Evaluation of Expression and Phosphorylation of Progesterone Receptor in Endometrial Stromal Cells of Patients with Recurrent Implantation Failure Compared to Healthy Fertile Women

Hosseinirad, Hossein; Novin, Marefat Ghaffari; Nazarian, Hamid; Safaei, Zahra; Hashemi, Teibeh; Paktinat, Shahrokh; Mofarahe, Zahra Shams

doi:10.1007/s43032-020-00428-8

Cited by 8 publications

(3 citation statements)

References 33 publications

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“…This modification also plays an important role in regulating progesterone function in endometrial cells because it can stabilize the receptor and change its transcriptional activity, which can be induced when ligands are added ( Cope & Monsivais 2022 ). Compared with the HC group, the phosphorylation of the Ser294 residue of PR was significantly reduced in ESCs of RM patients ( Hosseinirad et al 2021 ). Among them, the MAPK signaling pathway plays an important regulatory role in the phosphorylation of PR, while SHP2 is necessary for the molecular processes of Ras–ERK ( Eaton et al 2013 ).…”

Section: Discussionmentioning

confidence: 97%

SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor

Cui

Zhao

et al. 2023

Reproduction

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Decidualization is the process of conversion of endometrial stromal cells (ESCs) into decidual stromal cells (DSCs), which is caused by progesterone production that begins during the luteal phase of the menstrual cycle and then increases throughout pregnancy dedicated to support embryonic development. Decidualization deficiency is closely associated with various pregnancy complications, such as recurrent miscarriage (RM). Here, we reported that Src-homology-2-containing phospho-tyrosine phosphatase (SHP2), a key regulator in the signal transduction process downstream of various receptors, plays an indispensable role in decidualization. SHP2 expression was upregulated during decidualization. SHP2 inhibitor RMC-4550 and shRNA mediated SHP2 reduction resulted in a decreased level of phosphorylation of ERK and aberrant cytoplasmic localization of progesterone receptor (PR), coinciding with reduced expression of IGFBP1 and various other target genes of decidualization. Solely inhibiting ERK activity recapitulated these observations. Administration of RMC-4550 led to decidualization deficiency and embryo absorption in mouse. Moreover, reduced expression of SHP2 was detected in decidua of RM patients. Our results revealed that SHP2 is key to PR's nuclear localization, thereby indispensable for decidualization and that reduced expression of SHP2 might be engaged in the pathogenesis of RM.

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Section: Discussionmentioning

confidence: 97%

SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor

Cui

Zhao

et al. 2023

Reproduction

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“…Embryo growth and development require the action of progesterone through its receptor inside the endometrium, as the maternal-fetal interactions, pregnancy recognition, and uterine receptivity are all regulated by the action of progesterone [4]. Recently, Hosseinirad et al showed that the expression of progesterone receptor is impaired in the endometrium of RIF patients [25]. Based on this available evidence, the effect of PRP on gene expression of endometrial cells can be considered as another mechanism in improving the pregnancy rate and reducing the spontaneous abortion rate and subsequently increasing the live birth rate.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Autologous Platelet-Rich Plasma on Pregnancy Outcomes in Repeated Implantation Failure Patients Undergoing Frozen Embryo Transfer: A Randomized Controlled Trial

et al. 2021

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Repeated implantation failure (RIF) is a disorder in which good-quality embryos fail to implant in the endometrium following several in vitro fertilization (IVF) cycles. This study aimed to evaluate the efficiency and safety of intrauterine infusion of plateletrich plasma (PRP) in improvement of pregnancy outcomes in RIF patients undergoing frozen embryo transfer (FET). A total of 438 women with a history of RIF undergoing FET were assessed for eligibility to enter the study. Patients were randomly assigned to the intervention (PRP) and control groups. The intervention group received an intrauterine infusion of 0.5 ml PRP 48 h before embryo transfer while the control group received standard treatment. The rates of chemical and clinical pregnancy were defined as the primary outcome values. All women were followed up until the study endpoints that included the number of neonates born and pregnancy-related complications. Three hundred and ninety-three participants accomplished the study and their data were analyzed. The chemical pregnancy, clinical pregnancy, and live birth rates were higher in the PRP group than control group (p value: <0.0001; p value: <0.0001; p value: <0.0001 respectively). However, there were no significant differences between the two groups in terms of multiple pregnancies and pregnancy complications except for spontaneous abortion. The spontaneous abortion rate was significantly higher in the control group compared to the PRP group (p value = 0.0262). These results suggest that intrauterine infusion of PRP is an effective and safe route to improve pregnancy outcomes in RIF patients undergoing FET.

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“…Indeed, a recent study with a group of infertile patients showed those with unexplained infertility had the lowest endometrial epithelial expression levels of both PGR-A and PGR-B [ 92 ]. Moreover, the recurrent implantation failure (RIF) phenomenon has been associated with not only lower classical PGR expression in the endometrium [ 93 ] but also with the expression of other classical PGR polymorphisms [ 149 ]. In particular, the so-called PROGINS polymorphism leads to amino acid substitution in exon 4.…”

Section: Pgr In the Uterusmentioning

confidence: 99%

What Do We Know about Classical and Non-Classical Progesterone Receptors in the Human Female Reproductive Tract? A Review

Medina-Laver

Rodríguez-Varela

Salsano

et al. 2021

IJMS

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The progesterone hormone regulates the human menstrual cycle, pregnancy, and parturition by its action via the different progesterone receptors and signaling pathways in the female reproductive tract. Progesterone actions can be exerted through classical and non-classical receptors, or even a combination of both. The former are nuclear receptors whose activation leads to transcriptional activity regulation and thus in turn leads to slower but long-lasting responses. The latter are composed of progesterone receptors membrane components (PGRMC) and membrane progestin receptors (mPRs). These receptors rapidly activate the appropriate intracellular signal transduction pathways, and they can subsequently initiate specific cell responses or even modulate genomic cell responses. This review covers our current knowledge on the mechanisms of action and the relevance of classical and non-classical progesterone receptors in female reproductive tissues ranging from the ovary and uterus to the cervix, and it exposes their crucial role in female infertility.

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Evaluation of Expression and Phosphorylation of Progesterone Receptor in Endometrial Stromal Cells of Patients with Recurrent Implantation Failure Compared to Healthy Fertile Women

Cited by 8 publications

References 33 publications

SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor

SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor

The Effects of Autologous Platelet-Rich Plasma on Pregnancy Outcomes in Repeated Implantation Failure Patients Undergoing Frozen Embryo Transfer: A Randomized Controlled Trial

What Do We Know about Classical and Non-Classical Progesterone Receptors in the Human Female Reproductive Tract? A Review

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