Effects of the combination of prenatal androgenization and a high-fat diet on mice sexual development and adult reproductive function

Abstract

Polycystic ovary syndrome (PCOS) is associated with reproductive problems and/or subfertility. Some studies have identified a male PCOS phenotype. The administration of dihydrotestosterone (DHT) to pregnant females causes a PCOS-like phenotype in their offspring. In previous studies, we detected that DHT accelerated the sexual maturation of the offspring (males and females) and, in adulthood, altered their reproductive physiology. In the present study, we aimed to assess whether the co-administration of a high-fat diet (HFD) to pups, from weaning, exacerbates the effects of prenatal androgenization.

We worked with the male and female offspring (F1) of F0 mice (Albino swiss N/NIH) androgenized (DHT group) or not (C group) during their pregnancy (DHT=250µg/day during gestational days 16.5-18.5). These pups received from weaning, a control diet (CD) or a HFD (commercial pellet with 30% pork fat). Thus, the effect of these four treatments (DHT-CD; C-CD; DHT-HFD and C-HFD; n=2-8 litters/treatment) on pups sexual development of and their adult reproductive function was evaluated. Data were analyzed using ANAVA (two-way or repeated measures).

No differences were found in pups´ weight gain. DHT delayed, or even inhibited, vaginal opening. 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 and DHT-CD vs C-CD). In adulthood, DHT females (DHT-CD and DHT-HFD) presented lower pregnancy rates than controls (C-CD and C-HFD); 67% vs 100%. Furthermore, the DHT-HFD group had significantly fewer pups than the rest of the groups, with morphological abnormalities in their reproductive tract. In addition, C-HFD females had significantly smaller litters than C-CD (9.0±0.6 pups vs 12.5±0.5 pups). In males, we found no alteration in testicular descent or in adult sperm quality.

Our results suggest that prenatal androgenization negatively impacts the sexual development and adult reproductive function of female offspring, and that this effect is exacerbated by the administration of a HFD.