Oxidative stress (OS) and disrupted antioxidant defense mechanisms play a pivotal role in the etiology of male infertility. The alterations in reactive oxygen species (ROS) production and calcium (Ca²⁺) homeostasis are the main activators for the mitochondrial permeability transition pore (mPTP) opening. The mPTP opening is one of the main mechanisms involved in mitochondrial dysfunction in spermatozoa. This alteration in mitochondrial function adversely affects energy supply, sperm motility, and fertilizing capacity and contributes to the development of male infertility. In human spermatozoa, the mPTP opening has been associated with ionomycin-induced endogenous oxidative stress and peroxynitrite-induced nitrosative stress; however, the effect of exogenous oxidative stress on mPTP opening in sperm has not been evaluated. The aim of this study was to determine the effect of exogenous oxidative stress induced by hydrogen peroxide (H₂O₂) on mPTP opening, mitochondrial function, motility, and cell death markers in human spermatozoa. Human spermatozoa were incubated with 3 mmol/L of H₂O₂ for 60 min, and intracellular Ca²⁺ concentration, mPTP opening, mitochondrial membrane potential (ΔΨm), ATP levels, mitochondrial reactive oxygen species (mROS) production, phosphatidylserine (PS) externalization, DNA fragmentation, viability, and sperm motility were evaluated. H₂O₂-induced exogenous oxidative stress caused increased intracellular Ca²⁺, leading to subsequent mPTP opening and alteration of mitochondrial function, characterized by ΔΨm dissipation, decreased ATP levels, increased mROS production, and the subsequent alteration of sperm motility. Furthermore, H₂O₂-induced opening of mPTP was associated with the expression of apoptotic cell death markers including PS externalization and DNA fragmentation. These results highlight the role of exogenous oxidative stress in causing mitochondrial dysfunction, deterioration of sperm motility, and an increase in apoptotic cell death markers, including PS externalization and DNA fragmentation, through the mPTP opening. This study yielded new knowledge regarding the effects of this type of stress on mitochondrial function and specifically on mPTP opening, factors that can contribute to the development of male infertility, considering that the role of mPTP in mitochondrial dysfunction in human sperm is not completely elucidated. Therefore, these findings are relevant to understanding male infertility and may provide an in vitro model for further research aimed at improving human sperm quality.

Background/Purpose: Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disease most common in patients of childbearing age. This pathology is associated with clinical, metabolic, and reproductive complications. We evaluated the diversity of the vaginal microbiota (VM), the vaginal inflammatory reaction (VIR), the proinflammatory state, and the activation of polymorphonuclear neutrophils (PMN) with the production of neutrophil extracellular traps (NETs). Methods: Thirty-three patients who attended a consultation at the Hospital UTPL-Santa Inés, Loja, Ecuador, from May to August 2023 who were diagnosed with PCOS participated in this study. Blood samples, vaginal discharge, and a survey were obtained. Results: A high number of patients, 23/33 (69.7%), presented altered microbiota in clinical variables associated with PCOS phenotypes A and B, sexual partners (>2), and oligomenorrhoea. A significant statistical association was only observed for sexually transmitted infections at sampling (p = 0.023) and insulin (p = 0.002). All eight cases studied with VIR had PMN/NETotic activity. A high frequency of proinflammatory states was observed in all vaginal microbiota states. Conclusions: These results suggest that the PCOS could trigger a proinflammatory state in the vaginal epithelium independently of the state of the vaginal microbiota. Furthermore, the presence of NETs observed in the cases studied could decrease fertility in these PCOS patients.

Contreras-Mellado P, et al. World J Mens Health. 2024 Sep;42:e83. https://doi.org/10.5534/wjmh.240085

The etiology of male infertility is linked to oxidative stress, which is an imbalance caused by an excess of reactive oxygen species (ROS) that can negatively impact sperm function. It is known that a strong stimulus to induce excessive ROS production by spermatozoa is an intracellular calcium (Ca²⁺) overload; however, the link between Ca²⁺ dysregulation, ROS production, and impaired sperm function is still an area requiring further research. This investigation aimed to characterize the intracellular Ca²⁺ overload detrimental effects on human sperm quality. The intracellular Ca²⁺ overload was achieved by dose-dependent incubation with ionomycin, followed by analysis of key functional sperm parameters. Ca²⁺ overload caused an increase in cytosolic and mitochondrial ROS production, dissipation of mitochondrial membrane potential (ΔΨm), reduction in ATP content, cAMP levels, and motility. Furthermore, Ca²⁺ overload promoted phosphatidylserine externalization and a decrease in sperm viability. This study provides novel insights into the interplay between ROS and Ca²⁺ signaling, highlighting that disruption of homeostasis induces OS, leading to impairment of sperm quality. These findings not only contribute to the understanding of the mechanisms underlying male infertility but also provide an in vitro model for future research aimed at optimizing human sperm quality in patients with seminal OS.