Prenatal androgen excess alters the uterine PPAR system

LEANDRO MARTIN VELEZ; ALICIA BEATRIZ MOTTA; MARIA FLORENCIA HEBER; SILVANA FERREIRA; GISELLE ADRIANA ABRUZZESE

REPRODUCTION FERTILITY AND DEVELOPMENT

CSIRO PUBLISHING

Lugar: Collingwood; Año: 2019

1031-3613

It is known that androgen excess induces alterations in fetal programming that affect several physiological pathways. The peroxisome proliferator-activated receptors alpha, delta and gamma are key mediators of female reproductive functions, in particular in uterine tissues. Thus, we aimed to study the effect of prenatal hyperandrogenization on the uterine PPAR system. Rats were treated with 2 mg of testosterone from days 16 to 19 of pregnancy. Female offspring (PH group) were followed until 90 days of life (sacrifice). The PH group displayed an anovulatory phenotype. We quantified the uterine mRNA levels of PPAR alpha, delta, gamma, their regulators (PGC1a and NCoR), cyclooxygenase-2 (COX-2), and assessed the lipid peroxidation (LP) index and the levels of glutathione (GSH) and PGE2. The PH group showed decreased levels of all uterine PPAR isoforms. The PH group also showed increased levels of PGE2 and COX-2, which led to a uterine pro-inflammatory environment, and increased LP, which led to a pro-oxidant status that GSH was not able to compensate. Our results suggest that prenatal exposure to androgen excess has a fetal programming effect that affects the gene expression of the PPAR isoforms, and creates a misbalanced oxidant/antioxidant state and a pro-inflammatory status.