Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima Street 10, 10-747 Olsztyn, Poland.
Toxicol Appl Pharmacol. 2010 Sep 15;247(3):243-9. doi: 10.1016/j.taap.2010.07.003. Epub 2010 Jul 13.
Chloro-organic compounds are persistent environmental pollutants and affect many reproductive processes. Oxytocin (OT) synthesized in luteal cells is a local regulator of ovarian activity and uterine contractions. Therefore the effect of xenobiotics on the OT prohormone synthesis, secretion of OT and progesterone (P4) from luteal cells and on myometrial contractions during early pregnancy in cows was investigated. Luteal cells and myometrial strips from a cow at early pregnancy were treated with polychlorinated biphenyl 77 (PCB 77), dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE) and hexachlorocyclohexane (HCH) (1 or 10 ng/ml). The mRNA expression of neurophysin-I/oxytocin (NP-I/OT) and peptidyl-glycine-alpha-amidating mono-oxygenase (PGA) and concentration of OT and P4 were determined by RT-PCR and EIA, respectively. Moreover, the effect of xenobiotics given with P4 (12 ng/ml) on the basal and OT (10(-7)M) stimulated contractions of myometrial strips was studied. Xenobiotics increased (P<0.05) OT secretion but DDE only stimulated P4 secretion. The ratio of P4 to OT in culture medium was decreased by all xenobiotics during 9-12 weeks of pregnancy. All xenobiotics, except HCH, increased (P<0.05) mRNA expression of NP-I/OT during all stages of pregnancy and all treatments decreased (P<0.05) expression of mRNA for PGA during 9-12 weeks of pregnancy. Myometrial strips were relaxed (P<0.01) after pre-incubation with P4, while each of the xenobiotics jointly with P4 increased (P<0.01) myometrial contractions. In conclusion, the xenobiotics used increased both expression of mRNA for genes involved in OT synthesis and secretion of OT from luteal cells. This decreases the ratio of P4 to OT and presumably, in this manner, the chloro-organic compounds can influence uterine contractions and enhance risk of abortions in pregnant females.
氯代有机化合物是持久性环境污染物，会影响许多生殖过程。黄体细胞合成的催产素（OT）是卵巢活动和子宫收缩的局部调节剂。因此，本研究旨在探讨外源性化学物质对 OT 前体合成、黄体细胞 OT 和孕酮（P4）分泌以及奶牛妊娠早期子宫平滑肌收缩的影响。用多氯联苯 77（PCB 77）、滴滴涕（DDT）、二氯二苯二氯乙烯（DDE）和六氯环己烷（HCH）（1 或 10ng/ml）处理妊娠早期奶牛的黄体细胞和子宫平滑肌条。通过 RT-PCR 和 EIA 分别测定神经垂体素 I/催产素（NP-I/OT）和肽基甘氨酸-α-酰胺化单加氧酶（PGA）的 mRNA 表达和 OT 和 P4 的浓度。此外，还研究了外源性化学物质与 P4（12ng/ml）共同作用对子宫平滑肌条基础收缩和 OT（10（-7）M）刺激收缩的影响。外源性化学物质增加了 OT 的分泌（P<0.05），但 DDE 仅刺激 P4 的分泌。在妊娠 9-12 周期间，所有外源性化学物质均降低了培养基中 P4 与 OT 的比值。除 HCH 外，所有外源性化学物质在妊娠的所有阶段均增加了 NP-I/OT 的 mRNA 表达（P<0.05），而所有处理均降低了妊娠 9-12 周时 PGA 的 mRNA 表达（P<0.05）。用 P4 预孵育后，子宫平滑肌条松弛（P<0.01），而每种外源性化学物质与 P4 共同作用均增加了子宫平滑肌条的收缩（P<0.01）。总之，所使用的外源性化学物质均增加了参与 OT 合成的基因的 mRNA 表达以及黄体细胞中 OT 的分泌。这降低了 P4 与 OT 的比值，并且可能会以这种方式影响子宫收缩并增加妊娠雌性动物流产的风险。
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