Abstract
Methoxychlor (MXC), an organochlorine pesticide, has adverse effects on male reproduction at toxicological doses. Humans and wild animals are exposed to MXC mostly through contaminated dietary intake. Higher concentrations of MXC have been found in human milk, raising the demand for the risk assessment of offspring after maternal exposure to low doses of MXC. In this study, pregnant mice (F0) were given intraperitoneal daily evening injections of 1 mg/kg/d MXC during their gestational (embryonic day 0.5, E0.5) and lactational periods (postnatal day 21.5, P21.5), and the F1 males were assessed. F1 testes were collected at P0.5, P21.5 and P45.5. Maternal exposure to MXC disturbed the testicular development. Serum testosterone levels decreased, whereas estradiol levels increased. To understand the molecular mechanisms of exposure to MXC in male reproduction, the F1 testes were examined for changes in the expression of steroidogenesis- and spermatogenesis- related genes. RT-PCR analysis demonstrated that MXC significantly decreased Cyp11a1 and increased Cyp19a1; furthermore, it downregulated certain spermatogenic genes (Dazl, Boll, Rarg, Stra8 and Cyclin-a1). In summary, perinatal exposure to low-dose MXC disturbs the testicular development in mice. This animal study of exposure to low-dose MXC in F1 males suggests similar dysfunctional effects on male reproduction in humans.
Highlights
Endocrine-disrupting compounds (EDCs) are synthetic or natural compounds that interfere with endogenous endocrine actions [1]
Most previous studies were carried out using toxicological doses of MXC [22,23], even though it is logically implausible that humans or wild life would be exposed under such conditions
It is widely accepted that EDCs have a great influence on human and animal reproduction at toxicological doses, the knowledge on the exposure of humans to lower or environmentally relevant doses of EDCs or of related effects on offspring remains limited
Summary
Endocrine-disrupting compounds (EDCs) are synthetic or natural compounds that interfere with endogenous endocrine actions [1]. Perinatal exposure to high-dose MXC is able to cause many reproductive abnormalities in adult male mice or rat [15,16,17,18,19,20,21]. Amstislavsky et al reported that transient exposure to 166.7 mg/kg/d MXC at embryonic day (E) 2 to E4 significantly increased the seminal vesicles weight and decreased the testosterone (T) level in male mice at 6 months [15]. Most previous studies were carried out using toxicological doses of MXC (over 100 mg/kg/d) [22,23], even though it is logically implausible that humans or wild life would be exposed under such conditions. To clarify the molecular mechanisms of exposure to MXC on male reproduction, we conducted a study examining MXC exposure during the perinatal period to determine its effect on fetal development, as well as the long-term impacts on the male reproductive systems of C57BL/6 mice
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
