Increased fetal abortion rate in autoimmune thyroid disease is related to circulating TPO autoantibodies in an autoimmune thyroiditis animal model

Abstract

Objective: To determine the fertility and abortion rates in a mouse model of autoimmune thyroiditis and its relationship with circulating anti-thyroid peroxidase (TPO) antibody.

Design: Experimental animal study.

Setting: University research laboratory.

Animal(s): C57bl/6 mice.

Intervention(s): Female C57bl/6 mice immunized with recombinant mouse TPO (rmTPO) in complete Freund adjuvant (CFA) or glutathione-S-transferase (GST-CFA) were allowed to mate. The pregnant mice were killed on day 14 of pregnancy for assessment of fetal development. The effects of TPO antibody on preimplantation embryo development and implantation rate were also studied.

Main outcome measure(s): Litter size, resorption rate, preimplantation embryo development, and implantation rate.

Result(s): All of the mice immunized with rmTPO-CFA possessed anti-TPO antibody. They had reduced litter size and increased incidence of resorbed fetus compared with the control. Higher serum TSH levels, but not T(4) levels, were demonstrated after rmTPO-CFA immunization. Anti-TPO antibody bound to preimplantation embryos. Treatment of the embryos with the antibody marginally decreased the formation of 3/4-cell embryos but had no effect on the subsequent development and implantation compared with the nonimmune control sera.

Conclusion(s): Autoimmune thyroiditis is associated with reduced fertility and higher incidence of fetal loss. The anti-TPO antibody may affect post-implantation embryo development, leading to fetal loss.