Perinatal testosterone exposure and maternal care effects on the female rat's development and sexual behaviour.

Natural variations in maternal care have profound influences on offspring behaviour, brain activity and hormone release. Measuring the amount of time that a rat dam spends licking/grooming (LG) her pups during their first week of life allows for characterisation of distinctive Low, Mid and High LG phenotypes. We have previously found that female offspring of High LG mothers are less sexually receptive, less motivated to mate and show a later onset of puberty relative to Low LG offspring. Given that High LG females are exposed to greater levels of testosterone in utero, we hypothesise that differences in sexual behaviour between High and Low LG female offspring are driven in part by differences in prenatal hormone exposure. To test this hypothesis, pregnant dams pre-characterised as Low, Mid, or High LG mothers were implanted with testosterone or placebo on gestational day (GD) 16. Offspring body weight and anogenital index were assessed at GD 21 and in adulthood. Age of vaginal opening and oestrous cyclicity were assessed to determine the timing of pubertal onset. Testosterone exposure removed the difference between LG phenotypes in pubertal onset by delaying vaginal opening and the appearance of first pro-oestrus. In adulthood, sexual behaviour in a paced mating chamber after sham surgery or ovariectomy with steroid-replacement was examined. Our findings show that Low, Mid and High LG female offspring are differentially affected by perinatal testosterone exposure, and that this exposure removes the precocial pubertal onset of Low LG offspring and increases the sexual proceptivity and receptivity of High LG offspring. These results suggest that maternal programming of the female reproductive system may be mediated, in part, through differences in perinatal testosterone exposure, instead of solely through maternal behaviour.

Variation in maternal care influences ventromedial hypothalamus activation in the rat.

Natural variation in maternal care in the rat is an important source of individual differences in the female neuroendocrine system and sexual behaviours. Thus, females reared by low licking and grooming (LG) mothers are sexually more receptive to males, showing higher lordosis ratings, and are more motivated to mate compared to female offspring of high LG mothers. In the present study, we investigated the effect of natural variations in maternal care on the ventrolateral part of the ventromedial hypothalamus (VMHvl) cell population and on the reproductive success of the female rat. Immunohistochemistry for phosphorylated oestrogen-receptor (pER) α and progesterone receptor (PR) were used to study the VMHvl of female offspring of high and low LG mothers at pro-oestrus and dioestrus. A second experiment investigated sexual behaviour and the effect of mating on c-Fos expression in the VMHvl of pro-oestrus and ovariectomised high and how female offspring. Lastly, we investigated the maternal effect on the establishment of the progestational state. A greater number of VMHvl pERα immunoreactive cells was found in the pro-oestrous female offspring of low LG mothers and PR was most abundant at pro-oestrus compared to dioestrus in both high and low LG females. Interestingly it is the less receptive high females that show the greater c-Fos expression in the VMH after mating in the pro-oestrous group. The difference in c-Fos expression after mating disappeared when the two groups were ovariectomised and received steroid replacement. Finally, low LG female offspring reached pseudopregnancy more often when receiving only seven intromissions at a 5-min interval compared to high LG females. Lower levels of maternal care may favour the reproductive success of low LG offspring by increasing pERα and oestrogen-dependent lordosis behaviour and lowering c-Fos after mating, resulting in inhibition of termination of oestrus.

Epigenetic programming of phenotypic variations in reproductive strategies in the rat through maternal care.

Studies across multiple organisms reveal considerable phenotypic variation in reproductive tactics. In some species, this variation is associated with maternal effects in which variation in maternal investment results in stable individual differences in reproductive function. Recent studies with the rat suggest that maternal effects can alter the function of neuroendocrine systems associated with female sexual behaviour as well as maternal behaviour. These maternal effects appear to be mediated by epigenetic modifications at the promoter for oestrogen receptor alpha (ERalpha) and subsequent effects on gene expression. The tissue-specific nature of such effects may underlie the co-ordinated variation in multiple forms of reproductive function, resulting in distinct reproductive strategies.

Fos expression after mating in noradrenergic cells of the A1 and A2 areas of the medulla is altered by adrenalectomy.

In the female rat, the integrity of the ventral noradrenergic bundle (VNAB) is necessary to carry stimuli from the uterine cervix and vagina to brain areas involved in mating-induced pseudopregnancy. Because adrenal hormones are known to alter noradrenergic function, we examined whether adrenalectomy altered mating-induced Fos expression in the A1 and A2 noradrenergic cell groups that project through the VNAB. Ovariectomized females were adrenalectomized (ADX) or sham-operated (Sham) and, 2 weeks after surgery, were given oestrogen and progesterone and mated. They received 15 intromissions, five intromissions or 15 mounts-without-intromission (mounts-only) from a male. Two hours after mating, rats were perfused and brains were collected; controls were perfused after being taken directly from their home cage. After immunocytochemical staining, Fos-immunoreactive (Fos-IR) and dopamine-beta-hydroxylase-immunoreactive (DBH-IR) cells and the percentage of DBH cells that were labelled with Fos (% DBH/Fos) were counted. In the A1 area, Fos-IR and percentage DBH/Fos were not affected by adrenalectomy. Although an overall effect of mating treatment was found for both measures, no specific mating treatment increased labelled cells above home cage levels. In the caudal, middle and rostral A2, 15 intromissions induced a significant increase in Fos-IR in Sham females above all other groups and a higher percentage of DBH/Fos in the middle and rostral A2 areas. ADX females showed no rise in either Fos-IR or percentage DBH/Fos after 15 intromissions. However, in the middle and rostral A2, ADX females showed significantly increased Fos-IR and percentage DBH/Fos after mounts-only treatment above Sham mounts-only females and all other ADX groups. These results demonstrate that adrenal hormones suppress activation of A2 cells to mounts-only stimuli but contribute to A2 activation in response to intromissions from males. The latter effect may result from stress associated with receipt of vaginocervical stimulation during mating.