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Article

Kcnj16 (Kir5.1) Gene Ablation Causes Subfertility and Increases the Prevalence of Morphologically Abnormal Spermatozoa

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Section of Pathology, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy
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Department of Physiology, Faculty of Medicine, Kuwait University, Safat 13110, Kuwait
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Department of Chemistry Biology and Biotechnology, University of Perugia, 06123 Perugia, Italy
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Section of Physiology & Biochemistry, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy
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Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK
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Department of Pharmacy-Drug Sciences, University of Bari ‘‘Aldo Moro”, 70125 Bari, Italy
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Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 17666, United Arab Emirates
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Department of Physiology & Biochemistry, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta
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Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 17666, United Arab Emirates
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Elisabeth Pinart
Int. J. Mol. Sci. 2021, 22(11), 5972; https://doi.org/10.3390/ijms22115972
Received: 26 April 2021 / Revised: 26 May 2021 / Accepted: 27 May 2021 / Published: 1 June 2021
The ability of spermatozoa to swim towards an oocyte and fertilize it depends on precise K+ permeability changes. Kir5.1 is an inwardly-rectifying potassium (Kir) channel with high sensitivity to intracellular H+ (pHi) and extracellular K+ concentration [K+]o, and hence provides a link between pHi and [K+]o changes and membrane potential. The intrinsic pHi sensitivity of Kir5.1 suggests a possible role for this channel in the pHi-dependent processes that take place during fertilization. However, despite the localization of Kir5.1 in murine spermatozoa, and its increased expression with age and sexual maturity, the role of the channel in sperm morphology, maturity, motility, and fertility is unknown. Here, we confirmed the presence of Kir5.1 in spermatozoa and showed strong expression of Kir4.1 channels in smooth muscle and epithelial cells lining the epididymal ducts. In contrast, Kir4.2 expression was not detected in testes. To examine the possible role of Kir5.1 in sperm physiology, we bred mice with a deletion of the Kcnj16 (Kir5.1) gene and observed that 20% of Kir5.1 knock-out male mice were infertile. Furthermore, 50% of knock-out mice older than 3 months were unable to breed. By contrast, 100% of wild-type (WT) mice were fertile. The genetic inactivation of Kcnj16 also resulted in smaller testes and a greater percentage of sperm with folded flagellum compared to WT littermates. Nevertheless, the abnormal sperm from mutant animals displayed increased progressive motility. Thus, ablation of the Kcnj16 gene identifies Kir5.1 channel as an important element contributing to testis development, sperm flagellar morphology, motility, and fertility. These findings are potentially relevant to the understanding of the complex pHi- and [K+]o-dependent interplay between different sperm ion channels, and provide insight into their role in fertilization and infertility. View Full-Text
Keywords: Kir4.1; KCNJ10; Kir4.2; KCNJ15; KCNJ16; Kir5.1; potassium channel; testis; epididymis; spermatozoa; flagellar morphology; sperm motility; male fertility Kir4.1; KCNJ10; Kir4.2; KCNJ15; KCNJ16; Kir5.1; potassium channel; testis; epididymis; spermatozoa; flagellar morphology; sperm motility; male fertility
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MDPI and ACS Style

Poli, G.; Hasan, S.; Belia, S.; Cenciarini, M.; Tucker, S.J.; Imbrici, P.; Shehab, S.; Pessia, M.; Brancorsini, S.; D'Adamo, M.C. Kcnj16 (Kir5.1) Gene Ablation Causes Subfertility and Increases the Prevalence of Morphologically Abnormal Spermatozoa. Int. J. Mol. Sci. 2021, 22, 5972. https://doi.org/10.3390/ijms22115972

AMA Style

Poli G, Hasan S, Belia S, Cenciarini M, Tucker SJ, Imbrici P, Shehab S, Pessia M, Brancorsini S, D'Adamo MC. Kcnj16 (Kir5.1) Gene Ablation Causes Subfertility and Increases the Prevalence of Morphologically Abnormal Spermatozoa. International Journal of Molecular Sciences. 2021; 22(11):5972. https://doi.org/10.3390/ijms22115972

Chicago/Turabian Style

Poli, Giulia, Sonia Hasan, Silvia Belia, Marta Cenciarini, Stephen J. Tucker, Paola Imbrici, Safa Shehab, Mauro Pessia, Stefano Brancorsini, and Maria C. D'Adamo 2021. "Kcnj16 (Kir5.1) Gene Ablation Causes Subfertility and Increases the Prevalence of Morphologically Abnormal Spermatozoa" International Journal of Molecular Sciences 22, no. 11: 5972. https://doi.org/10.3390/ijms22115972

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