The genetic basis of male infertility with “multiple morphological abnormalities of the flagella” and its intervention strategies

<p indent="0mm">The sperm flagellum is essential for sperm motility. Thousands of proteins are assumed to be involved in the biogenesis and assembly of sperm flagella. “Multiple morphological abnormalities of the flagella” (MMAF) is featured with a mosaic of morphological defects of sperm flagella (incuding short, coiled, absent, bent, and/or irregular flagella), and causes abnormal sperm motility and male infertility. Owing to the development of the high-throughput sequencing and gene editing techniques, over 40 MMAF pathogenic genes have been identified, and the pathogenic genes of most MMAF patients have been identified. However, the outcomes of assisted reproduction vary among different MMAF pathogenic genes. In this review, we summarize the progress on the study of the genetic basis for MMAF, including the relationship between flagellar structure and sperm motility, the techniques for identifying MMAF pathogenic genes, the functions of representative MMAF genes, and the current and potential strategies to overcome male infertility. We hope to provide an insight into the the analysis and intervention of the MMAF and similar diseases.