Endocrine-disrupting chemicals found in many commercial products may interfere with the normal functioning of the endocrine system and are unsafe because of their cumulative effect on the human body. However, little is known about the effects of combinations of endocrine-disrupting chemicals in humans. Methoxychlor and bisphenol A are toxic to male reproductive organs. Therefore, we studied the effects of methoxychlor and bisphenol A on male reproductive function. Male mice were divided into four treatment groups: control, 400 mg methoxychlor, 1 mg bisphenol A, and 400 mg methoxychlor + 1 mg bisphenol A/kg/day. Methoxychlor and bisphenol A were dissolved in sesame oil and acetone and administered orally for 4 weeks. After administration, the weight and histological changes in the testicles and epididymis, sperm count and health were observed biochemical tests and whole blood counts were performed. The results showed that the mice in the bisphenol A and methoxychlor + bisphenol A groups gained more weight than those in the control and methoxychlor group. The weights of the testes and epididymis were higher in the experimental groups than in the control. Sperm motility and progression were significantly reduced in the bisphenol A and methoxychlor + bisphenol A groups. Histological observation showed a reduced number of sperm, smaller seminiferous tubules, and destroyed lumen in the methoxychlor + bisphenol A group compared to the other groups. In conclusion, our study showed that methoxychlor and bisphenol A destroy male reproductive tissues and decrease sperm quality.

Methoxychlor (MXC) was developed to be a replacement for the banned pesticide DDT. HPTE [2,2-bis (p-hydroxyphenyl) -1,1,1-trichloroethane], which is an in vivo metabolite of MXC, has strong oestrogenic and anti-androgenic effects. MXC and HPTE are thought to produce potentially adverse effects by acting through oestrogen and androgen receptors. Of the two, HPTE binds to sex-steroid receptors with greater affinity, and it inhibits testosterone biosynthesis in Leydig cells by inhibiting cholesterol side-chain cleavage enzyme activity and cholesterol utilisation. In a previous study, MXC was shown to induce Leydig cell apoptosis by decreasing testosterone concentrations. I focused on the effects of MXC on male mice that resulted from interactions with sex-steroid hormone receptors. Sexsteroid hormones affect other organs including the kidney and liver. Accordingly, I hypothesised that MXC can act through sex-steroid receptors to produce adverse effects on the testis, kidney and liver, and I designed our experiments to confirm the different effects of MXC exposure on the male reproductive system, kidney and liver. In these experiments, I used pre-pubescent ICR mice; the puberty period in ICR mice is from postnatal day (PND) 45 to PND60. I treated the experimental group with 0, 100, 200, 400 mg MXC/kg b.w. delivered by an intra-peritoneal injection with sesame oil used as vehicle for 4 weeks. At the end of the experiment, the mice were sacrificed under anaesthesia. The testes and accessory reproductive organs were collected, weighed and prepared for histological investigation. I performed a chemiluminescence immune assay to observe the serum levels of testosterone, LH and FSH. Blood biochemical determination was also performed to check for other effects. There were no significant differences in our histological observations or relative organ weights. Serum testosterone levels were decreased in a dose-dependent manner; a greater dose resulted in the production of less testosterone. Compared to the control group, testosterone concentrations differed in the 200 and 400 mg/kg dosage groups. In conclusion, I observed markedly negative effects of MXC exposure on testosterone concentrations in pre-pubescent male mice. From our biochemical determinations, I observed some changes that indicate renal and hepatic failure. Together, these data suggest that MXC produces adverse effects on the reproductive system, kidney and liver.

Background & Objectives: Methoxychlor(MET), an organochlorine insecticide, has been thought a potent endocrine disrupting chemical. The present study was undertaken to examine whether short-term exposure to MET can alter the onset of puberty and the associated reproductive parameters such as hormone receptor expressions in prepubertal female rats. Method: MET (1, 10 and 100 mg/kg/day) was administered daily from postnatal day 25 (PND 25) through the PND 34, and the animals were sacrificed on the PND 35. The first V.O. day was monitored, and the weights of reproductive tissues were measured. To assess the structural alterations in the ovary and uterus, the tissues were embedded in paraffin and stained for histological analysis. The transcriptional activities of hypothalamic and pituitary genes were measured using quantitative RT-PCRs. The uterine and hypothalamic proteins were extracted and used for the ER western blotting. Results: As a result, 100 mg group showed advanced V.O. than control, 1 mg group and 10 mg group. The wet weights of ovaries from MET-treated animal dose-dependently increased. The uterine weights were increased in 1 mg group and 10 mg group, while the 100 mg group samples were not significantly different from control tissues. The adrenal, kidney, spleen and thymus weights were not shown any significant change. Corpora lutea and fully grown follicles were observed in the ovaries from the 100 mg group, while numerous primary and secondary follicles were observed in the ovaries from control group. Myometrial thickness of MET-treated group was dose-dependently increased. Epithelial hypertrophy and well-developed glands were observed in the uterus from the 10 mg groups. Conclusions: The present study demonstrated that the short-term exposure to MET during the critical period of prepubertal stage could activate a reproductive endocrine system, resulting the early onset of puberty in immature female rats. Our study suggests that MET’s disrupting effect might be derived from premature activation of key reproduction-related genes in hypothalamus-pituitary neuroendocrine circuit.