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多囊卵巢综合症与表观遗传DNA甲基化调控的研究进展
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Abstract:
多囊卵巢综合征(polycystic ovary syndrome, PCOS)是育龄妇女中最常见的内分泌疾病。尽管它的发生率很高，也被认为是无排卵性不孕症的主要原因，但人们对这种综合征知之甚少，并且仍然未得到充分诊断与治疗，致使女性患者的治疗方案研究进展缓慢。这种复杂疾病的异质性是遗传、环境、内分泌和行为因素共同发生的结果。通常与卵巢增大和功能失调、雄激素水平过高、胰岛素抵抗等有关。目前来说，没有单一的病因学因素可以完全解释PCOS的发病机制，大多证据表明PCOS是一种复杂的多因素疾病，且具有高度的遗传性。而表观遗传是指基因组和基因表达的可遗传改变，但DNA序列没有发生任何变化，表观遗传包括DNA甲基化、组蛋白修饰(乙酰化、磷酸化、甲基化等)和非编码RNA (ncRNA)含量的变化。现有研究表明表观遗传学，尤其是DNA甲基化，在PCOS的发病机制中起关键作用。
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of childbearing age. Despite its high incidence and being considered the main cause of anovulatory infertility, the syndrome is still poorly understood and remains underdiagnosed and undertreated, leading to slow progress in the research of treatment options for female patients. The heterogeneity of this complex disease is the result of a combination of genetic, environmental, endocrine, and behavioral factors. It is commonly associated with enlarged and dysfunctional ovaries, elevated levels of androgens, and insulin resistance. At present, there is no single etiological factor that can fully explain the pathogenesis of PCOS. Most evidence suggests that PCOS is a complex multifactorial disease with a high degree of heritability. Epigenetics refers to heritable changes in genome and gene expression without any alterations in DNA sequence. Epigenetics includes changes in DNA methylation, histone modifications (acetylation, phosphorylation, methylation, etc.), and non coding RNA (ncRNA) content. Existing research suggests that epigenetics, particularly DNA methylation, plays a crucial role in the pathogenesis of PCOS.
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