Li Piani Letizia, Vigano' Paola, Somigliana Edgardo
Department of Clinical Sciences and Community Health, Università Degli Studi di Milano, Milan, Italy.
Infertility Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Front Cell Dev Biol. 2023 Mar 21;11:1121231. doi: 10.3389/fcell.2023.1121231. eCollection 2023.
Worldwide increase in life expectancy has boosted research on aging. Overcoming the concept of chronological age, higher attention has been addressed to biological age, which reflects a person's real health state, and which may be the resulting combination of both intrinsic and environmental factors. As epigenetics may exert a pivotal role in the biological aging, epigenetic clocks were developed. They are based on mathematical models aimed at identifying DNA methylation patterns that can define the biological age and that can be adopted for different clinical scopes (i.e., estimation of the risks of developing age-related disorders or predicting lifespan). Recently, epigenetic clocks have gained a peculiar attention in the fertility research field, in particular in the female counterpart. The insight into the possible relations between epigenetic aging and women's infertility might glean additional information about certain conditions that are still not completely understood. Moreover, they could disclose significant implications for health promotion programs in infertile women. Of relevance here is that the impact of biological age and epigenetics may not be limited to fertility status but could translate into pregnancy issues. Indeed, epigenetic alterations of the mother may transfer into the offspring, and pregnancy itself as well as related complications could contribute to epigenetic modifications in both the mother and newborn. However, even if the growing interest has culminated in the conspicuous production of studies on these topics, a global overview and the availability of validated instruments for diagnosis is still missing. The present narrative review aims to explore the possible bonds between epigenetic aging and fertility timeline. In the "infertility" section, we will discuss the advances on epigenetic clocks focusing on the different tissues examined (endometrium, peripheral blood, ovaries). In the "pregnancy" section, we will discuss the results obtained from placenta, umbilical cord and peripheral blood. The possible role of epigenetic aging on infertility mechanisms and pregnancy outcomes represents a question that may configure epigenetic clock as a bond between two apparently opposite worlds: infertility and pregnancy.
全球预期寿命的增加推动了对衰老的研究。突破了按时间顺序计算年龄的概念后，人们对生物年龄给予了更高的关注，生物年龄反映了一个人的真实健康状况，它可能是内在因素和环境因素共同作用的结果。由于表观遗传学可能在生物衰老过程中发挥关键作用，因此开发了表观遗传时钟。它们基于数学模型，旨在识别能够定义生物年龄的DNA甲基化模式，并可用于不同的临床领域（即评估患年龄相关疾病的风险或预测寿命）。最近，表观遗传时钟在生育研究领域，尤其是女性生育研究领域受到了特别关注。深入了解表观遗传衰老与女性不孕之间的可能关系，可能会获得关于某些尚未完全理解的状况的更多信息。此外，它们可能会揭示对不孕女性健康促进计划的重大影响。这里需要注意的是，生物年龄和表观遗传学的影响可能不仅限于生育状况，还可能转化为妊娠问题。事实上，母亲的表观遗传改变可能会传递给后代，而妊娠本身以及相关并发症可能会导致母亲和新生儿的表观遗传修饰。然而，尽管对这些主题的研究兴趣日益浓厚，相关研究成果显著，但仍缺乏对这些主题的全面概述以及经过验证的诊断工具。本叙述性综述旨在探讨表观遗传衰老与生育时间表之间的可能联系。在“不孕”部分，我们将讨论表观遗传时钟在不同组织（子宫内膜、外周血、卵巢）研究方面的进展。在“妊娠”部分，我们将讨论从胎盘、脐带和外周血中获得的结果。表观遗传衰老在不孕机制和妊娠结局中的可能作用代表了一个问题，这个问题可能使表观遗传时钟成为不孕和妊娠这两个看似相反的世界之间的纽带。
