Maternal Factors Are Associated with the Expression of Placental Genes Involved in Amino Acid Metabolism and Transport

Abstract

Introduction: Maternal environment and lifestyle factors may modify placental function to match the mother's capacity to support the demands of fetal growth. Much remains to be understood about maternal influences on placental metabolic and amino acid transporter gene expression. We investigated the influences of maternal lifestyle and body composition (e.g. fat and muscle content) on a selection of metabolic and amino acid transporter genes and their associations with fetal growth.

Methods: RNA was extracted from 102 term Southampton Women's Survey placental samples. Expression of nine metabolic, seven exchange, eight accumulative and three facilitated transporter genes was analyzed using quantitative real-time PCR.

Results: Increased placental LAT2 (p = 0.01), y+LAT2 (p = 0.03), aspartate aminotransferase 2 (p = 0.02) and decreased aspartate aminotransferase 1 (p = 0.04) mRNA expression associated with pre-pregnancy maternal smoking. Placental mRNA expression of TAT1 (p = 0.01), ASCT1 (p = 0.03), mitochondrial branched chain aminotransferase (p = 0.02) and glutamine synthetase (p = 0.05) was positively associated with maternal strenuous exercise. Increased glutamine synthetase mRNA expression (r = 0.20, p = 0.05) associated with higher maternal diet quality (prudent dietary pattern) pre-pregnancy. Lower LAT4 (r = -0.25, p = 0.05) and aspartate aminotransferase 2 mRNA expression (r = -0.28, p = 0.01) associated with higher early pregnancy diet quality. Lower placental ASCT1 mRNA expression associated with measures of increased maternal fat mass, including pre-pregnancy BMI (r = -0.26, p = 0.01). Lower placental mRNA expression of alanine aminotransferase 2 associated with greater neonatal adiposity, for example neonatal subscapular skinfold thickness (r = -0.33, p = 0.001).

Conclusion: A number of maternal influences have been linked with outcomes in childhood, independently of neonatal size; our finding of associations between placental expression of transporter and metabolic genes and maternal smoking, physical activity and diet raises the possibility that their effects are mediated in part through alterations in placental function. The observed changes in placental gene expression in relation to modifiable maternal factors are important as they could form part of interventions aimed at maintaining a healthy lifestyle for the mother and for optimal fetal development.

Fig 1. Associations between maternal pre-pregnancy smoking and placental relative mRNA expression levels.

Maternal pre-pregnancy smoking was associated with increased LAT2, y+LAT2 and aspartate aminotransferase 2 (GOT2) and decreased aspartate aminotransferase 1 (GOT1) placental relative mRNA expression; n = 76 for not smoking, n = 26 for smoking. Data are mean ± SD, * p < 0.05.

Fig 2. Maternal strenuous exercise was associated with increased placental TAT1, ASCT1, mitochondrial branched chain amino transferase (BCATm) and glutamine synthetase (GLUL) relative mRNA expression; n = 39 for no strenuous exercise, n = 63 for strenuous exercise.

Data are mean ± SD, * p < 0.05, ** p < 0.001.

Fig 3. Faster walking speed was associated with reduced placental TAT1, SNAT2, aspartate aminotransferase 2 (GOT2) and EAAT3 relative mRNA expression; n = 47 faster than normal walking, n = 55 for normal or slower walking speed.

Data are mean ± SD, *p < 0.05, **p < 0.01.

Fig 4. Placentas from multiparous woman had increased placental relative mRNA expression of ASCT2, EAAT3, cytosolic branched chain amino transferase (BCATc) and aspartate aminotransferase 2 (GOT2) and decreased mitochondrial glutamate dehydrogenase (GLUD), n = 46 for nulliparous, n = 56 for multiparous.

Data are mean ± SD, *p < 0.05, **p < 0.01.