Implantation failure in rats with subclinical hypothyroidism is associated with LIF/STAT3 signaling

BACKGROUND: Pregnant women with subclinical hypothyroidism are associated with an increased risk of spontaneous abortion. This study aim to investigate the mechanisms underlying the effects of maternal subclinical hypothyroidism during early pregnancy on abortion in the uterus, focusing upon the LIF/STAT3 signaling pathway. METHODS: 105 Wistar rats were randomly divided into three groups (35 rats in each group): control (CON) group, subclinical hypothyroidism (SCH) group, and overt hypothyroidism (OH) group. We examined the weight of rat uteri, rat placenta and embryos. We also determined the number of implantation sites and the embryo absorption rates. The protein and mRNA expressions of TSHR, TR-α, TR-β, LIFR, gp130, JAK1, p-STAT3, and STAT3 were measured by immunohistochemical staining, real-time polymerase chain reaction (PCR), and western blotting. RESULTS: The weights of rat uteri, rat placenta and embryos were significantly reduced in the SCH and OH groups. The number of implantation sites were significantly decreased in the SCH and OH groups, while embryo absorption rates were significantly increased. The mRNA and protein expressions of TSHR were upregulated in the SCH and OH groups, while TR-α and TR-β showed no difference when compared between the three groups. The expressions of LIFR, gp130, JAK1, and p-STAT3 were significantly higher in the SCH and OH groups. CONCLUSIONS: Clinical and subclinical hypothyroidism during early pregnancy might cause adverse pregnancy outcomes. Implantation failure in rats with subclinical hypothyroidism was associated with abnormal LIF/STAT3 signaling.