Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain
Hum Reprod Update. 2015 Mar-Apr;21(2):249-61. doi: 10.1093/humupd/dmu060. Epub 2014 Nov 20.
Obesity and overweight are significantly involved in several reproductive pathologies contributing to infertility in men and women. In addition, several cancers of the reproductive system, such as endometrial, ovarian, breast, testicular and prostate cancers, are strongly influenced by obesity. However, the molecular mechanisms involved in the association between obesity and reproductive disorders remain unclear. Our proposal is to review the current scientific evidence regarding the effect of obesity-related factors as the core of the collective mechanisms directly and indirectly involved in the relationship between obesity and reproductive disorders, with a special and original focus on the effect of the obesity state microenvironment on the epigenetic profile as a reversible mechanistic link between obesity and the reproductive disorders.
A PubMed search was performed using keywords related to obesity and adipose-related factors and epigenetics and associated with keywords related to reproduction. Full-text articles and abstracts in the English language published prior to 31 December 2013 were reviewed.
The obesity state notably contributes to a reproductive dysfunction in both men and women, ranging from infertility to oncological outcomes. Several epidemiological and experimental studies demonstrate that factors secreted by the adipose tissue and gut in an obesity state can directly induce reproductive disturbances. Relevantly, these same factors are able to alter the epigenetic regulation of genes, a dynamic and reversible mechanism by which the organism responds to environmental pressures critical to the reproductive function.
This review outlines the evidence showing that the association between the reproductive pathologies and obesity is not inevitable but is potentially preventable and reversible. The epigenetic marks related to obesity could constitute a therapeutic target for the reproductive disorders associated with obesity.
肥胖和超重与男性和女性不孕的多种生殖病理密切相关。此外,几种生殖系统癌症,如子宫内膜癌、卵巢癌、乳腺癌、睾丸癌和前列腺癌,也受到肥胖的强烈影响。然而,肥胖与生殖障碍之间关联的分子机制仍不清楚。我们建议回顾目前关于肥胖相关因素对生殖障碍影响的科学证据,肥胖相关因素是肥胖与生殖障碍之间直接和间接相关的共同机制的核心,特别关注肥胖状态微环境对表观遗传特征的影响,作为肥胖与生殖障碍之间的一种可逆机制联系。
使用与肥胖和脂肪相关因素以及与生殖相关的表观遗传学相关的关键词,在 PubMed 上进行了搜索。对截至 2013 年 12 月 31 日之前发表的英文全文文章和摘要进行了回顾。
肥胖状态显著导致男性和女性生殖功能障碍,从不孕到肿瘤发生。一些流行病学和实验研究表明,肥胖状态下脂肪组织和肠道分泌的因子可以直接诱导生殖紊乱。相关地,这些相同的因子能够改变基因的表观遗传调控,这是一种动态的、可逆的机制,生物体通过这种机制对生殖功能至关重要的环境压力做出反应。
本综述概述了表明生殖病理与肥胖之间的关联并非不可避免,但具有潜在的可预防和可逆性的证据。与肥胖相关的表观遗传标记可能成为与肥胖相关的生殖障碍的治疗靶点。