Effect of lindane on CYP‐mediated steroid hormone metabolism in male mice following in utero exposure

Abstract

A wide number of pesticides, including highly persistent organochlorinated compounds, such as lindane (LIN), may induce reproductive and developmental alterations by directly binding to the estrogen/androgen receptors or altering steroid hormone metabolism. In the present work, we have investigated whether LIN in utero exposure of CD1 mice affects the reproductive system in male offspring by causing an impairment of the CYP-dependent steroid hormone metabolism. Dam exposure to 25 mg kg(-1) b.w. LIN occurred during critical developmental periods, from gestational days 9 to 16. Effects on hepatic CYP-mediated testosterone (TST) hydroxylase, aromatase activities and testicular parameters were tested at postnatal days (PND 50, 65-69, 100) that are critical for sexual maturation in CD1 mice. In the adult F1 mice significant changes of male reproductive endpoints (testis weight, spermatid number) as well as dramatic effects on CYP-mediated TST metabolism were observed on PND 65-69, in the absence of any of systemic toxicity. The levels of TST 6beta- and 2alpha-hydroxylation and dehydrogenation showed the highest level of reduction, suggesting CYP 3A and 2C families as the major target of LIN induced effects. All changes were almost recovered on PND 100. No effects on aromatase activity were evidenced. Overall, these findings provide useful information for a better characterization of the LIN mode of action. They suggest that LIN-induced toxicity in males is linked to an impairment of steroid hormone homeostasis, due to CYP-mediated TST catabolism modulation and differs from LIN receptor-mediated mechanism previously reported in females.

Interaction Effects between Organochlorine Pesticides and IsoflavonesIn VitroandIn Vivo

“…Exposure to γ -HCH with dose of 25 mg/kg bw in vivo could increase absolute and relative uterus weight in F1 pups on postnatal day 22 and change vaginal patency and reduce diameters of primary oocytes at fully sexual maturity [22]. According to findings of Huang et al, both chlordane and γ -HCH treatment could increase estrogen, reduce testosterone, and alter morphology of the masculine appendage in shrimp [23].…”

Endocrine Disrupters and Food Safety

“…Experimental toxicology studies provide an ample range of examples. Lindane, a persistent chlorinated compound widely use in the past as insecticide, does alter the female reproductive development through the interaction with ER-beta [35]; lindane also reduces spematogenesis in male mice exposed in utero, an effect which might be related to an enhanced, CYP-mediated testosterone catabolism [36], suggesting a sex-related differential mechanism. The widespread neurotoxic insecticide chlorpyrifos acts as an ED in rodents only when exposure does occure in utero: the adult offspring of mouse dams exposed to non-neurotoxic dose levels show alterations of oxytocin and vasopressin brain levels [37] as well as of thyroid hormone balance [38], more pronounced in males.…”

Untitled

“…It will disappear from the water by secondary mechanisms such as adsorption on sediment, biological breakdown by microflora and fauna, and adsorption by fish through gills, skin, and food (Lawson et al, 2011). Although no clinical signs have been observed in aquatic organisms subjected to lindane toxicity, lindane toxicity affects the endocrine system of fish as a result of biochemical changes, resulting in hormonal imbalance due to the breakdown of steroidogenesis in the ovary, and a significant decrease in egg production (Singh et al, 1993;Ensenbach and Nagel, 1997;Pesando et al, 2004;Consiglio et al, 2009;Lawson et al, 2011;Mnif et al, 2011).…”