Testis-Specific Isoform of Na<sup>+</sup>-K<sup>+</sup> ATPase and Regulation of Bull Fertility

An advanced understanding of sperm function is relevant for evidence-based male fertility prediction and addressing male infertility. A standard breeding soundness evaluation (BSE) merely identifies gross abnormalities in bulls, whereas selection based on single nucleotide polymorphisms and genomic...

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Main Authors: Saurabh Tiwari, Gayathri Rajamanickam, Veena Unnikrishnan, Mina Ojaghi, John P. Kastelic, Jacob C. Thundathil
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/14/7936
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author Saurabh Tiwari
Gayathri Rajamanickam
Veena Unnikrishnan
Mina Ojaghi
John P. Kastelic
Jacob C. Thundathil
author_facet Saurabh Tiwari
Gayathri Rajamanickam
Veena Unnikrishnan
Mina Ojaghi
John P. Kastelic
Jacob C. Thundathil
author_sort Saurabh Tiwari
collection DOAJ
description An advanced understanding of sperm function is relevant for evidence-based male fertility prediction and addressing male infertility. A standard breeding soundness evaluation (BSE) merely identifies gross abnormalities in bulls, whereas selection based on single nucleotide polymorphisms and genomic estimated breeding values overlooks sub-microscopic differences in sperm. Molecular tools are important for validating genomic selection and advancing knowledge on the regulation of male fertility at an interdisciplinary level. Therefore, research in this field is now focused on developing a combination of in vitro sperm function tests and identifying biomarkers such as sperm proteins with critical roles in fertility. The Na<sup>+</sup>-K<sup>+</sup> ATPase is a ubiquitous transmembrane protein and its α4 isoform (ATP1A4) is exclusively expressed in germ cells and sperm. Furthermore, ATP1A4 is essential for male fertility, as it interacts with signaling molecules in both raft and non-raft fractions of the sperm plasma membrane to regulate capacitation-associated signaling, hyperactivation, sperm-oocyte interactions, and activation. Interestingly, ATP1A4 activity and expression increase during capacitation, challenging the widely accepted dogma of sperm translational quiescence. This review discusses the literature on the role of ATP1A4 during capacitation and fertilization events and its prospective use in improving male fertility prediction.
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spelling doaj.art-89fbd75aa7a94da5bd8e6e74c5bfbe202023-11-30T21:06:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012314793610.3390/ijms23147936Testis-Specific Isoform of Na<sup>+</sup>-K<sup>+</sup> ATPase and Regulation of Bull FertilitySaurabh Tiwari0Gayathri Rajamanickam1Veena Unnikrishnan2Mina Ojaghi3John P. Kastelic4Jacob C. Thundathil5Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaDepartment of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaDepartment of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaDepartment of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaDepartment of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaDepartment of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaAn advanced understanding of sperm function is relevant for evidence-based male fertility prediction and addressing male infertility. A standard breeding soundness evaluation (BSE) merely identifies gross abnormalities in bulls, whereas selection based on single nucleotide polymorphisms and genomic estimated breeding values overlooks sub-microscopic differences in sperm. Molecular tools are important for validating genomic selection and advancing knowledge on the regulation of male fertility at an interdisciplinary level. Therefore, research in this field is now focused on developing a combination of in vitro sperm function tests and identifying biomarkers such as sperm proteins with critical roles in fertility. The Na<sup>+</sup>-K<sup>+</sup> ATPase is a ubiquitous transmembrane protein and its α4 isoform (ATP1A4) is exclusively expressed in germ cells and sperm. Furthermore, ATP1A4 is essential for male fertility, as it interacts with signaling molecules in both raft and non-raft fractions of the sperm plasma membrane to regulate capacitation-associated signaling, hyperactivation, sperm-oocyte interactions, and activation. Interestingly, ATP1A4 activity and expression increase during capacitation, challenging the widely accepted dogma of sperm translational quiescence. This review discusses the literature on the role of ATP1A4 during capacitation and fertilization events and its prospective use in improving male fertility prediction.https://www.mdpi.com/1422-0067/23/14/7936ATP1A4capacitationmale fertilitysignalingsperm
spellingShingle Saurabh Tiwari
Gayathri Rajamanickam
Veena Unnikrishnan
Mina Ojaghi
John P. Kastelic
Jacob C. Thundathil
Testis-Specific Isoform of Na<sup>+</sup>-K<sup>+</sup> ATPase and Regulation of Bull Fertility
International Journal of Molecular Sciences
ATP1A4
capacitation
male fertility
signaling
sperm
title Testis-Specific Isoform of Na<sup>+</sup>-K<sup>+</sup> ATPase and Regulation of Bull Fertility
title_full Testis-Specific Isoform of Na<sup>+</sup>-K<sup>+</sup> ATPase and Regulation of Bull Fertility
title_fullStr Testis-Specific Isoform of Na<sup>+</sup>-K<sup>+</sup> ATPase and Regulation of Bull Fertility
title_full_unstemmed Testis-Specific Isoform of Na<sup>+</sup>-K<sup>+</sup> ATPase and Regulation of Bull Fertility
title_short Testis-Specific Isoform of Na<sup>+</sup>-K<sup>+</sup> ATPase and Regulation of Bull Fertility
title_sort testis specific isoform of na sup sup k sup sup atpase and regulation of bull fertility
topic ATP1A4
capacitation
male fertility
signaling
sperm
url https://www.mdpi.com/1422-0067/23/14/7936
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