, Jinsoo; Kim, Sung-Hwan; Lee, In-Chul; Baek, Hyung-Seon; Shin, In-Sik; Moon, Changjong; Kim, Sung-Ho; Kim, Jong-Choon

    2014-08-01

    Although the potential risk of silver nanoparticles (AgNPs) to humans has recently increased due to widespread application, the potential effects of AgNPs on embryo-fetal development have not yet been determined. This study investigated the potential effects of AgNPs on pregnant dams and embryo-fetal development after maternal exposure on gestational days (GD) 6-19 in rats. AgNPs were administered to pregnant rats by gavage at concentrations of 0, 100, 300, and 1000 mg/kg/day. All dams were subjected to Cesarean section on GD 20 and the fetuses were examined for signs of embryotoxic and teratogenic effects. Examinations of hepatic oxidant/antioxidant balance and serum biochemistry were also added to the routine developmental toxicity study. Treatment with AgNPs caused a decrease in catalase and glutathione reductase activities at ≥100 mg/kg/day and a reduction in glutathione content at 1000 mg/kg/day in maternal liver tissues. However, no treatment-related deaths or clinical signs were observed in any of the animals treated with AgNPs. No treatment-related differences in maternal body weight, food consumption, gross findings, serum biochemistry, organ weight, gestation index, fetal deaths, fetal and placental weights, sex ratio, or morphological alterations were observed between the groups. The results show that repeated oral doses of AgNPs during pregnancy caused oxidative stress in hepatic tissues at ≥100 mg/kg/day, but did not cause developmental toxicity at doses of up to 1000 mg/kg/day. The no-observed-adverse-effect level of AgNPs is considered to be <100 mg/kg/day for dams and 1000 mg/kg/day for embryo-fetal development.

  6. Early exposure of dams to a westernized diet has long-term consequences on food intake and physiometabolic homeostasis of the rat offspring.

    PubMed

    Ferro Cavalcante, Taisy Cinthia; Marcelino da Silva, Amanda Alves; Lira, Maria Cláudia Alheiros; do Amaral Almeida, Larissa Cavalcanti; Marques, Ana Patricia Jaques; do Nascimento, Elizabeth

    2014-12-01

    This study evaluated the long-term effects of a westernized diet during pregnancy and lactation. Female Wistar rats (n = 12) were divided into two groups according to their food intake, namely, control (C) or westernized (W) diet, throughout pregnancy/lactation. On the 21st day, the male pups were weaned on a standard diet as follows: Control diet (CC) (n = 8) and westernized diet in perinatal life followed by control diet post weaning (WC) (n = 8). The levels of fasting (12 h) serum glucose, triglycerides (TG), and total cholesterol and fraction in the pups were determined. During weaning, the WC group showed 14% greater body weight (p < 0.001). In the adulthood, the offspring from dams fed on westernized diet showed hyperphagia, hyperinsulinism, hypertriglyceridemia, higher fat visceral weight, higher very-low-density-lipoprotein cholesterol level, decreased high-density-lipoprotein cholesterol level, and altered glucose tolerance test. In conclusion, maternal western-style diet in early life altered long-term food intake, visceral fat pad, insulin, glucose and lipid serum, and increased risk of metabolic disorders.

  7. The effect of an exteroceptive stimulus on milk ejection in lactating rats

    PubMed Central

    Deis, R. P.

    1968-01-01

    1. The exteroceptive stimulus emanating from a lactating rat and the litter while suckling was used to induce milk ejection in another lactating mother 15 min before the replacement of her own litter. The effect of the external stimulus on milk ejection during one 30 min period and four 15 min periods of nursing was studied. 2. After being isolated for 9 hr the litter from the mother subjected to the exteroceptive nursing stimulus (induced rat) obtained a significantly greater amount of milk during 30 min of nursing than that obtained by the litter from the control mother. 3. When deaf mother rats were used the gain of milk by the litter showed no difference between the control and the induced mother. This result indicated that the effective external stimulus is an auditory one and is probably produced by the mother rat and the young while suckling. 4. The administration of oxytocin (Syntocinon, Sandoz) 20 m-u./100 g body wt., 15 min before the replacement of the litter produced a milk ejection similar to that obtained under the influence of the auditory stimulus. This would indicate that the exteroceptive stimulus probably evokes the release of oxytocin from the neurohypophysis. 5. When nursing was performed in four periods of 15 min each the litter of the control mother obtained milk only in the second period of nursing while the litter of the induced mother obtained milk in all four periods of nursing and the amount of milk obtained in the whole hour was greater than that from the control rat. 6. The administration of oxytocin just before the replacement of the litter every 15 min produced milk ejection only in the first two periods of suckling in the control rats but the induced rats were capable of ejecting milk during all four periods. 7. The most satisfactory conclusion for the results obtained is that the C.N.S. regulates both the release of oxytocin in response to suckling and the response of the mammary gland to oxytocin, in the lactating rat. PMID

  8. Susceptibility of fetal, virgin, pregnant and lactating rats for the induction of mammary tumors by gamma rays

    SciTech Connect

    Inano, Hiroshi; Suzuki, Heiko; Onoda, Makoto; Yamanouchi, Hiroshi

    1996-06-01

    Pregnant Wistar-MS rats received a whole-body irradiation of 0-2.6 Gy {gamma} rays at day 20 of pregnancy. The mother rats were implanted with a diethylstilbestrol (DES) pellet 30 days after weaning, and the female pups delivered by the irradiated mother were treated with DES after maturation. Lactating rats were irradiated with {gamma} rays 21 days after parturition and then treated with DES. Virgin rats 70 days of age were also irradiated and then administered DES. The rats which received intrauterine irradiation did not develop mammary tumors in the mother rats and lactating rats increased in a dose-dependent manner with increasing doses of {gamma} rays up to 2.1 Gy. With 0.1-1 Gy, the incidence of adenocarcinoma in the mother rats was significantly lower than that observed in the lactating rats. However, the incidence in the mother rats irradiated with 1.0-1.5 Gy was significantly higher than that of virgin rats treated with the corresponding {gamma}-ray doses. These findings suggest that the susceptibility of the mammary glands to radiation depends upon the differentiation at the time of exposure. 22 refs., 4 figs., 2 tabs.

  9. [Activity of digestive enzymes in offspring of rats fed a ration contaminated by heavy metals during lactation].

    PubMed

    Sadykov, B A; Kuchkarova, L S; Ermatova, S U; Ergashev, N A

    2009-01-01

    Is was shown the consumption of heavy metal's salts with food by lactating rats, essential influences on formation of mechanisms of cavity and membrane digestive in offspring. This influence is shown in repression of activity of pancreatic alpha-amylase and enteral saccrase, maltase as well as in induction of lactase activity in growing rats.

  10. Developmental delays in offspring of rats undernourished or zinc deprived during lactation.

    PubMed

    Eberhardt, M J; Halas, E S

    1987-01-01

    Offspring of rats who were zinc or calorie deprived during lactation were administered a battery of reflex and motor tests from postnatal Day 4 to Day 21. Compared to offspring of ad lib-fed control rats, both zinc deprived and undernourished offspring exhibited developmental delays in reflexes which appeared after the first postnatal week (auditory startle, air righting, and rope descent). As the deficiencies continued the delays appeared to be more pronounced. The zinc deficiency did not add to the deficits associated with calorie restriction alone because there were no significant differences between the zinc deficient and undernourished pups on any of the measures except eye opening. When rehabilitated offspring were tested at 45 and 60 days of age for motor deficits there were no significant impairments resulting from preweaning dietary conditions. However, the growth retardation of zinc deprived and undernourished rats persisted long after dietary rehabilitation was implemented.

  11. In utero and lactational exposure to fluoxetine delays puberty onset in female rats offspring.

    PubMed

    Dos Santos, Alice Hartmann; Vieira, Milene Leivas; de Azevedo Camin, Nathália; Anselmo-Franci, Janete Aparecida; Ceravolo, Graziela Scalianti; Pelosi, Gislaine Garcia; Moreira, Estefânia Gastaldello; Kiss, Ana Carolina Inhasz; Mesquita, Suzana de Fátima Paccola; Gerardin, Daniela Cristina Ceccatto

    2016-07-01

    Depression is one of the most prevalent disorders in the world and may occur during pregnancy and postpartum periods. Fluoxetine (FLX) has been widely prescribed for use during depression in pregnancy and lactation. This study aimed to investigate if in utero and lactational exposure to FLX could compromise reproductive parameters in female offspring. Wistar rats received, by daily gavage, FLX 5mg/kg or 0.3ml of water (control group) from the first gestational day until weaning (21 days). Assessments in the female offspring included: body weight, anogenital distance, vaginal opening, first estrus, estrous cycle, reproductive organs weight, uterine morphometric analyses, ovarian follicle and corpora lutea counting, estradiol plasmatic concentration, sexual behavior, maternal behavior and fertility test. Exposure to FLX delayed the puberty onset in female pups. The present study demonstrated that developmental exposure to FLX can deregulate the neuroendocrine hormonal control of female offspring during prepubertal and pubertal periods. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Hypothyroidism decreases JAK/STAT signaling pathway in lactating rat mammary gland.

    PubMed

    Campo Verde Arboccó, Fiorella; Persia, Fabio Andres; Hapon, María Belén; Jahn, Graciela A

    2017-07-15

    Thyroid pathologies have deleterious effects on lactation. Especially hypothyroidism (HypoT) induces premature mammary involution at the end of lactation and decreases milk production and quality in mid lactation. Milk synthesis is controlled by JAK2/STAT5 signaling pathway and prolactin (PRL), which activates the pathway. In this work we analyzed the effect of chronic 6-propyl-2-thiouracil (PTU)-induced HypoT on PRL signaling pathway on mammary glands from rats on lactation (L) days 2, 7 and 14. HypoT decreased prolactin receptor expression, and expression and activation of Stat5a/b protein. Expression of members of the SOCS-CIS family, inhibitors of the JAK-STAT pathway, decreased in L2 and L7, possibly as a compensatory response of the mammary cells to maintain PRL responsiveness. However, on L14, the level of these inhibitors was normal and the transcription of α-lactoalbumin (lalba), a target gene of the PRL pathway, decreased by half. HypoT altered the transcriptional capacity of the cell and decreased mRNA levels of Prlr and Stat5b on L14. Stat5b gene has functional thyroid hormone response elements in the regulatory regions, that bind thyroid hormone receptor β (TRβ) differentially and in a thyroid hormone dependent manner. The overall decrease in the PRL signaling pathway and consequently in target gene (lalba) mRNA transcription explain the profound negative impact of HypoT on mammary function through lactation. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Continuous and simultaneous electrochemical measurements of glucose, lactate, and ascorbate in rat brain following brain ischemia.

    PubMed

    Lin, Yuqing; Yu, Ping; Hao, Jie; Wang, Yuexiang; Ohsaka, Takeo; Mao, Lanqun

    2014-04-15

    Developing new tools and technologies to enable recording the dynamic changes of multiple neurochemicals is the essence of better understanding of the molecular basis of brain functions. This study demonstrates a microfluidic chip-based online electrochemical system (OECS) for in vivo continuous and simultaneous monitoring of glucose, lactate, and ascorbate in rat brain. To fabricate the microfluidic chip-based detecting system, a microfluidic chip with patterned channel is developed into an electrochemical flow cell by incorporating the chip with three surface-modified indium-tin oxide (ITO) electrodes as working electrodes, a Ag/AgCl wire as reference electrode, and a stainless steel tube as counter electrode. Selective detection of ascorbate is achieved by the use of single-walled carbon nanotubes (SWNTs) to largely facilitate the electrochemical oxidation of ascorbate, while a dehydrogenase-based biosensing mechanism with methylene green (MG) adsorbed onto SWNTs as an electrocatalyst for the oxidation of dihydronicotiamide adenine dinucleotide (NADH) is employed for biosensing of glucose and lactate. To avoid the crosstalk among three sensors, the sensor alignment is carefully designed with the SWNT-modified electrode in the upstream channel and paralleled glucose and lactate biosensors in the downstream channels. With the microfluidic chip-based electrochemical flow cell as the detector, an OECS is successfully established by directly integrating the microfluidic chip-based electrochemical flow cell with in vivo microdialysis. The OECS exhibits a good linear response toward glucose, lactate, and ascorbate with less crosstalk. This property, along with the high stability and selectivity, enables the OECS for continuously monitoring three species in rat brain following brain ischemia.

  14. Carrier-mediated L-lactate transport in brush-border membrane vesicles from rat placenta during late gestation.

    PubMed Central

    Alonso de la Torre, S R; Serrano, M A; Alvarado, F; Medina, J M

    1991-01-01

    The mechanism for L-lactate transport across microvillous membrane vesicles prepared from rat placenta was examined. Uptake of L-lactate into these vesicles was mainly the result of transport into the intravesicular (osmotically active) space. The initial rate of L-lactate uptake was not affected by the presence of an inward gradient of either Na+ or K+. In the presence of an inward-directed proton gradient, L-lactate uptake was markedly stimulated, accumulating at concentrations 6-7-fold higher than the equilibrium. Lower transmembrane pH gradients were associated with slower initial uptakes and smaller overshoots. L-Lactate uptake determined under an inside-directed pH gradient was strongly inhibited by p-chloromercuriphenylsulphonic acid, a protein-thiol oxidizing agent. L-Lactate uptake was: (1) saturable as a function of the concentration of L-lactate, (2) inhibited by monocarboxylic acids such as pyruvate, D-lactate, beta-hydroxybutyrate and alpha-cyano-4-hydroxycinnamic acid, and (3) temperature-dependent. When present inside the vesicles, L-lactate, pyruvate and beta-hydroxybutyrate caused trans-stimulation of L-lactate uptake both in the presence and in the absence of an inside-directed pH gradient, indicating that L-lactate transport is a reversible process that can be shared by other monocarboxylic acids. There were no significant changes in maximal initial rate or in the kinetic parameters of L-lactate transport during the last 3 days of gestation. PMID:1654886

  15. Aspects of the Development of Housing for the Spaceflight of Pregnant and Lactating Rats with Neonates

    NASA Technical Reports Server (NTRS)

    Hinds, William E.; Mayer, David J.; Evans, Juli; Spratt, Shahn; Lane, Philip K.; Rodriguez, Shari L.; Navidi, Meena; Armstrong, Rachel; Lemos, Bonnie; Dalton, Bonnie P. (Technical Monitor)

    1996-01-01

    Recent and upcoming spaceflights are investigating the effect of weightlessness on developing neural and organ systems. Pregnant rats and dams with neonates have to be accommodated in cages that support the special requirements of these animals. Extensive ground testing of cage concepts, the effect of launch and landing stresses on the maintenance of pregnancy and maternal behavior at different neonatal ages, and techniques for monitoring adaptability to change are discussed. A spaceflight opportunity for the NlH.R3 payload of rat families at three different postnatal ages demonstrated that the survival of very young animals was not good but that older newborns could be returned to Earth in reasonably good health. The development of cages for the Research Animal Holding Facility (RAHF) to support the flight of neonates on Neurolab was continued and incorporated modifications that were demonstrated by the NIH.R3 flight. Other modifications to the RAHF are discussed. Data from biocompatibility and experiment verification testing are presented.

  16. Aspects of the Development of Housing for the Spaceflight of Pregnant and Lactating Rats with Neonates

    NASA Technical Reports Server (NTRS)

    Hinds, William E.; Mayer, David J.; Evans, Juli; Spratt, Shahn; Lane, Philip K.; Rodriguez, Shari L.; Navidi, Meena; Armstrong, Rachel; Lemos, Bonnie; Dalton, Bonnie P. (Technical Monitor)

    1996-01-01

    Recent and upcoming spaceflights are investigating the effect of weightlessness on developing neural and organ systems. Pregnant rats and dams with neonates have to be accommodated in cages that support the special requirements of these animals. Extensive ground testing of cage concepts, the effect of launch and landing stresses on the maintenance of pregnancy and maternal behavior at different neonatal ages, and techniques for monitoring adaptability to change are discussed. A spaceflight opportunity for the NlH.R3 payload of rat families at three different postnatal ages demonstrated that the survival of very young animals was not good but that older newborns could be returned to Earth in reasonably good health. The development of cages for the Research Animal Holding Facility (RAHF) to support the flight of neonates on Neurolab was continued and incorporated modifications that were demonstrated by the NIH.R3 flight. Other modifications to the RAHF are discussed. Data from biocompatibility and experiment verification testing are presented.

  17. The effects of pregnancy, lactation, and primiparity on object-in-place memory of female rats.

    PubMed

    Cost, Katherine Tombeau; Lobell, Thomas D; Williams-Yee, Zari N; Henderson, Sherryl; Dohanich, Gary

    2014-01-01

    Maternal physiology and behavior change dramatically over the course of pregnancy to nurture the fetus and prepare for motherhood. Further, the experience of motherhood itself continues to influence brain functioning well after birth, shaping behavior to promote the survival of offspring. To meet these goals, cognitive abilities, such as spatial memory and navigation, may be enhanced to facilitate foraging behavior. Existing studies on pregnant and maternal rats demonstrate enhanced cognitive function in specific spatial domains. We adopted a novel object-in-place task to assess the ability of female rats to integrate information about specific objects in specific locations, a critical element of foraging behavior. Using a longitudinal design to study changes in spatial memory across pregnancy and motherhood, an advantage in the object-in-place memory of primiparous female rats compared to nulliparous females emerged during lactation not during pregnancy, and was maintained after weaning at 42 days postpartum. This enhancement was not dependent on the non-mnemonic variables of anxiety or neophobia. Parity did not affect the type of learning strategy used by females to locate a cued escape platform on a dual-solution water maze task. Results indicate that the enhancement of object-in-place memory, a cognitive function that facilitates foraging, emerged after pregnancy during the postpartum period of lactation and persisted for several weeks after weaning of offspring.

  18. A high multivitamin diet fed to Wistar rat dams during pregnancy increases maternal weight gain later in life and alters homeostatic, hedonic and peripheral regulatory systems of energy balance.

    PubMed

    Pannia, Emanuela; Cho, Clara E; Kubant, Ruslan; Sánchez-Hernández, Diana; Huot, Pedro S P; Chatterjee, Diptendu; Fleming, Alison; Anderson, G Harvey

    2015-02-01

    High multivitamin (10-fold, HV) and high folic acid (Fol) diets fed to pregnant Wistar rats increase body weight and characteristics of the metabolic syndrome in their offspring. Our objective was to determine the effects of a HV maternal diet on dams and whether methyl vitamins contribute to these effects. Pregnant Wistar rats were fed AIN-93G diets containing either (1) recommended multivitamins (RV, control), (2) HV, (3) HV with recommended Fol (HVRF; 1-fold Fol), or (4) RV with high methyl group vitamins (HMethyl; 10-fold Fol, vitamin B12 and B6). All groups were fed a RV diet during lactation until weaning and a RV high fat (HF; 60% fat) diet for 16 weeks post-weaning. The HV, HVRF and HMethyl diet fed dams gained 45% more weight from 2 to 15 weeks post-weaning and their weight gain (WG) was positively associated with cumulative post-weaning food intake (FI). However, only HV dams had a reduced preference for a sucrose solution, lower mesolimbic dopamine (DA) turnover in the nucleus accumbens (NAc), and higher expression of several genes involved in FI regulation in the arcuate nucleus of the hypothalamus (ARC). Energy conserving peroxisome proliferator-activated receptor (Ppar)-γ in adipose and -α in liver was also greater in these dams consistent with their WG. In conclusion, HV, HVRF and HMethyl maternal diets exacerbate maternal WG when dams are exposed to a HF diet post-weaning. However, the diets differed in their effects on central and peripheral regulatory systems of energy balance. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Influence of cafeteria diet and fish oil in pregnancy and lactation on pups' body weight and fatty acid profiles in rats.

    PubMed

    Sánchez-Blanco, Clara; Amusquivar, Encarnación; Bispo, Kenia; Herrera, Emilio

    2016-06-01

    The aim was to determine the effects of cafeteria diet (CD) and fish oil supplements given to pregnant and lactating rats on the birth weight and fatty acid profiles of their offspring. Female rats were given standard diet (STD) or CD for 22 days before pregnancy. After mating, some animals remained on STD or CD; for some CD rats, the diet was supplemented with 8.78 % fish oil (CD-FO). After 12 days, half the CD-FO group returned to CD (CD-FO12) and the others remained on CD-FO. At birth, body weights of pups of the three CD groups were lower than STD, maintained until 21 days in the CD-FO group only. At the end of lactation, dams of the CD groups had increased plasma triacylglycerols (TAG), non-esterified fatty acids, and glycerol concentrations, whereas most n-6 long-chain polyunsaturated fatty acids (LCPUFA) were decreased, the effect being greatest in the CD-FO group, where most n-3 LCPUFA were increased and indices of Δ(5) and Δ(6) desaturase activities decreased. The 21-day-old pups of the CD group had increased plasma TAG, not present in the CD-FO group, which had increased 3-hydroxybutyrate concentrations. In both 2- and 21-day-old CD pups, plasma concentrations of ARA were lower than STD, and even lower in the two CD-FO groups. The effect of CD and CD-FO decreasing pups body weight could be related to decreased concentrations of ARA, caused by the inhibition of the Δ(5) and Δ(6) desaturases in the pathway of n-6 LCPUFA biosynthesis.

  20. Reducing dietary intake of linoleic acid of mouse dams during lactation increases offspring brain n-3 LCPUFA content.

    PubMed

    Schipper, L; Oosting, A; Scheurink, A J W; van Dijk, G; van der Beek, E M

    2016-07-01

    Omega (n-)3 and n-6 long chain polyunsaturated fatty acids (LCPUFA) accumulation in the infant brain after birth is strongly driven by dietary supply of n-3 and n-6 LCPUFAs and their C18 precursors through breast milk or infant formula. n-3 LCPUFA accretion is associated with positive effects on neurodevelopmental outcome whereas high n-6 LCPUFA accumulation is considered disadvantageous. Maternal diet is crucial for breast milk fatty acid composition. Unfortunately, global increases in linoleic acid (C18:2n-6; LA) intake have dramatically increased n-6 LCPUFA and reduced n-3 LCPUFA availability for breastfed infants. We investigated the effects of reducing maternal dietary LA, or increasing n-3 LCPUFA, during lactation on milk and offspring brain fatty acids in mice. Offspring brain n-3 LCPUFA was higher following both interventions, although effects were mediated by different mechanisms. Because of competitive interactions between n-3 and n-6 fatty acids, lowering maternal LA intake may support neurodevelopment in breastfed infants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Exposure to a novel feedstuff by goat dams during pregnancy and lactation versus pregnancy alone does not further improve post-weaning acceptance of this feedstuff by their kids.

    PubMed

    Vu Hai, Phan; Schonewille, J Thomas; Dam Van, Tien; Everts, Henk; Hendriks, Wouter H

    2016-04-01

    Previous experiments demonstrated the existence of in utero learning in goats. However, in contrast to other animal species, in goats there is no information about the potential of flavour transmission from maternal feed to goat kids during lactation. The aim of the current study was to assess the role of post-natal exposure of Chromonaela odorata leaf meal (COLM) in relation to the preferences to this feedstuff by goat kids after weaning. It was hypothesised that exposure of COLM to the dams during both pregnancy and lactation versus pregnancy alone, additionally affects post-weaning intake of COLM by their offspring. Consumption of COLM by the goat kids was similar during the first week post-weaning for all treatments. However, after 4 weeks the intake of COLM was at least 1.8 times greater when kids were exposed to COLM during pregnancy whereas it remained virtually unchanged when kids were exposed to COLM during lactation only. The increase in COLM consumption was in line with the observations on latency to eat and meal size. Transmission of feeding behaviour from goat dams to offspring does not occur during lactation. However, the concept of in utero learning in goats was confirmed. © 2015 Society of Chemical Industry.

  2. IN UTERO EXPOSURE TO ATRAZINE INDUCES DELAYED PUBERTY OF LONG EVANS RATS: DAM-MEDIATED EFFECTS IN FEMALES

    EPA Science Inventory

    IN UTERO EXPOSURE TO ATRAZINE INDUCES DELAYED PUBERTY OF LONG EVANS RATS: DAM-MEDIATED EFFECTS IN FEMALES.

    J L Rayner1 and S E Fenton2.

    1 University of North Carolina at Chapel Hill, School of Public Health, Chapel Hill, NC, and 2 Reproductive Toxicology Divisio...

  3. Lactate dehydrogenase expression at the onset of altered loading in rat soleus muscle.

    PubMed

    Washington, Tyrone A; Reecy, James M; Thompson, Raymond W; Lowe, Larry L; McClung, Joseph M; Carson, James A

    2004-10-01

    Both functional overload and hindlimb disuse induce significant energy-dependent remodeling of skeletal muscle. Lactate dehydrogenase (LDH), an important enzyme involved in anaerobic glycolysis, catalyzes the interconversion of lactate and pyruvate critical for meeting rapid high-energy demands. The purpose of this study was to determine rat soleus LDH-A and -B isoform expression, mRNA abundance, and enzymatic activity at the onset of increased or decreased loading in the rat soleus muscle. The soleus muscles from male Sprague-Dawley rats were functionally overloaded for up to 3 days by a modified synergist ablation or subjected to disuse by hindlimb suspension for 3 days. LDH mRNA concentration was determined by Northern blotting, LDH protein isoenzyme composition was determined by zymogram analysis, and LDH enzymatic activity was determined spectrophotometrically. LDH-A mRNA abundance increased by 372%, and LDH-B mRNA abundance decreased by 43 and 31% after 24 h and 3 days of functional overload, respectively, compared with that in control rats. LDH protein expression demonstrated a shift by decreasing LDH-B isoforms and increasing LDH-A isoforms. LDH-B activity decreased 80% after 3 days of functional overload. Additionally, LDH-A activity increased by 234% following 3 days of hindlimb suspension. However, neither LDH-A or LDH-B mRNA abundance was affected following 3 days of hindlimb suspension. In summary, the onset of altered loading induced a differential expression of LDH-A and -B in the rat soleus muscle, favoring rapid energy production. Long-term altered loading is associated with myofiber conversion; however, the rapid changes in LDH at the onset of altered loading may be involved in other physiological processes.

  4. Effect of maternal exposure to Tityus bahiensis scorpion venom during lactation on the offspring of rats.

    PubMed

    Martins, Adriana do Nascimento; Nencioni, Ana Leonor Abrahão; Dorce, Ana Leticia Coronado; Paulo, Maria Eliza F V; Frare, Eduardo Osório; Dorce, Valquíria Abrão Coronado

    2016-01-01

    Scorpion stings are a public health problem in Brazil and lactating women may be affected. We aimed to study the effects of Tityus bahiensis venom in the offspring of rats treated during lactation. Mothers received a subcutaneous injection of saline (1.0ml/kg) or venom (2.5mg/kg) or an intraperitoneal injection of LPS (lipopolysaccharide) (100μg/kg) on postnatal (PN) days 2 (PN2), 10 (PN10) or 16 (PN16). The offspring were evaluated during the childhood and adulthood. Pups showed a delay in physical and reflexological development, and a decrease in motor activity. Adults displayed low anxiety. There was an increase in the number of viable neuronal cells in hippocampal areas CA1 and CA4. The levels of IFN-γ (interferon-gamma) increased in the experimental groups. Several of the parameters analyzed showed important differences between the sexes. Thus, the scorpion venom affects the development in the offspring of mothers envenomed during the lactation. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Vasoconstrictors alter oxygen, lactate, and glycerol metabolism in the perfused hindlimb of a rat kangaroo.

    PubMed

    Ye, J M; Edwards, S J; Rose, R W; Rattigan, S; Clark, M G; Colquhoun, E Q

    1995-05-01

    The Tasmanian bettong (Bettongia gaimardi) is a small marsupial rat kangaroo without detectable brown adipose tissue (BAT). The hindlimb was perfused with constant flow at 25 degrees C after cannulation under anesthesia of the femoral artery and vein to one hindlimb. Norepinephrine (NE, 25 nM-2.5 microM) and vasopressin (VP, 10 nM-0.1 microM) each increased perfusion pressure, oxygen consumption (VO2), and lactate and glycerol efflux of the perfused hindlimb. NE-mediated increases in VO2 and the efflux of lactate and glycerol were unaffected by propranolol (10 microM) but were completely blocked by the further addition of phentolamine (10 microM). In contrast, serotonin (5-HT; 0.1-2.5 microM) inhibited VO2 and inhibited lactate efflux. The changes induced by NE, VP, and 5-HT were all rapidly reversed by nitroprusside. These results suggest that resting thermogenesis in bettong hindlimb can be differentially controlled by the vasculature, which may also contribute to the induced VO2. This vascular control of skeletal muscle VO2 appears widespread in homeotherm evolution.

  6. The effect of an exteroceptive stimulus on the concentration of melanocyte-stimulating hormone in the pituitary of lactating rats

    PubMed Central

    Deis, R. P.; Orias, R.

    1968-01-01

    1. A study was made of the effect of an exteroceptive stimulus, produced by a team of lactating rats and of litters while suckling, on the pituitary melanocyte-stimulating hormone (MSH) activity of a group of lactating rats. 2. After being isolated for 9 hr from their litter, one group of lactating rats was killed after being allowed to nurse for 30 min, another group was subjected to the exteroceptive stimulus for 15 min and then killed. Control rats were killed after 9 hr of isolation from the litter without being subjected to either suckling or the exteroceptive stimulus. 3. The group of rats which had suckled their young showed a pituitary MSH activity equal to 35 ± 2·29%, and the group exposed to the exteroceptive stimulus an activity equal to 59·5 ± 3·16% of that in the control animals. 4. When deaf rats were used, only the suckled mother showed a decrease of the pituitary MSH activity which was similar to that obtained with the normal suckled mother, indicating that the exteroceptive stimulus depended on hearing for its effect. 5. A light dose of sodium pentobarbitone was sufficient to block the effect of suckling and the auditory stimuli on the pituitary MSH activity. 6. The role of the central nervous system in this phenomenon and the possibility that MSH is implicated in the process of lactation are discussed. PMID:5691946

  7. "Green odor" inhalation by stressed rat dams reduces behavioral and neuroendocrine signs of prenatal stress in the offspring.

    PubMed

    Fujita, Sayaka; Ueki, Shiori; Miyoshi, Michio; Watanabe, Tatsuo

    2010-07-01

    Chronic maternal stress during pregnancy results in the "prenatally stressed" offspring displaying behavioral and neuroendocrine alterations that persist into adulthood. We investigated how inhalation of green odor (a mixture of equal amounts of trans-2-hexenal and cis-3-hexenol) by stressed dams might alter certain indices of prenatal stress in their offspring. These indices were depression-like behavior (increased immobility time in the forced-swim test) and acute restraint stress-induced changes in hypothalamo-pituitary-adrenocortical (HPA) axis activity [plasma corticosterone (CORT) and ACTH levels and the number of Fos-immunoreactive cells in the hypothalamic paraventricular nucleus (an index of neuronal activity)]. Pregnant rats were exposed to restraint stress for 60 min/day for 10 days (gestational days 10-19). The prenatally stressed offspring exhibited significant increases in depression-like behavior and in restraint stress-induced ACTH, CORT, and Fos responses, unless their dam had been exposed to green odor. The behavioral effect of the odor was also seen in offspring that were fostered by unstressed dams. The results obtained in the dams themselves were as follows. In vehicle-exposed stressed dams, but not in green odor-exposed ones, total body and adrenal weights were significantly decreased or increased, respectively. Depression-like behavior was not observed in the vehicle-exposed stressed dams themselves. Green odor inhalation prevented the impairment of maternal behavior induced by restraint stress. Thus, exposure of dams to stress may affect both the fetal brain and fetal HPA axis, and also maternal behavior, leading to altered behavioral and neuroendocrine responses in the offspring. Such effects may be prevented by the stressed dams inhaling green odor.

  8. Gestational and lactational exposure to atrazine via the drinking water causes specific behavioral deficits and selectively alters monoaminergic systems in C57BL/6 mouse dams, juvenile and adult offspring.

    PubMed

    Lin, Zhoumeng; Dodd, Celia A; Xiao, Shuo; Krishna, Saritha; Ye, Xiaoqin; Filipov, Nikolay M

    2014-09-01

    Atrazine (ATR) is one of the most frequently detected pesticides in the U.S. water supply. This study aimed to investigate neurobehavioral and neurochemical effects of ATR in C57BL/6 mouse offspring and dams exposed to a relatively low (3 mg/l, estimated intake 1.4 mg/kg/day) concentration of ATR via the drinking water (DW) from gestational day 6 to postnatal day (PND) 23. Behavioral tests included open field, pole, grip strength, novel object recognition (NOR), forced swim, and marble burying tests. Maternal weight gain and offspring (PND21, 35, and 70) body or brain weights were not affected by ATR. However, ATR-treated dams exhibited decreased NOR performance and a trend toward hyperactivity. Juvenile offspring (PND35) from ATR-exposed dams were hyperactive (both sexes), spent less time swimming (males), and buried more marbles (females). In adult offspring (PND70), the only behavioral change was a sex-specific (females) decreased NOR performance by ATR. Neurochemically, a trend toward increased striatal dopamine (DA) in dams and a significant increase in juvenile offspring (both sexes) was observed. Additionally, ATR exposure decreased perirhinal cortex serotonin in the adult female offspring. These results suggest that perinatal DW exposure to ATR targets the nigrostriatal DA pathway in dams and, especially, juvenile offspring, alters dams' cognitive performance, induces sex-selective changes involving motor and emotional functions in juvenile offspring, and decreases cognitive ability of adult female offspring, with the latter possibly associated with altered perirhinal cortex serotonin homeostasis. Overall, ATR exposure during gestation and lactation may cause adverse nervous system effects to both offspring and dams. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. Lactation reduces stress-caused dopaminergic activity and enhances GABAergic activity in the rat medial prefrontal cortex.

    PubMed

    Arriaga-Avila, Virginia; Martínez-Abundis, Eduardo; Cárdenas-Morales, Beatriz; Mercado-Gómez, Octavio; Aburto-Arciniega, Erick; Miranda-Martínez, Alfredo; Kendrick, Keith M; Guevara-Guzmán, Rosalinda

    2014-04-01

    We investigated the effect of restraint on the release of dopamine, GABA and glutamate in the medial prefrontal cortex (mPFC) of lactating compared with virgin Wistar female rats; besides the expression of D1, neuropeptide Y Y2, GABA receptors and corticotropin-releasing factor (CRF). Results from microdialysis experiments showed that basal dopamine and GABA, but not glutamate, concentrations were higher in lactating rats. In virgin animals, immobilization caused significant increase in dopamine, whereas GABA was unchanged and glutamate reduced. In lactating animals, restrain significantly decreased dopamine concentrations and, in contrast to virgin animals, GABA and glutamate concentrations increased. We found a higher expression of CRF, as well as the D1 and neuropeptide Y Y2 receptors in the left mPFC of virgin stressed rats; also, only stressed lactating animals showed a significant increase in immunopositive cells to GABA in the left cingulate cortex; meanwhile, a significant decrease was measured in virgin rats after stress in the left prelimbic region. The increased inhibition of the mPFC dopamine cells during stress and the down-regulated expression of the neuropeptide Y Y2 receptor may explain the lower CRF and hyporesponse to stress measured in lactating animals. Interestingly, participation of mPFC in stress regulation seems to be lateralized.

  10. TRANSGENERATIONAL (IN UTERO/LACTATIONAL) EXPOSURE PROTOCOL TO INVESTIGATE THE EFFECTS OF ENDOCRINE DISRUPTING COMPOUNDS (EDCS) IN RATS

    EPA Science Inventory

    This protocol is designed to evaluate the effects of Endocrine Disrupting Compounds (EDCs) through fetal (transplacental) and/or neonatal (via the dam's milk) exposure during the critical periods of reproductive organogenesis in the rat. Continued direct exposure to the F1 pups...

  11. TRANSGENERATIONAL (IN UTERO/LACTATIONAL) EXPOSURE PROTOCOL TO INVESTIGATE THE EFFECTS OF ENDOCRINE DISRUPTING COMPOUNDS (EDCS) IN RATS

    EPA Science Inventory

    This protocol is designed to evaluate the effects of Endocrine Disrupting Compounds (EDCs) through fetal (transplacental) and/or neonatal (via the dam's milk) exposure during the critical periods of reproductive organogenesis in the rat. Continued direct exposure to the F1 pups...

  12. Effects of postnatal aluminum lactate exposure on neuromotor maturation in the rat

    SciTech Connect

    Bernuzzi, V.; Desor, D.; Lehr, P.R.

    1989-03-01

    In alkaline or neutral soils, aluminum is insoluble, but its solubility progressively increases with acidity, so acid precipitations have a considerable influence in mobilizing aluminum in natural waters, leading to higher alimentary ingestion of this element. In normal subjects aluminum is absorbed by the gastrointestinal tract and is excreted in urine. But even discrete renal failure may lead to Al accumulation in various tissues. Certain neurologic diseases have been related to Al intoxication. In patients undergoing chronic hemodialysis and ingesting aluminum-containing drugs, Al exposure is considered to be the causal factor for a high incidence of dialysis encephalopathy. Microcytic anemia and osteomalacia usually appeared before the neurologic symptoms. The authors have recently reported that the surviving pups of rats treated with aluminum during gestation showed a delay in their neuromotor development, as well as weight delay during the first postnatal week. This paper examines the effects of postnatal aluminum lactate exposure on mortality, weight evolution and neuromotor maturation in the rat.

  13. The Antidiabetic Drug Metformin Stimulates Glycolytic Lactate Production in Cultured Primary Rat Astrocytes.

    PubMed

    Westhaus, Adrian; Blumrich, Eva Maria; Dringen, Ralf

    2017-01-01

    Metformin is the most frequently used drug for the treatment of type 2 diabetes in humans. However, only little is known about effects of metformin on brain metabolism. To investigate potential metabolic consequences of an exposure of brain cells to metformin, we incubated rat astrocyte-rich primary cultures with this compound. Metformin in concentrations of up to 30 mM did not acutely compromise the viability of astrocytes, but caused a time- and concentration-dependent increase in cellular glucose consumption and lactate production. For acute incubations in the hour range, the presence of 10 mM metformin doubled the glycolytic flux, while already 1 mM metformin doubled glycolytic flux during incubation for 24 h. In addition to metformin, also other guanidino compounds increased astrocytic lactate production. After 4 h of incubation, half-maximal stimulation of glycolysis was observed for metformin, guanidine and phenformin at concentrations of around 3 mM, 3 mM and 30 µM, respectively. The acute stimulation of glycolytic lactate production by metformin was persistent after removal of extracellular metformin and was also observed, if glucose was absent from the incubation medium or replaced by other hexoses. The metformin-induced stimulation of glycolytic flux was not prevented by compound C, an inhibitor of AMP-dependent protein kinase, nor was it additive to the stimulation of glycolytic flux caused by respiratory chain inhibitors. These data demonstrate that the antidiabetic drug metformin has the potential to strongly activate glycolytic lactate production in brain astrocytes.

  14. The Spatial Organization of Proton and Lactate Transport in a Rat Brain Tumor

    PubMed Central

    Grillon, Emmanuelle; Farion, Régine; Fablet, Katell; De Waard, Michel; Tse, Chung Ming; Donowitz, Mark; Rémy, Chantal; Coles, Jonathan A.

    2011-01-01

    Tumors create a heterogeneous acidic microenvironment which assists their growth and which must be taken into account in the design of drugs and their delivery. In addition, the acidic extracellular pH (pHe) is itself exploited in several experimental techniques for drug delivery. The way the acidity is created is not clear. We report here the spatial organization of key proton-handling proteins in C6 gliomas in rat brain. The mean profiles across the tumor rim of the Na+/H+ exchanger NHE1, and the lactate-H+ cotransporter MCT1, both showed peaks. NHE1, which is important for extension and migration of cells in vitro, showed a peak 1.55 times higher than in extratumoural tissue at 0.33 mm from the edge. MCT1 had a broader peak, further into the tumor (maximum 1.76 fold at 1.0 mm from the edge). In contrast, MCT4 and the carbonic anhydrase CAIX, which are associated with hypoxia, were not significantly upregulated in the rim. The spatial distribution of MCT4 was highly correlated with that of CAIX, suggesting that their expression is regulated by the same factors. Since protons extruded by NHE1 diffuse away through extracellular clefts, NHE1 requires a continuous source of intracellular protons. From the stoichiometries of metabolic pathways that produce or consume H+, and the greater availability of glucose compared to oxygen in most parts of a tumor, we support the classic view that most of the net proton efflux from C6 gliomas originates in glycolytic formation of lactate and H+ inside the tumor, but add that some lactate is taken up into cells in the rim on MCT1, and some lactate diffuses away, leaving its associated protons available to re-enter cells for extrusion on NHE1. Therapeutic inhibition of NHE1, MCT1 or CAIX is predicted to affect different parts of a tumor. PMID:21390324

  15. Rat Gestation During Space Flight: Outcomes for Dams and Their Offspring Born After Return to Earth

    NASA Technical Reports Server (NTRS)

    Wong, Andre M.; DeSantis, Mark

    1997-01-01

    Sprague-Dawley rats were studied to learn whether gestation in the near-zero gravity, high radiation environment of space impacts selected mammalian postnatal events. Ten rats spent days nine to twenty of pregnancy aboard the space shuttle orbiter Atlantis (STS-66). Their movement was studied shortly after return to Earth; subsequently, several of their offspring were cross-fostered and examined through postnatal day 81 (P81) for whole body growth and somatic motor development. Values for the flight animals were compared to ground-based control groups. Relative to controls, the pregnant flight rats showed a marked paucity of locomotion during the first few hours after returning to Earth. There was greater likelihood of perinatal morbidity for the offspring of flight dams when compared to the control groups. Whole body weight of surviving offspring, averaged for each group separately, showed typical sigmoidal growth curves when plotted against postnatal age. The flight group for our study had a larger ratio of female to male pups, and that was sufficient to account for the lower average daily weight gained by the flight animals when compared to the control groups. Walking was universally achieved by P13 and preceded eye opening, which was complete in all pups by P17. Thus, both of these developmental horizons were attained on schedule in the flight as well as the control rats. Characteristic changes were observed in hind limb step length and gait width as the pups grew. These patterns occurred at the same time in each group of rats. Therefore, prenatal space flight from days nine to twenty of gestation did not interfere with the establishment of normal patterns for hind paw placement during walking.

  16. Rat gestation during space flight: outcomes for dams and their offspring born after return to Earth.

    PubMed

    Wong, A M; DeSantis, M

    1997-01-01

    Sprague-Dawley rats were studied to learn whether gestation in the near-zero gravity, high radiation environment of space impacts selected mammalian postnatal events. Ten rats spent days nine to twenty of pregnancy aboard the space shuttle orbiter Atlantis (STS-66). Their movement was studied shortly after return to Earth; subsequently, several of their offspring were cross-fostered and examined through postnatal day 81 (P81) for whole body growth and somatic motor development. Values for the flight animals were compared to ground-based control groups. Relative to controls, the pregnant flight rats showed a marked paucity of locomotion during the first few hours after returning to Earth. There was greater likelihood of perinatal morbidity for the offspring of flight dams when compared to the control groups. Whole body weight of surviving offspring, averaged for each group separately, showed typical sigmoidal growth curves when plotted against postnatal age. The flight group for our study had a larger ratio of female to male pups, and that was sufficient to account for the lower average daily weight gained by the flight animals when compared to the control groups. Walking was universally achieved by P13 and preceded eye opening, which was complete in all pups by P17. Thus, both of these developmental horizons were attained on schedule in the flight as well as the control rats. Characteristic changes were observed in hind limb step length and gait width as the pups grew. These patterns occurred at the same time in each group of rats. Therefore, prenatal space flight from days nine to twenty of gestation did not interfere with the establishment of normal patterns for hind paw placement during walking.

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

    PubMed

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

    2016-05-01

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

  18. [Reproductive and developmental toxicity studies of FUT-187. (III)--Postnatal study in rat F1 offspring from dams treated orally with FUT-187 during the period of fetal organogenesis].

    PubMed

    Kawanishi, H; Shiraishi, M; Igarashi, Y; Takeshima, T; Toyohara, S; Imai, S; Shimamura, K; Maruden, A

    1992-12-01

    A postnatal study of F1 offspring exposed to FUT-187 during fetal organogenesis was carried out using Crj : CD rat. FUT-187 was dosed by gavage at 0, 50, 200 and 800 mg/kg/day from day 7 to 17 of gestation. All pregnant rats were allowed to deliver newborns, and F1 offspring were examined for development indices and reproduction and learning ability. Effects at 800 mg/kg included temporary salivation, body weight depression and decreased food intake. There were no adverse effects on delivery and lactation and no significant changes on neonatal development, growth, reproduction and learning ability in the F1 offspring. These results indicate that the no effect dose level of FUT-187 is 200 mg/kg/day in dams, and 800 mg/kg/day in offspring.

  19. Administration of zinc against arsenic-induced nephrotoxicity during gestation and lactation in rat model

    PubMed Central

    Nasiry Zarrin Ghabaee, Davood; Talebpour Amiri, Fereshteh; Esmaeelnejad Moghaddam, Amir; Khalatbary, Ali Reza; Zargari, Mehryar

    2017-01-01

    Background Free radicals production by toxicity of arsenic (Ar) is most important in the nephrotoxicity. There is accumulating evidence that zinc (Zn), has anti-oxidant properties. Objectives The aim of present study was to evaluate protective and ameliorative effects of Zn against Ar-induced nephrotoxicity in rat pups during gestation and lactation. Materials and Methods Twenty-four adult pregnant wistar rats were randomly divided into four groups (n = 6). Group one was given vehicle only. Group two received Zn (ZnSO4) at 20 mg/kg/d. Group three received Ar at 5 mg/kg/d as sodium meta-arsenite. Group four received Ar + Zn at the same dose that mentioned in groups of two and three. At the end of the study, 24 hours after the last treatment, samples were killed with overdose of sodium pentobarbital and kidneys were harvested for measuring malondialdehyde (MDA), glutathione (GSH) and histopathological assessment. Results The MDA level in kidney was increased in the Ar group, which was decreased after Zn administration in the Ar + Zn group. The GSH level in kidney was decreased in the Ar group, which were increased after Zn administration in the Ar + Zn group. Also, the histopathological changes which were detected in the Ar group attenuated after Zn consumption. Conclusions Our findings suggested that administration of Zn during gestation and lactation could have protective and prevent effect in Ar-induced oxidative stress in kidney tissue. PMID:28491857

  20. Brain extracellular γ-hydroxybutyrate concentrations are decreased by L-lactate in rats: Role in the treatment of overdoses

    PubMed Central

    Roiko, Samuel A.; Vijay, Nisha; Felmlee, Melanie A.; Morris, Marilyn E.

    2013-01-01

    Purpose L-lactate represents a potential treatment for GHB overdose by inhibiting GHB renal reabsorption mediated by monocarboxylate transporters. Our objective was to assess the dose-dependence of L-lactate treatment, with and without D-mannitol, on GHB toxicokinetics/toxicodynamics (TK/TD). Methods Rats were administered GHB 600 mg/kg i.v. with L-lactate (low and high doses), D-mannitol, or L-lactate (low dose) with D-mannitol. GHB-induced sleep time and GHB plasma, urine and brain extracellular fluid (ECF) concentrations (by LC/MS/MS) were determined. The effect of L-lactate and D-mannitol on the uptake and efflux of GHB was assessed in rat brain endothelial RBE4 cells. Results L-lactate treatment increased GHB renal clearance from 1.4 ± 0.1 ml/min/kg (control) to 2.4 ± 0.2 and 4.7 ± 0.5 ml/min/kg after low and high doses, respectively, and reduced brain ECF AUC values to 65 and 25% of control. Sleep time was decreased from 137 ± 12 minutes (control) to 91 ± 16 and 55 ± 5 minutes (low and high L-lactate, respectively). D-mannitol did not alter GHB TK/TD and did not alter L-lactate’s effects on GHB TK/TD. L-lactate, but not D-mannitol, inhibited GHB uptake, and increased GHB efflux from RBE4 cells. Conclusions L-lactate decreases plasma and brain ECF concentrations of GHB, decreasing sedative/hypnotic effects. PMID:23319173

  1. [Lactate dehydrogenase isoenzymatic makeup of the skeletal muscles of rats after a flight on the Kosmos-690 biosatellite].

    PubMed

    Petrova, N V

    1978-01-01

    The isoenzyme composition of lactate dehydrogenase in the soleus and plantaris muscles of rats which had flown for 20.5 days onboard the biosatellite Cosmos-690 equipped with a radiation source was studied. Difference in the isoenzyme composition of lactate dehydrogenase in flight and synchronous rats disappeared 27 days after the experiments; however, some changes persisted as compared with vivarium controls. The data obtained give evidence that irradiation-induced effects in skeletal muscles manifested themselves at a far later stage than weightlessness-induced changes.

  2. Chronic treatment with polychlorinated biphenyls (PCB) during pregnancy and lactation in the rat

    SciTech Connect

    Cocchi, Daniela; Tulipano, Giovanni; Colciago, Alessandra; Sibilia, Valeria; Pagani, Francesca; Vigano, Daniela; Rubino, Tiziana; Parolaro, Daniela; Bonfanti, Patrizia; Colombo, Anita; Celotti, Fabio

    2009-06-01

    Polychlorinated biphenyls (PCBs) are pollutants detected in animal tissues and breast milk. The experiments described in the present paper were aimed at evaluating whether the four PCB congeners most abundant in animal tissues (PCB-138, -153, -180 and -126), administered since fetal life till weaning, can induce long-term alterations of GH-axis activity and bone mass in the adult rat. We measured PCB accumulation in rat brain and liver, somatic growth, pituitary GH expression and plasma hormone concentrations at different ages. Finally, we studied hypothalamic somatostatin expression and bone structure in adulthood, following long-term PCB exposure. Dams were treated during pregnancy from GD15 to GD19 and during breast-feeding. A constant reduction of the growth rate in both male and female offspring from weaning to adulthood was observed in exposed animals. Long-lasting alterations on hypothalamic-pituitary GH axis were indeed observed in PCB-exposed rats in adulthood: increased somatostatin expression in hypothalamic periventricular nucleus (both males and females) and lateral arcuate nucleus (males, only) and decreased GH mRNA levels in the pituitary of male rats. Plasma IGF-1 levels were higher in PCB-exposed male and female animals as compared with controls at weaning and tended to be higher at PN60. Plasma testosterone and thyroid hormone concentrations were not significantly affected by exposure to PCBs. In adulthood, PCBs caused a significant reduction of bone mineral content and cortical bone thickness of tibiae in male rat joint to increased width of the epiphyseal cartilage disk. In conclusion, the developmental exposure to the four selected PCB compounds used in the present study induced far-reaching effects in the adult offspring, the male rats appearing more sensitive than females.

  3. Low protein diet during gestation and lactation increases food reward seeking but does not modify sucrose taste reactivity in adult female rats.

    PubMed

    da Silva, Amanda Alves Marcelino; Oliveira, Mayara Matias; Cavalcante, Taisy Cinthia Ferro; do Amaral Almeida, Larissa Cavalcanti; de Souza, Julliet Araújo; da Silva, Matilde Cesiana; de Souza, Sandra Lopes

    2016-04-01

    Nutritional deficiencies during neural development may lead to irreversible changes, even after nutritional rehabilitation, promoting morphological and functional adaptations of structures involved with various behaviours including feeding behaviour. However, the ability of the exposure low protein diet during gestation and lactation to affect the hedonic component of food intake is still poorly understood, especially in females. Wistar rats were divided into two groups according to the diet offered to the dams during pregnancy and lactation: control female (CF; diet with 17% protein, n=7) and low protein female (LPF; diet with 8% protein, n=7). The following parameters were evaluated: (a) body weight during weaning, 30, 45, 60, 75, 90 days of life; (b) standard diet intake from 110 to 132 days of life; (c) fat diet and consumption of simple carbohydrates (HFHS) for 1h at 145 days of life; (d) incentive runway task 60 days after 82 days of life; (e) taste reactivity at 90 days of life; and (f) neuronal activation in the caudate putamen, amygdala, paraventricular nucleus of the hypothalamus under stimulus HFHS at 145 days of life. The exposure, a low protein diet during gestation and lactation, decreased the body weight throughout the study period from weaning to 90 days of life. However, there was no significant change in the body weight of low protein females from 110 to 132 days of life compared with the control females. There was an increase in the rate of the search for reward and reduced the latency of the perception of bitter taste. The exposure, a low protein diet during gestation and lactation, also promoted hypophagy in adult females compared with control animals. The low protein female had increased HFHS diet consumption compared with the control. Undernutrition increased neuronal activation in response to HFHS diet consumption compared with female controls in the amygdala and in the caudate putamen. Females subjected to the exposure, a low protein diet

  4. Inhibition of the osteogenic differentiation of mesenchymal stem cells derived from the offspring of rats treated with caffeine during pregnancy and lactation.

    PubMed

    Reis, Amanda Maria Sena; Ocarino, Natália de Melo; Boeloni, Jankerle Neves; Gomes, Dawidson Assis; Goes, Alfredo Miranda; Ferreira, Andrea da Fonseca; Serakides, Rogéria

    2016-01-01

    Caffeine is an alkaloid that is widely consumed due to its presence in drugs, coffee, tea, and chocolate. This compound passes to offspring through the placenta and milk; can cause teratogenic mutations; and reduces the formation, growth, and mass of bone. Because mesenchymal stem cells (MSCs) are responsible for generating the entire skeleton, we hypothesized that these cells are targets of caffeine. This study evaluated the osteogenic differentiation of MSCs derived from the offspring of rats treated with caffeine during pregnancy and lactation. Twenty-four adult Wistar rats were randomly divided into four groups, including one control group and three experimental groups treated with 25, 50, or 100 mg/kg of caffeine. At weaning, three 21-day-old pups from each dam in each group were euthanized for extraction of bone marrow cells for in vitro tests. Caffeine doses of 50 and 100 mg/kg significantly reduced the activity of alkaline phosphatase at 7, 14, and 21 days and the expression of collagen I at 21 days. However, the expression of gene transcripts for alkaline phosphatase, Runx-2, and bone sialoprotein, as well as the synthesis of mineralization nodules, decreased significantly in all groups treated with caffeine. The expression of osteocalcin was significantly reduced only in the group treated with 50 mg/kg caffeine. The caffeine that passes from the mother to the offspring during pregnancy and lactation reduces the osteogenic differentiation of MSCs. We propose that this reduction in the osteogenic potential of MSCs may be involved in the pathogenesis of osteopenia resulting from caffeine consumption.

  5. Increase in lactate dehydrogenase isoenzyme-4 and splenocyte toxicity in methomyl-treated rats.

    PubMed

    Lohitnavy, O; Sinhaseni, P

    1998-09-01

    The toxic effect of methomyl was studied in rats after a single or repeated oral administration. Rats treated with a single dose of methomyl (3, 5, or 7 mg/kg) showed significant increase (P < 0.05) in total lactate dehydrogenase (LDH) activity on day 1. The highest level of LDH activity was observed on day 3 in rats receiving 7 mg/kg of methomyl. The total LDH activity returned to normal on day 7 after dosing. Specific increases in LDH-3 and LDH-4 isoenzyme activities were observed. In rats treated with a single dose of 6 and 8 mg/kg of methomyl, spleen weight and splenocyte viability significantly dropped (P < 0.05) on days 1 and 3, respectively. Splenotoxicity was prevented by pretreatment with 60 mg/kg of N-acetylcysteine. The results suggest that the splenotoxic effect of methomyl is more likely directly related to oxidative cell injury than to cholinesterase inhibition. The significance of cytotoxic effects and the nature of cytotoxicity in relation to reactive oxidative damage deserve further investigation.

  6. Maternal nicotine exposure during lactation alters hypothalamic neuropeptides expression in the adult rat progeny.

    PubMed

    Younes-Rapozo, Viviane; Moura, Egberto G; Manhães, Alex C; Pinheiro, Cintia R; Santos-Silva, Ana Paula; de Oliveira, Elaine; Lisboa, Patricia C

    2013-08-01

    Maternal exposure to nicotine during lactation causes hyperleptinemia in the pups and, at adulthood, these animals are overweight and hyperleptinemic, while, in their hypothalamus, the leptin signaling pathway is reduced, evidencing a central leptin resistance. Then, we evaluated the expression of pro-opiomelanocortin (POMC), alpha-melanocyte stimulating hormone (α-MSH), cocaine and amphetamine-regulated transcript (CART), neuropeptide Y (NPY), agouti-related peptide (AgRP) and others in different hypothalamic nuclei in order to better understand the mechanisms underlying the obese phenotype observed in these animals at adulthood. On the 2nd postnatal day (P2), dams were subcutaneously implanted with osmotic minipumps releasing nicotine (NIC-6 mg/kg/day) or saline for 14 days. Offspring were killed in P180 and immunohistochemistry and Western blot analysis were carried out. Significance data had p<0.05. Adult NIC offspring showed more intense NPY staining in the paraventricular nucleus (PVN) (+21%) and increased number of POMC-positive cells in the: arcuate nucleus (+33%), as an increase in fiber density of α-MSH in PVN (+85%). However, the number of CART-positive cells was reduced in the PVN (-25%). CRH staining was more intense in NIC offspring (+136%). Orexins and AgRP were not altered. Thus, maternal nicotine exposure changes hypothalamic neuropeptides in the adult progeny that is partially compatible with leptin resistance.

  7. A maternal low protein diet during pregnancy and lactation in the rat impairs male reproductive development

    PubMed Central

    Zambrano, E; Rodríguez-González, GL; Guzmán, C; García-Becerra, R; Boeck, L; Díaz, L; Menjivar, M; Larrea, F; Nathanielsz, PW

    2005-01-01

    Nutrient restriction during pregnancy and lactation impairs growth and development. Recent studies demonstrate long-term programming of function of specific organ systems resulting from suboptimal environments during fetal life and development up to weaning. We determined effects of maternal protein restriction (50% control protein intake) during fetal development and/or lactation in rats on the reproductive system of male progeny. Rats were fed either a control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. After delivery mothers received either C or R diet until weaning to provide four groups: CC, RR, CR and RC. We report findings in male offspring only. Maternal protein restriction increased maternal serum corticosterone, oestradiol and testosterone (T) concentrations at 19 days gestation. Pup birth weight was unchanged but ano-genital distance was increased by maternal protein restriction (P < 0.05). Testicular descent was delayed 4.4 days in RR, 2.1 days in CR and 2.2 days in RC and was not related to body weight. Body weight and testis weight were reduced in RR and CR groups at all ages with the exception of CR testis weight at 270 days postnatal age (PN). At 70 days PN luteinizing hormone and T concentrations were reduced in RR, CR and RC. mRNA for P450 side chain cleavage (P450scc) was reduced in RR and CR at 21 days PN but was unchanged at 70 days PN. Fertility rate was reduced at 270 days PN in RC and sperm count in RR and RC. We conclude that maternal protein delays sexual maturation in male rats and that some effects only emerge in later life. PMID:15611025

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

    PubMed Central

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

    2014-01-01

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

  9. Effect of Lactation on myocardial vulnerability to ischemic insult in rats.

    PubMed

    Askari, Sahar; Imani, Alireza; Sadeghipour, Hamidreza; Faghihi, Mahdieh; Edalatyzadeh, Zohreh; Choopani, Samira; Karimi, Nasser; Fatima, Sulail

    2017-05-01

    Cardiovascular diseases are the leading cause of mortality and long-term disability worldwide. Various studies have suggested a protective effect of lactation in reducing the risk of cardiovascular diseases. This study was designed to assess the effects of pregnancy and lactation on the vulnerability of the myocardium to an ischemic insult. Eighteen female rats were randomly divided into three groups: ischemia-reperfusion (IR), in which the hearts of virgin rats underwent IR (n = 6); lactating, in which the rats nursed their pups for 3 weeks and the maternal hearts were then submitted to IR (n = 6); and non-lactating, in which the pups were separated after birth and the maternal hearts were submitted to IR (n = 6). Outcome measures included heart rate (HR), left ventricular developed pressure (LVDP), rate pressure product (RPP), ratio of the infarct size to the area at risk (IS/AAR %), and ventricular arrhythmias - premature ventricular contraction (PVC) and ventricular tachycardia (VT). The IS/AAR was markedly decreased in the lactating group when compared with the non-lactating group (13.2 ± 2.5 versus 39.7 ± 3.5, p < 0.001) and the IR group (13.2 ± 2.5 versus 34.0 ± 4.7, p < 0.05). The evaluation of IR-induced ventricular arrhythmias indicated that the number of compound PVCs during ischemia, and the number and duration of VTs during ischemia and in the first 5 minutes of reperfusion in the non-lactating group were significantly (p < 0.05) higher than those in the lactating and IR groups. Lactation induced early-onset cardioprotective effects, while rats that were not allowed to nurse their pups were more susceptible to myocardial IR injury. As doenças cardiovasculares são a principal causa de mortalidade e invalidez a longo prazo a nível mundial. Diversos estudos têm sugerido um efeito protetor da lactação na redução do risco para doenças cardiovasculares. Este estudo foi desenvolvido para avaliar os efeitos da gestação e da lactação sobre a

  10. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose response (BBDR) Model***

    EPA Science Inventory

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the 1-IPT axis. Model calibrations, carried out by adjusting key model...

  11. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose-response model

    EPA Science Inventory

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (BPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the HPT axis. Model calibrations, carried out by adjusting key model p...

  12. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose-response model

    EPA Science Inventory

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (BPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the HPT axis. Model calibrations, carried out by adjusting key model p...

  13. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose response (BBDR) Model***

    EPA Science Inventory

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the 1-IPT axis. Model calibrations, carried out by adjusting key model...

  14. Hypothyroxinemia induced by maternal mild iodine deficiency impairs hippocampal myelinated growth in lactational rats.

    PubMed

    Wei, Wei; Wang, Yi; Dong, Jing; Wang, Yuan; Min, Hui; Song, Binbin; Shan, Zhongyan; Teng, Weiping; Xi, Qi; Chen, Jie

    2015-11-01

    Hypothyroxinemia induced by maternal mild iodine deficiency causes neurological deficits and impairments of brain function in offspring. Hypothyroxinemia is prevalent in developing and developed countries alike. However, the mechanism underlying these deficits remains less well known. Given that the myelin plays an important role in learning and memory function, we hypothesize that hippocampal myelinated growth may be impaired in rat offspring exposed to hypothyroxinemia induced by maternal mild iodine deficiency. To test this hypothesis, the female Wistar rats were used and four experimental groups were prepared: (1) control; (2) maternal mild iodine deficiency diet inducing hypothyroxinemia; (3) hypothyroidism induced by maternal severe iodine deficiency diet; (4) hypothyroidism induced by maternal methimazole water. The rats were fed the diet from 3 months before pregnancy to the end of lactation. Our results showed that the physiological changes occuring in the hippocampal myelin were altered in the mild iodine deficiency group as indicated by the results of immunofluorescence of myelin basic proteins on postnatal day 14 and postnatal day 21. Moreover, hypothyroxinemia reduced the expressions of oligodendrocyte lineage transcription factor 2 and myelin-related proteins in the treatments on postnatal day 14 and postnatal day 21. Our data suggested that hypothyroxinemia induced by maternal mild iodine deficiency may impair myelinated growth of the offspring.

  15. Lactate dehydrogenase and alkaline phosphatase isoenzymes and protein-bound sialic acid in regenerating rat liver.

    PubMed

    Allalouf, D; Schwarzman, S; Levinsky, H; Feller, N; Hart, J; Zoher, S; Menache, R

    1986-01-01

    Lactate dehydrogenase (LDH) and alkaline phosphatase (AP) isoenzyme patterns and protein-bound sialic acid content were compared between normal, regenerating rat liver 10 days after partial hepatectomy and fetal rat liver. For this purpose, liver from ten adult rats and two pools of ten fetal livers each were examined. Isoenzymes were separated by electrophoresis on cellulose acetate and their percent distribution calculated after quantitation by densitometry of the bands. LDH-5 and LDH-4 combined represented in all the tissues examined 90%-94% of the total activity. LDH-5/LDH-4 ratios were nearly equivalent in the normal and regenerated liver (7.14, 6.41), but substantially lower in fetal liver (2.50). Two bands of AP were visualized in electropherograms. AP-1/AP-2 ratio was lower in regenerated liver (1.57) as compared to normal liver (2.27) and still lower in fetal liver (1.06). Protein-bound sialic acid was, on protein basis, slightly but not significantly higher in regenerated liver (1.71 microgram/mg protein) than in normal liver (1.43), and significantly higher in fetal liver (1.87). The relatively small differences in isoenzyme patterns and in protein-bound sialic acid between regenerated and normal liver as compared to those between fetal and normal tissue add support to the view that the cells in regenerated liver are not of embryonic origin.

  16. Long-term effects of in utero and lactational exposure to butyl paraben in female rats.

    PubMed

    Guerra, Marina Trevizan; Sanabria, Marciana; Cagliarani, Stephannie Vieira; Leite, Gabriel Adan Araújo; Borges, Cibele Dos Santos; De Grava Kempinas, Wilma

    2017-03-01

    Parabens are used as preservatives in cosmetic, pharmaceutical, and food industries, and are frequently detected as contaminants in human fluids and tissues. The endocrine disrupting effects of parabens in female rodents include uterotrophic response, steroidogenesis impairment, and ovarian disturbances. The objective of this study was to determine the effects of maternal butyl paraben (BP) exposure on female sexual development. Pregnant Wistar rats were treated subcutaneously with either corn oil or BP at doses of 10, 100, or 200 mg/kg, from gestational day (GD) 12 until GD 20 for female foetal gonad evaluation, and from GD 12 until the end of lactation to evaluate sexual parameters on the female offspring. Immature female rats were also used in the uterotrophic assay to evaluate the possible estrogenic action of parabens. Our results revealed that, in this experimental protocol, BP did not show estrogenic activity at the doses used and did not impair sexual development and fertility capacity in the female rats, but impaired sexual behavior. We conclude that brain sexual development may be more sensitive to BP effects and we speculate that doses higher than 100 mg/kg (the male lowest observed adverse effect level (LOAEL) for rodent reproductive parameters) would be necessary to promote damages in the female reproduction, regarding the same protocol of exposure. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 776-788, 2017.

  17. Urinary concentrating mechanism and Aquaporin-2 abundance in rats chronically treated with aluminum lactate.

    PubMed

    Mahieu, Stella; Millen, Néstor; Contini, María del Carmen; Gonzalez, Marcela; Molinas, Sara M; Elías, María Mónica

    2006-06-15

    The aim of this work was to study the effects of chronic administration of aluminum (Al) on the urinary concentrating and diluting mechanisms in the distal tubules and collecting ducts. Male Wistar rats were chronically treated with aluminum lactate for 12 weeks (0.575 mg Al/100g of body weight, i.p., three times per week). After 12 weeks, renal function of control and Al-treated rats was evaluated by clearance techniques. To study urinary concentrating mechanisms, renal function was also measured in control and Al-treated rats deprived of water, after the administration of desmopressin (vasopressin agonist) and after the infusion of hypertonic saline at increasing infusion rates. Sodium and water balance were impaired. We found decreased urinary concentrating ability in situations in which endogenous (thirst or infusion of hypertonic saline) or exogenous plasma antidiuretic hormone was increased. Solute-free water formation, measured during the infusion of hypotonic saline showed normal transport in the thick ascending limb. Aquaporin-2 (AQP2) expression was measured by Western blot to evaluate water permeability in collecting ducts. We found that Al produced downregulation of AQP2 in plasma membranes and intracellular vesicles, that could account for the impaired water handling. Administration of desmopressin increased AQP2 in plasma membranes, suggesting that Al did not impair trafficking of this protein, but could interfere with AQP2 synthesis.

  18. Maternal Flaxseed Oil During Lactation Enhances Bone Development in Male Rat Pups.

    PubMed

    Pereira, Aline D'Avila; Ribeiro, Danielle Cavalcante; de Santana, Fernanda Carvalho; de Sousa Dos Santos, Aline; Mancini-Filho, Jorge; do Nascimento-Saba, Celly Cristina Alves; Velarde, Luis Guillermo Coca; da Costa, Carlos Alberto Soares; Boaventura, Gilson Teles

    2016-08-01

    Flaxseed oil is an alpha linolenic acid source important in the growth and body development stage; furthermore, this acid acts on adipose tissue and bone health. The aim of this study was to evaluate body composition, fatty acid composition, hormone profile, retroperitoneal adipocyte area and femur structure of pups at weaning, whose mothers were fed a diet containing flaxseed oil during lactation. After birth, pups were randomly assigned: control (C, n = 12) and flaxseed oil (FO, n = 12), rats whose mothers were treated with diet containing soybean or flaxseed oil. At 21 days, the pups were weaned and body mass, length, body composition, biochemical parameter, leptin, osteoprotegerin, osteocalcin, fatty acids composition, intra-abdominal fat mass and femur structure were analyzed. FO showed (p < 0.05): higher body mass (+12 %) and length (+9 %); body fat mass (g, +45 %); bone mineral density (+8 %), bone mineral content (+55 %) and bone area (+35 %), osteocalcin (+173 %) and osteoprotegerin (+183 %). Arachidonic acid was lower (p < 0.0001), alpha-linolenic and eicosapentaenoic were higher (p < 0.0001). Intra-abdominal fat mass was higher (+25 %), however, the retroperitoneal adipocytes area was lower (-44 %). Femur mass (+10 %), distance between epiphyses (+4 %) and bone mineral density (+13 %) were higher. The study demonstrates that adequate flaxseed oil content during a lactation diet plays an important role in the development of pups.

  19. Immune activation in lactating dams alters sucklings' brain cytokines and produces non-overlapping behavioral deficits in adult female and male offspring: A novel neurodevelopmental model of sex-specific psychopathology.

    PubMed

    Arad, Michal; Piontkewitz, Yael; Albelda, Noa; Shaashua, Lee; Weiner, Ina

    2017-02-08

    Early immune activation (IA) in rodents, prenatal through the mother or early postnatal directly to the neonate, is widely used to produce behavioral endophenotypes relevant to schizophrenia and depression. Given that maternal immune response plays a crucial role in the deleterious effects of prenatal IA, and lactation is a critical vehicle of immunological support to the neonate, we predicted that immune activation of the lactating dam will produce long-term abnormalities in the sucklings. Nursing dams were injected on postnatal day 4 with the viral mimic poly-I:C (4mg/kg) or saline. Cytokine assessment was performed in dams' plasma and milk 2h, and in the sucklings' hippocampus, 6h and 24h following poly-I:C injection. Male and female sucklings were assessed in adulthood for: a) performance on behavioral tasks measuring constructs considered relevant to schizophrenia (selective attention and executive control) and depression (despair and anhedonia); b) response to relevant pharmacological treatments; c) brain structural changes. Maternal poly-I:C injection caused cytokine alterations in the dams' plasma and milk, as well as in the sucklings' hippocampus. Lactational poly-I:C exposure led to sex-dimorphic (non-overlapping) behavioral abnormalities in the adult offspring, with male but not female offspring exhibiting attentional and executive function abnormalities (manifested in persistent latent inhibition and slow reversal) and hypodopaminergia, and female but not male offspring exhibiting despair and anhedonia (manifested in increased immobility in the forced swim test and reduced saccharine preference) and hyperdopaminergia, mimicking the known sex-bias in schizophrenia and depression. The behavioral double-dissociation predicted distinct pharmacological profiles, recapitulating the pharmacology of negative/cognitive symptoms and depression. In-vivo imaging revealed hippocampal and striatal volume reductions in both sexes, as found in both disorders. This is

  20. Lactating and nonlactating rats differ to renal toxicity induced by mercuric chloride: the preventive effect of zinc chloride.

    PubMed

    Favero, Alexandre M; Oliveira, Cláudia S; Franciscato, Carina; Oliveira, Vitor A; Pereira, Juliana S F; Bertoncheli, Claudia M; da Luz, Sônia C A; Dressler, Valderi L; Flores, Erico M M; Pereira, Maria E

    2014-07-01

    This study evaluated the effects of HgCl2 on renal parameters in nonlactating and lactating rats and their pups, as well as the preventive role of ZnCl2 . Rats received 27 mg kg(-1) ZnCl2 for five consecutive days and 5 mg kg(-1) HgCl2 for five subsequent days (s.c.). A decrease in δ-aminolevulinic acid dehydratase (δ-ALA-D) activity in the blood and an increase in urine protein content in renal weight as well as in blood and urine Hg levels were observed in lactating and nonlactating rats from Sal-Hg and Zn-Hg groups. ZnCl2 prevented partially the δ-ALA-D inhibition and the proteinuria in nonlactating rats. Renal Hg levels were increased in all HgCl2 groups, and the ZnCl2 exposure potentiated this effect in lactating rats. Nonlactating rats exposed to HgCl2 exhibited an increase in plasma urea and creatinine levels, δ-ALA-D activity inhibition and histopathological alterations (necrosis, atrophic tubules and collagen deposition) in the kidneys. ZnCl2 exposure prevented the biochemical alterations. Hg-exposed pups showed lower body and renal weight and an increase in the renal Hg levels. In conclusion, mercury-induced nephrotoxicity differs considerably between lactating and nonlactating rats. Moreover, prior exposure with ZnCl2 may provide protection to individuals who get exposed to mercury occupationally or accidentally. Copyright © 2014 John Wiley & Sons, Ltd.

  1. Effects of lactational exposure to soy isoflavones on reproductive system in neonatal female rats.

    PubMed

    Liu, Zhaoping; Zhang, Xiaopeng; Li, Li; Zhang, Wenzhong; Cui, Wenming; Song, Yan; Wang, Wei; Jia, Xudong; Li, Ning; Yan, Weixing

    2008-03-01

    To examine effects of lactational exposure to soy isoflavones on female reproductive system, soy isoflavones, 0 (control), 10, 50, 100, 150 or 200 mg/kg body weight, were administered to maternal rats by gavage daily during postnatal days 5-10. Ten female litters were killed on day 11. Uterine and ovary weights, serum oestradiol and progesterone concentrations, proliferating cell nuclear antigen, mRNA expressions of oestrogen receptor, androgen receptor and progesterone receptor in uterus or ovary were measured. When compared to the control group, litters in the 150 and 200 mg/kg body weight groups had significantly higher ovary and uterine weights (P < 0.05). Endometrial thickness was also significantly increased. Isoflavone-treated groups had increased proliferating cell nuclear antigen staining in comparison to the control group. Litters in the 50, 150 and 200 mg/kg body weight groups had significantly higher oestradiol concentration while lower progesterone concentrations than those in the control group (P < 0.05 or P < 0.01). All soy isoflavone-treated groups had androgen receptor mRNA expressions in ovary and uterus comparable to the control group. Progesterone receptor mRNA expression in the 150 and 200 mg/kg body weight groups was significantly lower than that in control group (P < 0.01). However, ovaries in the 150 and 200 mg/kg body weight groups had significantly higher oestrogen receptor mRNA expression while the uterus in these two treatment groups had significantly lower expressions, when compared to the control group (P < 0.05 or P < 0.01). In conclusion, lactational exposure to isoflavones could result in oestrogen-like actions on the reproductive system of neonate female rats, which mechanisms may be, at least, involved with modifications of hormone production and steroid receptor transcription in the reproductive system.

  2. Prediction of ATLS hypovolemic shock class in rats using the perfusion index and lactate concentration.

    PubMed

    Choi, Soo Beom; Park, Jee Soo; Chung, Jai Won; Kim, Sung Woo; Kim, Deok Won

    2015-04-01

    It is necessary to quickly and accurately determine Advanced Trauma Life Support (ATLS) hemorrhagic shock class for triage in cases of acute hemorrhage caused by trauma. However, the ATLS classification has limitations, namely, with regard to primary vital signs. This study identified the optimal variables for appropriate triage of hemorrhage severity, including the peripheral perfusion index and serum lactate concentration in addition to the conventional primary vital signs. To predict the four ATLS classes, three popular machine learning algorithms with four feature selection methods for multicategory classification were applied to a rat model of acute hemorrhage. A total of 78 anesthetized rats were divided into four groups for ATLS classification based on blood loss (in percent). The support vector machine one-versus-one model with the Kruskal-Wallis feature selection method performed best, with 80.8% accuracy, relative classifier information of 0.629, and a kappa index of 0.732. The new hemorrhage-induced severity index (lactate concentration/perfusion index), diastolic blood pressure, mean arterial pressure, and the perfusion index were selected as the optimal variables for predicting the four ATLS classes by support vector machine one-versus-one with the Kruskal-Wallis method. These four variables were also selected for binary classification to predict ATLS classes I and II versus III and IV for blood transfusion requirement. The suggested ATLS classification system would be helpful to first responders by indicating the severity of patients, allowing physicians to prepare suitable resuscitation before hospital arrival, which could hasten treatment initiation.

  3. Contribution of several amino acids and lactate to gluconeogenesis in hepatocytes isolated from rats fed various diets

    SciTech Connect

    Kaloyianni, M.; Freedland, R.A. )

    1990-01-01

    The contribution under various nutritional regimens of several amino acids and lactate to gluconeogenesis was estimated by measuring the glucose formation from 14C-labeled substrates. Isolated rat hepatocytes were incubated for 60 min in a Krebs-Ringer bicarbonate buffer pH 7.4 containing lactate, pyruvate and all the amino acids at concentrations similar to their physiological levels found in rat plasma, with one precursor labeled in each flask. In all conditions, lactate was the major glucose precursor, providing over 60% of the glucose formed. Glutamine and alanine were the major amino acid precursors of glucose, contributing 9.8% and 10.6% of the glucose formed, respectively, in hepatocytes isolated from starved rats. Serine, glycine and threonine also contributed to gluconeogenesis in the starved liver cells at 2.6, 2.1 and 3.8%, respectively, of the glucose formed. The rate of glucose formation from the isolated hepatocytes of the starved rats and those fed either high protein or high fat was higher than that from rats fed a nonpurified diet.

  4. Incidence of neuronal coupling in supraoptic nuclei of virgin and lactating rats: estimation by neurobiotin and lucifer yellow.

    PubMed

    Hatton, G I; Yang, Q Z

    1994-07-04

    Dye coupling among neurons has been shown to reflect electrotonic coupling. Recent work in retina has revealed that the incidence of coupling is greater when estimated by neurobiotin (NB) transfer than by Lucifer yellow (LY). Several previous studies have shown that the incidence of LY coupling among supraoptic nucleus (SON) neurons of lactating rats is 2- to 4-fold higher than is observed in virgin females. We compared the incidence of coupling among SON neurons following simultaneous injections of LY and NB into the same cells in slices from virgin or lactating rats. As seen in previous studies, there were 4-fold more LY-coupled neurons per injection in lactating as compared to virgin rats. Under both conditions, the numbers of NB-coupled neurons per injection were 4-fold greater than was observed for LY; possible mechanisms are discussed. Individual NB-filled neurons were coupled to as many as 10 other cells distributed over a large area of the SON. These results confirm previous findings of more coupling in lactating than virgin SONs, and suggest that both the incidence and spatial extent of interneuronal coupling are greater and thus probably more important functionally than has been heretofore appreciated.

  5. A maternal high-fat/high-caloric diet delays reflex ontogeny during lactation but enhances locomotor performance during late adolescence in rats.

    PubMed

    Cadena-Burbano, Erika Vanesa; Cavalcanti, Carolina Cadete Lucena; Lago, Amanda Braz; Benjamim, Raquel de Arruda Campos; Oliveira, Thaynan Raquel Dos Prazeres; Silva, Jacqueline Maria; Manhães-De-Castro, Raul; Da Silva Aragão, Raquel

    2017-07-28

    The main goal of the present study was to investigate the effects of two maternal high-fat diets with different energy densities on the somatic growth, reflex ontogeny, and locomotor activity of offspring. Twenty-nine female Wistar rats (220-250 g) were mated and grouped into three different dietary conditions: control (n = 11, AIN-93G diet, 3.6 kcal/g), high-fat/high-caloric (HH, n = 9, 51% of the calories from fat, 4.62 kcal/g), and high-fat/isocaloric (HI, n = 9, 51% of the calories from fat, 3.64 kcal/g). The fat source was mainly lard. The dietary groups were maintained during gestation and lactation. From postnatal day 1 (PND1) until weaning, the somatic growth, maturation of physical features, and reflex ontogeny of the male pups were evaluated. The locomotor activity was evaluated in an open field at PND8, PND14, PND17, PND21, PND30, PND45, and PND60. HH dams had a lower food intake but no difference in caloric intake or body weight gain. The HH pups had higher body weights, greater tail and body lengths, and an increased axis of the head at weaning. The prediction of ear unfolding, delayed palmar grasp, and cliff avoidance maturation were also observed in the HH offspring. At PND60, the HH pups showed an increased average speed as well as an average potency and kinetic energy in the open field. A high-fat/high-caloric maternal diet increases somatic growth, predicts the maturation of physical features, and delays reflex ontogeny during lactation, and it enhances motor performance during late adolescence. A maternal HI diet does not elicit the same influences on offspring development compared with the HH diet.

  6. Role of hypoxia-induced anorexia and right ventricular hypertrophy on lactate transport and MCT expression in rat muscle.

    PubMed

    Py, Guillaume; Eydoux, Nicolas; Lambert, Karen; Chapot, Rachel; Koulmann, Natahlie; Sanchez, Hervé; Bahi, Lahoucine; Peinnequin, André; Mercier, Jacques; Bigard, André-Xavier

    2005-05-01

    To dissect the independent effects of altitude-induced hypoxemia and anorexia on the capacity for cardiac lactate metabolism, we examined the effects of 21 days of chronic hypobaric hypoxia (CHH) and its associated decrease in food intake and right ventricle (RV) hypertrophy on the monocarboxylate transporter 1 and 4 (MCT) expression, the rate of lactate uptake into sarcolemmal vesicles, and the activity of lactate dehydrogenase isoforms in rat muscles. In comparison with control rats (C), 1 mmol/L lactate transport measured on skeletal muscle sarcolemmal vesicles increased by 33% and 58% in hypoxic (CHH, barometric pressure = 495 hPa) and rats pair-fed an equivalent quantity of food to that consumed by hypoxic animals, respectively. The increased lactate transport was higher in PF than in CHH animals ( P < .05). No associated change in the expression of MCT1 protein was observed in skeletal muscles, whereas MCT1 mRNA decreased in CHH rats, in comparison with C animals (42%, P < .05), partly related to caloric restriction (30%, P < .05). MCT4 mRNA and protein increased during acclimatization to hypoxia only in slow-oxidative muscles (68%, 72%, P < .05, respectively). The MCT4 protein content did not change in the plantaris muscle despite a decrease in transcript levels, related to hypoxia and caloric restriction. In both the left and right ventricles, the MCT1 protein content was unaffected by ambient hypoxia or restricted food consumption. These results suggest that MCT1 and MCT4 gene expression in fast-glycolytic muscles is mainly regulated by posttranscriptional mechanisms. Moreover, the results emphasize the role played by caloric restriction on the control of gene expression in response to chronic hypoxia and suggest that hypoxia-induced right ventricle hypertrophy failed to alter MCT proteins.

  7. Effect of selenium on hypothyroidism induced by methimazole (MMI) in lactating rats and their pups.

    PubMed

    Amara, Ibtissem Ben; Bouaziz, Hanen; Guermazi, Fadhel; Zeghal, Najiba

    2010-06-01

    The present study was undertaken to assess the effect of selenium (Se) on hypothyroidism induced by methimazole (MMI) in lactating rats and their pups. Rats were randomly divided into four groups of six each: group I served as a negative control which received standard diet; group II received orally MMI (250 mg L -1 ); group II received both MMI (250 mg L -1 , orally) and Se (0.5 mg/kg of diet); group IV served as a positive control and received Se (0.5 mg Na 2 SeO 3 /kg of diet). Treatments were started from the 14th day of pregnancy until postnatal day 14. In the MMI-exposed group, the body weight of 14-day-old pups diminished compared to controls; besides, a hypertrophy of the thyroid glands was observed. Co-administration of Se through the diet restored these parameters to near normal values. In the MMI-treated group, thyroid iodine contents and plasma thyroid hormone levels significantly decreased, while plasma TSH levels increased in pups and their mothers. These biochemical modifications corresponded histologically to closed follicles, increased vascularity and a reduction in colloid volume. Co-treatment with Se ameliorated these parameters. We concluded that the supplementation of Se in diet had beneficial effects on hypothyroidism during a critical period of life.

  8. Prenatal or lactational exposure of male rats to lead acetate. Effect on reproductive function

    SciTech Connect

    Thoreux-Manlay, A.; Pinon-Lataillade, G.; Coffigny, H.; Masse, R.; Soufir, J.C.

    1995-02-01

    Lead is an environmental pollutant which has received much attention, partly because of the particular sensitivity of children to this element. As regards the consequences of exposure to lead during fetal life or childhood, epidemiological studies have so far focused on its neuropsychological effects and little is known about the consequences of fetal or childhood exposure for reproduction. With respect to animals, the reproductive toxicity of lead in males exposed during prenatal life or the suckling period has only been considered in a few studies. Four such studies concerned the rat, the most current model of lead toxicity for male reproduction; two of studies considered the long term effects (i.e. during adulthood) of moderate in utero lead exposure, another covered the prenatal and neonatal periods and focused on the possible impact of lead intoxication on steriodogenesis before weaning, while the remaining study dealt with pituitary hormone level at the end of lead gavage in newborns. None of these investigations compared the effects of exposure during prenatal life to those of exposure via lactation, or the early effects (at about weaning time) to the long-term consequences during adulthood. Because of the paucity of data on these points, we conducted two experiments: in one, rats were exposed to lead prenatally, and in the other via maternal milk. In both cases male reproductive function at weaning and adulthood was examined. 12 refs., 1 fig., 2 tabs.

  9. Lactogenic actions of different growth hormone preparations in pregnant and lactating rats.

    PubMed

    Carón, R W; Jahn, G A; Deis, R P

    1994-09-01

    We studied the capacity of different GH preparations, natural human (h)GH, recombinant hGH (rhGH), rat (r)GH, ovine (o)GH, bovine (b)GH and porcine (p)GH, and ovine prolactin (oPRL), to stimulate lactogenesis in ovario-hysterectomized pregnant rats or intact lactating rats treated with bromocriptine (BC). Ovariohysterectomy (OVX-HYS) performed at 0800 h on day 19 of pregnancy induced lactogenesis, i.e. increases in mammary casein and lactose and positive response to the oxytocin test, 28 h later. Lactogenesis was prevented by treatment with BC (1.5 mg/kg) immediately after surgery (OVX-HYS-BC). The hormones were given at doses of 0.25 or 0.5 mg/rat (except rhGH given only at 0.5 mg/rat) at 1200 and 2000 h on day 19. Casein was increased by both doses of oPRL and hGH, rhGH and 0.25 mg oGH, and lactose by both doses of oPRL, rhGH and 0.25 mg rGH. The other GH preparations had no effect. The oxytocin test demonstrated the presence of milk in the mammary tissues of the OVX-HYS rats and in the OVX-HYS-BC plus oPRL (0.25 and 0.5 mg) or rhGH-treated groups. Injection of BC to pregnant rats at 2000 h on day 20 and at 0800 h on day 21 decreased litter growth on the first 4 days postpartum. Two-thirds of the litters resumed growth after day 4, indicating the recuperation of milk production, while the rest never recuperated. Serum prolactin in BC-treated rats was reduced until day 4 postpartum. On day 6 the rats which had recuperated had normal values, while those which had still not recuperated had lower values. BC-treated rats were injected s.c. with 0.25 mg each of oPRL, hGH, rGH, oGH, bGH or pGH, or 0.25 or 0.5 mg rhGH/rat, immediately postpartum and 12, 24 and 36 h later. hGH and 0.5 mg rhGH induced levels of milk production similar to controls except on day 3. oPRL and rhGH (0.25 mg), induced a partial reversion of the effect of BC. rGH and oGH had a slight effect on days 1 and 2 and all the litters resumed growth on day 7. In contrast, pGH and bGH were inactive. The

  10. Comparative effects of repeated administration of cadmium chloride during pregnancy and lactation and selenium protection against cadmium toxicity on some organs in immature rats' offsprings.

    PubMed

    Bekheet, Souad H M

    2011-12-01

    This research comprises studies on the transfer of cadmium (CdCl(2)) from the lactating dam to the pup via milk and absorbed in the suckling, showing that cadmium is transferred to the testes, ovary, cerebellum, and thyroid gland during development. The present studies were carried out in order to assess the protective effects of selenium against cadmium toxicity in pregnant rats. On the sixth day of gestation, the females were dosed subcutaneously either with cadmium or with cadmium and selenium in the following doses (mg/kg of body weight): 0, 1 Cd, 1 Cd + 1 Se, 2 Cd, 2 Cd + 2 Se. In groups treated with cadmium, no maternal or embryonic toxicities were observed; however, an increase in testes diameters of seminiferous tubules, a progressive sloughing of germ cells, vacuolization of Sertoli cells, and Leydig cells hyperplasia were noted. The reduction in the ovary size and inhibited folliculogenesis resulted in diminution of the numbers of primordial, growing, and tertiary follicles. The pathological change in the cerebellum, the migration of granular cells from the external germinal layer to the internal granular layer, was strongly retarded. Also, the formation of many microfollicles in the thyroid gland which mimic the changes was seen in thyrotoxicosis. It also appears that selenium used at a low-enough dose could be a very effective protection against cadmium-induced developmental toxicity in the testes, ovary, cerebellum, and thyroid gland but not in the higher dose in the ovary and cerebellum.

  11. Exposure to maternal consumption of cafeteria diet during the lactation period programmes feeding behaviour in the rat.

    PubMed

    Wright, Thomas M; Fone, Kevin C F; Langley-Evans, Simon C; Voigt, Jörg-Peter W

    2011-12-01

    Lactational overfeeding programmes obesity in the adult rat, and also impacts on adult emotional behaviour. The present study investigated the impact of exposing the lactating female to a hypercaloric diet on structural aspects of feeding behaviour in the adult offspring as measured by the behavioural satiety sequence (BSS). Lactating Wistar rats were fed a hypercaloric cafeteria diet (CD) in addition to chow. Controls were fed on chow only. All offspring were chow fed after weaning. BSS was tested in 12-15 week old offspring. At 20 weeks of age, monoamine neurotransmitter levels were measured in selected brain regions. When exposed to a palatable 1-h test meal, offspring responded with the same latency to feed, regardless of lactational diet. Total food intake during the test was unaffected by lactational diet. Control offspring showed a normal BSS pattern. Male CD offspring displayed shorter feeding bouts (P<0.05) with an overall higher bout frequency (P<0.001) and their latency to rest was delayed (P<0.001). Overall eating frequency (P<0.05), but not duration was increased in male CD offspring. Although the transition from feeding to resting was not affected by lactational CD, CD males fed for longer at the beginning of the test meal and were more active towards the end. CD females displayed an increased number of feeding bouts (P<0.05) and they spent more time eating (P<0.05). Resting latency was delayed (P<0.05) and overall time spent resting was shortened (P<0.01). Frequency of eating was increased in the middle of the test meal. The onset of satiety as indicated by the transition point between eating and resting was delayed in CD females (P<0.001). In both sexes, hypothalamic 5-hydroxytryptamine (5-HT) was increased (P<0.05 in females, P<0.01 in males) and 5-HT turnover was reduced by lactational CD (P<0.001 in females, P<0.01 in males). Lactational CD led also to an increase in dopamine (DA) (P<0.01). Hypothalamic DA metabolism (DOPAC+HVA/DA ratio) was

  12. Uteroplacental insufficiency and lactational environment separately influence arterial stiffness and vascular function in adult male rats.

    PubMed

    Tare, Marianne; Parkington, Helena C; Bubb, Kristen J; Wlodek, Mary E

    2012-08-01

    Early life environmental influences can have lifelong consequences for health, including the risk of cardiovascular disease. Uteroplacental insufficiency causes fetal undernutrition and impairs fetal growth. Previously we have shown that uteroplacental insufficiency is associated with impaired maternal mammary development, compromising postnatal growth leading to hypertension in male rat offspring. In this study we investigated the roles of prenatal and postnatal nutritional environments on endothelial and smooth muscle reactivity and passive wall stiffness of resistance arteries of male rat offspring. Fetal growth restriction was induced by maternal bilateral uterine vessel ligation (restricted) on day 18 of pregnancy. Control offspring were from mothers that had sham surgery (control) and another group from mothers with their litter size reduced (reduced; litter size reduced to 5 at birth, equivalent to the restricted group). On postnatal day 1, offspring (control, restricted, and reduced) were cross-fostered onto control or restricted mothers. At 6 months, mesenteric and femoral arteries were studied using wire and pressure myography. In restricted-on-restricted rats, wall stiffness was increased, and sensitivity to phenylephrine and relaxation evoked by endothelium-derived hyperpolarizing factor and sodium nitroprusside were impaired in mesenteric arteries. In femoral arteries, relaxation to sodium nitroprusside was reduced, whereas wall stiffness was unaltered. Cross-fostering restricted offspring onto control mothers alleviated deficits in vascular stiffness and reactivity. Control or reduced offspring who suckled a restricted mother had marked vascular stiffening. In conclusion, prenatal and early postnatal environments separately influence vascular function and stiffness. Furthermore, the early postnatal lactational environment is a determinant of later cardiovascular function.

  13. Potential risks of maternal administration of Mucophylline on the pups of albino rats during lactation.

    PubMed

    Hamdi, Hamida; Ali, Heba

    2017-03-02

    The present study was undertaken to evaluate the potential risks of the mucolytic and broncholytic drug, Theophylline derivatives (Mucophylline) maternally administered on the pups. The nursing rats orally administered from 1st postpartum day (PPD) to 21th PPD with two different doses 30.83mg/kg (low dose) and 66.61mg/kg (Human equivalent dose (HED)). On the 21th PPD, the postnatal developmental signs, skeletal malformation and the histopathology of neonatal liver, kidney and brain were examined. Our results showed that Mucophylline induced a significant reduction in the neonatal weight and length, delayed, weak and incomplete ossification, wavy ribs and the neonatal liver revealed histopathological changes, pyknotic hepatocytes, cytoplasmic vacuolization, dilated sinusoid and necrotic area. Kidney revealed alternation changes, enlargement of the glomerulus, renal tubules degeneration and lymphatic infiltration. Brain (cerebral cortex and cerebellum) showed neurodegenerative changes, vacuolization of neuropil, congested and dilated blood vessel and dark stain neurons. Our results showed that the activities of non-enzymatic (GSH) and enzymatic (GST, CAT) antioxidants were insignificantly decrease in both neonatal brain and liver tissues of rats administered with 30.83mg/kg and 61.66mg/kg of Mucophylline and insignificant increase in MDA levels in both neonatal brain and liver tissues. However, significant reduction (P≤0.05) in the content of GR was recorded in neonatal brain tissue of rats administered with 30.83mg/kg and 61.66mg/kg of Mucophylline during lactation period in comparison with control. These support and proof the potential risks of the maternal administration of Mucophylline on pups.

  14. Milk yield, suckling behaviour and milk ejection in the lactating rat nursing litters of different sizes.

    PubMed Central

    Russell, J A

    1980-01-01

    1. The quantitative relationship between the suckling stimulus and several suckling-dependent variables was studied in lactating rats. 2. The intensity of the suckling stimulus, measured as the product of duration and number of pups suckling was in proportion to litter size for litters of one, ten or twenty-two pups. 3. Pups in the litters of ten grew fastest. Single-pup litters grew most slowly, some not at all. Litter weight gain, corrected for inevitable losses, was used to estimate milk yield. Total milk yield was greater for litters of twenty-two to twenty-four pups than for litters of ten pups only in the first week. Milk yield for single pups was up to 7% of the yield for ten pups. Milk yield per mammary gland sucked was similar for the larger litters but less for single pups. 4. The number of milk ejections, measured as pup stretch reactions, in observation periods of 225 min, was similar for litters of ten and twenty-two to twenty-four pups, but less for single-pup litters. 5. The suckling stimulus applied by single-pup litters inhibited ovarian growth less effectively than did the stimulus applied by larger litters. 6. There was no change in serum osmolality during lactation. 7. It is concluded that litters of ten or twenty-two to twenty-four pups applied suckling stimuli of different intensities, but these had similar effects on the daily secretion rate of oxytocin, milk production and suppression of ovarian growth. Single-pup litters were less effective. PMID:7431242

  15. Maternal prolactin inhibition during lactation affects physical performance evaluated by acute exhaustive swimming exercise in adult rat offspring.

    PubMed

    Casimiro-Lopes, G; Lisboa, P C; Koury, J C; Boaventura, G; Passos, M C F; Moura, E G

    2012-02-01

    Maternal prolactin inhibition at the end of lactation programs for metabolic syndrome and hypothyroidism in adult offspring, which could negatively affect exercise performance. We evaluated the effects of maternal hypoprolactinemia in late lactation on physical performance in adult progeny. Lactating Wistar rats were treated with bromocriptine (BRO, 1 mg per day) or saline on days 19, 20, and 21 of lactation and offspring were followed until 180 days old. Physical performance was recorded in untrained rats at 90 and 180 days by an acute exhaustive swimming test (exercise group-Ex). At day 90, BRO offspring showed higher visceral fat mass, higher plasma thiobarbituric acid reactive substances, lower total antioxidant capacity, higher liver glycogen, lower glycemia, and normal insulinemia. Although thyroid hormones (TH) levels were unchanged, mitochondrial glycerol phosphate dehydrogenase (mGPD) activity was lower in muscle and in brown adipose tissue (BAT). At this age, BRO-Ex offspring showed higher exercise capacity, lower blood lactate, higher serum T3, and higher muscle and BAT mGPD activities. At day 180, BRO offspring showed central obesity, hypothyroidism, insulin resistance, and lower EDL (extensor digitorum longus) muscle glycogen with unaltered plasma oxidative stress markers. This group showed no alteration of exercise capacity or blood lactate. After exercise, EDL and liver glycogen were lower, while T3 levels, BAT and muscle mGPD activities were normalized. Liver glycogen seem to be related with higher exercise capacity in younger BRO offspring, while the loss of this temporary advantage maybe related to the hypothyroidism and insulin resistance developed with age.

  16. The effect of maternal malnutrition during lactation on the endometrial ERalpha expression, collagen type, and blood vessels in the rats offspring at puberty.

    PubMed

    Bittencourt Brasil, Flávia; Silva Faria, Tatiane; Barcellos Sampaio, Francisco José; da Fonte Ramos, Cristiane

    2010-01-01

    The aim of this manuscript was to evaluate the effects of maternal protein-energy-restriction and energy restriction during lactation on endometrial collagen and blood vessels, uterus Eralpha expression, and estradiol serum levels in the rats offspring at puberty. At parturition, dams were grouped as: control group (C), with free access to standard rat chow containing 23% protein and 17,038.7 KJ/Kg; protein-energy restricted group (PER), with free access to formulated chow containing 8% protein but made isoenergetic to the C diet (17,038.7 KJ/Kg); and energy-restricted group (ER), which received standard rat chow containing 23% protein based on the mean ingestion of the PER group corresponding to 60% of that consumed by the control group. After weaning, all female pups had free access to standard laboratory chow until puberty, when they were killed at the diestrum stage. The uterine ERalpha expression was determined by Western-Blot and estradiol serum levels by radioimmunoassay. Endometrial collagen and blood vessels were quantified by stereology. The volumetric density of blood vessels (C = 70.7 +/- 2.2; PER = 29.2 +/- 2.4; ER = 32.3 +/- 3.6; P < 0.001) and endometrial collagen (C = 31.1 +/- 1; PER = 26.9 +/- 1.0; ER = 26.5 +/- 0.7; P < 0.05) were significantly reduced in both malnourished groups. The ER group presented higher estradiol serum levels (C = 69.2 +/- 6.4; PER = 73.4 +/- 5.5; ER = 101.0 +/- 5.4; P < 0.01) in relation to C and PER groups. ERalpha expression was greater in both malnourished groups (C = 0.11 +/- 0.02; PER = 0.41 +/- 0.12; ER = 0.35 +/- 0.03; P < 0.05). In conclusion, maternal malnutrition during lactation caused changes in endometrial angiogenesis, collagen deposition, and Eralpha expression in female offspring that will appear in puberty and could affect the reproductive biology of the female offspring. (c) 2009 Wiley-Liss, Inc.

  17. Changes in Blood Parameters and the Expression of Coagulation-Related Genes in Lactating Sprague–Dawley Rats

    PubMed Central

    Urasoko, Yoshinaka; He, Xi Jun; Masao, Takano; Kinoshita, Yuichi; Edamoto, Hiroshi; Hatayama, Kazuhisa; Asano, Yuzo; Tamura, Kazutoshi; Mochizuki, Masahiro

    2012-01-01

    This study measured blood parameters, particularly those related to coagulation, and alterations in the expression levels of blood-coagulation–related genes in lactating Sprague–Dawley rats. The day of delivery was designated as lactation day 0 (LD 0). On the day after delivery (LD 1), prothrombin time and overall activity of vitamin-K–dependent coagulation factors were decreased, whereas fibrinogen contents, platelet counts and antithrombin III concentrations were increased as compared with those in nonpregnant rats. In addition, hepatic expression of blood-coagulation–related genes in the liver was increased at LD 0 as compared with that in nonpregnant rats. These changes may be physiologic responses to prevent prolonged bleeding at delivery. Except for fibrinogen content, which remained elevated, the described changes returned to baseline on and after LD 7. Activities of AST, ALT, and ALP were increased on LD 7, 14, and 21 as compared with nonpregnant rats. In contrast, total protein, albumin, Cl, and Ca were consistently lower on LD 7, 14, or 21 as compared with levels in nonpregnant rats. These results provide background data for evaluation of nursing rats. PMID:22776112

  18. Micronucleated erythrocytes in newborns of rat dams exposed to ultraviolet-A light during pregnancy; protection by ascorbic acid supplementation.

    PubMed

    Zúñiga-González, Guillermo M; Gómez-Meda, Belinda C; Zamora-Perez, Ana L; Martínez-González, María A; Muñoz de Haro, Ilse A; Pérez-Navarro, Adhoksaja E; Armendáriz-Borunda, Juan; Gallegos-Arreola, Martha P

    2015-04-01

    Pregnant hairless rat dams were exposed to ultraviolet-A light (UVA) to induce micronucleated erythrocytes (MNE) in their fetuses. The control group was exposed to conventional light; the experimental groups were exposed to UVA (365nm) during gestational days 16-21. In some cases, ascorbic acid (Asc) was administered in the drinking water from gestational day 15 until delivery. Dams were sampled at 48-h intervals during gestation, from day 16 until delivery. Blood was also obtained from neonates at birth; MNE, micronucleated polychromatic erythrocytes (MNPCE), and polychromatic erythrocytes (PCE) were scored. Increased MNE and MNPCE were observed in neonates born to mothers exposed to UVA for 40, 80 or 160min, compared to the control group. Asc treatment reduced MNE and MNPCE induction.

  19. Reduction of reactive oxygen species ameliorates metabolism-secretion coupling in islets of diabetic GK rats by suppressing lactate overproduction.

    PubMed

    Sasaki, Mayumi; Fujimoto, Shimpei; Sato, Yuichi; Nishi, Yuichi; Mukai, Eri; Yamano, Gen; Sato, Hiroki; Tahara, Yumiko; Ogura, Kasane; Nagashima, Kazuaki; Inagaki, Nobuya

    2013-06-01

    We previously demonstrated that impaired glucose-induced insulin secretion (IS) and ATP elevation in islets of Goto-Kakizaki (GK) rats, a nonobese model of diabetes, were significantly restored by 30-60-min suppression of endogenous reactive oxygen species (ROS) overproduction. In this study, we investigated the effect of a longer (12 h) suppression of ROS on metabolism-secretion coupling in β-cells by exposure to tempol, a superoxide (O2(-)) dismutase mimic, plus ebselen, a glutathione peroxidase mimic (TE treatment). In GK islets, both H2O2 and O2(-) were sufficiently reduced and glucose-induced IS and ATP elevation were improved by TE treatment. Glucose oxidation, an indicator of Krebs cycle velocity, also was improved by TE treatment at high glucose, whereas glucokinase activity, which determines glycolytic velocity, was not affected. Lactate production was markedly increased in GK islets, and TE treatment reduced lactate production and protein expression of lactate dehydrogenase and hypoxia-inducible factor 1α (HIF1α). These results indicate that the Warburg-like effect, which is characteristic of aerobic metabolism in cancer cells by which lactate is overproduced with reduced linking to mitochondria metabolism, plays an important role in impaired metabolism-secretion coupling in diabetic β-cells and suggest that ROS reduction can improve mitochondrial metabolism by suppressing lactate overproduction through the inhibition of HIF1α stabilization.

  20. Peritoneal dialysis fluid-induced angiogenesis in rat mesentery is increased by lactate in the presence or absence of glucose.

    PubMed

    Albrektsson, Ann; Bazargani, Farhan; Wieslander, Anders; Braide, Magnus

    2006-01-01

    Angiogenesis may be an important mechanism behind the functional deterioration of the peritoneum leading to ultrafiltration failure in peritoneal dialysis. The present study was designed to compare the angiogenic properties of lactate-, bicarbonate-, and pyruvate-buffered fluids, evaluated separately with and without glucose. Five different fluids (lactate and bicarbonate with and without 2.5% glucose and pyruvate without glucose) were studied for 5 weeks of twice-daily injections in rats. The respective buffers (40 mmol/l) were adjusted to pH 7.2, and sodium, chloride, calcium, and magnesium were present at standard concentrations. The mesenteric window model, based on observation of the translucent peritoneal sections of the small intestine mesentery, was used for immunohistochemical imaging of microvessels (RECA-1 antigen) and macrophages (ED1 and ED2 antigens). All fluids induced angiogenesis as compared with untreated controls. The lactate-buffered fluids induced larger vascularized zones than did their bicarbonate- and pyruvate-buffered counterparts. Angiogenesis was accompanied by a local recruitment of ED1 macrophages from blood. Addition of glucose to the lactate- and bicarbonate-buffered fluids did not seem to alter their pro-angiogenic properties. In conclusion, intraperitoneal exposure to lactate buffer, compared with bicarbonate, stimulates angiogenesis in the presence or absence of glucose.

  1. Carcinogens in rat milk. Transfer of ingested diethylnitrosamine into milk by lactating rats.

    PubMed

    Schoental, R; Gough, T A; Webb, K S

    1974-09-01

    Mothers of 5-day old rats were given diethylnitrosamine (DEN) (130 mg/kg body weight) by stomach tube. The milk removed from the stomachs of the suckling young contained 5, 16 and 36 parts/10(6) of DEN at 2, 4 and 6 hours respectively after they started suckling the treated mothers. After 49 hours, DEN was no more detectable in the milk.

  2. Physiologically Based Pharmacokinetic Modeling of the Lactating Rat and Nursing Pup: a Multiroute Exposure Model for Trichloroethylene and its Metabolite, Trichloroacetic Acid

    DTIC Science & Technology

    1990-01-01

    determined by vial equilibration, and metabolic costants for TICE oxidation, by gas uptake methods. i7the blood/air and the fat /blood PCs for the dam were...methods. The blood/air and the fat /blood PCs for the dam were 13.1 and 34.2, and for the pup, 10.6 and 42.3, respectively. The milk/ blood PC for the...pups were killed. The PHYSIOLOGICALLY BASED PHARMACOKINETIC MOL&LING IN LACTATION 499 ADULT PUP ALVEOLAR ALVEOLAR SPACE SPACE LUNG LOOD LUNG BLOOD FAT

  3. MATERNAL FLAXSEED DIET DURING PREGNANCY OR LACTATION INCREASES FEMALE RAT OFFSPRING’S SUSCEPTIBILITY TO CARCINOGEN-INDUCED MAMMARY TUMORIGENESIS

    PubMed Central

    Khan, Galam; Penttinen, Pauliina; Cabanes, Anna; Foxworth, Aaron; Chezek, Antonia; Masterpole, Kristen; Yu, Bin; Smeds, Annika; Halttunen, Teemu; Good, Carolyn; Mäkelä, Sari; Hilakivi-Clarke, Leena

    2013-01-01

    Flaxseed contains several dietary components that have been linked to low breast cancer risk; i.e., n-3 polyunsaturated fatty acids (PUFAs), lignans and fiber, but it also contains detectable levels of cadmium, a heavy metal that activates the estrogen receptor (ER). Since estrogenic exposures early in life modify susceptibility to develop breast cancer, we wondered whether maternal dietary intake of 5% or 10% flaxseed during pregnancy or lactation (between postpartum days 5 and 21) might affect 7,12-dimethylbenz[a]anthracene (DMBA) -induced mammary tumorigenesis in the rat offspring. Our data indicated that both in utero and postnatal 5% and 10% flaxseed exposures shortened mammary tumor latency, and 10% flaxseed exposure increased tumor multiplicity, compared to the controls. Further, when assessed in 8-week-old rats, in utero 10% flaxseed exposure increased lobular ER-α protein levels, and both in utero and postnatal flaxseed exposures dose-dependently reduced ER-β protein levels in the lobules and terminal end buds (TEBs). Exposures to flaxseed did not alter the number of TEBs or affect cell proliferation within the TEBs, lobules or ducts. In a separate group of immature rats that were fed 5% defatted flaxseed diet (flaxseed source different than in the diets fed to pregnant or lactating rats) for 7 days, cadmium exposure through the diet was 7-fold higher than allowed for humans by World Health Organization, and cadmium significantly accumulated in the liver and kidneys of the rats. It remains to be determined whether the increased mammary cancer in rats exposed to flaxseed through a maternal diet in utero or lactation was caused by cadmium present in flaxseed, and whether the reduced mammary ER-β content was causally linked to increased mammary cancer risk among the offspring. PMID:17398067

  4. Cocaine- and Amphetamine-Regulated Transcript (CART) Expression is Differentially Regulated in the Hypothalamic Para ventricular Nucleus of Lactating Rats Exposed to Suckling or Cold Stimulation

    PubMed Central

    Sánchez, Edith; Fekete, Csaba; Lechan, Ronald M.; Joseph-Bravo, Patricia

    2007-01-01

    Neural stimuli, such as suckling or cold exposure, increase TRH mRNA in the paraventricular nucleus (PVN) of the rat hypothalamus, yet only suckling induces prolactin secretion. As TRH co-localizes with cocaine-and amphetamine-regulated transcript (CART) in hypophysiotropic neurons of the PVN, and CART inhibits TRH-induced prolactin release but not TRH-induced TSH release in adenohypophyseal cell cultures, we raised the possibility that differential regulation of CART gene expression in the PVN may explain the differences in prolactin secretion following each of the two stimuli. Primiparous female rats were mated and handled daily during the pre- and postpartum periods. After delivery, the litter was adjusted to 8 pups and at mid-lactation, dams were separated from their pups for 8 hours and exposed to either 1h of cold or 30 min of suckling. Long term effects of suckling were studied by separating pups from their mothers for 24h, followed by a 12h period of continuous suckling. Serum TSH levels increased in response to cold exposure, while prolactin levels were increased by suckling and diminished by cold exposure. CART mRNA levels increased in rostral and mid parts of the medial parvocellular PVN following cold exposure but not after suckling stimulation. These data demonstrate a differential regulation of CART gene expression in hypophysiotropic neurons in response to stimuli that increase TRH mRNA levels, and suggest that CART activation in the PVN may contribute to the decrease in PRL release when the thyroid axis is activated by cold exposure. Section: Regulatory systems PMID:17174283

  5. Prenatal and lactational lead exposure enhanced oxidative stress and altered apoptosis status in offspring rats' hippocampus.

    PubMed

    Lu, Xiaobo; Jin, Cuihong; Yang, Jinghua; Liu, Qiufang; Wu, Shengwen; Li, Dandan; Guan, Yangyang; Cai, Yuan

    2013-01-01

    Oxidative stress and apoptosis facilitation in the developing central nervous system (CNS) have been inferred as two mechanisms related to lead's neurotoxicity, and excessive reactive oxygen species (ROS) can promote oxidative stress and apoptosis facilitation. Few studies systematically investigated the potential relationship among oxidative stress, ROS generation, and apoptosis facilitation after lead exposure in earlier life as a whole. To better understand the adverse effect on the developing central nervous system (CNS) after lead exposure during pregnancy and lactation, the indexes of oxidative stress, apoptosis status, and Bax and Bcl-2 expression of offspring rats' hippocampus were determined. Pregnant rats were randomly divided into four groups and given free access to drinking water which contained 0 %, 0.05 %, 0.1 %, and 0.2 % Pb(AC)(2) respectively from gestation day 0 to postnatal day 21 (PND21). Results showed that ROS and malondialdehyde level of either PND7 or PND21 pups' hippocampus were significantly raised; reduced glutathione level and superoxide dismutase activity were obviously decreased following the increase of blood and brain lead level. Similar to apoptotic indexes, Bax/Bcl-2 ratio increased after 0.1 % and 0.2 % Pb(AC)(2) exposure, especially for the pups on PND7. Comparing with cortex, the hippocampus seemed much more sensitive to damage induced by lead. We concluded that the disruption of pro-oxidant and antioxidant balance and apoptosis facilitation could be associated with the mechanisms of neurotoxicity after lead exposure in earlier life.

  6. Exposure to sorbitol during lactation causes metabolic alterations and genotoxic effects in rat offspring.

    PubMed

    Cardoso, Felipe S; Araujo-Lima, Carlos F; Aiub, Claudia A F; Felzenszwalb, Israel

    2016-10-17

    Sorbitol is a polyol used by the food industry as a sweetener. Women are consuming diet and light products containing sorbitol during pregnancy and in the postnatal period to prevent themselves from excessive weight gain and maintain a slim body. Although there is no evidence for the genotoxicity of sorbitol in the perinatal period, this study focused on evaluating the effects of the maternal intake of sorbitol on the biochemical and toxicological parameters of lactating Wistar rat offspring after 14days of mother-to-offspring exposure. A dose-dependent reduction of offspring length was observed. An increase in sorbitol levels determined in the milk was also observed. However, we detected an inverse relationship between the exposition dose in milk fructose and triacylglycerols concentrations. There was an increase in the plasmatic levels of ALT, AST and LDLc and a decrease in proteins, cholesterol and glucose levels in the offspring. Sorbitol exposure caused hepatocyte genotoxicity, including micronuclei induction. Maternal sorbitol intake induced myelotoxicity and myelosuppression in their offspring. The Comet assay of the blood cells detected a dose-dependent genotoxic response within the sorbitol-exposed offspring. According to our results, sorbitol is able to induce important metabolic alterations and genotoxic responses in the exposed offspring. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Inhibition of liver trans-sulphuration pathway by propargylglycine mimics gene expression changes found in the mammary gland of weaned lactating rats: role of glutathione.

    PubMed Central

    Zaragozá, Rosa; García, Concha; Rus, A Diana; Pallardó, Federico V; Barber, Teresa; Torres, Luis; Miralles, Vicente J; Viña, Juan R

    2003-01-01

    In the lactating mammary gland, weaning produces mitochondrial cytochrome c release and nuclear DNA fragmentation, as determined by gel electrophoresis. This is followed by a significant decrease in lactation. Weaning for 2 h produces an early induction of the tumour suppressor/transcription factor p53, whereas the oncoprotein c-Jun and c-Jun N-terminal kinase are elevated after 24 h of weaning when compared with controls. The expression of p21(cip1) and p27(kip1), cyclin-dependent kinase inhibitors, was significantly higher in weaned rats when compared with control lactating rats. All the changes mentioned above also happen in the lactating mammary gland when propargylglycine, an inhibitor of the liver trans-sulphuration pathway, is administered. This effect is partially reversed by N -acetylcysteine administration. The administration of buthionine sulphoximine, an irreversible inhibitor of gamma-glutamylcysteine synthetase, to lactating rats produces a decrease in GSH levels and changes in protein concentrations and gene transcripts similar to those in rats with impaired trans-sulphuration pathway. These data suggest that the inter-tissue flux of GSH is an important mechanism of L-cysteine delivery to the lactating mammary gland and emphasize the importance of this physiological event in maintaining the gene expression required to sustain lactation. PMID:12723969

  8. Cytophotometric analysis of reaction rates of succinate and lactate dehydrogenase activity in rat liver, heart muscle and tracheal epithelium.

    PubMed

    Van Noorden, C J; Vogels, I M

    1989-01-01

    Reaction rates of succinate and lactate dehydrogenase activity in cryostat sections of rat liver, tracheal epithelium and heart muscle were monitored by continuous measurement of formazan formation by cytophotometry at room temperature. Incubation media contained polyvinyl alcohol as tissue protectant and Tetranitro BT as final electron acceptor. Control media lacked either substrate or substrate and coenzyme. Controls were also performed by adding malonate (a competitive inhibitor of succinate dehydrogenase), pyruvate (a non-competitive inhibitor of lactate dehydrogenase), oxalate (a competitive inhibitor of lactate dehydrogenase) or N-ethylmaleimide (a blocker of SH groups). A specific malonate-sensitive linear test minus control response for succinate dehydrogenase activity was obtained in liver (1.6 mumol H2cm-3 min-1) and tracheal epithelium (0.8 mumol H2cm-3 min-1) but not in heart muscle. All variations in the incubation conditions tested did not result in a linear test minus control response in the latter tissue. Because the reaction was sensitive to malonate, it was concluded that the initial reaction rate was the specific rate of succinate dehydrogenase activity in heart muscle (9.1 mumol H2 cm-3 min-1). Test minus control reactions for lactate dehydrogenase activity were distinctly non-linear for all tissues tested. This appeared to be due to product inhibition by pyruvate generated during the reaction and therefore it was concluded that the appropriate control reaction was the test reaction in the presence of 20 mM pyruvate. The initial rate of the test minus this control was the true rate of lactate dehydrogenase activity. The lactate dehydrogenase activity thus found in liver parenchyma was 5.0 mumol of H2 generated per cm3 liver tissue per min.

  9. Evidences of Basal Lactate Production in the Main White Adipose Tissue Sites of Rats. Effects of Sex and a Cafeteria Diet

    PubMed Central

    Arriarán, Sofía; Agnelli, Silvia; Sabater, David; Remesar, Xavier; Fernández-López, José Antonio; Alemany, Marià

    2015-01-01

    Female and male adult Wistar rats were fed standard chow or a simplified cafeteria diet for one month. Then, the rats were killed and the white adipose tissue (WAT) in four sites: perigonadal, retroperitoneal, mesenteric and subcutaneous (inguinal) were sampled and frozen. The complete WAT weight in each site was measured. Gene expression analysis of key lipid and glucose metabolism enzymes were analyzed, as well as tissue and plasma lactate and the activity of lactate dehydrogenase. Lactate gradients between WAT and plasma were estimated. The influence of sex and diet (and indirectly WAT mass) on lactate levels and their relationships with lactate dehydrogenase activity and gene expressions were also measured. A main conclusion is the high production of lactate by WAT, practically irrespective of site, diet or sex. Lactate production is a direct correlate of lactate dehydrogenase activity in the tissue. Furthermore, lactate dehydrogenase activity is again directly correlated with the expression of the genes Ldha and Ldhb for this enzyme. In sum, the ability to produce lactate by WAT is not directly dependent of WAT metabolic state. We postulate that, in WAT, a main function of the lactate dehydrogenase path may be that of converting excess available glucose to 3C fragments, as a way to limit tissue self-utilization as substrate, to help control glycaemia and/or providing short chain substrates for use as energy source elsewhere. More information must be gathered before a conclusive role of WAT in the control of glycaemia, and the full existence of a renewed glucose-lactate-fatty acid cycle is definitely established. PMID:25741703

  10. Evidences of basal lactate production in the main white adipose tissue sites of rats. Effects of sex and a cafeteria diet.

    PubMed

    Arriarán, Sofía; Agnelli, Silvia; Sabater, David; Remesar, Xavier; Fernández-López, José Antonio; Alemany, Marià

    2015-01-01

    Female and male adult Wistar rats were fed standard chow or a simplified cafeteria diet for one month. Then, the rats were killed and the white adipose tissue (WAT) in four sites: perigonadal, retroperitoneal, mesenteric and subcutaneous (inguinal) were sampled and frozen. The complete WAT weight in each site was measured. Gene expression analysis of key lipid and glucose metabolism enzymes were analyzed, as well as tissue and plasma lactate and the activity of lactate dehydrogenase. Lactate gradients between WAT and plasma were estimated. The influence of sex and diet (and indirectly WAT mass) on lactate levels and their relationships with lactate dehydrogenase activity and gene expressions were also measured. A main conclusion is the high production of lactate by WAT, practically irrespective of site, diet or sex. Lactate production is a direct correlate of lactate dehydrogenase activity in the tissue. Furthermore, lactate dehydrogenase activity is again directly correlated with the expression of the genes Ldha and Ldhb for this enzyme. In sum, the ability to produce lactate by WAT is not directly dependent of WAT metabolic state. We postulate that, in WAT, a main function of the lactate dehydrogenase path may be that of converting excess available glucose to 3C fragments, as a way to limit tissue self-utilization as substrate, to help control glycaemia and/or providing short chain substrates for use as energy source elsewhere. More information must be gathered before a conclusive role of WAT in the control of glycaemia, and the full existence of a renewed glucose-lactate-fatty acid cycle is definitely established.

  11. Studies of the membrane topology of the rat erythrocyte H+/lactate cotransporter (MCT1).

    PubMed Central

    Poole, R C; Sansom, C E; Halestrap, A P

    1996-01-01

    1. Hydrophobicity analysis of the monocarboxylate/proton cotransporter MCT1 (lactate transporter) suggests a structure with 12 transmembrane (TM) segments, presumed to be alpha-helical. 2. A series of anti-peptide antibodies have been raised against regions of the MCT1 sequence, which each recognize a polypeptide of approx. 40 kDa in rat erythrocytes. The topology of rat MCT1 was investigated by studying the immunoreactive fragments derived from proteolytic digestion of the protein in intact rat erythrocytes and leaky membranes. 3. Reactivity with an anti-(C-terminus) antibody was prevented on treatment of leaky membranes, but not intact cells, with carboxypeptidase Y, indicating that the C-terminus of the protein is cytoplasmically disposed. 4. Treatment of intact cells in saline buffer with trypsin, chymotrypsin, bromelain and protease K (up to 1 mg/ml) resulted in no degradation of MCT1, indicating the absence of any large exposed extracellular loop. In a buffer of low ionic strength (containing sucrose), cleavage was observed with bromelain at an extracellular site, probably TM9/10.5. Treatment of leaky membranes with low (less than 100 micrograms/ml) concentrations of several proteases resulted in fragmentation of MCT1, reflecting cleavage at the cytoplasmic face of the membrane. These treatments generated N-terminal fragments of apparent molecular mass approx. 17-19 kDa that were resistant to further degradation. The epitopes for the TM6/7 and C-terminal antibodies were either lost from the membrane or destroyed under most of these conditions, indicating that these regions of the protein are located in the cytoplasm. 6. More detailed structural prediction analysis of MCT-related sequences was made assuming the constraints placed upon the possible arrangements by the experimental data outlined above. This analysis provided additional strong evidence for the 12-TM-segment model, with cytoplasmic N- and C-terminal ends and a large internal loop between TM6 and

  12. Lactate dehydrogenase activity of rat epididymis and spermatozoa: effect of constant light.

    PubMed

    Ponc, R H; Carriazo, C S; Vermouth, N T

    2001-01-01

    During its passage through the epididymis, the gamete undergoes a process of "maturation" leading to the acquisition of its fertilizing ability. The epididymis displays regional variations in the morphology and metabolic properties of its epithelium which are relevant for the progressive development of mature sperm characteristics. The epididymis has spontaneous peristaltic contractions and receives sympathetic innervation that is modulated by melatonin, a hormone synthesized and released by the pineal gland. Constant lighting disrupts melatonin synthesis and secretion. We have studied the effect of constant light on lactate dehydrogenase (LDH; EC 1.1.1.27) and its isozyme C4 activities and protein content in whole epididymis, epididymal tissue and in spermatozoa from caput and cauda segments. Animals were exposed from birth to an illumination schedule of 14 h light:10 h dark (group L:D). At 60 days of age one group of animals was submitted to constant light over 50 days (group L:L). In order to test the fertilizing ability, the rats of each group were mated with soliciting estrous females. The percentage of pregnancies in females mated with males maintained in L:L was remarkably lower than those in females mated with males maintained in the L:D photoperiod (44% and 88% respectively). Constant light increased protein concentration and LDH activity in caput as well as in cauda of total epididymis. On the contrary, in epididymal tissue, the protein content decreased in both epididymal sections compared with controls. When enzymatic activity was expressed in Units per spermatozoa, constant light induced a significant reduction of total LDH and LDHC4 in caput and cauda spermatozoa while LDH activity of epididymal tissue was not affected. In spite of the decrease in LDH per sperm cell when rats were exposed to constant light, in total epididymis (epididymis tissue plus sperm cells content) and in spermatozoa, values of enzyme activities expressed per weight unit were

  13. Maternal and affective behaviors of lactating rats reared in overlapping litters.

    PubMed

    Uriarte, Natalia; Fernández, María Victoria; Agrati, Daniella; Zuluaga, María José; Ferreño, Marcela; Ferreira, Annabel

    2014-01-01

    Postpartum mating in rats gives rise to complex family units consisting of the mother and two overlapping litters. As a consequence, newborn pups of the second litter, since the moment they are born, acquire experience not only from interaction with the mother and age-matched littermates but also from interaction with older siblings. Newborn pups reared in overlapping litters (OLs) receive a different pattern of maternal stimulation compared to those reared in single litters (SL: one litter of same aged pups), as the mothers reduce some maternal behavior components and juvenile pups from the first litter develop maternal behavior. Since there is strong evidence showing that variations in maternal behavior are transmitted throughout generations, we hypothesized that the altered pattern of maternal stimulation received by OL reared females would modify their behavior during motherhood. To test this hypothesis maternal behavior, maternal aggression and experimental anxiety of dams reared under OL and SL conditions during the first postpartum week were compared. No differences were found between the groups in their maternal behavior and aggression. This result may be explained by the maternal behavior of the juveniles that could compensate for the deficits in the caregiving behaviors received by OL litters. However, a subtle temporal reorganization of the licking behavior was found in OL reared mothers, together with an increased anxiety-related behavior in the plus maze test. These results suggest dissociation in the effects provoked by early environmental alterations on different behavioral systems, and more importantly, that independently of their early family composition, both groups can cope effectively with the changing demands of the pups.

  14. Chronic treatment with polychlorinated biphenyls (PCB) during pregnancy and lactation in the rat

    SciTech Connect

    Colciago, A.; Casati, L.; Mornati, O.; Vergoni, A.V.; Santagostino, A.; Celotti, F. Negri-Cesi, P.

    2009-08-15

    The gender-specific expression pattern of aromatase and 5alpha-reductases (5alpha-R) during brain development provides neurons the right amount of estradiol and DHT to induce a dimorphic organization of the structure. Polychlorinated biphenyls (PCBs) are endocrine disruptive pollutants; exposure to PCBs through placental transfer and breast-feeding may adversely affect the organizational action of sex steroid, resulting in long-term alteration of reproductive neuroendocrinology. The study was aimed at: a) evaluating the hypothalamic expression of aromatase, 5alpha-R1 and 5alpha-R2 in fetuses (GD20), infant (PN12), weaning (PN21) and young adult (PN60) male and female rats exposed to PCBs during development; b) correlating these parameters with the time of testicular descent, puberty onset, estrous cyclicity and copulatory behavior; c) evaluating possible alterations of some non reproductive behaviors (locomotion, learning and memory, depression/anxiety behavior). A reconstituted mixture of four indicator congeners (PCB 126, 138, 153 and 180) was injected subcutaneously to dams at the dose of 10 mg/kg daily from GD15 to GD19 and then twice a week till weanling. The results indicated that developmental PCB exposure produced important changes in the dimorphic hypothalamic expression of both aromatase and the 5alpha-Rs, which were still evident in adult animals. We observed that female puberty onset occurs earlier than in control animals without cycle irregularity, while testicular descent in males was delayed. A slight but significant impairment of sexual behavior and an important alteration in memory retention were also noted specifically in males. We conclude that PCBs might affect the dimorphic neuroendocrine control of reproductive system and of other neurobiological processes.

  15. Differential incorporation of dietary conjugated linolenic and linoleic acids into milk lipids and liver phospholipids in lactating and suckling rats.

    PubMed

    Cao, Ying; Chen, Jingnan; Yang, Lin; Chen, Zhen-Yu

    2009-09-01

    Interest in health benefits of conjugated fatty acids is growing. The present study compared the incorporation pattern of dietary conjugated linolenic acids (CLnA) into milk with that of conjugated linoleic acids (CLA). Lactating Sprague-Dawley rats (Day 1) were divided into five groups fed the control diet (n=4) or one of four experimental diets supplemented with 1-2% CLA or CLnA mixture (n=8 each). Supplementation of 1% and 2% CLA led to enrichment of 4.17% and 8.57% CLA, respectively, while supplementation of 1% and 2% CLnA resulted in enrichment of only 0.98% and 1.71% CLnA in the milk lipids, demonstrating the transfer of CLnA from maternal diet to milk was discriminated. When the lactating rats were given a diet containing a CLnA mixture of 9t,11t,13t-, 9c,11t,13t- and 9c,11t,13c-CLnA isomers, two CLA isomers, namely, 9t,11t (0.59-0.90%) and 9c,11t (1.21-1.96%), were found in the milk, suggesting that three CLnA isomers were Delta-13 saturated. Dietary CLnA at 1-2% had no effect on liver phospholipid (PL) fatty acid composition of both maternal and suckling rats, whereas dietary CLA increased docosahexaenoic acid (4c,7c,10c,13c,16c,19c-22:6) and palmitic acid (16:0) proportionally in the PL of maternal rats, but it suppressed 16:0 in the PL of suckling rats. It is concluded that maternal rats incorporate CLnA isomers into milk differently from that of CLA isomers. Most interesting is that maternal rats can metabolically convert CLnA to CLA.

  16. Dietary flax oil during pregnancy and lactation retards disease progression in rat offspring with inherited kidney disease.

    PubMed

    Sankaran, Deepa; Bankovic-Calic, Neda; Peng, Claudia Yu-Chen; Ogborn, Malcolm R; Aukema, Harold M

    2006-12-01

    Dietary flax oil (FO) retards disease progression in growing or adult animal models of kidney disease. To determine whether dietary flax oil during the perinatal period would alter renal disease progression in offspring, Han-SPRD-cy rats with inherited cystic kidney disease were given diets with either 7% FO or corn oil (CO), throughout pregnancy and lactation. At 3 wk of age, offspring were then given either the same or the alternate diet for 7 wk. Rats given FO during the maternal period had 15% less renal cyst growth compared with rats given FO only in the postweaning period. Dietary FO, compared with CO, in the maternal period also resulted in 12% lower cell proliferation and 15% less oxidant injury in diseased kidneys of offspring. Including FO in both the maternal and postweaning period resulted in 29-34% less renal interstitial fibrosis and 22-23% lower glomerular hypertrophy. Along with improved histology, these rats exhibited 13% less proteinuria and 30% lower creatinine clearance when dietary FO was given in the maternal period. The potential for dietary FO during pregnancy and lactation to positively modulate adult renal disease has significant implications for the 1 in 1000 individuals with congenital cystic kidney disease.

  17. Regulation by endogenous opioids of suckling-induced prolactin secretion in pregnant and lactating rats: role of ovarian steroids.

    PubMed

    Soaje, M; de Di Nasso, E G; Deis, R P

    2002-02-01

    Evidence suggests that endogenous opioid peptides are implicated in the suckling-induced prolactin rise. We explored the role of the opioid system and the participation of ovarian hormones in the regulation of prolactin induced by the suckling stimulus at the end of pregnancy in rats with developed maternal behavior, and during lactation. Suckling for 24 h induced a significant increase in serum prolactin on day 19 of pregnancy, which was increased more than three times when naloxone (2 mg/kg s.c.) or mifepristone (2 mg/kg) was administered. The combination of naloxone and mifepristone did not increase serum prolactin more than either compound alone. Administration of tamoxifen (500 microg/kg orally) on days 14 and 15 of pregnancy completely abolished the effect of naloxone, indicating a role for estrogens in establishing this inhibitory role of opioids. To examine the participation of the opioid system during lactation, we used groups of rats on days 1, 3, 5, 12 and 19 postpartum either (i) isolated from the pups for 4 h, or (ii) isolated from the pups for 3.5 h and reunited with them and suckled for 30 min. Naloxone, given just before replacing the pups, prevented the increase in serum prolactin levels observed in the suckled group of rats but had no effect on the basal levels of the isolated rats. To examine whether the participation of the opioid system in the release of prolactin is dependent on the variation of progesterone levels, rats on day 20 of pregnancy were implanted with two cannulae containing progesterone (that blocked postpartum ovulation) or cholesterol, and cesarean surgery was performed on day 21. To maintain lactation, pups (1-3 days old) were replaced every 24 h, and 4 days after the cesarean eight pups were placed in the cage at 1800 h to maintain a strong suckling stimulus during the following 24 h. Naloxone administration significantly reduced serum prolactin levels in control (cholesterol) rats but progesterone implants prevented the

  18. Safflower (Carthamus tinctorius L.) oil during pregnancy and lactation influences brain excitability and cortex oxidative status in the rat offspring.

    PubMed

    Mendes-da-Silva, Rosângela Figueiredo; Ferreira, Diorginis José Soares; Lopes-de-Morais, Andréia Albuquerque Cunha; de Macêdo, Patrícia Fortes Cavalcanti; Lagranha, Cláudia J; Batista-de-Oliveira-Hornsby, Manuella

    2017-08-07

    To evaluate how safflower oil (SFO) influences brain electrophysiology and cortical oxidative status in the offspring, mothers received a diet with SFO during brain development period. Beginning on the 14th day of gestation and throughout lactation, rats received safflower (safflower group - SG) or soybean oil (control group - CG) in their diet. At 65 days old, cortical spreading depression (CSD) and cortex oxidative status were analyzed in the offspring. SG presented reduction of the CSD velocity as compared to the CG (SG: 3.24 ± 0.09; CG: 3.37 ± 0.07 mm/min). SFO reduced levels of lipid peroxidation by 39.4%. SG showed the following increases: glutathione-S-transferase, 40.8% and reduced glutathione, 34.3%. However, SFO decreased superoxide dismutase by 40.4% and catalase by 64.1%. To control for interhemispheric effects, since CSD was recorded only in the right cortex, we evaluated the oxidative status in both sides of the cortex; no differences were observed. Data show that when SFO is consumed by the female rats during pregnancy and lactation, the offspring present long-term effects on brain electrophysiology and cortical oxidative state. The present study highlights the relevance of understanding the SFO intake of pregnant and lactating mammals.

  19. Maternal protein restriction in pregnancy and/or lactation affects seminiferous tubule organization in male rat offspring.

    PubMed

    Rodríguez-González, G L; Vigueras-Villaseñor, R M; Millán, S; Moran, N; Trejo, R; Nathanielsz, P W; Larrea, F; Zambrano, E

    2012-10-01

    Maternal protein restriction (MPR) during pregnancy impaired the reproduction of male offspring. We investigated, during the first wave of spermatogenesis, whether MPR exerts deleterious effects on germ cell proliferation and differentiation, as well as androgen receptor (AR) protein expression, which was used as a marker for Sertoli cell (SC) maturation. At the beginning of pregnancy (day 0), dams were fed a control diet (C: 20% casein) or a restricted isocaloric diet (R: 10% casein). After birth, four groups were established: CC, RR, CR and RC (first letter diet during pregnancy and second during lactation). Male offspring were studied at postnatal days 14, 21 and 36. At birth, pup body weight was unchanged. Body weight and testis weight were reduced in RR and CR groups at all ages evaluated. MPR delayed the germinal epithelium development at all ages evaluated. On performing Western blot and immunohistochemistry, AR expression was found to be lower in the three restricted groups. The results suggest that MPR during pregnancy and/or lactation delays SC maturation and germ cell differentiation, and affects intratubular organization. These changes might be responsible for the lower fertility rate at older ages.

  20. Effects of tobacco smoke exposure during lactation on nutritional and hormonal profiles in mothers and offspring.

    PubMed

    Santos-Silva, A P; Oliveira, E; Pinheiro, C R; Nunes-Freitas, A L; Abreu-Villaça, Y; Santana, A C; Nascimento-Saba, C C; Nogueira-Neto, J F; Reis, A M; Moura, E G; Lisboa, P C

    2011-04-01

    Exposure to tobacco smoke is related to changes in energy balance regulation and several endocrine dysfunctions. Previously, we showed that maternal nicotine (the main addictive compound of tobacco) exposure exclusively during lactation affects biochemical profiles in mothers, milk, and pups. As the possible consequences for mothers and offspring of maternal smoking during lactation are still unknown, we evaluated the effects of tobacco smoke exposure on nutritional, biochemical, and hormonal parameters in dams and pups at weaning. After 72 h from birth, lactating rats were divided into two groups: smoke-exposed (S) in a cigarette-smoking machine, 4 × 1 h per day throughout the lactation period without pups; control (C), rats were treated the same as the experimental group but exposed to filtered air. Dams and pups were killed at weaning (21 days of lactation). Body weight and food intake were evaluated. Milk, blood, visceral fat, adrenal, and carcass were collected. S dams showed hyperprolactinemia (+50%), hypoinsulinemia (-40%), hypoleptinemia (-46%), as well as lower triglycerides (-53%) and very low-density lipoprotein cholesterol (-50%). Milk of S dams had higher lactose (+52%) and triglycerides (+78%). S pups presented higher body protein (+17%), lower total (-24%) and subcutaneous fat contents (-25%), hypoglycemia (-11%), hyperinsulinemia (+28%), hypocorticosteronemia (-40%), lower adrenal catecholamine content (-40%), hypertriglyceridemia (+34%), higher high-density lipoprotein cholesterol (+16%), and lower low-density lipoprotein cholesterol (-45%). In conclusion, tobacco smoke exposure leads to changes in nutritional, biochemical, and hormonal parameters in dams and, passively through the milk, may promote several important metabolic disorders in the progeny.

  1. Trans-18:1 isomers in rat milk fat as effective biomarkers for the determination of individual isomeric trans-18:1 acids in the dams' diet.

    PubMed

    Wolff, Robert L

    2003-11-01

    Female rats were fed a diet containing by weight 10% partially hydrogenated sunflower oil, 2% sunflower oil, and 1% rapeseed oil during gestation and lactation. The trans-18:1 isomer profile of the fat supplement was (in % of total trans 18:1 acids in the fat supplement): delta4, 0.5; delta5, 1.0; delta6-delta8, 18.0; delta9 (elaidic), 13.5; delta10, 22.2; delta11 (vaccenic), 16.0; delta12, 11.3; delta13-delta14, 12.8; delta15, 2.5; and delta16, 2.2 (total trans 18:1 acids in the fat supplement: 40.6%). The cis 18:1 isomer profile was (in % of total cis-18:1 isomers): delta6-delta8, 2.1; delta9 (oleic), 70.9; delta10, 6.1; delta11, 8.3; delta12, 4.0; delta13, 2.8; delta14, 4.6, and delta15, 1.2 (total cis-18:1 acids in the fat supplement: 32.6%). Suckling rats from four litters were sacrificed at day 17 or 18 after birth, and their stomach content (milk) was analyzed. The trans-18:1 isomer profile of milk was (relative proportions, in % of total): delta4, 0.3; delta5, 1.1; delta6-delta8, 16.8; delta9, 15.3; delta10, 22.0; delta11, 16.7; delta12, 11.8; delta13-14, 11.8; delta15, 2.5, and delta16, 1.9 (total trans 18:1 acids in milk: %). That of cis-18:1 isomers was (proportions in % relative to total cis-18:1 isomers): delta6-delta8, 4.7; delta9, 72.5; delta10, 4.0; delta11, 8.0; delta12, 7.1; delta13, 1.9; delta14, 1.0, and delta15, 0.7 (total cis-18:1 acids in milk: %). These results demonstrate that all isomeric acids, independent of the geometry and the position of the ethylenic bond, are incorporated into milk lipids. With regard to trans-18:1 isomers, the distribution profile in milk is identical to that in the dams' diet, i.e., there is no discrimination against any positional isomer between their ingestion and their deposition into milk lipids. As a consequence, this study indicates that the trans-18:1 isomer profile of milk reflects that in the dams' diet and supports our earlier hypothesis that the profile of trans-18:1 isomers in milk can be used to

  2. Effect of oligomer procyanidins on reperfusion arrhythmias and lactate dehydrogenase release in the isolated rat heart.

    PubMed

    Al-Makdessi, Samar; Sweidan, Hicham; Jacob, Ruthard

    2006-01-01

    The antiarrhythmic effect of an oral 3-week-pretreatment with oligomer procyanidins derived from Vitis vinifera was investigated on the isolated perfused heart after global no-flow ischemia (procyanidin-treated group: n = 9, control group: n = 13). Hearts were perfused with a modified Krebs-Henseleit solution in which the K+ content was reduced to 3.0 mmol/l in order to lower the fibrillation threshold. Monophasic action potentials in addition to ECG were recorded. The durations of ischemia and reperfusion were 20 and 30 min, respectively. Arrhythmias including ventricular fibrillation (VF), ventricular tachycardia (VT), flutter (Fl) and bradycardia were evaluated. During the reperfusion, irreversible VF occurred in most of control hearts. The incidence of VF (percentage of the hearts in which VF occurred) was lowered by oligomer procyanidins from 84.6 to 55.6 %, and the duration of the episodes of VF (expressed as percentage relative to the total duration) was significantly shortened from 76.1 +/- 27.9 % to 36.6 +/- 40.6 % (p = 0.036). Simultaneously, the percentage of duration of normal sinus rhythm (NSR) increased from 19.5 +/- 30.3 % to 46.2 +/- 35.9 % (n.s.). VF occuring in the procyanidin-treated hearts could be reversed in two hearts within few minutes to a stage of "reversible arrhythmias" consisting of short episodes (1 to 60 s) of either Fl or VT or bradycardia or NSR alternating with each other. LDH (lactate dehydrogenase) release in the first drops appearing from the reperfused heart was significantly reduced in the procyanidin-treated rats (66.7 +/- 36.2 mU/min, n = 8) in comparison to controls (159.7 +/- 79.0 mU/min, n = 10; p = 0.010). These results demonstrate an antiarrhythmic and cytoprotective effect of oral pretreatment with oligomer procyanidins under the given experimental conditions.

  3. [Effect of diphenylhydantoin administered during gestation and lactation on the motor development and cerebellar histology of the young rat].

    PubMed

    Desor, D; Royer, R J; Netter, P; Guedenet, J C; Faure, G; Krafft, B; Grignon, G

    1978-01-01

    Rattus norvegicus females were treated by diphenylhydantoin (D.P.H.), all along pregnancy and lactation. 4 groups were constituted: a 100 mg DPH/kg/day group, a 50 mg DPH/kg/day group; a placebo group (treated with pure water), and control group. D.P.H. was given twice a day by a gastric tube. The cerebellar Purkinje cells studied through light microscopy and transmission electron microscopy in young rats (25 days old) showed no visible alteration. 2 motorcoordination tests were applied to the young rats, during their 2nd and 3rd weeks of post-natal life. Young rats of DPH 100, DPH 50 and placebo groups showed a backwardness relatively to control. This backwardness may be attributed to the maternal forced feeding stress, but not to a specific action of the DPH.

  4. The effects of exposure to titanium dioxide nanoparticles during lactation period on learning and memory of rat offspring.

    PubMed

    Mohammadipour, Abbas; Hosseini, Mahmoud; Fazel, Alireza; Haghir, Hossein; Rafatpanah, Houshang; Pourganji, Masoume; Bideskan, Alireza Ebrahimzadeh

    2016-02-01

    Nanoscale titanium dioxide (TiO2), which is massively produced and widely used in living environment, seems to have a potential risk on human health. The central nervous system (CNS) is the potential susceptible target of nanoparticles, but the studies on this aspect are limited so far. The aim of this study was to evaluate the effects of exposure to TiO2 nanoparticles during lactation period on learning and memory of offspring. Lactating Wistar rats were exposed to TiO2 nanoparticles (100 mg/kg; gavage) for 21 days. The Morris water maze and passive avoidance tests showed that the exposure to TiO2 nanoparticles could significantly impair the memory and learning in the offspring. Therefore, the application of TiO2 nanoparticles and the effects of their exposure, especially during developmental period on human brain should be cautious.

  5. Creatine supplementation increases glucose oxidation and AMPK phosphorylation and reduces lactate production in L6 rat skeletal muscle cells

    PubMed Central

    Ceddia, Rolando B; Sweeney, Gary

    2004-01-01

    Recent observations have suggested that creatine supplementation might have a beneficial effect on glucoregulation in skeletal muscle. However, conclusive studies on the direct effects of creatine on glucose uptake and metabolism are lacking. The objective of this study was to investigate the effects of creatine supplementation on basal and insulin-stimulated glucose transporter (GLUT4) translocation, glucose uptake, glycogen content, glycogen synthesis, lactate production, glucose oxidation and AMP-activated protein kinase (AMPK) phosphorylation in L6 rat skeletal muscle cells. Four treatment groups were studied: control, insulin (100 nm), creatine (0.5 mm) and creatine + insulin. After 48 h of creatine supplementation the creatine and phosphocreatine contents of L6 myoblasts increased by ∼9.3- and ∼5.1-fold, respectively, but the ATP content of the cells was not affected. Insulin significantly increased 2-deoxyglucose uptake (∼1.9-fold), GLUT4 translocation (∼1.8-fold), the incorporation of D-[U-14C]glucose into glycogen (∼2.3-fold), lactate production (∼1.5-fold) and 14CO2 production (∼1.5-fold). Creatine neither altered the glycogen and GLUT4 contents of the cells nor the insulin-stimulated rates of 2-DG uptake, GLUT4 translocation, glycogen synthesis and glucose oxidation. However, creatine significantly reduced by ∼42% the basal rate of lactate production and increased by ∼40% the basal rate of 14CO2 production. This is in agreement with the ∼35% increase in citrate synthase activity and also with the ∼2-fold increase in the phosphorylation of both α-1 and α-2 isoforms of AMPK after creatine supplementation. We conclude that 48 h of creatine supplementation does not alter insulin-stimulated glucose uptake and glucose metabolism; however, it activates AMPK, shifts basal glucose metabolism towards oxidation and reduces lactate production in L6 rat skeletal muscle cells. PMID:14724211

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

    PubMed

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

    2015-10-01

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

  7. Lactational hexavalent chromium exposure-induced oxidative stress in rat uterus is associated with delayed puberty and impaired gonadotropin levels.

    PubMed

    Samuel, Jawahar B; Stanley, Jone A; Roopha, Dailiah P; Vengatesh, Ganapathy; Anbalagan, Jaganathan; Banu, Sakhila K; Aruldhas, Michael M

    2011-02-01

    Hexavalent chromium (CrVI) is a transition element utilized in many fields of modern industries. CrVI is a reproductive metal toxicant that can traverse the placental barrier and cause a wide range of fetal effects. Therefore, the present study was carried out to determine the CrVI-induced utero-toxicity. In the present study, lactating rats received drinking water containing CrVI (50 mg/L and 200 mg/L) from postnatal days (PND) 1-21. During PND 1-21, the pups received CrVI via the mother's milk. Pups from both control and treatment groups were continued on regular diet and water from PND-21 onwards and euthanized on PND-45 and -65. Specific activities antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) were estimated. Hydrogen peroxide (H₂O₂), lipid peroxidation (LPO) and serum gonadotropins viz. Luteinizing hormone (LH) and follicle stimulating hormone (FSH) were also assayed. Specific activities of SOD, CAT, GPX, GR and GST and serum testosterone and progesterone were significantly decreased, while H₂O₂, LPO and serum FSH was increased in 50-parts per million (ppm) and 200 ppm-treated rats in an age-dependent manner. These results suggest that lactational CrVI exposure induces oxidative stress in rat uterus by decreasing antioxidant enzymes, which were associated with delayed puberty and altered steroids and gonadotrophin levels.

  8. The effect of zinc supplementation of lactating rats on short-term and long-term memory of their male offspring.

    PubMed

    Karami, Mohammad; Ehsanivostacolaee, Simin; Moazedi, Ali Ahmad; Nosrati, Anahita

    2013-01-01

    In this study the effect of zinc chloride (ZnCl2) administration on the short-term and long-term memory of rats were assessed. We enrolled six groups of adult female and control group of eight Wistar rats in each group. One group was control group with free access to food and water, and five groups drunk zinc chloride in different doses (20, 30, 50, 70 and 100 mg/kg/day) in drinking water for two weeks during lactation .One month after birth, a shuttle box used to short- term and long-term memory and the latency in entering the dark chamber as well. This experiment showed that maternal 70 mg/kg dietary zinc during lactation influenced the working memory of rats' offspring in all groups. Rats received 100 mg/kg/day zinc during lactation so they had significant impairment in working memory (short-term) of their offspring (P<0.05). There was no significant difference in reference (long-term) memory of all groups. Drug consumption below70 mg/kg/day zinc chloride during lactation had no effect. While enhanced 100 mg/ kg/ day zinc in lactating rats could cause short-term memory impairment.

  9. Regulation of collagen production in freshly isolated cell populations from normal and cirrhotic rat liver: Effect of lactate

    SciTech Connect

    Cerbon-Ambriz, J.; Cerbon-Solorzano, J.; Rojkind, M. )

    1991-03-01

    Previous work has shown that lactic acid, and to a lesser extent pyruvic acid, is able to increase collagen synthesis significantly in liver slices of CCl4-treated rats but not normal rats. The purpose of this report is to document which cells in the cirrhotic liver are responsible for the lactate-stimulated increase in collagen synthesis. It was found that (a) incorporation of 3H-proline into protein-bound 3H-hydroxyproline is increased threefold to fourfold in hepatocytes from CCl4-treated rats as compared with normal rat hepatocytes; (b) neither the hepatocytes from normal nor those from CCl4-treated rats modify their collagen synthesizing capacity when 30 mmol/L lactic acid was added to the incubation medium; (c) nonparenchymal cells obtained from livers of CCl4-treated rats synthesize much less collagen than hepatocytes, but their synthesis is stimulated twofold by lactic acid; (d) from the different nonparenchymal cells, only fat-storing (Ito) cells increase collagen synthesis when lactic acid is present in the incubation medium. These results suggest that the increased lactic acid levels observed in patients with alcoholic hepatic cirrhosis may play an important role in the development of fibrosis by stimulating collagen production by fat-storing (Ito) cells.

  10. Oxidative stress and thyroid impairment after gibberellic acid treatment in pregnant and lactating rats and their offspring.

    PubMed

    Troudi, Afef; Amara, Ibtissem Ben; Samet, Amira Mahjoubi; Fetoui, Hamadi; Soudani, Nejla; Guermazi, Fadhel; Boudawara, Tahia; Zeghal, Najiba

    2011-01-01

    Gibberellic acid (GA₃) has been worldwide used in agriculture as a plant growth regulator. The purpose of this study is to assess the effects of GA₃ on the morphology and the thyroid hormone levels in adult rats and their suckling pups. Animals were given daily 200 ppm GA₃ in drinking water from the 14th day of pregnancy until day 14 after delivery. Compared with a control group, GA₃-treated mothers and pups showed an increase in body and thyroid weights, a decrease in plasma FT₄ and FT₃ levels, which were more pronounced in pups than in their mothers. Thyroid iodine content was also decreased in pups. These biochemical modifications corresponded histologically; the majority of follicles had cubical epithelial cells, which surrounded empty vesicular cavities. Toxicity was objectified by a significant increase in plasma malondialdehyde, protein carbonyls, and advanced oxidation protein products levels in GA₃-treated dams and their suckling pups; while, the activities of superoxide dismutase, catalase, and glutathione peroxidase were decreased in plasma of both dams and their pups. Moreover, a significant decline was observed in plasma glutathione, nonprotein thiols, and vitamin C levels. We conclude that GA₃ treatment affects thyroid function and plasma antioxidant status in adult rats and their progeny. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.

  11. PRENATAL EXPOSURE TO THE FUNGICIDE PROCHLORAZ ALTERS THE ONSET OF PARTURITION IN THE DAM AND SEXUAL DIFFERENTIATION IN MALE RAT OFFSPRING

    EPA Science Inventory

    Prenatal Exposure to the Fungicide Prochloraz alters the onset of Parturition in
    the Dam and Sexual Differentiation in Male Rat Offspring.
    N. Noriega1; E. Gray1; J. Ostby1; C. Lambright1; V. Wilson1
    1. RTD, NHEERL, ORD, USEPA, RTP, NC, USA;

    Prochloraz...

  12. Receptors and neurotransmitters involved in the dual modulation of prolactin release by the serotoninergic system in pregnant and lactating rats.

    PubMed

    Jahn, G A; Kalia, V; Hole, D; Wilson, C A; Deis, R P

    1999-07-01

    The receptors and neurotransmitter pathways that may participate in the inhibitory action of 5-hydroxytryptamine (5HT) on prolactin release during late pregnancy and lactation in rats were studied. Administration of the 5HT synthesis inhibitor, p-chlorophenylalanine, to late pregnant rats induced a significant increase in serum prolactin concentrations at 17:00 h on day 19 of pregnancy that was partially blocked by injections of the 5HT precursor, 5-hydroxytryptophan, or the 5HT agonists, 8-hydroxy-2-(di-n-propylamino)-tetralin hydrobromide (S1a), 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (S2) and N-(3-chlorophenyl)imidodicarbonimide diamide HCl (S3), but not by RU 24969 (S1b) or 1-meta-(chlorophenyl)-piperazine-2-HCl (S1a-2c). The 5HT neurotoxins, fenfluramine and p-chloroamphetamine, which selectively destroy fine axon serotoninergic fibres but not coarse ones, prevented the increase in circulating prolactin observed at 18:00 h on pro-oestrus and on day 21 of pregnancy, but did not modify serum prolactin concentrations at 17:00 h on day 19 of pregnancy. Administration of the adrenergic antagonists, metoprolol or prazosin, also prevented the stimulatory effects of p-chlorophenylalanine or ketanserin in pregnant rats on day 19 (17:00 h) or on days 10-12 (16:30 h) in lactating rats separated from their litters. Administration of p-chlorophenylalanine to pregnant rats on day 19 reduced dopamine concentrations in the arcuate nucleus and in the anterior hypothalamus and noradrenaline concentrations in the anterior hypothalamus and the suprachiasmatic nucleus. These results indicate that the inhibitory actions of 5HT on prolactin release in pregnant and lactating rats are mediated by S1a, S2a and S3 receptors and by the coarse axon serotoninergic fibres. In addition, the inhibitory actions of 5HT may modulate the action of a stimulatory adrenergic pathway, as well as the concentrations of noradrenaline and dopamine in different hypothalamic areas, which, in turn

  13. Exposure to flaxseed during lactation does not alter prostate area or epithelium height but changes lipid profile in rats.

    PubMed

    Ferreira Medeiros de França Cardozo, L; Alves Chagas, M; Leal Soares, L; Andrade Troina, A; Teles Bonaventura, G

    2010-01-01

    Flaxseed intake has increased owing to beneficial effects to health and prevention of diseases. Provided that it's an important source of lignan, a phytoestrogen, the present study aimed at evaluating the possible effect of the intake of this seed during lactation upon prostate, sexual hormones and lipidic profile of the offspring in adult life. 16 female Wistar rats were used. After delivery, they were divided into two different groups to receive one of the following diets during lactation: Control group (CG), with a casein based diet and Flaxseed group (FG), with a flaxseed based diet containing 25% flaxseed. At weaning, male pups received commercial chow until adult life (170 days old), when they were sacrificed. No differences were perceived concerning offspring food intake and body weight at 170 days. There was a reduction in total cholesterol levels (FG = 45.71 +/- 8.96 mg/dL; CG = 63.43 +/- 15.69 mg/dL, p = 0.02) and triglycerides (FG = 54.29 +/- 11.10 mg/dL; CG = 79.86 +/- 25.68 mg/dL, p = 0.03). Also, no alterations were observed in prostatic morphology, testosterone or estradiol levels in the two groups analyzed. Flaxseed intake during lactation did not produce histological alterations in prostatic alveolus or in sexual hormones, but programmed to a reduction in lipid profile in adult life with decreased cardiovascular risk.

  14. Hyperbaric oxygen therapy or hydroxycobalamin attenuates surges in brain interstitial lactate and glucose; and hyperbaric oxygen improves respiratory status in cyanide-intoxicated rats.

    PubMed

    Lawson-Smith, P; Olsen, N V; Hyldegaard, O

    2011-01-01

    Cyanide (CN) intoxication inhibits cellular oxidative metabolism and may result in brain damage. Hydroxycobalamin (OHCob) is one among other antidotes that may be used following intoxication with CN. Hyperbaric oxygen (HBO2) is recommended when supportive measures or antidotes fail. However, the effect of hydroxycobalamin or HBO2 on brain lactate and glucose concentrations during CN intoxication is unknown. We used intracerebral microdialysis to study the in vivo effect of hydroxycobalamin or HBO2 treatment on acute CN-induced deterioration in brain metabolism. Anesthetized rats were allocated to four groups receiving potassium CN (KCN) 5.4 mg/kg or vehicle intra-arterially: 1) vehicle-treated control rats; 2) KCN-poisoned rats; 3) KCN-poisoned rats receiving hydroxycobalamin (25 mg); and 4) KCN-poisoned rats treated with HBO2 (284 kPa for 90 minutes). KCN alone caused a prompt increase in interstitial brain lactate and glucose concentrations peaking at 60 minutes. Both hydroxycobalamin and HBO2 abolished KCN-induced increases in brain lactate and glucose concentration. However, whereas HBO2 treatment increased cerebral PtO2 and reduced respiratory distress and cyanosis, OHCob did not have this beneficial effect. In conclusion, CN intoxication in anesthetized rats produces specific uncoupling of cerebral oxidative metabolism resulting in interstitial lactate and glucose surges that may be ameliorated by treatment with either hydroxycobalamin or HBO2.

  15. Maternal Western diet increases adiposity even in male offspring of obesity-resistant rat dams: early endocrine risk markers.

    PubMed

    Frihauf, Jennifer B; Fekete, Éva M; Nagy, Tim R; Levin, Barry E; Zorrilla, Eric P

    2016-12-01

    Maternal overnutrition or associated complications putatively mediate the obesogenic effects of perinatal high-fat diet on developing offspring. Here, we tested the hypothesis that a Western diet developmental environment increases adiposity not only in male offspring from obesity-prone (DIO) mothers, but also in those from obesity-resistant (DR) dams, implicating a deleterious role for the Western diet per se. Selectively bred DIO and DR female rats were fed chow (17% kcal fat) or Western diet (32%) for 54 days before mating and, thereafter, through weaning. As intended, despite chow-like caloric intake, Western diet increased prepregnancy weight gain and circulating leptin levels in DIO, but not DR, dams. Yet, in both genotypes, maternal Western diet increased the weight and adiposity of preweanlings, as early as in DR offspring, and increased plasma leptin, insulin, and adiponectin of weanlings. Although body weight normalized with chow feeding during adolescence, young adult Western diet offspring subsequently showed decreased energy expenditure and, in DR offspring, decreased lipid utilization as a fuel substrate. By mid-adulthood, maternal Western diet DR offspring ate more chow, weighed more, and were fatter than controls. Thus, maternal Western diet covertly programmed increased adiposity in childhood and adulthood, disrupted relations of energy regulatory hormones with body fat, and decreased energy expenditure in offspring of lean, genetically obesity-resistant mothers. Maternal Western diet exposure alone, without maternal obesity or overnutrition, can promote offspring weight gain. Copyright © 2016 Frihauf et al.

  16. Effect of Four Weeks of β-alanine Supplementation on Muscle Carnosine and Blood Serum Lactate during Exercise in Male Rats.

    PubMed

    Naderi, Alireza; Hemat Far, Ahmad; Willems, Mark E T; Sadeghi, Mehdi

    2016-01-01

    β-alanine (BA) supplementation may increase muscle buffering capacity and affect physiological responses during exercise. We examined the effects of 4 weeks of BA supplementation on muscle carnosine and serum lactate in male rats. Rats (n = 24, age: 2 months, body weight: 265±22 g) were divided into a BA supplementation or control group. Along with aerobic acclimatization exercise (15 m·min(-1), 8-10 min·day(-1), 4 days·week(-1) for 4 weeks), the BA group had access to BA powder in their drinking water (1.8%) with the control group having access to plain water for 4 weeks. After 4 weeks, rats ran on a treadmill at speeds of 15, 20, 25, 30, and 35 m·min(-1), respectively, each for 4 min, in order to measure post-exercise serum lactate. Muscle carnosine and serum lactate levels were measured with high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbant assay (ELISA) procedures, respectively. Following BA supplementation, carnosine content in the m.rectus femoris increased by 117% (p < .01) and serum lactate decreased by 7.4% (p < .01). It was concluded that β-alanine supplementation increases muscle carnosine content and reduces serum lactate; these changes may indicate an adaptation of rat skeletal muscles to postpone peripheral muscle fatigue during high-intensity exercise.

  17. Increased cholesterol 7α-hydroxylase expression and size of the bile acid pool in the lactating rat

    PubMed Central

    Wooton-Kee, Clavia Ruth; Cohen, David E.; Vore, Mary

    2008-01-01

    Maximal bile acid secretory rates and expression of bile acid transporters in liver and ileum are increased in lactation, possibly to facilitate increased enterohepatic recirculation of bile acids. We determined changes in the size and composition of the bile acid pool and key enzymes of the bile acid synthetic pathway [cholesterol 7α-hydroxylase (Cyp7a1), sterol 27-hydroxylase (Cyp27a1), and sterol 12α-hydroxylase (Cyp8b1)] in lactating rats relative to female virgin controls. The bile acid pool increased 1.9 to 2.5-fold [postpartum (PP) days 10, 14, and 19–23], compared with controls. A 1.5-fold increase in cholic acids and a 14 to 20% decrease in muricholic acids in lactation significantly increased the hydrophobicity index. In contrast, the hepatic concentration of bile acids and small heterodimer partner mRNA were unchanged in lactation. A 2.8-fold increase in Cyp7a1 mRNA expression at 16 h (10 h of light) demonstrated a shift in the diurnal rhythm at day 10 PP; Cyp7a1 protein expression and cholesterol 7α-hydroxylase activity were significantly increased at this time and remained elevated at day 14 PP but decreased to control levels by day 21 PP. There was an overall decrease in Cyp27a1 mRNA expression and a 20% decrease in Cyp27a1 protein expression, but there was no change in Cyp8b1 mRNA or protein expression at day 10 PP. The increase in Cyp7a1 expression PP provides a mechanism for the increase in the bile acid pool. PMID:18292185

  18. [Effects of malnutrition in utero and during lactation on various parameters of the small intestine in rats].

    PubMed

    Gutiérrez, J M; Alvarez-Ordás, I; Fernández, S; Marín, B; Menéndez-Patterson, A

    1988-12-01

    Short and long term effects of malnutrition on the small intestine, applied to the rat in uterus and lactation, have been studied. Malnutrition was induced by feeding the pregnant rats on 14 g daily during pregnancy and 21 g during lactation. In the pups (0, 15, 30, 90 and 150 days old), body weight and wet and dry weight and length of small intestine were measured. At 2.5-3 months of age, food transformation efficiency was studied, at 3 and 5 months of age in vivo intestinal absorption of D-glucose (11 mM) was measured. The results indicate a significant decrease in intestinal morphometric parameters in malnourished animals from birth to the age of 5 months. At the age of 3 months both food transformation efficiency and in vivo absorption of glucose were significantly higher in early undernourished animals, whereas at 5 months, glucose absorption was significantly higher in control. It can thus be concluded that early malnutrition altered the small intestine development and functionality and that total recovery did not occur after 4 months on a normal diet.

  19. Effect of sex and age on the activities of lactate dehydrogenase and alkaline phosphatase in the lungs of rats.

    PubMed Central

    Lopez, A; Yong, S; Sharma, A; Morwood-Clark, M; Lillie, L E; Albassam, M

    1986-01-01

    Since toxicity studies among different laboratories generally involve rats of different sex and age, this study was conducted to investigate the effect of sex, age and animal to animal variation in the activities of lactate dehydrogenase and alkaline phosphatase from bronchoalveolar lavage fluid, bronchoalveolar cell lysate and lung homogenate. Correlation between numbers of bronchoalveolar cells recovered from lungs and enzyme activity in bronchoalveolar cell lysate or lung homogenate supernatant were also investigated. Male rats showed significantly (p less than 0.05) higher activities of alkaline phosphatase in the bronchoalveolar lavage fluid and lung homogenate. Animal to animal variation for lactate dehydrogenase and alkaline phosphatase was higher in lungs than in serum. The number of bronchoalveolar cells recovered from lungs revealed a significant (p less than 0.01) positive correlation with the activities of both enzymes in the supernatant of cell lysates but not in the bronchoalveolar fluid. These results indicated that in an inhalation study interindividual variation in the levels of pulmonary enzymes should be considered in order to minimize the numerous possible sources of experimental error. PMID:3742377

  20. Enhancement of calcium-dependent afterpotentials in oxytocin neurons of the rat supraoptic nucleus during lactation

    PubMed Central

    Teruyama, Ryoichi; Armstrong, William E

    2005-01-01

    The firing pattern of oxytocin (OT) hormone synthesizing neurons changes dramatically immediately before each milk ejection, when a brief burst of action potentials is discharged. OT neurons possess intrinsic currents that would modulate this burst. Our previous studies showed the amplitude of the Ca2+-dependent afterhyperpolarization (AHP) following spike trains is significantly larger during lactation. In the present study we sought to determine which component of the AHP is enhanced, and whether the enhancement could be related to changes in whole-cell Ca2+ current or the Ca2+ transient in identified OT or vasopressin (VP) neurons during lactation. We confirmed, with whole-cell current-clamp recordings, our previous finding from sharp electrodes that the size of the AHP following spike trains increased in OT, but not VP neurons during lactation. We then determined that an apamin-sensitive medium-duration AHP (mAHP) and an apamin-insensitive slow AHP (sAHP) were specifically increased in OT neurons. Simultaneous Ca2+ imaging revealed that the peak change in somatic [Ca2+]i was not altered in either cell type, but the slow decay of the Ca2+ transient was faster in both cell types during lactation. In voltage clamp, the whole-cell, Ca2+ current was slightly larger during lactation in OT cells only, but current density was unchanged when corrected for somatic hypertrophy. The currents, ImAHP and IsAHP, also were increased in OT neurons only, but only the apamin-sensitive ImAHP showed an increase in current density after adjusting for somatic hypertrophy. These findings suggest a specific modulation (e.g. increased number) of the small-conductance Ca2+-dependent K+ (SK) channels, or their interaction with Ca2+, underlies the increased mAHP/ImAHP during lactation. This larger mAHP may be necessary to limit the explosive bursts during milk ejection. PMID:15878948

  1. Comparison of the developmental milestones and preweaning neurobehavioral parameters in rat pups exposed to lead (Pb) during gestation, lactation and pregestation period.

    PubMed

    Rao Barkur, Rajashekar; Bairy, Laxminarayana K

    2016-01-01

    Studies in urban children exposed to low lead (Pb) have shown neurobehavioral deficits in the domains of intelligence, reaction time and attention. The structures - hippocampus (vital for learning and memory) and cerebellum (play a role in motor behavior and cognition) - which develop postnatally, are affected by developmental Pb exposure. The effect of low level of Pb exposure during specific periods of early brain development on early neurobehavioral outcomes in rat pups has not been studied. So in this study, pregnant albino Wistar strain rats were exposed to low levels of Pb in drinking water during gestation period (G group), lactation period (L group), both gestation and lactation period (GL group) and prior to pregnancy (a period of 1 month) (PG group). The rat pups born in each of these groups were assessed in preweaning neurobehavioral parameters including surface righting reflex, swimming development, negative geotaxis and ascending wire mesh test. The swimming development scores were low in the GL group of rats. The negative geotaxis score in GL and G groups were altered. The day of achievement of ascending wire mesh test was significantly delayed in GL, G and L groups of rats. To conclude, results show that (a) low level of Pb exposure during gestation and lactation period of brain development causes significant alterations in the early neurobehavioral and sensorimotor reflex development in the absence of concomitant weight loss and (b) gestation period only and lactation period only, Pb exposure causes alteration in some of the neurobehavioral outcomes.

  2. A maternal 'junk food' diet in pregnancy and lactation promotes an exacerbated taste for 'junk food' and a greater propensity for obesity in rat offspring.

    PubMed

    Bayol, Stéphanie A; Farrington, Samantha J; Stickland, Neil C

    2007-10-01

    Obesity is generally associated with high intake of junk foods rich in energy, fat, sugar and salt combined with a dysfunctional control of appetite and lack of exercise. There is some evidence to suggest that appetite and body mass can be influenced by maternal food intake during the fetal and suckling life of an individual. However, the influence of a maternal junk food diet during pregnancy and lactation on the feeding behaviour and weight gain of the offspring remains largely uncharacterised. In this study, six groups of rats were fed either rodent chow alone or with a junk food diet during gestation, lactation and/or post-weaning. The daily food intakes and body mass were measured in forty-two pregnant and lactating mothers as well as in 216 offspring from weaning up to 10 weeks of age. Results showed that 10 week-old rats born to mothers fed the junk food diet during gestation and lactation developed an exacerbated preference for fatty, sugary and salty foods at the expense of protein-rich foods when compared with offspring fed a balanced chow diet prior to weaning or during lactation alone. Male and female offspring exposed to the junk food diet throughout the study also exhibited increased body weight and BMI compared with all other offspring. This study shows that a maternal junk food diet during pregnancy and lactation may be an important contributing factor in the development of obesity.

  3. Self-selection of a high calcium diet by vitamin D-deficient lactating rats increases food consumption and milk production.

    PubMed

    Brommage, R; DeLuca, H F

    1984-08-01

    Lactating and nonlactating rats, both deficient and replete in cholecalciferol, were allowed a free selection among three diets containing 0.47% Ca, 0.3% P (normal Ca, normal P diet); 2.0% Ca, 0.3% P (high Ca diet); and 0.47% Ca, 1.0% P (high P diet). An additional group of vitamin D-deficient lactating rats was fed only the normal Ca, normal P diet. Vitamin D-deficient rats showed a strong selection preference for the high Ca diet but avoided the high P diet, whereas cholecalciferol-replete rats consumed the normal Ca, normal P diet predominantly. Compared to the nonselecting rats, the selection of the high Ca diet by the lactating rats deficient in vitamin D resulted in an increase in plasma calcium levels, hypophosphatemia, a doubling of food consumption, a reduction in maternal body weight loss and a stimulation of milk production as indicated by pup growth. These results demonstrate that vitamin D-deficient rats select a high Ca diet and that the decrease in milk production found in vitamin D deficiency results from a decrease in food consumption and that this anorexia is at least partially dependent on the hypocalcemia normally occurring in vitamin D deficiency.

  4. Paradoxical effects of alcohol and thiamine deficiency on the eye opening in rat pups.

    PubMed

    Bâ, Abdoulaye

    2012-11-01

    The present study attempts to determine whether developmental thiamine (B1 vitamin) deficiency and developmental ethanol exposure disturb eye opening in Wistar rat pups. During gestation and lactation, Wistar rat dams were exposed to the following treatments: (1) Prenatal thiamine-deficient dams; (2) perinatal thiamine-deficient dams; (3) postnatal thiamine-deficient dams; (4) 12% alcohol/water drinking mothers; (5) mothers drinking 12% alcohol/water + thiamine hydrochloride mixture; (6) ad libitum control dams. Pair-feeding treatments controlled malnutrition related to thiamine deficiency: (7) Prenatal pair-fed dams; (8) perinatal pair-fed dams; (9) postnatal pair-fed dams and included also the control of alcohol consummation: (10) pair-fed saccharose dams. After birth, from postnatal day 10 (P10) to P18, eye opening was observed in the pups bred by ten different experimental dams. The present experiments showed eye opening to be delayed strongly in perinatal thiamine-deficient pups only. Consequently, our study suggests perinatal thiamine deficiency to interfere with photoreceptors differentiation in the rat retina. In addition, our results reveal that developmental alcohol exposure-induced premature eye opening contrasted paradoxically with perinatal thiamine deficiency-induced delayed opening. The results suggest differential actions of alcohol and thiamine deficiency on cellular genesis in the rat retina.

  5. Prenatal stress increases HPA axis activity and impairs maternal care in lactating female offspring: implications for postpartum mood disorder.

    PubMed

    Bosch, Oliver J; Müsch, Werner; Bredewold, Remco; Slattery, David A; Neumann, Inga D

    2007-04-01

    Early life stress is believed to constitute a risk factor for the development of mood disorders later in life. In the present study, we hypothesized that prenatal stress (PS) exerts long-lasting effects in female rat offspring, resulting in impaired adaptations to stress during lactation and, as such, may be a contributory factor to postpartum mood disorders. PS increased anxiety in adult virgin females compared with controls. During lactation, PS dams nursed significantly less and spent less time with pups compared with controls, whereas dams did not differ in pup retrieval or maternal aggression. HPA axis reactivity was elevated in response to a mild stressor in PS dams compared to their controls, but not in virgins, with the delta corticosterone response returning to the higher level seen in virgins. Moreover, corticotropin-releasing hormone (CRH) mRNA expression within the parvocellular region of the paraventricular nucleus (PVN) was increased in both virgins and dams exposed to PS compared with the relative controls, while the attenuation in expression in lactating controls was abolished following PS. In addition, arginine vasopressin (AVP) mRNA was increased in the parvocellular, but not magnocellular part of the PVN, in both PS-exposed virgins and lactating dams compared with their relative controls; although expression was also higher in controls during lactation compared with virgins. Thus, the present study demonstrates that exposure to PS results in long-lasting behavioural and neuroendocrine alterations in the female offspring, which are manifested during the lactation period. Furthermore, it implicates PS as a potential risk factor for the development of postpartum mood disorders, and that alterations in the HPA axis reactivity, at least partially, are involved.

  6. Exposure to a glyphosate-based herbicide during pregnancy and lactation induces neurobehavioral alterations in rat offspring.

    PubMed

    Gallegos, Cristina E; Bartos, Mariana; Bras, Cristina; Gumilar, Fernanda; Antonelli, Marta C; Minetti, Alejandra

    2016-03-01

    The impact of sub-lethal doses of herbicides on human health and the environment is a matter of controversy. Due to the fact that evidence particularly of the effects of glyphosate on the central nervous system of rat offspring by in utero exposure is scarce, the purpose of the present study was to assess the neurobehavioral effects of chronic exposure to a glyphosate-containing herbicide during pregnancy and lactation. To this end, pregnant Wistar rats were exposed through drinking water to 0.2% or 0.4% of a commercial formulation of glyphosate (corresponding to a concentration of 0.65 or 1.30g/L of glyphosate, respectively) during pregnancy and lactation and neurobehavioral alterations in offspring were analyzed. The postnatal day on which each pup acquired neonatal reflexes (righting, cliff aversion and negative geotaxis) and that on which eyes and auditory canals were fully opened were recorded for the assessment of sensorimotor development. Locomotor activity and anxiety levels were monitored via open field test and plus maze test, respectively, in 45- and 90-day-old offspring. Pups exposed to a glyphosate-based herbicide showed early onset of cliff aversion reflex and early auditory canal opening. A decrease in locomotor activity and in anxiety levels was also observed in the groups exposed to a glyphosate-containing herbicide. Findings from the present study reveal that early exposure to a glyphosate-based herbicide affects the central nervous system in rat offspring probably by altering mechanisms or neurotransmitter systems that regulate locomotor activity and anxiety. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Differential gene expression in liver and small intestine from lactating rats compared to age-matched virgin controls detects increased mRNA of cholesterol biosynthetic genes

    PubMed Central

    2011-01-01

    Background Lactation increases energy demands four- to five-fold, leading to a two- to three-fold increase in food consumption, requiring a proportional adjustment in the ability of the lactating dam to absorb nutrients and to synthesize critical biomolecules, such as cholesterol, to meet the dietary needs of both the offspring and the dam. The size and hydrophobicity of the bile acid pool increases during lactation, implying an increased absorption and disposition of lipids, sterols, nutrients, and xenobiotics. In order to investigate changes at the transcriptomics level, we utilized an exon array and calculated expression levels to investigate changes in gene expression in the liver, duodenum, jejunum, and ileum of lactating dams when compared against age-matched virgin controls. Results A two-way mixed models ANOVA was applied to detect differentially expressed genes. Significance calls were defined as a p < 0.05 for the overall physiologic state effect (lactation vs. control), and a within tissue pairwise comparison of p < 0.01. The proportion of false positives, an estimate of the ratio of false positives in the list of differentially expressed genes, was calculated for each tissue. The number of differentially expressed genes was 420 in the liver, 337 in the duodenum, 402 in the jejunum, and 523 in the ileum. The list of differentially expressed genes was in turn analyzed by Ingenuity Pathways Analysis (IPA) to detect biological pathways that were overrepresented. In all tissues, sterol regulatory element binding protein (Srebp)-regulated genes involved in cholesterol synthesis showed increased mRNA expression, with the fewest changes detected in the jejunum. We detected increased Scap mRNA in the liver only, suggesting an explanation for the difference in response to lactation between the liver and small intestine. Expression of Cyp7a1, which catalyzes the rate limiting step in the bile acid biosynthetic pathway, was also significantly increased in liver. In

  8. Changes in concentrations of methylglyoxal, D-lactate and glyoxalase activities in liver and plasma of rats fed a 3'-methyl-4-dimethylaminoazobenzene-rich diet.

    PubMed

    Kawase, M; Tada, M; Akagi, S; Ohmori, S

    1996-01-01

    Donryu male albino rats were fed a diet containing 0.064% 3'-methyl-4-dimethylaminoazobenzene (MDAB) for 21 weeks. During the ensuing rat liver carcinogenesis, changes in the concentrations of methylglyoxal, D-lactate and glutathione as well as activities of glyoxalase I and II in liver and plasma were examined. After the start of the diet, hepatic contents of methylglyoxal and D-lactate increased to about 7 and 3 times that of the control, respectively. However, after 21 weeks the D-lactate content decreased from the elevated level, but remained at a higher level of 1.4 times the control. The hepatic glyoxalase I activity increased 1.2 to 1.7 times over the control during carcinogenesis, while glyoxalase II activity increased 160% during the precancerous state and decreased to 55% of control at 21 weeks. the hepatic level of reduced glutathione (GSH) increased and peaked after 4 weeks of the MDAB diet and decreased thereafter to 57% of the control level after 21 weeks. Both pyruvate and L-lactate levels increased in the liver and plasma of MDAB-fed rats when rats had obvious symptoms of hepatoma.

  9. Maternal protein reserves and their influence on lactational performance in rats. 2. Effects of dietary protein restriction during gestation and lactation on tissue protein metabolism and Na+, K(+)-ATPase (EC 3.6.1.3) activity.

    PubMed

    Pine, A P; Jessop, N S; Allan, G F; Oldham, J D

    1994-08-01

    Changes in tissue protein synthesis and an associated membrane transport system in rats were investigated during lactation and under conditions of dietary protein restriction. Following mating, female Sprague-Dawley rats (second parity) were caged individually and offered a high-protein diet (H; 215 g crude protein (N x 6.25; CP)/kg dry matter (DM)) ad lib. until day 12 of gestation. Subsequently half continued to receive diet H, whilst the remainder were offered a low-protein diet (L; 65 g CP/kg DM) until parturition. On day 1 of lactation females were then allocated to either diet H or another low-protein diet (L2; 90 g CP/kg DM) which were offered ad lib. until day 13 of lactation, giving four lactation groups HH, LH, HL2 and LL2. On days 1 and 13 of lactation groups of females were used in the estimation of tissue protein synthesis (flooding dose of [3H] phenylalanine) and Na+, K(+)-ATPase (EC 3.6.1.3) activity (polarographically) in skeletal muscle, mammary gland, liver and duodenal mucosa. By day 1 of lactation diet L had reduced fractional and absolute synthesis rates (FSR and ASR) of muscle protein (P < 0.05) and the O2 consumption associated with Na+, K(+)-ATPase, although not significantly (P < 0.10). Rates of protein synthesis in the other tissues studied were not affected on day 1 of lactation by the gestation dietary treatment. By day 13 of lactation the feeding of diet L2 had reduced muscle FSR and ASR of group HL2 to rates that were lower than those on day 1 (P < 0.05), comparable to those of group LL2 and lower than those of groups HH and LH (P < 0.05). Diet H had allowed group LH to increase their muscle protein synthesis compared with that on day 1 (P < 0.05). Muscle Na+, K(+)-ATPase activity on day 13 of lactation was also lower in groups offered diet L2 (P < 0.05). Mammary protein synthesis was increased during lactation with the feeding of diet H (P < 0.05), which was prevented by diet L2 such that rates of groups HL2 and LL2 were lower than

  10. Reduction of mammary and liver lipogenesis and alteration of milk composition during lactation in rats by hypothyroidism.

    PubMed

    Hapon, María Belén; Varas, Silvia M; Giménez, María S; Jahn, Graciela A

    2007-01-01

    The profound impairment in litter growth produced by untreated maternal hypothyroidism (HypoT) may be a consequence of maternal metabolic dysfunctions affecting lactation. In this work we studied the effects of HypoT on mammary and liver lipid metabolism and its consequences on milk quality. We studied the effects of prolonged 6-propyl-2-thiouracil (PTU)-induced HypoT (0.01% PTU in drinking water starting 8 days before mating until sacrifice) on milk macronutrient composition, liver and mammary lipid metabolism and content and serum lipid, and glucose and insulin concentrations in rats on days 7, 15 (L15), and 20 (L20) of lactation. Mammary and hepatic mRNA abundances of lipogenic enzymes were measured using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on L15 and L20. Milk lactose and triglycerides (TG) were reduced by HypoT, as well as mammary acetyl CoA carboxylase (ACC) activity on L15 and L20, and ACC and lipoprotein lipase (LPL) mRNA on L20. HypoT also decreased hepatic ACC activity on both days, ACC mRNA on L15 and liver [(3)H]H(2)O incorporation to TGs and TG content on L20. HypoT diminished insulinemia, increased serum total lipids, and decreased serum TGs on some or all the days of lactation studied. HypoT produces a drastic decrease in milk TGs; the main cause for this seems to be the decreases in liver TG synthesis and in circulating TGs, which, along with reduced mammary uptake of fatty acids caused by decreased LPL expression and possibly diminished mammary lipogenesis, result in an impaired mammary output of TGs to the milk. Thus, the impaired growth of the litters of HypoT mothers can be largely attributed to the low milk quality along with the impaired milk ejection.

  11. Simultaneous telemetric monitoring of brain glucose and lactate and motion in freely moving rats.

    PubMed

    Rocchitta, Gaia; Secchi, Ottavio; Alvau, Maria Domenica; Farina, Donatella; Bazzu, Gianfranco; Calia, Giammario; Migheli, Rossana; Desole, Maria Speranza; O'Neill, Robert D; Serra, Pier A

    2013-11-05

    A new telemetry system for simultaneous detection of extracellular brain glucose and lactate and motion is presented. The device consists of dual-channel, single-supply miniature potentiostat-I/V converter, a microcontroller unit, a signal transmitter, and a miniaturized microvibration sensor. Although based on simple and inexpensive components, the biotelemetry device has been used for accurate transduction of the anodic oxidation currents generated on the surface of implanted glucose and lactate biosensors and animal microvibrations. The device was characterized and validated in vitro before in vivo experiments. The biosensors were implanted in the striatum of freely moving animals and the biotelemetric device was fixed to the animal's head. Physiological and pharmacological stimulations were given in order to induce striatal neural activation and to modify the motor behavior in awake, untethered animals.

  12. Lactation Consultant

    MedlinePlus

    ... human lactation. Job description Lactation consultants educate women, families, health professionals, and the community about breast feeding and human lactation; facilitate the development of policies which protect, promote, and support breastfeeding; ...

  13. Locomotor activity and sensory-motor developmental alterations in rat offspring exposed to arsenic prenatally and via lactation.

    PubMed

    Gumilar, Fernanda; Lencinas, Ileana; Bras, Cristina; Giannuzzi, Leda; Minetti, Alejandra

    2015-01-01

    Arsenic (As) is one of the most toxic naturally occurring contaminants in the environment. The major source of human exposure to inorganic As (iAs) is through contaminated drinking water. Although both genotoxicity and carcinogenicity derived from this metalloid have been thoroughly studied, the effects of iAs on the development and function of the central nervous system (CNS) have received less attention and only a few studies have focused on neurobehavioral effects. Thus, in order to characterize developmental and behavioral alterations induced by iAs exposure, pregnant Wistar rats were exposed to 0.05 and 0.10 mg/L iAs through drinking water during gestation and lactation. Sensory-motor reflexes in each pup were analyzed and the postnatal day when righting reflex, cliff aversion and negative geotaxis were recorded. Functional Observational Battery (FOB) and locomotor activity in an open field were assessed in 90-day-old offspring. Results show that rats exposed to low iAs concentrations through drinking water during early development evidence a delay in the development of sensory-motor reflexes. Both FOB procedure and open-field tests showed a decrease in locomotor activity in adult rats. This study reveals that exposure to the above-mentioned iAs concentrations produces dysfunction in the CNS mechanisms whose role is to regulate motor and sensory development and locomotor activity.

  14. The effect of crotoxin on the release of acetylcholine and lactate dehydrogenase from rat brain cortical slices.

    PubMed

    Araújo, D A; Beirão, P S; Gomez, M V

    1992-01-01

    1. We have studied the effects of crotoxin, the neurotoxin of the South American rattlesnake Crotalus durissus terrificus, on the release of acetylcholine and lactate dehydrogenase from rat brain cortical slices. 2. Crotoxin enhances the release of [3H]-acetylcholine from cortical slices (control values 92.8 +/- 5.9 and 150.3 +/- 11.7 DPM/mg and crotoxin values 199.1 +/- 7.0 and 336.0 +/- 26.0 DPM/mg, at 60 and 120 min incubation, respectively) in parallel with the release of lactate dehydrogenase (control values 50.4 +/- 16.8 and 80.3 +/- 19.5 U/mg and crotoxin values 162.5 +/- 39.1 and 355.7 +/- 38.2 U/mg, at 60 and 120 min incubation, respectively). Both effects are markedly reduced when substituting Sr2+ for Ca2+ in the incubation medium. 3. It is concluded that the phospholipase activity of crotoxin is responsible for the observed effects.

  15. Hematological effects of arsenic in rats after subchronical exposure during pregnancy and lactation: the protective role of antioxidants.

    PubMed

    Antonio Garcia, Maria Teresa; Herrera Dueñas, Amparo; Pineda Pampliega, Javier

    2013-07-01

    Free radicals production is involved in the toxicity of arsenic. The aim of this study was to determine whether biochemical changes occurred in the blood of arsenic-exposed pups during gestation and lactation, and additionally to investigate the potential beneficial role of the administration of certain antioxidants against arsenic exposure damage. Pregnant wistar rats received the following treatments as drinking water: (1) distilled water; (2) arsenic (50 mg/L); (3) antioxidants: zinc (20 mg/L)+vitamin C (2 g/L)+vitamin E (500 mg/L); (4) arsenic (50 mg/L)+antioxidants: zinc (20 mg/L)+vitamin C (2 g/L)+vitamin E (500 mg/L). We found a normocytic and normochromic anemia as well as a significant increase in hemolysis, TBARS production and catalase activity in the blood of arsenic intoxicated pups. Moreover, this metalloid produced a significant increase of serum cholesterol, triglicerids and urea levels whereas the proteins diminished. These effects were palliated in some extent by the coadministration of vitamins and zinc. Our findings suggest that administration of antioxidants during gestation and lactation could prevent some of the negative effects of arsenic. Copyright © 2012 Elsevier GmbH. All rights reserved.

  16. Atrazine-induced reproductive tract alterations after transplacental and/or lactational exposure in male Long-Evans rats

    SciTech Connect

    Rayner, Jennifer L.; Enoch, Rolondo R.; Wolf, Douglas C.; Fenton, Suzanne E. . E-mail: fenton.suzanne@epa.gov

    2007-02-01

    Studies showed that early postnatal exposure to the herbicide atrazine (ATR) delayed preputial separation (PPS) and increased incidence of prostate inflammation in adult Wistar rats. A cross-fostering paradigm was used in this study to determine if gestational exposure to ATR would also result in altered puberty and reproductive tissue effects in the male rat. Timed-pregnant Long-Evans (LE) rats were dosed by gavage on gestational days (GD) 15-19 with 100 mg ATR/kg body weight (BW) or 1% methylcellulose (controls, C). On postnatal day (PND)1, half litters were cross-fostered, creating 4 treatment groups; C-C, ATR-C, C-ATR, and ATR-ATR (transplacental-milk as source, respectively). On PND4, male offspring in the ATR-ATR group weighed significantly less than the C-C males. ATR-ATR male pups had significantly delayed preputial separation (PPS). BWs at PPS for C-ATR and ATR-ATR males were reduced by 6% and 9%, respectively, from that of C-C. On PND120, lateral prostate weights of males in the ATR-ATR group were significantly increased over C-C. Histological examination of lateral and ventral prostates identified an increased distribution of inflammation in the lateral prostates of C-ATR males. By PND220, lateral prostate weights were significantly increased for ATR-C and ATR-ATR, but there were no significant changes in inflammation in either the lateral or ventral prostate. These results suggest that in LE rats, gestational ATR exposure delays PPS when male offspring suckle an ATR dam, but leads to increased lateral prostate weight via transplacental exposure alone. Inflammation present at PND120 does not increase in severity with time.

  17. Comparative effect of lidocaine and bupivacaine on glucose uptake and lactate production in the perfused working rat heart

    SciTech Connect

    Cronau, L.H. Jr.; Merin, R.G.; Aboulish, E.; Steenberg, M.L.; Maljorda, A.

    1986-03-01

    It has been suggested that at equivalent therapeutic concentrations, lidocaine and bupivacaine may have different cardiotoxic potency. In the isolated working rat heart preparation, the effect of a range of lidocaine and bupivacaine concentrations on glucose uptake and lactate production (LP) were observed. Insulin was added, 10 ..mu../L, to Ringer's solution containing /sup 3/H-labeled glucose to measure the glycolytic flux (GF). The effect of the local anesthetics on LP at the indicated concentrations were similar. Lidocaine appears to depress the glycolytic flux from exogenous glucose to a lesser degree. Bupivacaine, 10 mg/L, depresses VO/sub 2/ to a greater degree than does lidocaine, 40 mg/L.

  18. Decreased liver triglyceride content in adult rats exposed to protein restriction during gestation and lactation: role of hepatic triglyceride utilization

    PubMed Central

    Qasem, Rani J.; Li, Jing; Tang, Hee Man; Browne, Veron; Mendez, Claudia; Yablonski, Elizabeth; Pontiggia, Laura; D’mello, Anil P.

    2015-01-01

    We have previously demonstrated that protein restriction throughout gestation and lactation reduced liver triglyceride content in adult rat offspring. The mechanism(s) mediating the decrease in liver triglyceride content are not understood. The objective of the current study was to use a new group of pregnant animals and their offspring and determine the contribution of increased triglyceride utilization via the hepatic fatty acid oxidation and triglyceride secretory pathways to the reduction in liver triglyceride content. Pregnant Sprague-Dawley rats received either a control or a low protein diet throughout pregnancy and lactation. Pups were weaned onto laboratory chow on day 28 and sacrificed on day 65. Liver triglyceride content was reduced in male, but not female, low protein offspring both in the fed and fasted states. The reduction was accompanied by a trend towards higher liver carnitine palmitoyltransferase-1a activity suggesting increased fatty acid transport into the mitochondrial matrix. However, medium chain acyl CoA dehydrogenase activity within the mitochondrial matrix, expression of nuclear peroxisome proliferator activated receptor-α, and plasma levels of β-hydroxybutyrate were similar between low protein and control offspring indicating a lack of change in fatty acid oxidation. Hepatic triglyceride secretion, assessed by blocking peripheral triglyceride utilization and measuring serum triglyceride accumulation rate, and the activity of microsomal transfer protein were similar between low protein and control offspring. Since enhanced triglyceride utilization is not a significant contributor, the decrease in liver triglyceride content in male low protein offspring is likely due to alterations in liver fatty acid transport or triglyceride biosynthesis. PMID:25641378

  19. l-Lactate mediates neuroprotection against ischaemia by increasing TREK1 channel expression in rat hippocampal astrocytes in vitro.

    PubMed

    Banerjee, Aditi; Ghatak, Swagata; Sikdar, Sujit Kumar

    2016-07-01

    Brain ischaemia is a highly debilitating condition where shortage of oxygen and glucose leads to profuse cell death. Lactate is a neuroprotective metabolite whose concentrations increase up to 15-30 mmol/L during ischaemia and TREK1 is a neuroprotective potassium channel which is upregulated during ischaemia. The aim of this study was to investigate the effect of l-lactate on TREK1 expression and to evaluate the role of l-lactate-TREK1 interaction in conferring neuroprotection in ischaemia-prone hippocampus. We show that 15-30 mmol/L l-lactate increases functional TREK1 protein expression by 1.5-3-fold in hippocampal astrocytes using immunostaining and electrophysiology. Studies with transcription blocker actinomycin-D and quantitative PCR indicate that the increase in TREK1 expression is due to enhanced TREK1 mRNA transcription. We further report that l-lactate-mediated increase in TREK1 expression is via protein kinase A (PKA)-dependent pathway. This is the first report of an ischaemic metabolite affecting functional expression of an ion channel. Our studies in an in vitro model of ischaemia using oxygen glucose deprivation show that 30 mmol/L l-lactate fails to reduce cell death in rat hippocampal slices treated with TREK1 blockers, PKA inhibitors and gliotoxin. The above effects were specific to l-lactate as pyruvate failed to increase TREK1 expression and reduce cell death. l-Lactate-induced TREK1 upregulation is a novel finding of physiological significance as TREK1 channels contribute to neuroprotection by enhancing potassium buffering and glutamate clearance capacity of astrocytes. We propose that l-lactate promotes neuronal survival in hippocampus by increasing TREK1 channel expression via PKA pathway in astrocytes during ischaemia. Insufficient blood supply to the brain leads to cerebral ischaemia and increase in extracellular lactate concentrations. We incubated hippocampal astrocytes in lactate and observed increase in TREK1 channel expression via

  20. Nutritional Recovery with a Soybean Diet after Weaning Reduces Lipogenesis but Induces Inflammation in the Liver in Adult Rats Exposed to Protein Restriction during Intrauterine Life and Lactation

    PubMed Central

    Reis, Sílvia Regina de Lima; Feres, Naoel Hassan; Ignacio-Souza, Leticia Martins; Veloso, Roberto Vilela; Arantes, Vanessa Cristina; Kawashita, Nair Honda; Colodel, Edson Moleta; Botosso, Bárbara Laet; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2015-01-01

    We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and CS rats had low body weight, normal basal serum triglyceride levels, increased ALT concentrations, and high HOMA-IR indices compared with LC and CC rats. The soybean diet reduced PPARγ as well as malic enzyme and citrate lyase contents and activities. The lipogenesis rate and liver fat content were lower in LS and CS rats relative to LC and CC rats. TNFα mRNA and protein levels were higher in LS and CS rats than in LC and CC rats. NF-κB mRNA levels were lower in the LC and LS groups compared with the CC and LC groups. Thus, the soybean diet prevented hepatic steatosis at least in part through reduced lipogenesis but resulted in TNFα-mediated inflammation. PMID:25892856

  1. Effect of protein quality on /sup 14/C glucose utilization in isolated rat mammary acini

    SciTech Connect

    Masor, M.L.; Grundleger, M.L.; Jansen, G.R.

    1986-03-01

    Poor protein quality has a deleterious effect on lactation in rats. Dams consuming a 13% wheat gluten (WG) diet are unable to maintain litters. Glucose utilization in isolated mammary acini taken from dams at either day 20 of gestation (G20) or day 4 of lactation (L4) was examined in dams consuming 13% WG vs 13% casein-methionine (CM) diets from day of breeding. Dams consuming WG had significantly smaller inguinal-abdominal mammary glands than CM dams at both G20 and L4, and mammary glands of CM but not WG dams were larger at L4 than G20. Both average pup weight and pup daily gain were smaller in WG litters. Basal levels of /sup 14/C glucose oxidation (GO) and /sup 14/C glucose incorporation into lipid (GL) and lactose were examined. A large significant increase in GO and GL occurred in CM dams from G20 to L4 but not in WG dams. Both GO and GL were higher in CM dams on L4 but not at G20. The ratio of GO:GO+GL changed at parturition in CM but not WG dams. The normal changes in glucose utilization by mammary epithelial cells which occur at parturition were impaired by the WG diet.

  2. Metabolic syndrome and selenium during gestation and lactation.

    PubMed

    Nogales, Fátima; Ojeda, M Luisa; Del Valle, Paulina Muñoz; Serrano, Alejandra; Murillo, M Luisa; Carreras Sánchez, Olimpia

    2017-03-01

    Selenium (Se) has a dual role in metabolic syndrome (MS) development as it has an antioxidant action against both "good" and "bad" reactive oxygen species. This study evaluates Se body profile in dams which present MS during gestation and lactation, in order to elucidate a normal dietary Se's implication in this pathology. Rats were randomized into control (C) and fructose (F) groups. The rich fructose diet (65 %) during gestation and lactation periods induced MS in dams. Se body distribution was determined by atomic absorption spectrophotometry, and the hepatic activity of the four antioxidant enzymes and the bimolecular oxidation were determined by spectrophotometry. The cardiac activity was monitored using the indirect tail occlusion method. Lipid and glucidic profile was also analyzed. Despite the fact that the diet supplied has 0.1 ppm of Se, the minimal dietary requirement for rats, F dams ate less amount of food, and therefore, they had lower Se retention. However, they had normal levels of Se in serum and milk. Dams with MS had Se depletion in heart and muscle joint to hypertension and a lower heart rate, and Se repletion in liver and kidney. Despite the increase in hepatic glutathione peroxidase (GPx) and catalase activity found, lipid oxidation occurred-probably because superoxide dismutase activity was diminished. In heart, the activity and expression of the selenoprotein GPx1 were decreased. With these results, it is not possible to elucidate whether a dietary Se supplementation or a Se-restricted diet are good for MS; because despite the fact that GPx activity is increased in liver, it is also found, for the first time, that heart Se deposits are significantly decreased during MS.

  3. Maternal protein restriction during lactation modulated the expression and activity of rat offspring hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2, and CYP2E1 during development.

    PubMed

    Da Costa, N Meireles; Visoni, S B C; Dos Santos, I L; Barja-Fidalgo, T C; Ribeiro-Pinto, L F

    2016-01-01

    Early nutrition plays a long-term role in the predisposition to chronic diseases and influences the metabolism of several drugs. This may happen through cytochromes P450 (CYPs) regulation, which are the main enzymes responsible for the metabolism of xenobiotics. Here, we analyzed the effects of maternal protein restriction (MPR) on the expression and activity of hepatic offspring's CYPs during 90 days after birth, using Wistar rats as a mammal model. Hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2 and CYP2E1 mRNA and protein expression, and associated catalytic activities (ECOD, EROD, MROD, BROD, PROD and PNPH) were evaluated in 15-, 30-, 60-, and 90-day-old offspring from dams fed with either a 0% protein (MPR groups) or a standard diet (C groups) during the 10 first days of lactation. Results showed that most CYP genes were induced in 60- and 90-day-old MPR offspring. The inductions detected in MPR60 and MPR90 were of 5.0- and 2.0-fold (CYP1A2), 3.7- and 2.0-fold (CYP2B2) and 9.8- and 5.8- fold (CYP2E1), respectively, and a 3.8-fold increase of CYP2B1 in MPR90. No major alterations were detected in CYP protein expression. The most relevant CYP catalytic activities' alterations were observed in EROD, BROD and PNPH. Nevertheless, they did not follow the same pattern observed for mRNA expression, except for an induction of EROD in MPR90 (3.5-fold) and of PNPH in MPR60 (2.2-fold). Together, these results suggest that MPR during lactation was capable of altering the expression and activity of the hepatic CYP enzymes evaluated in the offspring along development.

  4. Maternal protein restriction during lactation modulated the expression and activity of rat offspring hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2, and CYP2E1 during development

    PubMed Central

    Da Costa, N. Meireles; Visoni, S.B.C.; Dos Santos, I.L.; Barja-Fidalgo, T.C.; Ribeiro-Pinto, L.F.

    2016-01-01

    Early nutrition plays a long-term role in the predisposition to chronic diseases and influences the metabolism of several drugs. This may happen through cytochromes P450 (CYPs) regulation, which are the main enzymes responsible for the metabolism of xenobiotics. Here, we analyzed the effects of maternal protein restriction (MPR) on the expression and activity of hepatic offspring’s CYPs during 90 days after birth, using Wistar rats as a mammal model. Hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2 and CYP2E1 mRNA and protein expression, and associated catalytic activities (ECOD, EROD, MROD, BROD, PROD and PNPH) were evaluated in 15-, 30-, 60-, and 90-day-old offspring from dams fed with either a 0% protein (MPR groups) or a standard diet (C groups) during the 10 first days of lactation. Results showed that most CYP genes were induced in 60- and 90-day-old MPR offspring. The inductions detected in MPR60 and MPR90 were of 5.0- and 2.0-fold (CYP1A2), 3.7- and 2.0-fold (CYP2B2) and 9.8- and 5.8– fold (CYP2E1), respectively, and a 3.8-fold increase of CYP2B1 in MPR90. No major alterations were detected in CYP protein expression. The most relevant CYP catalytic activities’ alterations were observed in EROD, BROD and PNPH. Nevertheless, they did not follow the same pattern observed for mRNA expression, except for an induction of EROD in MPR90 (3.5-fold) and of PNPH in MPR60 (2.2-fold). Together, these results suggest that MPR during lactation was capable of altering the expression and activity of the hepatic CYP enzymes evaluated in the offspring along development. PMID:27828666

  5. Grape seed procyanidins administered at physiological doses to rats during pregnancy and lactation promote lipid oxidation and up-regulate AMPK in the muscle of male offspring in adulthood.

    PubMed

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

    2015-09-01

    The aim of the present study was to test whether the administration of a grape seed procyanidin extract (GSPE) during pregnancy and lactation, at doses extrapolated to human consumption, programs male offspring toward improved metabolism in adulthood. For this purpose, female rats were fed a normal-fat diet (NFD) and treated with either GSPE (25 mg kg(-1) of body weight/day) or vehicle during gestation and lactation. The metabolic programming effects of GSPE were evaluated in the male offspring fed NFD from 30 to 170 days of life. No changes were observed in body weight, adiposity, circulating lipid profile and insulin sensitivity between the offspring of dams treated with GSPE (STD-GSPE group) and their counterparts (STD-veh). However, the STD-GSPE offspring had lower circulating levels of C-reactive protein and lower respiratory quotient values, shifting whole-body energy catabolism from carbohydrate to fat oxidation. Furthermore, the STD-GSPE animals also exhibited increased levels of total and phosphorylated AMP-activated protein kinase (AMPK) and an over-expression of the mRNA levels of key genes related to fatty acid uptake (Fatp1 and CD36) and β-oxidation (pparα and had) in skeletal muscle. Our results indicate that GSPE programs healthy male offspring towards a better circulating inflammatory profile and greater lipid utilisation in adulthood. The metabolic programming effects of GSPE that are related to the enhancement of fatty acid oxidation in skeletal muscle seem to be mediated, at least in part, by AMPK. These findings could be of relevance in the prevention of pathologies associated to lifestyle and aging, such as obesity and insulin resistance.

  6. Effects of rat odour and shelter on maternal behaviour in C57BL/6 dams and on fear and stress responses in their adult offspring.

    PubMed

    Coutellier, Laurence; Friedrich, Anne-Christin; Failing, Klaus; Marashi, Vera; Würbel, Hanno

    2008-06-09

    Recent studies in rats and mice suggest that developmental plasticity of HPA-stress and fear responses could be mediated by environment-dependent variations in maternal behaviour. The present study was designed to examine this question further by varying the adversity of the maternal environment to study its effects on nest-attendance and maternal care and on the HPA and fear responses in the adult offspring. C57BL/6 dams and their litter were housed in a cage system composed of a nest cage (NC) and a foraging cage (FC) connected by a tunnel. Using a 2 x 2 factorial design, we varied the maternal foraging environment (FC) by the presence or absence of rat odour (feces) and shelters (MouseHouse and tube) from postnatal days 1-14 and assessed the adult offspring's corticosterone response to isolation/novelty stress and their behaviour in three tests of fearfulness (elevated-O-maze, open-field, free exploration). While the presence of shelters in the FC reduced time spent in the NC (nest site attendance), the presence of rat odour in the FC increased active maternal care without altering nest site attendance. Alterations of the offspring's HPA and fear responses were rather subtle. The presence of shelters in the dam's foraging environment decreased fearfulness in the offspring in the free exploration test. In addition, males reared by dams exposed to rat odour were less fearful in the open-field test, and both males and females reared by dams without shelters and rat odour in the FC showed a greater corticosterone response to isolation/novelty stress. Multiple regression analysis indicated a negative relationship between maternal licking/grooming and fearfulness in males and a positive relationship between nest site attendance and fearfulness in females. Taken together, these results indicate that mouse dams adjust specific aspects of maternal behaviour in response to the specific properties of their environment, and that active maternal care and nest site attendance

  7. Maternal arachidonic acid supplementation improves neurodevelopment in young adult offspring from rat dams with and without diabetes.

    PubMed

    Zhao, Jinping; Del Bigio, Marc R; Weiler, Hope A

    2011-01-01

    Maternal diabetes may compromise infant arachidonic acid (AA) status and development. This study tested if maternal AA supplementation improves neurodevelopment in adult offspring. Rat dams were randomized into 6 groups: Saline-Placebo, streptozotocin-induced diabetes with glucose controlled at <13mmol/L, or poorly controlled at 13-20mmol/L using insulin; and fed either a Control or AA (0.5% fat) diet throughout reproduction. Weaned-offspring were fed regular chow to 12 weeks of age. Testing included exploratory behavior, rota rod and water maze (WM). Poorly controlled offspring showed longer (p≤0.018) escape-latency on testing-day 1 WM but not thereafter (p>0.05). Maternal glucose concentration positively correlated with (p=0.006) male offspring testing-day 1 WM latency. The AA-diet offspring performed better in WM and rota rod (p≤0.032) and showed higher exploratory behavior (p=0.008) than Control-diet offspring. These data suggest maternal hyperglycemia has longstanding consequences to initial stages of learning in the offspring. Maternal AA supplementation and training positively influence learning outcomes.

  8. Exposure to the widely used fungicide mancozeb causes thyroid hormone disruption in rat dams but no behavioral effects in the offspring.

    PubMed

    Axelstad, Marta; Boberg, Julie; Nellemann, Christine; Kiersgaard, Maria; Jacobsen, Pernille Rosenskjold; Christiansen, Sofie; Hougaard, Karin Sørig; Hass, Ulla

    2011-04-01

    The widely used fungicide mancozeb has been shown to cause hypothyroxinemia and other adverse effects on the thyroid hormone system in adult experimental animals. In humans, hypothyroxinemia early in pregnancy is associated with adverse effects on the developing nervous system and can lead to impaired cognitive function and motor development in children. The aim of the present study was therefore to assess whether perinatal mancozeb exposure would cause developmental neurotoxicity in rats. Groups of 9-21 time-mated Wistar rats were dosed with 0, 50, 100, or 150 mg mancozeb/kg body weight (bw)/day by gavage from gestation day (GD) 7 to postnatal day (PND) 16, and total thyroxine (T(4)) levels were measured in dams during gestation. On PND 16, hormone levels and several organ weights were measured in the offspring, whereas motor activity, startle response, and cognitive function were assessed in the adult offspring. The dose of 150 mg/kg/day caused neurotoxicity in the pregnant dams and was therefore reduced to 100 mg/kg bw/day in mid study. T(4) levels showed a dose-dependent and significant decrease in dams from all three dose groups on GD 15, whereas offspring T(4) levels, thyroid weights, and histology were unaffected on PND 16. No effects on reproductive organ weights were seen, and no behavioral changes were observed. Taken together, these results indicate that in rats, moderate maternal hypothyroxinemia during gestation does not necessarily lead to hyperactivity or reduced special learning abilities in the offspring. Mancozeb exposure did, however, reduce T(4) levels in dams and may therefore still be a potential contributor to thyroid disruption in humans and in result adversely affects the developing brain.

  9. Characterization of the autonomic innervation of mammary gland in lactating rats studied by retrograde transynaptic virus labeling and immunohistochemistry.

    PubMed

    Köves, Katalin; Györgyi, Z; Szabó, F K; Boldogkői, Zs

    2012-06-01

    The aim of experiments was to characterize the neurons of the autonomic chain that innervates the nipple and the mammary gland of lactating rats using retrograde transynaptic virus labeling and neurotransmitter and neuropeptide immunohistochemistry. Two days after injection of green fluorescence protein labeled virus in two nipples and underlying mammary glands, labeling was observed in the ipsilateral paravertebral sympathetic trunk and the lateral horn. Three days after inoculation the labeling appeared in the brain stem and the hypothalamic paraventricular nucleus. Above the spinal cord the labeling was bilateral. A subpopulation of virus labeled cells in the paraventricular nuclei synthesized oxytocin. Labeled neurons in the lateral horn showed cholinergic immunoreactivity. These cholinergic neurons innervated the paravertebral ganglia where the virus labeled neurons were partially noradrenergic. The noradrenergic fibers in the mammary gland innervate the smooth muscle wall of vessels, but not the mammary gland in rats. The neurons in the lateral horn receive afferents from the brain stem, and paraventricular nucleus and these afferents are noradrenergic and oxytocinergic. New findings in our work: Some oxytocinergic fibers may descend to the neurons of the lateral horn which innervate noradrenergic neurons in the paravertebral sympathetic trunk, and in turn these noradrenergic neurons reach the vessels of the mammary gland.

  10. Simultaneous detection of histamine release and lactate production in rat mast cells induced by compound 48/80 using sup 1 H NMR

    SciTech Connect

    Yoshizaki, Kazuo; Arizono, Naoki )

    1991-04-01

    {sup 1}H NMR spectroscopy was used to evaluate histamine release and lactate production in intact mast cells isolated from rats. The resonance lines of the aromatic histamine protons in mast cells, detected by the selective spin-excitation technique, were broader and located in a lower magnetic field than those in free histamine solution. When exocytosis of mast-cell granules was induced by compound 48/80, free histamine appeared, with a corresponding decrease in the amount of histamine in the mast cells; the lactate signal was also detected in the spectrum. On the addition of compound 48/ 80, there was a further release of histamine from mast cells, accompanied by further production of lactate. This result indicates that the mechanisms which induce the exocytosis of granules, and/or the events following exocytosis, activate glycolysis.

  11. Serotonin and dopamine in the hypothalamus of control and malnourished mother rats during pregnancy and lactation and body composition of their offspring.

    PubMed

    Manjarrez-Gutiérrez, Gabriel; González-Ramírez, Misael; Boyzo-Montes de Oca, Alfonso; Herrera-Márquez, Rocío; Hernández-Rodríguez, Jorge

    2013-09-01

    To determine concentrations of serotonin and dopamine in the hypothalamus of undernourished rats and controls during pregnancy and lactation and body composition of their offspring. Malnourished rats along with control rats were used during pregnancy and lactation. At birth of their offspring, control mothers nursed their young and malnourished rats and the undernourished mothers nursed their offspring and control pups. On days 5, 10, 15, and 21 of lactation (at the beginning and end of a feeding), L-tryptophan (L-Trp)-free, bound and total, plasma prolactin (PRL) and milk composition were determined. Serotonin and dopamine were measured in the hypothalamus. Body composition of offspring was determined. Increase of free L-Trp was confirmed in undernourished mothers. Furthermore, hypothalamic serotonin was elevated at the start of suckling and decreased at termination. There was also a decrease in dopamine in the hypothalamus at the beginning and end of suckling followed by an increase of plasma PRL that was greater in control mothers who breastfed malnourished offspring. Interestingly, undernourished offspring consumed more milk and showed a clear recovery of body composition with accumulation of body fat. Changes observed in hypothalamic neurotransmitters appear to be closely related to nutritional status and to the response and control of PRL production, possibly to adapt the offspring to the metabolic changes. It was also confirmed that on-demand feeding of undernourished offspring is the main factor involved in nutritional recovery and a predisposition to overweight in the recovered undernourished animals.

  12. Histological and Metabolic State of Dams Suckling Small Litter or MSG-Treated Pups.

    PubMed

    Capriglioni Cancian, Claudia Regina; Leite, Nayara Carvalho; Montes, Elisangela Gueiber; Fisher, Stefani Valeria; Waselcoski, Leticia; Lopes Stal, Emily Caroline; Christoforo, Renata Zanardini; Grassiolli, Sabrina

    2016-01-01

    Lactation is an important function that is dependent on changes in the maternal homeostasis and sustained by histological maternal adjustments. We evaluated how offspring manipulations during the lactational phase can modulate maternal morphologic aspects in the mammary gland, adipose tissue, and pancreatic islets of lactating dams. Two different models of litter-manipulation-during-lactation were used: litter sizes, small litters (SL) or normal litters (NL) and subcutaneous injections in the puppies of monosodium glutamate (MSG), or saline (CON). SL Dams and MSG Dams presented an increase in WAT content and higher plasma levels of glucose, triglycerides, and insulin, in relation to NL Dams and CON Dams, respectively. The MG of SL Dams and MSG Dams presented a high adipocyte content and reduced alveoli development and the milk of the SL Dams presented a higher calorie and triglyceride content, compared to that of the NL Dams. SL Dams presented a reduction in islet size and greater lipid droplet accumulation in BAT, in relation to NL Dams. SL Dams and MSG Dams present similar responses to offspring manipulation during lactation, resulting in changes in metabolic parameters. These alterations were associated with higher fat accumulation in BAT and changes in milk composition only in SL Dams.

  13. Histological and Metabolic State of Dams Suckling Small Litter or MSG-Treated Pups

    PubMed Central

    Capriglioni Cancian, Claudia Regina; Montes, Elisangela Gueiber; Fisher, Stefani Valeria; Waselcoski, Leticia; Lopes Stal, Emily Caroline; Christoforo, Renata Zanardini; Grassiolli, Sabrina

    2016-01-01

    Lactation is an important function that is dependent on changes in the maternal homeostasis and sustained by histological maternal adjustments. We evaluated how offspring manipulations during the lactational phase can modulate maternal morphologic aspects in the mammary gland, adipose tissue, and pancreatic islets of lactating dams. Two different models of litter-manipulation-during-lactation were used: litter sizes, small litters (SL) or normal litters (NL) and subcutaneous injections in the puppies of monosodium glutamate (MSG), or saline (CON). SL Dams and MSG Dams presented an increase in WAT content and higher plasma levels of glucose, triglycerides, and insulin, in relation to NL Dams and CON Dams, respectively. The MG of SL Dams and MSG Dams presented a high adipocyte content and reduced alveoli development and the milk of the SL Dams presented a higher calorie and triglyceride content, compared to that of the NL Dams. SL Dams presented a reduction in islet size and greater lipid droplet accumulation in BAT, in relation to NL Dams. SL Dams and MSG Dams present similar responses to offspring manipulation during lactation, resulting in changes in metabolic parameters. These alterations were associated with higher fat accumulation in BAT and changes in milk composition only in SL Dams. PMID:28004032

  14. Bcl-2 gene family expression in the brain of rat offspring after gestational and lactational dioxin exposure.

    PubMed

    Chang, Shwu-Fen; Sun, Yu-Yo; Yang, Liang-Yo; Hu, Ssu-Yao; Tsai, Shih-Ying; Lee, Wen-Sen; Lee, Yi-Hsuan

    2005-05-01

    Recent epidemiological studies have shown that dioxin, a persistent organic pollutant, is related to cognitive and behavioral abnormalities in the offspring of exposed cohort. In order to investigate the possible impact of dioxin in survival gene expression during brain development, we established an animal model of gestational and lactational dioxin-exposed rat offspring. The expressions of dioxin-responsive gene cytochrome P450 1A1 (CYP1A1), apoptotic gene Bax, and anti-apoptotic genes Bcl-2 and Bcl-xL were examined in rat liver and brains using Western blot analysis and RT-PCR. The results showed that treatment of pregnant rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (2 microg/kg body weight through oral delivery) at gestation day 15 resulted in an increase of Bcl-xL in offspring male liver and cerebral cortex, but a decrease in female offspring. In contrast, the expression of Bcl-xL in the cerebellum was decreased in male, but increased in female. Bcl-2, another anti-apoptotic gene, was also downregulated in P0 female liver, cerebral cortex, but was not observed in male. In the 4-month-old offspring, however, the Bcl-2 protein levels in the liver and cerebellum of both male and female pups were higher in the TCDD group as compared with the control group. However, the Bcl-2 level in the cerebral cortex of TCDD-treated groups was higher than the control group only in female but not male offspring at 4 months old. The expression of Bax showed no significant changes upon TCDD exposure at P0 stage, but was significantly reduced in the 4-month-old male cortex. These results indicate that early exposure of dioxin could affect the development of certain brain regions with gender difference, in terms of its differential effect on expressions of Bcl-xL, Bcl-2, and Bax.

  15. Early Fluid Resuscitation by Lactated Ringer's Solution Alleviate the Cardiac Apoptosis in Rats with Trauma-Hemorrhagic Shock.

    PubMed

    Lin, Kuan-Ho; Liu, Chien-Liang; Kuo, Wei-Wen; Paul, Catherine Reena; Chen, Wei-Kung; Wen, Su-Ying; Day, Cecilia Hsuan; Wu, Hsi-Chin; Viswanadha, Vijaya Padma; Huang, Chih-Yang

    2016-01-01

    Cardiac trauma has been recognized as a complication associated with blunt chest trauma involving coronary artery injury, myocardium contusion and myocardial rupture. Secondary cardiac injuries after trauma supposed to be a critical factor in trauma patients, but the mechanism is not fully explored. Overproduction of TNF-alpha had been reported in multiple trauma animals, this induces oxidative stress resulting in cardiac apoptosis. Apoptosis gradually increases after trauma and reaches to a maximum level in 12 h time. TNF-alpha increases the expression of NFkB, and induces the expression of caspase-3 and resulted in cell apoptosis. The effect can be attenuated by non-selective caspase inhibitor and IL10. Fas induced cardiac apoptosis and hypertrophy in ischemic heart disease. In this study, we demonstrated a trauma-hemorrhagic shock (THS) model in rats and resuscitated rats by lactated Ringer's (L/R) solution after shock in different hours (0 hour, 4 hours, 8 hours). NFkB gradually increased after the first 8 hours of shock, and can be reduced by fluid resuscitation. NFkB is known as a downstream pathway of Fas related apoptosis, we found Fas ligand, caspase-8 levels elevate after shock, and can be reduced by resuscitation. In addition, resuscitation can activate insulin-like growth factor (IGF-1)/Akt pathway, at the same time. It can block mitochondrial damage by decrease the effect of tBid. In conclusion, THS can induce secondary cardiac injury. Fas showed to be an important element in caspase cascade induced myocardium apoptosis. By L/R fluid resuscitation, the suppression of caspase cascade and activation of IGF-I/Akt pathway showed antiapoptotic effects in traumatic heart of rats.

  16. Effect of various partial separations of the litters from their mother on plasma prolactin levels of lactating rats.

    PubMed

    Bánky, Z; Nagy, G M; Halász, B

    1994-01-01

    Removal of the pups results in an abrupt and marked depression in plasma prolactin (PRL) level of the lactating mother. The present studies were undertaken to investigate what kind of sensory input (smell, sound, visual, touch etc.) from the pups is essential for the mother to avoid the pituitary PRL response to pup-removal. Therefore, various partial separations were made and their effect on plasma PRL levels tested: a. The pups were placed into a small glass having holes on its cover; b. they were put into a long measuring tube not covered; c. the pups were placed into the feeding trough made of a wireframe; d. a dividing wall made of glass or metal was slowly let down when the mother spontaneously went away from her pups; e. the nipples were covered by a cotton plaster. Pituitary PRL responses were almost identical after all these separations and similar to that one obtained after removal of the pups from the cage. In addition, separation of the mother resulted in a rise in plasma corticosterone concentrations. The findings suggest that the pup-removal induced inhibition of PRL secretion is a very complex event for the mother and cannot be prevented by partial separations when the mother can see, smell her pups, or hear them or even can touch them with her nose. We assume that separation of the pups is a stress for the mother and cannot simply be due to the lack of just one kind of sensory input from the pups. This assumption is in line with our recent observations indicating that in lactating rat stress causes a decrease in plasma PRL level.

  17. A maternal "junk food" diet in pregnancy and lactation promotes nonalcoholic Fatty liver disease in rat offspring.

    PubMed

    Bayol, Stéphanie A; Simbi, Bigboy H; Fowkes, Robert C; Stickland, Neil C

    2010-04-01

    With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring.

  18. A Maternal “Junk Food” Diet in Pregnancy and Lactation Promotes Nonalcoholic Fatty Liver Disease in Rat Offspring

    PubMed Central

    Bayol, Stéphanie A.; Simbi, Bigboy H.; Fowkes, Robert C.; Stickland, Neil C.

    2010-01-01

    With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring. PMID:20207831

  19. Maternal high fructose and low protein consumption during pregnancy and lactation share some but not all effects on early-life growth and metabolic programming of rat offspring.

    PubMed

    Arentson-Lantz, Emily J; Zou, Mi; Teegarden, Dorothy; Buhman, Kimberly K; Donkin, Shawn S

    2016-09-01

    Maternal nutritional stress during pregnancy acts to program offspring metabolism. We hypothesized that the nutritional stress caused by maternal fructose or low protein intake during pregnancy would program the offspring to develop metabolic aberrations that would be exacerbated by a diet rich in fructose or fat during adult life. The objective of this study was to characterize and compare the fetal programming effects of maternal fructose with the established programming model of a low-protein diet on offspring. Male offspring from Sprague-Dawley dams fed a 60% starch control diet, a 60% fructose diet, or a low-protein diet throughout pregnancy and lactation were weaned onto either a 60% starch control diet, 60% fructose diet, or a 30% fat diet for 15 weeks. Offspring from low-protein and fructose-fed dam showed retarded growth (P<.05) at weaning (50.3, 29.6 vs 59.1±0.8 g) and at 18 weeks of age (420, 369 vs 464±10.9 g). At 18 weeks of age, offspring from fructose dams expressed greater quantities (P<.05) of intestinal Pgc1a messenger RNA compared with offspring from control or low-protein dams (1.31 vs 0.89, 0.85; confidence interval, 0.78-1.04). Similarly, maternal fructose (P=.09) and low-protein (P<.05) consumption increased expression of Pgc1a in offspring liver (7.24, 2.22 vs 1.22; confidence interval, 2.11-3.45). These data indicate that maternal fructose feeding is a programming model that shares some features of maternal protein restriction such as retarded growth, but is unique in programming of selected hepatic and intestinal transcripts. Copyright © 2016. Published by Elsevier Inc.

  20. A maternal cafeteria diet during gestation and lactation promotes adiposity and impairs skeletal muscle development and metabolism in rat offspring at weaning.

    PubMed

    Bayol, Stéphanie A; Simbi, Bigboy H; Stickland, Neil C

    2005-09-15

    We examined the effects of a maternal cafeteria diet on skeletal muscle and adipose tissue development in the offspring at weaning. Rats born to mothers fed the cafeteria diet either during gestation alone or during both gestation and lactation exhibited a 25% reduction in muscle cross-sectional area with approximately 20% fewer fibres compared with pups fed a balanced chow diet. Maintaining the cafeteria diet during lactation increased intramuscular lipid content and fat pad weights characterized by adipocyte hypertrophy but not hyperplasia. These pups also had elevated muscle IGF-1, IGF-1 receptor, and PPARgamma mRNA levels, which may indicate an attempt to maintain normal insulin sensitivity. The increased adiposity and elevated IGF-1, IGF-1 receptor and PPARgamma mRNAs were not seen in the pups rehabilitated to the balanced diet during lactation. However, these pups exhibited reduced muscle cell proliferation (PCNA) with reduced insulin receptor and a trend towards reduced glucose transporter (GLUT)-4 mRNAs when compared with pups fed a balanced chow diet, indicating possible alterations in glucose uptake by muscle tissue. Therefore, rats born to mothers fed a cafeteria diet during gestation alone or during both gestation and lactation exhibited impaired skeletal muscle development and metabolic disorders normally associated with insulin resistance as early as the weaning stage.

  1. The occurrence of pituitary prolactin depletion-transformation in lactating rats: dependence on strain of rats, homogenization conditions and method of assay.

    PubMed

    Lawson, D M; Haisenleder, D J; Gala, R R; Moy, J A

    1987-04-01

    The objectives of this study were to determine whether pre-release transformation (depletion) of pituitary prolactin occurs as the result of suckling to the same extent in several strains of lactating rats, the molecular nature of the transformed hormone, whether the quantity of transformed (depleted) prolactin recovered is dependent upon the type of homogenization buffer used and whether the method of assay influences the extent to which transformed prolactin is detected. During the course of these experiments other factors such as the methods of handling and storing pituitaries and homogenates were also found to influence the amount of prolactin recovered. The results indicated that transformation of prolactin is a very labile event which is affected by many factors. Strain and supplier of rats was critical to the observation of suckling-induced depletion of prolactin, with Spartan- and Holtzman-derived Sprague-Dawley strains exhibiting the most consistent responses. When transformation was observed, it mattered little which buffer was used for homogenization; however, alkaline or acidic buffers extracted more prolactin than did neutral buffers. Triton X-100 also significantly enhanced the efficiency of extraction by neutral buffers. Maintaining pituitaries on dry ice immediately upon removal from the animal increased the amount of prolactin recovered, as did freezing the homogenate for 1-5 weeks before assay. The addition of the protease inhibitor, benzamidine hydrochloride, did not affect the pituitary content of prolactin. Assay of prolactin by polyacrylamide electrophoresis and densitometry yielded more prolactin than either radioimmunoassay or the Nb2 lymphoma bioassay. The molecular nature of pituitary prolactin, extracted at neutral pH, as judged by gel filtration was altered slightly but consistently by suckling, such that large molecular forms increased at the expense of the smallest molecular form. We conclude from these studies that great care must be

  2. High saturated fat diet alters the lipid composition of triacylglycerol and polar lipids in the femur of dam and offspring rats.

    PubMed

    Miotto, Paula M; Castelli, Laura M; Amoye, Foyinsola; Ward, Wendy E; LeBlanc, Paul J

    2015-06-01

    Previous work has shown that dietary lipids alter femur lipid composition. Specifically, we have shown that exposure to high saturated fatty acid (SFA) diets in utero, during suckling, or post-weaning alters femur total lipid composition, resulting in higher percent bone mass in males and females and bone mineral density (BMD) in female offspring with no effect on bone mineral outcomes in dams. Comparatively, high n-3 polyunsaturated fatty acid (PUFA) diets increase femur polar (PL) lipid n-3 content, which has been associated with increased bone mineral content and strength. However, the extent that PL or triacylglycerol (TAG) lipids change with high SFA diets is unknown. The current investigation examined the influence of a high SFA diet (20 % lard by weight) on femur PL and TAG lipid composition in 5-month old female Wistar rats (fed high SFA diet from age 28 days onwards; dams) and their 19-day old offspring (exposed to high SFA in utero and during suckling; pups). High SFA exposure resulted in increased monounsaturates and decreased n-3 and n-6 PUFA in the TAG fraction in both dams and pups, and higher SFA and n-6:n-3 ratio in dams only. The PL fraction showed decreased n-6 PUFA in both dams and pups. The magnitude of the diet-mediated responses, specifically TAG 18:1 and PL n-6 PUFA, may have contributed to the previously reported altered BMD, which was supported with correlation analysis. Future research should investigate the relationship of diet-induced changes in bone lipids on bone structure, as quantified through micro-computed tomography.

  3. Mechanisms for increased expression of cholesterol 7α-hydroxylase (Cyp7a1) in lactating rats

    PubMed Central

    Wooton-Kee, Clavia Ruth; Coy, Donna J; Athippozhy, Antony T; Zhao, Tianyong; Jones, Brett R; Vore, Mary

    2009-01-01

    Cholesterol 7α-hydroxylase (Cyp7a1) and the bile acid pool size are increased 2–3 fold in lactating postpartum rats. We investigated the interaction of nuclear receptors with the Cyp7a1 proximal promoter and the expression of regulatory signaling pathways in postpartum rats at day 10 (PPd10) vs female controls to identify the mechanisms of increased expression of Cyp7a1, which is maximal at 16 h. Liver X receptor (LXRα) and RNA Polymerase II (RNA Pol II) recruitment to Cyp7a1 chromatin were increased 1.5- and 2.5-fold, respectively, at 16 h on PPd10. Expression of nuclear receptors farnesoid X receptor (FXR), LXRα, liver receptor homologue (LRH-1), hepatocyte nuclear factor 4α (HNF4α), and short heterodimer partner (SHP) mRNA and co-activator peroxisome proliferators-activated receptor γ coactivator-1α (PGC-1α) mRNA was unchanged in PPd10 vs controls at 16 h, while chicken ovalbumin upstream transcription factor II (COUP-TFII) was decreased 40% at 16 h. Investigation of a repressive signaling pathway, the cJun-N-terminal kinase (JNK) signaling pathway in PPd10 vs controls, showed decreased mRNA expression of hepatocyte growth factor (HGF; decreased 60% at 16 h) and tyrosine kinase receptor cMet (decreased 44–50% at 16 h), but these were not accompanied by decreased expression of phosphorylated c-Jun. Importantly, expression of Fibroblast Growth Factor 15 (FGF15) mRNA in the ileum was decreased 70% in PPd10 vs controls, while phosphorylated mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (Erk1/2) protein expression in liver was decreased 88% at 16 h. Conclusion The increased recruitment of LXRα, a Cyp7a1 stimulatory pathway, and decreased expression of FGF15 and phosphorylated Erk1/2, a Cyp7a1 repressive pathway, combined to increase Cyp7a1 expression during lactation. PMID:19957370

  4. Unlimited access to low-energy diet causes acute malnutrition in dams and alters biometric and biochemical parameters in offspring.

    PubMed

    do Nascimento, E; de Santana Muniz, G; das Graças de Santana Muniz, M; de Souza Alexandre, L; da Rocha, L S; Leandro, C G; de Castro, R M; Bolaños-Jimenez, F

    2014-02-01

    Here we analyze the outcomes of unlimited access to a low-energy (LE) diet in dams and their offspring. At 3 weeks' gestation, pregnant Wistar rats were divided into two groups: (1) the control group received a normoenergetic diet; and (2) the experimental group received the LE diet. In dams, lactation outcomes, food intake, body weight, plasma IGF-1, prealbumin, transferrin and retinol-binding protein levels were evaluated; in offspring, biometric and biochemical parameters and food intake were evaluated. No differences were observed during pregnancy. However, after lactation, dams that received the LE diet demonstrated significant reductions in body weight (P<0.05), plasma IGF-1 (P=0.01), prealbumin and visceral fat (P<0.001). Pups born to dams that received the LE diet demonstrated reduced body length and weight at weaning (P<0.001) and were lighter than the control animals at the end of the experimental period. Pups also demonstrated reduced plasma, low-density lipoprotein (P=0.04), triglycerides (P=0.002) and glucose levels (P<0.05), and differences were noted in visceral fat. These results indicate that feeding dams with LE diet during the reproductive period induces acute malnutrition and impairs the growth and development of offspring, as well as certain metabolic parameters.

  5. Alterations of tooth eruption and growth in pups suckling from diabetic dams.

    PubMed

    Villarino, Mariano E; Goya, Juan A; DE Lucca, Romina C; Ubios, Angela M

    2005-10-01

    Several studies have confirmed a decrease in the quality and quantity of milk of mothers with diabetes during lactation. However, it remains unclear how maternal diabetes affects the offspring specifically during lactation. The aim of this study was to evaluate body and mandibular growth and tooth eruption in pups suckling from diabetic dams. The study was performed on 13 Wistar rat pups that were born to dams that were subjected to experimental diabetes on the day of parturition. Body weight and body size were recorded regularly throughout the study. The experimental pups and a group of eight age-matched pups suckling from nondiabetic dams were killed at weaning. Both hemimandibles were excised and fixed. Right hemimandibles were radiographed to assess mandibular growth and tooth eruption. The left hemimandibles were processed to obtain buccolingually oriented sections at the level of the first mesial root of the first lower molar. Histologic and histomorphometric studies were performed. Results showed that body weight and body size were significantly lower in experimental animals at weaning compared with their age-matched controls. Smaller mandible size and reduced tooth eruption in experimental animals compared with controls were observed. The length, width, and bone volume of the developing alveolus were reduced in experimental animals compared with controls. The results obtained in this study allow the conclusion that suckling from diabetic dams results in reduced body, mandible size, and tooth eruption of the pups at weaning.

  6. 106. DAM EARTH DIKE SUBMERSIBLE DAMS & DIKE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    106. DAM - EARTH DIKE - SUBMERSIBLE DAMS & DIKE CONN. AT MOVABLE DAM (ML-8-52/2-FS) March 1940 - Upper Mississippi River 9-Foot Channel, Lock & Dam No. 8, On Mississippi River near Houston County, MN, Genoa, Vernon County, WI

  7. Gestational stress and fluoxetine treatment differentially affect plasticity, methylation and serotonin levels in the PFC and hippocampus of rat dams.

    PubMed

    Gemmel, Mary; Rayen, Ine; van Donkelaar, Eva; Loftus, Tiffany; Steinbusch, Harry W; Kokras, Nikolaos; Dalla, Christina; Pawluski, Jodi L

    2016-07-07

    Women are more likely to develop depression during childbearing years with up to 20% of women suffering from depression during pregnancy and in the postpartum period. Increased prevalence of depression during the perinatal period has resulted in frequent selective serotonin reuptake inhibitor (SSRI) antidepressant treatment; however the effects of such medications on the maternal brain remain limited. Therefore, the aim of the present study is to investigate the effects of the SSRI medication, fluoxetine, on neurobiological differences in the maternal brain. To model aspects of maternal depression, gestational stress was used. Sprague-Dawley rat dams were exposed to either gestational stress and/or fluoxetine (5mg/kg/day) to form the following four groups: 1. Control+Vehicle, 2. Stress+Vehicle, 3. Control+Fluoxetine, and 4. Stress+Fluoxetine. At weaning maternal brains were collected. Main findings show that gestational stress alone increased synaptophysin and serotonin metabolism in the cingulate cortex2 region of the cortex while fluoxetine treatment after stress normalized these effects. In the hippocampus, fluoxetine treatment, regardless of gestational stress exposure, decreased both global measures of methylation in the dentate gyrus, as measured by Dnmt3a immunoreactivity, as well as serotonin metabolism. No further changes in synaptophysin, PSD-95, or Dnmt3a immunoreactivity were seen in the cortical or hippocampal areas investigated. These findings show that gestational stress and SSRI medication affect the neurobiology of the maternal brain in a region-specific manner. This work adds to a much needed area of research aimed at understanding neurobiological changes associated with maternal depression and the role of SSRI treatment in altering these changes in the female brain. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Effects of hyperbaric oxygen on glucose, lactate, glycerol and anti-oxidant enzymes in the skeletal muscle of rats during ischaemia and reperfusion.

    PubMed

    Bosco, Gerardo; Yang, Zhong-jin; Nandi, Jyotirmoy; Wang, Jingping; Chen, Chung; Camporesi, Enrico M

    2007-01-01

    1. Hyperbaric (HBO(2)) and topical oxygen represent two accepted options to oxygenate tissues. The aim of the present study was to investigate the effect of HBO(2) on energy metabolism and anti-oxidant enzymes in a rat model of ischaemia-reperfusion (IR) skeletal muscle injury. 2. In the first study, 16 rats were randomized to a HBO(2)-treated group (Group 1; n = 8) and an untreated group (Group 2; n = 8). Under general anaesthesia, right hind limb ischaemia was produced by application of a rubber-band tourniquet for 3 h. After 2 h ischaemia, Group 1 rats received HBO(2) during the last hour of ischaemia. The HBO(2) consisted of 100% oxygen delivered at 282.8 kPa absolute pressure. Group 2 rats were not treated. Following the ischaemic period, the tourniquet was released for 1 h. A microdialysis probe was used to sample lactate, glucose and glycerol concentrations in the muscle extracellular tissue every 15 min throughout each experiment. 3. In the second study, 24 rats were randomized into four groups (n = 6 each). The first two groups were subjected to the IR injury protocol outlined above and either treated (Group 1) or untreated (Group 2) with HBO(2). Group 3 rats were anaesthetized, did not undergo IR injury, but underwent HBO(2) treatment. Group 4 rats were anaesthetized but did not undergo either IR injury or HBO(2) treatment. At end of each experiment, the biceps femoris muscle was removed and assayed for superoxide dismutase (SOD) and catalase (CAT) activity. Malondialdehyde (MDA) was measured to estimate the extent of membrane lipid peroxidation. 4. Three hours of skeletal muscle ischaemia resulted in a gradual decrease in the glucose concentration and a gradual increase in the lactate concentration within the extracellular fluid of the affected skeletal muscle tissue. Treatment with HBO(2) had no effect on the glucose concentration; however, HBO(2) significantly attenuated the ischaemia-induced increase in lactate and glycerol. In both groups, glucose

  9. Lactational exposure to hexavalent chromium delays puberty by impairing ovarian development, steroidogenesis and pituitary hormone synthesis in developing Wistar rats

    SciTech Connect

    Banu, Sakhila K. Samuel, Jawahar B.; Arosh, Joe A.; Burghardt, Robert C.; Aruldhas, Michael M.

    2008-10-15

    Hexavalent chromium (Cr-VI) is used in a wide range of industries. Cr-VI from chromate industries and atmospheric emissions contribute to the Cr contamination in the environment. Cr is a reproductive metal toxicant that can traverse the placental barrier and cause a wide range of fetal effects including ovotoxicity. Therefore, the goal of this study was to investigate the basic mechanisms involved in Cr(VI)-induced ovotoxicity, and the protective role of vitamin C on ovarian follicular development and function in Cr(VI)-induced reproductive toxicity using both in vivo and in vitro approaches. Lactating rats received potassium dichromate (200 mg/L) with or without vitamin C (500 mg/L), through drinking water from postpartum days 1-21. During postnatal days (PND) 1-21 the pups received Cr(VI) via the mother's milk. Pups from both control and treatment groups were continued on regular diet and water from PND-21 onwards, and euthanized on PND-21, -45 and -65. Cr(VI) decreased steroidogenesis, GH and PRL, increased FSH and did not alter LH. Cr(VI) delayed puberty, decreased follicle number, and extended estrous cycle. Spontaneously immortalized rat granulosa cells were treated with 12.5 {mu}M (IC{sub 50}) potassium dichromate for 12 and 24 h, with or without vitamin C pre-treatment. Cr(VI) decreased the mRNA expressions of StAR, SF-1, 17{beta}-HSD-1, 17{beta}-HSD-2, FSHR, LHR, ER{alpha} and ER{beta}. Vitamin C pre-treatment protected ovary and granulosa cells from the deleterious effects of Cr(VI) toxicity, both in vivo and in vitro. Therefore, Cr(VI) toxicity could be a potential risk to the reproductive system in developing females, and vitamin C plays a protective role against Cr(VI)-induced ovotoxicity.

  10. Thiamine administration during chronic alcohol intake in pregnant and lactating rats: effects on the offspring neurobehavioural development.

    PubMed

    Bâ, A; Seri, B V; Han, S H

    1996-01-01

    A number of mechanisms may be involved in the pathogenesis of thiamine deficiency in the alcoholic. Among these mechanisms are inadequate dietary intake of thiamine, impaired intestinal transport of the vitamin and decreased conversion of thiamine to the active coenzyme. The present study was undertaken to further investigate the mechanism by which alcohol can interfere with thiamine deficiency in the brain. Thus, the neurobehavioural development of rat pups (E) nursed by 12% ethanol/water-drinking mothers, or pups (E-T) nursed by mothers drinking 12% ethanol/water + thiamine hydrochloride mixture, was monitored from the 1st to 45th postnatal days. Appropriate pair-fed saccharose (S) and ad libitum controls (C) were assessed. Histological studies were performed at the age of 45 days on the hippocampal CA3 pyramidal neurons of the offspring from each treatment. Exposing rat pups to ethanol during pregnancy and lactation showed a significant impairment of neurobehavioural development, more cornered pyramidal cells in the hippocampal field CA3, reduced cell number and cell size. The results point out long-lasting effects of maternal alcohol exposure in the offspring. Both functional and structural studies showed that neurotoxic effects of developmental alcohol exposure were not reversed by thiamine administration. However, adverse effects of undernutrition following developmental alcohol exposure were suppressed by thiamine administration. From this work, we suggest that inadequate dietary intake of thiamine and impaired intestinal transport of the vitamin are not critical mechanisms leading to thiamine deficiency in chronic alcoholism. The most prevalent mechanism contributing to ethanol-induced thiamine deficiency in chronic alcoholics would be the alteration of thiamine metabolism, and particularly the reduction of the vitamin conversion to its metabolically active form TPP (thiamine pyrophosphate).

  11. Maternal malnutrition during lactation alters gonadotropin-releasing hormone expression in the hypothalamus of weaned male rat pups.

    PubMed

    Ramos, Cristiane da Fonte; Lima, Sebastião Sérgio; Rocha, Michael Luis Martins; Lotufo, Bruna Messias; Sampaio, Francisco José Barcelos; Barradas, Penha Cristina; Tenório, Frank

    2010-08-01

    Gonadotropin-releasing hormone (GnRH) is the key hormone regulating reproduction. Its feedback regulation is exercised by estradiol. The early postnatal period is critical for sexual differentiation. Despite the fact that malnutrition-related reproductive suppression in rats is a well-documented phenomenon, we had no knowledge, until now, on how maternal malnutrition affects GnRH expression and estradiol serum concentrations of weaned pups. Six pregnant Wistar rats were separated into three groups at delivery with 6 pups each: control group (C) with free access to a standard diet containing 23% protein; protein energy restricted group (PER) with free access to an isoenergy and 8% protein diet; and an energy-restricted (ER) group receiving a standard diet in restricted quantities, which were calculated according to the mean ingestion of the PER group. At 21 days post partum, the animals were killed and the serum estradiol was evaluated by radioimmunoassay. Immunohistochemistry for GNRH was performed. The serum estradiol concentration was decreased in PER and ER groups compared with C (PER, 34%; ER, 19%;P < 0.01) and the staining of GNRH was restricted to arcuate nucleus and median eminence in the control group while in PER and ER stained processes aligned with the third ventricle wall (periventricular nucleus) were present. In conclusion, our data reinforce the concept that the maternal nutritional state during lactation is critical for sexual maturation since maternal malnutrition resulted in a neuron migration delay evidenced by an altered GnRH expression profile, probably a consequence of low estradiol serum levels.

  12. Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production.

    PubMed Central

    Sharpe, R M; Fisher, J S; Millar, M M; Jobling, S; Sumpter, J P

    1995-01-01

    This study assessed whether exposure of male rats to two estrogenic, environmental chemicals, 4-octylphenol (OP) and butyl benzyl phthalate (BBP) during gestation or during the first 21 days of postnatal life, affected testicular size or spermatogenesis in adulthood (90-95 days of age). Chemicals were administered via the drinking water or concentrations of 10-1000 micrograms/l (OP) or 1000 micrograms/l (BBP), diethylstilbestrol (DES; 100 micrograms/l) and an octylphenol polyethoxylate (OPP; 1000 micrograms/l), which is a weak estrogen or nonestrogenic in vitro, were administered as presumptive positive and negative controls, respectively. Controls received the vehicle (ethanol) in tap water. In study 1, rats were treated from days 1-22 after births in studies 2 and 3, the mothers were treated for approximately 8-9 weeks, spanning a 2-week period before mating throughout gestation and 22 days after giving birth. With the exception of DES, treatment generally had no major adverse effect or body weight: in most instances, treated animals were heavier than controls at day 22 and at days 90-95. Exposure to OP, OPP, or BBP at a concentration of 1000 micrograms/1 resulted in a small (5-13%) but significant (p < 0.01 or p < 0.0001) reduction in mean testicular size in studies 2 and 3, an effect that was still evident when testicular weight was expressed relative to body, weight or kidney weight. The effect of OPP is attributed to its metabolism in vivo to OP. DES exposure caused similar reductions in testicular size but also caused reductions in body weight, kidney weight, and litter size. Ventral prostate weight was reduced significantly in DES-treated rats and to minor extent in OP-treated rats. Comparable but more minor effects of treatment with DES or OP on testicular size were observed in study 1. None of the treatments had any adverse effect on testicular morphology or on the cross-sectional area of the lumen or seminiferous epithelium at stages VII-VIII of the

  13. The ammonium-induced increase in rat brain lactate concentration is rapid and reversible and is compatible with trafficking and signaling roles for ammonium.

    PubMed

    Provent, Peggy; Kickler, Nils; Barbier, Emmanuel L; Bergerot, Astrid; Farion, Régine; Goury, Sarah; Marcaggi, Païkan; Segebarth, Christoph; Coles, Jonathan A

    2007-11-01

    The glutamate-glutamine shuttle requires a flux of fixed N from neurons to astrocytes. The suggestion that some or all of this N is ammonium has received support from reports that ammonium (as NH(4)(+)) rapidly enters astrocytes. Ammonium might also help control astrocyte energy metabolism by increasing lactate production. If ammonium has these functions, then its effect on brain metabolism must be rapid and reversible. To make a minimal test of this requirement, we have followed the time courses of the changes induced by a 4 min venous infusion of 1 mol/L NH(4)Cl, 2.5 mmol/kg body weight, in rat. Extracellular [NH(4)(+)] in cortex, monitored with ion-selective microelectrodes, reached a peak of approximately 0.7 mmol/L 1.65 mins after the end of the infusion, then recovered. Brain metabolites were monitored non-invasively every 4 mins by (1)H magnetic resonance spectroscopy. Lactate peak area during the 3.2 min acquisition starting at the end of the infusion was 1.84+/-0.24 times baseline (+/-s.e.m., P=0.009, n=9). Lactate increased until 13.2+/-2.1 mins after the end of the infusion and recovered halfway to baseline by 31.2 mins. Glutamate decreased by at least 7.1% (P=0.0026). Infusion of NaCl caused no change in lactate signal. Cerebral blood flow, measured by arterial magnetization labeling, more than doubled, suggesting that the lactate increase was not caused by hypoxia. At least three consecutive ammonium-induced increases in lactate signal could be evoked. The results are compatible with an intercellular trafficking/signaling function for ammonium.

  14. Insufficient insulin administration to diabetic rats increases substrate utilization and maintains lactate production in the kidney.

    PubMed

    Laustsen, Christoffer; Lipsø, Kasper; Ostergaard, Jakob Appel; Nørregaard, Rikke; Flyvbjerg, Allan; Pedersen, Michael; Palm, Fredrik; Ardenkjær-Larsen, Jan Henrik

    2014-12-01

    Good glycemic control is crucial to prevent the onset and progression of late diabetic complications, but insulin treatment often fails to achieve normalization of glycemic control to the level seen in healthy controls. In fact, recent experimental studies indicate that insufficient treatment with insulin, resulting in poor glycemic control, has an additional effect on progression of late diabetic complications, than poor glycemic control on its own. We therefore compared renal metabolic alterations during conditions of poor glycemic control with and without suboptimal insulin administration, which did not restore glycemic control, to streptozotocin (STZ)-diabetic rats using noninvasive hyperpolarized (13)C-pyruvate magnetic resonance imaging (MRI) and blood oxygenation level-dependent (BOLD) (1)H-MRI to determine renal metabolic flux and oxygen availability, respectively. Suboptimal insulin administration increased pyruvate utilization and metabolic flux via both anaerobic and aerobic pathways in diabetic rats even though insulin did not affect kidney oxygen availability, HbA1c, or oxidative stress. These results imply direct effects of insulin in the regulation of cellular substrate utilization and metabolic fluxes during conditions of poor glycemic control. The study demonstrates that poor glycemic control in combination with suboptimal insulin administration accelerates metabolic alterations by increasing both anaerobic and aerobic metabolism resulting in increased utilization of energy substrates. The results demonstrate the importance of tight glycemic control in insulinopenic diabetes, and that insulin, when administered insufficiently, adds an additional burden on top of poor glycemic control.

  15. The “metabolic sensor” function of rat supraoptic oxytocin and vasopressin neurons is attenuated during lactation but not in diet-induced obesity

    PubMed Central

    Stevens, Wanida; Song, Zhilin; Johnson, Ginger C.; MacLean, Paul S.

    2015-01-01

    The oxytocin (OT) and vasopressin (VP) neurons of the supraoptic nucleus (SON) demonstrate characteristics of “metabolic sensors”. They express insulin receptors and glucokinase (GK). They respond to an increase in glucose and insulin with an increase in intracellular [Ca2+] and increased OT and VP release that is GK dependent. Although this is consistent with the established role of OT as an anorectic agent, how these molecules function relative to the important role of OT during lactation and whether deficits in this metabolic sensor function contribute to obesity remain to be examined. Thus, we evaluated whether insulin and glucose-induced OT and VP secretion from perifused explants of the hypothalamo-neurohypophyseal system are altered during lactation and by diet-induced obesity (DIO). In explants from female day 8 lactating rats, increasing glucose (Glu, 5 mM) did not alter OT or VP release. However, insulin (Ins; 3 ng/ml) increased OT release, and increasing the glucose concentration in the presence of insulin (Ins+Glu) resulted in a sustained elevation in both OT and VP release that was not prevented by alloxan, a GK inhibitor. Explants from male DIO rats also responded to Ins+Glu with an increase in OT and VP regardless of whether obesity had been induced by feeding a high-fat diet (HFD). The HFD-DIO rats had elevated body weight, plasma Ins, Glu, leptin, and triglycerides. These findings suggest that the role of SON neurons as metabolic sensors is diminished during lactation, but not in this animal model of obesity. PMID:26661099

  16. The "metabolic sensor" function of rat supraoptic oxytocin and vasopressin neurons is attenuated during lactation but not in diet-induced obesity.

    PubMed

    Sladek, Celia D; Stevens, Wanida; Song, Zhilin; Johnson, Ginger C; MacLean, Paul S

    2016-02-15

    The oxytocin (OT) and vasopressin (VP) neurons of the supraoptic nucleus (SON) demonstrate characteristics of "metabolic sensors". They express insulin receptors and glucokinase (GK). They respond to an increase in glucose and insulin with an increase in intracellular [Ca(2+)] and increased OT and VP release that is GK dependent. Although this is consistent with the established role of OT as an anorectic agent, how these molecules function relative to the important role of OT during lactation and whether deficits in this metabolic sensor function contribute to obesity remain to be examined. Thus, we evaluated whether insulin and glucose-induced OT and VP secretion from perifused explants of the hypothalamo-neurohypophyseal system are altered during lactation and by diet-induced obesity (DIO). In explants from female day 8 lactating rats, increasing glucose (Glu, 5 mM) did not alter OT or VP release. However, insulin (Ins; 3 ng/ml) increased OT release, and increasing the glucose concentration in the presence of insulin (Ins+Glu) resulted in a sustained elevation in both OT and VP release that was not prevented by alloxan, a GK inhibitor. Explants from male DIO rats also responded to Ins+Glu with an increase in OT and VP regardless of whether obesity had been induced by feeding a high-fat diet (HFD). The HFD-DIO rats had elevated body weight, plasma Ins, Glu, leptin, and triglycerides. These findings suggest that the role of SON neurons as metabolic sensors is diminished during lactation, but not in this animal model of obesity. Copyright © 2016 the American Physiological Society.

  17. Postpartum Behavioral Profiles in Wistar Rats Following Maternal Separation - Altered Exploration and Risk-Assessment Behavior in MS15 Dams.

    PubMed

    Daoura, Loudin; Hjalmarsson, My; Oreland, Sadia; Nylander, Ingrid; Roman, Erika

    2010-01-01

    The rodent maternal separation (MS) model is frequently used to investigate the impact of early environmental factors on adult neurobiology and behavior. The majority of MS studies assess effects in the offspring and few address the consequences of repeated pup removal in the dam. Such studies are of interest since alterations detected in offspring subjected to MS may, at least in part, be mediated by variations in maternal behavior and the amount of maternal care provided by the dam. The aim of this study was to investigate how daily short (15 min; MS15) and prolonged (360 min; MS360) periods of MS affects the dam by examining postpartum behavioral profiles using the multivariate concentric square field (MCSF) test. The dams were tested on postpartum days 24-25, i.e., just after the end of the separation period and weaning. The results reveal a lower exploratory drive and lower risk-assessment behavior in MS15 dams relative to MS360 or animal facility reared dams. The present results contrast some of the previously reported findings and provide new information about early post-weaning behavioral characteristics in a multivariate setting. Plausible explanations for the results are provided including a discussion how the present results fit into the maternal mediation hypothesis.

  18. Sodium selenite supplementation during pregnancy and lactation promotes anxiolysis and improves mnemonic performance in wistar rats' offspring.

    PubMed

    Laureano-Melo, Roberto; Império, Güínever Eustáquio do; da Silva-Almeida, Claudio; Kluck, George Eduardo Gabriel; Cruz Seara, Fernando de Azevedo; da Rocha, Fábio Fagundes; da Silveira, Anderson Luiz Bezerra; Reis, Luís Carlos; Ortiga-Carvalho, Tania Maria; da Silva Côrtes, Wellington

    2015-11-01

    Selenium is a micronutrient which is part of selenoprotein molecules and participates in a vast number of physiological roles and, among them,we have fetal and neonatal development. Therefore, the aimof this studywas to evaluate possible behavioral changes in offspring of female rats supplemented during pregnancy and lactation with sodium selenite. To address that, we treated two groups of female rats by saline or sodium selenite at a dose of 1mg/kg through oral route and performed neurochemical and behavioral tests. In the offspring, the thyroid profile and hippocampal neurochemistrywere evaluated. Behavioral testswere performed in pups both during childhood and adulthood. We found out that selenium (Se) supplementation increased serum levels of triiodothyronine (25%, p b 0.001) and thyroxine (18%, p b 0.05) and promoted a tryptophan hydroxylase 2 (TPH 2) expression decrease (17%, p b 0.01) and tyrosine hydroxylase (TH) expression increase (202%, p b 0.01) in the hippocampus. The cholinesterase activity was decreased (28%, p b 0.01) in Se supplemented rats, suggesting a neurochemical modulation in the hippocampal activity. During childhood, the Sesupplemented offspring had a reduction in anxiety-like behavior both in elevated plus maze test and in light–dark box test. In adulthood, Se-treated pups had an increase in the locomotor activity (36%, p b 0.05) and in rearing episodes (77%, p b 0.001) in the open field test, while in the elevated plus maze test they also exhibited an increase in the time spent in the open arms (243%, p b 0.01). For the object recognition test, Se-treated offspring showed increase in the absolute (230.16%, p b 0.05) and relative index discrimination (234%, p b 0.05). These results demonstrate that maternal supplementation by sodium selenite promoted psychobiological changes both during childhood and adulthood. Therefore, the behavioral profile observed possibly can be explained by neurochemical changes induced by thyroid hormones during

  19. Forced but not free-choice nicotine during lactation alters maternal behavior and noradrenergic system of pups: Impact on social behavior of adolescent isolated male rats.

    PubMed

    Chirico, Doriana; Romano, Emilia; Famele, Marco; Draisci, Rosa; Mancinelli, Rosanna; Pascucci, Tiziana; Adriani, Walter

    2017-10-11

    Adverse effects of nicotine during pregnancy have been greatly studied, while nowadays few works are focused on consequences of maternal tobacco smoking after birth. The present study investigated the behavioral and early neurochemical effects of nicotine treatment during first weeks of post-natal life in rats. We used "free choice" treatment (H2O+NIC dams could drink from two bottles, containing 10mg/L nicotine hydrogen tartrate salt, or water) versus "forced choice" (NIC+NIC mothers could drink from two bottles both containing nicotine hydrogen tartrate salt, range from 0.75mg/L to 4.09mg/L). We found that only "forced nicotine" had impact on maternal behavior, causing increased high-quality maternal care. This immediately impacted on neuro-chemical development, affecting NE levels (only males) in pup's striatum and prefrontal cortex (pFC) at PND 12. After weaning, animals were reared in normal conditions (two brother rats) or in Social Isolation. After two weeks, they were tested with Social Interaction Test (isolated rats met non-isolated opponents, siblings vs. non-siblings). As expected, isolated rats displayed an aggressive form of soliciting behavior: when facing an isolated unknown partner, the non-isolated rat tried to escape. Interestingly, if their dams were exposed to forced nicotine, both rats sooner behaved very affiliative (possibly empathic) between non-sibling partners. As expected, being exposed to post-natal nicotine could alter neuro-chemical development, but with important interactions between both maternal care and adolescent social behavior. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Periaqueductal gray μ and κ opioid receptors determine behavioral selection from maternal to predatory behavior in lactating rats.

    PubMed

    Klein, Marianne Orlandini; Cruz, Aline de Mello; Machado, Franciele Corrêa; Picolo, Gisele; Canteras, Newton Sabino; Felicio, Luciano Freitas

    2014-11-01

    Every mother must optimize her time between caring for her young and her subsistence. The rostro lateral portion of the periaqueductal grey (rlPAG) is a critical site that modulates the switch between maternal and predatory behavior. Opioids play multiple roles in both maternal behavior and this switching process. The present study used a pharmacological approach to evaluate the functional role of rlPAG μ and κ opioid receptors in behavioral selection. Rat dams were implanted with a guide cannula in the rlPAG and divided into three experiments in which we tested the role of opioid agonists (Experiment 1), the influence of μ and κ opioid receptor blockade in the presence of morphine (Experiment 2), and the influence of μ and κ opioid receptor blockade (Experiment 3). After behavioral test, in Experiment 4, we evaluated rlPAG μ and κ receptor activation in all Experiments 1-3. The results showed that massive opioidergic activation induced by morphine in the rlPAG inhibited maternal behavior without interfering with predatory hunting. No behavioral changes and no receptor activation were promoted by the specific agonist alone. However, κ receptor blockade increased hunting behavior and increased the level of μ receptor activation in the rlPAG. Thus, endogenous opioidergic tone might be modulated by a functional interaction between opioid receptor subtypes. Such a compensatory receptor interaction appears to be relevant for behavioral selection among motivated behaviors. These findings indicate a role for multiple opioid receptor interactions in the modulation of behavioral selection between maternal and predatory behaviors in the PAG. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. A quantitative histochemical study of lactate dehydrogenase and succinate dehydrogenase activities in the membrana granulosa of the ovulatory follicle of the rat.

    PubMed

    Zoller, L C; Enelow, R

    1983-11-01

    Using a microdensitometer, lactate dehydrogenase and succinate dehydrogenase activities were measured in the membrana granulosa of the rat ovulatory follicle. Ovaries were removed on each day of the oestrous cycle; oestrus, dioestrus-1, dioestrus-2, and proestrus; and enzyme activities measured in the membrana granulosa as a whole and in four regions within it: peripheral (PR), antral (AR), cumulus oophorus (CO) and corona radiata (CR). Throughout the cycle, lactate dehydrogenase activity was greatest in PR. On oestrus, lactate dehydrogenase activity was progressively less in AR, CO and CR. On dioestrus-1, activity was identical in AR and CO and less in CR. On dioestrus-2, activity was greater in AR than in CO or CR. By proestrus, activity was equal in AR, CO and CR. In the membrana granulosa as a whole, and in each region, lactate dehydrogenase activity declined as ovulation approached. In contrast, succinate dehydrogenase activity in the membrana granulosa as a whole and in PR was constant throughout the cycle. Activity fluctuated in the other regions. Succinate dehydrogenase activity on oestrus was greatest in PR, less in AR and CO and least in CR. On the remaining days, succinate dehydrogenase activity was greatest in PR and less but equal in the remainder of the membrana granulosa.

  2. Increased Litter Size and Suckling Intensity Stimulate mRNA of RFamide-related Peptide in Rats.

    PubMed

    Noroozi, Atefeh; Jafarzadeh Shirazi, Mohammad Reza; Tamadon, Amin; Moghadam, Ali; Niazi, Ali

    2015-01-01

    RFamide-related peptide-3 (RFRP-3) inhibits gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) secretion in rats. This study evaluates the effects of litter size and suckling intensity on RFRP mRNA expression in the dorsomedial hypothalamic nucleus (DMH) of rats. A total of 32 pregnant and 4 non-lactating ovariectomized (control group) Sprague-Dawley rats were used in this experimental study. Lactating rats were allotted to 8 equal groups. In 3 groups, the litter size was adjusted to 5, 10, or 15 pups upon parturition. Dams were allowed to suckle their pups continuously until 8 days postpartum. In the other 3 groups, the litter size was adjusted to 5 pups following birth. These pups were separated from the dams for 6 hours on day 8 postpartum, after which the pups were allowed to suckle for 2.5, 5, or 7.5 minutes prior to killing the dams. In 2 groups, lactating rats with 10 and 15 pups were separated from their pups for 6 hours on day 8 postpartum. In these groups, the pups were allowed to suckle their dams for 5 minutes before the dams were killed. All rats were killed on day 8 postpartum and the DMH was removed from each rat. We evaluated RFRP mRNA expression using realtime polymerase chain reaction (PCR). The expression of RFRP mRNA in the DMH increased with increased litter size and suckling intensity compared to the controls. The effect of suckling intensity on the expression of RFRP mRNA was more pronounced compared to the litter size. Increased litter size and suckling intensity stimulated RFRP mRNA expression in the DMH which might contribute to lactation anestrus in rats.

  3. Increased Litter Size and Suckling Intensity Stimulate mRNA of RFamide-related Peptide in Rats

    PubMed Central

    Noroozi, Atefeh; Jafarzadeh Shirazi, Mohammad Reza; Tamadon, Amin; Moghadam, Ali; Niazi, Ali

    2015-01-01

    Background RFamide-related peptide-3 (RFRP-3) inhibits gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) secretion in rats. This study evaluates the effects of litter size and suckling intensity on RFRP mRNA expression in the dorsomedial hypothalamic nucleus (DMH) of rats. Materials and Methods A total of 32 pregnant and 4 non-lactating ovariectomized (control group) Sprague-Dawley rats were used in this experimental study. Lactating rats were allotted to 8 equal groups. In 3 groups, the litter size was adjusted to 5, 10, or 15 pups upon parturition. Dams were allowed to suckle their pups continuously until 8 days postpartum. In the other 3 groups, the litter size was adjusted to 5 pups following birth. These pups were separated from the dams for 6 hours on day 8 postpartum, after which the pups were allowed to suckle for 2.5, 5, or 7.5 minutes prior to killing the dams. In 2 groups, lactating rats with 10 and 15 pups were separated from their pups for 6 hours on day 8 postpartum. In these groups, the pups were allowed to suckle their dams for 5 minutes before the dams were killed. All rats were killed on day 8 postpartum and the DMH was removed from each rat. We evaluated RFRP mRNA expression using realtime polymerase chain reaction (PCR). Results The expression of RFRP mRNA in the DMH increased with increased litter size and suckling intensity compared to the controls. The effect of suckling intensity on the expression of RFRP mRNA was more pronounced compared to the litter size. Conclusion Increased litter size and suckling intensity stimulated RFRP mRNA expression in the DMH which might contribute to lactation anestrus in rats. PMID:26644862

  4. D-lactate increases pulmonary apoptosis by restricting phosphorylation of bad and eNOS in a rat model of hemorrhagic shock.

    PubMed

    Jaskille, Amín; Alam, Hasan B; Rhee, Peter; Hanes, William; Kirkpatrick, John R; Koustova, Elena

    2004-08-01

    Resuscitation with racemic lactated Ringer's solution (containing equal amounts of D and L isomers of lactate) has been shown to induce pulmonary apoptosis. Substitution of DL-isomer lactate with ketone bodies (beta-hydroxybutyrate, BHB), sodium pyruvate, or L-isomer of lactate decrease this injury without changing the energy status of the tissues or the expression of apoptotic genes. These modified solutions however alter the function of apoptotic proteins through an unknown mechanism. We postulated that DL-LR induces apoptosis by restricting the phosphorylation of key apoptotic proteins. Male Sprague Dawley rats (n = 30, 5/group) were subjected to a three stage, volume-controlled hemorrhage and randomized to the following groups. 1) No hemorrhage (Sham); 2) Hemorrhage and no resuscitation (NR); 3) Resuscitation with 3x shed blood volume of racemic LR (DL-LR); 4) Resuscitation with 3x shed blood volume of LR containing only the L-isomer of lactate (L-LR); 5) Resuscitation with 3s shed blood volume of pyruvate Ringer's (PR); 6) Resuscitation with 3s shed blood volume of ketone Ringer's (KR). The modified Ringer's solutions were identical to racemic LR except for equimolar substitution of DL-lactate for L-lactate, pyruvate and BHB respectively. Lung tissue was obtained 2 hours later and subjected to Western Blotting. The levels of Akt, Bad, and eNOS (total and phosphorylated) proteins were measured. Finally, the expression of gene coding for protein 14-3-3 was measured using RT-PCR. Resuscitation with DL-LR caused a significant (p < 0.05) increase in the total Bad and a decrease in phosphorylated Bad protein expression in the lung. It also caused an increase in the phosphorylated Akt levels and a decrease in gene coding for protein 14-3-3. These changes were consistent with signaling imbalances that favor apoptosis. Modified LR solutions, on the other hand, did not cause these alterations. Phosphorylation pattern of eNOS supported the involvement of PI3K/Akt pathway

  5. Effects of Maternal Dexamethasone Exposure During Lactation on Metabolic Imbalance and Oxidative Stress in the Liver of Male Offsprings of Wistar Rats.

    PubMed

    Jeje, S O; Raji, Yinusa

    2015-12-20

    It has been reported in human and animal studies that early exposure to glucocorticoids could retard growth and subsequent development of cardio metabolic diseases. Chronic exposure to glucocorticoids induced oxidative stress. Therefore, the role of oxidative stress in some of the observed metabolic imbalance needs to be elucidated. This study examined the effects of lactational dexamethasone exposure on metabolic imbalance and oxidative stress marker in the liver of male offspring of exposed mother. Twenty lactating dams were divided into 4 groups of 5 animals each. Group 1 was administered 0.02 ml/100gbwt/day normal saline through lactation days 1-21. Group 2, 3, and 4 were administered 100 µg/kgbwt/day dexamethasone for lactation days 1-7, 1-14, and 1-21 respectively. The male offspring were thereafter separated and sacrificed at 12weeks of age for evaluation of lipid profile and oxidative stress marker in the liver. Results from this study indicate that Total Cholesterol (TC), Triglycerides (TAG) and LDL- cholesterol (LDL-C) were significantly  higher in the Dex 1-7, Dex 1-14 and Dex 1-21 groups when compared with the control. HDL-Cholesterol (HDL-C) was significantly reduced in the Dex 1-7, Dex 1-14 and Dex 1-21 groups relative to the control. Basal Fasting Blood Sugar (FBS) was also significantly higher in the Dex 1-14 and Dex 1-21 groups when compared with the control. Liver malondialdehyde was significantly higher in the Dex1-14 and Dex1-21 group compared to the control. However, liver catalase and SOD activity were all significantly lower in Dex 1-7, Dex 1-14 and Dex 1-21 groups relative to control. Liver protein was significantly lower in the Dex1-14 and Dex1-21 treatment groups when compared with the control. Findings from this study suggest that there is possible increase in metabolic imbalance in the offspring of mother exposed to dexamethasone during lactation and these effects may be secondary to increase oxidative stress in the liver.

  6. In utero and lactational exposure to fipronil in female rats: Pregnancy outcomes and sexual development.

    PubMed

    de Barros, Aline Lima; Rosa, Josiane Lima; Cavariani, Marília Martins; Borges, Cibele Santos; Villela e Silva, Patrícia; Bae, Julie Heejoo; Anselmo-Franci, Janete Aparecida; Cristina Arena, Arielle

    2016-01-01

    Fipronil, a phenylpyrazole insecticide, is used in agriculture, veterinary medicine, and public health. Because this insecticide is considered a potential endocrine disruptor, the aim of this study was to examine the influence of perinatal exposure to fipronil on neonatal female reproductive system development. Pregnant rats were exposed (via gavage) daily to fipronil (0.03, 0.3, or 3 mg/kg) from gestational day 15 to day 7 after birth, and effects on the reproductive functions assessed on postnatal day (PND) 22. No signs of maternal toxicity were observed during daily treatment with fipronil. Perinatal exposure to the highest dose of fipronil (3 mg/kg) delayed the age of vaginal opening (VO) and first estrus without markedly affecting the anogenital distance (AGD). Further, exposure to 0.3 mg/kg fipronil produced a significantly shorter estrus cycle and reduced number of cycles during the period of evaluation. However, the other reproductive parameters analyzed, including fertility, hormone levels, sexual behavior, and histology of ovaries and uterus, displayed no marked alterations. In this experimental model, fipronil interfered with development of neonatal female reproductive system as evidenced by delay in VO and estrus cycle alterations without apparent significant effects on fertility. Further studies are needed to identify the mechanisms of action associated with the observed female reproductive system changes.

  7. Maternal exposure to fluoxetine during gestation and lactation affects the DNA methylation programming of rat's offspring: modulation by folic acid supplementation.

    PubMed

    Toffoli, L V; Rodrigues, G M; Oliveira, J F; Silva, A S; Moreira, E G; Pelosi, G G; Gomes, M V

    2014-05-15

    Fluoxetine is an antidepressant that has been largely used for treatment of depression in pregnancy. In the present study we evaluated the effects of the exposure to fluoxetine during gestation and lactation on DNA methylation of rat brain regions. Female Wistar rats were treated with 5mg/kg of fluoxetine during pregnancy and lactation. In order to assess the effects of fluoxetine in the context of maternal folic acid supplementation we performed an additional combined treatment composed by folic acid (8 mg/kg/day) and fluoxetine (5 mg/kg/day). On the postnatal day 22, male rats were euthanized and hippocampus, cortex, hypothalamus, and periaqueductal gray area were removed. Global DNA methylation was quantified using a high-throughput ELISA-based method. Neurofunctional changes were addressed using validated behavioral tests: hot plate, elevated plus maze and open field. A decrease in the global DNA methylation profile of hippocampus was associated to the exposure to fluoxetine, whereas an increase in methylation was observed in cortex. The combined treatment induced an increase in the methylation of hippocampus indicating the potential of folic acid to modulate this epigenetic alteration. Increase in the latency to the thermal nociceptive response was observed in animals exposed to fluoxetine whereas this effect was abolished in animals from the combined treatment. In summary we demonstrated that exposure to fluoxetine during gestation and lactation affect the DNA methylation of brain and the nociceptive response of rats. Furthermore our data reveal the potential of folic acid to modulate epigenetic and functional changes induced by early exposure to fluoxetine.

  8. Maternal “junk-food” feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring

    PubMed Central

    Ong, Z. Y.; Muhlhausler, B. S.

    2011-01-01

    Individuals exposed to high-fat, high-sugar diets before birth have an increased risk of obesity in later life. Recent studies have shown that these offspring exhibit increased preference for fat, leading to suggestions that perinatal exposure to high-fat, high-sugar foods results in permanent changes within the central reward system that increase the subsequent drive to overconsume palatable foods. The present study has determined the effect of a maternal “junk-food” diet on the expression of key components of the mesolimbic reward pathway in the offspring of rat dams at 6 wk and 3 mo of age. We show that offspring of junk-food-fed (JF) dams exhibit higher fat intake from weaning until at least 3 mo of age (males: 16±0.6 vs. 11±0.8 g/kg/d; females: 19±1.3 vs. 13±0.4 g/kg/d; P<0.01). mRNA expression of μ-opioid receptor (Mu) was 1.6-fold higher (P<0.01) and dopamine active transporter (DAT) was 2-fold lower (P<0.05) in JF offspring at 6 wk of age. By 3 mo, these differences were reversed, and Mu mRNA expression was 2.8-fold lower (P<0.01) and DAT mRNA expression was 1.9-fold higher (P<0.01) in the JF offspring. These findings suggest that perinatal exposure to high-fat, high-sugar diets results in altered development of the central reward system, resulting in increased fat intake and altered response of the reward system to excessive junk-food intake in postnatal life.—Ong, Z. Y., Muhlhausler, B. S. Maternal “junk-food” feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring. PMID:21427213

  9. Offspring's hydromineral adaptive responses to maternal undernutrition during lactation.

    PubMed

    Nuñez, P; Arguelles, J; Perillan, C

    2015-12-01

    Early development, throughout gestation and lactation, represents a period of extreme vulnerability during which susceptibility to later metabolic and cardiovascular injuries increases. Maternal diet is a major determinant of the foetal and newborn developmental environment; maternal undernutrition may result in adaptive responses leading to structural and molecular alterations in various organs and tissues, such as the brain and kidney. New nephron anlages appear in the renal cortex up to postnatal day 4 and the last anlages to be formed develop into functional nephrons by postnatal day 10 in rodents. We used a model of undernutrition in rat dams that were food-restricted during the first half of the lactation period in order to study the long-term effects of maternal diet on renal development, behaviour and neural hydromineral control mechanisms. The study showed that after 40% food restriction in maternal dietary intake, the dipsogenic responses for both water and salt intake were not altered; Fos expression in brain areas investigated involved in hydromineral homeostasis control was always higher in the offspring in response to isoproterenol. This was accompanied by normal plasma osmolality changes and typical renal histology. These results suggest that the mechanisms for the control of hydromineral balance were unaffected in the offspring of these 40% food-restricted mothers. Undernutrition of the pups may not be as drastic as suggested by dams' restriction.

  10. In utero and lactational β-carotene supplementation attenuates D-galactose-induced hearing loss in newborn rats.

    PubMed

    Yu, Fei; Hao, Shuai; Zhao, Yue; Yang, Hui; Fan, Xiao-Lan; Yang, Jun

    2011-08-01

    D-Galactose could give rise to free radical damage by disturbing the some maternal antioxidants. The oxidative stress induced by D-galactose is a potent inducer of apoptosis, which is accompanied by the activation of protein-splitting enzymes called caspases. Apoptosis is a crucial physiological determinant of embryonic and neonatal development, and play an essential role in the development of the inner ear structures. Recently the increasing of D-galactose exposure is due to high consumption of dairy foods or reduced galactose metabolism. An overwhelming presence of D-galactose is known to become highly ototoxicity to humans. The purpose of this study was to investigate whether supplementation of pregnant and lactational mothers with β-carotene could attenuate cochlear function damage and hair cells apoptosis induced by d-galactose in newborn rats. Pregnant rats were supplemented with D-galactose, or D-galactose and β-carotene from gestational day (GD) 7 until postnatal day (PND) 21. On PND 22, offspring were examined in the distortion product otoacoustic emission (DPOAE) task, cochleae were then harvested for assessment of apoptosis by immunohistochemical stain for cysteine-aspartic acid proteases 3 (caspase-3) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Maternal and offspring blood samples were then collected by direct cardiac puncture in heparin tubes, blood levels of D-galactose and β-carotene were measured, plasma was separated for malondialdehyde (MDA) analysis, erythrocytes were left for superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH). D-Galactose could significantly disturb the balance between maternal antioxidants and free radicals, and induce hearing loss in the offspring and cochlear hair cell apoptosis. In contrast, β-carotene supplementation, coincidentally with D-galactose exposure, ameliorated these changes. Our data offer a conceptual framework for designing

  11. Maternal trans fat intake during pregnancy or lactation impairs memory and alters BDNF and TrkB levels in the hippocampus of adult offspring exposed to chronic mild stress.

    PubMed

    Pase, Camila Simonetti; Roversi, Karine; Roversi, Katiane; Vey, Luciana Taschetto; Dias, Verônica Tironi; Veit, Juliana Cristiana; Maurer, Luana Haselein; Duarte, Thiago; Emanuelli, Tatiana; Duarte, Marta; Bürger, Marilise Escobar

    2017-02-01

    This study aimed to assess the influence of maternal dietary fat intake during pregnancy or lactation on memory of adult offspring after chronic mild stress (CMS) exposure. Female Wistar rats were supplemented daily with soybean oil/fish oil (SO/FO) or hydrogenated vegetable fat (HVF) by oral gavage (3.0g/kg body weight) during pregnancy or lactation. On post-natal day (PND) 60, half of the animals were exposed to CMS following behavioral assessments. While the adult offspring born under influence of SO/FO and HVF supplementations during pregnancy showed higher levels of n-3 and n-6 fatty acids (FA) series DHA and ARA metabolites, respectively, in the hippocampus, adult offspring born from supplemented dams during lactation showed higher levels of their precursors: ALA and LA. However, only HVF supplementation allowed TFA incorporation of adult offspring, and levels were higher in lactation period. Adult offspring born from dams supplemented with trans fat in both pregnancy and lactation showed short and long-term memory impairments before and after CMS. Furthermore, our study also showed higher memory impairment in offspring born from HVF-supplemented dams during lactation in comparison to pregnancy. BDNF expression was increased by stress exposure in offspring from both SO/FO- and HVF-supplemented dams during pregnancy. In addition, offspring from HVF-supplemented dams showed decreased TrkB expression in both supplemented periods, regardless of stress exposure. In conclusion, these findings show for the first time that the type of dietary FA as well as the period of brain development is able to change FA incorporation in brain neural membranes. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Differential regulation of hepatic transcription factors in the Wistar rat offspring born to dams fed folic acid, vitamin B12 deficient diets and supplemented with omega-3 fatty acids.

    PubMed

    Meher, Akshaya; Joshi, Asmita; Joshi, Sadhana

    2014-01-01

    Nutritional status of the mother is known to influence various metabolic adaptations required for optimal fetal development. These may be mediated by transcription factors like peroxisome proliferator activated receptors (PPARs), which are activated by long chain polyunsaturated fatty acids. The objective of the current study was to examine the expression of different hepatic transcription factors and the levels of global methylation in the liver of the offspring born to dams fed micronutrient deficient (folic acid and vitamin B12) diets and supplemented with omega-3 fatty acids. Female rats were divided into five groups (n = 8/group) as follows; control, folic acid deficient (FD), vitamin B12 deficient (BD) and omega-3 fatty acid supplemented groups (FDO and BDO). Diets were given starting from pre-conception and continued throughout pregnancy and lactation. Pups were dissected at the end of lactation. Liver tissues were removed; snap frozen and stored at -80°C. Maternal micronutrients deficiency resulted in lower (p<0.05) levels of pup liver docosahexaenoic acid (DHA) and arachidonic acid (ARA) as compared to the control group. Pup liver PPARα and PPARγ expression was lower (p<0.05) in the BD group although there were no differences in the expression of SREBP-1c, LXRα and RXRα expression. Omega-3 fatty acids supplementation to this group normalized (p<0.05) levels of both PPARα and PPARγ but reduced (p<0.05) SREBP-1c, LXRα and RXRα expression. There was no change in any of the transcription factors in the pup liver in the FD group. Omega-3 fatty acids supplementation to this group reduced (p<0.05) PPARα, SREBP-1c and RXRα expression. Pup liver global methylation levels were higher (p<0.01) in both the micronutrients deficient groups and could be normalized (p<0.05) by omega-3 fatty acid supplementation. Our novel findings suggest a role for omega-3 fatty acids in the one carbon cycle in influencing the hepatic expression of transcription factors in the

  13. Differential Regulation of Hepatic Transcription Factors in the Wistar Rat Offspring Born to Dams Fed Folic Acid, Vitamin B12 Deficient Diets and Supplemented with Omega-3 Fatty Acids

    PubMed Central

    Meher, Akshaya; Joshi, Asmita; Joshi, Sadhana

    2014-01-01

    Nutritional status of the mother is known to influence various metabolic adaptations required for optimal fetal development. These may be mediated by transcription factors like peroxisome proliferator activated receptors (PPARs), which are activated by long chain polyunsaturated fatty acids. The objective of the current study was to examine the expression of different hepatic transcription factors and the levels of global methylation in the liver of the offspring born to dams fed micronutrient deficient (folic acid and vitamin B12) diets and supplemented with omega-3 fatty acids. Female rats were divided into five groups (n = 8/group) as follows; control, folic acid deficient (FD), vitamin B12 deficient (BD) and omega-3 fatty acid supplemented groups (FDO and BDO). Diets were given starting from pre-conception and continued throughout pregnancy and lactation. Pups were dissected at the end of lactation. Liver tissues were removed; snap frozen and stored at −80°C. Maternal micronutrients deficiency resulted in lower (p<0.05) levels of pup liver docosahexaenoic acid (DHA) and arachidonic acid (ARA) as compared to the control group. Pup liver PPARα and PPARγ expression was lower (p<0.05) in the BD group although there were no differences in the expression of SREBP-1c, LXRα and RXRα expression. Omega-3 fatty acids supplementation to this group normalized (p<0.05) levels of both PPARα and PPARγ but reduced (p<0.05) SREBP-1c, LXRα and RXRα expression. There was no change in any of the transcription factors in the pup liver in the FD group. Omega-3 fatty acids supplementation to this group reduced (p<0.05) PPARα, SREBP-1c and RXRα expression. Pup liver global methylation levels were higher (p<0.01) in both the micronutrients deficient groups and could be normalized (p<0.05) by omega-3 fatty acid supplementation. Our novel findings suggest a role for omega-3 fatty acids in the one carbon cycle in influencing the hepatic expression of transcription factors

  14. Hypothyroidism advances mammary involution in lactating rats through inhibition of PRL signaling and induction of LIF/STAT3 mRNAs.

    PubMed

    Campo Verde Arboccó, Fiorella; Sasso, Corina V; Actis, Esteban A; Carón, Rubén W; Hapon, María Belén; Jahn, Graciela A

    2016-01-05

    Thyroid diseases have deleterious effects on lactation, litter growth and survival, and hinder the suckling-induced hormone release, leading in the case of hyperthyroidism, to premature mammary involution. To determine the effects of hypothyroidism (HypoT) on late lactation, we analyzed the effect of chronic 6-propyl-2-thiouracil (PTU)-induced HypoT on mammary histology and the expression of members of the JAK/STAT/SOCS signaling pathway, milk proteins, prolactin (PRLR), estrogen (ER), progesterone (PR) and thyroid hormone (TR) receptors, markers of involution (such as stat3, lif, bcl2, BAX and PARP) on lactation (L) day 21. HypoT mothers showed increased histological markers of involution compared with control rats, such as adipose/epithelial ratio, inactive alveoli, picnotic nuclei and numerous detached apoptotic cells within the alveolar lumina. We also found decreased PRLR, β-casein and α-lactoalbumin mRNAs, but increased SOCS1, SOCS3, STAT3 and LIF mRNAs, suggesting a decrease in PRL signaling and induction of involution markers. Furthermore, Caspase-3 and 8 and PARP labeled cells and the expression of structural proteins such as β-Actin, α-Tubulin and Lamin B were increased, indicating the activation of apoptotic pathways and tissue remodelation. HypoT also increased PRA (mRNA and protein) and erβ and decreased erα mRNAs, and increased strongly TRα1, TRβ1, PRA and ERα protein levels. These results show that lactating HypoT rats have premature mammary involution, most probably induced by the inhibition of prolactin signaling along with the activation of the LIF-STAT3 pathway. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Maternal caffeine ingestion during gestation and lactation influences respiratory adaptation to acute alveolar hypoxia in newborn rats and adenosine A2A and GABA A receptor mRNA transcription.

    PubMed

    Picard, N; Guénin, S; Larnicol, N; Perrin, Y

    2008-10-15

    Caffeine is a widely used psychostimulant freely crossing the placental barrier. At the doses usually absorbed, it acts as an antagonist of both A1 and A2A adenosine receptors. Pregnant women are generally not advised to limit their caffeine consumption and thus expose their progeny to the drug during the whole of gestation and lactation. The possibility that such caffeine exposure may have long-term consequences on brain development has led to several behavioral investigations on animal models. Despite the crucial role played by adenosine receptor systems in neonatal breathing control, few studies in vitro have been concerned with the consequences of maternal caffeine absorption on breathing, and none in the unrestrained intact animal. The present investigation analyzed the influence of caffeine exposure via placental and milk transfer on resting ventilation and on the response to moderate alveolar hypoxia of 0 to 2-day-old newborn rat (P0-P2) together with the possible underlying mechanisms. Dams absorbed caffeine (46+/-3 mg/kg/day) via drinking fluid (0.2 g/L) throughout gestation, in conditions mimicking moderate human consumption. Caffeine exposure did not significantly affect basal respiratory parameters. In contrast, it attenuated both the early increase and the secondary decrease in ventilation triggered by moderate alveolar hypoxia (11% O2 inhaled). The abolition of Fos protein expression evoked by hypoxia suggested that caffeine exposure may decrease the activity of O2-sensing peripheral chemoreceptor pathway. From real-time PCR data, those functional alterations were associated to increases in A2A adenosine receptor and alpha2 GABA(A) receptor subunit mRNAs in the medulla. This indicates that, even at moderate doses, maternal caffeine consumption may induce a series of subtle developmental alterations that may affect modulation of breathing control in the neonate in pathological situations such hypoxia.

  16. 107. DAM EARTH DIKE SUBMERSIBLE DAMS PLANS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    107. DAM - EARTH DIKE - SUBMERSIBLE DAMS - PLANS & SECTIONS (ML-8-52/3-FS) March 1940 - Upper Mississippi River 9-Foot Channel, Lock & Dam No. 8, On Mississippi River near Houston County, MN, Genoa, Vernon County, WI

  17. Simultaneous assay of glucose, lactate, L-glutamate and hypoxanthine levels in a rat striatum using enzyme electrodes based on neutral red-doped silica nanoparticles.

    PubMed

    Zhang, Fen-Fen; Wan, Qiao; Li, Chen-Xin; Wang, Xiao-Li; Zhu, Zi-Qiang; Xian, Yue-Zhong; Jin, Li-Tong; Yamamoto, Katsunobu

    2004-10-01

    An electrochemical method suitable for the simultaneous measurement of cerebral glucose, lactate, L-glutamate and hypoxanthine concentrations from in vivo microdialysis sampling has been successfully performed for the first time using a neutral red-doped silica (NRDS) nanoparticle-derived enzyme sensor system. These uniform NRDS nanoparticles (about 50 +/- 3 nm) were prepared by a water-in-oil (W/O) microemulsion method, and characterized by a TEM technique. The neutral red-doped interior maintained its high electron-activity, while the exterior nano-silica surface prevented the mediator from leaching out into the aqueous solution, and showed high biocompability. These nanoparticles were then mixing with the glucose oxidase (GOD), lactate oxidase (LOD), L-glutamate oxidase (L-GLOD) or xanthine oxidase (XOD), and immobilized on four glassy carbon electrodes, respectively. A thin Nafion film was coated on the enzyme layer to prevent interference from molecules such as ascorbic acid and uric acid in the dialysate. The high sensitivity of the NRDS modified enzyme electrode system enables the simultaneous monitoring of trace levels of glucose, L-glutamate, lactate and hypoxanthine in diluted dialysate samples from a rat striatum.

  18. Short- and long-term effects of maternal nicotine exposure during lactation on body adiposity, lipid profile, and thyroid function of rat offspring.

    PubMed

    Oliveira, E; Moura, E G; Santos-Silva, A P; Fagundes, A T S; Rios, A S; Abreu-Villaça, Y; Nogueira Neto, J F; Passos, M C F; Lisboa, P C

    2009-09-01

    Epidemiological studies show a higher prevalence of obesity in children from smoking mothers and smoking may affect human thyroid function. To evaluate the mechanism of smoking as an imprinting factor for these dysfunctions, we evaluated the programming effects of maternal nicotine (NIC) exposure during lactation. Two days after birth, osmotic minipumps were implanted in lactating rats, divided into: NIC (6 mg/kg per day s.c.) for 14 days; Control - saline. All the significant data were P<0.05 or less. Body weight was increased from 165 days old onwards in NIC offspring. Both during exposure (at 15 days old) and in adulthood (180 days old), NIC group showed higher total fat (27 and 33%). In addition, NIC offspring presented increased visceral fat and total body protein. Lipid profile was not changed in adulthood. Leptinemia was higher at 15 and 180 days old (36 and 113%), with no changes in food intake. Concerning the thyroid status, the 15-days-old NIC offspring showed lower serum-free tri-iodothyronine (FT(3)) and thyroxine (FT(4)) with higher TSH. The 180-days-old NIC offspring exhibited lower TSH, FT(3), and FT(4)). In both periods, liver type 1 deiodinase was lower (26 and 55%). We evidenced that NIC imprints a neonatal thyroid dysfunction and programs for a higher adiposity, hyperleptinemia, and secondary hypothyroidism in adulthood. Our study identifies lactation as a critical period to NIC programming for obesity, with hypothyroidism being a possible contributing factor.

  19. Lactational exposure to hydroxylated polychlorinated biphenyl (OH-PCB 106) causes hyperactivity in male rat pups by aberrant increase in dopamine and its receptor.

    PubMed

    Lesmana, Ronny; Shimokawa, Noriaki; Takatsuru, Yusuke; Iwasaki, Toshiharu; Koibuchi, Noriyuki

    2014-08-01

    Polychlorinated biphenyls (PCBs) are recognized as persistent environmental pollutants that may cause adverse health problems. Despite extensive investigations of PCB in neural function, little is known about behavioral traits by PCB exposure and its neurochemical mechanism. Here, we report the behavioral study of a rat pup that was exposed to hydroxylated-PCB 106 (OH-PCB 106; 4-hydroxy-2',3,3',4',5'-pentachlorobiphenyl) through maternal milk. The different groups of mothers received via gavage corn oil vehicle, 0.5, 5, or 50 mg/kg body weight of OH-PCB 106 every second day from day 3 to 13 after delivery. The exposure did not affect the body weight of the dams or the physical development of the newborn pups in both sexes. Male rats exposed to OH-PCB 106 showed hyperactivity that was characterized by increased locomotor activity in novel environment and circadian period. Interestingly, OH-PCB 106-exposed rat pups displayed abnormally high levels of dopamine and D2 dopamine receptor (D2DR), but not D1DR and D5DR, in the striatum, an important center for the coordination of behavior. These findings indicate that OH-PCB 106 has a significant neurotoxic effect on rat behavior, which may be associated with increased D2DR mediated signals. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

  20. Maternal protein restriction during gestation and lactation in the rat results in increased brain levels of kynurenine and kynurenic acid in their adult offspring.

    PubMed

    Honório de Melo Martimiano, Paula; de Sa Braga Oliveira, André; Ferchaud-Roucher, Véronique; Croyal, Mikaël; Aguesse, Audrey; Grit, Isabelle; Ouguerram, Khadija; Lopes de Souza, Sandra; Kaeffer, Bertrand; Bolaños-Jiménez, Francisco

    2017-01-01

    Early malnutrition is a risk factor for depression and schizophrenia. Since the offspring of malnourished dams exhibit increased brain levels of serotonin (5-HT), a tryptophan-derived neurotransmitter involved in the pathophysiology of these mental disorders, it is believed that the deleterious effects of early malnutrition on brain function are due in large part to altered serotoninergic neurotransmission resulting from impaired tryptophan (Trp) metabolism. However, tryptophan is also metabolized through the kynurenine (KYN) pathway yielding several neuroactive compounds including kynurenic (KA), quinolinic (QA) and xanthurenic (XA) acids. Nevertheless, the impact of perinatal malnutrition on brain kynurenine pathway metabolism has not been examined to date. Here, we used ultra-performance liquid chromatography-tandem mass spectrometry for the simultaneous quantification of tryptophan and a set of seven compounds spanning its metabolism through the serotonin and kynurenine pathways, in the brain of embryos and adult offspring of rat dams fed a protein-restricted (PR) diet. Protein-restricted embryos showed reduced brain levels of Trp, serotonin and KA, but not of KYN, XA, or QA. In contrast, PR adult rats exhibited enhanced levels of Trp in the brainstem and cortex along with increased concentrations of 5-HT, kynurenine and XA. The levels of XA and KA were also increased in the hippocampus of adult PR rats. These results show that early protein deficiency induces selective and long-lasting changes in brain kynurenine metabolism. Given the regulatory role of KYN pathway metabolites on brain development and function, these changes might contribute to the risk of developing psychiatric disorders induced by early malnutrition. © 2016 International Society for Neurochemistry.

  1. Melinjo (Gnetum gnemon) Seed Extract Consumption during Lactation Improved Vasodilation and Attenuated the Development of Hypertension in Female Offspring of Fructose-Fed Pregnant Rats.

    PubMed

    Uson-Lopez, Rachael A; Kataoka, Saori; Mukai, Yuuka; Sato, Shin; Kurasaki, Masaaki

    2017-09-19

    Fructose intake has been correlated with increased prevalence of metabolic disorders including hypertension. In pregnant rats, fructose intake has been reported to have adverse effects on the health of its offspring. This study investigated the effects of gestational maternal fructose consumption and if supplementation with melinjo seed extracts to the maternal diet during lactation could benefit the offspring in later life. Pregnant rats were randomly divided into three groups: untreated (CC), fructose-treated (FC), and fructose and melinjo-treated (FM). FC and FM groups received 100 g/L of D(-)-fructose solution by means of the drinking water during gestation while CC received normal drinking water. During lactation, CC and FC groups were given standard commercial laboratory diet, while the FM group was given commercial laboratory diet with 0.1% melinjo seed extracts. After weaning, the offspring were given normal drinking water and standard commercial diet until week 17. The blood pressure of the offspring was monitored until the 16th week. During week 17, the offspring were killed, and the kidneys were collected and analyzed. The level of renal phosphorylated AMP-activated protein kinase (pAMPK) in FM of 17-week female offspring was significantly higher compared with FC and CC groups. Maternal fructose intake down-regulated the renal endothelial isoform of nitric oxide synthetase expression in FC and maternal melinjo seed extract consumption maintained renal endothelial isoform of nitric oxide synthetase expression in FM of 17-week female offspring. In addition, maternal melinjo seed extract intake during lactation lowered the systolic blood pressure in FM of 17-week female offspring. Female offspring were more vulnerable to the effects of placental fructose and melinjo seed extracts, suggesting sex-specific sensitivities. In summary, our data show that melinjo seed extract consumption during lactation improved vasodilation and attenuated the development of

  2. Oral supplementation with physiological doses of leptin during lactation in rats improves insulin sensitivity and affects food preferences later in life.

    PubMed

    Sánchez, Juana; Priego, Teresa; Palou, Mariona; Tobaruela, Aixa; Palou, Andreu; Picó, Catalina

    2008-02-01

    We have previously described that neonate rats supplemented with physiological doses of oral leptin during lactation become more protected against overweight in adulthood. The purpose of this study was to characterize further the long-term effects on glucose and leptin homeostasis and on food preferences. Neonate rats were supplemented during lactation with a daily oral dose of leptin or the vehicle. We followed body weight and food intake of animals until the age of 15 months, and measured glucose, insulin, and leptin levels under different feeding conditions: ad libitum feeding, 14-h fasting, and 3-h refeeding after fasting. An oral glucose tolerance test and a leptin resistance test were performed. Food preferences were also measured. Leptin-treated animals were found to have lower body weight in adulthood and to eat fewer calories than their controls. Plasma insulin levels were lower in leptin-treated animals than in their controls under the different feeding conditions, as was the increase in insulin levels after food intake. The homeostatic model assessment for insulin resistance index was significantly lower in leptin-treated animals, and the oral glucose tolerance test also indicated higher insulin sensitivity in leptin-treated animals. In addition, these animals displayed lower plasma leptin levels under the different feeding conditions and were also more responsive to exogenous leptin administration. Leptin-treated animals also showed a lower preference for fat-rich food than their controls. These observations indicate that animals supplemented with physiological doses of oral leptin during lactation were more protected against obesity and metabolic features of the metabolic syndrome.

  3. Flaxseed flour (Linum usitatissinum) consumption improves bone quality and decreases the adipocyte area of lactating rats in the post-weaning period.

    PubMed

    Ribeiro, Danielle Cavalcante; Pereira, Aline D'Avila; da Silva, Paula Cristina Alves; dos Santos, Aline de Sousa; de Santana, Fernanda Carvalho; Boueri, Bianca Ferolla da Camara; Pessanha, Carolina Ribeiro; de Abreu, Maíra Duque Coutinho; Mancini-Filho, Jorge; da Silva, Eduardo Moreira; do Nascimento-Saba, Celly Cristina Alves; da Costa, Carlos Alberto Soares; Boaventura, Gilson Teles

    2016-01-01

    The aim of this work was to evaluate the effects of flaxseed flour in the intake on adiposity and femur structure of the lactating rats during the post-weaning period. After weaning, the lactating rats were divided into control (C, n = 6) and experimental (F, n = 6) groups treated with a diet containing flaxseed flour. Serum hormone and fatty acids composition, morphology of intra-abdominal adipocytes, computed tomography and biomechanical analyses of femur were determined. Food intake, body mass and hormone analysis have shown similar results. The F group showed the following (p < 0.05): lower arachidonic acid (-60%), total polyunsaturated fatty acids (-30%) and retroperitoneal adipocytes (-36%) area. Higher radiodensity of femoral head region (+29%) and higher maximum force (+18%), breaking strength (+18%) and rigidity (+31%). Fatty acid composition of flaxseed flour decreased the area of adipocytes and improved the bone quality, which may be associated with lower serum levels of arachidonic acid levels, during the post-weaning period.

  4. Brain docosahexaenoic acid status and learning in young rats submitted to dietary long-chain polyunsaturated fatty acid deficiency and supplementation limited to lactation.

    PubMed

    García-Calatayud, Salvador; Redondo, Carlos; Martín, Eva; Ruiz, José Ignacio; García-Fuentes, Miguel; Sanjurjo, Pablo

    2005-05-01

    N-3 fatty acid deficiency has been related to decreased docosahexaenoic acid (DHA) and increased docosapentaenoic acid (DPA) levels in brain and to learning disadvantages. The influence of n-3 deficiency and supplementation on brain fatty acids and learning were investigated in young rats. Newborn Wistar rats were assigned to three groups of cross-foster mothers. The control group (C) was nursed by mothers that received essential fatty acids during pregnancy and lactation, and the deficient group (D) was nursed by mothers that did not receive those fatty acids. The supplemental group (S) had the same conditions as D, receiving an additional DHA and arachidonic acid supplement during lactation. Cerebral cortex and hippocampus fatty acid composition was examined using thin-layer and capillary column gas chromatography, and learning was measured by passive-avoidance procedure. D brains showed low DHA and high DPA levels, but S brain composition was similar to C. Learning in the S group was unaffected, but in the D group, it was poorer than C. Learning was directly correlated with DHA levels and inversely with DPA levels in brain. Low DHA and high DPA brain levels both were correlated with poor learning. DPA seems not to be a suitable brain functional analogue of DHA, and DHA supplementation reversed both biochemical and learning adverse effects observed in n-3 deficiency.

  5. Exposure to lard-based high-fat diet during fetal and lactation periods modifies breast cancer susceptibility in adulthood in rats☆

    PubMed Central

    de Oliveira Andrade, Fábia; Fontelles, Camile Castilho; Rosim, Mariana Papaléo; de Oliveira, Tiago Franco; de Melo Loureiro, Ana Paula; Mancini-Filho, Jorge; Rogero, Marcelo Macedo; Moreno, Fernando Salvador; de Assis, Sonia; Barbisan, Luiz Fernando; Hilakivi-Clarke, Leena; Ong, Thomas Prates

    2015-01-01

    The present study investigated whether early life exposure to high levels of animal fat increases breast cancer risk in adulthood in rats. Dams consumed a lard-based high-fat (HF) diet (60% fat-derived energy) or an AIN93G control diet (16% fat-derived energy) during gestation or gestation and lactation. Their 7-week-old female offspring were exposed to 7,12-dimethyl-benzo[a]anthracene to induce mammary tumors. Pregnant dams consuming an HF diet had higher circulating leptin levels than pregnant control dams. However, compared to the control offspring, significantly lower susceptibility to mammary cancer development was observed in the offspring of dams fed an HF diet during pregnancy (lower tumor incidence, multiplicity and weight), or pregnancy and lactation (lower tumor multiplicity only). Mammary epithelial elongation, cell proliferation (Ki67) and expression of NFκB p65 were significantly lower and p21 expression and global H3K9me3 levels were higher in the mammary glands of rats exposed to an HF lard diet in utero. They also tended to have lower Rank/Rankl ratios (P=.09) and serum progesterone levels (P=.07) than control offspring. In the mammary glands of offspring of dams consuming an HF diet during both pregnancy and lactation, the number of terminal end buds, epithelial elongation and the BCL-2/BAX ratio were significantly lower and serum leptin levels were higher than in the controls. Our data confirm that the breast cancer risk of offspring can be programmed by maternal dietary intake. However, contrary to our expectation, exposure to high levels of lard during early life decreased later susceptibility to breast cancer. PMID:24746835

  6. Vitamin A supplementation in rats under pregnancy and nursing induces behavioral changes and oxidative stress upon striatum and hippocampus of dams and their offspring.

    PubMed

    Schnorr, Carlos Eduardo; da Silva Morrone, Maurílio; Simões-Pires, André; da Rocha, Ricardo Fagundes; Behr, Guilherme Antônio; Moreira, José Cláudio Fonseca

    2011-01-19

    Vitamin A is important for both development and maintenance of adult brain homeostasis. However, excessive vitamin A exposure has been linked to cognitive impairments and may induce congenital defects, including neuronal malformations. Recently, we demonstrated that vitamin A supplementation is able to alter behavioral parameters and induce a pro-oxidant state in hippocampus and striatum of adult male rat. Thus, the aim of the present work was to investigate the effects of vitamin A supplementation in pregnant and nursing rats on maternal and offspring striatum and hippocampus. Wistar female rats (7 per group) were orally supplemented with retinyl palmitate (2500, 12,500 and 25,000 IU/kg/day) or saline (control) throughout pregnancy and nursing. Homing test was performed at postnatal days (PND) 5 and 10 for offspring, while open field test (OFT) was carried out at PND19 and 20 for dams and offspring, respectively. Redox parameters were evaluated at PND21 for both. Vitamin A supplementation during pregnancy and nursing increased superoxide dismutase/catalase (SOD/CAT) ratio and oxidative damage in maternal and offspring striatum and hippocampus. Additionally, supplementation induced behavioral alterations. In conclusion, we suggest some caution regarding vitamin A intake during pregnancy and breastfeeding, since oxidative stress can disturb several biological phenomena, including neuronal signaling and neurotransmission, which may induce several behavioral deficits. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Supplementation with omega-3 fatty acids during gestation and lactation to a vitamin B12-deficient or -supplemented diet improves pregnancy outcome and metabolic variables in Wistar rats.

    PubMed

    Khaire, Amrita; Rathod, Richa; Kemse, Nisha; Kale, Anvita; Joshi, Sadhana

    2015-01-01

    Maternal vitamin B12 deficiency leads to an adverse pregnancy outcome and increases the risk for developing diabetes and metabolic syndrome in mothers in later life. Our earlier studies have demonstrated that vitamin B12 and n-3 polyunsaturated fatty acids (PUFA) are interlinked in the one carbon cycle. The present study for the first time examines the effect of maternal n-3 PUFA supplementation to vitamin B12 deficient or supplemented diets on pregnancy outcome, fatty-acid status and metabolic variables in Wistar rats. Pregnant dams were assigned to one of the following groups: control, vitamin B12 deficient, vitamin B12 supplemented, vitamin B12 deficient + n-3 PUFA or vitamin B12 supplemented + n-3 PUFA. The amount of vitamin B12 in the supplemented group was 0.50 μg kg(-1) diet and n-3 PUFA was alpha linolenic acid (ALA) 1.68, eicosapentaenoic acid 5.64, docosahexaenoic acid (DHA) 3.15 (g per 100g fatty acids per kg diet). Our findings indicate that maternal vitamin B12 supplementation did not affect the weight gain of dams during pregnancy but reduced litter size and weight and was ameliorated by n-3 PUFA supplementation. Vitamin B12 deficiency or supplementation resulted in a low percentage distribution of plasma arachidonic acid and DHA. n-3 PUFA supplementation to these diets improved the fatty-acid status. Vitamin B12 deficiency resulted in higher homocysteine and insulin levels, which were normalised by supplementation with either vitamin B12 or n-3 PUFA. Our study suggests that maternal vitamin B12 status is critical in determining pregnancy outcome and metabolic variables in dams and that supplementation with n-3 PUFA is beneficial.

  8. Single oral dose toxicity test of polycalcium, a mixed composition of polycan and calcium lactate-gluconate 1:9 (G/G) in SD rat.

    PubMed

    Kim, Joo-Wan; Choi, Jae-Suk; Ha, Yu-Mi; Choi, In Soon; Kim, Ki-Young; Cho, Hyung-rae; Rha, Chae-hun; Ku, Sae-Kwang

    2013-11-01

    The object of this study was to obtain acute oral toxicity information of Polycalcium, a mixed composition of Polycan and Calcium lactate-gluconate 1:9 (g/g), in Sprague-Dawely (SD) rats. In order to investigate the toxicity and identify target organs, Polycalcium were once orally administered to female and male SD rats at dose levels of 2000, 1000, 500 and 0 (control) mg/kg body weights. The mortality, changes on body weight and clinical signs were monitored during 14 days after treatment with gross observation, changes on the organ weights and histopathology of principle organs and treatment sites based on the recommendation of KFDA Guidelines [2009-116, 2009]. As the results of single oral treatment of Polycalcium, no treatment related mortalities were observed within 14 days after end of treatment up to 2000 mg/kg, the limited dosage of rodents in the both genders. In addition, no Polycalcium treatment related changes on the body and organ weights, clinical signs, necropsy and histopathological findings were detected. The results obtained in this study suggest that the Polycalcium is non-toxic in rats. The LD50 and approximate LD in rats after single oral dose of Polycalcium were considered over 2000 mg/kg in both female and male, respectively.

  9. Increased litter size and suckling intensity inhibit KiSS-1 mRNA expression in rat arcuate nucleus

    Pu