期刊论文详细信息
Reproductive Biology and Endocrinology
Deciphering a shared transcriptomic regulation and the relative contribution of each regulator type through endometrial gene expression signatures
Research
Jose Remohi1  Francisco Dominguez2  Patricia Diaz-Gimeno2  Patricia Sebastian-Leon2  Almudena Devesa-Peiro3  Antonio Parraga-Leo3  Diana Marti-Garcia3  Nuria Pellicer4 
[1] Department of Pediatrics, Obstetrics and Gynaecology, Universidad de Valencia, Av. Blasco Ibáñez 15, 46010, Valencia, Valencia, Spain;IVIRMA Global Research Alliance, IVIRMA Valencia, Plaza de La Policia Local 3, 46015, Valencia, Spain;IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Av. Fernando Abril Martorell 106, Torre A, Planta 1ª, 46026, Valencia, Valencia, Spain;IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Av. Fernando Abril Martorell 106, Torre A, Planta 1ª, 46026, Valencia, Valencia, Spain;Department of Pediatrics, Obstetrics and Gynaecology, Universidad de Valencia, Av. Blasco Ibáñez 15, 46010, Valencia, Valencia, Spain;IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Av. Fernando Abril Martorell 106, Torre A, Planta 1ª, 46026, Valencia, Valencia, Spain;IVIRMA Global Research Alliance, IVIRMA Valencia, Plaza de La Policia Local 3, 46015, Valencia, Spain;
关键词: CTCF;    GATA6;    Progesterone;    Estrogen;    miRNAs;    TFs;    Endometrial receptivity;    Recurrent implantation failure;    Infertility;    Menstrual cycle regulation;   
DOI  :  10.1186/s12958-023-01131-4
 received in 2023-06-21, accepted in 2023-08-22,  发布年份 2023
来源: Springer
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【 摘 要 】

BackgorundWhile various endometrial biomarkers have been characterized at the transcriptomic and functional level, there is generally a poor overlap among studies, making it unclear to what extent their upstream regulators (e.g., ovarian hormones, transcription factors (TFs) and microRNAs (miRNAs)) realistically contribute to menstrual cycle progression and function. Unmasking the intricacies of the molecular interactions in the endometrium from a novel systemic point of view will help gain a more accurate perspective of endometrial regulation and a better explanation the molecular etiology of endometrial-factor infertility.MethodsAn in-silico analysis was carried out to identify which regulators consistently target the gene biomarkers proposed in studies related to endometrial progression and implantation failure (19 gene lists/signatures were included). The roles of these regulators, and of genes related to progesterone and estrogens, were then analysed in transcriptomic datasets compiled from samples collected throughout the menstrual cycle (n = 129), and the expression of selected TFs were prospectively validated in an independent cohort of healthy participants (n = 19).ResultsA total of 3,608 distinct genes from the 19 gene lists were associated with endometrial progression and implantation failure. The lists’ regulation was significantly favoured by TFs (89% (17/19) of gene lists) and progesterone (47% (8 /19) of gene lists), rather than miRNAs (5% (1/19) of gene lists) or estrogen (0% (0/19) of gene lists), respectively (FDR < 0.05). Exceptionally, two gene lists that were previously associated with implantation failure and unexplained infertility were less hormone-dependent, but primarily regulated by estrogen. Although endometrial progression genes were mainly targeted by hormones rather than non-hormonal contributors (odds ratio = 91.94, FDR < 0.05), we identified 311 TFs and 595 miRNAs not previously associated with ovarian hormones. We highlight CTCF, GATA6, hsa-miR-15a-5p, hsa-miR-218-5p, hsa-miR-107, hsa-miR-103a-3p, and hsa-miR-128-3p, as overlapping novel master regulators of endometrial function. The gene expression changes of selected regulators throughout the menstrual cycle (FDR < 0.05), dually validated in-silico and through endometrial biopsies, corroborated their potential regulatory roles in the endometrium.ConclusionsThis study revealed novel hormonal and non-hormonal regulators and their relative contributions to endometrial progression and pathology, providing new leads for the potential causes of endometrial-factor infertility.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 预 览 】
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