OBJECTIVEMenopause is a singular phenomenon in trendy girls, as most mammalian species possess a reproductive interval comparable with their life span.
Menopause is brought on by the depletion of germ cell-containing ovarian follicles and in laboratory research is normally modeled in animals by which the ovarian operate is eliminated by ovariectomy or chemical poisoning of the germ cells.
Our goal was to discover and characterize the white spotting variant (Wv) mice which have lowered ovarian germ cell abundance, a results of a degree mutation within the c-kit gene that decreases kinase exercise, as a genetic model for use in menopause research.METHODSPhysiological and morphological options related to menopause have been decided in feminine Wv/Wv mice in contrast with age-matched wildtype controls.
Immunohistochemistry was used to guage the presence and variety of follicles in paraffin-embedded ovaries. Bone density and physique composition have been evaluated utilizing the PIXImus x-ray densitometer, and lipids, calcium, and hormone ranges have been decided in serum utilizing antigen-specific enzyme immunoassays. Heart and physique weight have been measured, and cardiac operate was evaluated utilizing transthoracic echocardiography.
RESULTSThe ovaries of the Wv/Wv females have a tremendously lowered variety of regular germ cells at beginning in contrast with wildtype mice.
The remaining follicles are depleted by round 2 months, and the ovaries develop benign epithelial lesions that resemble morphological modifications that happen throughout ovarian aging, whereas a standard mouse ovary has quite a few follicles in any respect phases of growth and retains some follicles even in superior age. Wv mice have elevated plasma gonadotropins and lowered estrogen and progesterone ranges, a major discount in bone mass density, and elevated serum ldl cholesterol and lipoprotein ranges.
Moreover, the Wv feminine mice have enlarged hearts and lowered cardiac operate.CONCLUSIONSThe discount of c-kit exercise in Wv mice results in a considerably diminished follicular endowment in new child mice and untimely depletion of follicles in younger mice, though mutant females have a standard life span after cessation of ovarian operate.
The Wv feminine mice exhibit constant physiological modifications that resemble widespread options of postmenopausal girls. These alterations embrace follicle depletion, morphological aging of the ovary, altered serum ranges of ldl cholesterol, gonadotropins and steroid hormones, decreased bone density, and lowered cardiac operate.
These modifications weren’t noticed in male mice, both age-matched male Wv/Wv or wildtype mice, and are improbably brought on by international lack of c-kit operate. The Wv mouse could also be a genetic, intact-ovary model that mimics intently the phenotypes of human menopause for use for additional research to know the mechanisms of menopausal biology.