Tracing the Putative Tissue Origin of Circulating Olfactory Receptor mRNAs in Gestational Hypothyroidism: Effects of Levothyroxine in Rats

Extra-olfactory receptors (ORs) are expressed in multiple tissues and implicated in cardiovascular regulation and placental biology. Thyroid hormones influence olfactory function, but their role in tissue-specific OR expression during pregnancy remains unclear. Methods: Pregnant Wistar rats were assigned to control, gestational hypothyroid, and levothyroxine (LT4)-treated hypothyroid groups. Hypothyroidism was induced by administering methimazole and an iodine-deficient diet; LT4 was administered at 5.0 μg/100 g body weight. Or5t5, Or10j5, Agtr1a, Oprm1, and Pgf mRNA expressions were quantified by RT-qPCR in blood, kidney, heart, and placenta on gestational day 14. Results: No OR expression was detected in the heart, and Pgf was undetectable in the LT4-treated group. Hypothyroidism reduced renal Or10j5 expression. Placental LT4 treatment increased Or5t5 and Agtr1a and reduced Oprm1 expression compared with hypothyroid animals. Correlation analyses showed that circulating ORs correlate with each other (except in controls) and with circulating Agtr1a in all samples and subgroups. The circulating ORs correlate with placental Or10j5 in the hypothyroidism group and with kidney Or10j5 in LT4-treated animals. Conclusions: Gestational thyroid dysfunction modified OR expression in the kidney and placenta. LT4 alters placental transcriptional profiles, suggesting hormone sensitivity of extra-olfactory receptor transcripts. The small sample size and ANN-imputed TSH warrant cautious interpretation.