Follicular fluid metabolomic analysis in women with Hashimoto’s thyroiditis

Abstract

Hashimotos thyroiditis is an autoimmune thyroid disease characterized by hypothyroidism and a high level of anti-thyroid autoantibodies. This disease has been linked to a negative impact on female fertility, but the mechanisms are unclear. Ovarian follicular fluid appears to be the key to understanding how Hashimoto's thyroiditis can affect fertility. Therefore, we aimed to evaluate the follicular fluid metabolic profile and its relationship with anti-thyroid autoantibody levels. For this, we collected follicular fluid from a total of 61 patients undergoing in vitro fertilization treatment, comprising 34 women with thyroid autoantibody positivity and 18 negative controls. Follicular fluid samples were analysed using metabolomics and thyroid autoantibodies were measured. Follicular fluid samples from Hashimotos thyroiditis patients presented 15 metabolites with higher concentrations than those in controls, which indicates five possible affected pathways: the glycerophospholipid, arachidonic acid, linoleic acid, alpha-linolenic acid, and sphingolipid metabolism pathways. These pathways are known to regulate ovarian functions. In addition, anti-thyroglobulin antibody concentrations were more than tenfold higher in women with Hashimotos thyroiditis than in controls, in both serum and follicular fluid. Our data showed that Hashimotos thyroiditis can change the metabolic profile of follicular fluid, suggesting a potential mechanistic explanation for the association of this disease with female infertility.