NCOA5 Haplo-insufficiency Results in Male Mouse Infertility through Increased IL-6 Expression in the Epididymis

Shenglan Gao; Yueqi Zhang; Chengfeng Yang; Gloria I. Perez; Hua Xiao

doi:10.1038/s41598-019-52105-9

NCOA5 Haplo-insufficiency Results in Male Mouse Infertility through Increased IL-6 Expression in the Epididymis

Shenglan Gao, Yueqi Zhang, Chengfeng Yang, Gloria I. Perez, Hua Xiao

Markey Cancer Center / Cancer Research Priority Initiative

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Male infertility might be caused by genetic and/or environmental factors that impair spermatogenesis and epididymal sperm maturation. Here we report that heterozygous deletion of the nuclear receptor coactivator-5 (Ncoa5) gene resulted in decreased motility and progression of spermatozoa in the cauda epididymis, leading to infertility in male mice. Light microscopic and ultrastructural analysis revealed morphological defects in the spermatozoa collected from the cauda epididymis of Ncoa5^+/− mice. Immunohistochemistry showed that interleukin-6 (IL-6) expression in epithelial cells of Ncoa5^+/− epididymis was higher than wild type counterparts. Furthermore, heterozygous deletion of Il-6 gene in Ncoa5^+/− male mice partially improved spermatozoa motility and moderately rescued infertility phenotype. Our results uncover a previously unknown physiological role of NCOA5 in the regulation of epididymal sperm maturation and suggest that NCOA5 deficiency could cause male infertility through increased IL-6 expression in epididymis.

Original language	English
Article number	15525
Journal	Scientific Reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-52105-9
State	Published - Dec 1 2019

Bibliographical note

Publisher Copyright:
© 2019, The Author(s).

Funding

We thank Dr. Chen Chen for helpful discussions and critical reading of the manuscript. We also thank the Center for Advanced Microscopy, Michigan State University and Andalucian Laboratory of Cellular Reprogramming, Seville, Spain for their help in ultrastructure analysis. This work was supported by the NIH grant (R01CA188305) and the NIH grant (R21CA185021) to H. X. Y. Z. was supported by the Continuation Fellowship award from Michigan State University, and the Aitch Fellowship award from the Aitch Foundation.

Funders	Funder number
Aitch Foundation
National Institutes of Health (NIH)
National Childhood Cancer Registry – National Cancer Institute	R21CA185021, R01CA188305
National Childhood Cancer Registry – National Cancer Institute
Michigan State University

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title = "NCOA5 Haplo-insufficiency Results in Male Mouse Infertility through Increased IL-6 Expression in the Epididymis",

abstract = "Male infertility might be caused by genetic and/or environmental factors that impair spermatogenesis and epididymal sperm maturation. Here we report that heterozygous deletion of the nuclear receptor coactivator-5 (Ncoa5) gene resulted in decreased motility and progression of spermatozoa in the cauda epididymis, leading to infertility in male mice. Light microscopic and ultrastructural analysis revealed morphological defects in the spermatozoa collected from the cauda epididymis of Ncoa5+/− mice. Immunohistochemistry showed that interleukin-6 (IL-6) expression in epithelial cells of Ncoa5+/− epididymis was higher than wild type counterparts. Furthermore, heterozygous deletion of Il-6 gene in Ncoa5+/− male mice partially improved spermatozoa motility and moderately rescued infertility phenotype. Our results uncover a previously unknown physiological role of NCOA5 in the regulation of epididymal sperm maturation and suggest that NCOA5 deficiency could cause male infertility through increased IL-6 expression in epididymis.",

author = "Shenglan Gao and Yueqi Zhang and Chengfeng Yang and Perez, {Gloria I.} and Hua Xiao",

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AU - Perez, Gloria I.

AU - Xiao, Hua

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Male infertility might be caused by genetic and/or environmental factors that impair spermatogenesis and epididymal sperm maturation. Here we report that heterozygous deletion of the nuclear receptor coactivator-5 (Ncoa5) gene resulted in decreased motility and progression of spermatozoa in the cauda epididymis, leading to infertility in male mice. Light microscopic and ultrastructural analysis revealed morphological defects in the spermatozoa collected from the cauda epididymis of Ncoa5+/− mice. Immunohistochemistry showed that interleukin-6 (IL-6) expression in epithelial cells of Ncoa5+/− epididymis was higher than wild type counterparts. Furthermore, heterozygous deletion of Il-6 gene in Ncoa5+/− male mice partially improved spermatozoa motility and moderately rescued infertility phenotype. Our results uncover a previously unknown physiological role of NCOA5 in the regulation of epididymal sperm maturation and suggest that NCOA5 deficiency could cause male infertility through increased IL-6 expression in epididymis.

AB - Male infertility might be caused by genetic and/or environmental factors that impair spermatogenesis and epididymal sperm maturation. Here we report that heterozygous deletion of the nuclear receptor coactivator-5 (Ncoa5) gene resulted in decreased motility and progression of spermatozoa in the cauda epididymis, leading to infertility in male mice. Light microscopic and ultrastructural analysis revealed morphological defects in the spermatozoa collected from the cauda epididymis of Ncoa5+/− mice. Immunohistochemistry showed that interleukin-6 (IL-6) expression in epithelial cells of Ncoa5+/− epididymis was higher than wild type counterparts. Furthermore, heterozygous deletion of Il-6 gene in Ncoa5+/− male mice partially improved spermatozoa motility and moderately rescued infertility phenotype. Our results uncover a previously unknown physiological role of NCOA5 in the regulation of epididymal sperm maturation and suggest that NCOA5 deficiency could cause male infertility through increased IL-6 expression in epididymis.

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NCOA5 Haplo-insufficiency Results in Male Mouse Infertility through Increased IL-6 Expression in the Epididymis

Abstract

Bibliographical note

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