title: Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism.
abstract: Prenatal hyperandrogenism is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS patients have high risk of developing fatty liver and steatosis. This study aimed to evaluate the role of prenatal hyperandrogenism in liver lipid metabolism and fatty liver development. Pregnant rats were hyperandrogenized with testosterone. At pubertal age, the prenatally hyperandrogenized (PH) female offspring displayed both ovulatory (PHov) and anovulatory (PHanov) phenotypes that mimic human PCOS features. We evaluated hepatic transferases, liver lipid content, the balance between lipogenesis and fatty acid oxidation pathway, oxidant/antioxidant balance and proinflammatory status. We also evaluated the general metabolic status through growth rate curve, basal glucose and insulin levels, glucose tolerance test, HOMA-IR index and serum lipid profile. Although neither PH group showed signs of liver lipid content, the lipogenesis and fatty oxidation pathways were altered. The PH groups also showed impaired oxidant/antioxidant balance, a decrease in the proinflammatory pathway (measured by prostaglandin E2 and cyclooxygenase-2 levels), decreased glucose tolerance, imbalance of circulating lipids and increased risk of metabolic syndrome. We conclude that prenatal hyperandrogenism generates both PHov and PHanov phenotypes with signs of liver alterations, imbalance in lipid metabolism and increased risk of developing metabolic syndrome. The anovulatory phenotype showed more alterations in liver lipogenesis and a more impaired balance of insulin and glucose metabolism, being more susceptible to the development of steatosis.
authors.affiliation: Laboratorio de Fisio-patología OváricaCentro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina giselleabruzzese@gmail.com.
authors.forename: Giselle Adriana
authors.initials: GA
authors.lastname: Abruzzese
authors.affiliation: Laboratorio de Fisio-patología OváricaCentro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina.
authors.forename: Maria Florencia
authors.initials: MF
authors.lastname: Heber
authors.affiliation: Laboratorio de Fisio-patología OváricaCentro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina.
authors.forename: Silvana Rocio
authors.initials: SR
authors.lastname: Ferreira
authors.affiliation: Laboratorio de Fisio-patología OváricaCentro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina.
authors.forename: Leandro Martin
authors.initials: LM
authors.lastname: Velez
authors.affiliation: Laboratorio de EndocrinologíaDepartamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina.
authors.forename: Roxana
authors.initials: R
authors.lastname: Reynoso
authors.affiliation: Laboratorio de Endocrinología Molecular y Transducción de SeñalesInstituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires (UBA), Buenos Aires, Argentina.
authors.forename: Omar Pedro
authors.initials: OP
authors.lastname: Pignataro
authors.affiliation: Laboratorio de Fisio-patología OváricaCentro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina.
authors.forename: Alicia Beatriz
authors.initials: AB
authors.lastname: Motta
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D017588:Hyperandrogenism / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000494:pharmacology
chemical_list: D007328:Insulin; D008055:Lipids; D013739:Testosterone; D051546:Cyclooxygenase 2
keywords: fatty liver; lipid metabolism; polycystic ovary syndrome; prenatal hyperandrogenism