Journal of Biotechnology & Biomaterials
Open Access

Abstract

Infertility is defined as the inability of a sexually active, non-contracepting couple to achieve pregnancy in one year of regular coitus. It affects 10-15% of the couples worldwide and nearly half of these can be attributed to the male partner. In more than 30-40% of the cases, no male-infertility-associated factor is found (idiopathic male infertility). Human male infertility is a multifactorial disorder encompassing a wide variety of genetic risk factors involved in the regulation of diverse biological pathways. We undertook a multi-pronged approach to investigate the etiology of male infertility and identify new players in spermatogenesis. The investigations consisted of candidate gene analysis, cytogenetic whole genome array and gene expression analysis of eighty-four genes of DNA repair pathways. The candidate genes were chosen from the various pathways such as one carbon folate pathway (MTHFR), detoxification pathway (GSTT1, GSTM1), apoptotic pathway (FAS, FASL, GRTH) and immunological pathways (IL1RN, IL1B). For the whole genome cytogenetic array, we employed Affymetrix CytoScan 750K array characterized by more than 750,000 markers for copy number analysis. Cytogenetic whole genome array is a highresolution genome analysis that allows screening of thousands of loci at a time. It also allows detection of sub-microscopic aberration screening for gains/losses (duplications/deletions) throughout the genome. Further, we performed the expression analysis of the candidate genes of DNA damage, repair and apoptotic pathways. The association studies revealed a significant association of a number of candidate gene variants with impaired spermatogenesis. The expression analysis revealed an altered expression of DNA damage, repair and apoptotic pathway genes in severely impaired testicular phenotypes. The genome analysis detected a common gain in the 19p13.3 region in 4 (28.5%) cases. The region harbors a number of genes, such as STK11, FSTL3, PTB1, KISS1R, ABCA7, GPX4, CIRBP that are known to play an important role in spermatogenesis. In conclusion, the present study suggests that the pathology of human male infertility is associated with a number of genetic variations involved in the regulation of diverse biological pathways and it opens up new horizons for further investigation of the role of these genes in spermatogenesis.

Biography

Vertika Singh is currently pursuing her PhD from the Reproductive Genetics Laboratory at the Department of Molecular and Human Genetics, Banaras Hindu University. Her areas of interest include genetics and genomics of human male infertility. She has published one paper entitled “Chromosome microarray analysis: A case report of infertile brothers with CATSPER gene deletion”.

Email: vertikasingh4@gmail.com