Liu Jianbing, Shen Chunling, Fan Weimin, Chen Yan, Zhang Aijun, Feng Yun, Li Zheng, Kuang Ying, Wang Zhugang
State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025, China.
Model Organism Division, E-Institutes of Shanghai Universities, SJTUSM , Shanghai 200025, China.
Acta Biochim Biophys Sin (Shanghai). 2016 Nov;48(11):1058-1065. doi: 10.1093/abbs/gmw096. Epub 2016 Sep 20.
PRSS37, a putative trypsin-like serine protease, is highly conserved during mammalian evolution as revealed by multiple sequence alignment. Mice deficient for Prss37 gene exhibit male infertility, but their mating behavior, spermatogenesis, sperm morphology, and motility remain unaffected, similar to a situation called unexplained male infertility (UMI) in men (human being). Here, we demonstrated that PRSS37 is restrictively expressed in human testis, where it is mainly located in the elongating and elongated spermatids during spermiogenesis as shown by immunohistochemical analysis of normal human testicular sections. In mature sperm, PRSS37 appears in the acrosome region and diminishes during acrosome reaction. Further examination reveals that PRSS37 contents in sperm from patients with UMI are dramatically lower than those in sperm from men with proven fertility or from sperm donors. Sperm with low PRSS37 contents exhibit abnormal activation of the proacrosin/acrosin system and premature proteolysis of ADAM2, which may impair the functional competence of human sperm in vivo However, the in vitro fertilization outcomes of sperm with low PRSS37 contents are not affected. Together, these data implicate an important role of PRSS37 for male fertility. PRSS37 can be used as a potential molecular biomarker for evaluating sperm fertilization capability in vivo but not in vitro.
PRSS37是一种假定的胰蛋白酶样丝氨酸蛋白酶，多序列比对显示其在哺乳动物进化过程中高度保守。Prss37基因缺陷的小鼠表现出雄性不育，但它们的交配行为、精子发生、精子形态和活力均未受影响，类似于人类中的不明原因男性不育（UMI）情况。在此，我们证明PRSS37在人类睾丸中限制性表达，免疫组化分析正常人睾丸切片显示，在精子发生过程中它主要位于伸长和已伸长的精子细胞中。在成熟精子中，PRSS37出现在顶体区域，并在顶体反应过程中减少。进一步检查发现，UMI患者精子中的PRSS37含量显著低于生育能力已证实的男性或精子捐献者的精子中的PRSS37含量。PRSS37含量低的精子表现出前顶体蛋白酶/顶体蛋白酶系统的异常激活以及ADAM2的过早蛋白水解，这可能会损害人类精子在体内的功能能力。然而，PRSS37含量低的精子的体外受精结果不受影响。总之，这些数据表明PRSS37对男性生育具有重要作用。PRSS37可作为一种潜在的分子生物标志物，用于评估精子在体内而非体外的受精能力。
