CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Androgen excess in utero programmes metabolic alterations that affect reproductive functions
Autor/es:
GISELLE ADRIANA ABRUZZESE
Lugar:
Woods Hole
Reunión:
Simposio; 20th Annual Symposium Frontiers in Reproduction; 2017
Institución organizadora:
FIR-MBL-UNIVERSITY OF CHICAGO
Resumen:
During in utero period, an adverse environment (as exposure to endocrine disruptors,undernutrition or hormonal imbalance) affects the developing embryo and may condition post-natal life. It has been reported that prenatal androgen exposure is able to induce endocrine andmetabolic abnormalities in several species. These alterations mimics those observed in humanpolycystic ovary syndrome (PCOS) phenotypes. In female mammals metabolic status and fertilityare tightly related and reciprocally regulated. Thus alterations in metabolism could impact onovarian energy balance affecting its functions and leading to fertility issues.The aim of this work is to evaluate the effect of prenatal hyperandrogenism on metabolic balanceand its impact on ovarian functions.Pregnant rats were hyperandrogenized with testosterone and a Control group was obtained byvehicle injection. The prenatally hyperandrogenized (PH) female offspring (N=150) and Controloffspring (N=96) were characterized according to the estrous cycle as ovulatory (PHov) andanovulatory (PHanov) phenotypes at pubertal age. To evaluate the effect of androgen excess ongeneral metabolic status we measured growth rate curve, basal glucose and insulin levels, glucosetolerance test, HOMA-IR index and serum lipid profile. To study the impact of prenatalhyerandrogenism on ovarian balance signaling and functions we evaluated ovarian histology,testosterone and estradiol serum levels. We quantified by qPCR the mRNA levels of: theadipokines Leptin, Adiponectin and Chemerin; PPARgamma and its co-activator PGC1alpha, thesteroidogenic enzymes StAR and aromatase (CYP19A).In the three independent repetitions of the animal procedure, Control rats showed (100%) regularestrous cycle at pubertal age. Within the PH group, 43?51% rats showed irregular estrous cyclesand were considered as PHov, whereas 27?39% presented anovulatory cycles and wereconsidered as PHanov. Our results showed that both PH groups presented decreased glucosetolerance, imbalance of circulating lipids and increased risk of metabolic syndrome. None of thegroups displayed body weight differences. We found that both PH groups also displayed highlevels of serum testosterone and alterations in ovarian morphology with excess of small antralfollicles and presence of cysts, thus mimicking human PCOS features. Estradiol levels were onlydecreased in PHanov (p<0.05), although the ratio estradiol/testosterone (a marker of hormonalbalance) was impaired in both PH groups (p<0.05). The adipokines secretion pattern was alteredin the PH groups. Leptin levels were lower in PHanov group than in Control and PHov groups(p<0.01). Adiponectin levels were higher in PHov group than in Control and PHanov groups(p<0.01). Chemerin levels were higher in PHov vs Control and PHanov (p<0.05). Both groupsshowed higher levels of PPARgamma and of its coactivator, PGC1alpha, than in Control group(p<0.05). Regarding steroidogenesis, StAR levels were increased in PHanov group (p<0.05) andaromatase levels were lower in PHanov than in Control and PHov (p<0.05).In conclusion, developmental programming by hyperandrogenism causes alterations in systemicmetabolic balance affecting lipid metabolism and glucose homeostasis and affects, in a phenotypespecific manner, ovarian functionality. These alterations involve fuel sensors such as adipokinesand the system of the master fuel sensor PPARgamma and impact on steroidogenesis.