Anilkumar Thottathil R, Devi Anandavalli N, Pillai Sathy M, Jayakrishnan Krishnapillai, Oommen Oommen V, Kumar Pradeep G
Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Poojappura, Thiruvananthapuram 695014, Kerala, India.
Samad IVF Hospital, Pattoor, Vanchiyoor Road, Thiruvananthapuram 695035, Kerala, India.
Reprod Fertil Dev. 2017 Oct;29(11):2100-2111. doi: 10.1071/RD16478.
Protocadherin 11 Y-linked (PCDH11Y), a member of the cadherin superfamily, is predominantly expressed in the central nervous system, is encoded by the Yp11.2 locus and exists in three isoforms: 11Ya, 11Yb and 11Yc. PCDH11Y is upregulated by retinoic acid signalling and is essential for spermatogonial differentiation and initiation of meiosis. PCDH11Y mediates Wnt signalling, which plays a crucial role in the differentiation of various cell types. PCDH11Y has been implicated in neuronal cell differentiation and proliferation, but its association with spermatogenesis has not yet been addressed. Hence, in order to address the possible role of PCDH11Y in relation to spermatogenesis, the expression analysis of PCDH11Y in the seminal germ cells of fertile and infertile males were carried out employing RT-PCR, western blotting and immunofluorescence analysis. In the present study, PCDH11Yb, but not PCDH11Ya or PCDH11Yc, was expressed in germ cells isolated from the semen of all 13 men with proven fertility. However, in several subjects from various infertility classes, there was complete absence or a significant reduction in the expression of PCDH11Yb. PCDH11Y exhibited prominent localisation on the head and midpiece region of spermatozoa from fertile men, whereas spermatozoa from infertile subjects had either weak or abnormal localisation patterns for PCDH11Y. In addition, downregulation of canonical Wnt signalling was correlated with defective expression of PCDH11Y in spermatozoa of infertile men, as evidenced by downregulation of the Wnt targets C-Myc and C-Jun. In conclusion, expression levels of PCDH11Yb in germ cells in the semen were correlated with the fertility status of men.
Y 连锁原钙黏蛋白 11（PCDH11Y）是钙黏蛋白超家族的成员，主要在中枢神经系统中表达，由 Yp11.2 位点编码，存在三种异构体：11Ya、11Yb 和 11Yc。PCDH11Y 受视黄酸信号上调，对精原细胞分化和减数分裂起始至关重要。PCDH11Y 介导 Wnt 信号，该信号在多种细胞类型的分化中起关键作用。PCDH11Y 与神经元细胞分化和增殖有关，但其与精子发生的关联尚未得到探讨。因此，为了研究 PCDH11Y 在精子发生中的可能作用，采用逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹和免疫荧光分析，对有生育能力和不育男性的生殖细胞中 PCDH11Y 的表达进行了分析。在本研究中，从 13 名已证实有生育能力的男性精液中分离出的生殖细胞中，表达的是 PCDH11Yb，而非 PCDH11Ya 或 PCDH11Yc。然而，在来自不同不育类别的几个受试者中，PCDH11Yb 的表达完全缺失或显著降低。PCDH11Y 在有生育能力男性精子的头部和中段区域表现出明显的定位，而不育受试者的精子对 PCDH11Y 的定位要么较弱，要么异常。此外，经典 Wnt 信号的下调与不育男性精子中 PCDH11Y 的缺陷表达相关，Wnt 靶标 C-Myc 和 C-Jun 的下调证明了这一点。总之，精液中生殖细胞中 PCDH11Yb 的表达水平与男性的生育状况相关。
