Effects of maternal HF diet and absence of TRPC1 gene on mouse placental growth and fetal intrauterine growth retardation (IUGR)

Authors: Larson, Kate; SINGH, BRIJ - University Of Texas At San Antonio; Bundy, Amy; BRUNELLE, DALE - Orise Fellow; Bukowski, Michael; Roemmich, James

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/9/2022
Publication Date: 4/1/2023
Citation: Larson, K.J., Singh, B., Bundy, A.N., Brunelle, D., Bukowski, M.R., Roemmich, J.N. 2023. Effects of maternal HF diet and absence of TRPC1 gene on mouse placental growth and fetal intrauterine growth retardation (IUGR). Journal of Nutritional Biochemistry. 114. Article 109162. https://doi.org/10.1016/j.jnutbio.2022.109162.
DOI: https://doi.org/10.1016/j.jnutbio.2022.109162

Interpretive Summary: Normal growth of placental tissue has been shown to beregulated by calcium levels within the placental cells. Other factors such aseating high fat diet also alter placental tissue lipid concentration, nutrienttransport to the fetus, and fetal development. Female mice lacking cellularcalcium transport were fed high fat diet during pregnancy to test if genetic influenceand diet influence can have an additive effect on fatty placenta and lower fetalweight when compared to normal mice.  Ourresults showed that limiting calcium transport within the placenta promotes fetalgrowth restriction and this adverse effect was exacerbated with a maternal highfat diet. These data demonstrate that both genetic background and maternal dietcan have additive adverse effects on fetal growth. 

Technical Abstract: Placental tissue intracellular calcium (Ca2+) regulates placental development and growth (e.g., blastocyst development through branching morphogenesis). Maternal high-fat (HF) diet results in placental lipid accumulation, increased inflammation, reduced nutrient transport expression and intrauterine growth restriction (IUGR). Currently, whether maternal HF diet differentially affects placental and fetal growth and development under reduced Ca2+ influx is not yet known. Thus, we hypothesized that maternal HF diet feeding decreases placental growth and development resulting in IUGR. We further hypothesized that reduction of Ca2+ influx in the placenta worsens maternal HF-induced placental dysfunction. Two-month-old female B6129SF2/J wild type (WT) and transient receptor potential canonical 1 (TRPC1) protein deficient (KO) mice were fed normal fat (NF, 16% fat) and high fat (HF, 45%) diets for 12 weeks. Fetuses and placentae were examined at mid- (D12) and late- (D19) gestation. Placental length, width, and weight as well as fetal weight were decreased in the TRPC1 KO mice at D12 and D19 compared to that of WT mice. Expression of placental growth factor (PLGF) mRNA was decreased at D12 in TRPC1 KO mice while vascular endothelial growth factor (VEGF) mRNA levels were increased at D19 compared to WT mice. These findings suggest that genotypic differences rather than maternal HF diet alter placental size and weight as well as fetal weight. Decreased PLGF mRNA may be responsible for the placental and fetal growth restriction while increased VEGF mRNA indicates compensatory adaptation to decreased PLGF-associated placental and fetal growth restriction. Future studies are needed to determine the signaling mechanism underlying Ca2+ influx reduction- induced placental dysfunction and IUGR.