Maternal hyperthyroidism alters the immunological mediators profile and population of natural killers cells in decidua of rats.

Luciano Cardoso Santos, Cíntia Almeida de Souza, Juneo Freitas Silva, Natália Melo Ocarino, Rogéria Serakides

Acta histochemica 2023 Apr

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Decidual immunological mediators modulate placental formation, decidualization and fetal development. However, the effect of maternal hyperthyroidism on decidual immunology needs further research. The aim of this study was to evaluate the population of uterine natural killer cells (uNKs) and the expression of immunological mediators in the decidua of female rats throughout pregnancy. Wistar rats were used and hyperthyroidism was induced by daily administration of L-thyroxine (T4) throughout pregnancy. The population of uNK cells in decidua was evaluated by immunostaining Lectin DBA, as well as the expression of interferon γ (INFγ), macrophage migration inhibitory factor (MIF), interleukin 15 (IL-15) and inducible nitric oxide synthase (iNOS) at 7, 10, 12, 14 and 19 days of gestation (DG). Maternal hyperthyroidism reduced the DBA+ uNK cell population in the decidua at 7 (P < 0.05) and 10 (P < 0.01) DGs compared to that in the control group, while it increased in the basal decidua (P < 0.05) and metrial gland (P < 0.0001) at the 12th DG. Hyperthyroidism also increased immunostaining of IL-15 (P < 0.0001), INFγ (P < 0.05), and MIF (P < 0.05) in the 7th DG, and increased immunostaining of IL-15 (P < 0.0001) and MIF (P < 0.01) in the 10th DG. However, excess thyroxine reduced IL-15 expression in the metrial gland and/or basal decidua in the 12th (P < 0.05), 14th (P < 0.01), and 19th (P < 0.001) DGs, as was also observed for INFγ in the basal decidua (P<0.001) and metrial gland (P < 0.0001) in the 12th DG. Regarding iNOS, an antiinflammatory cytokine, lower expression was observed in the basal decidua of hyperthyroid animals at 7 and 12 DGs (P < 0.05), whereas an increase occurred in the 10th DG (P < 0.05). These data demonstrate that maternal hyperthyroidism in female rats, particularly between 7 and 10 DGs, reduces the population of DBA+ uNKs in the decidua and increases the expression of inflammatory cytokines, suggesting a more proinflammatory environment in early pregnancy caused by this gestational disease. Copyright © 2023 Elsevier GmbH. All rights reserved.

Citation

Luciano Cardoso Santos, Cíntia Almeida de Souza, Juneo Freitas Silva, Natália Melo Ocarino, Rogéria Serakides. Maternal hyperthyroidism alters the immunological mediators profile and population of natural killers cells in decidua of rats. Acta histochemica. 2023 Apr;125(3):152026