Centre for Genetics & Genomics, Department of Anatomy, Mahatma Gandhi Institute of Medical Sciences, Wardha, Maharashtra, India.
Department of Obstetrics & Gynaecology, Mahatma Gandhi Institute of Medical Sciences, Wardha, Maharashtra, India.
Andrologia. 2022 Dec;54(11):e14581. doi: 10.1111/and.14581. Epub 2022 Sep 6.
Spermatogenesis is regulated by complex tissue specific gene expression in the testis to achieve normal male fertility. X-chromosome specific TATA binding protein (TBP)-associated factor 7L (hTAF7L) is one of the transcriptional regulator genes considered essential for spermatogenesis. The aim of this study was to evaluate the role of variants/mutations in the testis-specific hTAF7L gene in non-obstructive azoospermia and severe oligozoospermia male infertility. We studied 156 idiopathic non-obstructive azoospermic, severe oligozoospermic infertile males and 50 fertile proven controls. Infertile males and control subjects were genotyped for variants of the hTAF7L gene using polymerase chain reaction and a direct Sanger sequencing approach. The odds ratio evaluated the association of hTAF7L gene variants with idiopathic male infertility. The variants found in the hTAF7L gene were subjected to an in-silico analysis study. In infertile study subjects, we observed 11 single base pair nucleotide changes at various exons and three frameshift variants at exon 10 in the hTAF7L gene. We also found more than one variant in some non-obstructive azoospermia and severe oligozoospermia infertile males along with control subjects. All these variants changed the amino acid sequences in the hTAF7L gene. However, similar changes were also seen in fertile subjects, and the differences were not statistically significant. In-silico tools also predicted that the variants were likely to be benign. The variants in cDNA of the hTAF7L gene were typical SNPs. It is found that the hTAF7L gene is highly polymorphic and these missense variants are not directly associated with male infertility. However, we feel that more studies are needed to elucidate the role of multiple variants of the hTAF7L gene in the process of normal spermatogenesis.
精子发生是通过睾丸中复杂的组织特异性基因表达来调节的，以实现正常的男性生育能力。X 染色体特异性 TATA 结合蛋白（TBP）相关因子 7L（hTAF7L）是转录调节基因之一，被认为对精子发生至关重要。本研究旨在评估睾丸特异性 hTAF7L 基因中的变异/突变在非阻塞性无精子症和严重少精子症男性不育中的作用。我们研究了 156 名特发性非阻塞性无精子症、严重少精子症不育男性和 50 名生育能力正常的证实对照组。使用聚合酶链反应和直接 Sanger 测序方法对不育男性和对照个体的 hTAF7L 基因变体进行基因分型。比值比评估了 hTAF7L 基因变体与特发性男性不育的关联。对 hTAF7L 基因中的变体进行了体外分析研究。在不育研究对象中，我们在 hTAF7L 基因的不同外显子中观察到 11 个单碱基对核苷酸变化和外显子 10 中的三个移码变体。我们还在一些非阻塞性无精子症和严重少精子症不育男性以及对照组中发现了不止一个变体。所有这些变体都改变了 hTAF7L 基因的氨基酸序列。然而，在生育能力正常的受试者中也观察到了类似的变化，且差异无统计学意义。体外工具还预测这些变体很可能是良性的。hTAF7L 基因 cDNA 的变体是典型的 SNP。研究发现，hTAF7L 基因高度多态性，这些错义变体与男性不育症没有直接关联。然而，我们认为需要更多的研究来阐明 hTAF7L 基因的多个变体在正常精子发生过程中的作用。
