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 AR (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 AR plays an important role in female reproduction.

Primary dysmenorrhea (PDM) is the most prevalent gynecological disorder for women in the reproductive age. PDM patients suffer from lower abdominal pain that starts with the onset of the menstrual flow. Prolonged nociceptive input to the central nervous system can induce functional and structural alterations throughout the nervous system. In PDM, a chronic viscero-nociceptive drive of cyclic nature, indications of central sensitization and altered brain metabolism suggest a substantial central reorganization. Previously, we hypothesized that disinhibition of orbitofrontal networks could be responsible for increased pain and negative affect in PDM. Here, we further tested this hypothesis. We used an optimized voxel-based morphometry (VBM) approach to compare total and regional gray matter (GM) increases and decreases in 32 PDM patients with 32 healthy age and menstrual cycle matched (peri-ovulatory phase) controls. Abnormal decreases were found in regions involved in pain transmission, higher level sensory processing, and affected regulation while increases were found in regions involved in pain modulation and in regulation of endocrine function. Moreover, GM changes in regions involved in top-down pain modulation and in generation of negative affect were related to the severity of the experienced PDM pain. Our results demonstrate that abnormal GM volume changes are present in PDM patients even in the absence of pain. These changes may underpin a combination of impaired pain inhibition, increased pain facilitation and increased affect. Our findings highlight that longer lasting central changes may occur not only in sustained chronic pain conditions but also in cyclic occurring pain conditions.

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