Prenatal testosterone exposure and intergenerational developmental alterations: contribution of paternal and maternal effects

SILVANA FERREIRA; ALICIA BEATRIZ MOTTA; GISELLE ADRIANA ABRUZZESE; AIME FLORENCIA SILVA; MARÍA JOSÉ FERRER

Virtual

Congreso; 18 th Annual Meeting of Androgen Excess and PCOS Society.; 2020

Androgen Excess and PCOS Society

Prenatal androgen exposure is known to affect females´ reproductive and metabolic parameters, leading to phenotypes that resemble those of Polycystic Ovary Syndrome (PCOS). It has been proposed that prenatal androgen exposure may also alter males. In the past years, special attention has been given to the possibility of inter- and transgenerational effects of pathologies associated with developmental programming phenomena. In PCOS, a family aggregation of the syndrome has been reported, although genetic factors could not wholly account for the inheritance. This study aimed to investigate the impact of prenatal testosterone exposure and the maternal and paternal contribution to intergenerational effects on newborns development.Pregnant females (F0) were treated daily on gestational days 16 to 19 with 1mg of testosterone. A control group was daily injected with vehicle in the same window. The offspring from androgenized mothers were the prenatally hyperandrogenized (PH) group, and those from mothers injected with vehicle were the control group (C). Previous results from our lab showed that this treatment affects both female and male reproductive outcomes of the PH group. At adulthood, female(f) and male(m) offspring (F1) weight, glucose tolerance test and anogenital-distance were assessed. Also, the fertility rate was evaluated. For this, PH and C males and females were mated with healthy counterparts. Three groups were established from F1 breeding: CfxCm, PHf x Cm and Cf x PHm. During pregnancy, maternal glucose and weight were evaluated. One group was evaluated at 14 days of pregnancy, and embryo weight and embryo crown-rump length were assessed, and the placenta area and uterine weight were evaluated. Another group was evaluated after delivery, offspring (F2) parameters (anogenital distance, weight, and length) were analyzed until postnatal day (PND) 6.No differences were found in body weight of F1 at adulthood. PHf showed an altered glucose tolerance and increased anogenital distance as compared to Cf. Fertility studies revealed no alterations in the mating index, and the fecundity and fertility indexes of PH breeding as compared to control breeding. However, PHf showed an increase in the time to mating as compared to controls. Bodyweight gain during pregnancy showed no differences between the three groups of breeding. PHf showed an increase in basal glucose levels on day 14 of pregnancy. Regarding F2, we found no differences in embryos´ weight. However, embryos from PHm fathers showed an increased embryo crown-rump length compared to the control group´s offspring. On PND 3, F2 offspring from PHf mothers showed a decrease in body weight. On PND 6, F2 offspring of both PHf mothers and PHm fathers showed a decrease in body weight. Offspring from PHf also showed a decrease in body length in females and males and a decreased anogenital distance in females. No differences were found regarding the proportion of females to males born. In conclusion, our results suggest that prenatal androgen exposure affects not only the exposed generation but also the development of the subsequent generation. In conclusion, the F2 offspring of the PH group showed an altered body weight at birth in dams from both PHm and PHf. More alterations were detected in offspring from PHf. Our results suggest that prenatal androgen exposure affects not only the exposed generation but also the development of the subsequent generation.