Initiation of the human sperm acrosome reaction by thapsigargin

Previous studies have established that the mammalian sperm acrosome reaction (AR) is dependent upon an influx of extracellular Ca2+, but the involvement of a mobilizable store of intracellular Ca2+ has not been shown. In many other cells, the endoplasmic reticulum is the site of such a Ca(2+)-store....

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Bibliographic Details
Published inThe Journal of experimental zoology Vol. 267; no. 3; p. 350
Main Authors Meizel, S, Turner, K O
Format Journal Article
LanguageEnglish
Published United States 01.11.1993
Subjects
Acrosome - drug effects
Acrosome - physiology
Acrosome - ultrastructure
Calcium Channel Blockers - pharmacology
Humans
In Vitro Techniques
Lanthanum - pharmacology
Male
Nickel - pharmacology
Sperm Capacitation
Sperm Motility
Spermatozoa - drug effects
Spermatozoa - physiology
Spermatozoa - ultrastructure
Terpenes - pharmacology
Thapsigargin
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Summary:Previous studies have established that the mammalian sperm acrosome reaction (AR) is dependent upon an influx of extracellular Ca2+, but the involvement of a mobilizable store of intracellular Ca2+ has not been shown. In many other cells, the endoplasmic reticulum is the site of such a Ca(2+)-store. Here, we show that thapsigargin, a highly specific inhibitor of the endoplasmic reticulum Ca(2+)-ATPase Ca(2+)-pump (and thus a mobilizer of intracellular Ca2+) in other cells, can initiate the AR in capacitated human sperm. Thapsigargin at concentrations from 50-500 nM significantly increased the AR to the same extent when incubated with capacitated sperm for 1 min (assayed by indirect immunofluorescence). Transmission electron microscopy confirmed the occurrence of normal morphology in the AR initiated by thapsigargin. Thapsigargin (200 nM) did not initiate the AR in noncapacitated sperm. Initiation of the AR by thapsigargin apparently requires an influx of Ca2+ since 1 min preincubation with the calcium channel blockers La3+ (250 microM) or Ni2+ (250 microM) prior to addition of thapsigargin completely inhibits AR-initiation. Mobilization of an intracellular Ca(2+)-store by thapsigargin in capacitated human sperm may lead to an influx of extracellular Ca2+ and subsequently the AR. Putative sites for thapsigargin-sensitive intracellular Ca(2+)-stores in human sperm include the cytoplasmic droplet, the sperm nucleus and the acrosome.
ISSN:0022-104X
DOI:10.1002/jez.1402670312