Functional polymorphism in H2BFWT‐5′UTR is associated with susceptibility to male infertility

Abstract

Introduction Spermatogenesis involves the processes of germ cell proliferation and differentiation by mitosis and meiosis. During spermatogenesis, the chromatin of the spermatogenic cells is profoundly reorganized and somatic histones are partly replaced by testis-specifichistones [1]. The somatic histones that are present at the onset of the differentiation process undergo several transitions. In mature spermatozoa, protamines consist of the main chromosomal component [2,3]. In human beings, unlike other mammals including the mouse, core histones (H2A, H2B, H3 and H4) are not displaced completely during spermiogenesis and account for approximately 15% of the basic chromosomal proteins within the mature sperm [4][5][6].Human testis-specific histones are detected in spermatogonia as well as mature sperm [1,[7][8][9][10][11]. The functions of these proteins may be similar to their somatic counterparts, but this remains to be fully elucidated. Some functions of testis-specific histones during spermatogenesis have been previously reported [12][13][14][15]. Importantly, a decrease in testis-specific histone can result in sperm morphological abnormalities and male subfertility [16,17]

Spatiotemporal expression pattern of gonad-stimulating substance-like peptide of the sea cucumber, Apostichopus japonicus

“…2007), and there have been other reports on the polymorphism of the Deleted in Azoospermia gene (Kim et al. 2009) and the H2BFWT (H2B histone family, member W, testis‐specific) gene (Lee et al. 2009) in human testis and transferrin in the seminal plasma of carp ( Cyprinus carpio ) (Wojtczak et al.…”

Genetic association study of a single nucleotide polymorphism of kallikrein-related peptidase 2 with male infertility

“…This control group was consecutively enrolled from the Division of Genome Resources, National Genome Research Institute, National Institutes of Health, and from Korea [1,9]. From January 2002 to August 2006, 709 non-obstructive infertile men were identified following physical examinations and hormone assays.…”

Genetics of male infertility: from research to clinic

“…An example is the rs7885967 (c.-9COT) of the H2BFWT (H2B histone family, member W, testis-specific) gene encoding for a testis-specific histone with an essential role during meiotic chromatin reorganization (Gineitis et al 2001). This SNP maps to the 5'UTR of H2BFWT and has been demonstrated to affect the translation of the protein (Lee et al 2009). The two case-control studies found significant association (with moderate OR ranging from 1.51-1.88) with completely different semen phenotypes: azoospermia in the Chinese population (Ying & Scott 2012) whereas lack of association with azoospermia and association with non-azoospermia (a heterogenous group of oligo/ astheno/teratozoospermic men) in the Korean study (Lee et al 2009).…”

“…This SNP maps to the 5'UTR of H2BFWT and has been demonstrated to affect the translation of the protein (Lee et al 2009). The two case-control studies found significant association (with moderate OR ranging from 1.51-1.88) with completely different semen phenotypes: azoospermia in the Chinese population (Ying & Scott 2012) whereas lack of association with azoospermia and association with non-azoospermia (a heterogenous group of oligo/ astheno/teratozoospermic men) in the Korean study (Lee et al 2009). Such contradictory results clearly discourage further studies on this SNP.…”