Department of Biochemistry and Molecular Biology, University of British Columbia, Health Sciences Mall, Vancouver, British Columbia, Canada.
Reproduction. 2024 Sep 21;168(5). doi: 10.1530/REP-24-0198. Print 2024 Nov 1.
This point of view article focuses on the potential contribution of defects in protein synthesis (translation) to the incidence of oocyte meiotic failure. We discuss the potential cause of diminished oocyte translation during aging and the impact of these deficits on the function of the meiotic spindle.
Errors during female meiosis lead to embryonic aneuploidy and miscarriage and occur with increasing frequency during aging. The underlying molecular changes that drive female meiotic instability remain a subject of debate. Developing oocytes undergo a tremendous increase in cytoplasmic volume over several months of follicle development and rely on long-lived mRNAs and ribosomes accumulated during this growth phase for subsequent meiotic maturation. In this point of view article, we discuss how the unique reliance on stores of long-lived mRNAs and ribosomes may represent an Achilles' heel for oocyte function and how alterations that reduce the translational capacity of oocytes could be a factor significantly contributing to female infertility. Understanding these mechanisms could lead to new therapeutic strategies to improve fertility outcomes.
本文观点聚焦于蛋白质合成(翻译)缺陷对卵母细胞减数分裂失败发生率的潜在影响。我们讨论了卵母细胞翻译能力随年龄下降的潜在原因,以及这些缺陷对减数分裂纺锤体功能的影响。
女性减数分裂过程中的错误会导致胚胎非整倍体和流产,且随着年龄的增长,这种错误的发生频率会逐渐增加。导致女性减数分裂不稳定的潜在分子变化仍然存在争议。在数月的卵泡发育过程中,发育中的卵母细胞细胞质体积会大幅增加,并依赖于在生长阶段积累的长寿 mRNA 和核糖体,以进行随后的减数分裂成熟。在本文观点中,我们讨论了卵母细胞对长寿 mRNA 和核糖体的独特依赖如何成为卵母细胞功能的致命弱点,以及降低卵母细胞翻译能力的改变如何成为导致女性不孕的重要因素。了解这些机制可能会为改善生育结局带来新的治疗策略。