The Transcription Factor BCL6 Is Involved In Luteal Degeneration By Regulating PTGS2

Pregnancy is the process that begins with the formation of a fertilized egg from the union of sperm and egg,which is attached to the maternal uterus and develops into a mature embryo in the uterus and then begins to give birth.Late gestation progesterone withdrawal is the key to labor initiation.The corpus luteum is the main organ that secretes progesterone during pregnancy in animals,and the degeneration of corpus luteum is mainly the role of PGF2α originating from the uterus,while Prostaglandin-Endoperoxide Synthase 2(PTGS2)is the rate-limiting enzyme for the synthesis of prostaglandins.BCL6 is a transcription factor predicted to bind to the promoter region of porcine PTGS2.The aim of this study was to investigate the role of BCL6 in corpus luteum lysis and to provide new ideas for shortening the gestation period.The main results were as follows.1.A total of 791 upstream transcription factors of PTGS2 were obtained by screening using http://cisbp.ccbr.utoronto.ca/TFTools.php.Fluorescence quantitative PCR detected a significant down-regulation of the expression level of transcription factor BCL6 in the corpus luteum of Qingping pigs during late gestation and parturition(P <0.05).2.Transfection of BCL6 overexpression vector in luteal cells or treatment of luteal cells with BCL6 inhibitor revealed that: both PTGS2 mRNA and protein expression levels were inhibited after overexpression of BCL6;both PTGS2 mRNA and protein expression levels were significantly up-regulated after inhibition of BCL6(P < 0.05).The BCL6 overexpression vector was cotransformed into 293 T cells with a recombinant vector carrying the active site of PTGS2 promoter,and the fluorescence activity of the recombinant vector showed a highly significant decrease after cotransformation(P <0.01).3.Treatment of luteal cells with the BCL6 inhibitor FX1 resulted in significant upregulation of protein levels of both PTGS2 and prostaglandin F synthase(PGFS),promoting the secretion of prostaglandin PGF2α.The expression of 20α-hydroxy progesterone(20αHSD),BAX and caspase-3 shedder was increased.4.In Kunming rats at 15.5 d of late gestation,delivery was advanced by one day after intraperitoneal injection of FX1.Inhibition of BCL6 upregulated PGFS expression upregulation in PTGS2 ovaries,increased PGF2α secretion,suppressed ovarian CYP11A1 and HSD3B1 expression,and decreased cholesterol supply during progesterone synthesis;in the ovaries,with increased PGF2α secretion,downstream20αHSD and BAX expression was upregulated,promoting progesterone metabolism and luteal cell apoptosis.The increased secretion of PGF2α accelerates luteal degeneration,which leads to earlier progesterone withdrawal and promotes earlier labor.