Abstract
BackgroundThe transcription factor CCAAT/enhancer-binding protein (C/EBP) beta is a critical mediator of murine endometrial function during embryo implantation. Our objective is to characterize changes in C/EBP beta mRNA abundance and protein localization over the normal human menstrual cycle.MethodsFifty normally cycling volunteers without reproductive disorders were randomized to undergo endometrial sampling on a specific cycle day, with secretory phase samples timed using urinary LH surge. Samples were assessed for relative C/EBP beta mRNA expression using quantitative real-time RT-PCR and for C/EBP beta protein localization using immunohistochemistry. The semiquantitative histologic scoring (HSCORE) system was used to compare staining intensity in each tissue compartment between each cycle phase.ResultsC/EBP beta mRNA expression by whole endometrium peaks in the late secretory phase and is significantly higher than that in the proliferative and mid-secretory phases. A marked increase in nuclear C/EBP beta protein immunostaining is seen in stromal cells beginning about cycle day 20, coincident with the start of endometrial receptivity. This increased staining continues for the remainder of the cycle.ConclusionIn the normal human menstrual cycle, C/EBP beta mRNA and protein expression also change, with increased nuclear immunostaining in the mid-secretory phase, suggesting a possible role for C/EBP beta in human endometrial receptivity.
Highlights
The transcription factor CCAAT/enhancer-binding protein (C/EBP) beta is a critical mediator of murine endometrial function during embryo implantation
The transcription factor CCAAT/enhancer-binding protein (C/EBPβ) is a basic leucine zipper family transcription factor [1]. bZIP proteins are involved in the regulation of proliferation, differentiation, metabolic homeostasis, acute phase inflammation, and apoptosis [1,2,3]
Our mRNA results demonstrate peak C/EBPβ mRNA expression in the late secretory phase in whole samples of human endometrium, primarily at luteinizing hormone (LH)+13 and LH+14, with no increase seen in the mid-secretory phase
Summary
The transcription factor CCAAT/enhancer-binding protein (C/EBP) beta is a critical mediator of murine endometrial function during embryo implantation. The transcription factor CCAAT/enhancer-binding protein (C/EBPβ) is a basic leucine zipper (bZIP) family transcription factor [1]. BZIP proteins are involved in the regulation of proliferation, differentiation, metabolic homeostasis, acute phase inflammation, and apoptosis [1,2,3]. C/EBPβ is a critical mediator of murine endometrial function during embryo implantation. Murine C/EBPβ expression rises rapidly in endometrial epithelium at the time of blastocyst attachment and increases in the endometrial stromal cells around the conceptus during decidualization [8]. Administration of estrogen or progesterone to ovariectomized mice induces C/EBPβ expression in both uterine epithelium and stroma, suggesting that both hormones are involved in the regulation of this gene [8]
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