Hong Eui-Ju, Choi Kyung-Chul, Jeung Eui-Bae
Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
Biol Reprod. 2004 Aug;71(2):669-75. doi: 10.1095/biolreprod.103.026146. Epub 2004 Apr 7.
Environmental chemicals are proposed to possess hormone-like properties, such as mimicking natural hormones, inhibiting the action of hormones, and inducing abnormal gene expression. Among environmental chemicals, the alkylphenol products (APs), octylphenol (OP) and nonylphenol (NP), are derived from alkylphenol ethoxylates and have been reported to be environmentally persistent. Thus, in the present study, we examined the effect of two APs, OP and NP, on the expression of Calbindin-D(9k) (CaBP-9k) following maternal exposure during late pregnancy in maternal and fetal uteri. Treatment with a high dose (600 mg/kg body weight [BW]) of OP and NP resulted in an induction of CaBP-9k mRNA at Day 5 of lactation, as did a single treatment with diethylstilbestrol (DES) and 17beta-estradiol (E2) in maternal uteri. The expression of CaBP-9k mRNA was also induced following treatment with a high dose (600 mg/kg BW) of OP, transferred from the mother, exposed to fetuses during late pregnancy, and persisted through Day 5 of lactation. It is of interest that treatments with high doses of OP (400 and 600 mg/kg BW) reduced the expression of maternal estrogen receptor alpha (ERalpha) mRNA, as E2 did. However, all doses of NP resulted in an inhibition of neonatal ERalpha, while only the high does of OP (600 mg/kg BW) induced the reduction of neonatal ERalpha mRNA expression, as E2 did. Parallel to mRNA, the expression of CaBP-9k protein was significantly induced by treatment with a high dose of OP and NP. In conclusion, maternal exposure to APs, OP and NP, during late pregnancy increased the expressions of CaBP-9k mRNA and protein in maternal and neonatal uteri. These results suggest that the absorption and distribution of environmental estrogenic compounds in maternal and neonatal uteri are extremely rapid, and these chemicals can easily pass though the placenta during pregnancy to affect functions of neonatal reproductive tissues.
环境化学物质被认为具有类激素特性，比如模拟天然激素、抑制激素作用以及诱导异常基因表达。在环境化学物质中，烷基酚产品（APs），如辛基酚（OP）和壬基酚（NP），来源于烷基酚聚氧乙烯醚，据报道它们在环境中具有持久性。因此，在本研究中，我们检测了两种烷基酚产品OP和NP，在母鼠妊娠晚期暴露后，对母鼠和胎儿子宫中钙结合蛋白-D(9k)（CaBP-9k）表达的影响。高剂量（600毫克/千克体重[BW]）的OP和NP处理导致哺乳期第5天母鼠子宫中CaBP-9k mRNA的诱导，母鼠子宫中单次使用己烯雌酚（DES）和17β-雌二醇（E2）处理也有同样效果。高剂量（600毫克/千克BW）的OP处理后，CaBP-9k mRNA的表达也被诱导，该OP从母鼠转移而来，在妊娠晚期暴露于胎儿，并持续至哺乳期第5天。有趣的是，高剂量的OP（400和600毫克/千克BW）处理降低了母鼠雌激素受体α（ERα）mRNA的表达，E2处理也是如此。然而，所有剂量的NP都导致新生鼠ERα受到抑制，而只有高剂量的OP（600毫克/千克BW）像E2一样诱导新生鼠ERα mRNA表达降低。与mRNA情况平行，高剂量的OP和NP处理显著诱导了CaBP-9k蛋白的表达。总之，母鼠在妊娠晚期暴露于APs、OP和NP会增加母鼠和新生鼠子宫中CaBP-9k mRNA和蛋白的表达。这些结果表明，环境雌激素化合物在母鼠和新生鼠子宫中的吸收和分布极其迅速，并且这些化学物质在孕期能够轻易穿过胎盘影响新生鼠生殖组织的功能。
