Abstract
In the rat, the decidual tissue is an important component for maternal recognition of pregnancy. Decidualization can be induced by either the implantation of the blastocyst or by artificial stimuli. The process of decidua formation or decidualization, is characterized by growth and differentiation of endometrial stromal cells. Prostaglandin F2alpha (PGF2α) has been shown to be involved in inhibition of implantation, alteration of embryo development, induction of luteal regression, and the mediation of pregnancy loss induced by microorganism infections. In order to establish a direct role for PGF2α in decidual function, we have evaluated its effects on the expression of an extensive array of genes using primary decidual cell culture. Upon treatment with PGF2α sixty genes were significantly down-regulated whereas only six genes were up-regulated (from a total of 1176 genes studied). Interestingly, the majority of the genes inhibited by PGF2α are either directly or indirectly involved in the turnover of the extracellular matrix (ECM). Genes such as gelatinase A (MMP2), cathepsin L, tissue inhibitor metalloproteinases 2 (TIMP2) and 3 (TIMP3), plasminogen activator inhibitor1 (PAI1), tissue type plasminogen activator (tPA), urokinase plasminogen activator (tPA), endothelin 1, calponin, carboxypeptidase D and calponin acidic were down regulated. The opposite effect was observed for prostromelysin 53 kDa (proMMP3), plasma proteinase I alpha and alpha 1 antiproteinase, all of which were significantly up-regulated by PGF2α. The results strongly suggest that the abortificient role of elevated levels of PGF2α after implantation is due, in large part, to inhibition of genes involved in the normal turnover of the extracellular matrix necessary for decidual formation.
Highlights
The establishment of successful pregnancy requires a profound reorganization of uterine tissues
Effect of PGF2α on the expression of genes related to the extracellular matrix (ECM) The majority of genes whose expression was affected by PGF2α in primary decidual cells are genes involved in the regulation of the ECM
In this paper we present initial data demonstrating that elevated PGF2α can target the decidua, an endocrine tissue whose integrity is fundamental for the success of implantation and for the progression of pregnancy
Summary
The establishment of successful pregnancy requires a profound reorganization of uterine tissues. An increase of uterine PGE2 and PGF2α is observed on day 5 of pregnancy, allowing the decidualization process to take place. A high level of PGF2α is known to induce inhibition of implantation, alteration of embryo development, and induction of luteal regression [5]. An inflammatory response mediated by cytokines can be generated [7] This release of PGF2α can induce premature uterine contraction and premature labor [8]. Because an increase in PGF2α levels after implantation can be detrimental for the progression of pregnancy, the aim of this investigation was to determine whether PGF2α affects directly decidual cells and leads to disturbance in the expression of genes crucial for decidual survival
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