de Vrijer, B. | bioRxiv Science

bioRxiv2026

Altered Placental Pyruvate Metabolism in Spontaneous Intrauterine Growth Restricted near-term Pregnant Guinea Pigs

Abstract1IUGR is associated with increased risk of fetal compromise, yet can be difficult to detect and phenotype with routine clinical surveillance. Given placental insufficiency and hypoxia can remodel placental energy metabolism, methods that directly assess placental metabolic function may improve identification and phenotyping of growth-restricted pregnancies. We combined structural, body composition, and hyperpolarized metabolic MRI to characterize a near-term spontaneous IUGR (spIUGR) phenotype in the guinea pig. Twenty-two pregnant guinea pig sows (71 fetuses) underwent 1H and hyperpolarized 13C MRI at 60 {+/-} 1 days gestation to quantify fetal and placental volumes, maternal/fetal body composition, and quantify placental pyruvate metabolism. Fetuses were classified as spIUGR when [≥] 3 of 5 established markers were present (body weight, brain-body, brain-liver, brain-placenta ratios, and body weight relative to pregnancy mean); corresponding volume cut-offs were derived from weight cut-offs. MRI-derived fetal and placental volumes correlated strongly with collection weights and classified spIUGR consistently with weight-based criteria. Maternal adiposity (subcutaneous and visceral) was inversely associated with fetal adipose tissue volume, and maternal visceral fat PDFF was negatively associated with fetal adipose PDFF. Hyperpolarized MRI demonstrated IUGR phenotype-dependent placental pyruvate routing: LPR increased with asymmetric (brain-sparing) growth, showing a positive association with brain-body volume ratio (p = 0.02) and brain-body weight ratio (p = 0.04). In contrast, BPR was not significantly related to brain-body ratios (p = 0.09-0.11) but was inversely associated with absolute fetal size (body volume and weight, p = 0.02). These findings validate MRI volumetry for non-invasive identification of placental insufficiency spIUGR and link growth restriction severity and asymmetry to distinct placental metabolic signatures measurable in vivo.

biophysics↗

bioRxiv2025

Altered placental morphology and metabolomic profile in as-sociation with uncomplicated metabolically healthy obese pregnancy

Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) in pregnancy represent two distinct cardiometabolic populations, each potentially necessitating alternative clinical management. However, the understanding of the unique physiological effects of uncomplicated MHO or MUO on fetoplacental growth and metabolism remains limited. This study aimed to identify changes in placental morphology and metabolites concerning maternal obesity, independent of pregnancy-related cardiometabolic complications. Placentae from women with a pre-pregnancy body mass index (BMI) <25 kg/m2 (control; n = 15) and women with MHO (pre-pregnancy BMI >30 kg/m2 with no cardiometabolic diseases; n = 15) were analysed for indices of placental growth and untargeted metabolomics. Complementary measures of pro-inflammatory and antioxidant genes, as well as antioxidant proteins, enzymes, and lipid peroxidation markers were conducted. A clear placentomegaly without histopathological changes was observed in uncomplicated MHO pregnancies. The metabolite 3-aminoisobutanoic acid emerged as the top-ranked feature distinguishing MHO from control placentae, and cysteine, methionine, and vitamin B6 metabolism pathways were among the most distinct signatures identified. These findings illustrate an altered placental morphology and metabolomic profile specific to uncomplicated MHO, offering new insights into how obesity without cardiometabolic complications influences fetoplacental growth and metabolism. They also represent a crucial first step towards marker identification for MHO pregnancies and underscore the importance of alternative care pathways when obesity is present but metabolic comorbidities are absent.

physiology↗