Perinatal Testosterone Research Articles

Perinatal Androgenization Prevents Age-Related Neuron Loss in the Sexually Dimorphic Nucleus of the Preoptic Area in Female Rats

To investigate the effect of perinatal testosterone exposure, which simulates the endogenous testosterone peak, on neuron loss during aging, nuclear morphology was evaluated in male and female rats as well as in female rats treated with testosterone perinatally followed by ovariectomy (TE/Ovx). Additionally, neuronal apoptosis, which occurred primarily at postnatal day 8 (PND8), was identified by in situ TUNEL staining. Neuronal density, nuclear volume, total neuronal number and pyknotic ratio were estimated after HE stain at PND8, middle age and old age. The results showed that age-related decrease in neuronal nuclear volume and total neuron number in the sexually dimorphic nucleus of the preoptic area (SDN-POA) of female rats was significantly diminished by TE/Ovx. The pyknotic ratio in the SDN-POA of female rats at PND8 was significantly higher than that of males, and neuronal death was reversed by testosterone exposure, while no significant difference of pyknotic ratios was observed among male, female and TE/Ovx female rats at both middle and old age. Moreover, the high apoptotic incidence of female rats at PND8 was significantly diminished by testosterone exposure. These results suggest that neuron loss in the SDN-POA during aging may be predominantly determined by perinatal testosterone through modulation of postnatal neuronal apoptosis.

Perinatal exposure to low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin alters sex-dependent expression of hepatic CYP2C11.

The cytochrome P450 (CYP) isoform CYP2C11 is specifically expressed in the liver of adult male rats, and 5alpha-reductase is specifically expressed in the liver of the adult female rats. The sexually dimorphic expressions of these hepatic enzymes are regulated by the sex-dependent profiles of the circulating growth hormone (GH). However, it is not well known whether hormonal imprinting or activation factors in the neonatal brain influence the sexually dimorphic expression patterns of hepatic enzymes. We therefore examined the effect of perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on sex-dependent expressions of hepatic enzymes. Pregnant rats were treated with TCDD at a dose of 0, 200, or 800 ng/kg on gestation day 15, exposing the pups to the chemical. Although the expression of CYP2C11 protein in the livers of male pups on postnatal day (PND) 49 was significantly higher than that of the controls, but the 5alpha-reductase activities in the livers of female pups were not altered by exposure to TCDD. Focusing on perinatal periods, testosterone and estrogen levels significantly increased in the brain of male pups on PND 2. The results suggest that the alteration of testosterone and estrogen levels affect hormonal imprinting in the neonatal brain of male pups, and thus induces a change in the level of male-specific hepatic CYP2C11. We conclude that perinatal exposure to TCDD at low doses may change the sexual differentiation of the neonatal brain in male rats.

Long-term effects of neonatal cryoanesthesia on hypoxic ventilatory response in weanling rats depend on neonatal testosterone.

Among the factors known to interact with the developmental plasticity of the respiratory controller network, gender and perinatal testosterone secretion have recently been described to influence the ventilatory response to acute or chronic hypoxia before puberty (Mortola et al 1996; Joseph et al 1999; Joseph et al 2000). In the present experiments, we used cryoanesthesia as a tool to perform neonatal gonadectomy to address the hypothesis that endogenous neonatal testosterone secretion in male pups could affect the hypoxic ventilatory response (HVR - 10 % O2) in weanling (20-22 day-old) male rats. We selected weaning as an age of fully mature HVR (Joseph et al 2000), while rats are still sexually immature, thus allowing to discard any effect related to endogenous secretion of adult testes (Tatsumi et al. 1994). Our findings show that cryoanesthesia by itself produces a marked decrease of HVR in weanling rats, and this effect was dependent on the neonatal testosterone secretion. Because the cryoanesthesia approach is in many ways similar to surgical processes used for arterial switch operation in human neonates (performed under cardiopulmonary bypass, cardiocirculatory arrest and deep hypothermia), our findings may be potentially relevant for long term outcomes of infants submitted to this surgical procedure.KeywordsCarotid BodyVentilatory ResponseArterial Switch OperationDeep HypothermiaHypoxic Ventilatory ResponseThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Parental Responsiveness Is Feminized after Neonatal Castration in Virgin Male Prairie Voles, but Is Not Masculinized by Perinatal Testosterone in Virgin Females

We previously found a large sex difference in the parental responsiveness of adult virgin prairie voles (Microtus ochrogaster) such that most males are spontaneously parental, whereas most females are not. Because this sex difference is independent of the gonadal hormones normally circulating in adult virgin voles, the present study examined whether perinatal hormones influence the development of this sex difference. Males were treated prenatally (via their pregnant dam) with both the androgen receptor blocker flutamide (5 mg/day/dam) and the aromatase inhibitor ATD (1 mg/day/dam), or oil, for the last 2 weeks of gestation. Half of the subjects from each group were castrated on the day of birth and the other half received a sham surgery. As adults, intact males were castrated and all males received a silastic capsule filled with testosterone. Prenatal treatment with flutamide and ATD had no effect on males' behavior toward pups, but neonatal castration significantly reduced the percentage of males acting parentally. In a second experiment, females were exposed to testosterone propionate (TP; 50 μg/day/dam) or oil via their dam during the last 2 weeks of gestation. For the first neonatal week, half of the females from each group were injected with TP (1 mg/day) and the other half oil. As adults, females were ovariectomized and half from each group received a testosterone-filled capsule and the other half received an empty capsule. None of the perinatal TP treatments increased females' parental responsiveness, although females from all groups that received testosterone capsules as adults were highly parental. Therefore, although postnatal testicular hormones are necessary for high parental responsiveness in males, the behavior of females is not influenced by perinatal exposure to testosterone.

Prenatal testosterone and luteinizing hormone levels in male rats exposed during pregnancy to 2,3,7,8-tetrachlorodibenzo-p-dioxin and diethylstilbestrol

Changes in the perinatal testosterone surge have been related to demasculinization of the central nervous system and androgen-dependent growth of the reproductive organs in male mammals. Earlier reports suggest that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) interferes with androgen production, but the perinatal effects have remained elusive. In the present study we explored in utero-effects of TCDD (0.05, 0.1, 0.5, and 1.0 μg/kg), introduced on day 13.5 of pregnancy, on prenatal (day 19.5 post-conception [p.c.]) testosterone (T) surge and pituitary luteinizing hormone (LH) production in TCDD-resistant Han/Wistar (H/W) and TCDD-sensitive Long-Evans (L-E) rats. To elucidate estrogenic effects on T and LH production, Sprague-Dawley (S-D) fetuses with previously known DES-sensitivity were exposed in utero to diethylstilbestrol (DES, 100–300 μg/kg) on days 13.5, 15.5, and 17.5 p.c. For comparison, H/W fetuses that responded to TCDD treatments were exposed to DES at concentration of 100 μg/kg. It was found that TCDD has a stimulatory effect on testicular T synthesis in the H/W fetuses and that their circulating T concentrations increased significantly. The effect was not seen in the inbred L-E fetuses, which throughout the study showed considerably low testicular T levels. Pituitary LH concentrations also increased in the H/W fetuses exposed to TCDD. Effects of TCDD (1.0 μg/kg) in the H/W fetuses could be confirmed in vitro by human chorionic gonadotropin (hCG) stimulation assay showing the highest response rate in the TCDD exposed testes. Stimulation of cyclic AMP (adenosine-3′, 5′-cyclic monophosphate[cAMP]) production was not considerably altered by in utero TCDD exposure. A significant depression in testicular and plasma T content was seen in the DES-exposed S-D and H/W fetuses, but pituitary LH levels did not alter considerably. In the presence of hCG, DES-exposed testes showed lower in vitro T and cAMP production rates compared to the untreated testes. TCDD (1.0 μg/kg) increased and DES decreased the male body weight gain, but the changes were not sex-dependent. It is concluded that TCDD may increase the amplitude of the prenatal testosterone surge in male rats by stimulating pituitary LH production and enhancing the sensitivity of the fetal testis to LH. DES, on the contrary, apparently impairs testicular steroidogenesis and pituitary function.

Role of Astroglia and Insulin-Like Growth Factor-I in Gonadal Hormone-Dependent Synaptic Plasticity

Gonadal hormones exert a critical influence over the architecture of specific brain areas affecting the formation of neuronal contacts. Cellular mechanisms mediating gonadal hormone actions on synapses have been studied extensively in the rat arcuate nucleus, a hypothalamic center involved in the feed-back regulation of gonadotropins. Gonadal steroids exert organizational and activational effects on arcuate nucleus synaptic connectivity. Perinatal testosterone induces a sexual dimorphic pattern of synaptic contacts. Furthermore, during the preovulatory and ovulatory phases of the estrous cycle there is a transient disconnection of inhibitory synaptic inputs to the somas of arcuate neurons. This synaptic remodeling is induced by estradiol, blocked by progesterone, and begins with the onset of puberty in females. Astroglia appear to play a significant role in the organizational and the activational hormone effects on neuronal connectivity by regulating the amount of neuronal membrane available for the formation of synaptic contacts and by releasing soluble factors, such as insulin-like growth factor I (IGF-I), which promote the differentiation of neural processes. Recent evidence indicates that gonadal steroids and IGF-I may interact in their trophic effects on the neuroendocrine hypothalamus. Estradiol and IGF-I promote the survival and morphological differentiation of rat hypothalamic neurons in primary cultures. The effect of estradiol depends on IGF-I, while the effects of both estradiol and IGF-I depend on estrogen receptors. Furthermore, estrogen activation of astroglia in hypothalamic tissue fragments depends on IGF-I receptors. These findings indicate that IGF-I may mediate some of the developmental and activational effects of gonadal steroids on the brain and suggest that IGF-I may activate the estrogen receptor to induce its neurotrophic effects on hypothalamic cells. In addition, IGF-I levels in the neuroendocrine hypothalamus are regulated by gonadal steroids. IGF-I levels in tanycytes, a specific astroglia cell type present in the arcuate nucleus and median eminence, increase at puberty, are affected by neonatal androgen levels, show sex differences, and fluctuate in accordance to the natural variations in plasma levels of ovarian steroids that are associated with the estrous cycle. These changes appear to be mediated by hormonal regulation of IGF-I uptake from blood or cerebrospinal fluid by tanycytes. These results suggest that tanycytes may be involved in the regulation of neuroendocrine events in adult rats by regulating the availability of IGF-I to hypothalamic neurons. In summary, IGF-I and different forms of neuron–astroglia communication are involved in the effects of estradiol on synaptic plasticity in the hypothalamic arcuate nucleus.

Androgen Spares Androgen-Insensitive Motoneurons from Apoptosis in the Spinal Nucleus of the Bulbocavernosus in Rats

The spinal nucleus of the bulbocavernosus (SNB) is a sexually dimorphic motor nucleus in the rat lumbar spinal cord. The sex difference arises through the androgenic sparing of the motoneurons and their target muscles from ontogenetic cell death. Indirect evidence suggests that androgen acts on the target muscles rather than directly on SNB motoneurons to spare them from death. The testicular feminization mutation (Tfm), a defect in the androgen receptor (AR), blocks androgenic sparing of SNB motoneurons and their targets. The pattern of AR immunocytochemistry was previously found to be different in adultTfmand wild-type rats: immunostaining was nuclear in most SNB cells of wild-type rats, but very few SNB cells display nuclear AR immunostaining in affectedTfmrats. Because theTfmmutation is carried on the X chromosome, random X inactivation during development makes female carriers ofTfm(+/Tfm) genetic mosaics for androgen sensitivity.Tfmcarriers, their wild-type sisters, and affectedTfmmales were treated with perinatal testosterone and immunocytochemistry was used to detect androgen receptor in the SNB when the rats reached adulthood. Mosaic females could be distinguished from their wild-type sisters by external morphology. In such perinatally androgenized mosaics, adult SNB cells were equally divided between wild-type andTfmgenotype, as indicated by AR immunocytochemistry. In contrast, the pattern of AR immunocytochemistry in target muscles of mosaics appeared similar to that of wild-type females. These results indicate that early androgen spared both androgen-sensitive and -insensitive motoneurons from cell death, confirming a site of androgen action other than the motoneurons themselves.

Maternal insulin manipulations in rats organize body weight and noradrenergic innervation of the hypothalamus in gonadally intact male offspring

In previous work it has been shown that adult male, but not female, offspring of rats that have been injected with protamine zinc insulin (6 IU/kg) on days 15–20 of gestation, develop significant obesity beginning about 50 days of age. This obesity is accompanied by elevated medial hypothalamic extracellular norepinephrine levels. To examine whether the expression of obesity in male offspring is mediated by perinatal testosterone levels, male offspring of insulin-treated or control dams were either castrated or received sham surgery on postnatal day 1. Castrated male offspring of insulin-treated dams did not become obese like their gonadally intact male littermates. This perinatal suggests that testosterone levels may interact with developmental processes mediating the obesity in male offspring of insulin-treated dams. A second question addressed was whether the elevated hypothalamic extracellular norepinephrine levels observed in our earlier work are evident as morphological changes in norepinephrine-containing systems in the medial hypothalamus and locus coeruleus. We found a significant enhancement of dopamine-β-hydroxylase immunoreactivity in fibers innervating the paraventricular nucleus of the hypothalamus in 121-day-old, gonadally intact male offspring of insulin-injected dams. This suggests that the impact of maternal insulin injections on offspring obesity may be mediated through its organizing action on feeding-related fibers in the paraventricular nucleus.

Sexual differentiation of odor and partner preference in the rat

Previous studies have shown that adult male rats, in which brain estrogen formation was inhibited neonatally by SC administration of the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD), show an altered sexual partner preference. When tested in a three-compartment box, such gonadally intact ATD males approach and mate both with the estrous female and the sexually active male, whereas normal males prefer to approach and mate with the estrous female, avoiding the stimulus male. After castration in adulthood and estradiol treatment, ATD males prefer sexually active males. Similarly treated normal males prefer estrous females, and estrous females prefer to mate with males. In the present study, we asked what stimulus characteristics of active males vs. estrous females determined the different sexual preferences of males, ATD males, and of females. Were they chemosensory cues or more distal cues such as actually seeing and hearing the stimulus animals or the reward of sexual activity with the stimulus animals? Sex differences in preference were evident when animals were given a choice between soiled bedding from estrous females and from sexually active males. ATD and control males spent significantly more time on soiled bedding from estrous females than on soiled bedding from sexually active males. Control females spent significantly more time on soiled bedding from sexually active males than on soiled bedding from estrous females. More distal cues, such as seeing and hearing the stimulus animals, revealed differences in preference between control males and females, but not between ATD and control males. Physical interaction with the stimulus animals was a prerequisite for revealing differences in preference between ATD and control males. Then, the behavior of ATD males was clearly intermediate between that of normal male and female rats. In conclusion, neonatal estradiol is important for the psychosexual development of the male rat. However, the present data suggest that the psychosexual development of the male rat also requires either prenatal estradiol or perinatal testosterone.

Effects of perinatal testosterone on handedness of gerbils: Support for part of the Geschwind-Galaburda hypothesis.

Effects of perinatal testosterone on handedness of gerbils: Support for part of the Geschwind-Galaburda hypothesis.

The role of glia in the neuroendocrine hypothalamus: possible implications in hormone secretion.

Recent evidence indicates that glia may play a significant role in the link between the endocrine and nervous systems. Gonadal steroids modulate astroglia morphology, differentiation and gene expression in different brain areas. Hormonal effects on glia may have important consequences for neuronal development, metabolism and activity, for the formation and plasticity of synaptic connections, and for the modulation of hypothalamic hormone release. Perinatal and adult testosterone levels modulate the expression of the specific astroglia cytoskeletal marker glial fibrillary acidic protein in the arcuate nucleus of the rat hypothalamus. These changes parallel hormonal effects on the expression of growth hormone-releasing hormone (GHRH) and the number of GHRH neurones in the arcuate nucleus. The effects of testosterone and its metabolite oestradiol on hypothalamic neurones may be dependent on the release by hypothalamic astroglia of insulin-like growth factor I, a molecule involved in the control of growth hormone secretion.

Effects of perinatal testosterone on handedness of gerbils: support for part of the Geschwind-Galaburda hypothesis.

When assuming their species-typical tripodal stance, male Mongolian gerbils (Meriones unguiculatus) use their right forepaw for support more frequently than do females. This experiment determined whether, as N. Geschwind and A. M. Galaburda (1987) have proposed, the direction of such sexually dimorphic lateral asymmetry of forelimb use is affected by perinatal exposure to testosterone (TP). It was found that male gerbils injected with TP when 4 days old were significantly less likely to rest on their right forepaw when in a tripodal stance than were their oil-injected siblings. Female gerbils injected with TP when 6 days old were more likely than oil-injected controls to use their right forepaws for support. The findings demonstrate effects of perinatal exposure to TP on handedness in gerbils and suggest that the relationship between TP exposure and asymmetrical forelimb use is not always as direct as Geschwind and Galaburda's model suggests.

Motoneurons innervating guinea pig perineal muscles are sexually dimorphic in size but not number

Sexual differentiation occurs prenatally in guinea pigs but extends into the postnatal period in rats. Steroids affect the development of two motoneuron nuclei of the rat lumbar spinal cord that innervate sexually dimorphic perineal muscles. The spinal nucleus of the bulbocavernosus (SNB) innervates the bulbocavernosus (BC) and levator ani (LA) muscles while the dorsolateral nucleus (DLN) innervates the ischiocavernosus (IC). In male rats, perinatal testosterone prevents degeneration of these muscles and results in a sex difference in both motoneuron size and number in adulthood. For comparative purposes, we examined the guinea pig motoneurons innervating these muscles, as well as those innervating the retractor penis (RP) and retractor clitoris (RC), muscles that have no counterpart in rats. Injections of horseradish peroxidase localized the BC LA and IC motoneurons of guinea pigs to discrete columns in spinal levels L6 and S1, with the BC LA motoneurons occupying a more medial position. The RP RC motoneurons were found in L5. Motoneuronal soma area was larger in males in all examined motor pools, as was nuclear area of BC LA and IC motoneurons. Although raw counts suggested a sex difference in cell number in the motor columns containing BC LA and IC motoneurons, either of two different correction procedures for split nuclei error eliminated the sex difference in cell number, emphasizing the importance of such corrections when comparing neurons of different size.

Changes in the neonatal gonadal hormonal environment prevent behavioral sparing and alter cortical morphogenesis after early frontal cortex lesions in male and female rats.

The effects of perinatal exposure to testicular hormones were studied in male and female rats given medial prefrontal lesions (PFC) on Postnatal Day 7. Hormonally intact rats with PFC lesions showed recovery of performance of the Morris water task but no recovery on a forelimb reaching task. Recovery was abolished in both males gonadectomized at birth and in females given testosterone at birth. Male rats with PFC lesions showed an increase in pyramidal cell spine density. This was blocked in gonadectomized animals. In contrast, female rats with PFC lesions showed an increase in dendritic arbor. This was reduced by perinatal testosterone. Interference with the gonadal hormonal environment reduced the brain's ability to compensate for the effects of early cortical lesions.

Regulation of arcuate nucleus synaptology by estrogen.

Estrogen modulates the synaptology of the hypothalamic arcuate nucleus during sexual differentiation of the rat brain in both males and females. In males, testosterone of gonadal origin is converted to estrogen in the brain by an enzyme, aromatase, which is also present in females. The exposure of the male's hypothalamus to relatively high levels of estrogen (following a perinatal testosterone surge) leads to the development of a pattern of synaptogenesis which does not support an estrogen-induced gonadotrophin surge in the adult. In female rats, hypothalamic development occurs with permissively low levels of estrogen, enabling a midcycle estrogen-induced gonadotrophin surge and ovulation in adulthood. During adult reproductive life in female rats, circulating estrogen modulates the synaptology of the arcuate nucleus. The most physiological example of this is the 30-50% loss of axosomatic synapses following the preovulatory estrogen surge on diestrus-proestrus. Studies on post-synaptic membranes of the arcuate nucleus reveal sex differences in membrane organization and protein content which are estrogen-dependent. Estrogen apparently stimulates endocytosis of areas of post-synaptic membrane that are dense with small intramembranous protein particles, resulting in a reduction in the number of small intramembranous particles. This also appears to be the physiologic mechanism of neuronal changes in females during the estrus cycle. Repeated exposure to preovulatory levels of estrogen may lead to an age-related decline in reproductive capacity in female rats. Aging females lose the estrogen-induced gonadotrophin surge responsible for ovulation. This loss of function may result from a cumulative estrogen effect during the repeated ovarian cycles which results in a reorganization of the synaptology on which regulates the estrogen-induced gonadotrophin surge. The membrane organization of the senescent constant estrus aged female appears indistinguishable from the males. The hypothalamic circuits modulated by estrogen have yet to be delineated. However, recent research has shown that GABA, the monoamines, and several neuropeptides are participants in the estrogen-sensitive network which regulates GNRH secretion. In this regard, present work shows estrogen-induced changes in GABA and dopamine synapses in the arcuate nucleus.

Reproductive and no reproductive responsiveness to photoperiod in laboratory rats

Laboratory rats (Rattus norvegicus) have been traditionally considered nonphotoperiodic because reproductive function is unaffected by day length. However, at least three experimental manipulations of rats--perinatal androgen injection, peripubertal androgen implants, and peripubertal olfactory bulbectomy--have been reported to unmask reproductive responsiveness to photoperiod. The physiological means by which early testosterone treatment or olfactory bulbectomy affect the expression of photoperiodism were hypothesized to operate through similar underlying mechanism(s) that involved gonadotropin and prolactin blood levels. Short day lengths reduce blood levels of gonadotropins in so-called photoperiodic rodent species. Reduced prolactin levels result in virtually all reproductively photoperiodic species housed in short day lengths. In Experiment 1, male weanling rats either were olfactory-bulbectomized or received a sham-procedure and housed for 10 weeks in long (LD 16:8) or short (LD 8:16) days. Short-day rats reduced body mass, testicular sperm counts, and the size of their reproductive systems; olfactory bulbectomy amplified this inhibitory effect for some parameters including testicular and epididymal sperm counts. However, neither short days nor olfactory bulbectomy affected blood titers of follicle stimulating hormone (FSH) or prolactin. Pelage density was also unaffected by photoperiod, but rats retained their juvenile fur color; i.e., short-day rats remained white, but long-day rats became yellowish. In Experiment 2, male rats were injected with testosterone at 3 days of age, then housed in long or short days until 10 weeks of age. Day length alone did not affect any experimental parameter measured in Experiment 2 except fur color; again, short-day rats retained their juvenile fur color.(ABSTRACT TRUNCATED AT 250 WORDS)

Prenatal testosterone differentiates brain regions controlling gonadotropin release in guinea pigs.

Sexual differentiation of behavior and gonadotropin release in short-gestation mammalian species is affected by perinatal testosterone (T). Differentiation of dimorphic behaviors in two long-gestation species (guinea pigs and rhesus macaques) depends upon prenatal androgen exposure. The brain areas mediating gonadotropin release are not sexually differentiated in nonhuman primates, but similar information is not available for the guinea pig. To obtain new information on this subject, we treated pregnant guinea pigs with testosterone propionate (TP; 2.5, 5, or 10 mg/day) or vehicle (control) on Days 30-39 of gestation and 1.0 mg/day of TP on Days 40-55 of gestation. The length of gestation in this strain (Topeka) ranges from 66 to 73 days. We evaluated permanent treatment effects on gonadotropin release by challenging adult guinea pigs with 10 micrograms estradiol benzoate (EB, s.c.) 2 wk after gonadectomy. Serial serum samples were analyzed for LH by RIA. Control females (70.6%) released LH in surge quantities 40.1 +/- 0.7 h (mean +/- SEM, n = 24) after EB treatment. Prenatal T treatment in utero significantly decreased the number of EB-induced LH surges observed in adult females (0 of 5, 2.5 mg TP; 0 of 10, 5 mg TP; 0 of 7, 10 mg TP). No LH surges were induced by EB in any of the males. The postgonadectomy LH rise was 50 and 75% lower (p < 0.01) in females treated with 5 and 10 mg TP, respectively, than in other groups. Four days after the EB challenge, animals were infused with a bolus of GnRH (1 microgram/kg BW), and serial blood samples were taken.(ABSTRACT TRUNCATED AT 250 WORDS)

Hippocampal mossy fiber distributions in mice selected for aggression

The sizes of the hippocampal intra- and infrapyramidal mossy fiber terminal fields (IIPMF) of mice from two lines bidirectionally selected for attack latency were measured. Aggressive males possess smaller IIPMF than do non-aggressive ones. We hypothesize that both differences in aggression and sizes of the IIPMF may be mediated by perinatal testosterone.

Decreased postnatal testosterone surge in male rats exposed to ethanol during the last week of gestation.

Prenatal alcohol exposure in the rat is known to interfere with the neurobehavioral sexual differentiation of the male brain. Because normal sexual differentiation of the male brain requires adequate levels of perinatal testosterone, we examined the effect of prenatal ethanol exposure on (1) the postnatal surge of testosterone and (2) the in vitro secretion of testosterone in response to luteinizing hormone (LH) stimulation of testes from fetal alcohol exposed (FAE) animals and controls. Sprague-Dawley dams were administered a fortified liquid diet containing 35% ethanol-derived calories, a pair-fed (PF) isocaloric liquid diet, or given ad libitum access to dry lab chow (CF). Dams were administered the liquid diets from days 7 or 14 through parturition. The postnatal surge of testosterone in FAE males was studied only in animals exposed to ethanol from day 14 through parturition. In the first experiment, FAE and PF males and females were delivered by cesarean section on day 22 of gestation (E22) and trunk blood collected at 0, 60, 120, and 240 min after parturition. Experiment 2 measured plasma testosterone in male pups that were killed at 0, 60, 120, 240, 360, and 480 min after delivery. Results showed that the postnatal testosterone surge of FAE males in both experiments was significantly attenuated compared with PF controls. No effect of prenatal ethanol was observed in female offspring. Female testosterone levels were several fold lower than male littermates, and no evidence of a postnatal testosterone surge was observed. Production of testosterone from testes was studied using an automated perifusion system.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered adult sexual behavior in the male rat following chronic prenatal hypoxia

The last week of gestation is a critical period for the sexual differentiation of the brain in the rat. Exposure to prenatal stress during this period has been shown to demasculinize and/or feminize adult male sexual behavior. Many of the neurochemical and endocrine responses to hypoxia are similar to that observed under stressful conditions such as restraint stress. Therefore, we examined the postnatal consequences on reproductive and nonreproductive sexually dimorphic behaviors in male offspring of dams exposed to chronic hypoxia during the last week of gestation. In addition, we examined sensorimotor development in offspring of both sexes. Pregnant Sprague-Dawley dams were exposed to continuous hypoxia (10.5% O 2 from gestational day 15 to 21). Offspring were weaned at 22 days of age and group housed. Behavioral tests were conducted with littermate representatives. In adulthood, male rats prenatally exposed to hypoxia had significantly delayed initiation latencies of masculine sexual behavior and decreased number of ejaculations, but did not display a significant increase in feminine sex behavior potentials. Developmentally, animals exposed to prenatal hypoxia did not differ significantly from controls with respect to day of eye or ear opening, or the in times of righting reflex, negative geotaxis or cliff avoidance. Wire hanging latencies in hypoxic exposed animals were significantly greater than controls around the time of eye opening, but did not differ at earlier or later ages. A significant effect of hypoxia was detected on stride length at 95 days of age, but other aspects of gait patterns were similar to controls. No group differences in gait patterns were observed at 17 or 45 days of age. In addition, no significant differences were observed in open field activity, circadian locomotor activity, saccharin preference, or Morris water maze test. This hypoxia regimen did not influence the occurrence of the prenatal or postnatal surge of plasma testosterone. Overall, these results provide some evidence that, in males, mild, chronic prenatal hypoxia may result in incomplete masculinization of adult reproductive behavior in the absence of overt changes in perinatal testosterone surges.