Gene expression confirms a potentially receptive endometrium identified by histology in fertile women

• Published in: Human reproduction (Oxford) 2012-09, Vol.27 (9), p.2747-2755
• Main Authors: Evans, G.E., Phillipson, G.T.M., Sin, I.L., Frampton, C.M.A., Kirker, J.A., Bigby, S.M., Evans, J.J.
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Body Mass Index; Cell Proliferation; Embryo Implantation - genetics; Endometrium - embryology; Endometrium - metabolism; Female; Fertility - genetics; Fertilization in Vitro - methods; Gene Expression Profiling; Gene Expression Regulation; Gynecology. Andrology. Obstetrics; Humans; Luteinizing Hormone - metabolism; Medical sciences; Menstrual Cycle - metabolism; Nucleic Acid Hybridization; Oligonucleotide Array Sequence Analysis; RNA, Messenger - metabolism; Transcriptome
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/des233

BACKGROUND To use contemporary biochemical markers to characterize mRNA/gene expression in the potentially fertile secretory endometrium to confirm its identification based on histological characteristics in order to develop a clinically applicable test. METHODS Nine, fertile, cycling Caucasian women were sampled from one IVF clinic. Endometrial samples were collected from them in two to four menstrual cycles at 2 and 7 days post first significant rise in blood LH. Separate endometrial glands and stroma populations were obtained by laser microdissection. Linear polymerase chain reaction amplified mRNAs which were hybridized to both Affymetrix U133 Plus2 and Agilent 4×44K microarrays followed by gene set analysis. Four histopathologists reviewed the sample set using the same histological criteria to date and characterize the non-receptive and potentially receptive samples. RESULTS mRNA expression of microdissected glands and stroma provided molecular signatures that characterized the two specific phases of the cycle with distinct clustering patterns. Cell proliferation and five other associated biological pathways were significantly down-regulated when the endometrium is considered potentially receptive accompanied by an increase in secreted glycoproteins mRNAs in the potentially receptive glands. Reported histological findings identified the presence of one histological feature characteristic of each phase: glandular mitoses indicated a non-receptive endometrium, whereas a potentially receptive endometrium was distinguished by supranuclear vacuolation. CONCLUSIONS This study defined a transcriptome characteristic of active cell proliferation in the non-receptive samples with a marked overall down-regulation of this pathway in potentially receptive samples—suggesting a transitional state associated with receptivity but not implantation. However, microarrays involve expensive, specialized testing and require significant post-data analysis. Sampling according to endocrinological and molecular prediction improved the consistency of histological assessment and allowed reliable histological markers of glandular mitosis in the non-receptive phase and supranuclear vacuolation of the potentially receptive endometrium to be identified. Thus, histology can provide an affordable, clinically applicable test in the context of reproduction.