526. GENETIC POLYMORPHISMS IN INTERLEUKIN-1 FAMILY MEMBERS AND PREGNANCY OUTCOME

2009 ◽  
Vol 21 (9) ◽  
pp. 125
Author(s):  
R. C. Nowak ◽  
S. D. Thompson ◽  
J. Zhang ◽  
G. A. Dekker ◽  
C. T. Roberts
Keyword(s):  
Pregnancy Outcome ◽  
Head Circumference ◽  
Interleukin 1 ◽  
Competitive Inhibitor ◽  
Placental Weight ◽  
Trophoblast Invasion ◽  
Placental Development ◽  
Maternal Genotype ◽  
And Function ◽  
Fetal Genotype

Poor placental development is associated with a variety of common, potentially life-threatening pregnancy complications, including preeclampsia (PE) and small-for-gestational-age (SGA) babies. The placenta and fetus express a combination of maternal and paternal genes. Interleukin-1 alpha (IL-1α) and -1 beta (IL-1β) promote trophoblast invasion by upregulating expression of matrix metalloproteinases, while interleukin-1 receptor antagonist (IL-1RN) acts as a competitive inhibitor of IL-1 a and IL-1β by binding to the IL-1 receptor. We hypothesis that polymorphisms which decrease IL-1 activity, within IL-1α rs1800587 (C-allele) and rs17561 (T-allele), IL-1β rs16944 (C-allele) and IL-1RN rs454078 (A-allele) affect placental development and thus pregnancy outcome. To determine the effect of the IL-1 SNPs on pregnancy outcome, blood was collected prospectively from pregnant women at 15 weeks gestation and from their partners and babies at birth. DNA was extracted and genotyped by Sequenom MassArray. Pregnancies were fully characterised and classified into control or PE, PE+SGA, SGA after delivery by an experienced obstetrician. The IL-1α rs1800587 fetal genotype was associated with PE+SGA and smaller head circumference at birth. IL-1α rs17561 fetal genotype was associated with PE+SGA, and a smaller head circumference and body length at birth. The frequency of IL-1β C-allele was associated with PE in neonates, and in fathers the CC homozygote genotype was associated with decreased placental weight at birth. The IL-1RN rs454078 maternal genotype was associated with PE and maternal waist circumference while fetal AA genotype was associated with SGA and decreased placental weight at birth. Genotypes which decrease the production of IL-1α and IL-1β while increasing IL-1RN will reduce proinflammatory cytokines and thereby affect the invasive potential of placental trophoblasts. We have shown that these polymorphisms in both parents may be associated with poor pregnancy outcome. Suggesting that both partners contribute to placental differentiation and function.

scholarly journals Comparative studies of placentation and immunology in non-human primates suggest a scenario for the evolution of deep trophoblast invasion and an explanation for human pregnancy disorders

Reproduction ◽  
2011 ◽  
Vol 141 (4) ◽  
pp. 391-396 ◽  
Author(s):  
Anthony M Carter
Keyword(s):  
Human Interaction ◽  
Trophoblast Invasion ◽  
Old World Monkeys ◽  
Reproductive Disorders ◽  
Old World ◽  
Human Pregnancy ◽  
Uterine Natural Killer Cells ◽  
Maternal Genotype ◽  
Increased Risk ◽  
Fetal Genotype

Deep trophoblast invasion in the placental bed has been considered the hallmark of human pregnancy. It occurs by two routes, interstitial and endovascular, and results in transformation of the walls of the spiral arteries as they traverse the decidua and the inner third of the myometrium. Disturbances in this process are associated with reproductive disorders such preeclampsia. In contrast, trophoblast invasion in Old World monkeys occurs only by the endovascular route and seldom reaches the myometrium. Recently, it was shown that this pattern is maintained in gibbons, but that the human arrangement also occurs in chimpanzee and gorilla. There is an interesting parallel with results from placental immunology regarding the evolution of the major histocompatability complex class I antigen HLA-C and its cognate receptors. HLA-C is not present in Old World monkeys or gibbons. It emerged in the orangutan and became polymorphic in the lineage leading to gorilla, bonobo, chimpanzee, and human. Interaction between HLA-C1 and HLA-C2 on the surface of trophoblast and killer immunoglobulin-like receptors (KIRs) expressed by uterine natural killer cells are important regulators of trophoblast invasion. Evolution of this system in great apes may have been one prerequisite for deep trophoblast invasion but seems to have come at a price. The evidence now suggests that certain combinations of maternal genotype for KIRs and fetal genotype for HLA-C imply an increased risk of preeclampsia, fetal growth restriction, and recurrent abortion. The fetal genotype is in part derived from the father providing an explanation for the paternal contribution to reproductive disorders.

scholarly journals Alpha-1 Antitrypsin-Induced Endoplasmic Reticulum Stress Promotes Invasion by Extravillous Trophoblasts

2021 ◽  
Vol 22 (7) ◽  
pp. 3683
Author(s):  
Kanoko Yoshida ◽  
Kazuya Kusama ◽  
Yuta Fukushima ◽  
Takako Ohmaru-Nakanishi ◽  
Kiyoko Kato ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cell Invasion ◽  
Trophoblast Invasion ◽  
Placental Development ◽  
Functional Link ◽  
Inflammatory Conditions ◽  
Decidual Cells ◽  
Alpha 1 Antitrypsin ◽  
And Function

Alpha-1 antitrypsin (A1AT) is a glycoprotein that has been shown to protect tissues from proteolytic damage under various inflammatory conditions. Several studies show that A1AT may be associated with pre-eclampsia. However, the role of A1AT expression in placental physiology is not fully understood. In the present study, we aim to characterize the expression and function of placental A1AT. A1AT knockdown is found to reduce the expression of the serine protease HTRA1 in a trophoblast cell line. In addition, A1AT overexpression (A1AT-OE) increases the expression of HTRA1, IL6, CXCL8, and several markers of endoplasmic reticulum (ER) stress. Treatment with tunicamycin or thapsigargin, which induces ER stress, increases HTRA1 expression. Furthermore, immunohistochemistry reveals that HTRA1 is expressed in trophoblasts and the endometrial decidual cells of human placentas. An invasion assay shows that A1AT and HTRA1 stimulate cell invasion, but treatment with the ER stress inhibitors reduces the expression of HTRA1 and ER stress markers and prevents cell invasion in A1AT-OE trophoblasts. These results suggest that endogenous A1AT regulates inflammatory cytokine expression and HTRA1-induced trophoblast invasion via the induction of ER stress. It is concluded that an imbalance in the functional link between A1AT and ER stress at the maternal–fetal interface might cause abnormal placental development.

Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions

2020 ◽  
Vol 19 (2) ◽  
pp. 176-192
Author(s):  
Samantha Bedell ◽  
Janine Hutson ◽  
Barbra de Vrijer ◽  
Genevieve Eastabrook
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Maternal Obesity ◽  
Environmental Changes ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Placental Development ◽  
Exchange Site ◽  
And Function

: Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations.

scholarly journals 323: Pravastatin improves pregnancy outcome and placental development in heme oxygenase-1 deficient mice

2018 ◽  
Vol 218 (1) ◽  
pp. S202-S203
Author(s):  
Abraham Tsur ◽  
Flora Kalish ◽  
Jordan Burgess ◽  
Hui Zhao ◽  
Kerriann Casey ◽  
...  
Keyword(s):  
Pregnancy Outcome ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Placental Development ◽  
Deficient Mice

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.

scholarly journals Modelling the Human Placental Interface In Vitro—A Review

Micromachines ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 884
Author(s):  
Marta Cherubini ◽  
Scott Erickson ◽  
Kristina Haase
Keyword(s):  
Drug Testing ◽  
Cell Types ◽  
In Vitro Models ◽  
Placental Development ◽  
Scientific Challenge ◽  
Induced Pluripotent ◽  
And Function ◽  
And Control

Acting as the primary link between mother and fetus, the placenta is involved in regulating nutrient, oxygen, and waste exchange; thus, healthy placental development is crucial for a successful pregnancy. In line with the increasing demands of the fetus, the placenta evolves throughout pregnancy, making it a particularly difficult organ to study. Research into placental development and dysfunction poses a unique scientific challenge due to ethical constraints and the differences in morphology and function that exist between species. Recently, there have been increased efforts towards generating in vitro models of the human placenta. Advancements in the differentiation of human induced pluripotent stem cells (hiPSCs), microfluidics, and bioprinting have each contributed to the development of new models, which can be designed to closely match physiological in vivo conditions. By including relevant placental cell types and control over the microenvironment, these new in vitro models promise to reveal clues to the pathogenesis of placental dysfunction and facilitate drug testing across the maternal–fetal interface. In this minireview, we aim to highlight current in vitro placental models and their applications in the study of disease and discuss future avenues for these in vitro models.

Epigenetics of Placental Development and Function

2014 ◽  
pp. 285-295
Author(s):  
Shuhei Ito ◽  
Mitsuko Hirosawa ◽  
Koji Hayakawa ◽  
Shintaro Yagi ◽  
Satoshi Tanaka ◽  
...  
Keyword(s):  
Placental Development ◽  
And Function

scholarly journals The Ontogeny and Function of Placental Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Jake R. Thomas ◽  
Praveena Naidu ◽  
Anna Appios ◽  
Naomi McGovern
Keyword(s):  
Human Placenta ◽  
Outer Layer ◽  
New Technologies ◽  
Placental Development ◽  
Fetal Health ◽  
Hofbauer Cells ◽  
Recent Developments ◽  
Placental Macrophages ◽  
And Function ◽  
Insight Into

The placenta is a fetal-derived organ whose function is crucial for both maternal and fetal health. The human placenta contains a population of fetal macrophages termed Hofbauer cells. These macrophages play diverse roles, aiding in placental development, function and defence. The outer layer of the human placenta is formed by syncytiotrophoblast cells, that fuse to form the syncytium. Adhered to the syncytium at sites of damage, on the maternal side of the placenta, is a population of macrophages termed placenta associated maternal macrophages (PAMM1a). Here we discuss recent developments that have led to renewed insight into our understanding of the ontogeny, phenotype and function of placental macrophages. Finally, we discuss how the application of new technologies within placental research are helping us to further understand these cells.

scholarly journals The Dynamics of Cullin-1 Expression in Preeclamptic Placenta and its Association with Pregnancy Termination Time

2020 ◽  
Vol 8 (B) ◽  
pp. 210-215
Author(s):  
Makbruri Makbruri ◽  
Isabella Kurnia Liem ◽  
Ahmad Aulia Jusuf ◽  
Tantri Hellyanti
Keyword(s):  
Gestational Age ◽  
Pregnancy Termination ◽  
Age Groups ◽  
Trophoblast Invasion ◽  
Age Group ◽  
Placental Development ◽  
Very Preterm ◽  
Significant Difference ◽  
Cellular Factors ◽  
Termination Time

BACKGROUND: Preeclampsia is a systemic syndrome occurring in 3–5% of pregnancies, caused by disorders of cellular factors resulting in the disruption of trophoblast differentiation and invasion which is important for the placental development and maintaining pregnancy. Cullin-1 is a protein that plays a role in the process of maintaining pregnancy, development, and trophoblast invasion in the placenta. Until now, there have been no studies linking the expression of cullin-1 in preeclamptic patients with the timing of pregnancy termination. AIM: This study analyzed cullin-1 expression in preeclamptic patients and their relationship to the timing of pregnancy termination was carried out. METHODS: Placental samples were taken from preeclampsia patients consisting of three gestational age groups, then immunohistochemical staining was performed to see the dynamics of expression and distribution in each age group of pregnancy and to find out their relationship with the timing of pregnancy termination. RESULTS: Cullin-1 was expressed in syncytiotrophoblasts and cytotrophoblasts. The lowest cullin-1 level was obtained in the very preterm age group, and the highest was found in the moderate preterm gestational age group. There was a significant difference between cullin-1 optical density (OD) expression and termination time of pregnancy, and there was a significant difference (OD) in cullin-1 preeclamptic patients with very preterm gestational age with moderate preterm gestational age. CONCLUSION: Cullin-1 was expressed both in syncytiotrophoblasts and cytotrophoblasts and was associated with the timing of pregnancy termination.

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