TAAR1 induces a disturbed GSK3β phosphorylation in recurrent miscarriages through the ODC

TAAR1 通过 ODC 诱导复发性流产中的 GSK3β 磷酸化紊乱

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作者:Stavroula Stavrou, Michael Gratz, Eileen Tremmel, Christina Kuhn, Simone Hofmann, Helene Heidegger, Mina Peryanova, Kerstin Hermelink, Stefan Hutter, Bettina Toth, Doris Mayr, Sven Mahner, Udo Jeschke, Aurelia Vattai

Conclusions

Upregulation of placental TAAR1 may indicate an increased decarboxylation of thyroid hormones in miscarriages. Patients with RM may have a lack of T3 through an enhanced transformation of T3 into T1AM induced by the ODC. Future investigations could be carried out to analyse what role a prophylactic T3 substitution plays for patients.

Methods

Patients with SM (n = 15) and RM (n = 15) were compared with patients with healthy pregnancies (n = 15) (pregnancy weeks 7-13 each). Immunohistochemistry was applied to analyse placental TAAR1, pGSK3β and ODC expression. Protein expression of the receptors after stimulation with T3, T1AM and RO5203548 in BeWo trophoblast model cells was determined via Western blot. Double-immunofluorescence was used to determine placental expression of TAAR1 and ODC.

Results

Levels of TAAR1, pGSK3β and ODC were higher in placentas of RM in comparison to healthy controls. Stimulation of BeWo cells with T3, T1AM and RO5203548 significantly increased TAAR1 expression. ODC expression in BeWo cells was upregulated through T3. Via double-immunofluorescence, TAAR1 and ODC-positive EVT could be detected. Conclusions: Upregulation of placental TAAR1 may indicate an increased decarboxylation of thyroid hormones in miscarriages. Patients with RM may have a lack of T3 through an enhanced transformation of T3 into T1AM induced by the ODC. Future investigations could be carried out to analyse what role a prophylactic T3 substitution plays for patients.

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