Cafe Shenae L, Nixon Brett, Ecroyd Heath, Martin Jacinta H, Skerrett-Byrne David A, Bromfield Elizabeth G
Priority Research Centre for Reproductive Science, Faculty of Science, The University of Newcastle, Callaghan, NSW, Australia.
Molecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, Australia.
Front Cell Dev Biol. 2021 Apr 16;9:660626. doi: 10.3389/fcell.2021.660626. eCollection 2021.
For fully differentiated, long lived cells the maintenance of protein homeostasis (proteostasis) becomes a crucial determinant of cellular function and viability. Neurons are the most well-known example of this phenomenon where the majority of these cells must survive the entire course of life. However, male and female germ cells are also uniquely dependent on the maintenance of proteostasis to achieve successful fertilization. Oocytes, also long-lived cells, are subjected to prolonged periods of arrest and are largely reliant on the translation of stored mRNAs, accumulated during the growth period, to support meiotic maturation and subsequent embryogenesis. Conversely, sperm cells, while relatively ephemeral, are completely reliant on proteostasis due to the absence of both transcription and translation. Despite these remarkable, cell-specific features there has been little focus on understanding protein homeostasis in reproductive cells and how/whether proteostasis is "reset" during embryogenesis. Here, we seek to capture the momentum of this growing field by highlighting novel findings regarding germline proteostasis and how this knowledge can be used to promote reproductive health. In this review we capture proteostasis in the context of both somatic cell and germline aging and discuss the influence of oxidative stress on protein function. In particular, we highlight the contributions of proteostasis changes to oocyte aging and encourage a focus in this area that may complement the extensive analyses of DNA damage and aneuploidy that have long occupied the oocyte aging field. Moreover, we discuss the influence of common non-enzymatic protein modifications on the stability of proteins in the male germline, how these changes affect sperm function, and how they may be prevented to preserve fertility. Through this review we aim to bring to light a new trajectory for our field and highlight the potential to harness the germ cell's natural proteostasis mechanisms to improve reproductive health. This manuscript will be of interest to those in the fields of proteostasis, aging, male and female gamete reproductive biology, embryogenesis, and life course health.
对于完全分化的长寿细胞而言，蛋白质稳态（proteostasis）的维持成为细胞功能和生存能力的关键决定因素。神经元是这一现象最为人熟知的例子，其中大多数这类细胞必须存活整个生命周期。然而，雄性和雌性生殖细胞也独特地依赖蛋白质稳态的维持来实现成功受精。卵母细胞同样是长寿细胞，会经历长时间的停滞，并且在很大程度上依赖于生长期积累的储存mRNA的翻译，以支持减数分裂成熟和随后的胚胎发育。相反，精子细胞虽然相对短暂，但由于缺乏转录和翻译过程，完全依赖蛋白质稳态。尽管存在这些显著的细胞特异性特征，但对于生殖细胞中蛋白质稳态的理解以及在胚胎发育过程中蛋白质稳态如何/是否“重置”，人们关注甚少。在此，我们试图通过强调关于生殖系蛋白质稳态的新发现以及如何利用这些知识促进生殖健康，来抓住这一不断发展领域的契机。在这篇综述中，我们在体细胞和生殖系衰老的背景下阐述蛋白质稳态，并讨论氧化应激对蛋白质功能的影响。特别地，我们强调蛋白质稳态变化对卵母细胞衰老的作用，并鼓励关注这一领域，这可能会补充长期以来在卵母细胞衰老领域占据主导地位的对DNA损伤和非整倍体的广泛分析。此外，我们讨论常见的非酶促蛋白质修饰对雄性生殖系中蛋白质稳定性的影响、这些变化如何影响精子功能以及如何预防这些变化以维持生育能力。通过这篇综述，我们旨在为我们的领域揭示一条新的轨迹，并强调利用生殖细胞天然蛋白质稳态机制改善生殖健康的潜力。这篇手稿将引起蛋白质稳态、衰老、雄性和雌性配子生殖生物学、胚胎发育以及生命历程健康等领域的研究人员的兴趣。
