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Fetal programming by androgen excess impairs liver lipid content and PPARg expression in adult rats

Published online by Cambridge University Press:  19 July 2021

Aimé Florencia Silva Open the ORCID record for Aimé Florencia Silva [Opens in a new window] ,
Giselle Adriana Abruzzese Open the ORCID record for Giselle Adriana Abruzzese [Opens in a new window] ,
María José Ferrer Open the ORCID record for María José Ferrer [Opens in a new window] ,
María Florencia Heber ,
Silvana Rocío Ferreira ,
Gloria Edith Cerrone  and
Alicia Beatriz Motta
Aimé Florencia Silva*
Affiliation:
Laboratorio de Fisiopatología Ovárica, Centro de Estudios Farmacológicos y Botánicos (CEFyBO), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, CP1121, Ciudad Autónoma de Buenos Aires, Argentina
Giselle Adriana Abruzzese
Affiliation:
Laboratorio de Fisiopatología Ovárica, Centro de Estudios Farmacológicos y Botánicos (CEFyBO), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, CP1121, Ciudad Autónoma de Buenos Aires, Argentina
María José Ferrer
Affiliation:
Laboratorio de Fisiopatología Ovárica, Centro de Estudios Farmacológicos y Botánicos (CEFyBO), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, CP1121, Ciudad Autónoma de Buenos Aires, Argentina
María Florencia Heber
Affiliation:
Laboratorio de Fisiopatología Ovárica, Centro de Estudios Farmacológicos y Botánicos (CEFyBO), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, CP1121, Ciudad Autónoma de Buenos Aires, Argentina
Silvana Rocío Ferreira
Affiliation:
Laboratorio de Fisiopatología Ovárica, Centro de Estudios Farmacológicos y Botánicos (CEFyBO), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, CP1121, Ciudad Autónoma de Buenos Aires, Argentina
Gloria Edith Cerrone
Affiliation:
Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética, Cátedra de Genética, Junín 954, C1113 AAD, Ciudad Autónoma de Buenos Aires, Argentina
Alicia Beatriz Motta
Affiliation:
Laboratorio de Fisiopatología Ovárica, Centro de Estudios Farmacológicos y Botánicos (CEFyBO), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, CP1121, Ciudad Autónoma de Buenos Aires, Argentina
*
Address for correspondence: Aimé Florencia Silva, Center of Pharmacological and Botanical Studies, School of Medicine, University of Buenos Aires, Paraguay 2155, 17th Floor, CP1121, Buenos Aires, Argentina. Email: aime.095@hotmail.com
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Abstract

It is known that prenatal hyperandrogenization induces alterations since early stages of life, contributing to the development of polycystic ovary syndrome affecting the reproductive axis and the metabolic status, thus promoting others associated disorders, such as dyslipidemia, insulin resistance, liver dysfunction, and even steatosis. In this study, we aimed to evaluate the effect of fetal programming by androgen excess on the hepatic lipid content and metabolic mediators at adult life. Pregnant rats were hyperandrogenized with daily subcutaneous injections of 1 mg of free testosterone from days 16 to 19 of pregnancy. The prenatally hyperandrogenized (PH) female offspring displayed two phenotypes: irregular ovulatory phenotype (PHiov) and anovulatory phenotype (PHanov), with different metabolic and endocrine features. We evaluated the liver lipid content and the main aspect of the balance between fatty acid (FA) synthesis and oxidation. We investigated the status of the peroxisomal proliferator-activated receptors (PPARs) alpha and gamma, which act as lipid mediators, and the adipokine chemerin, one marker of liver alterations. We found that prenatal hyperandrogenization altered the liver lipid profile with increased FAs levels in the PHanov phenotype and decreased cholesterol content in the PHiov phenotype. FA metabolism was also disturbed, including decreased mRNA and protein PPARgamma levels and impaired gene expression of the main enzymes involved in lipid metabolism. Moreover, we found low chemerin protein levels in both PH phenotypes. In conclusion, these data suggest that prenatal hyperandrogenization exerts a negative effect on the liver and alters lipid content and metabolic mediators’ expression at adult age.

Keywords

prenatal hyperandrogenizationliver lipid metabolismPPARgPPARachemerin
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 13 , Issue 3 , June 2022 , pp. 300 - 309
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Copyright
© The Author(s), 2021. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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