The epigenomics of polycystic ovarian syndrome: from pathogenesis to clinical manifestations

Abstract

Polycystic ovarian syndrome (PCOS) is a complex condition of ovarian dysfunction and metabolic abnormalities with widely varying clinical manifestations resulting from interference of the genome and the environment through integrative biological mechanisms with the emerging field of epigenetics offering an appealing tool for studying the nature and nurture of the disease. We review the current literature of epigenetic studies on PCOS from disease development to the association analysis of the DNA methylome and to exploratory studies on the molecular mechanisms of disease heterogeneity and comorbidity. Recent data based on profiling of the DNA methylome of PCOS in different tissues provided consistent molecular evidence in support of epidemiological findings on disease comorbidity suggesting a possible autoimmune basis in the pathogenesis of the disease. We show that the field of epigenetics and epigenomics could serve to link molecular regulatory mechanisms with disease development and disease manifestation which could contribute to PCOS prevention and treatment and eventually promote reproductive health in fertile age women. We summarize the up-to-date findings and discuss the implications of various studies and point to new avenues of research on PCOS in the rapidly developing field of epigenetics and epigenomics.

Chinese abstract

多囊卵巢综合征(PCOS)是表现为卵巢功能障碍和代谢异常的一种非常复杂的状态, 由于基因及环境影响, 其临床表现多样, 通过综合生物学机制及表观遗传学的新兴发展, 为研究这个疾病的本质提供了具有吸引力的工具。我们复习了目前关于多囊卵巢综合征的表观遗传学的所有文献, 从疾病发展到基因组DNA甲基化相关分析, 再到疾病异质性及共病的分子学机制的探索性研究。最近基于PCOS不同组织中的DNA甲基化特征谱的数据提供了一致性的分子证据以支持关于疾病共病的流行病学发现, 表明在疾病的发病机理中可能存在自身免疫性基础。我们的分析显示: 表观遗传学和表观基因组学的研究可以用于连接分子调节机制与疾病发展和疾病表现, 有助于PCOS的预防和治疗, 并最终促进生育年龄妇女的生殖健康。我们总结了最新的研究发现并讨论各种研究的意义, 在表观遗传学和表观基因组学的迅速发展的领域, 指向PCOS新的研究途径。

Keywords:

• Association analysis
• clinical heterogeneity
• comorbidity
• DNA methylome
• polycystic ovarian syndrome

Declaration of interest

This work was supported by the Region of Southern Denmark 2012 research grant project no. 12/6629, the Novo Nordisk Foundation Medical and Natural Sciences Research Grant NNF13OC0007493 and the EFSD/CDS/Lilly Programme 2013: Epigenomic profiling in Chinese identical twins discordant for type 2 diabetes. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.