U.S. Department of Agriculture: Agricultural Research Service, Lincoln, Nebraska


Date of this Version


Document Type



BIOLOGY OF REPRODUCTION (2012) 86(4):109, 1–2; DOI 10.1095/biolreprod.112.099242


The importance of the ovarian reserve, defined as the supply of primordial follicles in the mammalian ovary, to women’s health [1, 2], mammalian fertility [3, 4], and mammalian assisted reproductive technologies [5, 6] has been the subject of much research. Depletion of the ovarian reserve is considered to be a major factor influencing reproductive senescence in female mammals, and menopause is associated with a number of health risks in women [2, 7]. Premature ovarian failure (POF; also known as premature ovarian dysfunction or primary ovarian insufficiency) causes premature menopause (also known as premature reproductive senescence), defined as menopause before age 40 in women [8]. Recent research has demonstrated both genetic predisposition [9] and autoimmune disorders [10] to be major factors contributing to the occurrence of POF.

The thymus is the organ responsible for T cell development and establishment of central tolerance, the process that allows the immune system to recognize self and prevent autoimmune disorders. T cells are derived from hematopoietic precursors that arise in the bone marrow and migrate to the thymus, where central tolerance is promoted by both positive and negative selection [11]. Positive selection sets the baseline T cell receptor (TCR) signaling threshold; negative selection occurs when the T cells migrate to the thymic medulla, where thymocytes with strong self-reactive TCRs undergo apoptosis, preventing them from initiating an autoimmune response in the peripheral tissues.