Age-Dependent Alterations in Semen Parameters and Human Sperm MicroRNA Profile

Area of Science:

• Reproductive Biology
• Genetics
• Aging Research

Background:

• Delayed parenthood is a growing trend, increasing the incidence of advanced paternal age (APA).
• APA (men >40 years) is associated with impaired fertility and adverse reproductive outcomes.
• Sperm microRNAs are increasingly recognized for their role in fertilization and embryonic development.

Purpose of the Study:

• To investigate the impact of male age on semen parameters.
• To analyze sperm microRNA profiles in relation to paternal age.
• To identify potential molecular mechanisms linking APA to reduced fertility.

Main Methods:

• Analysis of ejaculates from 333 Portuguese men (2018-2022) for conventional semen parameters.
• Sperm microRNA expression profiling in 16 normozoospermic men across four age groups (≤30, 31-35, 36-40, >40 years).
• Bioinformatic analysis of microRNA target genes and pathways using miRDB, TargetScan, and DAVID tools.

Main Results:

• No significant correlation between male age and conventional semen parameters, except for a decrease in ejaculate volume with age.
• Fifteen differentially expressed microRNAs (DEMs) were identified between age groups.
• Enrichment analysis revealed DEMs in older men are involved in embryonic development, morphogenesis, and male gonad development, with targets linked to aging pathways (senescence, autophagy, insulin, mTOR).

Conclusions:

• Conventional semen parameters may not fully reflect the impact of male aging on fertility.
• Alterations in sperm microRNA profiles associated with advanced paternal age could underlie reduced reproductive success.
• Sperm microRNAs represent a potential biomarker and therapeutic target for age-related fertility decline.