Haploinsufficiency of the folliclestimulating hormone receptor accelerates oocyte loss inducing early reproductive senescence and biological aging in mice

Female mice that are null for the FSH-receptor (FSH-R) gene are estrogen deficient, acyclic, and sterile. However, the hetero-zygous (1/2) mice initially have reduced fertility and stop breeding by 7–9 mo. The purpose of this study was to under-stand the basis of reduced fertility in mice with haploinsuffi-ciency of the FSH-R. Heterozygous females were compared to 1/1 females at 3, 7, and 12 mo of age. By 7 mo most of the 1/2 females were acyclic and,50 % delivered pups. The wild-type females were normal in these respects. None of the 1-yr-old 1/2 females gave viable offspring (73 % in 1/1). Many degenerative changes, including atresia and apoptosis, and pro-found loss of oocytes, were apparent in 1/2 mice by 7 mo. The 1-yr-old 1/2 ovary had very few follicles and consisted mostly of fibroid tissue and cysts. Our data support the hypothesis that reproductive deficits in 1/2 FSH-R mice occur because of ac-celerated oocyte loss due to increased cell death in the ovary. These events contribute to early reproductive senescence and biological aging in mice. Thus FSH-R status is an important de-terminant of ovarian aging and all phenomena that arise from subsequent estrogen deficiency and other aberrations. aging, apoptosis, follicle-stimulating hormone receptor, follicular development, ovar