Oral Presentation ESA-SRB-APEG-NZSE 2022

Prenatal alcohol exposure is associated with sex-specific alterations to placental methyl donors and reduced cerebroplacental ratio (#50)

Sarah E Steane 1 , Christopher Edwards 2 3 , Jade M Kubler 2 , Lisa K Akison 1 , James SM Cuffe 1 , Linda A Gallo 1 4 , Karen M Mortiz 1 , Vicki L Clifton 2
  1. School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia
  2. Mater Medical Research Institute, The University of Queensland, Woolloongabba, QLD, Australia
  3. School of Clinical Sciences, Queensland University of Technology, Kelvin Grove, QLD, Australia
  4. University of the Sunshine Coast, Petrie, QLD, Australia

Aims

Prenatal alcohol exposure (PAE) increases the risk of adverse pregnancy outcomes including miscarriage, low birthweight, and neurodevelopmental abnormalities, which may be mediated by altered placental development. PAE is associated with alterations to placental vasculature, gene expression, and DNA methylation (DNAm) (1). Choline and folate are dietary micronutrients that serve as methyl donors for DNAm, however their availability may be compromised by alcohol consumption (2). This study investigated the impact of PAE on maternal and placental methyl donors, placental growth and the cerebroplacental ratio (CPR).

Methods

Data and samples were collected from women from the Queensland Family Cohort and classified into PAE (n=302) or abstinent/control (n=109). Maternal diet, placental measurements and Doppler ultrasound measures were examined during the 3rd trimester. Plasma folate was measured using a COBAS analyser. Plasma choline and placental methyl donors were measured by mass spectrometry. Placental gene expression was quantified by qPCR. Placental data were analysed separately by fetal sex.

Results

PAE was reported by 73.5% of participants. Most women (77%) took supplements containing ≥400µg folic acid, while few (27%) met the adequate intake for choline. This was consistent across control and PAE groups. Placental content of folate and choline were not altered by PAE, however, in female placentas, the methyl donor s-adenosylmethionine was increased in the PAE group (P<0.05), as were expression of the choline transporter, CTL1, and placental growth factor (PlGF) (P<0.05). In male placentas, expression of DNA methyltransferases (DNMTs) and (PlGF) were reduced in the PAE group (P<0.05), and placental thickness was decreased (P<0.05). CPR was lower in the PAE group (<0.05), with 11% of male fetuses, but no female fetuses, falling below the normal range, indicative of placental insufficiency.

Conclusion

PAE is associated with sex-specific alterations in the placenta, which may result in male fetuses being more vulnerable to adverse outcomes.

  1. 1. Steane SE, Young SL, Clifton VL, Gallo LA, Akison LK, Moritz KM. Prenatal alcohol consumption and placental outcomes: a systematic review and meta-analysis of clinical studies. Am J Obstet Gynecol. 2021 Dec;225(6):607.e1-607.e22. doi: 10.1016/j.ajog.2021.06.078. Epub 2021 Jun 26. PMID: 34181895.
  2. 2. Steane SE, Kumar V, Cuffe JSM, Moritz KM, Akison LK. Prenatal Choline Supplementation Alters One Carbon Metabolites in a Rat Model of Periconceptional Alcohol Exposure. Nutrients. 2022 Apr 29;14(9):1874. doi: 10.3390/nu14091874. PMID: 35565848; PMCID: PMC9100923.