Spatiotemporal expression pattern of Progesterone Receptor Component (PGRMC) 1 in endometrium from patients with or without endometriosis or adenomyosis

Thieffry, Charlotte; Wynendaele, Marie Van; Samain, Lucie; Tyteca, Donatienne; Pierreux, Christophe E.; Marbaix, Étienne; Henriet, Patrick

doi:10.1016/j.jsbmb.2022.106153

Cited by 6 publications

(5 citation statements)

References 33 publications

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“…We measured both mRNA and protein levels of PGRMC1 after inducing decidualization and observed a rise-to-decline pattern. The observed increase and decrease of PGRMC1 protein expression ts into cyclic changes observed in vivo [30]. The overall dynamic changes of the PGRMC1 protein level during a normal menstrual cycle are composed of two peaks: one occurs in the secretory phase, as revealed in this study and the other one occurs in the proliferative phase as previously reported [9,30].…”

Section: Discussionsupporting

confidence: 84%

“…In a normal menstrual period, PGRMC1 mRNA level gradually decreased from the proliferative phase to the secretory (including early-, mid-, and late-) phase, manifesting the highest level in the proliferation phase and the lowest level in the late-secretory phase (Fig. 1A-B), consistent with previously reported data [9,30]. This indicates that PGRMC1 may have an important role in regulating cellular proliferation and may not be required for decidualization in the secretory phase as it is consecutively decreased at mRNA level after progesterone stimulation.…”

Section: Pgrmc1 Expression Is Dysregulated In Patients With Impaired ...supporting

confidence: 92%

“…The observed increase and decrease of PGRMC1 protein expression ts into cyclic changes observed in vivo [30]. The overall dynamic changes of the PGRMC1 protein level during a normal menstrual cycle are composed of two peaks: one occurs in the secretory phase, as revealed in this study and the other one occurs in the proliferative phase as previously reported [9,30]. It resembles estrogen dynamics during the menstrual cycle, suggesting PGRMC1 expression may be regulated by estrogen concentration or a similar mechanism [1][2][3].…”

Section: Discussionmentioning

confidence: 79%

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Progesterone-induced Progesterone Receptor Membrane Component 1 Rise-to- Decline Changes are Essential for Decidualization

Liu

Franken

Bielfeld

et al. 2023

Preprint

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Background Decidualization of endometrial cells is the prerequisite for embryo implantation and subsequent placenta formation and is induced by rising progesterone levels following ovulation. One of the hormone receptors contributing to endometrial homeostasis is Progesterone Receptor Membrane Component 1 (PGRMC1), a non-classical membrane-bound progesterone receptor with yet unclear function. In this study, we aimed to investigate how PGRMC1 contributes to human decidualization. Methods To gain insight into PGRMC1-implication in infertility-related diseases, we analyzed its expression profile in RNA-sequencing datasets of endometrial biopsies. To further explore the function of PGRMC1 in human decidualization, we implemented an inducible decidualization system, which is achieved by culturing two human endometrial stromal cell lines in decidualization-inducing medium containing medroxyprogesterone acetate and 8-Br-cAMP. In our system, we measured PGRMC1 expression during hormone induction as well as decidualization status upon PGRMC1 knockdown at different time points. We further conferred proximity ligation assay to identify PGRMC1 interaction partners. Results PGRMC1 expression was altered in patients with infertility-related diseases and impaired decidualization, being significantly downregulated in most datasets. In in vitro experiments, we observed that PGRMC1 expression follows a rise-to-decline pattern, in which its expression level initially increased during the first 6 days after induction (PGRMC1 increasing phase) and decreased in the following days (PGRMC1 decreasing phase). Knockdown of PGRMC1 expression before the induction led to a failed decidualization, while its knockdown after induction did not inhibit decidualization, suggesting that the progestin-induced ‘PGRMC1 increasing phase’ is essential for normal decidualization. Furthermore, we found that the interactions of PHB1 and PHB2 with PGRMC1 were induced upon progestin treatment. Knocking down either PHB individually or both slowed down the decidualization process compared to the control, suggesting that PGRMC1 cooperates with PHBs to regulate the decidualization. Conclusions According to our findings, PGRMC1 expression followed a progestin-induced rise-to-decline expression pattern during human endometrial decidualization process; and the correct execution of this expression program was crucial for successful decidualization. Thereby, the results of our in vitro model explained how PGRMC1 dysregulation in patients with impaired decidualization contributes to the manifestation of their disease.

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Section: Discussionsupporting

confidence: 84%

Section: Pgrmc1 Expression Is Dysregulated In Patients With Impaired ...supporting

confidence: 92%

Section: Discussionmentioning

confidence: 79%

See 1 more Smart Citation

Progesterone-induced Progesterone Receptor Membrane Component 1 Rise-to- Decline Changes are Essential for Decidualization

Liu

Franken

Bielfeld

et al. 2023

Preprint

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“…Menstrual cycle and diseases affecting the uterus are characterized by changes in the lipid metabolism of the tissues . In the course of a study of hormonal changes during the menstrual cycle and their relation with endometriosis, it was decided to test the matrix transfer protocol on human uterine tissue sections, a biological sample type that has never been studied in MSI to the best of our knowledge. Preliminary reference sample imaging using 30 keV Bi 5 + primary ions highlighted two different tissues, as shown in Figure a: (1) the myometrium, which is a muscular wall that allows the expulsion of the fetus, and (2) the endometrium, which is a dynamic tissue that grows, matures, and is degraded during the menstrual cycle.…”

Section: Resultsmentioning

confidence: 99%

Improvement of Lipid Detection in Mouse Brain and Human Uterine Tissue Sections Using In Situ Matrix Enhanced Secondary Ion Mass Spectrometry

Daphnis,

Tomasetti,

Delmez

et al. 2023

J. Am. Soc. Mass Spectrom.

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The potential of mass spectrometry imaging, and especially ToF-SIMS 2D and 3D imaging, for submicrometer-scale, label-free molecular localization in biological tissues is undisputable. Nevertheless, sensitivity issues remain, especially when one wants to achieve the best lateral and vertical (nanometerscale) resolution. In this study, the interest of in situ matrix transfer for tissue analysis with cluster ion beams (Bi n + , Ar n +) is explored in detail, using a series of six low molecular weight acidic (MALDI) matrices. After estimating the sensitivity enhancements for phosphatidylcholine (PC), an abundant lipid type present in almost any kind of cell membrane, the most promising matrices were softly transferred in situ on mouse brain and human uterine tissue samples using a 10 keV Ar 3000 + cluster beam. Signal enhancements up to 1 order of magnitude for intact lipid signals were observed in both tissues under Bi 5 + and Ar 3000 + bombardment. The main findings of this study lie in the in-depth characterization of uterine tissue samples, the demonstration that the transferred matrices also improve signal efficiency in the negative ion polarity and that they perform as well when using Bi n + and Ar n + primary ions for analysis and imaging.

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“…However, the expression of progesterone receptor (PR) is downregulated or absent in the ectopic lesions of AM patients compared with healthy controls, resulting in progesterone resistance. As a result, the proliferative effect of excess estrogen cannot be countered by progesterone ( Mehasseb et al, 2011 ; Thieffry et al, 2022 ). The increase in estrogen not only induces endometrial proliferation and repair through the estradiol receptor β (ERβ), but also promotes the secretion of oxytocin through the estradiol receptor α (ERα), which continuously stimulates the uterus to be in a state of peristalsis and damage, causing the uterus to enter a vicious cycle of chronic damage, proliferation and inflammation.…”

Section: Pathogenesis Of Ammentioning

confidence: 99%

Exosomes: potential diagnostic markers and drug carriers for adenomyosis

Cheng,

Wei,

Zhou

et al. 2023

Front. Pharmacol.

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Adenomyosis is a common benign gynecological disorder and an important factor leading to infertility in fertile women. Adenomyosis can cause deep lesions and is persistent and refractory in nature due to its tumor-like biological characteristics, such as the ability to implant, adhere, and invade. The pathogenesis of adenomyosis is currently unclear. Therefore, new therapeutic approaches are urgently required. Exosomes are nanoscale vesicles secreted by cells that carry proteins, genetic materials and other biologically active components. Exosomes play an important role in maintaining tissue homeostasis and regulating immune responses and metabolism. A growing body of work has shown that exosomes and their contents are key to the development and progression of adenomyosis. This review discusses the current research progress, future prospects and challenges in this emerging therapeutic tool by providing an overview of the changes in the adenomyosis uterine microenvironment and the biogenesis and functions of exosomes, with particular emphasis on the role of exosomes and their contents in the regulation of cell migration, proliferation, fibrosis formation, neovascularization, and inflammatory responses in adenomyosis.

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Spatiotemporal expression pattern of Progesterone Receptor Component (PGRMC) 1 in endometrium from patients with or without endometriosis or adenomyosis

Cited by 6 publications

References 33 publications

Progesterone-induced Progesterone Receptor Membrane Component 1 Rise-to- Decline Changes are Essential for Decidualization

Progesterone-induced Progesterone Receptor Membrane Component 1 Rise-to- Decline Changes are Essential for Decidualization

Improvement of Lipid Detection in Mouse Brain and Human Uterine Tissue Sections Using In Situ Matrix Enhanced Secondary Ion Mass Spectrometry

Exosomes: potential diagnostic markers and drug carriers for adenomyosis

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