Cyclic regulation of transcription factor C/EBP beta in human endometrium

Fifty 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.C/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.In 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.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 [1-3]. C/EBPβ, in particular, is known to regulate proliferation and differentiation in many target tissues, including liver, adipose tissue, immune cells, skin cells, the ovary, and mammary glands. Depending on the tissue type, C/EBPβ has been shown to either stimulate or inhibit cellular proliferation [1,4-7].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 dec