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Targeting programmed cell death in male infertility: pathogenic mechanisms and therapeutic strategies

Runtang Zhou1, Wenbo Lv1, Jinyuan Wang1,2

  • 1Clinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.

Molecular Biology Reports
|June 16, 2026
PubMed

Insights

Programmed cell death (PCD) pathways like apoptosis and autophagy are crucial in male infertility. Dysregulation of these processes disrupts sperm production and testicular health, offering potential therapeutic targets.

Area of Science:

  • Reproductive Biology
  • Cellular Biology
  • Pathology

Background:

  • Male infertility is linked to various pathological processes, with programmed cell death (PCD) being a significant factor.
  • PCD encompasses multiple regulated forms, including apoptosis, autophagy, pyroptosis, and ferroptosis, alongside efferocytosis for clearing dying cells.

Purpose of the Study:

  • To review recent advancements in understanding PCD pathways in male infertility.
  • To explore shared molecular mechanisms, pathway interactions, and potential therapeutic strategies for male infertility related to PCD.

Main Methods:

  • Literature review of recent scientific advances.
  • Focus on five key PCD pathways: apoptosis, autophagy, pyroptosis, ferroptosis, and efferocytosis.
  • Analysis of molecular nodes and pathway crosstalk.

Main Results:

  • PCD is an actively regulated process vital for testicular homeostasis, involving germ cells, Sertoli cells, and Leydig cells.
  • Aberrant PCD activation, driven by oxidative stress, inflammation, or metabolic issues, impairs spermatogenesis and the testicular environment.
  • Identified shared molecular nodes and crosstalk among PCD pathways.

Conclusions:

  • Understanding PCD mechanisms is critical for elucidating male infertility causes.
  • Targeting specific PCD pathways presents a promising avenue for therapeutic development in male infertility.
Keywords:
ApoptosisEfferocytosisFerroptosisMale infertilityProgrammed cell deathPyroptosis

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