Background The placenta is the functional interface between the mother and the fetus during pregnancy, and a critical determinant of fetal growth and life-long health. In the first trimester, it develops under a low-oxygen environment, which is essential for the conceptus who has little defense against reactive oxygen species produced during oxidative metabolism. However, failure of invasive trophoblasts to sufficiently remodel uterine arteries toward dilated vessels by the end of the first trimester can lead to reduced/intermittent blood flow, persistent hypoxia and oxidative stress in the placenta with consequences for fetal growth. Fetal growth restriction (FGR) is observed in ∼10% of pregnancies and is frequently seen in association with other pregnancy complications, such as preeclampsia (PE). FGR is one of the main challenges for obstetricians and pediatricians, as smaller fetuses have greater perinatal risks of morbidity and mortality and postnatal risks of neurodevelopmental and cardio-metabolic disorders. Objective and rationale The aim of this review was to examine the importance of placental responses to changing oxygen environments during abnormal pregnancy in terms of cellular, molecular and functional changes in order to highlight new therapeutic pathways, and to pinpoint approaches aimed at enhancing oxygen supply and/or mitigating oxidative stress in the placenta as a mean of optimizing fetal growth. Search methods An extensive online search of peer-reviewed articles using PubMed was performed with combinations of search terms including pregnancy, placenta, trophoblast, oxygen, hypoxia, high altitude, FGR and PE (last updated in May 2020). Outcomes Trophoblast differentiation and placental establishment are governed by oxygen availability/hypoxia in early pregnancy. The placental response to late gestational hypoxia includes changes in syncytialization, mitochondrial functions, endoplasmic reticulum stress, hormone production, nutrient handling and angiogenic factor secretion. The nature of these changes depends on the extent of hypoxia, with some responses appearing adaptive and others appearing detrimental to the placental support of fetal growth. Emerging approaches that aim to increase placental oxygen supply and/or reduce the impacts of excessive oxidative stress are promising for their potential to prevent/treat FGR. Wider implications There are many risks and challenges of intervening during pregnancy that must be considered. The establishment of human trophoblast stem cell lines and organoids will allow further mechanistic studies of the effects of hypoxia and may lead to advanced screening of drugs for use in pregnancies complicated by placental insufficiency/hypoxia. Since no treatments are currently available, a better understanding of placental adaptations to hypoxia would help to develop therapies or repurpose drugs to optimize placental function and fetal growth, with life-long benefits to human health.

Adaptations of the human placenta to hypoxia: opportunities for interventions in fetal growth restriction

Maternal hypothyroidism causes oxidative stress and endoplasmic reticulum stress in the maternal-fetal interface of rats.

PURPOSE Despite immense research highlighting maternal-fetal benefits of exercise during pregnancy, there remain concerns that exercise may undermine placental function. Although maternal exercise has demonstrated favorable aerobic conditioning responses in the mother, it is not known whether maternal exercise promotes increased angiogenesis in the placenta, perhaps at the expense of impaired endoplasmic reticulum (ER) homeostasis and/or oxidative stress. We investigated if a mild (30% heart rate reserve) and/or moderate (70% heart rate reserve) exercise regime in healthy pregnant women affected placental markers of angiogenesis, ER stress, and oxidative stress. We hypothesized that the improved aerobic conditioning of mothers who exercise is beneficial to enhance placental angiogenesis and normal maternal-fetal outcomes. METHODS Placental tissues were collected within 1 h of delivery from a convenience sample of 29 healthy mothers of full-term infants. Twenty-one women participated in routine exercise from midgestation (16-20 wk) until term of either mild or moderate intensity, whereas eight sedentary women served as controls. RESULTS No differences were identified between groups including gestational length, fetal-placental weight ratio, or APGAR scoring. All exercisers exhibited a significant 20-fold increase in the mRNA (as assessed by quantitative real-time polymerase chain reaction) and a 10-fold increase in the protein expression of angiogenin (e.g., ANG1) in the placenta. However, in both exercising groups, no increases in placental markers (i.e., HIF1α, VEGF), ER stress (i.e., spliced XBP1, ATF4, ATF6, CHOP, and BAX), or oxidative stress (i.e., SOD1, SOD2) were observed. CONCLUSIONS Overall, our study suggests that mild- and moderate-intensity exercise increases angiogenesis but does not increase placental oxidative or ER stress in healthy pregnancies, bolstering support for routine exercise as a part of standard care in pregnant women. Future studies are warranted to investigate the potential benefits of exercise on ANG1 in pathological pregnancies.

Exercise in Pregnancy Increases Placental Angiogenin without Changes in Oxidative or Endoplasmic Reticulum Stress.

Endoplasmic reticulum stress mediates osteocyte death under oxygen-glucose deprivation in vitro.

Ectopic pregnancy is an implantation occurring elsewhere than in the cavity of the uterus. It is the leading cause of maternal morbidity and mortality during the first trimester. While the incidence of extrauterine pregnancy has increased in recent years, the rapid development of multi-omics has also provided an effective method of prenatal diagnosis. This book focuses on the diagnosis and treatment of ectopic pregnancy, fetal malformation, and the different screening methods for prenatal diagnosis. 

Prenatal Diagnosis [Working Title]

Intermittent hypoxia (IH) is a prominent characteristic of many clinical complications such as obstructive sleep apnea syndrome (OSAS). OSAS is related to a higher incidence of adverse pregnancy outcomes, and IH has been suggested as the preliminary physiological etiology. However, further studies remain to be performed on the underlying cellular and molecular pathogenic mechanisms of OSAS-related IH on adverse pregnancy outcomes. Here, we used a trophoblast cell line (HTR8/SVneo), primary extravillous trophoblast cells (EVTs), and a normal-term placenta villi explant culture model in vitro in this research. The effects and possible molecular mechanisms of IH on trophoblast motility, cell cycle progression, and apoptosis were investigated. IH reduced HTR8/SVneo cell and EVT motility significantly, which could be partially attributed to the reduced secretion of matrix metalloproteinase 2. IH treatment blocked HTR8/SVneo cell proliferation significantly by modulating the expression of D-type Cyclins. IH also induced significant trophoblast cell apoptosis. Moreover, our study supports the premise that IH attenuates trophoblast cell motility and proliferation and induces excessive trophoblast cell apoptosis by specifically triggering the endoplasmic reticulum (ER) stress signaling pathway. Briefly, differing from the mechanism of trophoblast motility and proliferation inhibition, and apoptosis induction by hypoxia, IH is apt to weaken trophoblast viability mainly by activating the ER stress signaling pathway with a time-dependent pattern, which is further implicated in OSAS-associated adverse pregnancy outcomes.

Intermittent Hypoxia Impairs Trophoblast Cell Viability by Triggering the Endoplasmic Reticulum Stress Pathway.

Trisomy 21 is a common birth defect in humans. Screening for trisomy 21 is one of the most important tasks in routine prenatal care and robust noninvasive diagnostics are needed in clinical practic...

Urinary Proteomics for Noninvasive Prenatal Screening of Trisomy 21: New Biomarker Candidates.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Lei Gao

Author Tools

Chat about Author

Papers

Intermittent Hypoxia Impairs Trophoblast Cell Viability by Triggering the Endoplasmic Reticulum Stress Pathway.

Urinary Proteomics for Noninvasive Prenatal Screening of Trisomy 21: New Biomarker Candidates.