Gene Expression Profile Of Endometrium Research Articles

#235 : The Impact of Endometrial Scratch Performed in Mid-Luteal Phase on the Endometrium Whole Genome Transcriptomic Profiles in Following Menstrual Cycle

Background and Aims: To verify whether endometrial scratch in mid-luteal phase affect the genomic characteristics of peri-implantation endometrium in the following cycle. Method: A Retrospectively self-control cohort study was conducted in a university assisted reproductive unit. A total of eight women with recurrent implantation failure were included. Each participant had endometrial biopsy twice, one biopsy was done on day LH+7 in a natural cycle, and the second biopsy was performed on day LH+7 of the following cycle. R package was used for identifying differentially expressed genes between the first biopsy group and the second biopsy group, and for gene set enrichment analysis. Results: The paired sample showed no significant difference in gene expression profiles of endometrium before and after endometrial scratch. Conclusion: It suggests that endometrial scratch performed during previous mid-luteal phase did not affect the genomic profiles of endometrium on day LH+7 in women with recurrent implantation failure.

Controlled Ovarian Stimulation Protocols Alter Endometrial Histomorphology and Gene Expression Profiles.

Although it is well appreciated that ovarian stimulation protocols for in vitro fertilization (IVF) alter endometrial receptivity, the precise cellular mechanisms are not known. To gain insights into potential mechanisms by which different ovarian stimulation protocols alter the endometrium, we compared histologic and gene expression profiles of endometrium from women undergoing conventional ovarian stimulation for IVF (C-IVF) with those undergoing minimal stimulation with clomiphene citrate (MS-IVF). Sixteen women undergoing MS-IVF (n= 8) or C-IVF (n= 8) were recruited for endometrial biopsy at the time of oocyte retrieval. Endometrial glands were large, tortuous, and secretory with C-IVF but small and undifferentiated with MS-IVF. Whereas RNA sequencing did not reveal changes in estrogen receptor or its co-regulators or classic proliferation associated genes in MS-IVF, together with immunohistochemistry, Wnt signaling was disrupted in endometrium from MS-IVF cycles with significant upregulation of Wnt inhibitors. Secreted frizzled-related protein 1 (sFRP1) was increased fourfold (p< 0.01), and sFRP4 was upregulated sixfold (p< 0.01) relative to C-IVF. Further these proteins were localized to subepithelial endometrial stroma. These data indicate that MS-IVF protocols with CC do not seem to impact endometrial estrogen signaling as much as would be expected from the reported antiestrogenic properties of CC. Rather, the findings of this study highlight Wnt signaling as a major factor for endometrial development during IVF cycles.

Differential gene expression profiling of endometrium during the mid-luteal phase of the estrous cycle between a repeat breeder (RB) and non-RB cows

BackgroundRepeat breeding directly affects reproductive efficiency in cattle due to an increase in services per conception and calving interval. This study aimed to investigate whether changes in endometrial gene expression profile are involved in repeat breeding in cows. Differential gene expression profiles of the endometrium were investigated during the mid-luteal phase of the estrous cycle between repeat breeder (RB) and non-RB cows using microarray analysis.MethodsThe caruncular (CAR) and intercaruncular (ICAR) endometrium of both ipsilateral and contralateral uterine horns to the corpus luteum were collected from RB (inseminated at least three times but not pregnant) and non-RB cows on Day 15 of the estrous cycle (4 cows/group). Global gene expression profiles of these endometrial samples were analyzed with a 15 K custom-made oligo-microarray for cattle. Immunohistochemistry was performed to investigate the cellular localization of proteins of three identified transcripts in the endometrium.ResultsMicroarray analysis revealed that 405 and 397 genes were differentially expressed in the CAR and ICAR of the ipsilateral uterine horn of RB, respectively when compared with non-RB cows. In the contralateral uterine horn, 443 and 257 differentially expressed genes were identified in the CAR and ICAR of RB, respectively when compared with non-RB cows. Gene ontology analysis revealed that genes involved in development and morphogenesis were mainly up-regulated in the CAR of RB cows. In the ICAR of both the ipsilateral and contralateral uterine horns, genes related to the metabolic process were predominantly enriched in the RB cows when compared with non-RB cows. In the analysis of the whole uterus (combining the data above four endometrial compartments), RB cows showed up-regulation of 37 genes including PRSS2, GSTA3 and PIPOX and down-regulation of 39 genes including CHGA, KRT35 and THBS4 when compared with non-RB cows. Immunohistochemistry revealed that CHGA, GSTA3 and PRSS2 proteins were localized in luminal and glandular epithelial cells and stroma of the endometrium.ConclusionThe present study showed that endometrial gene expression profiles are different between RB and non-RB cows. The identified candidate endometrial genes and functions in each endometrial compartment may contribute to bovine reproductive performance.

Controlled Ovarian Stimulation Induces a Functional Genomic Delay of the Endometrium with Potential Clinical Implications

Controlled ovarian stimulation induces morphological, biochemical, and functional genomic modifications of the human endometrium during the window of implantation. Our objective was to compare the gene expression profile of the human endometrium in natural vs. controlled ovarian stimulation cycles throughout the early-mid secretory transition using microarray technology. Microarray data from 49 endometrial biopsies obtained from LH+1 to LH+9 (n=25) in natural cycles and from human chorionic gonadotropin (hCG) +1 to hCG+9 in controlled ovarian stimulation cycles (n=24) were analyzed using different methods, such as clustering, profiling of biological processes, and selection of differentially expressed genes, as implemented in Gene Expression Pattern Analysis Suite and Babelomics programs. Endometria from natural cycles followed different genomic patterns compared with controlled ovarian stimulation cycles in the transition from the pre-receptive (days LH/hCG+1 until LH/hCG+5) to the receptive phase (day LH+7/hCG+7). Specifically, we have demonstrated the existence of a 2-d delay in the activation/repression of two clusters composed by 218 and 133 genes, respectively, on day hCG+7 vs. LH+7. Many of these delayed genes belong to the class window of implantation genes affecting basic biological processes in the receptive endometrium. These results demonstrate that gene expression profiling of the endometrium is different between natural and controlled ovarian stimulation cycles in the receptive phase. Identification of these differentially regulated genes can be used to understand the different developmental profiles of receptive endometrium during controlled ovarian stimulation and to search for the best controlled ovarian stimulation treatment in terms of minimal endometrial impact.

Effect of an Intrauterine Device on the Gene Expression Profile of the Endometrium

The human endometrium acquires the ability to allow embryo attachment just for a specific period of time during each menstrual cycle. Understanding of the opposite functional status, referred to as refractoriness, can potentially be used to improve receptivity in infertile patients or as an interceptive approach to prevent gestation. The objective of the study was to analyze the endometrial gene expression profile induced by an inert intrauterine device (IUD) at the time of implantation. We used a microarray containing more than 16,000 cDNAs to investigate the gene expression profile of receptive vs. refractory endometrium in the same women induced by the presence of an IUD. We compared the gene expression profile of endometrium obtained at LH+7 (window of receptivity) from the same women (n = 5) at the following time points: month 1, corresponding to the natural cycle before IUD insertion; month 3, just before IUD removal; and months 5 and 15. Data were validated by quantitative RT-PCR for IGF binding protein-3, peroxisome proliferative activated receptor-gamma, glycodelin, and leukemia inhibitory factor and immunohistochemistry for glycodelin. We identified 147 genes significantly dysregulated in the refractory endometrium (78 up- and 69 down-regulated). Interestingly, 52 of these genes have previously been reported to be regulated during window of implantation. Surprisingly, the majority of genes (96.6%) remained dysregulated 2 months after IUD removal, but 1 yr later most of them (80%) returned to normal. Our results reveal that a refractory endometrium in a fertile woman produced by an IUD is induced by preventing the normal transition to a receptive gene expression profile through effects on a specific subset or cluster of genes that impact on endometrial receptivity.

Gene Expression Profiles and Structural/Functional Features of the Peri-Implantation Endometrium in Natural and Gonadotropin-Stimulated Cycles

It has been speculated that controlled ovarian hyperstimulation (COH), as performed during in vitro fertilization therapy, may negatively affect embryo implantation. The objective of this prospective and randomized study was to investigate gene expression profiles of the human endometrium during the window of implantation of gonadotropin-stimulated COH cycles compared with temporally matched natural cycles (d 21). Analysis was performed with high-density oligonucleotide microarrays. In addition, other structural and functional features of the endometrium were investigated. Results corroborated that COH cycles depicted advancement of pinopodes appearance, histological features, and steroid receptor down-regulation when compared with natural cycles. These changes were associated with significant, albeit small, variations in gene expression (18 genes/expressed sequence tags and -1.55- to +3.40-fold changes). Second, there were significant changes in gene expression when comparing cycles using a GnRH agonist vs. a GnRH antagonist (13 genes/expressed sequence tags and +1.42- to +2.10-fold changes). This is the first attempt to elucidate gene expression profiles of the endometrium during COH cycles. The observed differences in gene expression in COH cycles using state-of-the-art protocols may not have a major functional impact on embryo implantation.