RESUMEN
It is known that androgen excess induces changes in fetal programming that affect several physiological pathways. Peroxisome proliferator-activated receptors (PPARs) α, δ and γ are key mediators of female reproductive functions, in particular in uterine tissues. Thus, we aimed to study the effect of prenatal hyperandrogenisation on the uterine PPAR system. Rats were treated with 2mg testosterone from Day 16 to 19 of pregnancy. Female offspring (PH group) were followed until 90 days of life, when they were killed. The PH group exhibited an anovulatory phenotype. We quantified uterine mRNA levels of PPARα (Ppara ), PPARδ (Ppard ), PPARγ (Pparg ), their regulators peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Ppargc1a ) and nuclear receptor co-repressor 1 (Ncor1 ) and cyclo-oxygenase (COX)-2 (Ptgs2 ), and assessed the lipid peroxidation (LP) index and levels of glutathione (GSH) and prostaglandin (PG) E2 . The PH group showed decreased levels of all uterine PPAR isoforms compared with the control group. In addition, PGE2 and Ptgs2 levels were increased in the PH group, which led to a uterine proinflammatory environment, as was LP, which led to a pro-oxidant status that GSH was not able to compensate for. These results suggest that prenatal exposure to androgen excess has a fetal programming effect that affects the gene expression of PPAR isoforms, and creates a misbalanced oxidant-antioxidant state and a proinflammatory status.