title: Shortened estrous cycle length, increased FSH levels, FSH variance, oocyte spindle aberrations, and early declining fertility in aging senescence-accelerated mouse prone-8 (SAMP8) mice: concomitant characteristics of human midlife female reproductive aging.
abstract: Women experience a series of specific transitions in their reproductive function with age. Shortening of the menstrual cycle begins in the mid to late 30s and is regarded as the first sign of reproductive aging. Other early changes include elevation and increased variance of serum FSH levels, increased incidences of oocyte spindle aberrations and aneuploidy, and declining fertility. The goal of this study was to investigate whether the mouse strain senescence-accelerated mouse-prone-8 (SAMP8) is a suitable model for the study of these midlife reproductive aging characteristics. Midlife SAMP8 mice aged 6.5-7.85 months (midlife SAMP8) exhibited shortened estrous cycles compared with SAMP8 mice aged 2-3 months (young SAMP8, P = .0040). Midlife SAMP8 mice had high FSH levels compared with young SAMP8 mice, and mice with a single day of high FSH exhibited statistically elevated FSH throughout the cycle, ranging from 1.8- to 3.6-fold elevation on the days of proestrus, estrus, metestrus, and diestrus (P < .05). Midlife SAMP8 mice displayed more variance in FSH than young SAMP8 mice (P = .01). Midlife SAMP8 ovulated fewer oocytes (P = .0155). SAMP8 oocytes stained with fluorescently labeled antitubulin antibodies and scored in fluorescence microscopy exhibited increased incidence of meiotic spindle aberrations with age, from 2/126 (1.59%) in young SAMP8 to 38/139 (27.3%) in midlife SAMP8 (17.2-fold increase, P < .0001). Finally, SAMP8 exhibited declining fertility from 8.9 pups/litter in young SAMP8 to 3.5 pups/litter in midlife SAMP8 mice (P < .0001). The age at which these changes occur is younger than for most mouse strains, and their simultaneous occurrence within a single strain has not been described previously. We propose that SAMP8 mice are a model of midlife human female reproductive aging.
authors.affiliation: Pregmama, LLC (L.R.B.), Gaithersburg, Maryland 20886; Departments of Epidemiology and Public Health (L.R.B., A.C.L.M., I.M.) and Obstetrics, Gynecology, and Reproductive Sciences (C.L.C.), University of Maryland School of Medicine, Baltimore, Maryland 21201; Department of Gynecology and Obstetrics (L.R.B.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Departments of Veterinary Integrative Biosciences (L.R.B.) and Veterinary Physiology and Pharmacology (D.C.K.), Texas A&M College of Veterinary Medicine, College Station, Texas 77843; Divisions of Geriatric Medicine and Endocrinology (J.E.M., S.F.), St. Louis University School of Medicine, St. Louis, Missouri 63103; and St. Louis Veterans Affairs Medical Center (S.F.), St. Louis, Missouri 63106.
authors.forename: Lori R
authors.initials: LR
authors.lastname: Bernstein
authors.forename: Amelia C L
authors.initials: AC
authors.lastname: Mackenzie
authors.forename: Duane C
authors.initials: DC
authors.lastname: Kraemer
authors.forename: John E
authors.initials: JE
authors.lastname: Morley
authors.forename: Susan
authors.initials: S
authors.lastname: Farr
authors.forename: Charles L
authors.initials: CL
authors.lastname: Chaffin
authors.forename: István
authors.initials: I
authors.lastname: Merchenthaler
mesh_terms: D000375:Aging / Q000097:blood* / Q000502:physiology; D000818:Animals; D030762:Estrous Cycle / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000502:physiology; D005640:Follicle Stimulating Hormone / Q000097:blood*; D006801:Humans; D051379:Mice; D009865:Oocytes / Q000378:metabolism*
chemical_list: D005640:Follicle Stimulating Hormone