Regulation of olfactomedin isoform expressions in human endometrium

Abstract

Objective: Previous microarray studies showed that olfactomedin 1 (OLFM1) gene is down-regulated in the receptive window (LH+7) of human endometrium. In this study, the expression of OLFM mRNA isoforms in IVF patients was studied, and correlated with the lower pregnancy rate in excessive responders (serum E2 ≥20 000 pmol/L at hCG day) of the stimulated group. Methods: Quantitative PCR was carried out using TaqMan Assay probes to detect OLFM isoforms in endometria of IVF patients. Immunohistochemistry was carried out to study the localization of OLFM. Human endometrial stromal and epithelial primary cultures were isolated and treated with estrogen (E) and/or progesterone (P) to study the hormonal regulation of OLFMs. Results: Endometrial OLFM-1/-2 mRNA levels decrease significantly from proliferative to secretory phases of the menstruation cycle. OLFM protein was found to be highly expressed in glandular and luminal epithelium of human endometrium. Patients in natural cycles at LH+7 (n=15) had a higher expression of OLFM-1/-2 mRNA than those from stimulated cycles (15 moderate and 17 excessive responders). Yet, no significant difference was found between the stimulated groups. A significant reduction in OLFM-2 mRNA was detected under E or P treatment in cultured epithelial cells. Conclusion: The expression of OLFM-2 mRNA is down-regulated by hormones while the decreased expression of OLFM-1/-2 in the stimulated groups may not be the cause of lower pregnancy rate in the excessive-responders of IVF patients. (This work is supported in part by a CRCG grant to KFL and RGC grant HKU 7514/05M to PCH.)