PDCL2 Is Essential for Sperm Acrosome Formation and Male Fertility in Mice

Authors

Yoshitaka Fujihara
Kiyonori Kobayashi
Ferheen Abbasi
Tsutomu Endo
Zhifeng Yu
Masahito Ikawa
Martin M Matzuk

Publication Date

7-1-2023

Journal

Andrology

DOI

10.1111/andr.13329

PMID

36278277

PMCID

PMC10123174

PubMedCentral® Posted Date

7-1-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Animals, Male, Mice, Acrosome, Fertility, Infertility, Male, Nerve Tissue Proteins, Spermatozoa, Testis, Acrosome formation, CRISPR-Cas9, Globozoospermia, Infertility, Spermatogenesis

Abstract

BACKGROUND: Each year, infertility affects 15% of couples worldwide, with 50% of cases attributed to men. Globozoospermia is an uncommon cause of male factor infertility, characterized by defects in sperm acrosome formation, leading to round-headed spermatozoa.

OBJECTIVE: We generated Pdcl2 knockout mice to investigate the essential roles of PDCL2 in mammalian reproduction.

MATERIALS AND METHODS: We used reverse transcription-polymerase chain reaction to demonstrate that PDCL2 was expressed exclusively in the male reproductive tract in mice and humans. We created Pdcl2 knockout mice using the CRISPR-Cas9 system and analyzed their fertility. Pdcl2 null spermatozoa underwent further evaluation using computer-assisted sperm analysis, light microscopy, and ultrastructural microscopy. We used immunoblot analysis and immunofluorescence to elucidate relationships between PDCL2 and other acrosomal proteins.

RESULTS: The PDC family is highly conserved in eukaryotes. Mouse and human PDCL2 are testis enriched and localized to the testicular endoplasmic reticulum. Loss of the protein causes sterility because of abnormal acrosome biogenesis during spermiogenesis and immotility. Furthermore, Pdcl2 null spermatozoa have rounded heads, similar to globozoospermia in humans. Observation of the knockout testis shows a lack of acrosomal cap formation, aberrant localization of mitochondria in the sperm head, and misshapen nuclei.

CONCLUSION: PDCL2 is essential for sperm acrosome development and male fertility in mice and is a putative contraceptive target in men.