[O-279] ZINC FINGER PROTEINS 36 (ZFP36s) FAMILY AND LEUKEMIA INHIBITORY FACTOR (LIF) EXPRESSION IN THE HUMAN ENDOMETRIAL CYCLE: A PROSPECTIVE CASE-CONTROL STUDY.
E. Evans-Hoeker, S. L. Young, L. Yuan, B. Lessey, K. Caron, S. B. Ramos. Obstetrics and Gynecology, University of North Carolina at Chapel Hill, NC; Cell and Molecular Physiology, University of North Carolina at Chapel Hill, NC; Obstetrics and Gynecology, Greenville Hospital, Greenville, SC.
OBJECTIVE: The ZFP36 family of RNA-binding proteins (tristetraprolin (TTP), ZFP36L1 and ZFP36L2) regulate gene expression. Evidence suggests that this protein family modulates expression of LIF, a putative regulator of embryo implantation. The purpose of our study was to determine the relationships between the expression of ZFP36s and LIF in human endometrium in fertile and infertile women.
DESIGN: Prospective case-control study.
MATERIALS AND METHODS: Normal (NL, n=39) and unexplained infertility (UI, n=39) subjects were randomized to endometrial sampling during proliferative (P), early (ES), mid (MS), or late secretory phases, defined by urine LH detection. Relative LIF and ZFP36s (TTP, ZFP36L1, ZFP36L2) mRNA expression was assessed with quantitative, real-time RT-PCR. Spearman correlation and linear regression were used to assess relationships between LIF and ZPF36s. Wilcoxon rank-sum and Kruskal-Wallis tests were used to compare expression levels.
RESULTS: All ZFP36s and LIF levels were significantly higher in MS versus other phases in NL subjects, but did not differ in UI subjects. NL and UI MS LIF expression was similar (9.88[1.27-47.32], 17.93[2.17-26.05], p=1.0). NL subjects showed increased expression from ES to MS (0.27[0.07-1.54], 9.88[1.27-47.32], p=0.004), while UI did not (16.49[0.34-67.79], 17.93[2.17-26.05], p=0.94). All ZFP36s expression increased from ES to MS in NL but remained constant in UI subjects. Each ZFP36s correlated with LIF among NL subjects: TTP (p<0.0001, R2=0.40, slope 0.89); ZFP36L1 (p<0.0001, R2=0.37, slope 20.6); ZFP36L2 (p<0.0001, R2=0.39, slope 7.3). There was no significant co-variation between LIF expression and any of the ZFP36s in UI subjects.
CONCLUSION: Expression of each ZFP36s was cycle regulated in normal subjects and was directly correlated with LIF. This regulation and correlation were both disrupted in infertility. These data, in the context of previous findings suggest a role for ZFP36s in the regulation of endometrial LIF expression and fertility.
Supported by: UNC REI, NIH/NICHD R01HD067721.
Wednesday, October 24, 2012 11:15 AM
Oral Session: Reproductive Biology: Human Studies