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.
Highlights
Methoxychlor (MXC) is an insecticide that is acting as an Endocrine Disrupting Compound (EDC)
MXC had a significant effect both in males and in females on anogenital distance (AGD) from post-natal day (PD) 4 to PD 120, with males having a longer AGD than females, treated males having a shorter AGD than control males and treated females having a longer AGD than controls (Figure 1B)
The greatest difference between the two groups was observed at PD 27: the percentage of females showing vaginal opening was 3 times higher in the group perinatally exposed to MXC in comparison to the groups of control females
Summary
Methoxychlor (MXC) is an insecticide that is acting as an Endocrine Disrupting Compound (EDC). MXC is persistent in the environment [1] because significant amounts of MXC and deriving metabolites can be measured in human tissues, long after stopping its use [2]. MXC has been found in human tissue samples [3] and breast milk [4]. It has been demonstrated recently that MXC has the potential to promote the transgenerational inheritance of disease [5]. The health effects of MXC remain an important public health concern in humans. MXC is known to act as an agonist on estrogen receptor (ER) α and ERβ and as an antagonist of androgen receptor [AR [6]]. MXC contamination seems to occur mainly through ingestion: MXC is absorbed at the level of the gastrointestinal tract and is metabolized in the liver, following
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