Haploinsufficiency of the follicle-stimulating 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 heterozygous (+/-) mice initially have reduced fertility and stop breeding by 7-9 mo. The purpose of this study was to understand the basis of reduced fertility in mice with haploinsufficiency of the FSH-R. Heterozygous females were compared to +/+ females at 3, 7, and 12 mo of age. By 7 mo most of the +/- females were acyclic and <50% delivered pups. The wild-type females were normal in these respects. None of the 1-yr-old +/- females gave viable offspring (73% in +/+). Many degenerative changes, including atresia and apoptosis, and profound loss of oocytes, were apparent in +/- mice by 7 mo. The 1-yr-old +/- ovary had very few follicles and consisted mostly of fibroid tissue and cysts. Our data support the hypothesis that reproductive deficits in +/- FSH-R mice occur because of accelerated 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 determinant of ovarian aging and all phenomena that arise from subsequent estrogen deficiency and other aberrations.
Molecular Reproduction Research Laboratory, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7.
Natalia
N
Danilovich
M Ram
MR
Sairam
D000375:Aging / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D053938:DNA Fragmentation / Q000235:genetics / Q000502:physiology; D030762:Estrous Cycle / Q000235:genetics / Q000502:physiology; D005260:Female; D005298:Fertility / Q000235:genetics / Q000502:physiology; D005496:Follicular Atresia / Q000235:genetics / Q000502:physiology; D006239:Haplotypes; D020287:In Situ Nick-End Labeling; D007247:Infertility, Female / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009865:Oocytes / Q000502:physiology*; D006080:Ovarian Follicle / Q000166:cytology / Q000502:physiology; D010053:Ovary / Q000166:cytology / Q000502:physiology; D011962:Receptors, FSH / Q000235:genetics*; D012098:Reproduction / Q000235:genetics* / Q000502:physiology*; D012741:Sexual Maturation / Q000235:genetics / Q000502:physiology
D011962:Receptors, FSH