SYCP 3 T 657 C Gene Polymorphism Increases Risk of Developing Infertility in Non-Obstructive Azoospermic Cases in Indian Population — Oak Academic Publishing
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SYCP 3 T 657 C Gene Polymorphism Increases Risk of Developing Infertility in Non-Obstructive Azoospermic Cases in Indian Population
Human Molecular Genetics Laboratory, Department of Pathology/Lab Medicine, All India Institute of Medical Sciences, Patna, India
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Human Molecular Genetics Laboratory, Department of Pathology/Lab Medicine, All India Institute of Medical Sciences, Patna, India
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Human Molecular Genetics Laboratory, Department of Pathology/Lab Medicine, All India Institute of Medical Sciences, Patna, India
,
Human Molecular Genetics Laboratory, Department of Pathology/Lab Medicine, All India Institute of Medical Sciences, Patna, India
,
Human Molecular Genetics Laboratory, Department of Pathology/Lab Medicine, All India Institute of Medical Sciences, Patna, India
,
Human Molecular Genetics Laboratory, Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Patna, India
1 Human Molecular Genetics Laboratory, Department of Pathology/Lab Medicine, All India Institute of Medical Sciences, Patna, India
2 Human Molecular Genetics Laboratory, Department of Pathology/Lab Medicine, All India Institute of Medical Sciences, Patna, India
3 Human Molecular Genetics Laboratory, Department of Pathology/Lab Medicine, All India Institute of Medical Sciences, Patna, India
4 Human Molecular Genetics Laboratory, Department of Pathology/Lab Medicine, All India Institute of Medical Sciences, Patna, India
5 Human Molecular Genetics Laboratory, Department of Pathology/Lab Medicine, All India Institute of Medical Sciences, Patna, India
6 Human Molecular Genetics Laboratory, Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Patna, India
Etiopathology of male infertility is highly complex and chromosome rearrangements play an important role in non-obstructive azoospermia (NOA). Testes is the unique organ, where, spermatogenesis regulates the proliferation of germ cells and non-germinal cells (Sertoli cells & Leydig cells) work together in a synchronized fashion. Infertility is a genetic phenomenon and a variety of structural and numerical chromosome aberrations are well known to interfere with male infertility. The role of Sycp T 657 C gene polymorphism has been poorly documented in the Indian population with special reference to non-obstructive azoospermic (NOA) cases. The present study has been designed with the aim to evaluate the following: 1) Cytogenetics study for evaluating the frequency of both structural and numerical chromosome variations in (NOA) cases by short-term peripheral blood lymphocyte (PBL) cultures; 2) Genetic heterogenicity of the Sycp 3 gene polymorphism by evaluating the frequency of T/C alleles. PCR-based analysis was carried out to characterize bands on agarose gel after ethidium bromide staining and bands were visualized on Gel-Doc system. Karyotype showing two new loci involving chromatid breaks 46,XY2q34, and 46,XY4q32 with the loss of DNA fragment of > 8.0 Mbp. Difference in the frequency of Robertsonian translocation (20%) and mosaicism (46,XY/47,XYY) were observed in the same karyotype. SYCP 3 polymorphism shows significant changes in the frequency of TT genotype (43.33%) in homozygous conditions (wild type) and the calculated value of odd ratio (0.23) with a confidence interval varying from 0.08 - 0.71, suggesting an increased risk of developing infertility. To enhance the power of significance, two genotypes were combined together CC + TC which again showed significance with respect to controls. Data of the present study concludes that genetic heterogenicity of Sycp 3 gene polymorphism and chromosomal aberrations with loss of DNA (8 Mbp) together confirm of developing risk of infertility in the NOA population.
KeywordsSYCP 3 GeneMale infertilityNOAPolymorphismDNA Fragment
Saxena, A.K. (2020) Genes and Male Infertility in Human. Index of Sciences Ltd.
Kumar, N. and Singh, A. (2015) Trends of Male Factor Infertility, an Important Cause of Infertility: A Review of Literature. Journal of Human Reproductive Sciences , 8, Article 191. https://doi.org/10.4103/0974-1208.170370
Cioppi, F., Rosta, V. and Krausz, C. (2021) Genetics of Azoospermia. International Journal of Molecular Sciences , 22, Article 3264. https://doi.org/10.3390/ijms22063264
Krausz, C. and Riera-Escamilla, A. (2018) Genetics of Male Infertility. Nature Reviews Urology , 15, 369-384. https://doi.org/10.1038/s41585-018-0003-3
Peña, V.N., Kohn, T.P. and Herati, A.S. (2020) Genetic Mutations Contributing to Non-Obstructive Azoospermia. Best Practice & Research Clinical Endocrinology & Metabolism , 34, Article 101479. https://doi.org/10.1016/j.beem.2020.101479
Nuti, F. and Krausz, C. (2008) Gene Polymorphisms/Mutations Relevant to Abnormal Spermatogenesis. Reproductive BioMedicine Online , 16, 504-513. https://doi.org/10.1016/s1472-6483(10)60457-9
Crider, K.S., Yang, T.P., Berry, R.J. and Bailey, L.B. (2012) Folate and DNA Methylation: A Review of Molecular Mechanisms and the Evidence for Folate’s Role. Advances in Nutrition , 3, 21-38. https://doi.org/10.3945/an.111.000992
Saxena, A.K., Singh, V., Agarwal, M., Tiwari, M., et al . (2018) Penetrance of MTHFR, MTRR and SHMT Genes Polymorphism Modulate Folate Metabolism in Maternal Blood and Increase “Risk Factor” in the Development of Neural Tube Defects in Eastern India. Human Genetics and Embryology , 8, 1-9.
Saxena, A.K., Agarwal, M., Kumar, A. and Singh, C.K. (2020) Genetic Heterogenicity of MTHFR C677T Allele Modulate Hormonal Dysfunction Associated Risk Factors in the Cases of Male Infertility. International Journal of Development Research , 10, 42700-42705.
Hughes, J.F. and Page, D.C. (2016) The History of the Y Chromosome in Man. Nature Genetics , 48, 588-589. https://doi.org/10.1038/ng.3580
Arumugam, M., Prashanth Shetty, D., Shanker Kadandale, J. and Nalilu Kumari, S. (2021) Y Chromosome Microdeletion and Cytogenetic Findings in Male Infertility: A Cross-Sectional Descriptive Study. International Journal of Reproductive BioMedicine ( IJRM ), 19, 147-156. https://doi.org/10.18502/ijrm.v19i2.8473
Bar-Shira Maymon, B., Yogev, L., Yavetz, H., Lifschitz-Mercer, B., Schreiber, L., Kleiman, S.E., et al . (2003) Spermatogonial Proliferation Patterns in Men with Azoospermia of Different Etiologies. Fertility and Sterility , 80, 1175-1180. https://doi.org/10.1016/s0015-0282(03)02161-7
Grey, C. and de Massy, B. (2022) Coupling Crossover and Synaptonemal Complex in Meiosis. Genes & Development , 36, 4-6. https://doi.org/10.1101/gad.349286.121
Yuan, L., Pelttari, J., Brundell, E., Björkroth, B., Zhao, J., Liu, J., et al . (1998) The Synaptonemal Complex Protein SCP3 Can Form Multistranded, Cross-Striated Fibers in Vivo . The Journal of Cell Biology , 142, 331-339. https://doi.org/10.1083/jcb.142.2.331
Miyamoto, T., Hasuike, S., Yogev, L., Maduro, M.R., Ishikawa, M., Westphal, H., et al . (2003) Azoospermia in Patients Heterozygous for a Mutation in SYCP3. The Lancet , 362, 1714-1719. https://doi.org/10.1016/s0140-6736(03)14845-3
Handel, M.A. and Schimenti, J.C. (2010) Genetics of Mammalian Meiosis: Regulation, Dynamics and Impact on Fertility. Nature Reviews Genetics , 11, 124-136. https://doi.org/10.1038/nrg2723
Aarabi, M., Modarressi, M.H., Soltanghoraee, H., Behjati, R., Amirjannati, N. and Akhondi, M.M. (2006) Testicular Expression of Synaptonemal Complex Protein 3 (SYCP3) Messenger Ribonucleic Acid in 110 Patients with Nonobstructive Azoospermia. Fertility and Sterility , 86, 325-331. https://doi.org/10.1016/j.fertnstert.2005.12.070
Bolor, H., Mori, T., Nishiyama, S., Ito, Y., Hosoba, E., Inagaki, H., et al . (2009) Mutations of the SYCP3 Gene in Women with Recurrent Pregnancy Loss. The American Journal of Human Genetics , 84, 14-20. https://doi.org/10.1016/j.ajhg.2008.12.002
Sazegari, A., Kalantar, S.M., Pashaiefar, H., Mohtaram, S., Honarvar, N., Feizollahi, Z., et al . (2014) The T657C Polymorphism on the SYCP3 Gene Is Associated with Recurrent Pregnancy Loss. Journal of Assisted Reproduction and Genetics , 31, 1377-1381. https://doi.org/10.1007/s10815-014-0272-6
Zhang, F., Liu, M. and Gao, J. (2022) Alterations in Synaptonemal Complex Coding Genes and Human Infertility. International Journal of Biological Sciences , 18, 1933-1943. https://doi.org/10.7150/ijbs.67843
Saxena, A.K., Agarwal, M., Tiwari, M., Kumar, U., Shailendr, K., et al . (2021) SYCP-3 Gene Mutation and DNA Copy Number Variation Increase Genetic Susceptibility in the Cases of Non-Obstructive Azoospermia. International Journal of Gynecology & Women ’ s Health , 5, IGWHC.MS.ID.000203.
Saxena, A.K. and Aniket, K. (2019) Research Article Microdeletion of the AZFC Locus with High Frequency of Mosaicism 46,XY/47XYY in Cases of Non-Obstructive Azoospermia in Eastern Population of India. Genetics and Molecular Research , 18, gmr18349. https://doi.org/10.4238/gmr18349
Saxena, A.K., Tiwari, M., Agarwal, M. and Aprajita, K.A. (2020) Prediction of 3D Protein Structure Based on the Mutation of AKAP3 and PLOD3 Genes in the Case of Non-Obstructive Azoospermia. International Journal of Fertility Sterility , 14, 102-109.
Kern, C.H., Yang, M. and Liu, W. (2021) The PRAME Family of Cancer Testis Antigens Is Essential for Germline Development and Gametogenesis. Biology of Reproduction , 105, 290-304. https://doi.org/10.1093/biolre/ioab074
Mizutani, E., Suzumori, N., Ozaki, Y., Oseto, K., Yamada-Namikawa, C., Nakanishi, M., et al . (2011) SYCP3 Mutation May Not Be Associated with Recurrent Miscarriage Caused by Aneuploidy. Human Reproduction , 26, 1259-1266. https://doi.org/10.1093/humrep/der035
Yuan, L., Liu, J., Zhao, J., Brundell, E., Daneholt, B. and Höög, C. (2000) The Murine SCP3 Gene Is Required for Synaptonemal Complex Assembly, Chromosome Synapsis, and Male Fertility. Molecular Cell , 5, 73-83. https://doi.org/10.1016/s1097-2765(00)80404-9
Martínez, J., Bonache, S., Carvajal, A., Bassas, L. and Larriba, S. (2007) Mutations of SYCP3 Are Rare in Infertile Spanish Men with Meiotic Arrest. Fertility and Sterility , 88, 988-989. https://doi.org/10.1016/j.fertnstert.2006.11.163
Gurkan, H., Aydin, F., Kadıoglu, A. and Palanduz, S. (2012) Investigation of Mutations in the Synaptonemal Complex Protein 3 (SYCP3) Gene among Azoospermic Infertile Male Patients in the Turkish Population. Andrologia , 45, 92-100. https://doi.org/10.1111/j.1439-0272.2012.01317.x