Androstenedione induces abnormalities in morphology and function of developing oocytes, which impairs oocyte meiotic competence

Objective To obtain insight into the effects of androstenedione on ovarian folliculogenesis and oogenesis. Design Experimental study. Setting St. Marianna University School of Medicine. Animal(s) Prepubertal (14-day-old) BDF1 female mice. Intervention(s) Early secondary follicles were isolated from the ovaries and were cultured individually in vitro with or without androstenedione (10 −11 to 10 −5 M) for 12 days. Thereafter, the follicles were treated with hCG and epidermal growth factor (EGF). Main Outcome Measure(s) Diameters and morphology of follicles and oocytes; E 2 and P secretion; and chromatin configuration and expression of growth differentiation factor 9 (GDF9) in oocytes were examined. Result(s) Early secondary follicles developed to the preovulatory stage. Androstenedione treatments increased the follicle diameters, reduced survival rates of follicles, and promoted the formation of follicles with abnormal morphology, including misshapen oocyte. The secretion of E 2 and P was significantly higher in androstenedione-exposed follicles. Androstenedione prevented the alteration in chromatin configuration and reduced oocyte GDF9 expression. When follicles cultured with androstenedione were treated with hCG and EGF, the first polar body exclusion, chromosome alignment on metaphase plate, and spindle assembly were inhibited in the oocytes. Conclusion(s) These results demonstrate that excess androgen induces abnormalities in the morphology and function of developing oocytes, which impairs oocyte meiotic competence.