Estrogen receptors in mitochondrial metabolism: age-related changes and implications for pregnancy complications

Hinton, Antentor Jr.1,*; Neikirk, Kit1; Le, Han1; Harris, Chanel1,2; Oliver, Ashton1,2; Martin, Pamela2; Gaye, Amadou3

1Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN, USA

2Department of Biomedical Sciences, Meharry Medical College, Nashville, TN, USA

3Department of Integrative Genomics and Epidemiology, Meharry Medical College, Nashville, TN, USA

*Correspondence to: Antentor Hinton Jr., PhD, antentor.o.hinton.jr@vanderbilt.edu.

Abstract

Estrogen hormones are primarily associated with their role as female sex hormones responsible for primary and secondary sexual development. Estrogen receptors are known to undergo age-dependent decreases due to age-related changes in hormone production. In the mitochondria, estrogen functions by reducing the production of reactive oxygen species in the electron transport chain, inhibiting apoptosis, and regulating mitochondrial DNA content. Moreover, estrogen receptors may be the key components in maintaining mitochondrial membrane potential and structure. Although estrogen plays a crucial role in the development of pregnancy, our understanding of how estrogen receptors change with aging during pregnancy remains limited. During pregnancy, estrogen levels are significantly elevated, with a corresponding upregulation of estrogen receptors, which play various roles in pregnancy. However, the exact role of estrogen receptors in pregnancy complications remains to be further investigated. The paper reviews the role of estrogen receptors in the regulation of mitochondrial metabolism and in pregnancy complications, with a special focus on the effect of age-related changes on estrogen levels and estrogen receptors function. We also address how estrogen maintains mitochondrial function, including reducing the production of reactive oxygen species in the electron transport chain, inhibiting apoptosis, regulating mitochondrial DNA content, and maintaining mitochondrial membrane potential and structure. However, the effects of estrogen on mitochondria-endoplasmic reticulum contacts have not been well studied. Based on these emergent roles in mitochondria, the differential roles of estrogen receptors in pregnancy complications are of great relevance. The paper emphasizes the association between maternal health and estrogen receptors and indicates the need for future research to elucidate the interdependence of estrogen receptor-regulated maternal health with mitochondrial function and their relationship with the gut microbiome. Overall, we summarize the important role of estrogen receptors during pregnancy and highlight the need for further research to better understand the role of estrogen receptors in aging and pregnancy complications. This not only helps to reveal the mechanism underlying the role of estrogen in maternal health but also has potential clinical implications for the development of new therapies targeting age-related diseases and pregnancy complications.

线粒体代谢中的雌激素受体与年龄有关的变化及对妊娠并发症的影响：叙述性综述

摘要

雌性激素主要是作为女性性激素负责初级和次级性发育。众所周知，雌激素受体会随着年龄的增长而减少，这是因为激素分泌的变化与年龄有关。具体来说，雌激素通过减少电子传递链中活性氧的产生、抑制细胞凋亡和调节线粒体DNA 的含量来维持线粒体的功能。此外，雌激素受体可能是维持线粒体膜电位和结构的关键成分。虽然雌激素在妊娠发育过程中起着至关重要的作用，但我们对雌激素受体在妊娠期间如何随年龄变化的了解仍然有限。妊娠期间，雌激素水平显著升高，雌激素受体也相应上调，而雌激素受体在妊娠中发挥着不同的作用。然而，雌激素受体在妊娠并发症中的确切作用仍有待进一步研究。文章回顾了雌激素受体在调节线粒体代谢和妊娠并发症中的作用，特别关注了与年龄有关的变化对雌激素水平及其受体功能的影响。文章还探讨了雌激素如何维持线粒体功能，包括减少电子传递链中活性氧的产生、抑制细胞凋亡、调节线粒体 DNA 含量以及维持线粒体膜电位和结构。然而，雌激素对线粒体-内质网接触的影响尚未得到深入研究。基于线粒体的这些新作用，雌激素受体在妊娠并发症中的不同作用具有重要意义。文章强调了孕产妇健康与雌激素受体之间的关联，并指出未来研究的必要性，以阐明这些并发症与线粒体功能的相互依存关系，以及它们与肠道微生物组的关系。总之，文章总结了雌激素受体在孕期的重要作用，并强调了进一步研究的必要性，以更好地了解雌激素受体在衰老和孕期并发症中的作用。这不仅有助于揭示雌激素在孕产妇健康中的作用机制，而且对开发针对老年相关疾病和妊娠并发症的新疗法具有潜在的临床意义。