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Author Spotlight: Advancing Male Infertility Research by Unraveling Sperm Metabolism and Mitochondrial Function
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Mitochondrial permeability transition increases reactive oxygen species production and induces DNA fragmentation in

Favián Treulen1, Pamela Uribe1, Rodrigo Boguen1

  • 1Centre of Reproductive Biotechnology (BIOREN-CEBIOR), Faculty of Medicine, University of La Frontera, Temuco, Chile.

Human Reproduction (Oxford, England)
|February 10, 2015
PubMed
Abstract

Insights

Mitochondrial permeability transition (MPT) in human sperm, triggered by calcium, causes increased reactive oxygen species (ROS) and DNA damage. Modulating MPT may prevent oxidative stress in sperm.

Area of Science:

  • Reproductive Biology
  • Mitochondrial Biology
  • Spermatozoa Function

Background:

  • Oxidative stress significantly impairs sperm function and contributes to male infertility.
  • Mitochondrial permeability transition (MPT) in somatic cells involves pore opening in the inner mitochondrial membrane, leading to increased ROS and membrane potential dissipation.
  • The role of MPT in generating oxidative stress and DNA fragmentation in human spermatozoa remains uninvestigated.

Purpose of the Study:

  • To investigate whether calcium overload-induced mitochondrial permeability transition (MPT) causes reactive oxygen species (ROS) production and DNA fragmentation in human spermatozoa.
  • To elucidate the mechanism of oxidative stress and DNA damage in sperm.

Main Methods:

  • Human spermatozoa were treated with ionomycin to induce calcium overload.
  • Evaluated sperm inner mitochondrial membrane permeability, mitochondrial membrane potential (ΔΨm), intracellular ROS production, and DNA fragmentation.
  • Utilized calcein-AM/cobalt chloride, JC-1 staining, dihydroethidium, and TUNEL assay, analyzed via fluorescence and confocal microscopy, and flow cytometry.

Main Results:

  • Ionomycin treatment led to decreased calcein fluorescence, indicating MPT pore opening in the sperm inner mitochondrial membrane.
  • This MPT induction was associated with mitochondrial membrane potential (ΔΨm) dissipation and increased ROS production.
  • ROS production was observed to precede the dissipation of ΔΨm, and DNA fragmentation was also increased.

Conclusions:

  • MPT, induced by calcium influx and pore opening in the sperm inner mitochondrial membrane, is a significant contributor to increased ROS and DNA fragmentation.
  • These findings suggest that MPT is a key mechanism underlying oxidative stress-induced sperm damage.
  • Targeting agents that modulate MPT pore opening could offer a strategy for preventing oxidative stress-related damage in human spermatozoa.
Keywords:
infertilitymitochondrial membrane potentialmitochondrial permeability transition poremitochondrionreactive oxygen species

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