Dynamic effect of di-2-(ethylhexyl) phthalate on testicular toxicity: epigenetic changes and their impact on gene expression.

This study investigated epigenetic (specifically, DNA methylation) changes and their impact on gene expression in testes induced by maternal exposure to Di-2-(ethylhexyl) phthalate (DEHP) in mice. Testicular dysgenesis syndrome was induced in fetuses and pups by maternal exposure to DEHP at 500 mg/kg/d, and testes were excised for analysis on gestation day (GD) 19 and postnatal days (PNDs) 3, 21, 56, and 90. High-performance liquid chromatography (HPLC) was performed to analyze DNA methylation status, and expression levels of the DNA methyltransferases were examined by quantitative real-time polymerase chain reaction (qPCR). Testis-specific gene, insulin-like hormone 3 (Insl3), and testosterone production were also detected. DEHP significantly increased DNA methylation levels on GD 19 and PND 3 (P < .05 and P < .05) but not on PNDs 21, 56, and 90. DEHP also significantly increased the expression of DNA methyltransferases. For DNA methyltransferase 1, the difference was not significant on PND 21, and DNA methyltransferase 3a and 3b returned to normal levels on PND 56. Fetal testes were a main target for DEHP as evidenced by a reduction in Insl3 expression and testosterone production. Effects of DEHP on Insl3 expression continued until PND 21. The DEHP-induced suppression of testosterone had not recovered on PND 56. Changes in DNA methylation may play an important role in abnormal testicular function caused by environmental factors such as maternal exposure to DEHP, which may be a mechanism of DEHP-mediated testicular toxicity.

Combined Application of Dexamethasone and Tranexamic Acid to Reduce the Postoperative Inflammatory Response and Improve Functional Outcomes in Total Hip Arthroplasty.

OBJECTIVE: To evaluate the efficacy and safety of combined use of tranexamic acid (TXA) and dexamethasone (DEX) for anti-inflammatory and clinical outcomes after total hip arthroplasty (THA). METHODS: A total of 100 patients were included in this randomized, controlled study. Patients in the TXA + DEX group were administered TXA at a dose of 15 mg/kg, which was repeated 3 h after THA, and received 20 mg DEX. In contrast, patients in the TXA group were administered TXA at a dose of 15 mg/kg, which was repeated at 3 h postoperatively. C-reactive protein (CRP), interleukin-6 (IL-6) and pain levels, incidence of postoperative nausea and vomiting (PONV), total blood loss and transfusion rates, postoperative fatigue, range of motion (ROM), length of hospital stay (LOS), analgesic rescue and antiemetic rescue consumption, and complications were compared in both groups. RESULTS: The CRP and IL-6 levels were lower in the TXA + DEX group than in the TXA group (all P < 0.001) at 24 h, 48 h, and 72 h postoperatively. Patients in the TXA + DEX group had lower pain scores at rest and walking at 24 h postoperatively (all P < 0.001). In the TXA + DEX group, the incidence of PONV was lower (P = 0.005), postoperative fatigue (P < 0.001) was reduced, and analgesia and antiemetic rescue consumption were also reduced. The total blood loss, transfusion rate, LOS and hip ROM were similar in the two groups. There was no thrombosis, infection, or gastrointestinal bleeding in either group. CONCLUSION: Compared to TXA alone, the combination of TXA + DEX can reduce postoperative inflammatory response, relieve pain, and reduce PONV and fatigue, without increasing the risk of complications. Therefore, the present study suggested that the combination of TXA + DEX is an effective and safe accelerated rehabilitation strategy for patients receiving primary unilateral THA.

[Di-(2-ethylhexyl) phthalate increases the DNA methylation level of genomes in the mouse testis].

OBJECTIVE: To investigate the effect of the exposure to di- (2-ethylhexyl) phthalate (DEHP) during pregnancy on the DNA methylation level of genomes in the testis of the offspring in mice. METHODS: Pregnant KM mice were randomly divided into three groups, normal control, corn oil and DEHP-exposed. Corn oil and DEHP (500 mg/[kg x d]) were administrated respectively from gestation day 12.5 (GD 12.5) to postnatal day 3 (PND 3). The testes of the offspring were excised on PND 7, and their genomic DNA was treated with EcoR I /Msp I and EcoR I /Hpa II. The genome-wide DNA methylation patterns of the CCGG sites were detected by methylation-sensitive amplification polymorphism (MSAP). The samples were electrophoresed in the ABI 3730 DNA sequencer and the results analyzed by the Genescan3.1. RESULTS: The average incidence of DNA methylation was (34.03 +/- 3.05)% in the DEHP-exposed mice, obviously higher than (28.37 +/- 2.37)% in the normal control and (28.58 2.45)% in the corn oil group, with statistically significant differences (P < 0.05). CONCLUSION: Exposure to DEHP during pregnancy increases the DNA methylation level of the genome in the testis of the offspring and affects the apparent genetic modification of the genome, which may be one of the important toxicological causes of the lesion in the reproductive system.

Dynamic epigenetic changes involved in testicular toxicity induced by di-2-(ethylhexyl) phthalate in mice.

The aim of this study was to analyse epigenetic (specifically, DNA methylation) change in testes induced by maternal exposure to di-2-(ethylhexyl) phthalate (DEHP) in mice. Testicular dysgenesis syndrome was induced in foetuses by maternal exposure to DEHP. High-performance liquid chromatography was performed to analyse DNA methylation status, and expression levels of the DNA methyltransferases were examined by quantitative real-time polymerase chain reaction and western blotting. DEHP significantly had more than 10% relative increase in the global DNA methylation and also increased DNA methyltransferases' expression. Changes in DNA methylation may play an important role in abnormal testicular function caused by environmental factors such as maternal exposure to DEHP, which may be one possible mechanism of DEHP-mediated testicular toxicity.