Abstract

We have previously reported that androstenedione induces abnormalities of follicle development and oocyte maturation in the mouse ovary. In granulosa cells of the ovarian follicle, androstenedione is aromatized to 17β-estradiol (E2). To determine whether the androgen or estrogen acts directly on the follicle to induce the above-mentioned abnormalities, we compared the effects of a non-aromatizable androgen, 5α-dihydrotestosterone (DHT), with those of E2 on murine follicular development and oocyte maturation in a single follicle culture system. The high dose (10−6 M) of DHT prompted normal follicular development, and there was no effect on oocyte meiotic maturation after stimulation with human chorionic gonadotropin (hCG) and epidermal growth factor (EGF). In contrast, culture with the high dose (10−6 M) of E2 delayed follicular growth and also suppressed proliferation of granulosa cells and antrum formation. Furthermore, culture with E2 delayed or inhibited oocyte meiotic maturation, such as chromosome alignment on the metaphase plate and extrusion of the first polar body, after addition of hCG and EGF. In conclusion, these findings demonstrate that E2, but not DHT, induces abnormalities of follicular development, which leads to delay or inhibition of oocyte meiotic maturation.

Highlights

  • In mammals, the processes of ovarian folliculogenesis and oogenesis are regulated by interaction between the oocyte and the surrounding somatic cells of the follicle, such as granulosa cells and theca cells [1]

  • In the previous study using a single follicle culture system, we demonstrated that androstenedione induced morphologic and functional abnormalities of developing mouse follicles, and impaired oocyte meiotic maturation [9]; androstenedione treatment reduced follicle viability and led to the formation of abnormal follicles, including those with misshapen oocytes

  • When androstenedione-treated follicles were stimulated with human chorionic gonadotropin (hCG) and epidermal growth factor (EGF), spindle microtubule organization, chromosome alignment on the metaphase plate, and exclusion of the first polar body were inhibited in oocytes

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Summary

Introduction

The processes of ovarian folliculogenesis and oogenesis are regulated by interaction between the oocyte and the surrounding somatic cells of the follicle, such as granulosa cells and theca cells [1]. Ovarian steroid hormones, including androgens and estrogens, influence the processes of folliculogenesis and oogenesis through interaction with specific receptors [5,6]. T and androstenedione have been reported to increase the number of pyknotic granulosa cells and degenerating oocytes [7,8,9]. It has been demonstrated that T promotes growth during early folliculogenesis, since administration of T to rhesus monkeys significantly increases the number of preantral and small antral follicles, as well as stimulating the proliferation of granulosa and theca cells [10]. DHT promotes the transition of primary follicles to secondary follicles in cattle [12] and improves follicular viability in humans [13]

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