PGF2alpha induced differential expression of genes involved in turnover of extracellular matrix in rat decidual cells.
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 (PGF2alpha) 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 PGF2alpha 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 PGF2alpha 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 PGF2alpha 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 PGF2alpha. The results strongly suggest that the abortificient role of elevated levels of PGF2alpha after implantation is due, in large part, to inhibition of genes involved in the normal turnover of the extracellular matrix necessary for decidual formation.
Callegari
Eduardo A
EA
Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois, USA. ggibori@uic.edu
Ferguson-Gottschall
Susan
S
Gibori
Geula
G
D000818:Animals; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D003656:Decidua / Q000166:cytology* / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology* / Q000502:physiology; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D020411:Oligonucleotide Array Sequence Analysis; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation
D018925:Chemokines; D015237:Dinoprost; D046988:Proteasome Endopeptidase Complex; D019204:GTP-Binding Proteins