ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Reproduction
Dialogue between Nutrition and Reproduction: Preliminary Exploration of Sperm Quality Response to High-Fat Diet in Mice
Provisionally accepted
Yali Jiang
Wenge Zhang*- The Friendship Hospital of Ili Kazakh Autonomous Prefecture, Ili, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: High-fat diets are known to affect semen quality, potentially through metabolic and cellular stress mechanisms. Objectives: This study investigates the impact of a high-fat diet on semen quality in male mice and identifies the underlying mechanisms involved. Materials and Methods: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.Results: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 up-regulated and p62 down-regulated, 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.Conclusion: 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.
Keywords: Apoptosis, high-fat diet, Mice, Oxidative Stress, Semen quality
Received: 18 Jun 2025; Accepted: 11 Dec 2025.
Copyright: © 2025 Jiang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wenge Zhang
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.