Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

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

Thottathil R. Anilkumar A , Anandavalli N. Devi A , Sathy M. Pillai B , Krishnapillai Jayakrishnan C , Oommen V. Oommen D and Pradeep G. Kumar A E
+ Author Affiliations
- Author Affiliations

A Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Poojappura, Thiruvananthapuram 695014, Kerala, India.

B Samad IVF Hospital, Pattoor, Vanchiyoor Road, Thiruvananthapuram 695035, Kerala, India.

C KJK Hospital, Nalanchira, Trivandrum 695015, Kerala, India.

D Department of Zoology, University of Kerala, Kariyavattom, Trivandrum, 695581, Kerala, India.

E Corresponding author. Email: kumarp@rgcb.res.in

Reproduction, Fertility and Development 29(11) 2100-2111 https://doi.org/10.1071/RD16478
Submitted: 28 March 2016  Accepted: 4 January 2017   Published: 28 February 2017

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.

Additional keywords: male infertility, spermatogenesis, spermatozoa, testis.


References

Blanco, P., Sargent, C. A., Boucher, C. A., Mitchell, M., and Affara, N. A. (2000). Conservation of PCDHX in mammals; expression of human X/Y genes predominantly in brain. Mamm. Genome 11, 906–914.
Conservation of PCDHX in mammals; expression of human X/Y genes predominantly in brain.CrossRef | 1:CAS:528:DC%2BD3cXnsleiur4%3D&md5=5617f98258bd0c45d7c968834a7ec98fCAS |

Blanco-Arias, P., Sargent, C. A., and Affara, N. A. (2004). A comparative analysis of the pig, mouse, and human PCDHX genes. Mamm. Genome 15, 296–306.
A comparative analysis of the pig, mouse, and human PCDHX genes.CrossRef | 1:CAS:528:DC%2BD2cXjsVeqsLw%3D&md5=4da7e88d253811dc1a17b438eec88c92CAS |

Chandley, A. C. (1998). Chromosome anomalies and Y chromosome microdeletions as causal factors in male infertility. Hum. Reprod. 13, 45–50.
Chromosome anomalies and Y chromosome microdeletions as causal factors in male infertility.CrossRef | 1:CAS:528:DyaK1cXks1ajtrw%3D&md5=f6fcc34c15c917d487f980414e2631c4CAS |

Chen, M. W., Vacherot, F., De La Taille, A., Gil-Diez-De-Medina, S., Shen, R., Friedman, R. A., Burchardt, M., Chopin, D. K., and Buttyan, R. (2002). The emergence of protocadherin-PC expression during the acquisition of apoptosis-resistance by prostate cancer cells. Oncogene 21, 7861–7871.
The emergence of protocadherin-PC expression during the acquisition of apoptosis-resistance by prostate cancer cells.CrossRef | 1:CAS:528:DC%2BD38XosVektb8%3D&md5=bb6da39ac0915facb6d0330007b657a4CAS |

Chomczynski, P. (1993). A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques 15, 532–537.
| 1:CAS:528:DyaK3sXms1Grtrs%3D&md5=11196d04384986fad0634cdbadcddae0CAS |

Cooper, T. G., Noonan, E., von Eckardstein, S., Auger, J., Baker, H. W., Behre, H. M., Haugen, T. B., Kruger, T., Wang, C., Mbizvo, M. T., and Vogelsong, K. M. (2010). World Health Organization reference values for human semen characteristics. Hum. Reprod. Update 16, 231–245.
World Health Organization reference values for human semen characteristics.CrossRef |

Dam, A. H., Koscinski, I., Kremer, J. A., Moutou, C., Jaeger, A. S., Oudakker, A. R., Tournaye, H., Charlet, N., Lagier-Tourenne, C., van Bokhoven, H., and Viville, S. (2007). Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia. Am. J. Hum. Genet. 81, 813–820.
Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia.CrossRef | 1:CAS:528:DC%2BD2sXhtFSktrjO&md5=a88d9e3a11d09185245d8e726d0f6cfbCAS |

De Gendt, K., Swinnen, J. V., Saunders, P. T., Schoonjans, L., Dewerchin, M., Devos, A., Tan, K., Atanassova, N., Claessens, F., Lecureuil, C., Heyns, W., Carmeliet, P., Guillou, F., Sharpe, R. M., and Verhoeven, G. (2004). A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis. Proc. Natl Acad. Sci. USA 101, 1327–1332.
A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis.CrossRef | 1:CAS:528:DC%2BD2cXhtlWjtbw%3D&md5=2a41014b5d6bffdd4cfd7d5088ab2fb6CAS |

Devi, A. N., Anil Kumar, T. R., Pillai, S. M., Jayakrishnan, K., and Kumar, P. G. (2015). Expression profiles of NPHP1 in the germ cells in the semen of men with male factor infertility. Andrology 3, 685–693.
Expression profiles of NPHP1 in the germ cells in the semen of men with male factor infertility.CrossRef | 1:CAS:528:DC%2BC2MXht1GkurfJ&md5=820489c896e78dc9ced807fc2685dee7CAS |

Diemer, T., and Desjardins, C. (1999). Developmental and genetic disorders in spermatogenesis. Hum. Reprod. Update 5, 120–140.
Developmental and genetic disorders in spermatogenesis.CrossRef | 1:STN:280:DyaK1M3mslSnug%3D%3D&md5=ac432c3544a1231cd22e989978bd14a5CAS |

Dohle, G. R., Diemer, T., Kopa, Z., Krausz, C., Giwercman, A., and Jungwirth, A. (2012). European Association of Urology guidelines on vasectomy. Eur. Urol. 61, 159–163.
European Association of Urology guidelines on vasectomy.CrossRef |

Dravid, G., Ye, Z., Hammond, H., Chen, G., Pyle, A., Donovan, P., Yu, X., and Cheng, L. (2005). Defining the role of Wnt/beta-catenin signaling in the survival, proliferation, and self-renewal of human embryonic stem cells. Stem Cells 23, 1489–1501.
Defining the role of Wnt/beta-catenin signaling in the survival, proliferation, and self-renewal of human embryonic stem cells.CrossRef | 1:CAS:528:DC%2BD28Xmtw%3D%3D&md5=29b22634ff7ba59b5a3e2533786257e0CAS |

Egloff, M. P., Johnson, D. F., Moorhead, G., Cohen, P. T., Cohen, P., and Barford, D. (1997). Structural basis for the recognition of regulatory subunits by the catalytic subunit of protein phosphatase 1. EMBO J. 16, 1876–1887.
Structural basis for the recognition of regulatory subunits by the catalytic subunit of protein phosphatase 1.CrossRef | 1:CAS:528:DyaK2sXjt1Wls7c%3D&md5=fe32c8defda47093e766de462d7669feCAS |

Esteves, S. C. (2013). A clinical appraisal of the genetic basis in unexplained male infertility. J. Hum. Reprod. Sci. 6, 176–182.
A clinical appraisal of the genetic basis in unexplained male infertility.CrossRef |

Feigerlova, E., and Battaglia-Hsu, S.-F. (2016). Role of post-transcriptional regulation of mRNA stability in renal pathophysiology: focus on chronic kidney disease. FASEB J. , .
Role of post-transcriptional regulation of mRNA stability in renal pathophysiology: focus on chronic kidney disease.CrossRef |

Guo, X., Gui, Y. T., Tang, A. F., Lu, L. H., Gao, X., and Cai, Z. M. (2007). Differential expression of VASA gene in ejaculated spermatozoa from normozoospermic men and patients with oligozoospermia. Asian J. Androl. 9, 339–344.
Differential expression of VASA gene in ejaculated spermatozoa from normozoospermic men and patients with oligozoospermia.CrossRef | 1:CAS:528:DC%2BD2sXms1Ohu78%3D&md5=799f76006aa9fb40d7ebd1e5391ee606CAS |

Hamada, A. J., Esteves, S. C., and Agarwal, A. (2013). A comprehensive review of genetics and genetic testing in azoospermia. Clinics. (Sao Paulo) 68, 39–60.
A comprehensive review of genetics and genetic testing in azoospermia.CrossRef |

Hargreave, T. B. (2000). Genetic basis of male fertility. Br. Med. Bull. 56, 650–671.
Genetic basis of male fertility.CrossRef | 1:CAS:528:DC%2BD3MXot1CqtQ%3D%3D&md5=6bcea9e1b8b38e719743b96addca4b4dCAS |

Hendriks, B., and Reichmann, E. (2002). Wnt signaling: a complex issue. Biol. Res. 35, 277–286.
Wnt signaling: a complex issue.CrossRef | 1:CAS:528:DC%2BD3sXhtVWhurY%3D&md5=0b6840ba3996834eaac915f778304a9eCAS |

Henshall, D. C., Hamer, H. M., Pasterkamp, R. J., Goldstein, D. B., Kjems, J., Prehn, J. H., Schorge, S., Lamottke, K., and Rosenow, F. (2016). MicroRNAs in epilepsy: pathophysiology and clinical utility. Lancet Neurol. 15, 1368–1376.
MicroRNAs in epilepsy: pathophysiology and clinical utility.CrossRef | 1:CAS:528:DC%2BC28XhvVWmtr7F&md5=f94d303aabe5c7d7cb586e696cb7c3e9CAS |

Hirano, S., Yan, Q., and Suzuki, S. T. (1999). Expression of a novel protocadherin, OL-protocadherin, in a subset of functional systems of the developing mouse brain. J. Neurosci. 19, 995–1005.
| 1:CAS:528:DyaK1MXpvVWnuw%3D%3D&md5=dcd7d3a448edc9dce3dcaab779aa6945CAS |

Ji, J., Chen, X., Leung, S. Y., Chi, J. T., Chu, K. M., Yuen, S. T., Li, R., Chan, A. S., Li, J., Dunphy, N., and So, S. (2002). Comprehensive analysis of the gene expression profiles in human gastric cancer cell lines. Oncogene 21, 6549–6556.
Comprehensive analysis of the gene expression profiles in human gastric cancer cell lines.CrossRef | 1:CAS:528:DC%2BD38XmvVOqsbw%3D&md5=3a1bbfb2b48b4b0ae4f6d0dcb22f872dCAS |

Kobori, Y., Pfanner, P., Prins, G. S., and Niederberger, C. (2016). Novel device for male infertility screening with single-ball lens microscope and smartphone. Fertil. Steril. 106, 574–578.
Novel device for male infertility screening with single-ball lens microscope and smartphone.CrossRef |

Kumar, N., and Singh, A. K. (2015). Trends of male factor infertility, an important cause of infertility: A review of literature. J. Hum. Reprod. Sci. 8, 191–196.
Trends of male factor infertility, an important cause of infertility: A review of literature.CrossRef |

Kuroda-Kawaguchi, T., Skaletsky, H., Brown, L. G., Minx, P. J., Cordum, H. S., Waterston, R. H., Wilson, R. K., Silber, S., Oates, R., Rozen, S., and Page, D. C. (2001). The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men. Nat. Genet. 29, 279–286.
The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men.CrossRef | 1:CAS:528:DC%2BD3MXotlWhsLY%3D&md5=58f2b218c192cc9c65641e647eaeff6aCAS |

Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685.
Cleavage of structural proteins during the assembly of the head of bacteriophage T4.CrossRef | 1:CAS:528:DC%2BD3MXlsFags7s%3D&md5=64563e9eb12eab835214b4384676485eCAS |

Lustig, B., and Behrens, J. (2003). The Wnt signaling pathway and its role in tumor development. J. Cancer Res. Clin. Oncol. 129, 199–221.
| 1:STN:280:DC%2BD3s3itFGqtg%3D%3D&md5=e58207bbf4da4e1d6cdbf37bfd819262CAS |

Maekawa, S., Imamachi, N., Irie, T., Tani, H., Matsumoto, K., Mizutani, R., Imamura, K., Kakeda, M., Yada, T., Sugano, S., Suzuki, Y., and Akimitsu, N. (2015). Analysis of RNA decay factor mediated RNA stability contributions on RNA abundance. BMC Genomics 16, 154.
Analysis of RNA decay factor mediated RNA stability contributions on RNA abundance.CrossRef |

Nollet, F., Kools, P., and van Roy, F. (2000). Phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members. J. Mol. Biol. 299, 551–572.
Phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members.CrossRef | 1:CAS:528:DC%2BD3cXjs12nsbc%3D&md5=401a915aae93986e827692e7e807ac79CAS |

Nuti, F., and Krausz, C. (2008). Gene polymorphisms/mutations relevant to abnormal spermatogenesis. Reprod. Biomed. Online 16, 504–513.
Gene polymorphisms/mutations relevant to abnormal spermatogenesis.CrossRef | 1:CAS:528:DC%2BD1cXlsFOqs7s%3D&md5=c82d05b3ff34675e4cfa48e99d75e883CAS |

Ouimet, C. C., da Cruz e Silva, E. F., and Greengard, P. (1995). The alpha and gamma 1 isoforms of protein phosphatase 1 are highly and specifically concentrated in dendritic spines. Proc. Natl Acad. Sci. USA 92, 3396–3400.
The alpha and gamma 1 isoforms of protein phosphatase 1 are highly and specifically concentrated in dendritic spines.CrossRef | 1:CAS:528:DyaK2MXltFSnu78%3D&md5=d6b5bd10ad8c9f119d5489adc40c9befCAS |

Piven, O. O., Kostetskii, I. E., Macewicz, L. L., Kolomiets, Y. M., Radice, G. L., and Lukash, L. L. (2011). Requirement for N-cadherin–catenin complex in heart development. Exp. Biol. Med. (Maywood) 236, 816–822.
Requirement for N-cadherin–catenin complex in heart development.CrossRef | 1:CAS:528:DC%2BC3MXpvFeqsr4%3D&md5=8e02d5fa967ceee97677d0efe942d093CAS |

Purohit, S., Brahmaraju, M., Palta, A., Shukla, S., Laloraya, M., and Kumar, P. G. (2004). Impaired E-cadherin expression in human spermatozoa in a male factor infertility subset signifies E-cadherin-mediated adhesion mechanisms operative in sperm–oolemma interactions. Biochem. Biophys. Res. Commun. 316, 903–909.
Impaired E-cadherin expression in human spermatozoa in a male factor infertility subset signifies E-cadherin-mediated adhesion mechanisms operative in sperm–oolemma interactions.CrossRef | 1:CAS:528:DC%2BD2cXitFKgt7w%3D&md5=e2a395f64abe0cfd59d0b2ffa7de6136CAS |

Raverdeau, M., Gely-Pernot, A., Feret, B., Dennefeld, C., Benoit, G., Davidson, I., Chambon, P., Mark, M., and Ghyselinck, N. B. (2012). Retinoic acid induces Sertoli cell paracrine signals for spermatogonia differentiation but cell autonomously drives spermatocyte meiosis. Proc. Natl Acad. Sci. USA 109, 16582–16587.
Retinoic acid induces Sertoli cell paracrine signals for spermatogonia differentiation but cell autonomously drives spermatocyte meiosis.CrossRef | 1:CAS:528:DC%2BC38XhsFKltrjN&md5=9ed8a3b2640b4ae5ef99618f3bf93dedCAS |

Shevchenko, A., Tomas, H., Havlis, J., Olsen, J. V., and Mann, M. (2006). In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat. Protoc. 1, 2856–2860.
In-gel digestion for mass spectrometric characterization of proteins and proteomes.CrossRef | 1:CAS:528:DC%2BD2sXhtFGjt7nM&md5=5acd0642120b0afcccacbdbcf96c4a05CAS |

Terry-Lorenzo, R. T., Carmody, L. C., Voltz, J. W., Connor, J. H., Li, S., Smith, F. D., Milgram, S. L., Colbran, R. J., and Shenolikar, S. (2002). The neuronal actin-binding proteins, neurabin I and neurabin II, recruit specific isoforms of protein phosphatase-1 catalytic subunits. J. Biol. Chem. 277, 27716–27724.
The neuronal actin-binding proteins, neurabin I and neurabin II, recruit specific isoforms of protein phosphatase-1 catalytic subunits.CrossRef | 1:CAS:528:DC%2BD38XlvFKgsbw%3D&md5=ceeb3a024e19709362a50765aa175411CAS |

Thonneau, P., Marchand, S., Tallec, A., Ferial, M. L., Ducot, B., Lansac, J., Lopes, P., Tabaste, J. M., and Spira, A. (1991). Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988–1989). Hum. Reprod. 6, 811–816.
| 1:STN:280:DyaK38%2FpvVKmug%3D%3D&md5=e8e6230f0778a3d0fa9e43f797f85500CAS |

Towbin, H., Staehelin, T., and Gordon, J. (1992). Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. 1979. Biotechnology 24, 145–149.
| 1:STN:280:DyaK3s%2FksVWnsQ%3D%3D&md5=a70191459222256100d5e39eba453eeeCAS |

van Es, J. H., Barker, N., and Clevers, H. (2003). You Wnt some, you lose some: oncogenes in the Wnt signaling pathway. Curr. Opin. Genet. Dev. 13, 28–33.
You Wnt some, you lose some: oncogenes in the Wnt signaling pathway.CrossRef | 1:CAS:528:DC%2BD3sXmsFCjtA%3D%3D&md5=ab404f7c8f9b672545d609ce11c4ad48CAS |

Vanhalst, K., Kools, P., Staes, K., van Roy, F., and Redies, C. (2005). delta-Protocadherins: a gene family expressed differentially in the mouse brain. Cell Mol. Life Sci. 62, 1247–1259.
delta-Protocadherins: a gene family expressed differentially in the mouse brain.CrossRef | 1:CAS:528:DC%2BD2MXhtFCgs7nN&md5=8e75d80f2954efb86373162c0f1f4de6CAS |

Varghese, D. S., Chandran, U., Soumya, A., Pillai, S. M., Jayakrishnan, K., Reddi, P. P., and Kumar, P. G. (2016). Aberrant expression of TAR DNA binding protein-43 is associated with spermatogenic disorders in men. Reprod. Fertil. Dev. 28, 713–722.
Aberrant expression of TAR DNA binding protein-43 is associated with spermatogenic disorders in men.CrossRef | 1:CAS:528:DC%2BC28XmsFOltr8%3D&md5=beae2fbf31ef3e50f32f4b6cadbacb83CAS |

Vogt, P. H. (1998). Human chromosome deletions in Yq11, AZF candidate genes and male infertility: history and update. Mol. Hum. Reprod. 4, 739–744.
Human chromosome deletions in Yq11, AZF candidate genes and male infertility: history and update.CrossRef | 1:CAS:528:DyaK1cXmtFWksbo%3D&md5=7149961844c6db5580e1c669b551e6cdCAS |

Vogt, P. H. (2005). Azoospermia factor (AZF) in Yq11: towards a molecular understanding of its function for human male fertility and spermatogenesis. Reprod. Biomed. Online 10, 81–93.
Azoospermia factor (AZF) in Yq11: towards a molecular understanding of its function for human male fertility and spermatogenesis.CrossRef | 1:CAS:528:DC%2BD2MXhtF2lsLY%3D&md5=bb1fdfdef164874cbe1160f1bbbdb92eCAS |

Vogt, P. H., Edelmann, A., Kirsch, S., Henegariu, O., Hirschmann, P., Kiesewetter, F., Kohn, F. M., Schill, W. B., Farah, S., Ramos, C., Hartmann, M., Hartschuh, W., Meschede, D., Behre, H. M., Castel, A., Nieschlag, E., Weidner, W., Grone, H. J., Jung, A., Engel, W., and Haidl, G. (1996). Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum. Mol. Genet. 5, 933–943.
Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11.CrossRef | 1:CAS:528:DyaK28Xkt1Cntrk%3D&md5=691c4b95f03db375b5f2bf588bc54156CAS |

Yang, X., Chen, M. W., Terry, S., Vacherot, F., Chopin, D. K., Bemis, D. L., Kitajewski, J., Benson, M. C., Guo, Y., and Buttyan, R. (2005). A human- and male-specific protocadherin that acts through the wnt signaling pathway to induce neuroendocrine transdifferentiation of prostate cancer cells. Cancer Res. 65, 5263–5271.
A human- and male-specific protocadherin that acts through the wnt signaling pathway to induce neuroendocrine transdifferentiation of prostate cancer cells.CrossRef | 1:CAS:528:DC%2BD2MXltFemu7s%3D&md5=1c8bbc6ff7034fb3568af7096e2e8b3dCAS |

Zheng, L., Li, C., Sun, Y., Liu, Z., and Zhou, X. (2011). Expression of brain-derived neurotrophic factor in mature spermatozoa from fertile and infertile men. Clin. Chim. Acta 412, 44–47.
Expression of brain-derived neurotrophic factor in mature spermatozoa from fertile and infertile men.CrossRef | 1:CAS:528:DC%2BC3cXhsVGkurbM&md5=a4989c90d30f77963bbd9a6ff6bb5f4dCAS |



Rent Article (via Deepdyve) Supplementary MaterialSupplementary Material (1.8 MB) Export Citation

View Altmetrics