Objectives: Autoimmune thyroiditis (AIT) is a common cause of thyroid disease, characterised by auto-antibodies targeting proteins of the thyroid gland. Importantly, 1 in 5 women have these thyroid autoantibodies (TAbs) during pregnancy. TAb positivity (TAb+) is associated with increased risk of many pregnancy complications, including miscarriage and gestational diabetes. However, there is limited mechanistic research looking into how TAb+ leads to pregnancy dysfunction. This study aimed to establish an animal model of AIT during pregnancy to investigate the impact of TAb+ on maternal, placental and fetal physiology.

Methods: TAb+ was induced in female Lewis rats by combination of routine porcine thyroglobulin injection (2ug/ml) and daily administration of sodium iodide (0.5% w/v). Impacts to estrous cycling were assessed by vaginal impedance prior to mating. Plasma was collected 1-week prior to mating and at the end of pregnancy to assess TAb and hormone levels. All rats were culled at E20 and tissue collected for further analysis.

Results: TAb+ was associated with altered cycling but not pregnancy success. In addition to TAb+, AIT animals had elevated thyroxine in late gestation but no changes to TSH. TAb+ did not impact litter size but did impair male fetus survival. TAb+ impacted placental size and altered glycogen stores which may be linked to elevated maternal glucose. Placental expression of genes related to syncytialisation and angiogenesis were also altered by TAb+.

Conclusions: These findings demonstrate changes to thyroid status, including TAb+, can lead to altered reproductive function, reduced male fetal survival, and may be indicative of placental dysfunction. This preclinical model of TAb+ highlights the complex presentation of AIT in pregnancy and provides an important insight to potential pathological pathways through which TAb+ may contribute to infertility and pregnancy complications.