Role of epidermal growth factor (EGF) and its receptor in the development of the human placenta

1995 ◽  
Vol 7 (6) ◽  
pp. 1465 ◽  
Author(s):  
T Maruo ◽  
H Matsuo ◽  
T Otani ◽  
M Mochizuki
Keyword(s):  
Egf Receptor ◽  
Placental Lactogen ◽  
Immunocytochemical Staining ◽  
Placental Development ◽  
Ki 67 ◽  
Serum Free ◽  
C Cell ◽  
Serum Free Condition ◽  
And Function

To elucidate the role of EGF in human placental development, effects of EGF on the proliferation and differentiation of trophoblasts were investigated. Explants of trophoblastic tissues obtained from 4-5 week or 6-12 week placentas were, respectively, cultured with or without EGF, in the presence or absence of triiodo-L-thyronine (T3) in a serum-free condition. The proliferative activity was examined by immunocytochemical staining with an antibody Ki-67, and the differentiated function was assessed by the ability to secrete human chorionic gonadotrophin (hCG) and human placental lactogen (hPL). In 4-5 week placentas, EGF and EGF receptor were localized in cytotrophoblast (C-cell), and EGF augmented the proliferation of C-cell without affecting the ability to secrete hCG and hPL. In contrast, in 6-12 week placentas, EGF and EGF receptor were localized in syncytiotrophoblast (S-cell), and EGF stimulated the secretion of hCG and hPL without affecting the proliferation of C-cell. In situ hybridization with c-erb B probe revealed that c-erb B mRNA is expressed in the S-cell after 6 weeks' gestation. Column chromatography of the serum-free media obtained by 5-day culture of early placental tissues resulted in the elution of immunoreactive EGF. The addition of T3 (10(-8) mol L(-1)) resulted in increased secretion of immunoreactive EGF by placental explants. These findings suggest that EGF acts as an autocrine factor in regulating early placental growth and function in synergy with thyroid hormone.

scholarly journals A Potential Role and Contribution of Androgens in Placental Development and Pregnancy

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 644
Author(s):  
Agata M. Parsons ◽  
Gerrit J. Bouma
Keyword(s):  
Fetal Development ◽  
Fetal Loss ◽  
Membrane Receptors ◽  
Placental Development ◽  
Placental Function ◽  
Fetal Physiology ◽  
Estrogen Synthesis ◽  
And Function ◽  
Pregnancy Disorders

Successful pregnancy requires the establishment of a highly regulated maternal–fetal environment. This is achieved through the harmonious regulation of steroid hormones, which modulate both maternal and fetal physiology, and are critical for pregnancy maintenance. Defects in steroidogenesis and steroid signaling can lead to pregnancy disorders or even fetal loss. The placenta is a multifunctional, transitory organ which develops at the maternal–fetal interface, and supports fetal development through endocrine signaling, the transport of nutrients and gas exchange. The placenta has the ability to adapt to adverse environments, including hormonal variations, trying to support fetal development. However, if placental function is impaired, or its capacity to adapt is exceeded, fetal development will be compromised. The goal of this review is to explore the relevance of androgens and androgen signaling during pregnancy, specifically in placental development and function. Often considered a mere precursor to placental estrogen synthesis, the placenta in fact secretes androgens throughout pregnancy, and not only contains the androgen steroid nuclear receptor, but also non-genomic membrane receptors for androgens, suggesting a role of androgen signaling in placental function. Moreover, a number of pregnancy disorders, including pre-eclampsia, gestational diabetes, intrauterine growth restriction, and polycystic ovarian syndrome, are associated with abnormal androgen levels and androgen signaling. Understanding the role of androgens in the placenta will provide a greater understanding of the pathophysiology of pregnancy disorders associated with androgen elevation and its consequences.

Abstract 17312: Hand1 Impairs Angiogenesis in Heart and Placenta

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Jennifer A Courtney ◽  
Helen N Jones
Keyword(s):  
Histological Analysis ◽  
Heart Defects ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Placental Development ◽  
Hypoplastic Left Heart ◽  
Septal Defects ◽  
And Function ◽  
Left Heart Syndrome

Introduction: Congenital heart defects affect approximately 1% of live births, often requiring complex surgeries at birth. The most significant risk factor for surgery survival is birthweight. Proper placental development and function is vital for normal fetal growth. We have previously demonstrated abnormal placental development and vascularization in human CHD placentas. Hand1 has roles in heart and placental development and has been implicated in multiple types of CHD including double right outlet, hypoplastic left heart syndrome, and septal defects. We utilized the Hand1 A126fs/+ mouse to investigate the role of Hand1 in placentation and vascularization. Methods: Hand1 A126fs/+ female mice were time-mated with Nkx2.5cre or Cdh5cre males. Feto-placental units were harvested at E10.5 and E12.5 for histological analysis, vascular assessment by IHC for CD-31, and RNA expression by qPCR. Results: Nkx2.5cre/Hand1 a126fs/+ fetuses demonstrated embryonic lethality by E10.5 due to lack of placental labyrinth formation and vascularization (Figure 1). In contrast, ablation of Hand1 in vascular endothelium (Cdh5cre) did not disrupt placental labyrinth or heart at E12.5. Expression of VegFb, Ang1, Ang2, Flt1, Flk was reduced in Hand1 A126fs/+ ; Nkx2.5cre placentas compared to control littermates, but VegFa expression was increased. Conclusion: Our data demonstrate that Hand1 expression in placental trophoblast, but not endothelium, is necessary for vascularization of the labyrinth and may disrupt multiple angiogenic factors known to be expressed in trophoblast. Alterations in Hand1 may represent a mechanism for abnormal placentation in cases of CHD. Figure 1. H/E (A-C) and CD31 (D-F) images of Hand1 +/+ (A, D), Hand1 A126fs/+ ; Nkx2.5cre (B, E), and Hand1 A126fs/+ ; Cdh5cre (C, F) placentas at day E12.5. Hand1A 126fs/+ ; Nkx2.5cre placentas fail to form labyrinth and fetal vasculature, while Hand1 A126fs/+ ; Cdh5cre placentas develop normally at this timepoint.

scholarly journals The role of insulin in transdifferentiated hepatocyte proliferation and function in serum‐free medium

2019 ◽  
Vol 23 (6) ◽  
pp. 4165-4178 ◽  
Author(s):  
Ce Gu ◽  
Panpan Li ◽  
Wei Liu ◽  
Yan Zhou ◽  
Wen‐Song Tan
Keyword(s):  
Hepatocyte Proliferation ◽  
Serum Free Medium ◽  
Free Medium ◽  
Serum Free ◽  
And Function

scholarly journals Role of EGF Receptor Regulatory Networks in the Host Response to Viral Infections

2022 ◽  
Vol 11 ◽  
Author(s):  
Cathleen R. Carlin
Keyword(s):  
Regulatory Networks ◽  
Egf Receptor ◽  
Viral Infections ◽  
Mitogen Activated Protein Kinase ◽  
Egfr Ligands ◽  
Gene Therapy Vectors ◽  
Mitogen Activated Protein ◽  
Cellular Stresses ◽  
And Function

In this review article, we will first provide a brief overview of EGF receptor (EGFR) structure and function, and its importance as a therapeutic target in epithelial carcinomas. We will then compare what is currently known about canonical EGFR trafficking pathways that are triggered by ligand binding, versus ligand-independent pathways activated by a variety of intrinsic and environmentally induced cellular stresses. Next, we will review the literature regarding the role of EGFR as a host factor with critical roles facilitating viral cell entry and replication. Here we will focus on pathogens exploiting virus-encoded and endogenous EGFR ligands, as well as EGFR-mediated trafficking and signaling pathways that have been co-opted by wild-type viruses and recombinant gene therapy vectors. We will also provide an overview of a recently discovered pathway regulating non-canonical EGFR trafficking and signaling that may be a common feature of viruses like human adenoviruses which signal through p38-mitogen activated protein kinase. We will conclude by discussing the emerging role of EGFR signaling in innate immunity to viral infections, and how viral evasion mechanisms are contributing to our understanding of fundamental EGFR biology.

scholarly journals PPARγ/RXRα Heterodimers Are Involved in Human CGβ Synthesis and Human Trophoblast Differentiation

Endocrinology ◽  
2001 ◽  
Vol 142 (10) ◽  
pp. 4504-4514 ◽  
Author(s):  
Anne Tarrade ◽  
Kristina Schoonjans ◽  
Jean Guibourdenche ◽  
Jean Michel Bidart ◽  
Michel Vidaud ◽  
...  
Keyword(s):  
Regulatory Region ◽  
Additive Effect ◽  
Placental Lactogen ◽  
Placental Development ◽  
Trophoblast Differentiation ◽  
Human Trophoblast ◽  
Transcript Levels ◽  
Nuclear Extracts

Abstract Recent studies performed with null mice suggested a role of either RXRα or PPARγ in murine placental development. We report here that both PPARγ and RXRα are strongly expressed in human villous cytotrophoblasts and syncytiotrophoblasts. Moreover, specific ligands for RXRs or PPARγ (but not for PPARα or PPARδ) increase both human CGβ transcript levels and the secretion of human CG and its free β-subunit. When combined, these ligands have an additive effect on human CG secretion. Pan-RXR and PPARγ ligands also have an additive effect on the synthesis of other syncytiotrophoblast hormones such as human placental lactogen, human placental GH, and leptin. Therefore, in human placenta, PPARγ/RXRα heterodimers are functional units during cytotrophoblast differentiation into the syncytiotrophoblast in vitro. Elements located in the regulatory region of the human CGβ gene (β5) were found to bind RXRα and PPARγ from human cytotrophoblast nuclear extracts, suggesting that PPARγ/RXRα heterodimers directly regulate human CGβ transcription. Altogether, these data show that PPARγ/RXRα heterodimers play an important role in human placental development.

Knockdown of AXL Receptor Tyrosine Kinase in Osteosarcoma Cells Leads to Decreased Proliferation and Increased Apoptosis

2013 ◽  
Vol 26 (1) ◽  
pp. 179-188 ◽  
Author(s):  
Y. Zhang ◽  
Y-J. Tang ◽  
Y. Man ◽  
F. Pan ◽  
Z-H. Li ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Distant Metastases ◽  
Tnm Staging ◽  
Loss Of Function ◽  
Ki 67 ◽  
Axl Receptor Tyrosine Kinase ◽  
Induced Apoptosis ◽  
And Function

Dysregulation of the Axl receptor tyrosine kinase (RTK) has been implicated in the development and progression of a variety of malignancies. Axl is known to activate strong anti-apoptotic signaling pathways that promote oncogenesis. However, the role of Axl plays in osteosarcoma (OS) remains elusive. The present study aimed to investigate the clinical significance and function of Axl in human OS. Forty cases of OS and corresponding adjacent non-cancerous tissues (ANCT) were collected. The expression of Axl was assessed using immunohistochemical assay through tissue microarray procedure. A loss-of-function experiment was performed to investigate the effects of small hairpin RNA (shRNA)-mediated knockdown of Axl on the expression of p-AKT, poly ADP-ribose polymerase (PARP) and Ki-67, the proliferative activities, indicated by MTT assay, and the apoptotic index in OS MG-63 cells. As a result, the expression of Axl was found in OS tissues with higher strong reactivity rate, compared with the ANCT (75.0% vs 20.0%, P=0.000), but it did not associate with the age, gender, tumor size, TNM staging and distant metastases (each P>0.05). Furthermore, knockdown of Axl inhibited the proliferative activities and induced apoptosis in MG-63 cells with decreased expression of p-AKT, and Ki-67 and increased expression of PARP. In conclusion, our findings suggest that Axl is highly expressed in most of the OS tissues compared with the ANCT, and knockdown of Axl inhibits proliferation and induces apoptosis of OS cells possibly through downregulation of the AKT pathway, suggesting that our findings may provide new insights into the potential therapeutic target for cancer.

scholarly journals The Role of Congenital Cytomegalovirus Infection in Adverse Birth Outcomes: A Review of the Potential Mechanisms

Viruses ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 20
Author(s):  
Annete Njue ◽  
Carolyn Coyne ◽  
Andrea V. Margulis ◽  
Dai Wang ◽  
Morgan A. Marks ◽  
...  
Keyword(s):  
Birth Outcomes ◽  
Stem Cell Differentiation ◽  
Extravillous Trophoblast ◽  
Adverse Birth Outcomes ◽  
Placental Development ◽  
Low Passage ◽  
And Function

Human cytomegalovirus (CMV) is a major cause of nonhereditary adverse birth outcomes, including hearing and visual loss, neurologic deficits, and intrauterine growth retardation (IUGR), and may contribute to outcomes such as stillbirth and preterm delivery. However, the mechanisms by which CMV could cause adverse birth outcomes are not fully understood. This study reviewed proposed mechanisms underlying the role of CMV in stillbirth, preterm birth, and IUGR. Targeted literature searches were performed in PubMed and Embase to identify relevant articles. Several potential mechanisms were identified from in vitro studies in which laboratory-adapted and low-passage strains of CMV and various human placental models were used. Potential mechanisms identified included impairment of trophoblast progenitor stem cell differentiation and function, impairment of extravillous trophoblast invasiveness, dysregulation of Wnt signaling pathways in cytotrophoblasts, tumor necrosis factor-α mediated apoptosis of trophoblasts, CMV-induced cytokine changes in the placenta, inhibition of indoleamine 2,3-dioxygenase activity, and downregulation of trophoblast class I major histocompatibility complex molecules. Inherent challenges for the field remain in the identification of suitable in vivo animal models. Nonetheless, we believe that our review provides useful insights into the mechanisms by which CMV impairs placental development and function and how these changes could result in adverse birth outcomes.

scholarly journals The potential role of the ERRγ pathway in placental dysfunction

Reproduction ◽  
2020 ◽  
Author(s):  
Zhiyong Zou ◽  
Karen Forbes ◽  
Lynda K. Harris ◽  
Alexander E P Heazell
Keyword(s):  
Fetal Growth ◽  
Therapeutic Interventions ◽  
Placental Development ◽  
Human Trophoblast ◽  
Altered Expression ◽  
Placental Dysfunction ◽  
And Function ◽  
Upstream Regulators ◽  
Estrogen Related Receptor

Normal placental development and function is of key importance to fetal growth. Conversely aberrations of placental structure and function are evident in pregnancy complications including fetal growth restriction (FGR) and preeclampsia. Although trophoblast turnover and function is altered in these conditions, their underlying aetiologies and pathophysiology remains unclear, which hampers development of therapeutic interventions. Here we review evidence that supports a role for Estrogen Related Receptor-gamma (ERRγ) in the development of placental dysfunction in FGR and preeclampsia. This relationship deserves particular consideration because ERRγ is highly expressed in normal placenta, is reduced in FGR and preeclampsia and its expression is altered by hypoxia, which is thought to result from deficient placentation seen in FGR and preeclampsia. Several studies have also found microRNA or other potential upstream regulators of ERRγ negatively influence trophoblast function which could contribute to placental dysfunction seen in FGR and preeclampsia. Interestingly, microRNAs regulate ERRγ expression in human trophoblast. Thus, if ERRγ is pivotally associated with the abnormal trophoblast turnover and function it may be targeted by microRNAs or other possible upstream regulators in the placenta. This review explores altered expression of ERRγ and upstream regulation of ERRγ-mediated pathways resulting in the trophoblast turnover, placental vascularisation, and placental metabolism underlying placental dysfunctions. This demonstrates that the ERRγ pathway merits further investigation as a potential therapeutic target in FGR and preeclampsia.

scholarly journals The role of Sirtuin1–PPARγ axis in placental development and function

2018 ◽  
Vol 60 (4) ◽  
pp. R201-R212 ◽  
Author(s):  
Jonathan Pham ◽  
Kanaga Arul Nambi Rajan ◽  
Ping Li ◽  
Mana M Parast
Keyword(s):  
Pregnancy Complications ◽  
Intrauterine Growth Restriction ◽  
Multiple Pregnancy ◽  
Well Being ◽  
Sirtuin 1 ◽  
Hypertensive Disorder ◽  
Placental Development ◽  
Intrauterine Growth ◽  
And Function

Placental development is important for proper in utero growth and development of the fetus, as well as maternal well-being during pregnancy. Abnormal differentiation of placental epithelial cells, called trophoblast, is at the root of multiple pregnancy complications, including miscarriage, the maternal hypertensive disorder preeclampsia and intrauterine growth restriction. The ligand-activated nuclear receptor, PPARγ, and nutrient sensor, Sirtuin-1, both play a role in numerous pathways important to cell survival and differentiation, metabolism and inflammation. However, each has also been identified as a key player in trophoblast differentiation and placental development. This review details these studies, and also describes how various stressors, including hypoxia and inflammation, alter the expression or activity of PPARγ and Sirtuin-1, thereby contributing to placenta-based pregnancy complications.

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