Effects of estrogenic compounds on human spermatozoa: evidence for interaction with a nongenomic receptor for estrogen on human sperm membrane

Estrogens play an important role in the development and regulation of the m ale reproductive system. We have earlier shown that a nongenomic receptor. fur estradiol present on sperm plasma membrane mediates the effects exerted by this hormone on sperm intracellular calcium concentrations ([Ca2+](i)), as well as on the biological response to progesterone (P). In particular, 17 beta -estradiol (17 betaE(2)) shows an inhibitory effect on P-mediated c alcium influx and acrosome reaction (AR). In the present study, the effects of different anti-estrogens and xenoestrogens on [Ca2+](i) and AR stimulat ed by P have been investigated in human spermatozoa in order to better defi ne the pharmacological characteristics of the sperm membrane estrogen recep tor. The anti-estrogens tamoxifen (Tx) and ICI 164 384 (ICI) induce only a slight increase of [Ca2+](i), which, however, as in the case of 17 betaE(2) , results in a reduction of P-stimulated calcium influx. Moreover, both the compounds reduce the calcium response to 17 betaE(2) without affecting 17 betaE(2)-inhibition of calcium response to P. Concerning AR, Tx alone does not alter either spontaneous or P-stimulated AR but partially revert the in hibitory effect of 17 betaE(2). These results indicate that the two estroge ns act as pharmacological agonists of the membrane estrogen receptors of hu man spermatozoa. On the other hand, the xenoestrogens bisphenol A (BPA) and octyiphenol polyethoxilate (OP) do not exert any direct effect on calcium fluxes and AR in human spermatozoa either in basal conditions or in respons e to P challenge. Moreover, although these environmental estrogens have bee n suggested to mimic estrogen effects in the other cell types, probably act ing through genomic receptors, in human spermatozoa they do not interfere w ith 17 betaE(2) binding to its membrane receptor and with the short-term ef fects exerted by this steroid. In conclusion, our data indicate that the me mbrane receptor for estradiol in human spermatozoa shows both biochemical a nd pharmacological differences respect to the genomic receptor. (C) 2001 El sevier Science Ireland Ltd. All rights reserved.