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Fetal programming by androgen excess in rats affects ovarian fuel sensors and steroidogenesis

Published online by Cambridge University Press:  24 May 2019

Giselle Adriana Abruzzese Open the ORCID record for Giselle Adriana Abruzzese [Opens in a new window] ,
Maria Florencia Heber ,
Fiorella Campo Verde Arbocco ,
Silvana Rocio Ferreira  and
Alicia Beatriz Motta
Giselle Adriana Abruzzese*
Affiliation:
Laboratorio de Fisio-patología ovárica, Centro 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
Maria Florencia Heber
Affiliation:
Laboratorio de Fisio-patología ovárica, Centro 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
Fiorella Campo Verde Arbocco
Affiliation:
Laboratorio de Hormonas y Biología del Cáncer, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET, 5500 Mendoza, Argentina Laboratorio de Reproducción y Lactancia, IMBECU, Mendoza, Argentina Facultad de Ciencias Médicas, Universidad de Mendoza, Mendoza, Argentina
Silvana Rocio Ferreira
Affiliation:
Laboratorio de Fisio-patología ovárica, Centro 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
Alicia Beatriz Motta
Affiliation:
Laboratorio de Fisio-patología ovárica, Centro 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
*
Address for correspondence: G. A. Abruzzese, CEFYBO – CONICET, School of Medicine, University of Buenos Aires, Paraguay 2155, 17th Floor, Sector M3, Buenos Aires, C1121 ABG, Argentina. Email: giselleabruzzese@gmail.com
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Abstract

Fetal programming by androgen excess is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS is more than a reproductive disorder, as women with PCOS also show metabolic and other endocrine alterations. Since both ovarian and reproductive functions depend on energy balance, the alterations in metabolism may be related to reproductive alterations. The present study aimed to evaluate the effect of androgen excess during prenatal life on ovarian fuel sensors and its consequences on steroidogenesis. To this end, pregnant rats were hyperandrogenized with testosterone and the following parameters were evaluated in their female offspring: follicular development, PPARG levels, adipokines (including leptin, adiponectin, and chemerin as ovarian fuel sensors), serum gonadotropins (LH and FSH), the mRNA of their ovarian receptors, and the expression of steroidogenic mediators. At 60 days of age, the prenatally hyperandrogenized (PH) female offspring displayed both an irregular ovulatory phenotype and an anovulatory phenotype with altered follicular development and the presence of cysts. Both PH groups showed altered levels of both proteins and mRNA of PPARG and a different expression pattern of the adipokines studied. Although serum gonadotropins were not impaired, there were alterations in the mRNA levels of their ovarian receptors. The steroidogenic mediators Star, Cyp11a1, Cyp17a1, and Cyp19a1 were altered differently in each of the PH groups. We concluded that androgen excess during prenatal life leads to developmental programming effects that affect ovarian fuel sensors and steroidogenesis in a phenotype-specific way.

Keywords

Prenatal hyperandrogenismPCOSovaryPPARGadipokines
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 10 , Issue 6 , December 2019 , pp. 645 - 658
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2019 

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