Abstract
Objective: Seminal plasma (SP) Pb2+ levels of artificial insemination (AI) donors (n = 16) and unselected (US) semen donors (n = 22) varied widely (10 to >1500 μg/L). SP Pb2+ levels >430 μg/L correlated with decreased AI fecundity rates and decreased pregnancy by coitus (Spearman rank correlations [SC], respectively, r = −0.6, P < 0.0001 and r = −0.6, P < 0.002), without effect on sperm count (SC, respectively, r = −0.05 and r = 0.2, NS). Increasing SP Pb2+ decreased fertilizing potential by stimulating “spontaneous” acrosome loss (SAR) (SC, respectively, r = 0.7, P < 0.002 and r = 0.5, P < 0.01) and inhibiting progesterone (P)-induced acrosome reactions (PAR) (SC, respectively, r = −0.5, P < 0.01 and r = −0.7, P < 0.003). Studies of infertility patients had indicated that a voltage-gated potassium channel (VGKC) related to KCNA3 (Accession No. L23499) modulates SAR and PAR, and that Pb2+ enters human sperm via VGKC. In AI and US, SP Pb2+ between 430 and 800 μg/L was associated with sperm head expression of variant VGKCs resistant to charybdotoxin (CBTx), a potent inhibitor of delayed rectifier VGKC. SP Pb2+ >800 μg/L were associated with loss of sperm VGKC expression. Now we evaluate the relationship over time between SP Pb2+ levels and VGKC isoform expression by human sperm.
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