Andrology-Open Access
Open Access

Abstract

A new heterozygous deletion mutation of the SYCP2 gene caused male infertility due to non-obstructive azoospermia

Lin Tan, Qi Yang, Jianan Liu, Weijun Zhong, Zhongzhi Gan, Qian Liu, Xuedong Wu* and Fu Xiong

Infertility affects 10%-20% of heterosexual couples worldwide and 50% are due to male factors. The most severe type is non-obstructive azoospermia, which is distinguished by a total lack of sperm in the seminal fluid. However, the genetic causes of non-obstructive azoospermia have been incompletely understood. Here, an investigation was conducted on a Chinese family with non-obstructive azoospermia to examine its pathogenesis. Using whole-exome sequencing, we identified a new heterozygous deletion mutation (c.1937_1942delTAAATA, p. Ile646_Asn647del) in exon 24 of SYCP2 gene. SYCP2 is a synaptonemal complex protein that plays an essential role in meiosis. Conservation analysis indicated that amino acid at position 647 was highly conserved among different species. Moreover, there was a notable modification in the three-dimensional transformation of the mutant SYCP2 protein. In vitro functional experiments showed that the SYCP2 protein expression decreased in HEK293T cells transfected with plasmids containing SYCE2 c.1937_1942delTAAATA. Immunofluorescence staining showed that the subcellular localization of mutant SYCP2 protein altered, which was present in both the cytoplasm and nucleus, whereas wide-type SYCP2 was only found in the nucleus. In conclusion, our research suggests that the heterozygous deletion variant SYCP2 c.1937_1942delTAAATA causes non-obstructive azoospermia occurrence and ultimately result in male infertility. This study expands the variant spectrum of non-obstructive azoospermia-associated genes and highlights the essential role of SYCP2 in spermatogenesis.

Published Date: 2025-05-19; Received Date: 2024-03-13