MRKH综合征即先天性无阴道无子宫，为Müllerian管发育不全所致，严重危害女性身心健康，病因尚不明确。我们前期通过全基因组De novo CNV分析发现1例患者存在Y染色体片段，并证实其中的男性基因TSPY1确实存在于MRKH患者基因组中。由于MRKH患者Müllerian管尾端不发育与男性Müllerian管退化的生理过程相似，我们推测男性TSPY1基因可能参与调控Müllerian管退化，其异常存在于女性基因组中可能引起女性Müllerian管退化而出现MRKH表型。本项目在大鼠胚胎Müllerian管退化过程中观察Tspy1的表达及其与Müllerian管退化关键基因表达的关系，并在离体组织中调控Tspy1基因后观察其对Müllerian管退化的影响，最后在大样本临床标本中验证，以明确TSPY1在MRKH综合征中的作用。

MRKH syndrome, also called congenital absence of the uterus and vagina, is caused by aplasia of the caudal portion of the Müllerian duct.It severely affects women’s mental and physical health. The etiology of the disease remains unknown.We previously identified the presence of the Y chromosomal segment in 1 MRKH patient by genome-wide de novo copy number analysis,and confirmed the existence of male specific gene TSPY1 in certain patients. Since Müllerian duct aplasia in MRKH patients closely resembles the process of Müllerian duct regression in normal males during embryogenesis, we speculate that the TSPY1 gene in males is involved in Müllerian duct regression and its abnormal existence in the female genome can induce Müllerian duct regression and result in MRKH syndrome. In this study, we will detect the expression of the Tspy1 gene and its relationship with the key gene Amhr2 during the process of Müllerian duct regression in rat embryos.And we will use ex vivo magnetofection and siRNA to regulate the Tspy1 gene in organ culture,in order to observe the effects of Tspy1 on Müllerian duct regression. Finally amplification of the TSPY1 gene will be carried out in a large sample of MRKH cases to confirm the involvement of TSPY1 in the pathogenesis of the syndrome.