scholarly journals A role for maternally derived myokines to optimize placental function and fetal growth across gestation

2017 ◽  
Vol 42 (5) ◽  
pp. 459-469 ◽  
Author(s):  
Chantal Dubé ◽  
Céline Aguer ◽  
Kristi Adamo ◽  
Shannon Bainbridge
Keyword(s):  
Protective Effect ◽  
Fetal Growth ◽  
Skeletal Muscles ◽  
Strong Support ◽  
Therapeutic Interventions ◽  
Placental Development ◽  
Maternal Exercise ◽  
Exercise Induced ◽  
And Function ◽  
Exercise During Pregnancy

Exercise during pregnancy is associated with improved health outcomes for both mother and baby, including a reduced risk of future obesity and susceptibility to chronic diseases. Overwhelming evidence demonstrates a protective effect of maternal exercise against fetal birth weight extremes, reducing the rates of both large- and small-for-gestational-age infants. It is speculated that this protective effect is mediated in part through exercise-induced regulation of maternal physiology and placental development and function. However, the specific mechanisms through which maternal exercise regulates these changes remain to be discovered. We hypothesize that myokines, a collection of peptides and cytokines secreted from contracting skeletal muscles during exercise, may be an important missing link in the story. Myokines are known to reduce inflammation, improve metabolism and enhance macronutrient transporter expression and activity in various tissues of nonpregnant individuals. Little research to date has focused on the specific roles of the myokine secretome in the context of pregnancy; however, it is likely that myokines secreted from exercising skeletal muscles may modulate the maternal milieu and directly impact the vital organ of pregnancy—the placenta. In the current review, data in strong support of this potential role of myokines will be presented, suggesting myokine secretion as a key mechanism through which maternal exercise optimizes fetal growth trajectories. It is clear that further research is warranted in this area, as knowledge of the biological roles of myokines in the context of pregnancy would better inform clinical recommendations for exercise during pregnancy and contribute to the development of important therapeutic interventions.

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.

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.

Placental control of fetal growth

1995 ◽  
Vol 7 (3) ◽  
pp. 333 ◽  
Author(s):  
J Robinson ◽  
S Chidzanja ◽  
K Kind ◽  
F Lok ◽  
P Owens ◽  
...  
Keyword(s):  
Growth Factors ◽  
Fetal Growth ◽  
Placental Development ◽  
Maternal Environment ◽  
Adult Disease ◽  
Prenatal Growth ◽  
And Function ◽  
Subsequent Risk ◽  
Length Of Gestation ◽  
Insulin Like Growth Factors

The placenta exerts its effects on the growth of the fetus from the beginning of pregnancy via metabolic and endocrine mechanisms. To achieve this, the placenta exchanges a wide array of nutrients, endocrine signals, cytokines and growth factors with the mother and the fetus. These exchanges modulate or programme fetal growth and development. This review concentrates on the function and structure of the placenta in humans and in animals, and the effects of experimental perturbation of placental size and function on fetal growth. The consequences for fetal growth of varying the abundance of peptides or, by deleting genes, insulin-like growth factors or cytokines, are also described. Maternal nutritional and hormonal state from as early as the first few days after fertilization, can influence the growth rate of the placenta and the fetus and also the length of gestation. Influences on placental development and their consequences will clearly have an impact on the placental control of fetal growth. Variations in the maternal environment and consequent perturbation of the metabolic and endocrine environment of the placenta and fetus are implicated as being responsible for the associations between prenatal growth of the placenta and its fetus and the subsequent risk of adult disease. The next challenge will be to determine the dominant influences at each stage of fetal and placental growth.

Maternal Methyl-Cycle Amino Acid Profile and Kinetics: Relation with Placental Growth

2017 ◽  
Vol 54 (2) ◽  
pp. 118
Author(s):  
Sarita Devi ◽  
Julian Crasta ◽  
Tinku Thomas ◽  
Pratibha Dwarkanath ◽  
Annamma Thomas ◽  
...  
Keyword(s):  
Amino Acid ◽  
Pregnant Women ◽  
Fetal Growth ◽  
Secondary Analysis ◽  
Placental Development ◽  
Amino Acid Availability ◽  
South Indian ◽  
Methyl Cycle ◽  
And Function ◽  
Amino Acid Concentrations

Maternal intake of quality protein regulates placental development and function thereby affecting fetal growth. Considering the prevalence of inadequate intakes of quality protein in Indian pregnant women, understanding the interplay between maternal supply of protein, its metabolism and fetoplacental growth becomes important. A secondary analysis of data from an open labelled-randomized intervention trial with 500 ml milk/day on south Indian pregnant women with marginally low vitamin B12 status, was performed to assess the relations between placental parameters and maternal trimester 3 methyl-cycle amino acid status as well as kinetics. This analysis was performed for 42 pregnancies from the trial where placentae had been collected and placental parameters had been measured. For these pregnancies, data on trimester 3 methionine, serine and glycine kinetics as well as plasma free amino acid concentrations were available. Protein intake and plasma citrulline concentrations were positively correlated at trimester 3 (ρ = 0.34, P = 0.027). Placental weight correlated positively with methyl-cycle specific amino acid concentrations [methionine (ρ = 0.32, P = 0.0388), serine (ρ = 0.49, P = 0.0009)], methionine kinetics [total methionine flux rates (ρ = 0.42, P = 0.006), RM (ρ = 0.45, P = 0.003), TS (ρ = 0.32, P = 0.046), TM (ρ = 0.45, P = 0.004)] and with birth weight (ρ = 0.57, P < 0.001). Findings from the current study indicate that maternal amino acid availability and more importantly, maternal methionine kinetics, positively influenced placental growth, likely mediated by key amino acids such as citrulline, which is known to regulate placental blood flow and function. As an appropriately functioning placenta is indispensable for fetal growth, these findings will form the basis for detailed mechanistic explorations into the placental regulation of maternal supply of amino acid to the fetus for designing effective intervention strategies towards optimizing fetomaternal health during and after pregnancy.

scholarly journals Maternal growth factor regulation of human placental development and fetal growth

2010 ◽  
Vol 207 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Karen Forbes ◽  
Melissa Westwood
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Fetal Growth ◽  
Mechanism Of Action ◽  
Normal Development ◽  
Receptor Interaction ◽  
Placental Development ◽  
Maternal Circulation ◽  
Successful Pregnancy ◽  
And Function

Normal development and function of the placenta is critical to achieving a successful pregnancy, as normal fetal growth depends directly on the transfer of nutrients from mother to fetus via this organ. Recently, it has become apparent from both animal and human studies that growth factors within the maternal circulation, for example the IGFs, are important regulators of placental development and function. Although these factors act via distinct receptors to exert their effects, the downstream molecules activated upon ligand/receptor interaction are common to many growth factors. The expression of numerous signaling molecules is altered in the placentas from pregnancies affected by the fetal growth complications, fetal growth restriction, and macrosomia. Thus, targeting these molecules may lead to more effective treatments for complications of pregnancy associated with altered placental development. Here, we review the maternal growth factors required for placental development and discuss their mechanism of action.

scholarly journals Abnormalities of placental development and function are associated with the different fetal growth patterns of hypoplastic left heart syndrome and transposition of the great arteries

2018 ◽  
Author(s):  
Weston Troja ◽  
Kathryn J. Owens ◽  
Jennifer Courtney ◽  
Andrea C. Hinton ◽  
Robert B. Hinton ◽  
...  
Keyword(s):  
Hypoplastic Left Heart Syndrome ◽  
Fetal Growth ◽  
Weight Ratio ◽  
Growth Patterns ◽  
Left Heart ◽  
Placental Development ◽  
Hypoplastic Left Heart ◽  
Terminal Villi ◽  
And Function ◽  
Left Heart Syndrome

AbstractBackgroundBirthweight is a critical predictor of congenital heart disease (CHD) surgical outcomes. Hypoplastic left heart syndrome (HLHS) is cyanotic CHD with known fetal growth restriction and placental abnormalities. Transposition of the great arteries (TGA) is cyanotic CHD with normal fetal growth. Comparison of the placenta in these diagnoses may provide insights on the fetal growth abnormality of CHD.MethodsClinical data and placental histology from placentas associated with Transposition of the Great Arteries (TGA) were analyzed for gross pathology, morphology, maturity and vascularity and compared to both control and previously analyzed HLHS placentas [1]. RNA was isolated from HLHS, TGA and control placentas and sequenced by Illumina HiSeq.Gene, analysis was performed using TopHat, R and MSigDB. Cluster analysis was performed using GoElite and Pathway analysis performed using PANTHERdb Overrepresentation Test. Immunohistochemistry was utilized to assess placental nutrient transporter expression in all three groups.ResultsPlacental weight was reduced in TGA cases, and demonstrated reduced villous vasculature, immature terminal villi, and increased fibrin deposition in the parenchyma compared to controls and reflected our previous data from HLHS placentas. However, birth weight was not reduced in TGA cases compared to controls in contrast to the HLHS cohort and birthweight:placental weight ratio was significantly increased in TGA cases but not HLHS compared to control. Need to include RNA and IHC.ConclusionsDespite common vascular disturbances in placentas from HLHAs and TGA, these do not account for the

Adaptability and potential for treatment of placental functions to improve embryonic development and postnatal health

2016 ◽  
Vol 28 (2) ◽  
pp. 75 ◽  
Author(s):  
James C. Cross
Keyword(s):  
Fetal Growth ◽  
Growth And Development ◽  
Association Studies ◽  
Experimental Studies ◽  
Placental Development ◽  
Experimental Animals ◽  
And Function ◽  
The Impact ◽  
Lines Of Evidence ◽  
In Pregnancy

For an organ that is so critical for life in eutherian mammals, the placenta hardly gets the attention that it deserves. The placenta does a series of remarkable things, including implanting the embryo in the uterus, negotiating with the mother for nutrients but also protecting her health during pregnancy, helping establish normal metabolic and cardiovascular function for life postnatally (developmental programming) and initiating changes that prepare the mother to care for and suckle her young after birth. Different lines of evidence in experimental animals suggest that the development and function of the placenta are adaptable. This means that some of the changes observed in pathological pregnancies may represent attempts to mitigate the impact of fetal growth and development. Key and emerging concepts are reviewed here concerning how we may view the placenta diagnostically and therapeutically in pregnancy complications, focusing on information from experimental studies in mice, sheep and cattle, as well as association studies from humans. Hundreds of different genes have been shown to underlie normal placental development and function, some of which have promise as tractable targets for intervention in pregnancies at risk for poor fetal growth.

Maternal Exercise during Pregnancy, Physical Fitness, and Fetal Growth

1993 ◽  
Vol 137 (10) ◽  
pp. 1105-1114 ◽  
Author(s):  
Maureen C. Hatch ◽  
Xiao-Ou Shu ◽  
Diane E. McLean ◽  
Bruce Levin ◽  
Melissa Begg ◽  
...  
Keyword(s):  
Physical Fitness ◽  
Fetal Growth ◽  
Maternal Exercise ◽  
Exercise During Pregnancy

scholarly journals Influence of exercise-induced maternal stress on fetal outcome in Wistar rats: Inter-generational effects

1995 ◽  
Vol 73 (5) ◽  
pp. 645-653 ◽  
Author(s):  
Martina L. Pinto ◽  
P. S. Shetty
Keyword(s):  
Wistar Rats ◽  
Cumulative Effect ◽  
Fetal Outcome ◽  
Exercise Stress ◽  
Generational Effects ◽  
Pregnancy And Lactation ◽  
Maternal Exercise ◽  
Exercise Induced ◽  
Successive Generations ◽  
Exercise During Pregnancy

The effects of physical activity during pregnancy and lactation on the fetal outcome and the growth of pups was studied in Wistar rats (n 144). Rats were trained to swim for 2 h every day, 6 dsweek through pre-pregnancy, pregnancy and lactation. Maternal exercise during pregnancy, despite the dams having ad lib. access to food, resulted in low-birth-weight pups (5·6 (SD 0·7) g; n 178 in exercised dams v. 6·2(SD 0·8)g; n 238 in sedentary dams). Maternal exercise continued through lactation exaggerated further the growth retardation of these pups (30·0 (SD 4·7) g; n 78 in exercised dams v. 36·0 (SD 6·9) g; n 126 in sedentary dams). The effects of maternal exercise during pregnancy and lactation studied over two successive generations revealed a reduction in the growth rates of the second generation progeny of both exercised (5·3 (SD 0·9) g; n 125 at birth and 25·1 (SD 6·8) g; n 54 at weaning) and sedentary rats (6·0 (SD 0·2) g; n 110 at birth and 31·3 (SD 4·3) g at weaning) born to first-generation exercised rats. While slower growth in the former indicates a cumulative effect of exercise stress over two generations, that of the latter indicates that the generational effects are manifest even though the dams of the F1 generation were not exposed to exercise stress during pregnancy and lactation. These findings suggest that the adverse effect of maternal exercise during pregnancy and lactation on fetal outcome in one generation is transferred to the subsequent generation.

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