Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 101, Issue 31, Pages 11209-11214Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0404372101
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- NIDDK NIH HHS [R01 DK060905, DK60948, DK60905, R01 DK060948] Funding Source: Medline
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The roles of the androgen receptor (AR) in female fertility and ovarian function remain largely unknown. Here we report on the generation of female mice lacking AIR (AR(-/-)) and the resulting influences on the reproductive system. Female AR(-/-) mice appear normal but show longer estrous cycles and reduced fertility. The ovaries from sexually mature AR(-/-) females exhibited a marked reduction in the number of corpora lutea. After superovulation treatment, the AR(-/-) ovaries produced fewer oocytes and also showed fewer corpora lutea. During the periovulatory period, an intensive granulosa apoptosis event occurs in the AR(-/-) preovulatory follicles, concurrent with the down-regulation of p21 and progesterone receptor expression. Furthermore, the defective conformation of the cumulus cell-oocyte complex from the AR(-/-) females implies a lower fertilization capability of the AR(-/-) oocytes. In addition to insufficient progesterone production, the diminished endometrial growth in uteri in response to exogenous gonadotropins indicates that AR(-/-) females exhibit a luteal phase defect. Taken together, these data provide in vivo evidence showing that AIR plays an important role in female reproduction.
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