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.

Highlights

  • An increasing number of men are fathering children at an older age than in the past

  • After excluded differentially expressed miRNAs in oocytes, we found 101 miRNAs that were differentially expressed in sperm

  • As sperm miRNAs might participate in embryo development, we overlapped the specific miRNAs in sperm with the differentially expressed miRNAs in embryos, and obtained 33 miRNAs that might contain the contributor of embryo development from the sperm of aging males (Figure 1B)

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Summary

Introduction

An increasing number of men are fathering children at an older age than in the past. Due to societal pressures, increased life expectancy, assisted reproduction techniques (ART) and the use of modern contraception, the average reproductive age of couples has risen visibly in recent decades, with the mean age of their first reproduction in mid- or late-thirties in many countries [1]. Multiple epidemiologic studies have been conducted to examine the relationship between paternal age and semen quality, and numerous studies have reported agerelated declines in semen quality, including semen volume, sperm motility and sperm morphology [2,3,4]. A systematic review using data from 90 studies (93,839 subjects) indicated that semen volume, percentage motility, progressive motility and normal morphology declined with age, while DNA fragmentation increased with age [5]. These studies suggest that advanced paternal age tends to be associated with a decline in semen quality [5, 6]

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