Gene expression profiling of human endometrial receptivity on days LH+2 versus LH+7 by microarray technology

• Published in: Molecular human reproduction Vol. 9; no. 5; pp. 253 - 264
• Main Authors: Riesewijk, Anne, Martín, Julio, van Os, Roselinde, Horcajadas, José Antonio, Polman, Jan, Pellicer, Antonio, Mosselman, Sietse, Simón, Carlos
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-05-2003; Oxford Publishing Limited (England)
• Subjects: Adult; Biological and medical sciences; Endometrium - metabolism; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Gene Expression Regulation; Humans; In Situ Hybridization; Key words: endometrium/gene expression profiles/implantation/receptivity; Mammalian female genital system; Menstrual Cycle - metabolism; Morphology. Physiology; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Time Factors; Vertebrates: reproduction; Human; DNA chip; endometrium/gene expression profiles/implantation/receptivity; Gonadotropin; Gene expression; Pregnancy; Regulation(control); Adenohypophyseal hormone; Uterus; Ovum implantation; Female genital system; Luteinizing hormone; Female; Endometrium
• ISSN: 1360-9947; 1460-2407; 1460-2407
• DOI: 10.1093/molehr/gag037

In humans, embryonic implantation and reproduction depends on the interaction of the embryo with the receptive endometrium. To gain a global molecular understanding of human endometrial receptivity, we compared gene expression profiles of pre‐receptive (day LH+2) versus receptive (LH+7) endometria obtained from the same fertile woman (n = 5) in the same menstrual cycle in five independent experiments. Biopsies were analysed using the Affymetrix HG‐U95A array, a DNA chip containing ∼12 000 genes. Using the pre‐defined criteria of a fold change ≥3 in at least four out of five women, we identified 211 regulated genes. Of these, 153 were up‐regulated at LH+7 versus LH+2, whereas 58 were down‐regulated. Amongst these 211 regulated genes, we identified genes that were known to play a role in the development of a receptive endometrium, and genes for which a role in endometrial receptivity, or even endometrial expression, has not been previously described. Validation of array data was accomplished by mRNA quantification by real time quantitative fluorescent PCR (Q‐PCR) of three up‐regulated [glutathione peroxidase 3 (GPx‐3), claudin 4 (claudin‐4) and solute carrier family 1 member 1 (SLC1A1)] genes in independent LH+2 versus LH+7 endometrial samples from fertile women (n = 3) and the three up‐regulated genes throughout the menstrual cycle (n = 15). Human claudin‐4 peaks specifically during the implantation window, whereas GPx‐3 and SLC1A1 showed highest expression in the late secretory phase. In‐situ hybridization (ISH) experiments showed that GPx‐3 and SLC1A1 expression was restricted to glandular and luminal epithelial cells during the mid‐ and late luteal phase. The present work adds new and important data in this field, and highlights the complexity of studying endometrial receptivity even using global gene‐expression analysis.