Polycystic ovary syndrome is transmitted via a transgenerational epigenetic process.
Polycystic ovary syndrome is transmitted via a transgenerational epigenetic process.
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DOI：
10.1016/j.cmet.2021.01.004
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发表时间：
2021-03-02
期刊：
影响因子：
29
通讯作者：
Giacobini P
中科院分区：
文献类型：
--
作者：
Mimouni NEH;Paiva I;Barbotin AL;Timzoura FE;Plassard D;Le Gras S;Ternier G;Pigny P;Catteau-Jonard S;Simon V;Prevot V;Boutillier AL;Giacobini P
多囊卵巢综合征(PCOS)是影响育龄妇女最常见的生殖代谢障碍。PCOS具有很强的遗传成分，但其发病机制尚不清楚。在这里，我们对对照组和第三代PCOS样鼠的卵巢组织进行了RNA测序和全基因组DNA甲基化分析。我们发现，DNA低甲基化调控着与PCOS相关的关键基因，与健康对照组相比，PCOS患者血液样本中的几个差异甲基化基因也发生了变化。基于这一认识，我们用甲基供体S-腺苷蛋氨酸治疗多囊卵巢综合征小鼠模型，发现它纠正了转录、神经内分泌和代谢缺陷。这些发现表明，PCOS特征的传递是通过DNA甲基化的改变发生的，并建议将甲基组标记作为该疾病的可能诊断标志，同时也确定了基于表观遗传治疗的潜在候选者。PCOS特征在小鼠中的传递是通过改变的DNA甲基化格局发生的代谢和炎症相关的通路在PCOS模型中调节失调在PCOS小鼠模型和人类中常见的低甲基化特征PCOS多囊卵巢综合征(PCOS)是最常见的女性生殖和代谢障碍，但其发病机制尚不清楚。这里，Mimouni，Paiva等人。报告称，在小鼠中，PCOS样特征通过DNA甲基化和转录组表达的改变而传递给多代人。这些作者还确定了多囊卵巢综合征妇女中的甲基组标记作为可能的诊断里程碑和基于表观遗传的治疗候选。
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. Transmission of PCOS traits in mice occurs via an altered DNA methylation landscape Metabolic- and inflammatory-related pathways are dysregulated in models of PCOS Common hypomethylation signatures occur in a mouse model of PCOS and in humans Identification of a novel epigenetic-based therapeutic strategy for PCOS Polycystic ovary syndrome (PCOS) is the most common female reproductive and metabolic disorder, but its pathogenesis is still unknown. Here, Mimouni, Paiva et al. report that in mice, transmission of PCOS-like traits to multiple generations occurs via an altered landscape of DNA methylation and transcriptome expression. These authors also identify methylome markers in women with PCOS as possible diagnostic landmarks and candidates for epigenetic-based therapies.
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影响因子：
6.7
作者：
Crisosto, Nicolas;Ladron de Guevara, Amanda;Sir-Petermann, Teresa
通讯作者：
Sir-Petermann, Teresa
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
3.9
作者：
Anastasiadi D;Esteve-Codina A;Piferrer F
通讯作者：
Piferrer F
影响因子：
4.7
作者：
Chik, Flora;Machnes, Ziv;Szyf, Moshe
通讯作者：
Szyf, Moshe
影响因子：
3.6
作者：
FINDLAY, JK
通讯作者：
FINDLAY, JK