scholarly journals Maternal intermittent fasting during pregnancy induces fetal growth restriction and downregulated placental system A amino acid transport in the rat

2021 ◽  
Author(s):  
Alaa Alkhalefah ◽  
Warwick Dunn ◽  
James W Allwood ◽  
Kate L Parry ◽  
Franchesca Houghton ◽  
...  

During Ramadan, many pregnant Muslim women fast between dawn and sunset. Although the impacts of prolonged maternal intermittent fasting (IF) on fetal growth and placental function are under-researched, reported effects include reduced placental weight and birth weight. In this study, pregnant Wistar rats were used to model repeated cycles of IF on fetal development and placental function and to examine sex-specific effects. In the IF group, food was withdrawn daily from 17:00 to 09:00 over 21 days of gestation, while the control group received food ad libitum. Both groups had free water access. IF dams consumed less food, had significantly reduced weight compared to controls, with reduced plasma glucose and amino acids. Both fetal sexes were significantly lighter in the IF group, with reduced fetal plasma amino acids. Placental weights and morphology were unchanged. The profile of placental metabolites was altered in the IF group with sex-specific responses evident. Transplacental flux of 14C-methylaminoisobutyric acid (14C-MeAIB), a system A amino acid transporter substrate, was significantly reduced in both fetal sexes in the IF group. Sodium-dependent 14C-MeAIB uptake into isolated placental plasma membrane vesicles was unchanged. The gene expression of system A transporter Slc38a1, Slc38a2 and Slc38a4 was upregulated in IF male placentas only. No changes were observed in placental SNAT1 and SNAT2 protein expression. Maternal IF results in detrimental impacts on maternal physiology and fetal development, with changes in the placental and fetal metabolite profiles. Reduced placental system A transporter activity may be responsible for fetal growth restriction in both sexes.

2017 ◽  
Vol 63 (3) ◽  
pp. 266-271 ◽  
Author(s):  
T.N. Pogorelova ◽  
V.O. Gunko ◽  
V.V. Avrutskaya ◽  
L.V. Kaushanskaya ◽  
O.A. Durnitsyna

The content of the amino acids in the placenta during physiological pregnancy and fetal growth restriction (FGR) has been investigated my means of the method of ion-exchange chromatography. It has been found that in FGR the placental amino acid pool is characterized by a decreased content of arginine, proline, alanine, serine, cysteine, methionine, tryptophan, leucine, threonine, tyrosine, phenylalanine, glutamine and an increased content of dicarboxylic amino acids, lysine, histidine and glycine. These changes are accompanied by altered activity of some enzymes of amino acid metabolism, and the degree of these changes correlates with the level of corresponding amino acids.


2002 ◽  
Vol 282 (1) ◽  
pp. C153-C160 ◽  
Author(s):  
Stuart Cramer ◽  
Mark Beveridge ◽  
Michael Kilberg ◽  
Donald Novak

Fetal growth and development are dependent on the delivery of amino acids from maternal amino acid pools to the fetal blood. This is accomplished via transfer across the apical and basal plasma membrane of the placental syncytiotrophoblast. The aim of this study was to determine whether inhibition of system A (amino acid transporter) was associated with a decrease in fetal weight in the rat. System A is a ubiquitous Na+-dependent amino acid transporter that actively transports small zwitterionic amino acids. In brief, system A was inhibited by infusing a nonmetabolizable synthetic amino acid analog, 2-(methylamino)isobutyric acid from days 7–20 of gestation. On day 20, the rats were killed and tissues (maternal liver, fetuses, and placentas) were collected for analysis. The degree of system A inhibition was determined, as was the impact of said inhibition on fetal and maternal weights, system A-mediated placental transport, and placental system A-mediated transporter expression. Our results suggest that when system A is inhibited, fetal weight is diminished [control group: −3.55 ± 0.04 g ( n = 113), experimental group: −3.29 ± 0.04 g ( n = 128)], implying an integral role for system A transport in fetal growth and development in the rat.


2021 ◽  
Vol 74 (2) ◽  
pp. 213-219
Author(s):  
Varvara A. Berezhna ◽  
Tetiana V. Mamontova ◽  
Antonina M. Gromova

The aim: To elucidate the possible involvement of M1 and M2 macrophages in the placentas of women, whose pregnancies were complicated by fetal growth restriction (FGR) and resulted in term births after 37 weeks of gestation and preterm births up to 37 weeks of gestation. Materials and methods: CD68+ and CD163+ macrophages were studied by immunohistochemical method, placental morphology in the placentas of 16 women whose pregnancies were complicated by FGR and resulted in term births at a gestational age after 37 weeks (1-st group, n = 7) or resulted in preterm births at a gestational age up to 37 weeks (2-nd group, n = 9). The control group consisted of 10 placentas of women with physiological pregnancies and births. Results: Women 2-nd group showed significantly low weight of the placenta, a short gestation period at the time of delivery, and a prolonged labor period than women of the control group (p <0.001; p <0.001; p <0.05, respectively). The level of CD68+ and CD163+ macrophages in the placentas of women 2-nd group was significantly higher than in woman 1-st group (p <0.001, p <0.001, respectively). A significant correlation was found between the expression level of CD68+ monocytes in the intervillous space and the weight of a newborn (r = – 0.765; p = 0.016) in women 2-nd group. Conclusions: These studies suggest that in the placentas of women whose pregnancies were complicated by FGR and resulted in preterm births, the increased activation of CD68+ macrophages of the pro-inflammatory pool may be associated with disorders of the vascular and stromal component of the villous chorion with the development of involutive and dystrophic changes. In general, this fact probably determines the progress of chronic placental insufficiency and aggravates the development of fetal growth restriction.


2021 ◽  
Vol 9 ◽  
Author(s):  
Salvatore Tagliaferri ◽  
Pasquale Cepparulo ◽  
Antonio Vinciguerra ◽  
Marta Campanile ◽  
Giuseppina Esposito ◽  
...  

Current tests available to diagnose fetal hypoxia in-utero lack sensitivity thus failing to identify many fetuses at risk. Emerging evidence suggests that microRNAs derived from the placenta circulate in the maternal blood during pregnancy and may be used as non-invasive biomarkers for pregnancy complications. With the intent to identify putative markers of fetal growth restriction (FGR) and new therapeutic druggable targets, we examined, in maternal blood samples, the expression of a group of microRNAs, known to be regulated by hypoxia. The expression of microRNAs was evaluated in maternal plasma samples collected from (1) women carrying a preterm FGR fetus (FGR group) or (2) women with an appropriately grown fetus matched at the same gestational age (Control group). To discriminate between early- and late-onset FGR, the study population was divided into two subgroups according to the gestational age at delivery. Four microRNAs were identified as possible candidates for the diagnosis of FGR: miR-16-5p, miR-103-3p, miR-107-3p, and miR-27b-3p. All four selected miRNAs, measured by RT-PCR, resulted upregulated in FGR blood samples before the 32nd week of gestation. By contrast, miRNA103-3p and miRNA107-3p, analyzed between the 32nd and 37th week of gestation, showed lower expression in the FGR group compared to aged matched controls. Our results showed that measurement of miRNAs in maternal blood may form the basis for a future diagnostic test to determine the degree of fetal hypoxia in FGR, thus allowing the start of appropriate therapeutic interventions to alleviate the burden of this disease.


Author(s):  
Manel Mendoza ◽  
Raquel Ferrer-Oliveras ◽  
Erika Bonacina ◽  
Pablo Garcia-Manau ◽  
Carlota Rodo ◽  
...  

Objective This study aimed to analyze the effect of pravastatin on angiogenic factors, feto–maternal Doppler findings and pregnancy outcomes in women with early-onset fetal growth restriction (FGR) treated with pravastatin compared with nontreated controls. Study Design This was a pilot study conducted between March 2016 and September 2017. Women with single pregnancies and FGR diagnosed at ≤ 28 weeks of gestation were offered 40 mg of pravastatin daily. Doppler progression, soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) values, and pregnancy outcomes were assessed and compared with consecutive historical controls. Controls were matched to treated women for gestational age, maternal characteristics, maternal and obstetric history, Doppler severity classification, and angiogenic factors at diagnosis. The sFlt-1/PlGF was measured in maternal serum at two different times: before pravastatin was started (ratio M0) and during pravastatin treatment (ratio M1). Doppler severity was classified into four categories: normal, mild, moderate, and severe. Results A total of 38 women were enrolled in this study. No differences were observed in baseline characteristics between groups. However, when compared with the ratio M0, M1 was increased by a median (interquartile range) of 67.0 (−34.8 to 197.3) in the control group but decreased by a median (interquartile range) of −10.1 (−53.1 to −0.07) in the pravastatin treated group (p < 0.001). No significant differences were observed in Doppler progression throughout pregnancy. Median interval from diagnosis to delivery was extended by 16.5 days, the median newborn birthweight was increased from 1,040 to 1,300 g, and the number of women with preeclampsia decreased from 9 (47.4%) to 6 (31.6%) in treated women; however, these trends were not statistically significant. Conclusion In women with early-onset FGR, treatment with pravastatin 40 mg daily was associated with significant improvement in the angiogenic profile. Additionally, median pregnancy duration and median birthweight increased and the incidence of PE was reduced in treated women. Nevertheless, since this pilot study was underpowered, none of these differences were statistically significant. Key Points


2013 ◽  
Vol 73 (5) ◽  
pp. 602-611 ◽  
Author(s):  
Timothy R.H. Regnault ◽  
Barbra de Vrijer ◽  
Henry L. Galan ◽  
Randall B. Wilkening ◽  
Frederick C. Battaglia ◽  
...  

Author(s):  
Paddy J. Slator ◽  
Alison Ho ◽  
Spyros Bakalis ◽  
Laurence Jackson ◽  
Lucy C. Chappell ◽  
...  

AbstractThe placenta has a unique structure, which enables the transfer of oxygen and nutrients from the mother to the developing fetus. Abnormalities in placental structure are associated with major complications of pregnancy; for instance, changes in the complex branching structures of fetal villous trees are associated with fetal growth restriction. Diffusion MRI has the potential to measure such fine placental microstructural details. Here, we present in-vivo placental diffusion MRI scans from controls and pregnancies complicated by fetal growth restriction. We find that after 30 weeks’ gestation fractional anisotropy is significantly higher in placentas associated with growth restricted pregnancies. This shows the potential of diffusion MRI derived measures of anisotropy for assessing placental function during pregnancy.


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