Combination of prenatal androgenization and high-fat diet on sexual development and adult reproductive function of female mice.

TORRES PJ; MALDONADO R; RAMÍREZ ND; PÉREZ PA; LUQUE EM; CANTARELLI V; PONZIO MF; GUTIÉRREZ S; MARTINI AC

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias; 2023

SAIC, AACYTAL, ETC

Polycystic ovary syndrome (PCOS) is frequently associated with female subfertility. Injecting dihydrotestosterone (DHT) into pregnant dams leads to a PCOS-like phenotype in the female offspring. This study aims to evaluate whether coadministration of a high-fat diet (HFD) to the pups exacerbates the effects of prenatal androgenization and modifies plasma and ovarian Ghrelin (Ghrl) levels/expression.Pups received either a control diet (CD) or a HFD (commercial pellet + 30% pork fat) from weaning. We evaluated the impact of four treatments (DHT-CD; C-CD; DHT-HFD; and C-HFD) on sexual development, adult reproductive function, and plasma/ovarian Ghrl levels/expression (measured by western blot). Statistics: ANOVA (two-way or repeated measures); n=2-8 litters/treatment.No significant differences were found in pups' weight gain. DHT delayed or even inhibited vaginal opening, with this effect being exacerbated by the HFD (% vaginal opening on postnatal day 39: DHT-HFDa=25.0, DHT-CDbc=64.3, C-HFDb=100, C-CDbd=100; p<0.05 a vs b and c vs d). In adulthood, DHT-exposed females (DHT-CD and DHT-HFD) exhibited significantly lower pregnancy rates than controls (C-CD and C-HFD); 67% vs 100%. The addition of the HFD decreased litter size, with the most pronounced effects seen in DHT-HFD females, who also displayed morphological abnormalities in their uteri. Although plasma Ghrl levels did not vary significantly (C=13.72±5.93pg/ml vs DHT=12.05±2.33pg/ml; n=9 pups/treatment), ovarian Ghrl expression tended to decrease with DHT (37.51±6.12 vs 47.49±10.10; n=6 pups/treatment) and increase with the HFD (49.25±6.72 vs 35.75±9.27; n=6 pups/treatment).Our findings highlight the adverse effects of prenatal androgenization on the sexual development and fertility of female offspring. Moreover, they shed light on the synergistic impact of a HFD, which exacerbates those effects, emphasizing the intricate interplay between hormonal factors and dietary influences in shaping reproductive outcomes