| Objective:This work was designed to analyze the cadmium effects on steroidogenesis in the ovary and expression of estrogen receptor in both the ovary and the uterus in rats, and to determined mechanisms of sex hormone-disruption of cadmium.Methods:(1) 40 female rats were weighed, weight-ranked, and assigned randomly to four groups and were dosed subcutaneously with CdCl2 at doses of 0 ,1.25,2.5,and 5.0 mg Cd2+/kg /day, 5 days/wk, for 4 weeks. The rats were killed on the day of the diestrus stage during the 4 day period after administration. Steroidogenesis in ovary in vivo and in vitro,body weights,organ weights and organ coefficents of ovaries and uterus,expression of ER and HSP90αin both ovary and uterus were observed.(2) Using orthogonal experimental design with orthogonal layout of L16(45), effects of cadmium(0,100,1000,2000μmol/L) and estrous cycle(proestrous,estrous, postestrous, dioestrous)on steroidogenesis in the ovary were studied. (3) Using orthogonal experimental design with orthogonal layout of L9(34), effects of cadmium (0,8,128μmol/L)and incubation time(4,8,24h)on steroidogenesis in granulosa cells were studied.Results:Organ weight and organ coefficient of ovaries of the CdCl2 administration groups were not significantly different from the control group(P>0.05).Organ weight and organ coefficient of uteruses were significantly reduced in both the 5.0mg/kg group and the 2.5mg/kg group (P<0.001).Serum estradiol concentrations and serum progesterone concentrations were significantly decreased in both the 5.0mg/kg and the 2.5mg/kg group (P<0.05,P=0.001).Estradiol concentrations secreted in vitro by the ovaries of rats treated with 5.0 mgCd2+/kg were significantly decreased, and progesterone concentrations secreted in vitro by the ovaries of rats treated with 5.0 mgCd2+/kg and 1.25 mgCd2+/kg were significantly decreased (P<0.05).Intensity of ER immunostaining in stroma of ovaries of the 5.0 mgCd2+/kg group were significantly decreased compared with other groups (P<0.05).Intensity of ER immunostaining in endometria of the CdCl2 administration groups were not significantly different from the control group(P>0.05).Intensity of ER immunostaining in endometria of the 5.0 mgCd2+/kg group and the 2.5 mgCd2+/kg group were significantly different from the 1.25 mgCd2+/kg group(P<0.05).(6) Intensity of HSP90αimmunostaining in endometria of the CdCl2 administration groups were not significantly different from the control group (P>0.05). (7) In whole ovary culture, effects of cadmium on estradiol secretion were significantly(P<0.05),and effects of cadmium on progesterone secretion were not significantly (P>0.05).Effects of estrous cycle on estradiol and progesterone secretion in whole ovary culture were significantly (P<0.001,P<0.05). (8) Effects of cadmium on progesterone secretion in granulosa cells were significantly (P<0.01), and effects of cadmium on estradiol secretion were not significantly (P>0.05). Effects of incubation time on progesterone secretion in granulosa cells were not significantly (P>0.05), and effects of incubation time on estradiol secretion were significantly (P<0.05).Conclusions:(1) Cadmium is able to decrease serum concentrations of estradiol and progesterone, and shows effects of steroid disruption.(2) Cadmium can diminish progesterone production in granulosa cells. The site of cadmium interfering with the ovarian steroidogenic pathway of estradiol in rats does not appear in granulose cells.(3) Intact female rats exposed to high dosage of cadmium can not show oestrogen effects. (4) In this study, intensity of ER immunostaining in stroma of ovaries of the 5.0 mgCd2+/kg group were significantly decreased compared with other groups (P<0.05),and no significant fluctuation in the 5.0mg/kg group intensity of ER immunostaining in both endometria was observed. The role of ER in the mechanism of endocrine disruption of cadmium may be worth considering in studies.(5) Cadmium can not increase the intensity of HSP90αexpression in endometria...
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