Gegenschatz-Schmid Katharina, Verkauskas Gilvydas, Stadler Michael B, Hadziselimovic Faruk
Cryptorchidism Research Institute, Kindermedizinisches Zentrum Liestal, 4410 Liestal, Switzerland.
2Children's Surgery Centre, Faculty of Medicine, Vilnius of University, 01513 Vilnius, Lithuania.
Basic Clin Androl. 2019 Jun 3;29:8. doi: 10.1186/s12610-019-0089-3. eCollection 2019.
Undescended (cryptorchid) testes in patients with defective mini-puberty and low testosterone levels contain gonocytes that fail to differentiate normally, which impairs the development of Ad spermatogonia and ultimately leads to adult infertility. Treatment with the gonadotropin-releasing hormone agonist GnRHa increases luteinizing hormone and testosterone and rescues fertility in the majority of pathological cryptorchid testes. Several Y-chromosomal genes in the male-specific Y region (MSY) are essential for spermatogenesis, testis development and function, and are associated with azoospermia, infertility and cryptorchidism. In this study, we analyzed the expression of MSY genes in testes with Ad spermatogonia (low infertility risk patients) as compared to testes lacking Ad spermatogonia (high infertility risk) before and after curative GnRHa treatment, and in correlation to their location on the Y-chromosome.
Twenty genes that are up- or down-regulated in the Ad- group are in the X-degenerate or the ampliconic region, respectively. GnRHa treatment increases mRNA levels of 14 genes in the ampliconic region and decreases mRNA levels of 10 genes in the X-degenerate region.
Our findings implicate Y-chromosomal genes, including , some of which are known to be important for spermatogenesis, in the curative hormonal treatment of cryptorchidism-induced infertility.
青春期前性腺功能减退和睾酮水平低的患者中，隐睾内的生殖母细胞不能正常分化，这会损害A1型精原细胞的发育，最终导致成年后不育。促性腺激素释放激素激动剂（GnRHa）治疗可提高黄体生成素和睾酮水平，并挽救大多数病理性隐睾患者的生育能力。雄性特异性Y区域（MSY）中的几个Y染色体基因对精子发生、睾丸发育和功能至关重要，且与无精子症、不育症和隐睾症相关。在本研究中，我们分析了GnRHa治疗前后，具有A1型精原细胞的睾丸（低不育风险患者）与缺乏A1型精原细胞的睾丸（高不育风险）中MSY基因的表达情况，以及它们在Y染色体上的位置关系。
A1型精原细胞缺失组中上调或下调的20个基因分别位于X退化区域或扩增区域。GnRHa治疗可增加扩增区域中14个基因的mRNA水平，并降低X退化区域中10个基因的mRNA水平。
我们的研究结果表明，Y染色体基因，包括 ，其中一些已知对精子发生很重要，在隐睾症所致不育的激素治疗中具有治疗作用。
