An integrative analysis of endometrial steroid metabolism and transcriptome in relation to endometrial receptivity in in vitro fertilization patients.

Autor:	Stevens Brentjens LBPM; Department of Obstetrics and Gynecology, Maastricht University Medical Center+, Maastricht, the Netherlands; GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands. Electronic address: linda.brentjens@mumc.nl., Obukhova D; GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands; Department of Clinical Genetics, Maastricht University, Maastricht, the Netherlands., den Hartog JE; Department of Obstetrics and Gynecology, Maastricht University Medical Center+, Maastricht, the Netherlands; GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands., Delvoux B; Department of Obstetrics and Gynecology, Maastricht University Medical Center+, Maastricht, the Netherlands; GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands., Koskivuori J; University of Eastern Finland, School of Pharmacy, Kuopio, Finland., Auriola S; University of Eastern Finland, School of Pharmacy, Kuopio, Finland., Häkkinen MR; Department of Health Security, Finnish Institute for Health and Welfare (THL), Kuopio, Finland., Bui BN; Department of Gynecology and Reproductive Medicine, University Medical Centre Utrecht, Utrecht, the Netherlands., van Hoogenhuijze NE; Department of Gynecology and Reproductive Medicine, University Medical Centre Utrecht, Utrecht, the Netherlands., Mackens S; Center for Reproductive Medicine, UZ Brussel, Jette, Belgium., Mol F; Center for Reproductive Medicine, Reproduction and Development, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands., de Bruin JP; Department of Obstetrics and Gynecology, Jeroen Bosch Hospital-Hertogenbosch, the Netherlands., Besselink D; Department of Obstetrics and Gynecology, Radboud University Medical Centre, Nijmegen, the Netherlands., Teklenburg G; Isala Fertility Clinic, Isala Hospital, Zwolle, the Netherlands., Kukushkina V; Competence Centre on Health Technologies, Tartu, Estonia., Salumets A; Competence Centre on Health Technologies, Tartu, Estonia; Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia; Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden., Broekmans FJM; Department of Gynecology and Reproductive Medicine, University Medical Centre Utrecht, Utrecht, the Netherlands., van Golde RJT; Department of Obstetrics and Gynecology, Maastricht University Medical Center+, Maastricht, the Netherlands; GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands., Esteki MZ; GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands; Department of Clinical Genetics, Maastricht University, Maastricht, the Netherlands., Romano A; Department of Obstetrics and Gynecology, Maastricht University Medical Center+, Maastricht, the Netherlands; GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands.
Jazyk:	angličtina
Zdroj:	F&S science [F S Sci] 2023 Aug; Vol. 4 (3), pp. 219-228. Date of Electronic Publication: 2023 May 02.
DOI:	10.1016/j.xfss.2023.04.003
Abstrakt:	Objective: To study the relationship between the steroid concentration in the endometrium, in serum, and the gene expression level of steroid-metabolizing enzymes in the context of endometrial receptivity in in vitro fertilization (IVF) patients. Design: Case-control study of 40 IVF patients recruited in the SCRaTCH study (NTR5342), a randomized controlled trial investigating pregnancy outcome after "endometrial scratching." Endometrial biopsies and serum were obtained from patients with a first failed IVF cycle randomized to the endometrial scratch in the midluteal phase of the natural cycle before the next fresh embryo transfer during the second IVF cycle. Setting: University hopsital. Patients: Twenty women with clinical pregnancy were compared with 20 women who did not conceive after fresh embryo transfer. Cases and controls were matched for primary vs. secondary infertility, embryo quality, and age. Intervention: None. Main Outcome Measure(s): Steroid concentrations in endometrial tissue homogenates and serum were measured with liquid chromatography-mass spectrometry. The endometrial transcriptome was profiled by RNA-sequencing, followed by principal component analysis and differential expression analysis. False discovery rate-adjusted and log-fold change >|0.5| were selected as the threshold for differentially expressed genes. Result(s): Estrogen levels were comparable in both serum (n = 16) and endometrium (n = 40). Androgens and 17-hydroxyprogesterone were higher in serum than that in endometrium. Although steroid levels did not vary between pregnant and nonpregnant groups, subgroup analysis of primary women with infertility showed a significantly lower estrone concentration and estrone:androstenedione ratio in serum of the pregnant group (n = 5) compared with the nonpregnant group (n = 2). Expression of 34 out of 46 genes encoding the enzymes controlling the local steroid metabolism was detected, and estrogen receptor β gene was differentially expressed between pregnant and nonpregnant women. When only the primary infertile group was considered, 28 genes were differentially expressed between pregnant and nonpregnant women, including HSD11B2, that catalyzes the conversion of cortisol into cortisone. Conclusion(s): Steroidomic and transcriptomic analyses show that steroid concentrations are regulated by the local metabolism in the endometrium. Although no differences were found in endometrial steroid concentration in the pregnant and nonpregnant IVF patients, primary women with infertility showed deviations in steroid levels and gene expression, indicating that a more homogeneous patient group is required to uncover the exact role of steroid metabolism in endometrial receptivity. Clinical Trial Registration Number: The study was registered in the Dutch trial registry (www.trialregister.nl), registration number NL5193/NTR5342, available at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6687. The date of registration is July 31, 2015. The first enrollment is on January 1, 2016. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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