Expression of protocadherin 11Yb (PCDH11Yb) in seminal germ cells is correlated with fertility status in men

Abstract

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.

Genome-wide DNA methylation, imprinting, and gene expression in human placentas derived from Assisted Reproductive Technology

“…Interestingly, the upregulated genes ZFY, RPS4Y1, PCDH11Y, and DDX3Y in the ICSI placentas locate on chromosome Y and the expressions of them all correlated significantly with each other in ART male placentas, but not in the controls (Supplementary Table 7). Since male infertility was a common reason (44.4%) for the infertility among the analyzed ICSI male samples (Supplementary Table 17) the upregulated genes DDX3Y 46 , ZFY 47 , and PCDH11Y 48 , which all have been associated with male infertility in previous studies, are notable. Furthermore, the ICSI-associated DEGs MAP1B, HBA1, EPHX1, HBB , and HBG2 enriched in response-to-toxic-substance pathway are also interesting (FDR-corrected q -value < 0.05), considering that environmental exposures have been associated with male infertility in previous studies (Supplementary Table 18).…”

Impact of vitamin D depletion during development on mouse sperm DNA methylation

“…A large number of the genome-wide loss of methylation changes detected here localize to genes involved in Wnt (168 genes, 68 with effect size > 10%) and Cadherin (95 genes, 45 with effect size > 10%) signaling pathways, demonstrating enrichment of genes in these pathways, which could be indicative of perturbed sperm development [32,33] or perturbed development of the second generation which could inherit these changes. Any sperm developmental changes in these first generation animals would likely be subtle since our previous assessment of DVD in males showed no difference in sperm count or litter size [20].…”

Molecular characterization of the Yp11.2 region deletion in the Chinese Han population

“…PCDH11Y plays a role in cell-cell recognition during central nervous system development, belongs to the protocadherin family, and is very closely related to its paralog on the X chromosome. PCDH11Y is essential for spermatogonial differentiation and initiation of meiosis [ 13 ] and may also be a candidate marker for susceptibility to psychiatric disorders [ 14 ]. TSPY is expressed only in testicular tissue and may be involved in spermatogenesis.…”