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BACKGROUND Cold-inducible RNA-binding protein (CIRBP) is associated with cell stress. However, its upstream regulatory factors are still largely unknown. OBJECTIVES This study investigated whether CIRBP expression was regulated by transforming growth factor beta (TGF-β) during the process of heat-induced testicular damage. MATERIALS AND METHODS Ten male adult ICR mice were allocated to heat treatment (scrotal hyperthermia at 43 °C for 30 min, n = 5) and control group (n = 5); CIRBP and TGF-β1, TGF-β2, and TGF-β3 expression levels in the testis in mRNA and protein were analyzed. Then, we conducted in vivo and in vitro studies to investigate the regulatory effects of TGF-β on CIRBP. In the in vivo study, male adult ICR mice were subjected to testicular hyperthermia followed by a local testicular injection of TGF-β antagonist (non-selective TGF-β I/II receptor inhibitor, 5 μg or 10 μg). In the in vitro study, GC2-spd cells were cultured under 43 °C for 30 min or with different TGF-β isoforms (10 ng/mL), and CIRBP expression levels in the testis and GC2-spd cells were analyzed 24 and 48 h, respectively, after treatment. RESULTS As a result, heat treatment significantly downregulated the relative CIRBP mRNA and protein expression (p = 0.006 and 0.011), and significantly upregulated TGF-β2 and TGF-β3 expression levels (p = 0.022 and 0.04, for mRNA, and p = 0.001 for both protein levels). Local testicular injection of 10 μg TGF-β antagonist significantly attenuated heat-induced histological damage to the testes and CIRBP downregulation (p = 0.038). Furthermore, TGF-β2 and TGF-β3 significantly downregulated CIRBP mRNA and protein expression in GC2-spd cells (all p

Copper nanoparticles (Cu-NPs) have been used increasingly in various products and applications. Although recent studies have reported that exposure to Cu-NPs leads to organ accumulation and obvious toxicity, it remains unclear whether Cu-NPs can be translocated to and cause damage in the uterus. In this study, we investigated the potential for uterine injury and gene expression patterns in female rats exposed to 3.12, 6.25, or 12.5 mg/kg/d Cu-NPs via intraperitoneal injection for 14 consecutive days. The results indicated that exposure to Cu-NPs led to significant decreases in the relative uterine weight coefficients and increases in inflammatory cell infiltration, mitochondrial swelling and vacuolization, shortened and reduced endometrial epithelial cell microvilli, and apoptosis. Furthermore, exposure to Cu-NPs increased malondialdehyde (MDA) accumulation and decreased superoxide dismutase (SOD) levels. Signal transduction mechanism studies indicated that exposure to Cu-NPs activated caspases 3, 8, and 9 and BH3 interacting domain death agonist (tBid), reduced B cell leukemia/lymphoma 2 (Bcl-2) expression, and increased the expression of apoptotic peptidase activating factor 1 (Apaf-1), BCL2-associated X, apoptosis regulator (Bax), and cytochrome c. A microarray analysis revealed significant alterations in the expression of 963 genes; of these, 622 were upregulated and 341 were downregulated. The results of further evaluations of some altered genes, including matrix metallopeptidase 12 (Mmp12), using quantitative RT-PCR agreed with the microarray findings. These results provide strong evidence that Cu-NPs can trigger both intrinsic and extrinsic apoptotic pathways to mediate uterine injury, resulting in oxidative stress-related changes in gene expression.

Background Adverse pregnancy outcomes (APOs) are involved in a series of abnormal pregnancies like embryo growth arrest, spontaneous abortion, premature birth, stillbirth, fetal malformation, birth defects and other pathological pregnancy, and childbirth complications. Polymorphism of methylenetetrahydrofolate reductase gene (MTHFR, 607093) is one of the main genetic causes of APO. However, there is still debate on whether MTHFR 1298A>C, rs1801131, polymorphism is related to APO. For the lack of extensive research in the Chinese population at present, the study aim to investigate the relationship between MTHFR 1298A>C polymorphism with APO through a large number of data. Methods A total of 241 samples from patients with APO and 117 healthy controls in Yunnan province were used for MTHFR gene polymorphism analysis, with double fluorescence quantitative polymerase chain reaction (PCR). In consideration of the low frequency of MTHFR 1298C/C genotype, which might affect the statistic results, further datasets of MTHFR 1298A>C polymorphism were collected from literature and analyzed. Results No statistical difference was detected in the frequency of MTHFR1298A>C polymorphism between two groups in Yunnan. Our data showed that the frequency of MTHFR 1298A/A genotype had the decreasing tendency among Chinese population from northern to southern, as well as eastern to western of China. The frequency of MTHFR 1298A/C and 1298C/C genotypes had the adverse tendency. The frequency of MTHFR 1298C/C genotype was significantly different between two groups in Chinese populations. The significant difference was also observed in the frequency of MTHFR 1298C/C polymorphism between two groups from central China and southern China. Conclusion In summary, our data showed that MTHFR 1298C/C genotype was one of the important genetic factors of APO in China.