3-Monochloro-1,2-propanediol (3-MCPD) is a food contaminant that is often found in foods containing acid-hydrolyzed (AH) protein, like seasonings and savory food products. The purpose of the present study was to investigate the effects of 3-MCPD on male fertility, sperm, and hormonal levels and its antifertility mechanism. In vivo male fertility testing was performed to observe the adverse effects of 3-MCPD on the functioning of the male reproductive system and pregnancy outcome. 3-MCPD (0.01-5 mg/kg) was administered daily by gavage to Sprague-Dawley (SD) male rats for 4 wk. At the end of the pretreatment period, male rats were mated overnight with untreated females. Males successfully inducing pregnancy were sacrificed to assess sperm parameters, reproductive organ histopathology, and spermatogenesis. The resulting pregnant females were sacrificed on 20 of gestation to evaluate pregnancy outcome. The paternal administration of 3-MCPD (5 mg/kg) was found to result in adverse effects on male fertility and pregnancy outcome without inducing remarkable histopathological changes in testes and epididymides. Additionally, 3-MCPD (5 mg/kg) significantly reduced sperm motility, copulation, fertility indices, and the number of live fetuses showed steep dose-response curves. 3-MCPD did not affect spermatogenesis or induce hormonal changes in the blood and testes of male rats. An in vitro hormone assay using primary isolated Leydig cells showed no significant changes in related hormone levels after 3-MCPD treatment. To evaluate the effects of 3-MCPD on apoptotic induction and H+-ATPase levels in the testis and epididymis, 10 or 100 mg/kg of 3-MCPD was administered by gavage to male rats and testes and epididymides were examined at 3, 6, 12, and 24 h later. Apoptosis was not detected in the testes of animals treated with 100 mg/kg 3-MCPD. However, the level of H+-ATPase in the cauda epididymis was reduced by 3-MCPD treatment. These results indicate that 3-MCPD induced a spermatotoxic effect, which was mediated by reduced H+-ATPase expression in the cauda epididymis, and suggest that an altered pH level in the cauda epididymis might lead to a disruption of sperm maturation and the acquisition of motility.

Alcohol drinking during pregnancy results in abnormal fetal development, including fetal alcohol syndrome (FAS) in humans and experimental animals. FAS is characterized by two major effects, including central nervous system (CNS) dysfunction and multiple anomalies recognizable mainly as a typical face. However, the mechanisms of alcohol-induced embryotoxicity have not been clearly demonstrated. The aim of the present study was to investigate the possible mechanisms underlying ethanol-induced FAS in the developing embryo. First, ethanol-induced developmental abnormalities were investigated in vitro. Postimplantation embryos at gestation day (GD) 9.5 were cultured for 48 h and observed for morphological changes. Ethanol-mediated changes in proteins regulated apoptosis (p53 and bcl-2), antioxidant (vitamin E and catalase) activities, generation of reactive oxygen species (ROS), and oxidative DNA damage shown as 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured in embryonic midbrain cells. Alcohol or acetaldehyde significantly induced cytotoxicity in cultured rat embryonic midbrain cells. The levels of p53, bcl-2, and 8-OHdG were concomitantly changed by alcohol and acetaldehyde treatment in midbrain cells. Injured cells induced by ROS were increased by alcohol or acetaldehyde treatment in midbrain cells. Cotreatment with alcohol or acetaldehyde and catalase decreased cytotoxicity in midbrain cells. In postimplantation embryo culture, alcohol or acetaldehyde-treated embryos showed retardation of embryonic growth and development in a concentration-dependent manner. These results indicate that alcohol and its metabolite acetaldehyde induce fetal developmental abnormalities by disrupting cellular differentiation and growth. Data demonstrate that some antioxidants can partially protect against the alcohol-induced embryonic developmental toxicity.

This present study was undertaken to examine the effects of DBP and its metabolite mono-n-butyl phthalate (MBuP) on cytotoxicity and differentiation in cultured rat embryonic limb bud cells. When limb bud cells extracted from rats on gestation d 12.5 were treated with DBP or MBuP for 96 h, induction of cytotoxicity and inhibition of cell differentiation were observed in a concentration-dependent manner. However, MBuP elicited a toxic effect at higher concentrations than DBP. The IC50 values of DBP for cytotoxicity (measured by neutral red uptake) and cell differentiation (measured by alcian blue staining) were 25.54 microg/ml (91.75 microM) and 21.21 microg/ml (76.20 microM), respectively. The IC50 values of MBuP for cytotoxicity and cell differentiation were 307.24 microg/ml (1.38 mM) and 142.61 microg/ml (0.64 mM), respectively. in order to determine whether free radicals are related to induction of cytotoxicity and inhibition of differentiation by DBP in limb bud cells, DBP was coadministered with several antioxidants, including catalase and vitamin E acetate to limb bud cells. Cotreatment with catalase and vitamin E acetate decreased induction of cytotoxicity and inhibition of differentiation by DBP in limb bud cells. However, these compounds did not show any protective effect against MBuP. Results indicate that DBP and MBuP induced developmental toxicity in rat embryonic limb bud cells and suggest that this effect of DBP might be exerted through oxidative stress.