Gene expression profiling of human peri-implantation endometria between natural and stimulated cycles

Objective

To investigate the effect of high serum E₂ levels in gonadotropin-stimulated cycles (hCG+7) on the gene expression patterns of human endometrium compared with natural cycles on the seventh day of LH surge (LH+7) and elucidate the underlying molecular changes that may be related to endometrial receptivity.

Design

Observational study.

Setting

University Hospital.

Patients(s)

Infertile patients with normal menstrual cycles undergoing IVF treatment.

Intervention(s)

Gonadotropin stimulation and endometrial biopsy.

Main Outcome Measure(s)

Gene expression by microarray and quantitative polymerase chain reaction (qPCR).

Result(s)

Endometrial samples from natural (n = 5) and stimulated (n = 8) cycles were collected. Patients in the stimulated cycles were classified as moderate (n = 4) or excessive (n = 4) responders if their serum E₂ levels on the day of administration of hCG were ≤20,000 pmol/L or >20,000 pmol/L, respectively. The RNA transcripts were profiled by Affymetrix HG-U133A microarray. Clustering and principal component analysis demonstrated a significant difference (≥2-fold) in the expression patterns of 411 genes among the three groups. Putative estrogen response elements or progesterone response elements were identified in the promoter regions of 49 differentially expressed genes of diverse biologic functions. The qPCR confirmed the microarray result in 47 endometrial samples.

Conclusion(s)

High serum E₂ and/or progesterone modulate the gene expression profiles of human endometrium and may affect endometrial receptivity.

Key Words: Endometrium, implantation, microarray, steroid hormones, stimulated cycle