Ribeiro M L, Aisemberg J, Billi S, Farina M G, Meiss R, McCann S, Rettori V, Villalón M, Franchi A M
Laboratory of Physiopathology of Pregnancy and Labor, Center for Pharmacological and Botanical Studies, School of Medicine Paraquay 2155, Buenos Aires CP(1121), Argentina.
Proc Natl Acad Sci U S A. 2005 May 31;102(22):8048-53. doi: 10.1073/pnas.0502899102. Epub 2005 May 23.
We have previously reported that intrauterine (i/u) administration of epidermal growth factor (EGF 500 ng) on day (d) 21 of pregnancy delayed 19.0 +/- 0.6 h the onset of labor. Progesterone (P) is secreted by ovarian corpora lutea (CL) throughout gestation in the rat. Prepartum CL regression due to increased uterine cyclooxygenase I and prostaglandin F(2alpha) results in P withdrawal followed by labor. The aims of the present work were (i) to study whether EGF delayed-onset of labor was mediated by a mechanism that prevented CL regression; (ii) to determine amniotic fluid (AF) EGF in pregnant rats. Rats on d21 of pregnancy received i/u EGF (500 ng) and were killed 0, 4, 8, 12, 24, and 48 h later. Control AF from rats on d13 and 18-22 of pregnancy was obtained. EGF decreased uterine prostaglandin F(2alpha) synthesis 8 h after treatment. Twelve hours after EGF injection, P reached its highest serum level and uterine cyclooxygenase I expression was undetectable. CL from rats killed 8 and 12 h after EGF were similar to those from rats on d13 of pregnancy, when serum P is maximum. EGF in AF increased throughout gestation, reached a maximum on d21, and decreased before the onset of labor. We suggest that the effect of EGF on the onset of labor was mediated by an early effect on the uterus that prevented prepartum CL regression.
我们之前曾报道，在妊娠第21天经宫内（i/u）给予表皮生长因子（EGF，500 ng）可使分娩开始时间延迟19.0±0.6小时。在大鼠整个妊娠期，孕酮（P）由卵巢黄体（CL）分泌。由于子宫环氧化酶I和前列腺素F（2α）增加导致的产前CL退化会导致P撤退，随后引发分娩。本研究的目的是：（i）研究EGF延迟分娩开始是否是通过防止CL退化的机制介导的；（ii）测定妊娠大鼠羊水（AF）中的EGF。妊娠第21天的大鼠接受i/u EGF（500 ng），并在0、4、8、12、24和48小时后处死。获取妊娠第13天以及第18 - 22天大鼠的对照AF。治疗后8小时，EGF降低了子宫前列腺素F（2α）的合成。注射EGF 12小时后，P达到其最高血清水平，且子宫环氧化酶I表达无法检测到。在EGF处理后8小时和12小时处死的大鼠的CL与妊娠第13天大鼠的CL相似，此时血清P最高。AF中的EGF在整个妊娠期增加，在第21天达到最大值，并在分娩开始前下降。我们认为，EGF对分娩开始的影响是通过对子宫的早期作用介导的，该作用可防止产前CL退化。
