The anti-inflammatory drug celecoxib inhibits t-type Ca2+ currents in spermatogenic cells yet it elicits the acrosome reaction in mature sperm

Celecoxib (Cx), an anti-inflammatory drug designed to inhibit COX2, can affect some ion channels. T-type (CaV3) channels have been implicated in sperm physiology. Here we report and characterize the Cx induced inhibition of T-type channels in mouse spermatogenic cells. Unexpectedly, Cx can also induce the acrosome reaction (AR), an intracellular Ca2+ ([Ca2+]i) increase and a sperm depolarization. This [Ca2+]i increase possibly results from the ability Cx has to alkalinize intracellular pH (pHi), which is known to activate the sperm specific Ca2+ channel CatSper. As the Cx induced [Ca2+]i increase is sensitive to mibefradil, a CatSper blocker, this channel may mediate the Cx-induced Ca2+ entry leading to the AR. Our observations demonstrate that Cx can compromise fertilization.