IFN-gamma alters the human sperm membrane permeability to Ca²⁺

Abstract

Inflammation in the male genitourinary tract has been associated with the release of pro-inflammatory cytokines such as interferon-gamma (IFN-γ) and elevated reactive oxygen species, which affects spermatozoa capacitation, motility, and the acrosome reaction, along with functions regulated by the concentration of cytoplasmic Ca(2+) ([Ca(2+)]cyto). Though Ca(2+) signaling is of particular significance in sperm, the effect of IFN-γ intracellular calcium on these cells is still unknown. The present study evaluated the effect of IFN-γ on the [Ca(2+)]cyto and Ca(2+) permeability on human sperm. A cell suspension loaded with fura-2 was incubated with or without IFN-γ (from 0 to 2000 pg/ml) for 0, 30, 60, and 120 minutes, and the [Ca(2+)]cyto was measured. The permeability to Ca(2+) was evaluated by the change of the intracellular concentration following an extracellular Ca(2+) pulse. IFN-γ at low concentrations (≤ 500 pg/ml) did not affect the [Ca(2+)]cyto and Ca(2+) permeability of sperm. At a high concentration (2000 pg/ml), IFN-γ did not alter the [Ca(2+)](cyto), but significantly decreased the magnitude and velocity of Ca(2+) entry into the cell. This effect was dependent on incubation time and IFN-γ concentration. This alteration induced by IFN-γ was prevented by the simultaneous incubation of sperm with the antioxidant butylhydroxytoluene (BHT). In conclusion, in vitro, IFN-γ modifies Ca(2+) sperm membrane permeability, probably via lipid peroxidation. IFN-γ in high concentration, as observed in inflammation/infection, can affect [Ca(2+)](cyto) regulation and alter sperm fertilizing capacity.

Seminal Plasma Cytokines Are Predictive of the Outcome of Boar Sperm Preservation

“…For instance, the mitogen-activated protein kinase (MAPK) or the tyrosine kinase (JAK/STAT) (15, 20, 39), are both closely related with sperm motility (40) and the TGFβs IFN-γ, and IL-6 would be among the cytokines involved in these pathways (39). Focusing on IFN-γ, its SP concentrations were also found positively related to increased sperm membrane permeability, linked to LPO, and negatively related with sperm motility in human ejaculates (41, 42). Boar spermatozoa have receptors to IFN-γ (43) and the concentration measured in boar SP was higher than that reported in SP of healthy men (33).…”

ACE2 Receptor and Its Isoform Short-ACE2 Are Expressed on Human Spermatozoa

“…In addition, as anticipated, ACE2 is not the only entry point for the virus into the cells. TMPRSS2 is co-expressed with ACE2 in several organs and tissues [ 25 , 26 , 27 , 28 , 29 , 30 ]. In terms of virus response, it would be necessary to study their co-expression to determine the exact mechanism of action of ACE2.…”

Human Immune System Diseasome Networks and Female Oviductal Microenvironment: New Horizons to be Discovered

“…(2014). In that in vitro study, high concentrations of IFN-γ affected the intracellular calcium concentration, altering the sperm membrane permeability and thus impairing the sperm fertilizing ability (Carrasquel et al, 2014). Moreover, it has been demonstrated that an excess of the protein can also promote the generation of cytotoxic or CD8 + cells during the embryo implantation that later drives to fetal loss (Robertson et al, 2018), thus supporting its fundamental involvement as a regulator of the maternal-fetal immune relationship.…”

“…In reproduction, IFN-γ shows an important role on embryo implantation and pregnancy progression (Robertson et al, 2018). For instance, increased levels of IFN-γ have been associated with a reduced fertility (Carrasquel et al, 2014), as evidenced by the results of Carrasquel and coll. (2014).…”