The perinuclear theca protein FNDC8 interacts with CCIN and ACTL7A to ensure sperm head shaping during spermiogenesis

Sperm head shape is crucial for successful fertilization, and malformed sperm heads are often associated with severe male infertility. The sperm head is mainly shaped by the apical ectoplasmic specialization (ES), manchette, and perinuclear theca (PT). The PT is a specialized cytoskeletal structure that surrounds the nucleus of the sperm head during spermiogenesis. However, our understanding on the components and physiological functions of thePT in sperm head shaping remains limited. Here, we show that FNDC8 is a testis-predominantly expressed protein, and it is primarily localized to the PT. Disruption of this gene leads to male infertility due to the production of spermatozoa with acrosome detachment from the nuclear membrane and sperm head surface subsidence. Further studies revealed that FNDC8 interacts with both CCIN and ACTL7A during spermiogenesis, the depletion of this protein destablized these two proteins. Together, these results suggest that FNDC8 interacts with the above two proteins to maintain the integrity of the PT structure, facilitating proper sperm head shaping, suggesting that some mutations of FNDC8 might be associated with teratozoospermia in humans.