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. 2023 Sep 18;16(1):38.
doi: 10.1186/s13044-023-00180-6.

Expressions of mitochondria-related genes in pregnant women with subclinical hypothyroidism, and expressions of miRNAs in maternal and cord blood

Julie Kristine Guldberg Stryhn  1   2   3 , Jacob Larsen #  4   5 , Palle Lyngsie Pedersen #  4   6 , Peter Haulund Gæde  7   8
Affiliations

Expressions of mitochondria-related genes in pregnant women with subclinical hypothyroidism, and expressions of miRNAs in maternal and cord blood

Julie Kristine Guldberg Stryhn et al. Thyroid Res. .

Abstract

Background: Subclinical hypothyroidism in pregnancy and definition by upper thyrotropin (TSH) cutoff are controversial. As mitochondria are influenced by thyroid hormones, the purpose in this study was to measure expression of mitochondria-related genes in euthyroid and subclinical hypothyroid pregnant women to obtain more knowledge of potential metabolic consequences of maternal subclinical hypothyroidism. In addition, we wished to test if applied TSH-cutoff significantly changed our results of expressed gene-levels. Moreover, we aimed to identify potential microRNA-biomarkers for subclinical hypothyroidism - markers that could be traced to offspring as well.

Methods: From a cohort of at-term pregnant women undergoing planned cesarean section, 77 women had expression levels of the mitochondria-related genes Peroxisome Proliferator-activated Receptor-γ coactivator-1β (PGC-1β), mitochondrial Transcription Factor A (TFAM), Superoxide Dismutase 2 (SOD2) and Nuclear Respiratory Factor 2 (NRF-2) determined by qPCR from blood sampled in prior to delivery. Two TSH-cutoff levels defining subclinical hypothyroidism (> 3.0 and > 3.7 mIU/L) were applied for the procession of results, generating two data analyses of the same cohort. In 22 pairwise maternal-cord samples (subclinical hypothyroid/euthyroid-rate 0.5, TSH-cutoff > 3.0 mIU/L), microRNA-expressions (miRNA) were analyzed.

Results: All gene expressions were lower in the subclinical hypothyroid group regardless of applied TSH-cutoff, but insignificant except for PGC-1β at TSH cutoff > 3.0 mIU/L. Two miRNAs (hsa-let-7d-3p and hsa-miR-345-5p) were upregulated in blood from women and offspring (cord blood) with subclinical hypothyroidism.

Conclusions: A trend towards decreased mitochondrial gene expressions in subclinical hypothyroidism were demonstrated. The miRNAs hsa-let-7d-3p and hsa-miR-345-5p might be potential markers of maternal subclinical hypothyroidism. However, larger studies are needed to verify the findings.

Keywords: Biomarker; Blood; Genes; MicroRNAs; Mitochondrial; Pregnancy; Subclinical hypothyroidism; Thyroid reference range; Thyrotropin; Umbilical cord.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram
Fig. 2
Fig. 2
A-B Maternal euthyroid and subclinical hypothyroid gene-expressions. A by TSH-cutoff 3.0 mIU/L and B by TSH-cutoff 3.7 mIU/L. X-axis: TFAM, PGC1-β, NRF-2 and SOD2 expressions. Y-axis: Gene expression target/reference / a.u. Boxes = lower and upper quartile, horizontal line in box = median value, whiskers = range
Fig. 3
Fig. 3
A-B Maternal and offspring (cord) thyroid status in euthyroid and subclinical hypothyroid cohort, in miRNA screening. X-axis: maternal and cord TSH, fT3 and fT4. Y-axis: Units: TSH-values / mIU/L, fT3-and fT4-values / pmol/L. Boxes = lower and upper quartile, horizontal line in box = median value, whiskers = range
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