Abstract
An increasing number of studies suggest that subclinical hypothyroidism (SCH) is associated with complications of gestation, including spontaneous abortion (SA). However, the underlying mechanism is not clear. MicroRNA (miRNA) has been demonstrated to be closely related to gynecological reproductive diseases. We determined miRNA expression in patients with SCH, SCH with SA (SCH + SA), and in those with SA as well as healthy controls (HCs), and analyzed whether dysregulation in several miRNAs was specific to these cohorts. An Agilent Human miRNA array was used to explore miRNA levels in pooled serum samples as a pilot study, followed by a validation of selected miRNAs by real-time polymerase chain reaction in SCH (N = 24), SA (N = 19), SCH + SA (N = 21), and HC cohorts (N = 18). The relative expression of miR-940 was elevated in the SCH + SA group compared with SCH, SA, and HC groups. In addition, miR-486-5p was upregulated in the SCH + SA group compared with SA and HC groups, without a difference noted between SCH + SA and SCH groups. Further analysis suggested that miR-940 or miR-486-5p may be potential predictive biomarkers for the early diagnosis of SA in patients with SCH.
Highlights
Subclinical hypothyroidism (SCH) is the most common form of thyroid hormone deficiency [1]
MicroRNAs, a class of conservative, endogenous small non-coding RNAs, only 19–24 nucleotides in length, usually negatively regulate the expression of hundreds of genes by binding to the 3′-untranslated region (UTR) or 5′-UTR of their target mRNAs [9, 10]. miRNAs play a fundamental role in controlling various cellular functions, such as metabolism, apoptosis, and differentiation. miRNAs have been stably detected in extracellular fluids [11, 12], including plasma/serum, while circulating miRNAs seem to be resistant to endogenous ribonuclease activity [12]; they have emerged as biomarkers for the diagnosis of various diseases [13]
To validate potential biomarkers identified from screening results, serum levels of miRNAs were measured by qRT-polymerase chain reaction (PCR) in 24 patients with subclinical hypothyroidism (SCH), 21 patients with SCH + spontaneous abortion (SA), 19 patients with SA, and 18 patients with healthy controls (HCs)
Summary
Subclinical hypothyroidism (SCH) is the most common form of thyroid hormone deficiency [1]. SCH is characterized by elevated levels of serum thyroid-stimulating hormone (TSH) above the upper reference limit of the gestational maternal-specific reference [2] with normal free thyroid hormones. The newly published guidelines by the American Thyroid Association revised the upper limit of the TSH reference for the first trimester [6], epidemiological miRNA Critical to Abortion With SCH studies reported that women in early pregnancy with a serum TSH level between 2.5 mIU/L and the gestational-specific reference were more prone to SA [7, 8]. Studies have suggested that circulating miRNAs may be potential molecular biomarkers in the pathophysiological evolution of pregnancy, including SA [19, 20]. Studies investigating miRNA expression profiles in the pathogenesis of abortion associated with SCH are lacking
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