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

Carvajal, Guillermo; Brukman, Nicolás Gastón; Weigel Muñoz, Mariana; Battistone, María A.; Guazzone, Vanesa A.; Ikawa, Masahito; Haruhiko, Miyata; Lustig, Livia; Breton, Sylvie; Cuasnicu, Patricia S.

doi:https://doi.org/10.1038/s41598-018-35719-3

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

Carvajal, Guillermo; Brukman, Nicolás Gastón; Weigel Muñoz, Mariana et al.

Scientific Reports, 2018, 8(1), 17531

アクセス数:217件（2025-04-18 02:39 集計）

固定URL: https://hdl.handle.net/11094/78567

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タイトル	Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4
著者	著者名 Carvajal, Guillermo
	著者名 Brukman, Nicolás Gastón
	著者名 Weigel Muñoz, Mariana
	著者名 Battistone, María A.
	著者名 Guazzone, Vanesa A.
	NRID 1000020304066 1000020304066 ORCID 0000-0001-9859-6217 0000-0001-9859-6217 researchmap permalink read0054910 read0054910 Scopus Author ID 16689054500 16689054500 著者名 Ikawa, Masahito
	著者名 Haruhiko, Miyata
	著者名 Lustig, Livia
	著者名 Breton, Sylvie
	著者名 Cuasnicu, Patricia S.
内容	Carvajal, G., Brukman, N.G., Weigel Muñoz, M. et al. Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4. Sci Rep 8, 17531 (2018). https://doi.org/10.1038/s41598-018-35719-3
抄録	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.
出版者	Nature Research
収録物名	Scientific Reports
巻(号)	8(1)
ページ	17531
刊行年月	2018-12-03
言語	英語
ハンドルURL	https://hdl.handle.net/11094/78567
eISSN	20452322
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1038/s41598-018-35719-3
関連情報 (isIdenticalTo)	PMID 30510210
アクセス権	open access
権利情報	© 2018 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCTERMS.bibliographicCitation	Scientific Reports. 2018, 8(1), p. 17531
DC.title	Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4
DC.creator	Carvajal, Guillermo
	Brukman, Nicolás Gastón
	Weigel Muñoz, Mariana
	Battistone, María A.
	Guazzone, Vanesa A.
	Ikawa, Masahito
	Haruhiko, Miyata
	Lustig, Livia
	Breton, Sylvie
	Cuasnicu, Patricia S.
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2018-12-03
DC.identifier	https://doi.org/10.1038/s41598-018-35719-3
DC.description	Carvajal, G., Brukman, N.G., Weigel Muñoz, M. et al. Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4. Sci Rep 8, 17531 (2018). https://doi.org/10.1038/s41598-018-35719-3
DCTERMS.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.
DC.rights	© 2018 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	78567
citation_title	Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4
citation_author	Carvajal, Guillermo
	Brukman, Nicolás Gastón
	Weigel Muñoz, Mariana
	Battistone, María A.
	Guazzone, Vanesa A.
	Ikawa, Masahito
	Haruhiko, Miyata
	Lustig, Livia
	Breton, Sylvie
	Cuasnicu, Patricia S.
citation_publisher	Nature Research
citation_language	英語
citation_date	2018-12-03
citation_journal_title	Scientific Reports
citation_volume	8
citation_issue	1
citation_firstpage	17531
citation_doi	https://doi.org/10.1038/s41598-018-35719-3
citation_pmid	30510210
citation_public_url	https://hdl.handle.net/11094/78567

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

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