The effects of maternal hyperglycaemia during pregnancy on one-carbon metabolism — ASN Events
  1. Schedule
  2. Poster Listing: Preconception, pregnancy, postpartum and intrapartum health of women and babies
  3. The effects of maternal hyperglycaemia during pregnancy on one-carbon metabolism

The effects of maternal hyperglycaemia during pregnancy on one-carbon metabolism (#66)

Dayna A Zimmerman 1 , Thomas P Mullins 1 , Vinod Kumar 1 , Linda A Gallo 2 , James SM Cuffe 1
  1. School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia
  2. Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia

Gestational diabetes mellitus (GDM) is the most common metabolic disturbance during pregnancy. Numerous clinical studies have demonstrated that women with GDM have altered concentrations of circulating one-carbon metabolites and cofactors such as vitamin B12, B6, folate and homocysteine (Barzilay et al., 2018). Imbalances in these factors have been linked with poor placental development and adverse fetal outcomes (Vanhees et al., 2014). Currently, it is unknown if the hyperglycaemia caused by GDM results in lower concentrations of one-carbon metabolites or if reduced concentrations of one-carbon metabolites increase women’s risk of GDM. This study therefore examined the effects of maternal hyperglycaemia on one-carbon metabolism.

METHODS: Gestational hyperglycaemia was induced in pregnant C57BL/6 mice via D-glucose (1.55g/mL) filled osmotic mini-pumps (release rate of 0.5µl/hr) inserted subcutaneously at embryonic day 7 (E7). Control animals received 0.9% saline mini-pumps. Mice were euthanised via cervical dislocation on E18.5. Maternal plasma concentrations of one-carbon metabolites and cofactors were measured using liquid chromatography-mass spectrometry. Placental gene expression of enzymes involved in one-carbon metabolism and associated processes were measured using real-time PCR

RESULTS: Hyperglycaemia increased concentrations of several one-carbon factors in maternal plasma at E18. This included 5-methyl-THF, methionine, vitamin B6 and vitamin B12, with a subsequent decrease in homocysteine. Furthermore, relative S-Adenosyl methionine (SAM) concentrations were higher in the hyperglycaemic group compared to control, with no change in S-Adenosyl-L-homocysteine (SAH) levels. This ultimately led to a two-fold increase in methylation capacity. This was accompanied by increased gene expression of several one-carbon enzymes within the placenta, including methionine synthase and methylenetetrahydrofolate reductase. 

DISCUSSION: This study demonstrated that maternal hyperglycaemia increased one-carbon metabolites which contrasts with the decrease commonly seen clinically in women with GDM. Findings suggest that the hyperglycaemia alone as a result of GDM is not responsible for the decrease in one-carbon metabolites and cofactors demonstrated clinically.

 

  1. BARZILAY, E., MOON, A., PLUMPTRE, L., MASIH, S. P., SOHN, K.-J., VISENTIN, C. E., LY, A., MALYSHEVA, O., CROXFORD, R., CAUDILL, M. A., O'CONNOR, D. L., KIM, Y.-I. & BERGER, H. 2018. Fetal one-carbon nutrient concentrations may be affected by gestational diabetes. Nutr Res, 55, 57-64.
  2. VANHEES, K., VONHÖGEN, I. G. C., VAN SCHOOTEN, F. J. & GODSCHALK, R. W. L. 2014. You are what you eat, and so are your children: the impact of micronutrients on the epigenetic programming of offspring. Cell Mol Life Sci, 71, 271-285.
#qldwomenshealthforum2024