Lead Inhibits Human Sperm Functions by Reducing the Levels of Intracellular Calcium, cAMP, and Tyrosine Phosphorylation

Abstract

It is well known that there has been a worldwide decrease in human male fertility in recent years. One of the main factors affecting this is environmental pollution. Lead is one of the major heavy metal contaminants that threaten the health of animals and human beings in China. It preferentially accumulates in male reproductive organs and can be up to 10 µM in human seminal plasma. Lead impairs mammalian spermatogenesis and sperm quality in vivo. It also inhibits sperm functions in vitro but the underlying mechanisms remain unclear. Therefore, we aimed to investigate the in vitro toxicity of lead on human sperm functions and to elucidate the underlying mechanisms. Semen samples were collected from 20 healthy volunteers with different careers and backgrounds living in Nanchang, Jiangxi. Human sperm suspensions were treated with different concentrations of lead acetate (0, 0.5, 2.5, 10, 50, and 100 µM) and the viability, motility, capacitation and progesterone-induced acrosome reaction were examined. Treatment with 10-100 µ M lead acetate dose-dependently inhibited total and progressive motility measures, capacitation and progesterone-induced acrosome reaction. It also dose-dependently decreased the intracellular concentrations of cyclic adenosine monophosphate (cAMP) and calcium ([Ca 2+ ] i ), and reduced the tyrosine phosphorylation of sperm proteins, all of which are thought to be key factors in the regulation of sperm function. Our findings suggest that lead inhibits human sperm functions by reducing the levels of sperm intracellular cAMP, [Ca 2+ ] i and tyrosine phosphorylation of sperm proteins in vitro.

The role of physiologically occurring elements in semen and effect of heavy metals on semen

“…In a 2007 study from Telisman, high levels of lead in the blood were related to a higher percentage of abnormal spermatozoa [42]. Increased levels of lead in the seminal fluid had a negative impact on the quality of semen [13,24,31,40]. Similarly, in a Taiwanese study, increased levels of lead in the blood (> 50 μg/L) correlated with a low quality of semen [20].…”

“…This element accumulates in the male reproductive organs and can reach a concentration of up to 10 μM in seminal plasma. Lead impairs mammalian spermatogenesis and in vivo semen quality [40]. It also inhibits in vitro spermatozoa function by reducing the levels of intracellular cyclic adenosine monophosphate (cAMP) of sperm, calcium and the tyrosine phosphorylation of sperm proteins [40,41].…”

“…Lead impairs mammalian spermatogenesis and in vivo semen quality [40]. It also inhibits in vitro spermatozoa function by reducing the levels of intracellular cyclic adenosine monophosphate (cAMP) of sperm, calcium and the tyrosine phosphorylation of sperm proteins [40,41]. In 2012, the first prospective and non-randomised clinical study was published, which showed that a high level of lead accumulation in semen could reduce the sperm count, contributing to infertility in men without occupational exposure to lead (Pb) [41].…”

“…Pierwiastek ten gromadzi się w męskich narządach rozrodczych i może osiągnąć w plazmie nasienia stężenie do 10 μM. Ołów zaburza spermatogenezę ssaków i jakość nasienia in vivo [40]. Hamuje również funkcje plemników in vitro poprzez zmniejszenie poziomów wewnątrzkomórkowego cyklicznego monofosforanu adenozyny(cAMP) spermy, wapnia i fosforylacji tyrozyny białek plemników [40,41].…”

“…Ołów zaburza spermatogenezę ssaków i jakość nasienia in vivo [40]. Hamuje również funkcje plemników in vitro poprzez zmniejszenie poziomów wewnątrzkomórkowego cyklicznego monofosforanu adenozyny(cAMP) spermy, wapnia i fosforylacji tyrozyny białek plemników [40,41]. W 2012 r. opublikowano pierwsze prospektywne i nierandomizowane badanie kliniczne, które wykazało, że wysoki poziom akumulacji ołowiu w nasieniu może zmniejszyć liczbę plemników, przyczyniając się do niepłodności u mężczyzn bez narażenia zawodowego na ołów Pb [41].…”