# Dialogue between nutrition and reproduction: preliminary exploration of sperm quality response to high-fat diet in mice

## TL;DR

A high-fat diet in male mice leads to poor sperm quality and infertility due to oxidative stress and disrupted cellular processes.

## Contribution

This study reveals a pathogenic cascade linking high-fat diets to impaired spermatogenesis through oxidative stress and autophagy disruption.

## Key findings

- HFD caused obesity, reduced testosterone, and complete loss of fertility in mice.
- HFD increased oxidative stress and DNA damage in sperm while disrupting autophagy and apoptosis pathways.
- Region-specific molecular changes were observed in the reproductive tract of HFD-fed mice.

## Abstract

High-fat diets are known to affect semen quality, potentially through metabolic and cellular stress mechanisms.

This study investigates the impact of a high-fat diet on semen quality in male mice and identifies the underlying mechanisms involved.

Thirty male C57BL/6J mice were randomly assigned to a control diet (CD) or HFD for 12 weeks. Sperm parameters and fertility were assessed by computer-assisted sperm analysis and mating trials. Testicular oxidative stress indices, autophagy- and apoptosis-related proteins were analyzed by biochemical assays and Western blot. Mitophagy (LC3B–Grp75 co-localization), tissue morphology (H&E, TUNEL, electron microscopy) and sperm DNA damage (DNA fragmentation index, 8-hydroxy-2′-deoxyguanosine [8-OHdG]) were further evaluated. Serum lipids and testosterone were measured by enzymatic assays and ELISA.

HFD mice developed obesity, dyslipidemia, reduced testosterone, marked decreases in sperm count, progressive motility and normal morphology, and complete loss of fertility. Region-specific molecular alterations were observed along the reproductive tract: in epididymal caput, Beclin-1 and LC3B were upregulated and p62 downregulated, indicating enhanced autophagic flux; in cauda epididymis, pro-apoptotic markers increased and Bcl-2 decreased, consistent with augmented apoptosis; in testis, ATG5, Beclin-1, caspase-3 and Apaf-1 were elevated. HFD also increased testicular ROS and MDA, reduced SOD activity and mitochondrial membrane potential, and elevated sperm apoptosis, DNA fragmentation and 8-OHdG.

HFD induces a pathogenic cascade—oxidative stress, disrupted autophagy/mitophagy, and mitochondrial apoptosis-that collectively impair spermatogenesis and male fertility. Therapeutic strategies targeting antioxidant defenses, autophagic flux, and mitophagy may ameliorate obesity-related reproductive dysfunction.