研究揭示多囊卵巢综合征的传播基础
2021-02-06   阅读:365   来源:细胞

法国里尔大学Paolo Giacobini及斯特拉斯堡大学Anne-Laurence Boutillier小组合作的研究发现多囊卵巢综合征(PCOS)通过跨代表观遗传传播。这一研究成果于2021年2月3日在线发表在国际学术期刊《细胞-代谢》上。

研究人员对来自对照组和第三代PCOS样小鼠的卵巢组织进行了RNA测序和全基因组DNA甲基化分析。研究发现,DNA低甲基化调节了与PCOS相关的关键基因;与健康对照组相比,患有PCOS的雌性血液样本中一些差异甲基化基因也发生了改变。基于此,研究人员用甲基供体S-腺苷甲硫氨酸处理了PCOS模型小鼠,发现S-腺苷甲硫氨酸纠正了PCOS模型小鼠的转录组、神经内分泌和代谢缺陷。

这些发现表明,PCOS传递给后代是通过DNA甲基化完成的,并揭示了甲基化组标记物可作为该病诊断的潜在标志物,同时还确定了基于表观遗传学治疗的潜在靶点。

据了解,多囊卵巢综合症是影响生殖年龄段妇女最常见的生殖和代谢疾病。PCOS具有很强的遗传性,但其发病机理尚不清楚。

附:英文原文

Title: Polycystic ovary syndrome is transmitted via a transgenerational epigenetic process

Author: Nour El Houda Mimouni, Isabel Paiva, Anne-Laure Barbotin, Fatima Ezzahra Timzoura, Damien Plassard, Stephanie Le Gras, Gaetan Ternier, Pascal Pigny, Sophie Catteau-Jonard, Virginie Simon, Vincent Prevot, Anne-Laurence Boutillier, Paolo Giacobini

Issue&Volume: 2021-02-03

Abstract: Polycystic ovary syndrome (PCOS) is the most common reproductive and metabolic disorder affecting women of reproductive age. PCOS has a strong heritable component, but its pathogenesis has been unclear. Here, we performed RNA sequencing and genome-wide DNA methylation profiling of ovarian tissue from control and third-generation PCOS-like mice. We found that DNA hypomethylation regulates key genes associated with PCOS and that several of the differentially methylated genes are also altered in blood samples from women with PCOS compared with healthy controls. Based on this insight, we treated the PCOS mouse model with the methyl group donor S-adenosylmethionine and found that it corrected their transcriptomic, neuroendocrine, and metabolic defects. These findings show that the transmission of PCOS traits to future generations occurs via an altered landscape of DNA methylation and propose methylome markers as a possible diagnostic landmark for the condition, while also identifying potential candidates for epigenetic-based therapy.

DOI: 10.1016/j.cmet.2021.01.004

 

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