Research Paper|Volume 12, Issue 9|pp 8321—8338

Mitochondria-related miR-574 reduces sperm ATP by targeting ND5 in aging males

Jinzhao Ma^1,², Qiwei Chen¹, Shuxian Wang², Rujun Ma^1,², Jun Jing^1,², Yang Yang³, Yuming Feng^1,², Zhichuan Zou^1,², Yu Zhang⁴, Xie Ge^1,², Tongmin Xue⁵, Kuan Liang¹, Siyuan Cao⁶, Dandan Wang², Li Chen^1,², Bing Yao^1,^2,^4,^5,⁶

¹Center of Reproductive Medicine, Nanjing Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing 210002, Jiangsu, China
²Center of Reproductive Medicine, Nanjing Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, Jiangsu, China
³Institute of Laboratory Medicine, Nanjing Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, Jiangsu, China
⁴Center of Reproductive Medicine, Nanjing Jinling Hospital, School of Medicine, Jiangsu University, Zhenjiang 212002, Jiangsu, China
⁵Jinling Hospital Department Reproductive Medical Center, Nanjing Medicine University, Nanjing 210002, Jiangsu, China
⁶School of Life Science, Nanjing Normal University, Nanjing 210002, Jiangsu, China

* Equal contribution

Received: January 14, 2020Accepted: March 31, 2020Published: May 7, 2020

https://doi.org/10.18632/aging.103141

Copyright © 2020 Ma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Couples are delaying childbearing in recent decades. While women experience a notable decrease in oocyte production in their late thirties, the effect of advanced paternal age on reproduction is incompletely understood. Herein, we observed that numerous miRNAs, including miR-574, increased in the sperm of aging males, as indicated by high-throughput sequencing. We demonstrated that miR-574 was upregulated in the sperm of two aging mouse models and was related to inferior sperm motility as an adverse predictor. Moreover, we proved that miR-574 suppressed mitochondrial function and reduced cellular ATP production in GC2 cells. Mechanistically, we demonstrated that miR-574 regulated mitochondrial function by directly targeting mt-ND5. Our study revealed an important role of miR-574 in sperm function in aging males and provided a fresh view to comprehend the aging process in sperm.