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.
Danilovich
Natalia
N
Molecular Reproduction Research Laboratory, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7.
Sairam
M Ram
MR
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