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Age-Associated Metabolomic Changes in Human Spermatozoa.

Mohd Amin Beg1, Md Shawkat Khan1,2, Ishfaq Ahmad Sheikh1

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Male fertility declines with age due to changes in sperm metabolism. This study identified key sperm metabolites altered by aging, offering potential biomarkers for preserving reproductive health.

Keywords:
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Area of Science:

  • Reproductive Biology
  • Metabolomics
  • Aging Research

Background:

  • Aging-associated decline in male fertility is a growing concern.
  • The specific functional genomic and metabolic mechanisms underlying this decline are not well understood.
  • Spermatozoa undergo significant metabolic changes with age, impacting their function.

Purpose of the Study:

  • To investigate age-related alterations in the sperm metabolome of healthy fertile men.
  • To identify potential biomarkers associated with aging and sperm function.
  • To understand the impact of aging on sperm metabolite homeostasis (metabolostasis).

Main Methods:

  • Sperm samples were collected from three age groups of healthy fertile Arab men (young adult, late adult, advanced age).
  • Metabolomic profiling was performed using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).
  • Statistical and functional analyses were conducted using MetaboAnalyst-Pro, including Principal Component Analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA).

Main Results:

  • A total of 380 metabolites were identified, with 164 showing significant age-related differences (p < 0.05).
  • Distinct metabolomic profiles were observed between young adult and advanced age groups.
  • Key metabolites like L-homocysteine (undetectable in advanced age) and methyloctadecanoyl-CoA (abundant in advanced age) were identified. 137 potential aging-sperm biomarkers were discovered.

Conclusions:

  • Advancing age disrupts sperm metabolostasis, affecting sperm integrity and fertilization competence.
  • Identified biomarkers are involved in crucial sperm functions like motility, energy metabolism, and oxidative stress regulation.
  • These biomarkers represent promising targets for interventions aimed at preserving sperm health and mitigating age-related fertility decline.