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Regulation of HOXA-10 Expression by Testosterone in Vitro and in the Endometrium of Patients with Polycystic Ovary Syndrome

Department of Obstetrics and Gynecology (D.C., B.S., H.S.T.), Yale University School of Medicine, New Haven, Connecticut 06520

Address all correspondence and requests for reprints to: Hugh S. Taylor, M.D., Associate Professor, Department of Obstetrics and Gynecology, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208063, New Haven, Connecticut 06520. E-mail: hugh.taylor{at}yale.edu.

Polycystic ovary syndrome (PCOS) affects approximately 5% of reproductive-age women and is characterized by anovulation and increased androgen production. Despite the ability to correct ovulatory disorders, pregnancy rates remain paradoxically low, and spontaneous pregnancy loss rates are high. To determine whether uterine dysfunction contributed to the adverse reproductive outcomes in PCOS, we assessed the effect of the increased ovarian androgens on a well-characterized gene essential to endometrial receptivity. Up-regulation of HOXA10 in the endometrium is necessary for receptivity to embryo implantation. In vitro, HOXA10 expression was repressed by testosterone but not by dehydroepiandrosterone, dehydroepiandrosterone sulfate, or insulin. Testosterone also prevented the increased expression of HOXA10 previously reported with estradiol or progesterone. Dihydrotestosterone produced an effect similar to that of testosterone, whereas flutamide blocked the testosterone effect. Endometrial biopsies, obtained from women with PCOS, demonstrated decreased HOXA10 mRNA. Testosterone is a novel regulator of HOXA10. Diminished uterine HOXA10 expression may contribute to the diminished reproduction potential of women with PCOS.

This work was supported by NIH Grants HD-36887 and ES-10610.

Present address for D.C.: Department of Obstetric, Gynecology and Women’s Health, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103.

Abbreviations: DHA, Dehydroepiandrosterone; DHAS, DHA sulfate; DHT, dihydrotestosterone; PCOS, polycystic ovary syndrome.

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