Nippon Institute for Biological Science, Tokyo, Japan.
J Toxicol Sci. 2011 Jan;36(1):43-54. doi: 10.2131/jts.36.43.
Previously, we investigated endocrine disrupting effects of 17 β-estradiol (E(2)) on Japanese quail (Coturnix japonica) in the avian reproduction test according to the testing guidelines, in which new endpoints such as blood vitellogenin (VTG) concentration in parent quails and pathology of F(1) chicks were added, and consequently these additional endpoints suggested to be sensitive markers for detecting any impacts of endocrine disrupting effects (Shibuya et al., 2005b). In the present study, to investigate low dose effects of estrogenic endocrine disrupting chemicals in birds, the avian reproduction study of E(2) at low dose levels was conducted using Japanese quail with additional endpoints such as observations of F(1) chicks until 10 weeks of age, histopathology of F(1) chicks at 14 days and 10 weeks of age and blood VTG concentration in parent quails. Sixteen pairs of 10-week-old quails were fed a low phytoestrogen diet containing E(2) at 0 (control), 0.3, 3, and 30 ppm for 6 weeks, and parent quails, eggs and offspring were examined. F(1) chicks were maintained up to 14 days or 10 weeks of age. Serum E(2) and VTG concentrations in males of the E(2) 3- and 30-ppm groups and in females of the E(2) 30-ppm groups were significantly elevated. In the E(2) 30-ppm group, two parent females died, and toxic changes such as suppression of body weight gain, decrease in food consumption and atrophic and degenerative changes of the reproductive organs were observed in parent quails. In the same group, the number of eggs laid and the fertility rate of eggs were significantly decreased. In addition, the viability of F(1) chicks in the E(2) 30-ppm group were significantly decreased at 10 weeks of age. On the other hand, no abnormalities described above were observed in any parent quails, eggs and F(1) chicks in the E(2) 3- and 0.3-ppm groups, although the fertility rates of eggs in both groups were decreased and the body weight gain of F(1) females in the E(2) 3-ppm group was significantly suppressed. In the histopathological examination of F(1) chicks maintained up to 10 weeks of age, persistent right oviduct and atrophy of the oviduct gland were observed in females of E(2)-treatment groups with significantly high incidences. Moreover, cystic dilatation and tubular degeneration of the seminiferous tubules and atrophy of the cloacal gland were also observed in males of the E(2)-treatment groups. Thus, the dietary treatment of low dose E(2) (even 0.3 ppm) to parent quails resulted in decreased viability and induction of abnormalities in the oviduct, testis and cloacal gland in F(1) chicks maintained up to 10 weeks of age. These results suggest that additional endpoints such as observations of F(1) chicks until 10 weeks of age, histopathology of F(1) chicks at 14 days and 10 weeks of age and blood VTG concentration in parent quails would be useful and sensitive endpoints for evaluating estrogenic endocrine disrupting effects in the avian reproduction study.
先前,我们按照检测指南,使用鹌鹑进行了 17β-雌二醇(E2)的内分泌干扰效应的禽类繁殖试验研究,其中添加了新的终点,如亲代鹌鹑的血液卵黄蛋白原(VTG)浓度和 F1 雏鸡的病理学,这些额外的终点被认为是检测内分泌干扰效应的敏感标志物(Shibuya 等人,2005b)。在本研究中,为了研究低剂量雌激素类内分泌干扰化学物质对鸟类的影响,使用鹌鹑进行了低剂量雌二醇的禽类繁殖研究,并增加了其他终点,如 F1 雏鸡的观察直至 10 周龄、F1 雏鸡在 14 天和 10 周龄的组织病理学以及亲代鹌鹑的血液 VTG 浓度。16 对 10 周龄的鹌鹑用含有 E2 的低植物雌激素饮食喂养 6 周,E2 浓度分别为 0(对照)、0.3、3 和 30ppm,然后对亲代鹌鹑、鸡蛋和后代进行检查。F1 雏鸡饲养至 14 天或 10 周龄。E2 3 和 30ppm 组雄性和 E2 30ppm 组雌性的血清 E2 和 VTG 浓度显著升高。在 E2 30ppm 组中,有 2 只亲代雌性死亡,亲代鹌鹑出现体重增加抑制、采食量减少以及生殖器官萎缩和退行性变化等毒性变化。在同一组中,产卵量和卵的受精率显著降低。此外,E2 30ppm 组 F1 雏鸡的存活率在 10 周龄时显著降低。另一方面,E2 3 和 0.3ppm 组的亲代鹌鹑、鸡蛋和 F1 雏鸡均未出现上述异常,尽管两组的卵受精率均降低,E2 3ppm 组的 F1 雌性雏鸡体重增加显著受到抑制。在饲养至 10 周龄的 F1 雏鸡的组织病理学检查中,E2 处理组的雌性出现持续性右输卵管和输卵管腺萎缩,发生率显著升高。此外,E2 处理组的雄性出现精小管囊性扩张和管状变性以及泄殖腔腺萎缩。因此,给亲代鹌鹑低剂量 E2(甚至 0.3ppm)饮食处理会导致饲养至 10 周龄的 F1 雏鸡的存活率降低,并诱导输卵管、睾丸和泄殖腔腺异常。这些结果表明,直至 10 周龄的 F1 雏鸡的观察、F1 雏鸡在 14 天和 10 周龄的组织病理学以及亲代鹌鹑的血液 VTG 浓度等额外终点,对于评估禽类繁殖研究中的雌激素类内分泌干扰效应是有用且敏感的终点。