Research advances in TET enzyme and its intermediate product 5hmC / 中南大学学报(医学版)

DNA methylation is a significant epigenetic modification mode, which plays an important role in embryo reprogramming, stem cell differentiation and tumor occurrence. The ten-eleven translocation (TET) enzyme is a crucial demethylation enzyme, which can catalyze 5-methylcytosine(5mC) to 5-hydroxymethylcytosine(5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine(5caC). These bases represent the epigenetic modifications of DNA and regulate the process of DNA methylation. Understanding the role of TET enzyme in regulating the DNA methylation modification and gene expression can help us to gain the knowledge for the normal growth development and epigenetic regulation in human diseases.

Effect of adipose-derived mesenchymal stem cell transplantation on cyclophosphamide-induced ovarian damage in rats / 中南大学学报(医学版)

To explore the effect of adipose-derived mesenchymal stem cells (ADMSCs) on ovarian damage induced by cyclophosphamide (CTX) and its mechanism.
 Methods: ADMSCs isolated from adipose tissue of female SD rats were cultured and divided into a blank group and a CTX group (n=15 in each group). CTX (75 mg/kg) was injected intraperitoneally to establish a model of ovarian damage in rats. A total of 45 female SD rats were also divided into 3 groups: Group A (15 rats, only injected intraperitoneally with 75 mg/kg CTX diluted with 1 mL 0.9% saline), Group B [15 rats, injected intraperitoneally with 75 mg/kg CTX diluted with 1 mL 0.9% saline, after 4 estrus cycles, injected 0.6 mL ADMSCs (6×105 cells) by the tail vein], and Group C [15 rats, injected intraperitoneally with 75 mg/kg CTX diluted with 1 mL 0.9% saline, after 4 estrus cycles, injected 40 mL ADMSCs (20 mL per side, 2×104 cells) in situ ovarian]. After 4 estrus cycles, the changes of quality of life, ponderal growth were recorded, the sex hormone levels [estradiol (E2), follicle-stimulating hormone (FSH)] were tested by ELISA, and the morphology of ovarian tissue and follicle count were observed by HE staining. The expression of BMP-15, Bcl-2 and Bax in ovarian tissues were tested by immunohistochemistry, real-time PCR or Western blotting. The apoptosis rate of follicular cells was detected by TdT-mediated dUTP nick end labeling (TUNEL) assay.
 Results: After transplantation of ADMSCs, compared with the Group A, their quality of life of rats in the Group B and C was improved, and the ponderal growth was increased (both P0.05).
 Conclusion: ADMSCs transplantation can effectively repair ovarian damage induced by CTX in rats, which may be achieved by inhibiting mitochondrial apoptosis of granulosa cells.

Effect of letrozole on endometrosis and apoptosis of ectopic endometrial cells in rats / 中南大学学报(医学版)

OBJECTIVE@#To investigate the therapeutic mechanism of letrozole, the third-generation aromatase inhibitor, on endometriotic lesions in a rat model and its effect on the apoptosis of ectopic endometrial cells.@*METHODS@#Endometriosis was induced by autotransplanting pieces of uterus onto the peritoneum in rats. The rats with successful ectopic implants were divided into 2 groups: A letrozole group (n=15) and a control group (n=15). The volume, appearance, and histopathology of ectopic implant were determined before and after the treatment. Expression of P450arom, COX-2, bcl-2, and bax in the ectopic implant was detected by immunohistochemistry and RT-PCR in the 2 groups.@*RESULTS@#The volume of ectopic implant in the letrozole group was significantly reduced compared with the control group (P<0.05). The protein and mRNA levels of P450arom and COX-2 in the ectopic implant were significantly decreased in the letrozole group compared with the control group (P<0.05). There was a positive correlation between the expression of P450arom and the expression of COX-2 (r=0.943, P<0.001; r=0.913, P<0.001). The protein and mRNA expression of bcl-2 was significantly decreased (P<0.05), and the bax protein and mRNA expression was significantly increased (P<0.05) in the ectopic implant with an increased bax/bcl-2 ratio in the letrozole group compared with the control group (P<0.05).@*CONCLUSION@#Letrozole can obviously reduce the size of ectopic implant through decreasing P450arom and COX-2 expression, suppressing the secretion of estrogen, inhibiting the proliferation, and inducing the apoptosis of ectopic implants.