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Germline Telomere Attrition is Associated with Human Male Infertility

S. Pathak* , S. Pathak* , A.S. Multani* , S.H. Sohn** , N.J. Gupta*** , B.N. Chakravarty***

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Indian Journal of Genetics and Molecular Research 5(2):p 37-49, July - December 2016. | DOI: DOI: http://dx.doi.org/10.21088/ijgmr.2319.4782.5216.1

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Abstract

 Meiotic division requires pairing of homologous chromosomes for normal segregation, recombination, and production of haploid gametes. Early in meiotic prophase, chromosomes begin pairing off from the telomeric ends toward the centromere, irrespective of chromosome morphology. Since synaptonemal complex formation during zygotene/early pachytene begins at the telomeres, we hypothesized that in some infertile human males telomeric chromosomal DNA may be constitutionally reduced and, therefore, insufficient to initiate homologous synapsis, resulting in asynaptic meiosis and azoospermic infertility. To test this hypothesis, we measured and compared percent telomeric DNA in peripheral blood lymphocytes (PBLs) and testicular biopsies from infertile males (cases) and agematched normal fertile males (controls). Quantitative fluorescence in situ hybridization (QFISH) revealed that cases had significantly less telomeric DNA than did controls (P < 0.001; P = 0.002 respectively). In addition, in experiments with mouse testes exposed to the telomerase-inhibiting and sterility-inducing drug, cytarabine in vivo, silver staining and analysis of synaptonemal complexes showed that homologous chromosome pairing was prevented due to the loss of telomeric DNA. Taken together, these observations indicate that constitutionally reduced amounts of telomeric DNA in somatic and germ cells may be a crucial determinant in human male sterility.

Keywords: Homologous Pairing; Infertility; Pachytene; Synaptonemal Complex; Telomeric DNA.

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DOI: DOI: http://dx.doi.org/10.21088/ijgmr.2319.4782.5216.1

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