Submitted to: Biology of Reproduction
Publication Type: Other
Publication Acceptance Date: 1/19/2012
Publication Date: 4/1/2012
Citation: Cushman, R.A. 2012. Commentary: Evidence that the autoimmune regulator gene influences thymic production of ovarian antigens and prevents autoimmune-mediated premature reproductive senescence. Biology of Reproduction. 86(4):109. Interpretive Summary:
Technical Abstract: The importance of the ovarian reserve, defined as the supply of primordial follicles in the mammalian ovary, to women’s health, mammalian fertility, and mammalian assisted reproductive technologies has been the subject of much research. Depletion of the ovarian reserve is considered to be a major factor influencing reproductive senescence in mammalian females, and menopause is associated with a number of health risks in women. Premature ovarian failure (POF, aka premature ovarian dysfunction, or primary ovarian insufficiency) causes premature menopause (aka premature reproductive senescence), defined as menopause before age 40 in women. Recent research has demonstrated both genetic predisposition and autoimmune disorders to be major factors contributing to the occurrence of POF. This article by Jasti et al. reports on the influence of the Aire gene on premature reproductive senescence in mice because the thymic expression of ovarian genes under the control of Aire may be critical for preventing ovarian autoimmune disease. Aire-deficient mice had delayed puberty, although all attained puberty. While ovulation rate and litter size were unaffected, only half of the Aire-deficient mice gave birth to a litter and only 16% produced two litters. Histological evaluation of the ovaries revealed depletion of the ovarian reserve in 25% of virgin females by 8 weeks of age; by 20 weeks of age, 50% of Aire-deficient females had ovaries completely void of follicles. As would be expected, serum follicle stimulating hormone concentrations were elevated in the Aire-deficient mice, most likely due to reduced negative feedback from the ovary.