plays a role in the acrosome development during spermiogenesis.

BACKGROUND

Loss-of-function mutations in result in multiple morphological abnormalities of the flagella in humans and mice. Intriguingly, a recent study found that FSIP2 might regulate the expression of acrosomal proteins, indicating that might be involved in acrosome development in mice. However, whether also function in acrosome biogenesis in humans is largely unknown, and the underlying mechanism of which is unexplored.

OBJECTIVE

Our objective was to reveal potential function of FSIP2 in regulating sperm acrosome formation.

METHODS

We performed whole exome sequencing on four asthenoteratozoospermic patients. Western blot analysis and immunofluorescence staining were conducted to assess the protein expression of FSIP2. Proteomics approach, liquid chromatography-tandem mass spectrometry and co-immunoprecipitation were implemented to clarify the molecules in acrosome biogenesis regulated by FSIP2.

RESULTS

Biallelic variants were identified in four asthenoteratozoospermic individuals. The protein expression of MUT- was sharply decreased or absent in vitro or in vivo. Interestingly, aside from the sperm flagellar defects, the acrosomal hypoplasia was detected in numerous sperm from the four patients. FSIP2 co-localised with peanut agglutinin in the acrosome during spermatogenesis. Moreover, FSIP2 interacted with proteins (DPY19L2, SPACA1, HSP90B1, KIAA1210, HSPA2 and CLTC) involved in acrosome biogenesis. In addition, spermatozoa from patients carrying mutations showed downregulated expression of DPY19L2, ZPBP, SPACA1, CCDC62, CCIN, SPINK2 and CSNK2A2.

CONCLUSION

Our findings unveil that might involve in sperm acrosome development, and consequently, its mutations might contribute to globozoospermia or acrosomal aplasia. We meanwhile first uncover the potential molecular mechanism of FSIP2 regulating acrosome biogenesis.