Research

Pioglitazone administration alters ovarian gene expression in aging obese lethal yellow mice

John D Brannian^1,2 , Kathleen M Eyster¹ , Mitch Weber³ and Maureen Diggins³

¹  Department of Obstetrics and Gynecology and Division of Basic Biomedical Sciences Sanford School of Medicine of The University of South Dakota, Sioux Falls and Vermillion, SD, USA

²  Sanford Research USD, Sioux Falls, SD, USA

³  Department of Biology, Augustana College, Sioux Falls, SD, USA

author email corresponding author email

Reproductive Biology and Endocrinology 2008, 6:10doi:10.1186/1477-7827-6-10

Published:	18 March 2008

Abstract

Background

Women with polycystic ovary syndrome (PCOS) are often treated with insulin-sensitizing agents, e.g. thiazolidinediones (TZD), which have been shown to reduce androgen levels and improved ovulatory function. Acting via peroxisome proliferator-activated receptor (PPAR) gamma, TZD alter the expression of a large variety of genes. Lethal yellow (LY; C57BL/6J Ay/a) mice, possessing a mutation (Ay) in the agouti gene locus, exhibit progressive obesity, reproductive dysfunction, and altered metabolic regulation similar to women with PCOS. The current study was designed to test the hypothesis that prolonged treatment of aging LY mice with the TZD, pioglitazone, alters the ovarian expression of genes that may impact reproduction.

Methods

Female LY mice received daily oral doses of either 0.01 mg pioglitazone (n = 4) or an equal volume of vehicle (DMSO; n = 4) for 8 weeks. At the end of treatment, ovaries were removed and DNA microarrays were used to analyze differential gene expression.

Results

Twenty-seven genes showed at least a two-fold difference in ovarian expression with pioglitazone treatment. These included leptin, angiopoietin, angiopoietin-like 4, Foxa3, PGE1 receptor, resistin-like molecule-alpha (RELM), and actin-related protein 6 homolog (ARP6). For most altered genes, pioglitazone changed levels of expression to those seen in untreated C57BL/6J(a/a) non-mutant lean mice.

Conclusion

TZD administration may influence ovarian function via numerous diverse mechanisms that may or may not be directly related to insulin/IGF signaling.