Abstract

Abstract Study question Do endometrial gland factors influence recurrent pregnancy loss? Summary answer The endometrial gland transcriptome during the window of implantation is altered in women with recurrent pregnancy loss compared to controls. What is known already Secretions from endometrial glands contribute to the uterine environment that supports the attachment and implantation of the embryo in early pregnancy. Studies have attempted to identify an endometrial gene expression pattern associated with recurrent pregnancy loss however, the cellular heterogeneity within the endometrium may obscure important differences in specific cell populations. Study design, size, duration An observational study comparing controls and women with recurrent pregnancy loss. Participants/materials, setting, methods Endometrial samples were collected during the implantation period of the menstrual cycle from five matched participant egg donor controls and women with recurrent pregnancy loss. Endometrial glands were isolated from fresh endometrial biopsies and RNA sequencing was performed. A differential gene expression analysis and a gene ontology enrichment analysis was performed between egg donor controls and women with recurrent pregnancy loss. Main results and the role of chance This study reports a glandular epithelium specific gene expression profile and demonstrates differential gene expression of endometrial glands from women with recurrent pregnancy loss compared to controls. 18 genes were upregulated and 1 gene was downregulated in the endometrial glands from women with recurrent pregnancy loss compared to controls (5% false discovery rate). Biological processes which contain genes that were differentially expressed in women with recurrent pregnancy loss compared to controls include epithelial cell migration and regulation of secretion by the cell. Limitations, reasons for caution This is an observational study with a relatively small sample size. Wider implications of the findings: This study identified differences in gene expression in women with recurrent pregnancy loss that are specifically associated with endometrial glands rather than endometrium as a whole. These differences could be used to identify a perturbed endometrium, isolate causes of recurrent pregnancy loss and develop targeted therapies. Trial registration number Not applicable

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