Maternal subclinical hypothyroidism and behavioral problems in preschoolers: A cohort study / 中华内分泌代谢杂志

Objective:To investigate the effects of maternal subclinical hypothyroidism (SCH) on preschoolers′ behavioral problems.Methods:Based on the Ma′ anshan Birth Cohort, pregnant women who had their first antenatal checkup in Maternal and Child Health Center in Ma′ anshan were recruited from May 2013 to September 2014. Data on demographic, obstetric information, and maternal exposure were collected. Women′s fasting venous blood in the first, second, and third trimesters of pregnancy was collected. The levels of thyroid hormones [thyrotropin (TSH), free thyroxine (FT 4)] and thyroid autoantibodies [thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb)] in maternal blood were retrospectively detected by electrochemiluminescence immunoassay. Preschoolers′ behavioral problems were assessed by Achenbach Child Behavior Checklist (CBCL/1.5-5). Poisson regression models were adopted to examine the effect of maternal SCH on preschoolers′ internalizing and externalizing problems and the critical period. Results:In this study, the reference of maternal thyroid indexes was established (between 2.5 th and 97.5 th percentile). The reference of TSH in the first, second, and third trimester of pregnancy was 0.04-4.90 μIU/mL, 0.75-6.08 μIU/mL, and 0.58-5.59 μIU/mL respectively; and the reference of FT 4 was 13.19-23.27 pmol/L, 9.14-15.32 pmol/L, and 9.53-17.45 pmol/L respectively. In the first, second, and third trimester of pregnancy, the prevalence of SCH was found to be 2.0% (25/1 224), 1.6% (19/1 218), and 1.7% (21/1 220), respectively. After adjusting for confounding factors, maternal SCH in the first trimester was associated with the risk of anxiety and depression in preschool children ( OR=3.06, 95% CI 1.05-8.98). Maternal SCH in the second trimester was found to be associated with the risk of overreaction in preschool children ( OR=2.65, 95% CI 1.13-6.21). Conclusions:The establishment of thyroid hormones reference range for pregnant women in Ma′ anshan area is beneficial to the screening, diagnosis, and treatment of thyroid diseases during pregnancy in this area. Maternal SCH during pregnancy is associated with increased risk of behavioral problems in preschool children. In the first trimester, maternal SCH was associated with preschoolers′ anxiety and depression, and in the second trimester, maternal SCH was associated with preschoolers′ emotional reactivity.

DNase I improves blood-milk barrier integrity and alleviates inflammation induced by Staphylococcus aureus during mastitis.

Mastitis is an inflammation of mammary gland, which directly affects the milk production performance and causes huge economic losses in the dairy industry. During mastitis, the blood-milk barrier (BMB) loses its integrity and aggravates the severity of mastitis. Exogenous DNase I has been exerted protective effects in different model of tissue injury. Here, we designed a study to investigate the effects of DNase I on inflammation and BMB in a mice model of Staphylococcus aureus-induced mastitis. In the model, we found that DNase I treatment significantly alleviated the inflammatory response through decrease of inflammatory cells in mammary alveoli, MPO activity and cytokines in mammary gland. Furthermore, immunofluorescent staining and western blotting demonstrated that exogenous DNase I obviously reduced BMB permeability and changed the expression of tight junction proteins to support the re-establishment of the barrier integrity. Mechanismly, DNase I treatment inhibited NF-κB and enhanced AKT signaling pathways. Therefore, our results indicate that DNase I may be an effective treatment for attenuating mastitis.

Lysine-specific demethylase 1 (LSD1) serves as an potential epigenetic determinant to regulate inflammatory responses in mastitis.

It is well-established that lysine-specific demethylase 1 (LSD1) is the first identified histone demethylase. Based on its demethylase enzymatic activity, LSD1 plays a pivotal role in vast range of cellular processes and cancers, but the understanding of its effects on inflammation is relatively limited. Using in vivo models of lipopolysaccharide (LPS)-induced inflammation and in vitro assays in mouse mammary epithelial cells, we identified the novel regulatory roles and underlying mechanisms of LSD1 on LPS-induced mastitis. Mammary gland and cells were collected for the following experiments after treatment. Histological changes were determined by H&E. Western blot analysis was used to detect the protein expression. ELISA and real-time PCR were used to evaluate protein and mRNA expression of inflammatory genes. Our results showed that LPS treatment resulted in a significant increase in LSD1 protein expression. GSK-LSD1 is a selective inhibitor of LSD1 enzyme activity. Treatment of mice with GSK-LSD1 inhibited LSD1 activity, reduced inflammatory cells recruitment to tissues and attenuated LPS-induced damage in mammary gland. Mechanistic investigations suggested that LSD1 inhibition led to the increase of histone H3K4me2 and H3K9me2. Furthermore, GSK-LSD1 inhibition of LSD1 further inhibited nuclear factor κ-B (NF-κB) signaling cascades, and subsequently inhibited the production of cytokines (TNF-α, IL-6 and IL-1ß) in mammary gland. Taken together, our data reveal LSD1 as a potential regulator of inflammation and improve our understanding of epigenetic control on inflammation.