• Development and Reproduction
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• v.21 no.2
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• pp.121-130
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• 2017

4-Nonylphenol (NP) is a surfactant that is a well-known and widespread estrogenic endocrine disrupting chemical (EDC). Although it has been known that the affinity of NP to ERs is low, it has been suggested that low-dose NP has toxicity. In the present study, the endocrine disrupting effects on reproduction, and the weight of gonads, epididymis, and uterus were evaluated with the chronic lower-dose NP exposing. This study was designed by following the OECD test guideline 443 and subjected to a complete necropsy. In male, NP had an effect on the weight of the testis and epididymis in both $F_0$ and $F_1$. In females, NP decreased the weight of ovary and uterus in $F_0$ but not in pre-pubertal $F_1$ pubs. Fertility of male and female in $F_0$ or $F_1$ was no related with NP administration. The number of caudal-epididymal sperm by body weight (BW) was not different between groups in both $F_0$ and $F_1$. Besides, the difference of the sperm number between generations was not detected. The number of ovulated oocytes was similar between groups in $F_0$, but significantly decreased in NP 50 group of $F_1$. The litter size and sex ratios of offspring in $F_1$ and $F_2$ were not different. The accumulated mating rate and gestation period were not affected by the NP administration. Those results shows that chronic lower-dose NP administration has an effect of endocrine disruptor on the weight of gonads and epididymis of $F_0$ and $F_1$ but not in reproduction. Based on the results, it is suggested that chronic lower-dose NP exposing causes endocrine disruption in the weight of gonad and epididymis but not in the reproductive ability of next generations.

• Development and Reproduction
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• v.23 no.3
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• pp.263-275
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• 2019

Based on our preliminary results, we examined the possible role of low-dose and chronic-exposing of the chemicals those are known as endocrine disrupting chemical (EDC), on the proliferation of uterine endometrium and the localization of steroid receptors. Immunohistochemical or immunofluorochemical methodology were employed to evaluate the localization of antigen identified by monoclonal antibody Ki 67 protein (MKI67), estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), and progesterone receptor (PGR). In $133{\mu}g/L$ and $1,330{\mu}g/L$ di(2-ethylhexyl) phthalate (DEHP) and $50{\mu}g/L$ nonylphenol (NP) groups, the ratio of MKI67 positive stromal cells was significantly increased but not in $500{\mu}g/L$ NP group. The ratios of MKI67 positive glandular and luminal epithelial cells were also changed by the chronic administration of NP and DEHP in tissue with dose specific manner. ESR1 signals were localized in nucleus in glandular and luminal epithelia of control group but its localization was mainly in cytoplasm in DEHP and NP administered groups. On the other hand, it was decreased at nucleus of stromal cells in $1,330{\mu}g/L$ DEHP group. The colocalization patterns of these nuclear receptors were also modified by the administration of these chemicals. Such a tissue specific and dose specific localization of ESR2 and PGR were detected as ESR1 in all the uterine endometrial tissues. These results show that the chronic lows-dose exposing of NP or DEHP modify the localization and colocalization of ESRs and PGR, and of the proliferation patterns of the endometrial tissues.

• Development and Reproduction
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• v.22 no.4
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• pp.379-391
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• 2018

Through the development of organic synthetic skill, chemicals that mimic signaling mediators such as steroid hormones have been exposed to the environment. Recently, it has become apparent that this circumstance should be further studied in the field of physiology. Estrogenic action of chronic low-dose nonylphenol (NP) and di-(2-ethylhexyl) phthalate (DEHP) in mouse uterus was assessed in this study. Ten to twelve-week-old female mice (CD-1) were fed drinking water containing NP (50 or $500{\mu}g/L$) or DEHP (133 or $1,330{\mu}g/L$) for 10 weeks. Uterine diameter, the thickness of myometrium and endometrium, and the height of luminal epithelial cells were measured and the number of glands were counted. The expression levels of the known $17{\beta}$-estradiol ($E_2$)-regulated genes were evaluated with real-time RT-PCR methodology. The ration of uterine weight to body weight increased in $133{\mu}g/L$ DEHP. Endometrial and myometrial thickness increased in 133 and $1,330{\mu}g/L$ DEHP treated groups, and in 50, $500{\mu}g/L$ NP and $133{\mu}g/L$ DEHP, respectively. The height of luminal epithelial cell decreased in NP groups. The numbers of luminal epithelial gland were decreased in NP groups but increased in $50{\mu}g/L$ DEHP group. The histological characters of glands were not different between groups. The mRNA expression profiles of the known $17{\beta}$-estradiol ($E_2$) downstream genes, Esr1, Esr2, Pgr, Lox, and Muc1, were also different between NP and DEHP groups. The expression levels dramatically increased in some genes by the NP or DEHP. Based on these results, it is suggested that the chronic low-dose NP or DEHP works as estrogen-like messengers in uterus with their own specific gene expression-regulation patterns.

• Development and Reproduction
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• v.27 no.4
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• pp.213-220
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• 2023

Previously, we showed that a chronic-low-dose nonylphenol (NP) exposure resulted in histological changes with sexually dimorphic pattern in rat adrenal glands. We hypothesized that such structural changes are closely related to the hormonal secretory patterns. To test this hypothesis, we developed the short-term adrenal incubation method, and measured the levels of catecholamines and cortical steroids using the high-performance liquid chromatography with electrochemical detection (HPLC-ECD) and specific enzyme-linked immunosorbent assay, respectively. The norepinephrine (NE) levels in media from NP-treated female adrenal, except 100 pM NP, were significantly increased [control (CTL) vs 1 nM NP, p<0.001; vs 10 nM NP, p<0.05; vs 100 nM NP, p<0.001; vs 1 µM NP, p<0.01]. The NE secretion from male adrenal was higher when treated with 100 nM and 1 µM NP (CTL vs 100 nM NP, p<0.05; vs 1 µM NP, p<0.05, respectively). The aldosterone level in the female adrenal media treated with 100 pM NP was significantly decreased, on the other hand, that of media treated with 10 nM NP was significantly increased (CTL vs 100 pM NP, p<0.05; vs 10 nM NP, p<0.01). In male adrenal media, the aldosterone levels of 10 nM, 100 nM and 1 µM NP-treated media were significantly declined (CTL vs 10 nM NP, p<0.001; vs 100 nM NP, p<0.001; vs 1 µM NP, p<0.001). These results showed the NP treatment altered secretory pattern of aldosterone from adrenals of both sexes, showing sexual dimorphism. It may be helpful for understanding possible adrenal pathophysiology, and endocrine disrupting chemicals-related sexually dimorphic phenomena in adrenals.