上海交通大学Chunyu Liu等研究人员合作发现，顶体膜蛋白MFSD6L缺乏会导致人类和小鼠出现少精症。相关论文于2024年6月21日在线发表于国际学术期刊《遗传学报》。

研究人员进行了遗传分析，并从一个受少精子症影响的家族中鉴定出了MFSD6L的双等位功能缺失变体。敲除Mfsd6l的雄性小鼠也会出现雄性不育症，精子浓度和活力会降低，以及顶体畸形。进一步的机理分析表明，MFSD6L作为顶体膜蛋白，通过与顶体膜内膜蛋白SPACA1相互作用，在顶体形成过程中发挥重要作用。

此外，在使用MFSD6L缺陷的人和雄性小鼠的精子进行卵胞浆内精子注射处理后，持续观察到胚胎发育不良。总之，这些研究结果表明，MFSD6L是精子顶体锚定和头部成形所需的。缺乏MFSD6L会影响男性生育能力，并导致人类和小鼠出现少精症。

据介绍，少精症是影响男性生育能力的一个重要因素，而且已被发现与遗传因素有关。然而，仍有一部分少精症病例无法用已知的致病基因变异来解释。

附：英文原文

Title: Deficiency of MFSD6L, an acrosome membrane protein, causes oligoasthenoteratozoospermia in humans and mice

Author: Feng Zhang a b k, Yunxia Cao c d e, Chunyu Liu k

Issue&Volume: 2024/06/21

Abstract: Oligoasthenoteratozoospermia is an important factor affecting male fertility and has been found to be associated with genetic factors. However, there are still a proportion of oligoasthenoteratozoospermia cases that cannot be explained by known pathogenic genetic variants. Here, we perform genetic analyses and identify bi-allelic loss-of-function variants of MFSD6L from an oligoasthenoteratozoospermia affected family. Mfsd6l knock-out male mice also present male subfertility with reduced sperm concentration, motility, and deformed acrosomes. Further mechanistic analyses reveal that MFSD6L, as an acrosome membrane protein, plays an important role in the formation of acrosome by interacting with inner acrosomal membrane protein SPACA1. Moreover, poor embryonic development is consistently observed after intracytoplasmic sperm injection treatment using spermatozoa from MFSD6L-deficient man and male mice. Collectively, our findings reveal that MFSD6L is required for the anchoring of sperm acrosome and head shaping. The deficiency of MFSD6L affects male fertility and causes oligoasthenoteratozoospermia in humans and mice.

DOI: 10.1016/j.jgg.2024.06.008

Source: https://www.sciencedirect.com/science/article/abs/pii/S1673852724001498