Perinatal Testosterone Exposure and Maternal Care Effects on the Female Rat's Development and Sexual Behaviour

Abstract

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.

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“…Two female (at least 70 days old) rats were housed in a Plexiglas mating cage (22 × 23 × 45 cm) with a single male for seven days, after which both females were transferred into a standard cage and pair-housed for another week. For Experiment 1, vaginal smears were collected (with 0.9% saline) daily during the seven-day mating period, and the day of sperm detection was considered gestation day zero (GD 0) as previously described [27]. Females were separated at the end of the second week and single housed in standard cages with wood shavings as bedding material and allowed to give birth.…”

“…Maternal behaviors of lactating dams towards their pups were blindly scored by well-trained observers daily as initially described by Myers et al 1989 [52] and adapted and regularly used in our laboratory [27–31]. Observations occurred three times in the light cycle (1030, 1300, and 1700 h) and twice during the dark cycle (0700 and 2000 h), during 75-minute observation periods for the first 6 postnatal days (PND 1 – PND 6).…”

“…Even slight variations in maternal behavior may have an important impact on the psychological and physiological development of the young. Natural variations in maternal care in the rat are associated with differences in gene expression, in neurotransmitter and hormone release, and in behavior of the offspring [27–32]. The effects of maternal behavior on infant development persist to maturity and influence the offspring’s phenotype.…”

“…The effects of maternal behavior on infant development persist to maturity and influence the offspring’s phenotype. More specifically, lower levels of maternal licking/grooming (LG) result in early onset of puberty [27, 28], increase stress reactivity [33], influence reproductive strategy [29, 31, 33, 34], and increase alcohol self-administration [35]. Furthermore, maternal behavior has been shown to be transmitted across generations through epigenetic modification, such that female rats that have received low level of maternal care will also provide low levels of maternal care to their offspring [36, 37] Thus, maternal care in the rodent has a large impact on the offspring outcome.…”

Epigenetics and the developmental origins of vulnerability for mental disorders

“…It is nevertheless interesting to note that some of the phenotypic differences associated with variations in pup LG are only partly reversed with postnatal cross-fostering or neonatal handling (Table 25.1). These findings suggest possible in utero influences that have been confirmed at least with respect to the development of individual differences in hypothalamic-pituitary-ovarian function and sexual behavior in the female offspring (Cameron et al, 2008;Borrow et al, 2013) and metabolic function (Kappeler et al, unpublished). The differences in the HPA response to stress in the offspring of high and low LG mothers is mediated by a maternal effect on the expression of the GR gene (Nr3c1) in the hippocampus (Weaver et al, 2004, Weaver et al, 2007.…”