The study of progesterone action in human myometrial explants

Georgiou, Ektoras X; Lei, Kaiyu; Lai, Pei F.; Yulia, Angela; Herbert, Bronwen R.; Castellanos, Marcos; May, Sean; Sooranna, Suren R.; Johnson, Mark R.

doi:10.1093/molehr/gaw037

Cited by 17 publications

(30 citation statements)

References 42 publications

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“…Georgiou et al [80] compared gene expression in fresh myometrium, which was frozen at the time of Cesarean section, to ex vivo myometrial pieces, passage 4 primary myometrial cells, and hTERT myometrial cells. While whole-genome transcriptome analysis revealed that none of the in vitro models overlapped with the fresh tissue, in a principal component analysis plot [80], the gene expression profile of the tissue pieces most closely resembled that of the fresh tissue [80]. Upon direct comparison; 1444 genes varied between the ex vivo tissue pieces and fresh tissue; 3840 genes varied between passage 4 primary myometrial cells and fresh tissue; and 4603 genes varied between hTERT myometrial cells and fresh tissue [80].…”

Section: Tissue Pieces/explant Modelsmentioning

confidence: 99%

“…While whole-genome transcriptome analysis revealed that none of the in vitro models overlapped with the fresh tissue, in a principal component analysis plot [80], the gene expression profile of the tissue pieces most closely resembled that of the fresh tissue [80]. Upon direct comparison; 1444 genes varied between the ex vivo tissue pieces and fresh tissue; 3840 genes varied between passage 4 primary myometrial cells and fresh tissue; and 4603 genes varied between hTERT myometrial cells and fresh tissue [80]. A total of 555 genes varied commonly upon comparing all three in vitro groups (ex vivo tissue pieces, passage 4 primary myometrial cells and hTERT myometrial cells) to fresh tissue [80].…”

Section: Tissue Pieces/explant Modelsmentioning

confidence: 99%

“…Upon direct comparison; 1444 genes varied between the ex vivo tissue pieces and fresh tissue; 3840 genes varied between passage 4 primary myometrial cells and fresh tissue; and 4603 genes varied between hTERT myometrial cells and fresh tissue [80]. A total of 555 genes varied commonly upon comparing all three in vitro groups (ex vivo tissue pieces, passage 4 primary myometrial cells and hTERT myometrial cells) to fresh tissue [80]. Georgiou et al [80] validated the microarray results by examining genes associated with reproductive function and parturition, including PTGS2, OXTR, PGR and GJA1, as well as genes associated with the smooth muscle phenotype, including alpha smooth muscle actin (ACTA2) and MYL kinase (MYLK) [80].…”

Section: Tissue Pieces/explant Modelsmentioning

confidence: 99%

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Methods and Model Systems Used to Study Pregnant Human Uterine Smooth Muscle

Ilicic¹,

Paul²

2018

Muscle Cell and Tissue - Current Status of Research Field

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Successful pregnancy necessitates that the human uterus is maintained in a relaxed, quiescent state for the majority pregnancy, before ultimately transforming to a contractile phenotype capable of powerful, coordinated contractions to facilitate parturition. The exact mechanisms that regulate this transition are yet to be fully understood, and as such, we still do not understand the molecular mechanisms that trigger the onset of human labor. This is in large part due to the ethical considerations associated with human pregnancy, which, outside of clinical trials, primarily limits human studies to in vitro investigations on cell lines and biopsied tissues. Researchers have therefore devised numerous model systems for investigating pregnant human uterine smooth muscle, which have played vital roles in elucidating the fundamental biology and key regulatory pathways that underpin the transition from quiescence to contractility. This chapter describes in detail, those methods and model systems used to study pregnant human uterine smooth muscle, and explores the challenges associated with these model systems.

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Section: Tissue Pieces/explant Modelsmentioning

confidence: 99%

Section: Tissue Pieces/explant Modelsmentioning

confidence: 99%

Section: Tissue Pieces/explant Modelsmentioning

confidence: 99%

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Methods and Model Systems Used to Study Pregnant Human Uterine Smooth Muscle

Ilicic¹,

Paul²

2018

Muscle Cell and Tissue - Current Status of Research Field

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“…Indeed, it is known that P4 is an indispensable 32 factor for endometrium decidualization and for early stage of clinical pregnancy to 33 prepare an adequate immune environment for fetus and low LPL results abnormal 34 ongoing pregnancy [18,19,[29][30][31][32]. 35 Forward, it is increasingly clear that embryo implantation is dependent in one side 36 on immune local mechanisms and in another side on endocrine mechanisms related to 37 luteal P4 synthesis while their interactive reaction is still kept into question for 38 pregnancy achievement. For this reason, while our previous work [22] was based on the 39 implementation of PBMC immunotherapy for RIF patients and proving its efficiency 40 tripling the clinical outcomes, the present work was more focused on demonstrating the 41 correlation between LPL and immunotherapy success highlighting the interactive 42 reaction between luteal P4 synthesis by CL and immune system.…”

Section: Introductionmentioning

confidence: 99%

“…119 Nevertheless, it was commonly accepted that with insufficient P4 production causing 120 miscarriages could be solved simply by an exogenous P4 administration in order to 121 regulate the inflammatory mediators of pregnancy and even for patients undergoing IVF 122 process in fresh or frozen cycles to improve clinical outcomes prior embryo 123 transfer [29,35,36]. Indeed, P4 presents an anti-inflammatory action enhancing Th2 124 cytokines production to maintain pregnancy [37,38]. 125 However, our doubled clinical outcomes including implantation and clinical 126 pregnancy rates could have more evident explanation especially when LPL showed high 127 increase in PBMC-test compared to control (9ng/ml vs 4ng/ml) with positive Hypothesis of interactive effect of PBMC immunotherapy and luteal progesterone level for implantation and pregnancy success.…”

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confidence: 99%

Luteal progesterone level correlated with immunotherapy success of patients with repeated implantation failures

Sefrioui

Madkour

Bouamoud

et al. 2019

Preprint

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Immunotherapy using PBMC administration demonstrated relatively its effectiveness to treat RIF patients but it still unclear to explain some miscarriages. Luteal progesterone level (LPL) issued from corpus luteum after embryo implantation stage could be informative basis data to personalize immunotherapy for RIF patients predicting clinical outcomes. This randomized controlled study included 70 patients undergoing ICSI program presenting at least 3 RIF: 39 for Control of untreated patients and 31 for PBMC-test concerning treated patients with immunotherapy. For PBMC-test group, Peripheral Blood Mononuclear Cells (PBMCs) were isolated from patients on ovulation induction day and cultured three days to be administered to intrauterine cavity of patients two days before fresh embryo transfer. LPL was analyzed at day 15 after embryo transfer and clinical outcomes were calculated including implantation, clinical pregnancy and miscarriage rates. Clinical outcomes were doubly improved after immunotherapy including implantation and clinical pregnancy rates comparing Control versus PBMC-test (10% and 21% vs 24% and 45%). In the other hand, this strategy showed an increase over double in LPL (4ng/ml for Control vs 9ng/ml for PBMC-test) while the latter was correlated to clinical pregnancy. Bypassing the effectiveness of this immunotherapy approach for RIF patients, it is directly correlated to LPL proving the interactive reaction between immune profile of the treated patients and progesterone synthesis by corpus luteum. 2 embryo implantation, the major part of implantation establishment is bypassing embryo 3 quality and its genetic integrity highlighting the communication between embryo and the 4 mother. This cross talk is essentially orchestrated by hormonal and immune dialogues 5 November 17, 2018 1/10 in order to assure embryo invasion in the maternal endometrium without rejecting the 6 fetal allograft. Furthermore, it is already known that progesterone (P4) is one of the 7 most important implantation/pregnancy success keys for its effects on the endometrium 8 and early pregnancy survival while its removal results in miscarriage [1-3]. 9P4 is a hormonal key to modulate the maternal immune system by reducing natural 10 killer (NK)-cell activity [4], inhibiting cytotoxic T-cell activity [5], increasing HLA-G 11 production in trophoblast cells [6], increasing suppressor-cell levels [7] and as special 12 mechanism, it is able to induce lymphocyte-blocking proteins production such as 13 progesterone-induced blocking factor (PIBF) [8][9][10][11]. Generally, its anti-inflammatory 14 effect reported by several studies showing that it is essential to modify the cytokine 15 response from pro-inflammatory profile presented by Th1 during embryo implantation 16 to anti-inflammatory profile presented by Th2 for pregnancy maintain [12-16, 18, 19]. 17 Thus, Th1/Th2 unbalance could explain implantation failures in some patients with 18 RIF, RPL or recurrent miscarriages (RM) [20-22]. 19 129(r=0.28) (Table 2). However, 4 ng/ml of LPL was ...

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