Methyl-parathion decreases sperm function and fertilization capacity after targeting spermatocytes and maturing spermatozoa

Abstract

Paternal germline exposure to organophosphorous pesticides (OP) has been associated with reproductivefailures and adverse effects in the offspring. Methyl-parathion (Me-Pa), a worldwide-used OP, hasreproductive adverse effects and is genotoxic to sperm, possibly via oxidative damage. This studyinvestigated the stages of spermatogenesis susceptible to be targeted by Me-Pa exposure that impact onspermatozoa function and their ability to fertilize. Male mice were exposed to Me-Pa (20 mg/kg bw, i.p.) andspermatozoa from epididymis-vas deferens were collected at 7 or 28 days post-treatment (dpt) to assess theeffects on maturing spermatozoa and spermatocytes, respectively. Spermatozoa were examined for DNAdamage by nick translation (NT-positive cells) and SCSA (%DFI), lipoperoxidation (LPO) by malondialdehydeproduction, sperm function by spontaneous- and induced-acrosome reactions (AR), mitochondrialmembrane potential (MMP) by using the JC-1 fluorochrome, and fertilization ability by an in vitro assayand in vivo mating. Alterations on DNA integrity (%DFI and NT-positive cells) in spermatozoa collected at 7and 28 dpt, and decreases in sperm quality and induced-AR were observed; reduced MMP and LPO wereobserved at 7 dpt only. Negative correlations between LPO and sperm alterations were found. Altered spermfunctional parameters evaluated either in vitro or in vivo were associated with reduced fertilization rates atboth times. These results show that Me-Pa exposure of maturing spermatozoa and spermatocytes affectsmany sperm functional parameters that result in a decreased fertilizing capacity. Oxidative stress seems to bea likely mechanism of the detrimental effects of Me-Pa exposure in male germ cells.