IVIRMA Global Research Alliance, IVI Foundation, Valencia 46026, Spain.
Department of Pediatrics, Obstetrics and Gynecology, School of Medicine, University of Valencia, Valencia 46010, Spain.
Aging (Albany NY). 2023 Oct 16;15(20):10856-10874. doi: 10.18632/aging.205086.
Female fertility is negatively correlated with age, with noticeable declines in oocyte quantity and quality until menopause. To understand this physiological process and evaluate human approaches for treating age-related infertility, preclinical studies in appropriate animal models are needed. Thus, we aimed to characterize an immunodeficient physiological aging mouse model displaying ovarian characteristics of different stages during women's reproductive life. NOD/SCID mice of different ages (8-, 28-, and 36-40-week-old) were employed to mimic ovarian phenotypes of young, Advanced Maternal Age (AMA), and old women (~18-20-, ~36-38-, and >45-years-old, respectively). Mice were stimulated, mated, and sacrificed to recover oocytes and embryos. Then, ovarian reserve, follicular growth, ovarian stroma, mitochondrial dysfunction, and proteomic profiles were assessed. Age-matched C57BL/6 mice were employed to cross-validate the reproductive outcomes. The quantity and quality of oocytes were decreased in AMA and Old mice. These age-related effects associated spindle and chromosome abnormalities, along with decreased developmental competence to blastocyst stage. Old mice had less follicles, impaired follicle activation and growth, an ovarian stroma inconducive to growth, and increased mitochondrial dysfunctions. Proteomic analysis corroborated these histological findings. Based on that, NOD/SCID mice can be used to model different ovarian aging phenotypes and potentially test human anti-aging treatments.
女性生育能力与年龄呈负相关，随着卵母细胞数量和质量的明显下降，直至绝经。为了理解这一生理过程，并评估人类治疗与年龄相关的不孕的方法，需要在适当的动物模型中进行临床前研究。因此，我们旨在描述一种免疫缺陷的生理衰老小鼠模型，该模型在女性生殖期显示出不同阶段的卵巢特征。使用不同年龄（8 周、28 周和 36-40 周）的 NOD/SCID 小鼠来模拟年轻、高龄（AMA）和老年妇女（分别约 18-20 岁、约 36-38 岁和>45 岁）的卵巢表型。刺激、交配和处死小鼠以回收卵母细胞和胚胎。然后，评估卵巢储备、卵泡生长、卵巢基质、线粒体功能障碍和蛋白质组学特征。将年龄匹配的 C57BL/6 小鼠用于交叉验证生殖结果。AMA 和老年小鼠的卵母细胞数量和质量下降。这些与年龄相关的影响与纺锤体和染色体异常有关，同时胚胎发育能力下降到囊胚阶段。老年小鼠的卵泡较少，卵泡激活和生长受损，卵巢基质不利于生长，线粒体功能障碍增加。蛋白质组学分析证实了这些组织学发现。基于这些发现，NOD/SCID 小鼠可用于模拟不同的卵巢衰老表型，并可能测试人类抗衰老治疗方法。
