Endometrial receptivity revisited: endometrial transcriptome adjusted for tissue cellular heterogeneity

Abstract

(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.Thecopyright holder for this preprint . http://dx.doi.org/10.1101/357152 doi: bioRxiv preprint first posted online Jun. 28, 2018; 3 PARTICIPANTS/MATERIAL, SETTING, METHODS Paired early-and mid-secretory 50endometrial biopsies were obtained from thirty-five healthy, regularly cycling, fertile volun-51 teers, aged 23 to 36 years, and analysed by RNA sequencing. Differential gene expression 52 analysis was performed using two approaches. In one of them, computational deconvolution 53 was applied as an intermediate step to adjust for epithelial and stromal cells' proportions in 54 endometrial biopsy. The results were then compared to conventional differential expression 55 analysis. 56 MAIN RESULTS AND THE ROLE OF CHANCE The estimated average proportions of 57stromal and epithelial cells in early secretory phase were 65% and 35%, and during mid-secre-58 tory phase 46% and 54%, respectively, that correlated well with the results of histological eval-59 uation (r=0. 88, p=1.1×10 -6 ). Endometrial tissue transcriptomic analysis showed that approxi-60 mately 26% of transcripts (n=946) differentially expressed in receptive endometrium in cell-61 type unadjusted analysis also remain differentially expressed after adjustment for biopsy cel-62 lular composition. However, the other 74% (n=2,645) become statistically non-significant after 63 adjustment for biopsy cellular composition, underlining the impact of tissue heterogeneity on 64 differential expression analysis. The results suggest new mechanisms involved in endometrial 65 maturation involving genes like LINC01320, SLC8A1 and GGTA1P, described for the first time 66 in context of endometrial receptivity. 67

A molecular tool for menstrual cycle phase dating of endometrial samples in endometriosis transcriptome studies†

“…Sequencing data analysis was performed as described previously [3], and each sample was normalized using geometric mean of gene expression levels of four housekeeper genes. The same sequencing protocol was applied to 54 paired endometrial samples from 27 healthy parous women, collected at the histologically and biochemically [predicted from the luteinizing hormone (LH) peak in urine] confirmed ES and MS cycle phases (described in [5]). The resulting data were used to create a machine learning support vector machine (SVM) model for discrimination of ES and MS phase samples.…”

Determining the Molecular Background of Endometrial Receptivity in Adenomyosis

“…The difference in expression patterns between study groups was not statistically significant in the present study which might be due to whole-tissue samples used for analysis. Suhorutshenko et al [ 66 ] demonstrated that expression contribution of low abundant cell types in heterogeneous tissue could be masked by more abundant types. They compared paired endometrium biopsy samples collected in pre-receptive (early-secretory, ES) and receptive (mid-secretory, MS) states and estimated that ES samples consisted of 65% stromal and 35% epithelial cells, while the proportion of stromal and epithelial cells in MS samples was 46% and 54%, respectively.…”

Plasma membrane proteome of adhesion‐competent endometrial epithelial cells and its modulation by Rab11a

“…Human endometrium has been investigated extensively for its global molecular repertoire and modulation in response to hormones, drugs, and diseases. Majority of these investigations have focused on the transcriptome of whole tissue (Altmae et al, ; Borthwick et al, ; Carson et al, ; Haouzi et al, ; Horcajadas et al, ; Hu et al, ; Mirkin et al, ; Riesewijk et al, ; Suhorutshenko et al, ; Talbi et al, ). Strides have also been made to develop the endometrial proteome (Chen et al, ; DeSouza et al, ; Dominguez et al, ; Hood et al, ; Parmar et al, ; Rai, Kota, Sundaram, Deendayal, & Shivaji, ).…”

“…Dysfunctions in any of these cell types can lead to impaired endometrial functions and infertility. This has triggered efforts to develop endometrial cell‐type‐specific transcriptome or proteome (Evans et al, ; Suhorutshenko et al, ). However, data on the plasma membrane proteome of endometrial epithelial cells are scarce.…”