. Fetal Programming of Polycystic Ovary Syndrome: Prenatal Hyperandrogenism Disrupts Ovarian Functionality And Causes Reproductive Derangements

ALICIA BEATRIZ MOTTA; GISELLE ADRIANA ABRUZZESE; MARIA FLORENCIA HEBER

San Luis de Maranhao

Congreso; 5 Metabolic Programming and Stress th International Symposium on 2nd Meeting of Ibero-American DOHaD Chapter San Luis de Maranhao, Brasil, noviembre 2016; 2016

Prenatalhyperandrogenism is hypothesized as one of the main factors contributing topolycystic ovary syndrome (PCOS), an endocrine-metabolic disorder. We aimed to study the impact of prenatalhyperandrogenism on ovarian functionality at pubertal age. Pregnant ratswere hyperandrogenized with testosterone and a Control group was obtained byvehicle injection. The prenatally hyperandrogenized (PH) female offspring(N=150) and control offspring (N=96) were characterized according to theestrous cycle as ovulatory (PHov) and anovulatory (PHanov) phenotypes atpubertal age. We evaluated ovarian histology, testosterone and estradiol serumlevels. The mRNA levels of adipokines (Leptin, Adiponectin and Chemerin),steroidogenic enzymes and LH and FSH receptors were quantified by qPCR. None ofthe groups displayed body weight differences (p > 0.05). In threeindependent repetitions, Control rats showed (100%) regular estrous cycle.43?51% of PH group showed irregular estrous cycles (PHov), whereas 27?39%presented anovulatory cycles (PHanov). Ovaries from the PH offspring presentedcysts and an excess of small antral follicles. Testosterone levels wereincreased in both, PHov and PHanov groups (p<0.01), while estradiol wasdecreased only in PHanov (p<0.05). Leptin levels were lower in PHanov groupthan in Control and PHov groups (p<0.01). Adiponectin levels were higher inPHov group than in Control and PHanov groups (p<0.01). Chemerin levels werehigher in  PHov vs Control and PHanov(p<0.05). Regarding steroidogenesis, StAR levels were increased in PHanovgroup (p<0.05) and aromatase levels were lower in PHanov than in Control andPHov (p<0.05). LH-R was increased in PHanov (p<0.05); FSH-R was lower inPHov but remained unaltered in PHanov as compared to Control (p<0.05). Inconclusion, fetal programming causes alterations in ovarian functionalityaltering steroidogenesis and adipokines secretion, even in the absence ofoverweight. The differential deregulations of adipokines, steroidogenesis andLH-R and FSH-R are involved in the alterations displayed in PCOS phenotypes.