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Abstract

Volume 26, Issue 1 (January 2024) 26, 25–33; 10.4103/aja202329

Decreased AKAP4/PKA signaling pathway in high DFI sperm affects sperm capacitation

Zhang, Kun1,2,*; Xu, Xiu-Hua1,*; Wu, Jian1; Wang, Ning1; Li, Gang3; Hao, Gui-Min1; Cao, Jin-Feng1

1Hebei Key Laboratory of Infertility and Genetics, Department of Reproductive Medicine, Second Hospital of Hebei Medical University, Shijiazhuang 050000, China

2Department of Reproductive Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China

3Department of Neurology, The 980th Hospital of the People’s Liberation Army Joint Logistics Support Force (Bethune International Peace Hospital), Shijiazhuang 050000, China

Correspondence: Dr. JF Cao (jfcaoc@126.com)

Originally published: August 15, 2023 Received: March 12, 2023 Accepted: June 12, 2023

Abstract

The sperm DNA fragmentation index (DFI) is a metric used to assess DNA fragmentation within sperm. During in vitro fertilization-embryo transfer (IVF-ET), high sperm DFI can lead to a low fertilization rate, poor embryo development, early miscarriage, etc. A kinase anchoring protein (AKAP) is a scaffold protein that can bind protein kinase A (PKA) to subcellular sites of specific substrates and protects the biophosphorylation reaction. Sperm protein antigen 17 (SPA17) can also bind to AKAP. This study intends to explore the reason for the decreased fertilization rate observed in high sperm DFI (H-DFI) patients during IVF-ET. In addition, the study investigates the expression of AKAP, protein kinase A regulatory subunit (PKARII), and SPA17 between H-DFI and low sperm DFI (L-DFI) patients. SPA17 at the transcriptional level is abnormal, the translational level increases in H-DFI patients, and the expression of AKAP4/PKARII protein decreases. H2O2 has been used to simulate oxidative stress damage to spermatozoa during the formation of sperm DFI. It indicates that H2O2 increases the expression of sperm SPA17 protein and suppresses AKAP4/PKARII protein expression. These processes inhibit sperm capacitation and reduce acrosomal reactions. Embryo culture data and IVF outcomes have been documented. The H-DFI group has a lower fertilization rate. Therefore, the results indicate that the possible causes for the decreased fertilization rate in the H-DFI patients have included loss of sperm AKAP4/PKARII proteins, blocked sperm capacitation, and reduced occurrence of acrosome reaction.

Keywords: AKAP; PKA; SPA17; sperm capacitation; sperm DNA fragmentation index

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Asian Journal of Andrology CN 31-1795/R ISSN 1008-682X  Copyright © 2023  Shanghai Materia Medica, Chinese Academy of Sciences.  All rights reserved.