The sperm head-to-tail coupling apparatus (HTCA) ensures sperm head-tail integrity while defective HTCA causes acephalic spermatozoa, rendering males infertile. Here, we show that CENTLEIN is indispensable for HTCA integrity and function, and that inactivation of CENTLEIN in mice leads to sperm decapitation and male sterility. We demonstrate that CENTLEIN directly interacts with both SUN5 and PMFBP1, two proteins localized in the HTCA and related with acephalic spermatozoa syndrome. We find that the absence of Centlein sets SUN5 and PMFBP1 apart, the former close to the sperm head and the latter in the decapitated tail. We show that lack of Sun5 results in CENTLEIN and PMFBP1 left in the decapitated tail, while disruption of Pmfbp1 results in SUN5 and CENTLEIN left on the detached sperm head. These results demonstrate that CENTLEIN cooperating with SUN5 and PMFBP1 participates in the HTCA assembly and integration of sperm head to the tail, indicating that impairments of CENTLEIN might be associated with acephalic spermatozoa syndrome in humans.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363609PMC
http://dx.doi.org/10.1038/s41467-021-25227-wDOI Listing

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Background: The presence of predominantly headless sperm in semen is a hallmark of acephalic spermatozoa syndrome, which is primarily caused by gene mutations in humans.

Purpose: To identify genetic causes for acephalic spermatozoa syndrome.

Methods: Polymerase chain reaction and Sanger sequencing were performed to define mutations in SUN5 and PMFBP1.

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Article Synopsis
  • Male infertility can be caused by various factors, including genetic mutations leading to structural sperm defects known as teratozoospermia, which affect sperm count and motility.
  • A literature review categorized genes associated with sperm defects based on the types of abnormalities they cause and the evidence from human studies alongside mouse models.
  • The review identified 31 genes causing defects in sperm heads and 62 genes linked to sperm tail defects, highlighting the complex genetic basis of teratozoospermia.
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The sperm head-to-tail coupling apparatus (HTCA) ensures sperm head-tail integrity while defective HTCA causes acephalic spermatozoa, rendering males infertile. Here, we show that CENTLEIN is indispensable for HTCA integrity and function, and that inactivation of CENTLEIN in mice leads to sperm decapitation and male sterility. We demonstrate that CENTLEIN directly interacts with both SUN5 and PMFBP1, two proteins localized in the HTCA and related with acephalic spermatozoa syndrome.

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Acephalic spermatozoa syndrome is a rare form of teratozoospermia characterized by headless spermatozoa. Previous studies have found that variants in SUN5, PMFBP1, TSGA10, BRDT, and SPATC1L are associated with this phenotype. Many researchers have suggested that variants in TSGA10 without a proximal centriole might influence early embryonic development.

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Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.

Purpose: To identify the pathogenic mutation in PMFBP1 leading to acephalic spermatozoa syndrome.

Methods: Sanger sequencing was used to screen for mutations in the known pathogenic genes SUN5 and PMFBP1 in a patient with acephalic spermatozoa syndrome. Western blotting and immunofluorescence were used to detect the expression and localization of PMFBP1 in sperm.

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