Malnutrition in rats during pregnancy and lactation period: a study on body, spleen and thymus weights and hematologic parameters in dams and their offspring

Physiological changes in the rat dams and their offspring as sequelae of malnutrition during pregnancy and lactation and their capacity for recuperation from early malnutrition is studied. The dams were killed during the lactation period (15th and 30th days of postpartum) and the absolute and relative weights of the thymus and spleen were recorded. The following hematologic parameters were examined: red blood cell count, hemoglobin, hematocrit, mean cell volume, mean cell homoglobin, mean cell hemoglobin concentration, white blood cell count, lymphocytes, monocytes, eosinophils, polimorphonuclear neutrophil, basophils. The offspring were sacrificed at 15, 30 and 90 days of age. Their body weight and the same hematic parameters and organ weights as their mothers were determined. Results indicate a highly significant decrease in body weight and organ weights in experimental dams and an important alteration in their hematic parameters, which may be an important determinant of retardation of growth in pups, whose body and organ weights were significantly smaller than those of the controls. In addition, the hematologic parameters of the malnourished offspring were modified in relation to those of the controls at all times (15, 30 and 90 days old) studied.     

Maternal melatonin influences rates of somatic and reproductive organs postnatal development of male rat offspring

Female rat dams, housed in 12L:12D photoperiod, were pinealectomized or injected daily 1(1/2) h before onset of darkness with 250 mg melatonin/100 g BW., during pregnancy; control and pinealectomized dams received a placebo. Somatic, reproductive organs and gonadotropins levels luteinizing hormone (LH) and follicle stimulating hormone (FSH) of male offspring were examined at the following phases of their sexual development: neonate, infantile, juvenile or prepubertal and pubertal periods. Pinealectomy of the mother produced an altered developmental pattern in the offspring (PIN-X offspring). During the infantile period when pups are lacking maternal melatonin and their own melatonin rhythm is not yet established, a delayed growth of body and testis weights was observed. After the second week of life, from 15 to 25 days of age, coinciding with the initiation of the melatonin rhythm, a speed-up growth of body and testes was observed, followed by a delayed growth from 25 to 30 days, in the juvenile period; this also coinciding with reduced LH levels observed at 30 days of age. Indeed, in PIN-X offspring significantly greater growth rate was observed during the pubertal period than in control offspring, which could be due to the increase in LH secretion up to normal values observed in the PIN-X offspring. Seminal vesicles of the PIN-X offspring also showed delayed growth, which was overcome at the pubertal period. Melatonin (MEL) treatment during pregnancy produced minor alterations in postnatal development of the reproductive tract. Only increased pituitary gland weight was observed at 15 and decreased at 25 days of age. At 25 days of age, MEL offspring reached the highest LH values, and at 30 days of age, PIN-X offspring still show low values. Which suggests that other factors than the endocrine activity of the gland are affecting the somatic growth of the pituitary gland. Seminal vesicles weight was delayed at 25 days of age in the MEL offspring. These results indicate that maternal melatonin is necessary for a normal somatic growth and postnatal development of reproductive organs of the offspring.     

Effects of hypergravity exposure on plasma oxytocin concentration in pregnant and lactating rat dams

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.     

Brain Maturation Following Administration of Phenobarbital, Phenytoin, and Sodium Valproate to Developing Rats or to Their Dams: Effects on Synthesis of Brain Myelin and Other Subcellular Membrane Proteins

Abstract: The anticonvulsant drugs phenobarbital, phenytoin, sodium valproate, and phenytoin-sodium valproate in combination were administered daily to (a) pregnant rats starting on the 5th day after conception, and continued through 17 days postpartum, or (b) to developing rats between 3 and 17 days of age. Each drug was prepared in water and administered at either a therapeutic dose (TD), three times therapeutic dose (³TD), or 9TD. Drug administration had no discernible effect on litter size or sex ratio in the offspring; however, phenobarbital administration to dams caused small but significant reductions in birth weights. Body weights of developing rats treated with anticonvulsant drugs either via dams or directly by intraperitoneal injection lagged behind controls. At 20–24 days of age the brain weights of the offspring of phenobarbital (9TD)-exposed dams lagged control weights by 5% whereas brain weights in the offspring of the other treated groups were indistinguishable from controls. In contrast, administration of phenobarbital directly to developing rats caused no significant brain weight deficits whereas significant deficits were observed with phenytoin (9TD), sodium valproate (9TD), and phenytoin-sodium valproate (9TD) in combination. At 20–24 days of age the relative incorporation of radioactive leucine into purified myelin and crude nuclear proteins of drug-treated rats or the offspring of drug-treated dams was reduced by 10–20% in all cases. Dose-related differences were not observed however, and the effects of phenytoin and sodium valproate in combination approximated those of phenytoin administered alone.     

Influence of chlormadinone acetate on hypothalamic differentiation in male rats

The effect of chlormadinone acetate on adult male rats during the hypothalamic differentiation phase was studied. Psychic intersexuality with increased male and increased female sexual behavior was observed both before and after postpuberal castration and sex hormone replacement. Organ weights of testes, seminal vesicles, and ventral prostrates were normal, but penis and adrenal gland weights were significantly smaller. Body growth was also significantly reduced compared with control animals. The effects of chlormadinone acetate on androgen-dependent brain differentiation are discussed and compared with analogous effects of cyproterone acetate and orchidectomy.     

Results of the negative control chemical allyl alcohol in the 15-day intact adult male rat screening assay for endocrine activity

Development, standardization, and validation of methods to assess the potential of chemicals to disrupt hormonal homeostasis have been the focus of considerable research efforts over the past 10 years. As part of our validation effort, we evaluated the specificity of the 15-day intact adult male rat assay, using a negative control chemical, allyl alcohol, a known hepatotoxicant that was not expected to induce endocrine effects. Male rats were dosed for 15 days via oral gavage with 0, 10, 30, 40, or 50 mg/kg/day allyl alcohol. The endpoints evaluated included final body and organ weights, serum hormone concentrations, and a limited histopathology assessment. No mortality or adverse clinical signs were observed. Mean final body weight for rats in the 50-mg/kg/day dose group was decreased to 90% of control. Mean relative liver weights were increased at 40 and 50 mg/kg/day (115% and 117% of control, respectively). Serum testosterone and DHT concentrations were statistically significantly decreased at 50 mg/kg/day (72% of control). Serum prolactin concentrations were statistically significantly decreased at 40 mg/kg/day (58% of control), but not at 50 mg/kg/day. There were no effects on the other endpoints evaluated. Consistent with previous guidance for interpreting the 15-day intact adult male rat assay, histological and weight changes of target organs were given a higher weight-of-evidence than changes in serum hormone concentrations alone. Therefore, with only minimal changes in serum hormone concentrations and no effects on organ weights or microscopic alterations, the results of allyl alcohol in the 15-day intact adult male rat assay were considered negative and consistent with the predicted results.     

孕期低氧应激对子代雄性大鼠性行为的影响

目的:研究孕期低氧应激对子代雄性大鼠的繁殖行为及相关激素分泌的影响。方法:实验将配对获得的怀孕第14天的母鼠随机分为3组:对照组(Control)、3300m模拟高原低氧应激组和5000m模拟高原低氧应激组,实验组母鼠放入低氧舱中进行持续7天的模拟低氧应激处理,对照组在实验条件下常规饲养。结果:孕期经低氧应激子代雄性性成熟个体具有与雌性个体交配的能力,但是行为能力有不同程度的下降。同时,应激组个体肛阴距变短,血浆睾酮水平下降而皮质酮水平显著升高,而3组动物睾酮、附睾以及肾上腺指数间无显著差异。结论:出生前受到低氧应激对子代雄性个体的性行为能力产生持久的抑制影响。     

Maternal obesity at conception programs obesity in the offspring

Risk of obesity in adult life is subject to programming during gestation. To examine whether in utero exposure to maternal obesity increases the risk of obesity in offspring, we developed an overfeeding-based model of maternal obesity in rats utilizing intragastric feeding of diets via total enteral nutrition. Feeding liquid diets to adult female rats at 220 kcal/kg(3/4) per day (15% excess calories/day) compared with 187 kcal/kg(3/4) per day for 3 wk caused substantial increase in body weight gain, adiposity, serum insulin, leptin, and insulin resistance. Lean or obese female rats were mated with ad libitum AIN-93G-fed male rats. Exposure to obesity was ensured to be limited only to the maternal in utero environment by cross-fostering pups to lean dams having ad libitum access to AIN-93G diets throughout lactation. Numbers of pups, birth weight, and size were not affected by maternal obesity. Male offspring from each group were weaned at postnatal day (PND)21 to either AIN-93G diets or high-fat diets (45% fat calories). Body weights of offspring from obese dams did not differ from offspring of lean dams when fed AIN-93G diets through PND130. However, offspring from obese dams gained remarkably greater (P < 0.005) body weight and higher % body fat when fed a high-fat diet. Body composition was assessed by NMR, X-ray computerized tomography, and weights of adipose tissues. Adipose histomorphometry, insulin sensitivity, and food intake were also assessed in the offspring. Our data suggest that maternal obesity at conception leads to fetal programming of offspring, which could result in obesity in later life.     

Effects of Maternal Exposure to Piperonyl Butoxide (PBO) on Behavioral Development in F1‐Generation Mice

Female mice were exposed maternally to piperonyl butoxide (PBO) through diet to provide dietary levels of 0% (control), 0.01%, 0.03%, and 0.09% during gestation and lactation periods, and selected reproductive and neurobehavioral parameters were measured in the F₁ generation. There was no adverse effect of PBO on litter size, litter weight, or sex ratio at birth. The average body weights of male offspring decreased significantly in dose‐related manners on postnatal days (PNDs) 0, 4, 7, and 14 (p = 0.0019, 0.0096, 0.033, and 0.038, respectively) during the lactation period. In female offspring, the average body weights decreased in dose‐related manners on PNDs 0, 4, 7, and 14 (p = 0.0027, 0.0104, 0.0193, and 0.0062, respectively). The survival of dams slightly decreased (p = 0.0209) in the high‐dose group during the lactation period. With respect to behavioral developmental parameters, surface righting on PND 7 of male and female offspring was delayed significantly in a dose‐related manner (p < 0.001 in each). Swimming direction on PND 7 of male offspring was delayed significantly in a dose‐related manner (p < 0.01), and for female offspring it was delayed significantly in the high‐dose group (p < 0.05). Swimming head angle on PND 7 of male offspring was delayed significantly in a dose‐related manner (p < 0.05). Spontaneous behavior examination in males indicated that rearing increased in the high‐dose group in the F₁ generation. The dose levels of PBO in the present study produced some adverse effects in neurobehavioral parameters in mice     

Prevention of diet-induced obesity and impaired glucose tolerance in rats following administration of leptin to their mothers

Absence of leptin is known to disrupt the development of energy balance regulatory mechanisms. We investigated whether administration of leptin to normally nourished rats affects energy balance in their offspring. Leptin (2 mg.kg(-1).day(-1)) was administered from day 14 of pregnancy and throughout lactation. Male and female offspring were fed either on chow or on high-fat diets that elicited similar levels of obesity in the sexes from 6 wk to 15 mo of age. Treatment of the dams with leptin prevented diet-induced increases in the rate of weight gain, retroperitoneal fat pad weight, area under the intraperitoneal glucose tolerance curve, and fasting plasma insulin concentration in female offspring. In the male offspring, the diet-induced increase in weight gain was prevented and increased fat pad weight was reduced. Energy intake per rat was higher in response to the obesogenic diet in male offspring of saline-treated but not leptin-treated dams. A similar trend was seen in 3-mo-old female offspring. Energy expenditure at 3 mo of age was higher for a given body weight in female offspring of leptin-treated compared with saline-treated dams when these animals were fed on the obesogenic diet. A similar trend was seen for male rats fed on the obesogenic diet. Thus leptin levels during pregnancy and lactation can affect the development of energy balance regulatory systems in their offspring.     

The impact of prenatal circadian rhythm disruption on pregnancy outcomes and long-term metabolic health of mice progeny

Animal studies demonstrate that circadian rhythm disruption during pregnancy can be deleterious to reproductive capacity and the long-term health of the progeny. Our previous studies in rats have shown that exposure of pregnant dams to an environment that significantly disrupts maternal circadian rhythms programs increased adiposity and poor glucose metabolism in offspring. In this study, we used mice with a ClockΔ19 mutation to determine whether foetal development within a genetically disrupted circadian environment affects pregnancy outcomes and alters the metabolic health of offspring. Ten female ClockΔ19+MEL mutant mice were mated with 10 wildtype males, and 10 wildtype females were mated with 10 ClockΔ19+MEL mutant males. While genetically identical, the heterozygote foetuses were exposed to either a normal (wildtype dams) or disrupted (ClockΔ19+MEL mutant dams) circadian environment during gestation. Pregnancy outcomes including time to mate, gestation length, litter size and birth weight were assessed. One male and one female offspring from each litter were assessed for postnatal growth, body composition, intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test at 3 and 12 months of age. There was no effect of maternal genotype on pregnancy outcomes, with days to plug, gestation length, litter size and perinatal mortality not significantly different between wildtype and ClockΔ19+MEL mutant dams. Similarly, there was no effect of maternal genotype on weight of the offspring at birth or at any stage of postnatal growth. While there was an effect of sex on various tissue weights at 3 and 12 months of age, there were minimal effects of maternal genotype. Relative adrenal weight was significantly reduced (?32%) in offspring from ClockΔ19+MEL mutant dams, whereas gastrocnemius muscle was significantly increased (+16%) at 3 months of age only. Intraperitoneal glucose tolerance tests at 3 months of age revealed female offspring from ClockΔ19+MEL mutant dams had significantly reduced area under the curve following glucose administration (?25%), although no differences were found at 12 months of age. There was no effect of maternal genotype on intraperitoneal insulin tolerance at 3 or 12 months of age for either sex. These results demonstrate that foetal growth within a genetically disrupted circadian environment during gestation has no effect on pregnancy success, and only marginal impacts upon the long-term metabolic health of offspring. These results do not support the hypothesis that circadian rhythm disruption during pregnancy programs poor metabolic homeostasis in offspring. However, when maintained on a 12L:12D photoperiod, the ClockΔ19+MEL mutant dams display relatively normal patterns of activity and melatonin secretion, which may have reduced the impact of the mutation upon foetal metabolic programming.     

Effects of olive, corn, sesame or peanut oil on the body weights and reproductive organ weights of immature male and female rats.

Olive, corn, sesame or peanut oil which have been used as vehicles in the immature rat uterotrophic assay or Hershberger assay, for detection of endocrine disrupting effects of environmental chemicals, was administered to ten immature female rats by subcutaneous injection from postnatal day (PND) 21 for 3 or 7 days, and each oil was also administered to ten male rats from PND 21 for 7 and 10 days. The body weights, and the weights of sex and sex accessory organs in female and male rats were measured. There were no significant differences in body weights of female rats between each oil group and the control group, while the body weight of male rats in the group given peanut or olive oil was significantly increased from 8 or 9 days after administration. There were no changes in the sex and sex accessory organ weights of female or male rats related to the endocrine disrupters. The results of the body weights and organ weights demonstrate that each oil is a suitable vehicle for the immature rat uterotrophic assay. However, each oil is suggested to be unsuitable for the Hershberger assay, because the analysis of changes of sex accessory organ weights in this assay might be confused by the increased body weights.     

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.     

Maternal treatment with oleoyl-estrone induces resistance to lipid accrual in their descendants

Objective: To determine whether treatment of rat dams with oleoyl‐estrone (OE) has an effect on the offspring's long‐term response to diet restriction during lactation. Methods and Procedures: Control, OE‐treated, and diet‐restricted dams were treated up to day 15 of lactation. Changes in food intake and body weight were recorded for dams and their pups. After weaning, pups received a 4‐week standard diet followed by a 4‐week period of high‐fat diet. Lipid, protein, and energy content of pups plus energy intake and efficiency. Serum metabolites (glucose, urea, and cholesterol) and serum hormones (adiponectin, leptin, insulin, and sexual hormones). Results: Neither pups from dams in the OE‐treated nor in the diet‐restricted group showed significant changes in weight, though these two groups ingested 79% of food ingested by controls. At weaning, the pups from OE‐treated rats were smaller than those of the control or diet‐restricted groups. These pups maintained the differences in size and lipid content during the 4‐week standard‐diet period, whereas pups from diet‐restricted dams showed a sharp decrease in their lipid content. During the 4 weeks of high‐fat diet, the male offspring from OE‐treated dams increased the difference in lipid content in relation to the pups from control dams whereas in females the differences decreased. Female offspring from diet‐restricted dams showed the most marked changes in metabolite and hormone levels in relation to controls. Discussion: Treatment of lactating dams with OE programs the metabolic response of their offspring to resist the challenge of a high‐fat diet that would lead to obesity in adulthood.     

Food deprivation and leptin prioritize ingestive and sex behavior without affecting estrous cycles in Syrian hamsters

Energy consumption is critical for the energetically expensive processes related to reproduction, and thus, mechanisms that increase ingestive behavior are directly linked to reproductive success. Similarly, the mechanisms that inhibit hunger and ingestive behavior might be most adaptive when these mechanisms cause individuals to stop foraging, hoarding and eating in order to find and court potential mates. In the laboratory, ingestive behaviors are typically studied separately from reproductive behaviors even though it is likely that these behaviors evolved under conditions in which both food and mates were available. We examined the choice between paracopulatory and ingestive behaviors in a semi-natural environment in which both food and potential mates were available. Intact female Syrian hamsters showed a high preference for males on days 3 and 4 (day 4 being the day of ovulation and estrous behavior), and a 48-h period of food deprivation significantly decreased preference for sex and increased preference for eating and food hoarding on day 3 in 89% of the hamsters, although none became anestrous. The same period of food deprivation significantly decreased the level of vaginal marking without significant effects on plasma estradiol concentrations. Next, hamsters were either food deprived (FD) or fed ad libitum, and half of each group was treated with vehicle or the adipocyte hormone leptin. The percentage of females with a low preference for sex was significantly greater in the FD compared to the ad libitum-fed groups, and leptin treatment prevented this effect. Metabolic fuels, possibly acting through leptin and other hormones, might influence sensitivity to estradiol or enhance the downstream effects of estradiol, thereby increasing motivation for sex and decreasing the relative motivation to forage, hoard and eat food.     

Food-restricting first generation juvenile female hamsters (Mesocricetus auratus) affects sex ratio and growth of third generation offspring

Female hamsters (Generation 1) were fed ad libitum or were food-restricted to 65-75% of the amount consumed by controls during their first 50 days of life. Subjects were mated at 91 days of age. Their offspring (Generation 2) were fed ad libitum throughout the experiment, and female offspring were also mated at 91 days of age. Generation 3 litters were monitored every fifth day from birth until Day 25 post partum for litter size, sex ratio, and pup weights. Although there were no significant differences in Generation 3 litter sizes at birth, litters descended from food-restricted Generation 1 females (Group R) were significantly smaller on Days 5-25 than litters descended from control Generation 1 females (Group A). Sex ratios remained significantly greater in Group A than in Group R litters from birth to Day 25 but did not vary over time, suggesting similar post-partum mortality rates for both male and female pups. Weights of Generation 3 male and female pups did not vary significantly within treatments at any time. Group A males weighed significantly more than Group R males from birth through Day 25, but weights of Group A and Group R females were always similar. Food restriction early in life may have long-term consequences on sex ratios of subsequent generations in hamsters.     

High post-partum levels of corticosterone given to dams influence postnatal hippocampal cell proliferation and behavior of offspring: A model of post-partum stress and possible depression

Post-partum stress and depression (PPD) have a significant effect on child development and behavior. Depression is associated with hypercortisolism in humans, and the fluctuating levels of hormones, including corticosterone, during pregnancy and the post-partum, may contribute to PPD. The present study was developed to investigate the effects of high-level corticosterone (CORT) post-partum in the mother on postnatal neurogenesis and behavior in the offspring. Sprague-Dawley dams were treated with either CORT (40 mg/kg) or sesame oil injections daily for 26 days beginning the day after giving birth. Dams were tested in the forced swim test (FST) and in the open field test (OFT) on days 24-26 post-partum. Results showed that the dams exposed to CORT expressed "depressive-like" behavior compared to controls, with decreased struggling behavior and increased immobility in the FST. To investigate the effects of treatment on hippocampal postnatal cell proliferation and survival in the offspring, males and females from treated dams were injected with BrdU (50 mg/kg) on postnatal day 21 and perfused either 24 h (cell proliferation) or 21 days (cell survival) later. Furthermore, male and female offspring from each litter were tested in adulthood on various behavioral tests, including the forced swim test, open field test, resistance to capture test and elevated plus maze. Intriguingly, male, but not female, offspring of CORT-treated dams exhibited decreased postnatal cell proliferation in the dentate gyrus. Both male and female offspring of CORT-treated dams showed higher resistance to capture and greater locomotor activity as assessed in the open field test. As high levels of CORT may be a characteristic of stress and/or depression, these findings support a model of 'CORT-induced' post-partum stress and possibly depression and demonstrate that the offspring of affected dams can exhibit changes in postnatal neurogenesis and behavior in adulthood.     

“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.     

Neurogenesis of the cholinergic medial septum in female and male C57BL/6J mice

Sex differences exist in the structure and function of the cholinergic septo-hippocampal system throughout the lifespan of mammals. How and when these sex differences originate is unclear. Because estrogen modulates sexual differentiation of several brain regions during development and influences neurogenesis in adult mammals, we hypothesized that sexual dimorphism of the cholinergic septo-hippocampal system would extend to its neurogenesis. A birthdating agent 5'-bromo-2'-deoxyuridine (BrdU) was injected into pregnant dams on one of eight gestational days, ranging from embryonic day (E)10 to E17. The offspring were euthanized at 2 months of age, and brains were processed for BrdU and choline acetyltransferase (ChAT) immunoreactivity to label cholinergic neurons that became postmitotic on a given embryonic day and survived to adulthood. Unbiased stereology was used to compare the number of double-labeled neurons in the medial septum (MS) of female and male offspring. Cholinergic neurons in the MS were generated primarily between E11 and E14, similar to other published reports. We found sex differences in the pattern of peak neurogenesis but not in the length of neurogenesis, or in total number of neurons generated in the MS. Additionally, in adult female and male mice, we estimated the total number of cholinergic neurons using unbiased stereology and found no sex differences in the number of cholinergic neurons or in the volume of the MS in adulthood. These results suggest that sex differences noted in the function of the postnatal cholinergic septo-hippocampal system may originate from its neurogenesis.     

Prenatal stress and gender role behavior in girls and boys: a longitudinal,population study

Prenatal stress influences neural and behavioral sexual differentiation in rodents. Male offspring of stressed pregnancies show reduced masculine-typical characteristics and increased feminine-typical characteristics, whereas female offspring show the opposite pattern, reduced feminine-typical and increased masculine-typical characteristics. These outcomes resemble those seen following manipulations of gonadal hormones and are thought to occur because stress influences these hormones during critical periods of development. Research on prenatal stress and human sexual differentiation has produced inconsistent results, perhaps because studies have used small samples and assessed prenatal stress retrospectively. We related maternal self-reports of prenatal stress to childhood gender role behavior in a prospective, population study of 13,998 pregnancies resulting in 14,138 offspring. Neither stress reported during the first 18 weeks of pregnancy nor stress reported from week 19 of pregnancy to week 8 postnatal related to gender role behavior in male offspring at the age of 42 months. In female offspring, maternal reports of stress during both periods showed only small correlations with masculine-typical behavior. Although this relationship remained significant when other factors that related to stress were controlled, these other factors made larger contributions to girls' gender role behavior than did prenatal stress. In addition, in both boys and girls, older male or female siblings, parental adherence to traditional sex roles, maternal use of tobacco or alcohol during pregnancy, and maternal education all related significantly to gender role behavior. Our results suggest that prenatal stress does not influence the development of gender role behavior in boys and appears to have relatively little, if any, influence on gender role behavior in girls.