Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China.
Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan 250012, Shandong, China.
Aging (Albany NY). 2020 Dec 9;13(2):2118-2134. doi: 10.18632/aging.202214.
Advanced maternal-age is a major factor adversely affecting oocyte quality, consequently worsening pregnancy outcomes. Thus, developing strategies to reduce the developmental defects associated with advanced maternal-age would benefit older mothers. Multiple growth factors involved in female fertility have been extensively studied; however, the age-related impacts of various growth factors remain poorly studied. In the present study, we identified that levels of insulin-like growth factor 2 (IGF2) are significantly reduced in the serum and oocytes of aged mice. We found that adding IGF2 in culture medium promotes oocyte maturation and significantly increases the proportion of blastocysts: from 41% in the untreated control group to 64% (50 nM IGF2) in aged mice ( < 0.05). Additionally, IGF2 supplementation of the culture medium reduced reactive oxygen species production and the incidence of spindle/chromosome defects. IGF2 increases mitochondrial functional activity in oocytes from aged mice: we detected increased ATP levels, elevated fluorescence intensity of mitochondria, higher mitochondrial membrane potentials, and increased overall protein synthesis, as well as increased autophagy activity and decreased apoptosis. Collectively, our findings demonstrate that IGF2 supplementation in culture media improves oocyte developmental competence and reduces meiotic structure defects in oocytes from aged mice.
高龄是影响卵母细胞质量的一个主要因素,进而导致妊娠结局恶化。因此,开发减少与高龄相关的发育缺陷的策略将使高龄产妇受益。许多参与女性生育的生长因子已被广泛研究;然而,各种生长因子的年龄相关性影响仍研究不足。在本研究中,我们发现衰老小鼠的血清和卵母细胞中胰岛素样生长因子 2 (IGF2) 的水平显著降低。我们发现,在培养物中添加 IGF2 可促进卵母细胞成熟,并显著增加囊胚的比例:从不处理对照组的 41%增加到老年小鼠中的 64%(50 nM IGF2)(<0.05)。此外,培养基中 IGF2 的补充减少了活性氧的产生和纺锤体/染色体缺陷的发生率。IGF2 增加了衰老小鼠卵母细胞中的线粒体功能活性:我们检测到 ATP 水平升高、线粒体荧光强度增加、线粒体膜电位升高、总蛋白合成增加,以及自噬活性增加和凋亡减少。总的来说,我们的研究结果表明,在培养基中补充 IGF2 可提高卵母细胞的发育能力,并减少衰老小鼠卵母细胞减数分裂结构缺陷。