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Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4.

Abstract：

:Epididymal Cysteine Rich Secretory Proteins 1 and 4 (CRISP1 and CRISP4) associate with sperm during maturation and play different roles in fertilization. However, males lacking each of these molecules individually are fertile, suggesting compensatory mechanisms between these homologous proteins. Based on this, in the present work, we generated double CRISP1/CRISP4 knockout (DKO) mice and examined their reproductive phenotype. Our data showed that the simultaneous lack of the two epididymal proteins results in clear fertility defects. Interestingly, whereas most of the animals exhibited specific sperm fertilizing ability defects supportive of the role of CRISP proteins in fertilization, one third of the males showed an unexpected epididymo-orchitis phenotype with altered levels of inflammatory molecules and non-viable sperm in the epididymis. Further analysis showed that DKO mice exhibited an immature epididymal epithelium and abnormal luminal pH, supporting these defects as likely responsible for the different phenotypes observed. These observations reveal that CRISP proteins are relevant for epididymal epithelium differentiation and male fertility, contributing to a better understanding of the fine-tuning mechanisms underlying sperm maturation and immunotolerance in the epididymis with clear implications for human epididymal physiology and pathology.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Carvajal G,Brukman NG,Weigel Muñoz M,Battistone MA,Guazzone VA,Ikawa M,Haruhiko M,Lustig L,Breton S,Cuasnicu PS

doi

10.1038/s41598-018-35719-3

subject

Has Abstract

pub_date

2018-12-03 00:00:00

pages

17531

issue

1

issn

2045-2322

pii

10.1038/s41598-018-35719-3

journal_volume

8

pub_type

杂志文章

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