COMBINATION OF PRENATAL ANDROGENIZATION AND HIGH-FAT DIET ON SEXUAL DEVELOPMENT AND ADULT REPRODUCTIVE FUNCTION OF FEMALE MICE

PEDRO JAVIER,TORRES; ROCÍO, MALDONADO ; NICOLÁS DAVID, RAMÍREZ; PABLO A. PÉREZ; EUGENIA MERCEDES, LUQUE, ; VERÓNICA INÉS, CANTARELLI; MARINA FLAVIA, PONZIO; SILVINA GUTIERREZ; ANA C. MARTINI

Mar del Plata

Congreso; Reunion anual de Sociedad Argentina de Investigación Clínica; 2023

Sociedad Argentina de Investigación Clínica

Polycystic ovary syndrome (PCOS) is frequently associated with female subfertility. Theinjection of dihydrotestosterone (DHT) to pregnant dams causes in the female offspring aPCOS-like phenotype. In this study, we aim to evaluate if the coadministration of a high-fatdiet (HFD) to the pups, exacerbates the effects of prenatal androgenization, and if itmodifies plasma and ovarian Ghrelin (Ghrl) levels/expression.We studied the female offspring (F1) of F0 mice androgenized (DHT) or not (C) duringpregnancy (DHT=250µg/day at gestational days 16.5-18.5). Pups received since weaning,a control diet (CD) or a HFD (commercial pellet + 30% pork fat). Thus, the effect of fourtreatments (DHT-CD; C-CD; DHT-HFD and C-HFD) on sexual development, reproductivefunction and plasma/ovaries Ghrl levels/expression (by western blot) were evaluated. Datawere analyzed by ANAVA (two-way or repeated measures); n=2-8 litters/treatment.No differences were found in pups´ weight gain. DHT delayed, or even inhibited, vaginalopening. This effect was exacerbated by the HFD (% vaginal opening on postnatal day 39:DHT-HFD=25.0, DHT-CD=64.3, C-HFD=100, C-CD=100; p<0.05 DHT-HFD vs all andDHT-CD vs C-CD). In adulthood, DHT females (DHT-CD and DHT-HFD) showedsignificantly lower pregnancy rates than controls (C-CD and C-HFD); 67% vs 100%. Theaddition of the HFD decreased litter size, with the worst results in DHT-HFD females thatshowed also morphological abnormalities in their reproductive tract. Plasma Ghrl levels didnot vary significantly (C=13.72±5.93pg/ml vs DHT=12.05±2.33pg/ml; n=9 pups/treatment)but ovarian Ghrl expression tend to decrease with DHT (37.51±6.12 vs 47.49±10.10; n=6pups/treatment) and to increase with HFD (49.25±6.72 vs 35.75±9.27; n=6 pups/treatment).Our results show that prenatal androgenization negatively impacts on female´s offspringsexual development and fertility, and that these effects are exacerbated by thecoadministration of a HFD.