Platform Session 1. Uterine Development and Post-Implantation Embryonic Signaling
Sunday, July 24, 2005
3:00 PM–5:00 PM
Location: CCQ 202
(1) THE Sp/KRUPPEL-LIKE FAMILY (KLF) MEMBER, BASIC TRANSCRIPTION ELEMENT BINDING PROTEIN-1 (BTEB1) IS IMPORTANT FOR DEVELOPMENTAL SYNCHRONY OF EMBRYO AND UTERINE ENDOMETRIUM.
Velarde, Michael1, Geng, Yan2, Eason, Renea2, Simmen, Frank1, 2, Simmen, Rosalia1, 2, 1 University of Arkansas for Medical Sciences, Little Rock, AR2 Arkansas Children's Nutrition Center, Little Rock, AR
ABSTRACT- Basic Transcription Element Binding Protein-1 (BTEB1) functionally interacts with Progesterone Receptor (PR) to mediate progestin sensitivity of target genes in the uterine endometrium. Female mice null for the BTEB1 gene are sub-fertile, due in part, to reduced numbers of successfully implanting embryos. We hypothesized that the implantation defect is a consequence of developmental asynchrony between the embryo and uterine endometrium at peri-implantation. To address this, wild type (WT) and BTEB1 null female mice were mated with BTEB1 null and WT males, respectively to generate heterozygous embryos in a WT or BTEB1 null uterine environment, and endometrial proliferation (BrdU-labeling) and apoptosis (TUNEL) status from day post-coitum 0.5 to 5.5 (plug at dpc 0.5) were evaluated. There was a one-day delay in the peak of proliferation in luminal epithelium (LE) of BTEB1 null mice (dpc 3.5) relative to that of WT mice (dpc 2.5), while glandular epithelium (GE) and stromal (ST) proliferation were reduced (P<0.05) at dpc 2.5 in BTEB1 null when compared to WT mice. TUNEL-positive cells were higher (P<0.05) at dpc 2.5 in endometrial LE, GE, and ST of BTEB1 null than of WT mice, with similar levels noted at other dpc. The number of PR-positive ST cells was negatively correlated with that of proliferating LE (P=0.03) and GE (P=0.03) cells in WT mice at dpc 2.5 to 5.5, although this correlation was lost in BTEB1 null mice (LE, P =0.783; GE, P =0.180) and was not observed prior to dpc 2.5 for both genotypes. The numbers of ST cells positive for PR and its downstream target Hoxa10 were reduced in BTEB1 null mice at dpc 3.5 and 4.5. Serum estrogen (E) and progesterone (P) levels at dpc 0.5 to 5.5 did not differ between genotypes. Ovariectomized WT and BTEB1 null mice, treated with either sesame oil or E (100 ng) + P (1 mg) for 24 h, were evaluated for BrdU incorporation. The number of proliferating LE, GE, and ST cells was lower (P<0.05) in BTEB1 null than in WT mice, after E+P treatment. The number of PR- and Hoxa10-positive ST cells also was lower with BTEB-1 KO. Results suggest that BTEB1 mediates the paracrine control by ST PR, of LE cell proliferation by regulating PR expression and transactivation, and thus, is essential for maintaining developmental synchrony between the embryo and the endometrium requisite for successful implantation (NIH HD21961).
KEY WORDS: BTEB1, progesterone receptor, endometrium, peri-implantation