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 Epigenetics in Placental Development and the Etiology of Preeclampsia

2019 ◽  
Vol 20 (11) ◽  
pp. 2837 ◽  
Author(s):  
Clara Apicella ◽  
Camino S. M. Ruano ◽  
Céline Méhats ◽  
Francisco Miralles ◽  
Daniel Vaiman
Keyword(s):  
Maternal Blood ◽  
Placental Development ◽  
Post Translational Modifications ◽  
Epigenetic Marks ◽  
Placental Function ◽  
Non Coding Rna ◽  
The Impact ◽  
Long Non Coding Rna ◽  
Potential Use

In this review, we comprehensively present the function of epigenetic regulations in normal placental development as well as in a prominent disease of placental origin, preeclampsia (PE). We describe current progress concerning the impact of DNA methylation, non-coding RNA (with a special emphasis on long non-coding RNA (lncRNA) and microRNA (miRNA)) and more marginally histone post-translational modifications, in the processes leading to normal and abnormal placental function. We also explore the potential use of epigenetic marks circulating in the maternal blood flow as putative biomarkers able to prognosticate the onset of PE, as well as classifying it according to its severity. The correlation between epigenetic marks and impacts on gene expression is systematically evaluated for the different epigenetic marks analyzed.

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 Role of Placental VDR Expression and Function in Common Late Pregnancy Disorders

2017 ◽  
Vol 18 (11) ◽  
pp. 2340 ◽  
Author(s):  
Julia Knabl ◽  
Aurelia Vattai ◽  
Yao Ye ◽  
Julia Jueckstock ◽  
Stefan Hutter ◽  
...  
Keyword(s):  
Late Pregnancy ◽  
And Function ◽  
Pregnancy Disorders

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.

scholarly journals Role of Carboxyl Groups in the Secondary Structure and Function of Sturgeon Gonadotropin

2008 ◽  
Vol 62 (3) ◽  
pp. 110-114
Author(s):  
Henriks Zenkevičs ◽  
Ilze Vosekalna ◽  
Vija Vose
Keyword(s):  
Secondary Structure ◽  
Cd Spectroscopy ◽  
Structure And Function ◽  
Membrane Receptors ◽  
Carboxyl Groups ◽  
Gonadotropic Hormone ◽  
Glycine Ethyl Ester ◽  
And Function ◽  
Specific Membrane

Role of Carboxyl Groups in the Secondary Structure and Function of Sturgeon Gonadotropin Free negatively charged carboxyl groups were selectively modified (neutralised) in sturgeon (Acipenser güldenstädti Br.) gonadotropic hormone (GTH) α and β subunits. Eleven free carboxyl groups, three in the α and eight in the β subunit, were neutralised by reaction with glycine ethyl ester. Investigation of reassociated α-β dimers (recombinants) comprising one or both modified subunits showed that specific hormonal activity was completely lost while immunoreactivity was lowered in comparison with that of the standard α-β dimer. CD-spectroscopy of the modified subunits did not indicate any considerable changes in their spatial structure. A conclusion was made that free COOH groups of GTH were important as bearers of the negative charge necessary for the hormone activity on the level of the hormone-specific membrane receptors.

scholarly journals Identifying Stabilin-1 and Stabilin-2 Double Knockouts in Reproduction and Placentation: A Descriptive Study

2020 ◽  
Vol 21 (19) ◽  
pp. 7235
Author(s):  
Soon-Young Kim ◽  
Eun-Hye Lee ◽  
Eun Na Kim ◽  
Woo-Chan Son ◽  
Yeo Hyang Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Fetal Development ◽  
Knockout Mouse ◽  
Descriptive Study ◽  
Reproductive Capacity ◽  
Placental Development ◽  
Phenotypic Characteristics ◽  
Double Knockout ◽  
Study Offer

The placenta undergoes reconstruction at different times during fetal development to supply oxygen and nutrients required throughout pregnancy. To accommodate the rapid growth of the fetus, small spiral arteries undergo remodeling in the placenta. This remodeling includes apoptosis of endothelial cells that line spiral arteries, which are replaced by trophoblasts of fetal origin. Removal of dead cells is critical during this process. Stabilin-1 (Stab1) and stabilin-2 (Stab2) are important receptors expressed on scavenger cells that absorb and degrade apoptotic cells, and Stab1 is expressed in specific cells of the placenta. However, the role of Stab1 and Stab2 in placental development and maintenance remain unclear. In this study, we assessed Stab1 and Stab2 expression in the placenta and examined the reproductive capacity and placental development using a double-knockout mouse strain lacking both Stab1 and Stab2 (Stab1/2 dKO mice). Most pregnant Stab1/2 dKO female mice did not produce offspring and exhibited placental defects, including decidual hemorrhage and necrosis. Findings of this study offer the first description of the phenotypic characteristics of placentas and embryos of Stab1/2 dKO females during pregnancy, suggesting that Stab1 and Stab2 are involved in placental development and maintenance.

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