Aims: Autoimmune thyroiditis (AIT) is a common cause of thyroid disease, characterised by auto-antibodies targeting proteins of the thyroid gland. Importantly, 5-20% of reproductive-aged women have thyroid autoantibodies (TAbs). TAb positivity (TAb+) is associated with impaired reproductive health in women, including reduced ovarian reserve and infertility. However, there is limited mechanistic research investigating how TAb+ impacts reproductive function. This study aimed to establish a rodent model of AIT to investigate the impact of TAb+ on ovarian function.
Methods: Recombinant thyroid peroxidase (TPO) protein was produced, emulsified with Freund’s adjuvant, and injected into 6-week-old female rats (TPO, n=10) twice over the period of 4 weeks. Control animals were injected with PBS and Freund’s adjuvant (ADJ, n=10) or PBS only (PBS, n=8). Estrous cycling was assessed over 21 days using a vaginal impedance probe and by vaginal cytology. Plasma was collected at three timepoints to assess TAb+ and reproductive hormone concentrations. All rats were culled in estrus and tissues collected for further analysis. Immune cell populations in the ovary and spleen were assessed by flow cytometry, and ovarian morphology assessed by histology.
Results: The final cohort of this study has only recently been completed, so data on reproductive hormones, immune populations and morphology has not yet been analysed. Preliminary findings show immunisation with a recombinant TPO protein was not sufficient to induce TAb+ in this rodent model, as no significant differences in TAb+ between groups were found. Both the TPO and ADJ groups had altered estrus cycling compared with PBS controls.
Conclusions: While this study was unable to investigate the impacts of TAb+ on reproductive function, the findings suggest immunisation with Freund’s adjuvant alone may be sufficient to induce subtle changes in ovarian morphology. This highlights the need for appropriate control groups in future studies investigating immune-based disruptions to fertility.