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Placental phenotype and resource allocation to fetal growth are modified by the timing and degree of hypoxia during mouse pregnancy.

ABSTRACT: The placenta adapts its transport capacity to nutritional cues developmentally, although relatively little is known about placental transport phenotype in response to hypoxia, a major cause of fetal growth restriction. The present study determined the effects of both moderate hypoxia (13% inspired O2) between days (D)11 and D16 or D14 and D19 of pregnancy and severe hypoxia (10% inspired O2) from D14 to D19 on placental morphology, transport capacity and fetal growth on D16 and D19 (term?D20.5), relative to normoxic mice in 21% O2. Placental morphology adapted beneficially to 13% O2; fetal capillary volume increased at both ages, exchange area increased at D16 and exchange barrier thickness reduced at D19. Exposure to 13% O2 had no effect on placental nutrient transport on D16 but increased placental uptake and clearance of (3)H-methyl-D-glucose at D19. By contrast, 10% O2 impaired fetal vascularity, increased barrier thickness and reduced placental (14)C-methylaminoisobutyric acid clearance at D19. Consequently, fetal growth was only marginally affected in 13% O2 (unchanged at D16 and -5% at D19) but was severely restricted in 10% O2 (-21% at D19). The hypoxia-induced changes in placental phenotype were accompanied by altered placental insulin-like growth factor (IGF)-2 expression and insulin/IGF signalling, as well as by maternal hypophagia depending on the timing and severity of the hypoxia. Overall, the present study shows that the mouse placenta can integrate signals of oxygen and nutrient availability, possibly through the insulin-IGF pathway, to adapt its phenotype and optimize maternal resource allocation to fetal growth during late pregnancy. It also suggests that there is a threshold between 13% and 10% inspired O2 at which these adaptations no longer occur.

SUBMITTER: Higgins JS

PROVIDER: S-EPMC4771776 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Placental phenotype and resource allocation to fetal growth are modified by the timing and degree of hypoxia during mouse pregnancy.

Higgins J S JS Vaughan O R OR Fernandez de Liger E E Fowden A L AL Sferruzzi-Perri A N AN

The Journal of physiology 20151026 5

The placenta adapts its transport capacity to nutritional cues developmentally, although relatively little is known about placental transport phenotype in response to hypoxia, a major cause of fetal growth restriction. The present study determined the effects of both moderate hypoxia (13% inspired O2) between days (D)11 and D16 or D14 and D19 of pregnancy and severe hypoxia (10% inspired O2) from D14 to D19 on placental morphology, transport capacity and fetal growth on D16 and D19 (term∼D20.5), ...[more]

PMID: 26377136

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Project description:Birth timing is a key life-history characteristic that influences fitness and population performance. For migratory animals, however, appropriately timing birth on one seasonal range may be constrained by events occurring during other parts of the migratory cycle. We investigated how the use of capital and income resources may facilitate flexibility in reproductive phenology of migratory mule deer in western Wyoming, USA, over a 5-yr period (2015-2019). Specifically, we examined how seasonal interactions affected three interrelated life-history characteristics: fetal development, birth mass, and birth timing. Females in good nutritional condition at the onset of winter and those that migrated short distances had more developed fetuses (measured as fetal eye diameter in March). Variation in parturition date was explained largely by fetal development; however, there were up to 16 d of plasticity in expected birth date. Plasticity in expected birth date was shaped by income resources in the form of exposure to spring green-up. Although individuals that experienced greater exposure to spring green-up were able to advance expected birth date, being born early or late with respect to fetal development had no effect on birth mass of offspring. Furthermore, we investigated the trade-offs migrating mule deer face by evaluating support for existing theory that predicts that births should be matched to local peaks in resource availability at the birth site. In contrast to this prediction, only long-distance migrants that paced migration with the flush of spring green-up, giving birth shortly after ending migration, were able to match birth with spring green-up. Shorter-distance migrants completed migration sooner and gave birth earlier, seemingly trading off more time for offspring to grow and develop over greater access to resources. Thus, movement tactic had profound downstream effects on birth timing. These findings highlight a need to reconsider classical theory on optimal birth timing, which has focused solely on conditions at the birth site.

Project description:ObjectiveTo assess the value of in utero placental assessment in predicting adverse pregnancy outcome after reported reduced fetal movements (RFM).MethodA non-interventional prospective cohort study of women (N = 300) with subjective RFM at ≥28 weeks' gestation in singleton non-anomalous pregnancies at a UK tertiary maternity hospital. Clinical, sonographic (fetal weight, placental size and maternal, fetal and placental arterial Doppler) and biochemical (maternal serum hCG, hPL, progesterone, PlGF and sFlt-1) assessment was conducted. Multiple logistic regression identified combinations of measurements (models) most predictive of adverse pregnancy outcome (perinatal mortality, birth weight <10th centile, five minute Apgar score <7, umbilical arterial pH <7.1 or base excess <-10, neonatal intensive care admission). Models were compared by test performance characteristics (ROC curve, sensitivity, specificity, positive/negative predictive value, positive/negative likelihood ratios) against baseline care (estimated fetal weight centile, amniotic fluid index and gestation at presentation).Results61 (20.6%) pregnancies ended in adverse outcome. Models incorporating PlGF/sFlt-1 ratio and umbilical artery free loop Doppler impedance demonstrated modest improvement in ROC area for adverse outcome (baseline care 0.69 vs. proposed models 0.73-0.76, p<0.05). However, there was little improvement in other test characteristics (baseline vs. best proposed model: sensitivity 21.7% [95% confidence interval 13.1-33.6] vs. 35.8%% [24.4-49.3], specificity 96.6% [93.4-98.3] vs. 94.7% [90.7-97.0], PPV 61.9% [40.9-79.3] vs. 63.3% [45.5-78.1], NPV 82.8% [77.9-86.8] vs. 85.2% [80.0-89.2], positive LR 6.3 [2.8-14.6] vs. 6.7 [3.4-3.3], negative LR 0.81 [0.71-0.93] vs. 0.68 [0.55-0.83]) and wide confidence intervals. Negative post-test probability remained high (16.7% vs. 14.0%).ConclusionAntenatal placental assessment may improve identification of RFM pregnancies at highest risk of adverse pregnancy outcome but further work is required to understand and refine currently available outcome definitions and diagnostic techniques to improve clinical utility.

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Placental phenotype and resource allocation to fetal growth are modified by the timing and degree of hypoxia during mouse pregnancy.

Publications

Placental phenotype and resource allocation to fetal growth are modified by the timing and degree of hypoxia during mouse pregnancy.

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