The pesticide methoxychlor given orally during the perinatal/juvenile period, reduced the spermatogenic potential of males as adults by reducing their Sertoli cell number

Abstract

-Perinatal and juvenile oral treatment of rats with the insecticide, methoxychlor (MXC), reduced testicular size and other reproductive indices including the number of epididymal spermatozoa in those animals as adults [6]. The objective was to determine if these males exposed during development had fewer Sertoli cells which might explain these testicular effects. Rat dams were gavaged with MXC at 0, 5, 50, or 150 mg . kg -1 . day -1 for the week before and after they gave birth. Resulting male pups (15/group) then were dosed directly from postnatal day 7 to 42. Testes were fixed in Bouin's and in OsO4, embedded in Epon and sectioned at 0.5 mm, stained with toluidine blue, and evaluated stereologically or cut at 20 mm to measure Sertoli cell nuclei with Nomarski optics. Sertoli cell number was calculated as the volume density of the nucleus times the parenchymal weight (90% of testicular weight) divided by the volume of a single Sertoli cell nucleus. Across dose groups, there were no changes in the nuclear volume density, the volume of a single nucleus, or the number of Sertoli cells per g parenchyma. There were highly significant dose-related changes in the volume of Sertoli cell nuclei per testis and the number of Sertoli cells per testis. Reduced testicular weight (r = 0.94) and reduced numbers of epididymal spermatozoa (r = 0.43) were significantly (p < 0.01) correlated to reduced number of Sertoli cells per testis. Hence, perinatal and juvenile oral exposure to MXC can reduce spermatogenic potential of males as adults by reducing their number of Sertoli cells. methoxychlor / estrogenic / oral exposure / Sertoli cell number Reprod. Nutr. Dev. 42 (2002) 573-580 573

Two‐generation reproduction toxicity study in rats with methoxychlor

“…1997). Perinatal and juvenile oral exposure to methoxychlor is reported to reduce the number of Sertoli cells, which may in turn deteriorate spermatogenic potential of adult males (Johnson et al. 2002).…”

“…Methoxychlor, which was recently banned in the USA, and its active metabolite, hydroxyphenyltrichloroethane (HPTE), can bind to estrogen receptors (Shelby et al 1996;Bolger et al 1998;Kojima et al 2004;Okubo et al 2004) and induce typical uterotrophic responses, such as increases in wet and blotted weights and elevated epithelial cell proliferation of the uterus in rats and mice (Shelby et al 1996;Laws et al 2000;Kanno et al 2003). Although the reproductive toxicities of methoxychlor have also been well-characterized in several acute bioassays in which dams and/or their F1 offspring were treated with this compound during the gestation and/or lactation periods Chapin et al 1997;Johnson et al 2002;Takeuchi et al 2002;Masutomi et al 2003;Armenti et al 2008), a two-generation reproduction study in rats in accordance with the current guidelines has not been conducted as far as we know.…”

The effect of environmental contaminants on testicular function

“…30 Perinatal and juvenile exposure to MXC (at 5, 50 or 150 mg kg 21 ) has been reported to reduce spermatogenic potential by decreasing the volume of the Sertoli cell nucleus and the number of Sertoli cell which suggests that MXC impairs spermatogenesis by targeting the Sertoli cell population in the testis. 31 In male rats, intraperitoneal injection of 1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene (p,p9-DDE, a principal metabolite of DDT) at a dose of 60 or 100 mg kg 21 body weight for 10 days caused an increase in the levels of lipid peroxidation and a decrease in the activities of superoxide dismutase and glutathione peroxidase in the testis. An increase in the mRNA levels of Fas, FasL, caspase-3 and caspase-8 were also observed, which indicates that p,p9-DDE induces apoptosis through the Fas/FasL apoptotic pathway.…”

Similar causes of various reproductive disorders in early life

“…It was shown that the treatment of pregnant rats with methoxychlor (MXC) from gestational day 7 to 15 reduced the number of germ cells at the age of 17 dpc because of increased apoptosis 149. The treatment of perinatal and juvenile rats with MXC decreased the size of the Sertoli cell nuclei and the total Sertoli cell number, which was associated with an attenuated spermatogenic potential 150. In addition to MXC, 1,1-dichloro-2,2-bis ( p -chlorophenyl) ethylene ( p , p ’-DDE) and vinclozolin, a dicarboximide fungicide, were shown to suppress spermatogenesis by the activation of apoptosis 151.…”