The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (OMIM 277000) is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. While genetic causes have been identified for a small subset of patients and epigenetic mechanisms presumably contribute to the pathogenic unfolding, too, the etiology of the syndrome has remained largely enigmatic. A comprehensive understanding of gene activity in the context of the disease is crucial to identify etiological components and their potential interplay. So far, this understanding is lacking, primarily due to the scarcity of samples and suitable tissue. In order to close this gap, we profiled endometrial tissue of uterus rudiments in a large cohort of MRKH patients using RNA-seq and thereby provide a genome-wide view on the altered transcription landscape of the MRKH syndrome. Differential and co-expression analyses of the data identified cellular processes and candidate genes that converge on a core network of interconnected regulators that emerge as pivotal for the perturbed expression space. With these results and browsable access to the rich data through an online tool we seek to accelerate research to unravel the underlying biology of the syndrome.

Mayer-Rokitansky-Küster-Hauser (MRKH) 综合征 (OMIM 277000) 的特征是卵巢功能正常的女性子宫和阴道上部发育不全。虽然已经确定了一小部分患者的遗传原因，并且表观遗传机制可能也有助于致病性的展开，但该综合征的病因在很大程度上仍然是个谜。全面了解疾病背景下的基因活性对于确定病因成分及其潜在相互作用至关重要。到目前为止，这种认识还缺乏，主要是由于样本和合适组织的缺乏。为了弥补这一差距，我们使用 RNA-seq 对一大群 MRKH 患者的子宫内膜组织进行了分析，从而提供了 MRKH 综合征转录图谱改变的全基因组视图。对数据的差异和共表达分析确定了细胞过程和候选基因，这些细胞过程和候选基因汇聚在互连调节因子的核心网络上，这些调节因子对于扰动的表达空间至关重要。凭借这些结果以及通过在线工具可浏览的丰富数据，我们寻求加速研究，以揭示该综合征的潜在生物学原理。