SNAT2 expression and regulation in human growth-restricted placentas

Abstract

Background: Amino acid placental delivery is reduced in human intrauterine growth-restricted (IUGR) fetuses, and the activity of placental amino transporters has been consistently shown to be decreased in in vitro studies. We hypothesized lower placental expression and localization of sodium-coupled neutral amino acid transporter 2 (SNAT2 (also known as SLC38A2)), altered levels of intron-1 methylation, and altered distribution of single-nucleotide polymorphisms in human IUGR vs. normal pregnancies. Methods: We studied 88 IUGR and 84 control placentas from singleton pregnancies at elective caesarean section. SNAT2 expression was investigated by real-time PCR and immunohistochemistry. Intron-1 methylation levels were analyzed by pyrosequencing, and single-nucleotide polymorphism distribution was analyzed by allelic discrimination. results: mRNA levels were significantly decreased in IUGR placentas with reduced umbilical blood flows. Syncytiotrophoblast immunostaining was lower in IUGR placentas than in control placentas. Methylation levels were steadily low in both IUGR and control placentas. SNP genotype and allele frequencies did not differ between the two groups. conclusion: This is the first study investigating SNAT2 expression and regulation mechanisms in human IUGR placentas. We confirm previous results obtained in rats and cell cultures that support the fundamental role of SNAT2 in fetal growth and well-being, as well as a possible role of oxygen levels in regulating SNAT2 expression, indicating the relevance of hypoxia in IUGR.

Placental mitochondrial content and function in intrauterine growth restriction and preeclampsia

“…Indeed, strong links have been previously described between calorie restriction and changes in the mitochondrial machinery of different tissues (12, 30). Although maternal BMI was not different among groups in our study population, IUGR placentas are known to present in fact many characteristics leading to calorie restriction and mitochondrial defects, such as poor expression and activity of nutrient transporters (7,10,18,33,53), low activity of the glutamine-glutamate metabolism, and poor control of mitochondrial lipid peroxidation (33,50), with increased sensitivity to mitochondrial oxidative stress and ROS production. Moreover, micronutrient imbalance might also be involved in IUGR mitochondrial alterations (9,32).…”

Mid‐ to late term hypoxia in the mouse alters placental morphology, glucocorticoid regulatory pathways and nutrient transporters in a sex‐specific manner

“…Indeed in humans, it has recently been shown that Slc38a2 expression is reduced in the placentas of intrauterine growth restriction fetuses, with levels being directly correlated with umbilical vein oxygen content (Mando et al . ). Interestingly, cortisol (Jones et al .…”

1,25-Dihydroxy vitamin D3 stimulates system A amino acid transport in primary human trophoblast cells

“…For example, our previous studies showed pro-inflammatory cytokines stimulated SNTA2 expression in cultured PHT cells (Aye et al, 2015; Jones et al, 2009). In addition, placental SNAT2 down regulation has been demonstrated in animal models and human FGR (Chen et al, 2015; Jansson et al, 2006; Mando et al, 2013) suggesting that SNAT2 plays a crucial role in the control of amino acid transport and fetal growth.…”