Prenatal androgenization: its impact on offspring´s development and reproductive phenotype.

TORRES PJ; RAMÍREZ ND; LUQUE EM; MARTINI AC

CORDOBA

Jornada; XXIII Jornada de Investigación de la Facultad de Ciencias Médicas; 2022

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women at reproductive age. Among others, this disorder is characterized by reproductive disorders and even, subfertility. Animal models of PCOS use androgen administration protocols in critical periods (usually prenatal), since maternal exposure to androgens is postulated as the main causal factor. In this randomized controlled study, we tested whether androgenization of pregnant female mice (F0) elicits a PCOS-like phenotype in F1 offspring.We treated female Albino Swiss (N/NIH) mice (F0; n=5-6 females/treatment) s.c. during gestational days 16.5 to 18.5, with 250 µg/day of dihydrotestosterone (DHT), vehiculized in 100 µl of sesame oil. Control females (C) received vehicle at the same regimen. Parameters evaluated in F1 were: growth and physical development, sexual maturation and, in adulthood, reproductive function. Data were analyzed using ANOVA or repeated measures ANOVA as appropriate.The female offspring of the DHT group gained more weight from birth to adulthood than C group (DHT=23.38±0.40 vs C=21.7±0.5; n=5 litters/group; p<0.05); a very similar profile was seen in the male pups, although differences were not significant. Both female and male DHT pups exhibited advanced puberty onset (vaginal opening: on postnatal days 29, 30, and 33; p<0.05 vs C; testicular descent: on postnatal day 21 vs C; p<0.05). Anogenital distance was higher in the adult female offspring from the DHT group (DHT=7.62±0.08 vs C=7.30±0.11; n=20-25 animals/group; p<0.05). Regarding sperm functional activity, the adult male offspring of the DHT group showed lower percentages of motile spermatozoa (DHT=55.44±3.12 vs C=64.18±2.69; n=17-18 males/group ; p<0.05) and lower percentages of sperm viability (DHT=92.25±0.55 vs C=94.27±0.71; n=11-12 males/group; p<0.05). The reproductive function of the female pups did not change.In conclusion, prenatal androgenization exerts programming effects that include modifications in growth, sexual maturation, and sperm function in adult males. This phenotype is similar to that of PCOS.