Rechtman M P, Zhang J, Salamonsen L A
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
J Reprod Fertil. 1999 Sep;117(1):169-77. doi: 10.1530/jrf.0.1170169.
Implantation of the embryo into the endometrium is a highly regulated event that is critical for establishment of pregnancy. Molecules involved in this process provide potential targets for post-coital contraception. The aims of this study were to determine whether matrix metalloproteinases (MMPs) are present at implantation sites in rats and whether administration of a broad-based inhibitor of MMPs could inhibit embryo implantation. Uterine extracts from non-pregnant rats and from rats on days 3-9 of pregnancy were examined for the presence of MMPs. Doxycycline (5 or 15 mg day-1) was administered by gavage to rats from the day of mating (day 0) to day 7 of pregnancy and the uterus was examined for implantation sites. A number of MMPs were present in all uterine samples. MMP-2 reached a peak on day 3, whereas the highest expression of MMP-7 occurred on day 7. MMP-13 and MMP-3 were present in smaller amounts. MMP-9 was detectable only on day 9. Treatment of rats with doxycycline had no effect on the number of implantation sites or on the total uterine mass. However, in treated rats, the process of decidualization was impaired and both the width and length of the decidual zone was reduced, resulting in a decrease in total decidual area from 1.20 +/- 0.07 to 0.91 +/- 0.07 mm2 (mean +/- SEM, controls versus doxycycline treated, P < 0.02). It is concluded that administration of MMP inhibitors during early pregnancy retards decidual development, but does not block implantation.
胚胎植入子宫内膜是一个受到高度调控的过程，对妊娠的建立至关重要。参与这一过程的分子为性交后避孕提供了潜在靶点。本研究的目的是确定基质金属蛋白酶（MMPs）是否存在于大鼠的植入部位，以及给予一种广谱的MMP抑制剂是否能抑制胚胎植入。检测了未孕大鼠以及妊娠第3至9天大鼠的子宫提取物中MMPs的存在情况。从交配日（第0天）至妊娠第7天，通过灌胃给予大鼠强力霉素（5或15毫克/天），并检查子宫的植入部位。所有子宫样本中都存在多种MMPs。MMP-2在第3天达到峰值，而MMP-7的最高表达出现在第7天。MMP-13和MMP-3的含量较少。仅在第9天可检测到MMP-9。用强力霉素处理大鼠对植入部位的数量或子宫总质量没有影响。然而，在处理过的大鼠中，蜕膜化过程受到损害，蜕膜区的宽度和长度均减小，导致总蜕膜面积从1.20±0.07降至0.91±0.07平方毫米（平均值±标准误，对照组与强力霉素处理组相比，P<0.02）。结论是，在妊娠早期给予MMP抑制剂会延缓蜕膜发育，但不会阻止植入。
