EPIGENOMIC EFFECTS OF EXPOSURE OF PREGNANT RATS TO LOW DOSE OF BISPHENOL A REGARDING THE NEUROENDOCRINE SYSTEM OF THE MALE F1 GENERATION (short communication)

Aim: To study the long-term effects of exposure of pregnant Wistar rats to low dose of bisphenol A (BPA) by measuring to the level of steroid hormones and sexual behavior of adult male offspring of the first generation. Material and research methods: BPA as part of the Dorfman gel was gavaged during the last week of pregnancy, when androgen-dependent sexual brain differentiation occurs, in a daily dose of 25 mcg/kg b.w. (threshold teratogenic dose). Male sexual behavior was evaluated by proceptive reactions, the duration of latent and refractory periods, the number of mounts, intromissions and ejaculations in the presence of a receptive female. Female sexual behavior was assessed by lordosis reactions of orchidectomized and activated by the introduction of estradiol and progesterone males in the presence of a normal male. A neuromorphological analysis of the sex-dimorphic area of the brain, the medial preoptic nucleus of the hypothalamus, was performed by histological examination and karyometry of neurons. Results: Prenatally administered BPA caused a very slight increase in the anogenital distance in newborn animals and did not affect the terms of puberty. The levels of testosterone and corticosterone in the blood plasma of males of 6 months of age did not differ from the control indices. At 10 months of age, all experimental males showed sharply weakened sexual motivation for mating with females, and in 4 from 5 animals, copulative components of sexual behavior were absent. There was no ejaculations in the 5th male as well, while numbers of the mounts without intromissions and ones with intromissions significantly reduced. In the BPA group, all descendants showed active female behavior in the presence of a normal male, which manifested in lordosis reactions and a high lordosis index. According to the histological study of medial preoptic nucleus, the activity of neurocytes in the male offspring of BPA-exposed females was significantly reduced, and their nuclei volume distribution was some different from the control. Conclusions: The data obtained indicate epigenetic disorders of the sexual brain differentiation program due to the prenatal exposure to BPA in dose that does not cause significant teratogenic effects. This should be taken into account when evaluating the potential hazard of BPA for reproductive health. Key words: bisphenol A, prenatal effect, male rats, sexual behavior, corticosterone, testosterone.

Effects of gonadectomy and androgen on neuronal plasticity in motivation and reward related brain regions in the male rat

Gonadal hormones affect neuronal morphology to ultimately regulate behavior. Here, we investigated the effect of both castration and androgen replacement on spine plasticity in the nucleus accumbens shell and core (NAcSh and NAcC), caudate putamen (CPu), medial amygdala (MeA), and medial preoptic nucleus (MPN). Intact and castrated (GDX) male rats were treated with dihydrotestosterone (DHT, 1.5mg) or vehicle (oil) in 3 experimental groups: intact-oil, GDX-oil and GDX-DHT. Spine density and morphology, measured 24 hours after injection, were determined through 3D reconstruction of DiI-labeled dendritic segments. GDX decreased spine density in the MPN, which was rescued by DHT treatment. MeA spine density increased in GDX-DHT animals compared to intact-oil animals. In the NAcSh, DHT decreased spine density, and also rapidly increased the number of pCREB+ cell bodies. These findings indicate that androgen signaling plays a role in the regulation of spine plasticity within neurocircuits involved in motivated behaviors.