Sexually dimorphic patterns in maternal circulating microRNAs in pregnancies complicated by fetal growth restriction.

Background: Current methods fail to accurately predict women at greatest risk of developing fetal growth restriction (FGR) or related adverse outcomes, including stillbirth. Sexual dimorphism in these adverse pregnancy outcomes is well documented as are sex-specific differences in gene and protein expression in the placenta. Circulating maternal serum microRNAs (miRNAs) offer potential as biomarkers that may also be informative of underlying pathology.

Interaction between Metformin, Folate and Vitamin B and the Potential Impact on Fetal Growth and Long-Term Metabolic Health in Diabetic Pregnancies.

Metformin is the first-line treatment for many people with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to maintain glycaemic control. Recent evidence suggests metformin can cross the placenta during pregnancy, thereby exposing the fetus to high concentrations of metformin and potentially restricting placental and fetal growth. Offspring exposed to metformin during gestation are at increased risk of being born small for gestational age (SGA) and show signs of 'catch up' growth and obesity during childhood which increases their risk of future cardiometabolic diseases.

Hypoxia and oxidative stress induce sterile placental inflammation in vitro.

Fetal growth restriction (FGR) and stillbirth are associated with placental dysfunction and inflammation and hypoxia, oxidative and nitrative stress are implicated in placental damage. Damage-associated molecular patterns (DAMPs) are elevated in pregnancies at increased risk of FGR and stillbirth and are associated with increase in pro-inflammatory placental cytokines. We hypothesised that placental insults lead to release of DAMPs, promoting placental inflammation.

Placental Morphology and Cellular Characteristics in Stillbirths in Women With Diabetes and Unexplained Stillbirths.

Context.—: Women with diabetes have increased stillbirth risk. Although the underlying pathophysiological processes are poorly understood, stillbirth is frequently related to abnormal placental structure and function.

Increased placental macrophages and a pro-inflammatory profile in placentas and maternal serum in infants with a decreased growth rate in the third trimester of pregnancy.

Problem: There is growing evidence for the role of placental inflammation in the pathophysiology of pregnancy complications including fetal growth restriction (FGR). This study aimed to characterize the inflammatory profile in the maternal circulation and the placenta of infants who were growth restricted and those that were small for gestational age (SGA).

Method Of Study: Placental villous tissue and maternal serum were obtained from pregnancies where infants were SGA at birth or who had a decreasing growth rate (≥25 centiles) across the third trimester.

Effects of hydroxychloroquine on the human placenta-Findings from in vitro experimental data and a systematic review.

Hydroxychloroquine (HCQ), a toll like receptor (TLR) 7 and 9 antagonist, is used during pregnancy for inflammatory conditions with limited understanding of its placental toxicology. We hypothesized that HCQ does not have toxic effects on the placenta and can modulate cytokine release in response to TLR7/9 activation. A systematic review was conducted and no studies of HCQ on multicellular human placental tissue were identified.

MicroRNA changes in maternal serum from pregnancies complicated by twin-twin transfusion syndrome: A discovery study.

Objective: MicroRNAs (miRNAs) are used as biomarkers in cardiovascular disease and cancer. miRNAs are involved in placental development but have not previously been investigated in twin-twin transfusion syndrome (TTTS). Our aim is to explore the miRNA profile of TTTS pregnancies.

Effects of micronutrients on placental function: evidence from clinical studies to animal models.

Micronutrient deficiencies are common in pregnant women due to low dietary intake and increased requirements for fetal development. Low maternal micronutrient status is associated with a range of pregnancy pathologies involving placental dysfunction, including fetal growth restriction (FGR), small-for-gestational age (SGA), pre-eclampsia and preterm birth. However, clinical trials commonly fail to convincingly demonstrate beneficial effects of supplementation of individual micronutrients, attributed to heterogeneity and insufficient power, potential interactions and lack of mechanistic knowledge of effects on the placenta.

Placental dysfunction is associated with altered microRNA expression in pregnant women with low folate status.

Scope: Low maternal folate status during pregnancy increases the risk of delivering small for gestational age (SGA) infants, but the mechanistic link between maternal folate status, SGA, and placental dysfunction is unknown. microRNAs (miRNAs) are altered in pregnancy pathologies and by folate in other systems. We hypothesized that low maternal folate status causes placental dysfunction, mediated by altered miRNA expression.

eNOS knockout mouse as a model of fetal growth restriction with an impaired uterine artery function and placental transport phenotype.

Fetal growth restriction (FGR) is the inability of a fetus to reach its genetically predetermined growth potential. In the absence of a genetic anomaly or maternal undernutrition, FGR is attributable to "placental insufficiency": inappropriate maternal/fetal blood flow, reduced nutrient transport or morphological abnormalities of the placenta (e.g.