Perinatal Exposure to Methoxychlor Affects Reproductive Function and Sexual Behavior in Mice

Abstract

Numerous chemicals derived from human activity are now disseminated in the environment where their exert estrogenic endocrine disrupting effects, and therefore represent major health concerns. The present study explored whether Methoxychlor (MXC), an insecticide with xenoestrogens activities, given during the perinatal period (from gestational day 11 to postnatal day 8) and at an environmentally dose [20 µg/kg (body weight)/day], would affect reproductive physiology and sexual behavior of the offspring in mice. While MXC exposure did not induce any differences in the weight gain of animals from birth to 4 months of age, a clear difference (although in opposite direction according to the sexes) was observed on the anogenital distance between intact and exposed animals. A similar effect was also observed on preputial separation and vaginal opening, which reflects, respectively, in males and females, puberty occurrence. The advanced puberty observed in females was associated with an enhanced expression of kisspeptin cells in the anteroventral periventricular region of the medial preoptic area. Exposure to MXC did not induce in adult females changes in the estrous cycle or in the weight of the female reproductive tract. By contrast, males showed reduced weight of the epididymis and seminiferous vesicles associated with reduced testosterone levels and seminiferous tubule diameter. We also showed that both males and females showed deficits in mate preference tests. As a whole, our results show that MXC impacts reproductive outcomes.

Effects on Puberty of Nutrition-Mediated Endocrine Disruptors Employed in Agriculture

“…Delay in puberty onset in a dose-dependent manner was also observed among male SD rats indirectly exposed to methoxychlor at conception time, in utero and during lactation [55]. Moreover, when CD1 female mice were treated from GD 11 to PND 8 with methoxychlor at a very low dosage (20 µg/kg/day), their male offspring experienced balanopreputial separation later than nonexposed animals [30]. In summary, exposure to organochlorine insecticides during intrauterine and postnatal life delayed puberty onset among male animals.…”

“…Their female offspring, indirectly exposed during intrauterine life and lactation to methoxychlor, experienced earlier vaginal opening as well as a loss of regular estrus cyclicity at the age of 11 months [29]. Similarly, when CD1 female mice were treated from GD 11 to PND 8 with methoxychlor at a very low dosage (20 µg/kg/day), their female offspring experienced earlier vaginal opening and an increase in the number of kisspeptin neurons in the hypothalamus [30]. In female Wistar rats exposed to 10 and 100 mg/kg/day o,p -dichlorodiphenyltrichloroethane (DDT) sc from PND 6 to 10 (early and short-time exposure), vaginal opening occurred significantly earlier than in controls.…”