ERα phosphorylated at Ser309 participates in regulating luminal environment of efferent ducts and epididymis in mice

in Reproduction
Authors:
Jinhua Wei J Wei, Department of Human Anatomy, Histology and Embryology, Air Force Medical University, Xi'an, China

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Pang Cheng P Cheng, Department of Human Anatomy, Histology and Embryology, Air Force Medical University, Xi'an, China

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Binfang Ma B Ma, Department of Human Anatomy, Histology and Embryology, Air Force Medical University, Xi'an, China

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Xiao Feng X Feng, Department of Human Anatomy, Histology and Embryology, Air Force Medical University, Xi'an, China

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Junxian Ma J Ma, Department of Human Anatomy, Histology and Embryology, Air Force Medical University, Xi'an, China

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Jie Zhao J Zhao, Department of Human Anatomy, Histology and Embryology, Air Force Medical University, Xi'an, China

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Yanqiu Zhao Y Zhao, Department of Human Anatomy, Histology and Embryology, Air Force Medical University, Xi'an, China

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Zhen Li Z Li, Department of Human Anatomy, Histology and Embryology, Air Force Medical University, Xi'an, China

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Correspondence: Zhen Li, Email: lizhenhe@fmmu.edu.cn
DOI:
https://doi.org/10.1530/REP-24-0109
Volume/Issue:
Accepted Manuscripts
Article ID:
REP-24-0109
Article Type:
Research Article
Online Publication Date:
01 Jan 2025
Copyright:
© 2025 Society for Reproduction and Fertility 2025
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The estrogen receptor alpha (ERα) plays an important role in male reproduction and fertility. Its activity is modulated by phosphorylation of multiple amino acid residues. The ERα phosphorylated at serine 305 (S305) in human cells (homologous with serine 309 in mice) induces ligand-independent ERα activity. Here, we studied the effect of ERα phosphorylation at S309 on the reproductive function of male mice. ERα309 (p.S309A, ERαS309A) knock-in (KI) mice were generated by homologous recombination in mouse embryonic stem (ES) cells. The ERαS309A KI males were subfertile with decreased sperm motility, dilated lumen and thinned epithelium of efferent ducts. Ultrastructural observation showed that the area of endocytic vesicles and lysosomes in the non-ciliated cells, and the number of cilia in the cilia cells were significantly reduced in the efferent ducts of ERαS309A mice. The pH value of epididymal fluid was significantly higher in all regions of epididymis in the ERαS309A KI mice. Moreover, the expression of aquaporin 9 (AQP9) in the efferent ducts and carbonic anhydrase XII (CAR12) in the epididymis was decreased in ERαS309A KI mice. The results indicate that ERα phosphorylated at Ser309 participates in maintaining the unique luminal milieu by regulating the expression of critical regulators of fluid/ion transport in efferent ducts and epididymis.

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Print ISSN:
1470-1626
Online ISSN:
1741-7899