Piasek Martina, Laskey John W, Kostial Krista, Blanusa Maja
Institute for Medical Research and Occupational Health, Mineral Metabolism Unit, P O Box 291, HR-10001 Zagreb, Republic of Croatia.
Int Arch Occup Environ Health. 2002 Oct;75 Suppl:S36-44. doi: 10.1007/s00420-002-0351-3. Epub 2002 Jul 3.
The paper presents results of collaborative research on cadmium as an endocrine disruptor. To detect steroidogenic alterations in cycling and pregnant rats following cadmium exposures in vivo (at 3 or 5 mg/kg as a single s.c. dose) and in vitro (from 0 through 2000 microM Cd(2+)) whole-ovary culture was used. To evaluate steroid productions in rats fed low iron (10 ppm) and concomitantly exposed to cadmium (5 mg/kg total dose by s.c.-implanted osmotic pumps) during 19 days of pregnancy whole-placenta culture was also used. In human placental tissue cadmium and progesterone concentrations were assessed in relation to cigarette smoking.
Cultures of minced ovaries were evaluated for 1-h basal steroid production and following 1-h production stimulated with either human chorionic gonadotropin (hCG) or hCG and pregnenolone. Placental cultures were evaluated for average 1-h progesterone production following 3 h of unstimulated production. Steroid hormones were evaluated by specific radioimmunoassay. Placental cadmium concentrations were analyzed by atomic absorption spectrometry.
In-vivo cadmium exposure interfered with normal steroidogenesis in cycling rats and in early pregnancy, with ovarian estradiol production the most affected. Under in-vitro cadmium exposure the most affected was ovarian production of progesterone and testosterone in cycling (proestrous) rats with medial inhibitory concentrations under 500 micro M Cd(2+). Cadmium interfered with the steroidogenic pathway at more than one site. Linear and additive effects of low-iron feeding and concomitant cadmium exposure during pregnancy on placental progesterone production were found. In humans, we found that the placentas of smoking mothers contained twice as much cadmium and approximately half the amount of progesterone than did the placentas of non-smoking mothers.
Results of the research on cadmium-induced steroidogenic effects using cultures of whole rat ovary and/or placenta as well as human placental tissues point to cadmium as an endocrine disruptor that may compromise pregnancy outcome and fetal viability.
本文介绍了关于镉作为内分泌干扰物的合作研究结果。为了检测体内（单次皮下注射剂量为3或5 mg/kg）和体外（0至2000 microM Cd(2+)）镉暴露后，处于发情周期和怀孕大鼠的类固醇生成变化，采用了全卵巢培养法。为了评估在怀孕19天期间喂食低铁（10 ppm）并同时暴露于镉（通过皮下植入渗透泵给予总剂量5 mg/kg）的大鼠的类固醇生成，还采用了全胎盘培养法。在人胎盘组织中，评估了镉和孕酮浓度与吸烟的关系。
对切碎的卵巢培养物进行1小时基础类固醇生成评估，以及在用人绒毛膜促性腺激素（hCG）或hCG和孕烯醇酮刺激1小时后的生成评估。对胎盘培养物进行未刺激生成3小时后的平均1小时孕酮生成评估。通过特异性放射免疫测定法评估类固醇激素。通过原子吸收光谱法分析胎盘镉浓度。
体内镉暴露干扰了处于发情周期的大鼠和怀孕早期的正常类固醇生成，其中卵巢雌二醇生成受影响最大。在体外镉暴露下，处于发情周期（动情前期）的大鼠中，受影响最大的是卵巢孕酮和睾酮生成，其半数抑制浓度低于500 microM Cd(2+)。镉在多个位点干扰类固醇生成途径。发现孕期低铁喂养和同时镉暴露对胎盘孕酮生成具有线性和累加效应。在人类中，我们发现吸烟母亲的胎盘所含镉量是不吸烟母亲胎盘的两倍，孕酮量约为不吸烟母亲胎盘的一半。
使用大鼠全卵巢和/或胎盘培养物以及人胎盘组织进行的镉诱导类固醇生成效应研究结果表明，镉是一种内分泌干扰物，可能会损害妊娠结局和胎儿活力。
