Oral Presentation ESA-SRB 2023 in conjunction with ENSA

Understanding the role of thyroid antibodies in mediating complications of pregnancy (#72)

James Cuffe 1
  1. School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia

Thyroid antibodies are detectable in approximately 25% of pregnant women. These antibodies may contribute to thyroid dysfunction and changes to thyroid hormone concentrations. However, in the majority of women with high thyroid antibodies levels, no other changes to thyroid parameters can be detected. We and others have demonstrated that thyroid peroxidase antibodies (TPOab) or thyroglobulin antibodies (TGab) increase the risk of a range of pregnancy complications such as gestational diabetes mellitus, miscarriage and preterm birth.  As such, my laboratory has utilised a number of different approaches with the aim of investigating how these antibodies may be contributing to poor pregnancy outcomes. Two different rat models of TGab positivity in pregnancy were generated. The first rat model was established to look at how increased TGab and low T4 together contributed to poor outcomes. Rats given methimazole to impair thyroid hormone production had elevated TSH and TGab. These rats developed diabetes like symptoms in pregnancy, had placental dysfunction, fetal growth restriction and had changes to most metabolic parameters investigated. The second model was setup to investigate outcomes when thyroid autoimmunity is directly stimulated. Rats were immunised with thyroglobulin five times over the course of seven weeks before pregnancy was induced. These TGab positive rats had minimal thyroid pathology or changes to metabolic parameters. Instead, these TGab positive rats had impaired oestrous cycling, reduced survival of male fetuses and changes to fetal brain weights.  We are currently using a rat model of TPOab positivity to determine how different antibody types may cause different outcomes. Overall, rat models have proved useful in being able to start to dissect the actions of thyroid antibodies on pregnancy outcomes. There are a number of adverse pregnancy outcomes that seem to be directly linked to thyroid antibody concentrations and these models will be used in the future to test potential therapeutic interventions.