Department of Pharmacology and Toxicology, B.V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S.G. Road, Thaltej, Ahmedabad, India.
Syst Biol Reprod Med. 2011 Aug;57(4):186-9. doi: 10.3109/19396368.2010.539660. Epub 2010 Dec 30.
The site specific action of the calcium channel blocker diltiazem in blocking prostaglandin synthesis and hence causing blastocyst implantation failure has been previously described. Based on this understanding it was important to learn if this pathway was under the control of the fine balance in estradiol-progesterone (E2-P4) milieu, considered to be of the utmost significance for effective implantation. In the current study the circulating E2-P4 levels were monitored on the first 6 d of pregnancy at various time points using sensitive chemiluminescence based assays. Next, diltiazem was administered intra-luminally into the uterus at 10-20 h prior to implantation as this time has been previously implicated to be when the best anti-implantation activity of diltiazem can be observed. Following this, the E2-P4 in peripheral circulation was again monitored. On d 6 (post implantation) the implantation sites were observed in the uterus of both diltiazem treated and untreated groups using Chicago blue dye and correlated to the hormonal activity. The levels of both estradiol and progesterone were very similar in both untreated and diltiazem treated groups during and post implantation. However complete implantation failure was noted in the diltiazem treated group whereas prominent implantation sites were observed in the untreated animals. Thus, the previously reported inhibition of blastocyst implantation cascade by calcium channel blockers during the 'implantation window' seems to be an independent mechanism interfering with uterine receptivity without any direct estrogen-progesterone control and further studies to understand its regulation need to be performed.
先前已有描述，钙通道阻滞剂地尔硫卓可特异性阻断前列腺素合成，从而导致胚泡着床失败。基于这一认识，重要的是要了解这条途径是否受雌二醇-孕酮（E2-P4）环境细微平衡的控制，因为这种平衡被认为对有效着床至关重要。在目前的研究中，使用敏感的化学发光测定法，在妊娠的头 6 天，在不同时间点监测循环中的 E2-P4 水平。接下来，在着床前 10-20 小时，将地尔硫卓经子宫腔给药，因为先前的研究表明，这是观察地尔硫卓最佳抗着床活性的时间。在此之后，再次监测外周循环中的 E2-P4。在第 6 天（着床后），使用芝加哥蓝染料观察两组（地尔硫卓处理组和未处理组）子宫内的着床部位，并与激素活性相关联。在着床期间和之后，未处理组和地尔硫卓处理组的雌二醇和孕酮水平非常相似。然而，在接受地尔硫卓治疗的组中，着床完全失败，而在未接受治疗的动物中，着床部位明显。因此，先前报道的钙通道阻滞剂在“着床窗口期”抑制胚泡着床级联反应似乎是一种独立的机制，它会干扰子宫的接受性，而与雌激素-孕激素的直接控制无关，需要进一步研究以了解其调控机制。
