Disruption of Calcium Homeostasis in Human Spermatozoa: Implications on Mitochondrial Bioenergetics, ROS Production,...

Area of Science:

• Reproductive biology
• Biochemistry
• Cell biology

Background:

• Male infertility is often linked to oxidative stress, an imbalance of reactive oxygen species (ROS).
• Intracellular calcium (Ca2+) overload is a known inducer of excessive ROS production in spermatozoa.
• The precise relationship between Ca2+ dysregulation, ROS generation, and impaired sperm function requires further elucidation.

Purpose of the Study:

• To investigate the detrimental effects of intracellular Ca2+ overload on human sperm quality.
• To characterize the impact of Ca2+ overload on key functional sperm parameters.

Main Methods:

• Human sperm were incubated with ionomycin in a dose-dependent manner to induce intracellular Ca2+ overload.
• Key functional sperm parameters were analyzed, including ROS production, mitochondrial membrane potential, ATP and cAMP levels, motility, phosphatidylserine externalization, and viability.

Main Results:

• Intracellular Ca2+ overload significantly increased cytosolic and mitochondrial ROS production.
• Ca2+ overload led to dissipation of mitochondrial membrane potential (ΔΨm), reduced ATP and cAMP levels, and decreased sperm motility.
• Externalization of phosphatidylserine and reduced sperm viability were observed following Ca2+ overload.

Conclusions:

• Disruption of calcium homeostasis induces oxidative stress (OS), leading to impaired sperm quality.
• This study elucidates the interplay between ROS and Ca2+ signaling in the context of male infertility.
• The findings provide an in vitro model for future research on optimizing human sperm quality in patients with seminal OS.