Reduced and Mislocalized ACTL7A in Globozoospermia: Implications for Sperm Chromatin Integrity and Infertility

Actin-like protein 7A (ACTL7A) has been suggested to participate in sperm head formation and oocyte activation. This study investigates the expression and localization of ACTL7A in men with globozoospermia and explores its association with sperm chromatin integrity. Semen samples were collected from 10 infertile men diagnosed with 100% globozoospermia and carrying a DPY19L2 deletion, alongside samples from 10 fertile controls. Sperm analysis was conducted according to WHO-2021 guidelines. Sperm DNA fragmentation was assessed using flow cytometry (SCSA), histone retention via aniline blue staining, and chromatin structure through toluidine blue staining. Compared to fertile controls, globozoospermic men showed significantly reduced sperm motility and increased morphological abnormalities. Chromatin analysis revealed elevated DNA fragmentation and impaired chromatin packaging. Additionally, ACTL7A protein expression was markedly reduced in globozoospermic individuals. Localization studies indicated decreased ACTL7A presence in the equatorial segment and aberrant overexpression in the neck region. These findings suggest that altered ACTL7A expression and localization may be associated with abnormalities in sperm structure and function. Its reduced expression and mislocalization may be associated with globozoospermia and male infertility. Given the success of intracytoplasmic sperm injection (ICSI) combined with artificial oocyte activation (ICSI-AOA) in treating PLCZ1-deficient infertility, this approach may also be considered in similar clinical contexts, although further studies are required.