205. Homeobox gene TGIF is increased in human idiopathic fetal growth restriction

2008 ◽  
Vol 20 (9) ◽  
pp. 5
Author(s):  
P. Murthi ◽  
N. Pathirage ◽  
A. Borg ◽  
S. Brennecke ◽  
B. Kalionis
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Homeobox Gene ◽  
Growth Restriction ◽  
Growth Potential ◽  
Mrna Levels ◽  
Developmental Abnormalities ◽  
Clinical Criteria ◽  
Targeted Mutation ◽  
Clinically Significant

Fetal Growth Restriction (FGR) is a clinically significant pregnancy disorder in which the fetus fails to achieve its full growth potential in utero. Recently, we identified a novel homeobox gene TGIF, in the placenta using microarray expression profiling (1). Targeted mutation of tgif in mouse results in placental dysfunction (2). In this study, we have investigated TGIF expression levels in idiopathic FGR. FGR-affected placental samples were collected based on strict clinical criteria to ensure inclusion of cases at the severe end of the spectrum of the disease. TGIF mRNA expression was analysed in placentae obtained from pregnancies complicated by idiopathic FGR and gestation-matched control pregnancies (n = 25 each). Real-time PCR showed a significant increase in TGIF mRNA levels in FGR-affected placentae and gestation-matched controls [1.29 ± 0.06 FGR v. 0.78 ± 0.04 Control, P < 0.001]. western blotting using a TGIF polyclonal antibody revealed significantly increased levels of TGIF protein in term FGR-affected placentae compared with term controls [3970 ± 1101 (n = 10) v. 2323 ± 644 (n = 10), P < 0.05]. The spatial distribution of TGIF protein by immunohistochemistry revealed immunoreactive TGIF protein in residual cytotrophoblast cells, syncytiotrophoblast cells, microvascular endothelial cells and in stromal cells. We conclude that increased expression of homeobox gene TGIF may be a contributing factor to the developmental abnormalities seen in the FGR-affected placentae. (1) Murthi P, Hiden U, Rajaraman G, Kalionis B. Placenta May 29, [Epub ahead of print]. (2) Bartholin L, Melhuish TA et al. Dev Biol. 2008 May 2. [Epub ahead of print].

Decorin expression is decreased in human idiopathic fetal growth restriction

2010 ◽  
Vol 22 (6) ◽  
pp. 949 ◽  
Author(s):  
B. C. Swan ◽  
P. Murthi ◽  
G. Rajaraman ◽  
N. A. Pathirage ◽  
J. M. Said ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Dermatan Sulfate ◽  
Growth Restriction ◽  
Growth Potential ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Clinically Significant ◽  
Normal Placenta

Fetal growth restriction (FGR) is a clinically significant pregnancy disorder in which the fetus fails to achieve its full growth potential in utero. Most cases of FGR are idiopathic and are associated with placental thrombosis. Previous studies suggest that proteoglycans, such as decorin, that contain the glycosaminoglycan dermatan sulfate are the principal anticoagulants in the normal placenta. The present study investigated decorin expression in placentas from pregnancies complicated by idiopathic FGR (n = 26) and gestation-matched controls (n = 27). Real-time polymerase chain reaction demonstrated significantly reduced decorin mRNA expression in FGR compared with control (1.52 ± 0.14 v. 2.21 ± 0.22, respectively; P < 0.01). Immunoblotting revealed decreased decorin protein (40 kDa) expression in FGR compared with controls (420.8 ± 39.0 v. 690.1 ± 42.2, respectively; n = 12 in each group; P = 0.0007). Immunohistochemistry demonstrated the presence of immunoreactive decorin protein in the placental villous stroma surrounding the fetal capillaries and a significant decrease in decorin protein presence in FGR compared with control (1.75 ± 0.66 v. 2.98 ± 1.12, respectively; n = 6 in each group; P < 0.01, t-test). This is the first study to demonstrate reduced decorin in idiopathic FGR, indicating a potentially significant role for decorin in the aetiology of placental thrombosis in idiopathic FGR.

INTRAUTERINE GROWTH RETARDATION - A REVIEW ARTICLE

2018 ◽  
pp. 184-195
Author(s):  
Minh Son Pham ◽  
Vu Quoc Huy Nguyen ◽  
Dinh Vinh Tran
Keyword(s):  
Fetal Growth ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Fetal Growth Restriction ◽  
Growth Restriction ◽  
Growth Potential ◽  
National Guidelines ◽  
Intrauterine Growth ◽  
No Gold Standard

Small for gestational age (SGA) and fetal growth restriction (FGR) is difficult to define exactly. In this pregnancy condition, the fetus does not reach its biological growth potential as a consequence of impaired placental function, which may be because of a variety of factors. Fetuses with FGR are at risk for perinatal morbidity and mortality, and poor long-term health outcomes, such as impaired neurological and cognitive development, and cardiovascular and endocrine diseases in adulthood. At present no gold standard for the diagnosis of SGA/FGR exists. The first aim of this review is to: summarize areas of consensus and controversy between recently published national guidelines on small for gestational age or fetal growth restriction; highlight any recent evidence that should be incorporated into existing guidelines. Another aim to summary a number of interventions which are being developed or coming through to clinical trial in an attempt to improve fetal growth in placental insufficiency. Key words: fetal growth restriction (FGR), Small for gestational age (SGA)

Identification of newborns with Fetal Growth Restriction (FGR) in weight and/or length based on constitutional growth potential

2006 ◽  
Vol 165 (10) ◽  
pp. 717-725 ◽  
Author(s):  
Nicole Mamelle ◽  
Magali Boniol ◽  
Olivier Rivière ◽  
Marie O. Joly ◽  
Georges Mellier ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Growth Restriction ◽  
Growth Potential

Fetal growth restriction: unresolved issues of risk stratification, early diagnosis, and obstetric management

2021 ◽  
Vol 20 (5) ◽  
pp. 76-86
Author(s):  
N.M. Podzolkova ◽  
◽  
Yu.V. Denisova ◽  
M.Yu. Skvortsova ◽  
T.V. Denisova ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Risk Stratification ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Growth Restriction ◽  
Diagnostic Methods ◽  
Growth Potential ◽  
Increased Risk ◽  
Obstetric Management ◽  
Language Literature

Fetal growth restriction (FGR) refers to pregnancy complications associated with an increased risk of perinatal morbidity and mortality and is defined in the Russian-language literature as the fetal size and weight retardation in relation to the norm for a given gestational age, and in the English-language literature – as the inability of the fetus to realize its genetically determined growth potential. FGR is the cause of 43% of stillbirths of unspecified etiology, and some cases remain undiagnosed even in high-risk populations due to the lack of universal diagnostic standards for this pathology. The review presents a critical analysis of the existing definitions of FGR, the latest data on risk factors, an assessment of diagnostic methods for its early and late forms, the prospects of using biomarkers and instrumental methods of examination in predicting adverse perinatal outcomes, and an algorithm for the management of pregnancy complicated by FGR. For a more complete coverage of the literature and deeper understanding of the nosology, attention is focused on FGR that is not accompanied by preeclampsia and other hypertensive disorders, which occur in about 30% of cases. Key words: placental insufficiency, fetometry, percentile, pulsatility index, fetal growth restriction For citation: Podzolkova N.M., Denisova Yu.V., Skvortsova M.Yu., Denisova T.V., Shovgenova D.S. Fetal growth restriction: unresolved issues of risk stratification, early diagnosis, and obstetric management. Vopr. ginekol. akus. perinatol. (Gynecology, Obstetrics and Perinatology). 2021; 20(5): 76–86. (In Russian). DOI: 10.20953/1726-1678-2021-5-76-86

scholarly journals Phosphorylation of Yes-associated protein impairs trophoblast invasion and migration: implications for the pathogenesis of fetal growth restriction†

2020 ◽  
Vol 103 (4) ◽  
pp. 866-879
Author(s):  
Hao Wang ◽  
Ping Xu ◽  
Xiaofang Luo ◽  
Mingyu Hu ◽  
Yamin Liu ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Cell Function ◽  
Hippo Pathway ◽  
Growth Restriction ◽  
Growth Potential ◽  
Biomechanical Analysis ◽  
Trophoblast Invasion ◽  
Invasion And Migration ◽  
And Migration

Abstract Fetal growth restriction (FGR) is a condition in which a newborn fails to achieve his or her prospective hereditary growth potential. This condition is associated with high newborn mortality, second only to that associated with premature birth. FGR is associated with maternal, fetal, and placental abnormalities. Although the placenta is considered to be an important organ for supplying nutrition for fetal growth, research on FGR is limited, and treatment through the placenta remains challenging, as neither proper uterine intervention nor its pathogenesis have been fully elucidated. Yes-associated protein (YAP), as the effector of the Hippo pathway, is widely known to regulate organ growth and cancer development. Therefore, the correlation of the placenta and YAP was investigated to elucidate the pathogenic mechanism of FGR. Placental samples from humans and mice were collected for histological and biomechanical analysis. After investigating the location and role of YAP in the placenta by immunohistochemistry, we observed that YAP and cytokeratin 7 have corresponding locations in human and mouse placentas. Moreover, phosphorylated YAP (p-YAP) was upregulated in FGR and gradually increased as gestational age increased during pregnancy. Cell function experiments and mRNA-Seq demonstrated impaired YAP activity mediated by extracellular signal-regulated kinase inhibition. Established FGR-like mice also recapitulated a number of the features of human FGR. The results of this study may help to elucidate the association of FGR development with YAP and provide an intrauterine target that may be helpful in alleviating placental dysfunction.

scholarly journals Homeobox Gene HLX1Expression Is Decreased in Idiopathic Human Fetal Growth Restriction

2006 ◽  
Vol 168 (2) ◽  
pp. 511-518 ◽  
Author(s):  
Padma Murthi ◽  
Vicki Doherty ◽  
Joanne Said ◽  
Susan Donath ◽  
Shaun P. Brennecke ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Homeobox Gene ◽  
Growth Restriction

INTRAUTERINE GROWTH RETARDATION - A REVIEW ARTICLE

2018 ◽  
Vol 8 (6) ◽  
pp. 184-195
Author(s):  
Son Pham Minh ◽  
Huy Nguyen Vu Quoc ◽  
Vinh Tran Dinh
Keyword(s):  
Fetal Growth ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Fetal Growth Restriction ◽  
Growth Restriction ◽  
Growth Potential ◽  
National Guidelines ◽  
Intrauterine Growth ◽  
No Gold Standard

Small for gestational age (SGA) and fetal growth restriction (FGR) is difficult to define exactly. In this pregnancy condition, the fetus does not reach its biological growth potential as a consequence of impaired placental function, which may be because of a variety of factors. Fetuses with FGR are at risk for perinatal morbidity and mortality, and poor long-term health outcomes, such as impaired neurological and cognitive development, and cardiovascular and endocrine diseases in adulthood. At present no gold standard for the diagnosis of SGA/FGR exists. The first aim of this review is to: summarize areas of consensus and controversy between recently published national guidelines on small for gestational age or fetal growth restriction; highlight any recent evidence that should be incorporated into existing guidelines. Another aim to summary a number of interventions which are being developed or coming through to clinical trial in an attempt to improve fetal growth in placental insufficiency. Key words: fetal growth restriction (FGR), Small for gestational age (SGA)

scholarly journals Decreased STAT3 in human idiopathic fetal growth restriction contributes to trophoblast dysfunction

Reproduction ◽  
2015 ◽  
Vol 149 (5) ◽  
pp. 523-532 ◽  
Author(s):  
A J Borg ◽  
H E J Yong ◽  
M Lappas ◽  
S A Degrelle ◽  
R J Keogh ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Growth Restriction ◽  
Mrna Levels ◽  
Protein Levels ◽  
Bewo Cells ◽  
Villous Trophoblast ◽  
Β Hcg ◽  
Stat Pathway

Abnormal trophoblast function is associated with fetal growth restriction (FGR). The JAK–STAT pathway is one of the principal signalling mechanisms by which cytokines and growth factors modulate cell proliferation, differentiation, cell migration and apoptosis. The expression of placental JAK–STAT genes in human idiopathic FGR is unknown. In this study, we propose the hypothesis that JAK–STAT pathway genes are differentially expressed in idiopathic FGR-affected pregnancies and contribute to abnormal feto-placental growth by modulating the expression of the amino acid transporter SNAT2, differentiation marker CGB/human chorionic gonadotrophin beta-subunit (β-hCG) and apoptosis markers caspases 3 and 8, and TP53. Expression profiling of FGR-affected placentae revealed that mRNA levels of STAT3, STAT2 and STAT5B decreased by 69, 52 and 50%, respectively, compared with gestational-age-matched controls. Further validation by real-time PCR and immunoblotting confirmed significantly lower STAT3 mRNA and STAT3 protein (total and phosphorylated) levels in FGR placentae. STAT3 protein was localised to the syncytiotrophoblast (ST) in both FGR and control placentae. ST differentiation was modelled by in vitro differentiation of primary villous trophoblast cells from first-trimester and term placentae, and by treating choriocarcinoma-derived BeWo cells with forskolin in cell culture. Differentiation in these models was associated with increased STAT3 mRNA and protein levels. In BeWo cells treated with siRNA targeting STAT3, the mRNA and protein levels of CGB/β-hCG, caspases 3 and 8, and TP53 were significantly increased, while that of SNAT2 was significantly decreased compared with the negative control siRNA. In conclusion, we report that decreased STAT3 expression in placentae may contribute to abnormal trophoblast function in idiopathic FGR-affected pregnancies.

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