缩短的发情周期长度、升高的 FSH 水平、FSH 变异、卵母细胞纺锤体异常以及衰老加速敏感 8 号（SAMP8）小鼠的早期生育力下降：与人类中年女性生殖衰老的伴随特征。
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.
机构信息
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.
出版信息
Endocrinology. 2014 Jun;155(6):2287-300. doi: 10.1210/en.2013-2153. Epub 2014 Mar 21.
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.
女性在生殖功能上会随着年龄经历一系列特定的转变。从中年后期到晚期，月经周期开始缩短，这被认为是生殖衰老的第一个迹象。其他早期变化包括血清 FSH 水平升高和波动增加、卵母细胞纺锤体异常和非整倍体发生率增加，以及生育能力下降。本研究的目的是探讨衰老加速敏感 8 号小鼠（SAMP8）是否是研究这些中年生殖衰老特征的合适模型。与 2-3 月龄（年轻 SAMP8）的 SAMP8 相比，6.5-7.85 月龄（中年 SAMP8）的中年 SAMP8 雌鼠发情周期缩短（P =.0040）。与年轻 SAMP8 相比，中年 SAMP8 雌鼠的 FSH 水平较高，且仅一天 FSH 升高的小鼠在整个周期中 FSH 水平均升高，发情前期、发情期、间情期和发情后期升高 1.8-3.6 倍（P <.05）。与年轻 SAMP8 相比，中年 SAMP8 雌鼠的 FSH 波动更大（P =.01）。中年 SAMP8 雌鼠排卵的卵母细胞较少（P =.0155）。用荧光标记的抗微管抗体染色并用荧光显微镜评分的 SAMP8 卵母细胞显示，随着年龄的增长，减数分裂纺锤体异常的发生率增加，从年轻 SAMP8 的 126 个卵母细胞中有 2 个（1.59%）增加到中年 SAMP8 的 139 个卵母细胞中有 38 个（27.3%）（增加 17.2 倍，P <.0001）。最后，SAMP8 的生育力从年轻 SAMP8 的每窝 8.9 只减少到中年 SAMP8 的每窝 3.5 只（P <.0001）。这些变化发生的年龄比大多数小鼠品系都要早，而且在同一品系中同时发生尚未有过报道。我们提出，SAMP8 小鼠是人类中年女性生殖衰老的模型。
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