Chronic corticosterone during pregnancy and postpartum affects maternal care, cell proliferation and depressive-like behavior in the dam

Stress during pregnancy and the postpartum can influence the well-being of both the mother and her offspring. Prolonged elevated levels of glucocorticoids are associated with depression and we developed an animal model of postpartum depression/stress based on high levels of corticosterone (CORT) during the postpartum. Gestational stress is a risk factor for postpartum depression and prenatal and/or postnatal high levels of CORT may have differential effects on the mother. Thus the present study was conducted to investigate the effects of low (10 mg/kg) or high levels of CORT (40 mg/kg) given to dams either during gestation, postpartum or across both gestation and postpartum on maternal care, depressive-like behavior and hippocampal cell proliferation in the dam. Only the high dose of CORT administered during the postpartum increased depressive-like behavior in the dam. Furthermore the high dose of CORT altered maternal care (reduced time spent on the nest and nursing) regardless of whether administration of CORT was during gestation or postpartum. Gestational and/or postpartum treatment with high CORT and postpartum low CORT reduced cell proliferation in the dentate gyrus of postpartum dams compared to oil-treated controls. Thus prolonged treatment with high levels of CORT postpartum reduced maternal care, hippocampal cell proliferation and induced depressive-like behavior in the dam and therefore might be considered an animal model of postpartum depression. More research is needed to understand the effects of stress hormones during different phases of reproduction and how they affect the brain and behavior of the mother and her offspring.     

Chronic corticosterone during pregnancy and postpartum affects maternal care,cell proliferation and depressive-like behavior in the dam

Stress during pregnancy and the postpartum can influence the well-being of both the mother and her offspring. Prolonged elevated levels of glucocorticoids are associated with depression and we developed an animal model of postpartum depression/stress based on high levels of corticosterone (CORT) during the postpartum. Gestational stress is a risk factor for postpartum depression and prenatal and/or postnatal high levels of CORT may have differential effects on the mother. Thus the present study was conducted to investigate the effects of low (10 mg/kg) or high levels of CORT (40 mg/kg) given to dams either during gestation, postpartum or across both gestation and postpartum on maternal care, depressive-like behavior and hippocampal cell proliferation in the dam. Only the high dose of CORT administered during the postpartum increased depressive-like behavior in the dam. Furthermore the high dose of CORT altered maternal care (reduced time spent on the nest and nursing) regardless of whether administration of CORT was during gestation or postpartum. Gestational and/or postpartum treatment with high CORT and postpartum low CORT reduced cell proliferation in the dentate gyrus of postpartum dams compared to oil-treated controls. Thus prolonged treatment with high levels of CORT postpartum reduced maternal care, hippocampal cell proliferation and induced depressive-like behavior in the dam and therefore might be considered an animal model of postpartum depression. More research is needed to understand the effects of stress hormones during different phases of reproduction and how they affect the brain and behavior of the mother and her offspring.     

Distribution and Speciation of Arsenic by Transplacental and Early Life Exposure to Inorganic Arsenic in Offspring Rats

The amount of arsenic compounds was determined in the liver and brain of pups and in breast milk in the pup's stomach in relation to the route of exposure: transplacental, breast milk, or drinking water. Forty-eight pregnant rats were randomly divided into four groups, each group was given free access to drinking water that contained 0, 10, 50, and 100 mg/L NaAsO₂ from gestation day 6 (GD 6) until postnatal day 42 (PND 42). Once pups were weaned, they started to drink the same arsenic-containing water as the dams. Contents of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and trimethylarsenic acid (TMA) in livers and brains of the pups on PND 0, 15, 28, and 42 and breast milk taken from the pup's stomach on PND 0 and 15 were detected using the hydride generation atomic absorption spectroscopy method. Concentrations of iAs, MMA, and DMA in the breast milk, the brain, and the liver of the pups increased with the concentration of arsenic in drinking water on PND 0, 15, 28, and 42. Compared to the liver or brain, breast milk had the lowest arsenic concentrations. There was a significant decrease in the levels of arsenic species on PND 15 compared to PND 0, 28, or 42. It was confirmed that arsenic species can pass through the placental barrier from dams to offspring and across the blood–brain barrier in the pups, and breast milk from dams exposed to arsenic in drinking water contains less arsenic than the liver and brain of pups.     

Maternal LPS Exposure during Pregnancy Impairs Testicular Development,Steroidogenesis and Spermatogenesis in Male Offspring

Lipopolysaccharide (LPS) is associated with adverse developmental outcomes including embryonic resorption, fetal death, congenital teratogenesis and fetal growth retardation. Here, we explored the effects of maternal LPS exposure during pregnancy on testicular development, steroidogenesis and spermatogenesis in male offspring. The pregnant mice were intraperitoneally injected with LPS (50 µg/kg) daily from gestational day (GD) 13 to GD 17. At fetal period, a significant decrease in body weight and abnormal Leydig cell aggregations were observed in males whose mothers were exposed to LPS during pregnancy. At postnatal day (PND) 26, anogenital distance (AGD), a sensitive index of altered androgen action, was markedly reduced in male pups whose mothers were exposed to LPS daily from GD13 to GD 17. At PND35, the weight of testes, prostates and seminal vesicles, and serum testosterone (T) level were significantly decreased in LPS-treated male pups. At adulthood, the number of sperm was significantly decreased in male offspring whose mothers were exposed to LPS on GD 13–17. Maternal LPS exposure during gestation obviously diminished the percent of seminiferous tubules in stages I–VI, increased the percent of seminiferous tubules in stages IX–XII, and caused massive sloughing of germ cells in seminiferous tubules in mouse testes. Moreover, maternal LPS exposure significantly reduced serum T level in male mice whose mothers were exposed to LPS challenge during pregnancy. Taken together, these results suggest that maternal LPS exposure during pregnancy disrupts T production. The decreased T synthesis might be associated with LPS-induced impairments for spermatogenesis in male offspring.     

Effects of Maternal Diet and Exercise during Pregnancy on Glucose Metabolism in Skeletal Muscle and Fat of Weanling Rats

Obesity during pregnancy contributes to the development of metabolic disorders in offspring. Maternal exercise may limit gestational weight gain and ameliorate these programming effects. We previously showed benefits of post-weaning voluntary exercise in offspring from obese dams. Here we examined whether voluntary exercise during pregnancy influences lipid and glucose homeostasis in muscle and fat in offspring of both lean and obese dams. Female Sprague-Dawley rats were fed chow (C) or high fat (F) diet for 6 weeks before mating. Half underwent voluntary exercise (CE/FE) with a running wheel introduced 10 days prior to mating and available until the dams delivered; others remained sedentary (CS/FS). Male and female pups were killed at postnatal day (PND)19 and retroperitoneal fat and gastrocnemius muscle were collected for gene expression. Lean and obese dams achieved similar modest levels of exercise. At PND1, both male and female pups from exercised lean dams were significantly lighter (CE versus CS), with no effect in those from obese dams. At PND19, maternal obesity significantly increased offspring body weight and adiposity, with no effect of maternal exercise. Exercise significantly reduced insulin concentrations in males (CE/FE versus CS/FS), with reduced glucose in male FE pups. In males, maternal obesity significantly decreased muscle myogenic differentiation 1 (MYOD1) and glucose transporter type 4 (GLUT4) mRNA expressions (FS vs CS); these were normalized by exercise. Maternal exercise upregulated adipose GLUT4, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1α) mRNA expression in offspring of dams consuming chow. Modest voluntary exercise during pregnancy was associated with lower birth weight in pups from lean dams. Maternal exercise appeared to decrease the metabolic risk induced by maternal obesity, improving insulin/glucose metabolism, with greater effects in male than female offspring.     

Effects of In utero environment and maternal behavior on neuroendocrine and behavioral alterations in a mouse model of prenatal trauma

Maternal posttraumatic stress disorder (PTSD) following trauma exposure during pregnancy is associated with an increased risk of affective disorders in children. To investigate the mechanisms by which prenatal trauma and/or maternal PTSD affect brain development and behavior we established a mouse model of prenatal traumatic (PT) experience based on the application of an electric foot shock to C57Bl/6N female mice on the gestational day 12 during their pregnancy. The model is based on a previously validated animal model of PTSD. We found high anxiety levels and poor maternal care along with reduced serum prolactin and increased corticosterone levels in dams following maternal trauma (MT). PT‐pups were born smaller and stayed smaller throughout their life. We show increased time and frequency of ultrasonic calls in PT‐pups when separated from the mothers on the postnatal day (PND) 9. Cross‐fostering experiments reveal lower anxiety levels in PT pups raised by healthy mothers as compared to trauma‐naive pups raised by MT‐dams. Importantly, the combination of prenatal trauma and being raised by a traumatized mother leads to: (1) the highest corticosterone levels in pups, (2) longest USV‐call time and (3) highest anxiety levels in comparison to other experimental groups. Our data indicates a distinct change in maternal care following MT which is possibly associated with trauma‐induced decrease in prolactin levels. Furthermore, we show that maternal behavior is crucial for the development of the offspring anxiety and specific aspects in maternal care overwrite to a significant extend the effects of in utero and postnatal environment. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1254–1265, 2016     

Lead-exposure of neonatal rats through maternal milk

Lead-exposed neonatal rats are frequently used as a model for plumbism in children. In most studies,PPb is administered to the dam, and it is assumed that the pups are exposed to Pb primarily from the dam's milk. Rat pups, however, are coprophagic and begin to consume the maternal feces in their second postnatal week. This experiment was designed to determine whether the maternal feces are a significant source of Pb in pups exposed via the lactating dam. Dams were administered Pb as lead acetate (PbAc), either through their drinking water (500 ppm PbAc) or through twice daily intubations (3 mg PbAc/Kg body wt) from postpartum d 1 (P1) to P21 (P0=day of birth). Control dams were administered deionized water. The dams were housed with their litters in stainless-steel hanging cages with wire-screened bottoms. Litters of exposed and control dams treated through their drinking water had access to either Pb-containing or Pb-free maternal fecal matter for 2 h/d during the late lactation period. Half of the litters from intubated dams had continuous access to maternal feces throughout the lactation period, whereas access was curtailed at P14 in the other litters. Lead content of the feces from Pb-exposed dams ranged from 1000 to 5000 μg Pb/g wet wt. At P21, Pb concentrations were 2–4 times higher in blood, brain, bone, and liver of pups that had access to Pb-contaminated feces than in pups that were exposed to Pb primarily through the mother's milk. When estimating exposure levels in pups receiving Pb through the lactating dam, coprophagy and the high content of Pb in the dam's feces must be taken into consideration.     

Different uptake and handling of oleoyl-estrone by fetuses and neonatal rats.

To determine whether oleoyl-estrone can be transferred from mothers to their offspring either during pregnancy or lactation, a gavage of tracer dose of (3)H-Oleoyl-estrone was given to 21-day pregnant rats and to lactating rats on day 15 after delivery. In pregnant rats, the label was found in maternal blood as well as in liver and fetal serum, the latter showing the highest specific activity observed. In lactating rats, oleoyl-estrone label was found both in the mammary gland and maternal serum; in the pups, label was found in their stomach contents (i.e., clotted milk) and serum. The results suggest that the placenta effectively blocks the passage of oleoyl-estrone to the fetuses probably because of its high esterase activity. On the other hand, oleoyl-estrone is easily transferred from dams to pups, as a component of milk.     

Perinatal exposure of rats to a maternal diet with varying protein quantity and quality affects the risk of overweight in female adult offspring

The maternal protein diet during the perinatal period can program the health of adult offspring. This study in rats evaluated the effects of protein quantity and quality in the maternal diet during gestation and lactation on weight and adiposity in female offspring. Six groups of dams were fed a high-protein (HP; 47% protein) or normal-protein (NP; 19% protein) isocaloric diet during gestation (_G) using either cow's milk (M), pea (P) or turkey (T) proteins. During lactation, all dams received the NP diet (protein source unchanged). From postnatal day (PND) 28 until PND70, female pups (n=8) from the dam milk groups were exposed to either an NP milk diet (NPM_W) or to dietary self-selection (DSS). All other pups were only exposed to DSS. The DSS design was a choice between five food cups containing HPM, HPP, HPT, carbohydrates or lipids. The weights and food intakes of the animals were recorded throughout the study, and samples from offspring were collected on PND70. During the lactation and postweaning periods, body weight was lower in the pea and turkey groups (NP_G and HP_G) versus the milk group (P<.0001). DSS groups increased their total energy and fat intakes compared to the NPM_W group (P<.0001). In all HP_G groups, total adipose tissue was increased (P=.03) associated with higher fasting plasma leptin (P<.05). These results suggest that the maternal protein source impacted offspring body weight and that protein excess during gestation, irrespective of its source, increased the risk of adiposity development in female adult offspring.     

Effects of prolactin deficiency during the early postnatal period on the development of maternal behavior in female rats: Mother's milk makes the difference

During early life, prolactin (PRL) ingested by the pups through the milk participates in the development of neuroendocrine, immunological and reproductive systems. The present study tested whether a deficiency in PRL in the dam's milk during early lactation affected the offspring in terms of the maternal responsiveness in the sensitization paradigm and behavioral response to a novel environment in the offspring. Thus, lactating rats were injected (sc) on postnatal days (PND) 2–5 with bromocriptine (125 μg/day), bromocriptine + ovine PRL (125 μg + 300 μg/day), or vehicle. As juveniles (at PND 24) or adults (PND 90–100), one female from each litter was exposed to 5 foster pups continuously for 8 days and their maternal responsiveness was recorded. Female offspring were also tested in an open field arena. Adult, but not juvenile, female offspring of bromocriptine-treated mothers showed an increased latency to become maternal, in comparison to latencies displayed by the offspring of control mothers. Furthermore, the proportion of adult, but not juvenile, offspring of bromocriptine-treated mothers that became maternal was lower than that showed by the offspring of vehicle-treated mothers. In comparison to female offspring of vehicle-treated mothers, female offspring of bromocriptine-treated mothers spent less time hovering over the pups (as juvenile females), body licking (as both juvenile and adult females), and in close proximity to pups (as adult females) during the maternal behavior test. Simultaneous administration of ovine PRL and bromocriptine reversed almost all the negative effects of bromocriptine. These data suggest that maternally-derived PRL participates during the early postnatal period in the development of neural systems that underlie the control of maternal behavior.     

“Green odor” inhalation by stressed rat dams reduces behavioral and neuroendocrine signs of prenatal stress in the offspring

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.     

Acute embryonic exposure to corticosterone alters physiology,behaviour and growth in nestlings of a wild passerine

Maternally-derived glucocorticoids can modify the normal development of young animals. To date, little is known about maternal effects that are mediated by acute embryonic exposure to glucocorticoids. In birds, elevated maternal transmission of corticosterone (CORT) to egg albumen is mainly dependent on acute stress. In this study, we increased CORT levels in the egg albumen of a wild passerine, the great tit (Parus major), breeding in favourable deciduous and less suitable coniferous habitat. Subsequently we measured the somatic growth, baseline and acute glucocorticoid responses, immunity and behaviour of prenatally manipulated offspring with respect to control siblings. We found that prenatally CORT-exposed nestlings had lower baseline CORT levels, a more rapid decline in CORT during recovery from a standardized stressor, and a reduced heterophil/lymphocyte ratio compared with controls. Although stress-induced total CORT levels remained unchanged, free CORT levels were significantly lower and the levels of corticosteroid binding globulins (CBG) significantly higher in experimental offspring. Prenatally CORT-exposed offspring begged longer after hatching than controls. Stress-induced behavioural activity of fledglings did not differ between treatments, while its association with baseline CORT levels was significant in the control group only. The body mass and tarsus length of fledglings was positively affected by manipulation in unfavourable coniferous habitat only. We conclude that maternal effects related to elevated levels of albumen CORT modify diverse aspects of offspring phenotype and potentially increase offspring performance in resource poor environments. Moreover, our results indicate that maternal glucocorticoids may suppress the effect of hormones on behavioural responses.     

Chronic hypoxia exposure during pregnancy is associated with a decreased active nursing activity in mother and an abnormal birth weight and postnatal growth in offspring of rats

Stress during pregnancy is known to have a significant impact on animal's behavior and offspring development. The effects of gestational hypoxia on maternal behavior have not been studied. In the present study, we investigated the effects of gestational hypoxia exposure on dam's maternal behavior, offspring's growth and plasma corticosterone levels after parturition in rats. Altitude hypoxia (3 and 5 km) was simulated in the hypobaric chambers during the last week of pregnancy and the effects were compared to those found in controls exposed at sea level. We found that gestational hypoxia significantly decreased dam's arched-back nursing activity across the lactation period. The effect was more profound in 5 km group. Gestational hypoxia also altered other maternal behaviors such as blanket and passive nursing. Hypoxia exposure was associated with abnormal birth weight and postnatal growth in pups, with a significantly higher and lower birth weight than control found in 3 and 5 km groups, respectively, and accelerated growth in both stressed groups. Gestational hypoxia exposure significantly elevated plasma corticosterone levels in dams at the time of weaning and in pups across the measurement days. Taken together, the present results indicate that hypoxia, particularly severe hypoxia during the late phase of pregnancy has a significantly adverse impact on animal's behavior, endocrine function and offspring development. The higher birth weight found in the offspring of 3 km group suggests a compensatory system counteracting with the inhibitory effects of hypoxia on fetus growth at this altitude.     

Lactational performance, consummatory behavior, and suppression of estrous cyclicity in rats suckling underfed pups

The role of pups' appetite in the regulation of maternal consummatory behavior (food intake of nursing mothers), lactational performance and postpartum diestrus was studied over a period of 45 days postpartum in rats chronically exposed to either underfed or normally fed pups. Experimental rats (n = 10) daily received 5 pups, 4-10-days-old, that had been deprived of food for the preceding 24 h while under the care of nonlactating foster mothers. Control rats (n = 10) received normally fed pups obtained daily from lactating foster mothers. Throughout the experimental period, the daily milk yield (estimated by litter weight gain), the intake of food and water by the mother, as well as the ratio of litter weight gain to mother's intake of food and water were all markedly higher in rats nursing underfed pups than in rats nursing normally fed pups. After a peak in lactation around Day 15 postpartum, experimental rats produced the same amount of milk during extended lactation as they did in the beginning of lactation, while control rats produced only half the amount of milk during extended lactation as they did in early lactation. Regardless of the nutritional state of the suckling pups, maternal body weight increased progressively over the first four weeks of lactation and remained unchanged during the time of extended lactation. The postpartum diestrus and the subsequent diestrous phase in the time of extended lactation were considerably longer in duration in rats that nursed underfed pups. On Day 45 of lactation, prolactin levels were higher and the adrenal glands were larger in experimental rats than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Maternal LPS Exposure during Pregnancy on Metabolic Phenotypes in Female Offspring

It is increasingly recognized that intra-uterine growth restriction (IUGR) is associated with an increased risk of metabolic disorders in late life. Previous studies showed that mice exposed to LPS in late gestation induced fetal IUGR. The present study investigated the effects of maternal LPS exposure during pregnancy on metabolic phenotypes in female adult offspring. Pregnant mice were intraperitoneally injected with LPS (50 µg/kg) daily from gestational day (GD)15 to GD17. After lactation, female pups were fed with standard-chow diets (SD) or high-fat diets (HFD). Glucose tolerance test (GTT) and insulin tolerance test (ITT) were assessed 8 and 12 weeks after diet intervention. Hepatic triglyceride content was examined 12 weeks after diet intervention. As expected, maternal LPS exposure during pregnancy resulted in fetal IUGR. Although there was an increasing trend on fat mass in female offspring whose dams were exposed to LPS during pregnancy, maternal LPS exposure during pregnancy did not elevate the levels of fasting blood glucose and serum insulin and hepatic triglyceride content in female adult offspring. Moreover, maternal LPS exposure during pregnancy did not alter insulin sensitivity in adipose tissue and liver in female adult offspring. Further analysis showed that maternal LPS exposure during pregnancy did not exacerbate HFD-induced glucose tolerance and insulin resistance in female adult offspring. In addition, maternal LPS exposure during pregnancy did not aggravate HFD-induced elevation of hepatic triglyceride content in female adult offspring. In conclusion, LPS-induced IUGR does not alter metabolic phenotypes in adulthood.     

Gestational and Early Postnatal Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants: General Toxicity and Skeletal Variations

Brominated flame retardants (BFRs) are stable environmental contaminants known to exert endocrine‐disrupting effects. Developmental exposure to polybrominated diphenyl ethers (PBDEs) is correlated with impaired thyroid hormone signaling, as well as estrogenic and anti‐androgenic effects. As previous studies have focused on a single congener or technical mixture, the purpose of the current study was to examine the effects of gestational and early postnatal exposure to an environmentally relevant mixture of BFRs designed to reflect house dust levels of PBDEs and hexabromocyclododecane on postnatal developmental outcomes. Pregnant Sprague‐Dawley rats were exposed to the PBDE mixture from preconception to weaning (PND 21) through the diet containing 0, 0.75, 250, and 750 mg mixture/kg diet. BFR exposure induced transient reductions in body weight at PND 35 in male and from PND 30–45 in female offspring (250 and 750 mg/kg). Liver weights (PND 21) and xenobiotic metabolizing enzyme activities (PND 21 and 46) were increased in both male and female offspring exposed to 250 and 750 mg/kg diets. Furthermore, serum T4 levels were reduced at PND 21 in both,male and female offspring (250 and 750 mg/kg). At PND 21, Serum alkaline phosphatase (ALP) was decreased in males exposed to 750 mg/kg dietat, and females exposed to 250 and 750 mg/kg diets. At PND 46 ALP was significantly elevated in males (250 and 750 mg/kg). Variations in the cervical vertebrae and phalanges were observed in pups at PND 4 (250 and 750 mg/kg). Therefore, BFR exposure during gestation through to weaning alters developmental programming in the offspring. The persistence of BFRs in the environment remains a cause for concern with regards to developmental toxicity     

Fish oil supplementation of maternal rats on an n-3 fatty acid-deficient diet prevents depletion of maternal brain regional docosahexaenoic acid levels and has a postpartum anxiolytic effect

Docosahexaenoic acid (DHA) and arachidonic acid (AA) are the major polyunsaturated fatty acids (PUFA) in the neuronal membrane. Most DHA and AA accumulation in the brain occurs during the perinatal period via placenta and milk. This study examined whether maternal brain levels of DHA and AA are depleted during pregnancy and lactation due to meeting the high demand of the developing nervous system in the offspring and evaluated the effects of the reproductive cycle on serotonin metabolism and of fish oil (FO) on postpartum anxiety. Pregnant rats were fed during pregnancy and lactation with a sunflower oil-based n-3 PUFA-deficient diet without or with FO supplementation, which provided 0.37% of the energy source as n-3 PUFA, and the age-matched virgin rats were fed the same diets for 41 days. In both sets of postpartum rats, decreased DHA levels compared to those in virgin females were seen in the hypothalamus, hippocampus, frontal cortex, cerebellum, olfactory bulb and retina, while AA depletion was seen only in the hypothalamus, hippocampus and frontal cortex. Serotonin levels were decreased and turnover increased in the brainstem and frontal cortex in postpartum rats compared to virgin rats. FO supplementation during pregnancy and lactation prevented the decrease in maternal brain regional DHA levels, inhibited monoamine oxidase-A activity in the brainstem and decreased anxiety-like behavior. We propose that the reproductive cycle depletes maternal brain DHA levels and modulates maternal brain serotonin metabolism to cause postpartum anxiety and suggest that FO supplementation may be beneficial for postpartum anxiety in women on an n-3 PUFA-deficient diet.     

Effects of neonatal paternal deprivation or early deprivation on anxiety and social behaviors of the adults in mandarin voles

This study examined whether neonatal paternal deprivation (PD: father was removed and pups were raised just by mother) or early deprivation (ED: pups were raised by both parents except separated from not only the dam but also the peers for three hours a day from PND 0 to 13) has long-term effects on anxiety and social behaviors of adult mandarin voles. Newborn mandarin voles of F2 generation were randomly assigned to one of three groups: bi-parental care (PC: pups were raised by both parents), PD and ED. The parental care behaviors of F1 generation were observed at the age of 0, 13 and 21 days (PND 0, 13, 21) of F2 generation of PC and PD groups. Moreover, each mandarin vole of F2 generation received an open field test and a social interaction test on PND 70 and PND 75, respectively. No significant differences of parental behavior were observed between mothers and fathers from PC families, showing typical parental behavior of socially monogamous rodents. In addition, no significant differences of maternal behaviors were found between mothers from PC and PD families, indicating no maternal compensation towards pups for the absence of the paternal care. In the open field test, mandarin voles from both PD and ED families displayed higher levels of anxiety and lower locomotor activity, relative to offspring of PC family. In the social interaction test, both PD and ED mandarin voles also showed lower levels of social behavior and higher levels of anxiety. Thus, both PD and ED significantly increase anxiety and reduce social behavior of adult mandarin voles, suggesting that variation in parental investment may lead to variation in anxiety and social behaviors in rodents with different mating systems.     

The effects of stress on plasma ACTH and corticosterone in young and aging pregnant rats and their fetuses

Compared to younger rats, old rats exhibit prolonged elevations of plasma ACTH and corticosterone (CORT) in response to stress. In addition, CORT crosses the placenta. To investigate whether fetuses of older rats may be exposed to higher concentrations of CORT during development than fetuses of young rats, we compared the effects of stress on hypothalamic-pituitary-adrenal (HPA) axis function in young and aging pregnant rats and their 19-day-old fetuses. The plasma of the mothers and fetuses was assayed for ACTH and CORT by radioimmunoassay. Both young and aging pregnant rats showed a significant increase in plasma ACTH and CORT immediately after exposure to stress. However, aging rats had more prolonged elevations of ACTH and CORT than young rats. This suggests that, like old male rats, aging pregnant rats have an alteration in feedback inhibition of the HPA axis. Prolonged elevation of CORT was also seen in fetuses of aging mothers. These results have important implications concerning the effects of stress during pregnancy at different maternal ages, and for the potential deleterious consequences of prolonged prenatal elevation in stress hormones on the offspring of aging females.