An overview of different methods to establish a murine premature ovarian failure model.

Premature ovarian failure (POF)is defined as the loss of normal ovarian function before the age of 40 and is characterized by increased gonadotropin levels and decreased estradiol levels and ovarian reserve, often leading to infertility. The incomplete understanding of the pathogenesis of POF is a major impediment to the development of effective treatments for this disease, so the use of animal models is a promising option for investigating and identifying the molecular mechanisms involved in POF patients and developing therapeutic agents. As mice and rats are the most commonly used models in animal research, this review article considers studies that used murine POF models. In this review based on the most recent studies, first, we introduce 10 different methods for inducing murine POF models, then we demonstrate the advantages and disadvantages of each one, and finally, we suggest the most practical method for inducing a POF model in these animals. This may help researchers find the method of creating a POF model that is most appropriate for their type of study and suits the purpose of their research.

Reduced inflammation following human endometrial stromal/stem cell injection into male Wistar rats with cisplatin-induced acute kidney injury.

Introduction: Inflammation is one of the most important mechanisms involved in cisplatin-induced acute kidney injury (AKI). Mesenchymal stromal/stem cells (MSCs) exhibit anti-inflammatory and immunomodulatory abilities. Human endometrial stromal/stem cells (hEnSCs) exhibit similar properties to MSCs. These cells secrete immunoregulators, so we investigated the inflammatory aspect of hEnSCs in the treatment of cisplatin-induced AKI in Wistar rats. Methods: Each group consisted of 6 male Wistar rats. Groups were as follows: sham, model (5 mg/kg cisplatin, IP), and treatment (1 million hEnSCs, IV, 3 hours after cisplatin). Renal function, histopathology, proliferation rate, infiltration of CD3+ T cell, and expression of Il-10 and cystatin c (Cst3) were assessed on day 5. DiI-labeled cells were tracked in kidney and liver on days 4 and 14. Results: HEnSC transplantation improved cisplatin-induced injuries such as renal dysfunction and tissue damage. The highest levels of pathologic scores and hyaline cast formation were observed in the model group while hEnSCs transplantation resulted in their reduction (154.00 ± 14.95, 8.00 ± 1.41 vs. 119.40 ± 5.43, 2.50 ± 1.05). The percentage of Ki-67 positive cells in the treatment group increased while cisplatin decreased proliferation (39.91 ± 5.33 vs. 23.91 ± 3.57 in glomeruli and 39.07 ± 2.95 vs. 16.61 ± 3.25 in tubules). The expression of Cst3 and Il-10 was higher in the model and treatment groups, respectively. DiI-labeled cells were observed in the renal tubules and liver lobes on days 4 and 14. Conclusion: HEnSCs may ameliorate cisplatin-induced AKI through anti-inflammatory and immunomodulatory effects and/or through paracrine effects.

Human Endometrial Stromal/Stem Cells Inhibit Apoptosis in Cisplatin-Induced Acute Kidney Injury in Male Wistar Rats.

OBJECTIVE: Acute kidney injury (AKI) is referred to as sudden decline in the function of kidney. Human endometrial stromal/stem cells (hEnSCs) are mesenchymal stem cell (MSC)-like cells, which are suitable candidates for regenerative medicine purposes, yet the effect of hEnSCs on cisplatin-induced AKI has not been studied; therefore, the present study was conducted to investigate this gap in the literature. MATERIALS AND METHODS: In this experimental study, hEnSCs were obtained from endometrial biopsy using collagenase I and were then cultured in DMEM/F12 medium. A total of 48 male Wistar rats (150-200 g) were classified into four groups: intact -receiving no treatment, model -receiving 5 mg/kg of body weight cisplatin, as well as phosphate-buffered saline (PBS) and cell -receiving either PBS or hEnSCs for three hours after cisplatin injection, respectively. Biochemical parameters, pathologic scores, apoptosis assay, Bcl-2 and Tnf-α expression were evaluated on day 5. RESULTS: On day 5 post-transplantation we observed that HEnSCs injection has led to a decrease in both blood urea nitrogen (BUN) and serum creatinine (SCr), compared to the model and PBS groups (0.82 ± 0.03 vs. 1.42 ± 0.06, 1.09 ± 0.05 mg/dl and 61.53 ± 3.07 vs. 116.60 ± 2.12, 112.00 ± 1.35 mg/dl, respectively). The highest levels of pathologic scores were observed in model and PBS groups, while hEnSCs transplantation resulted in a decrease in pathologic scores (149.10 ± 7.03, 141.50 ± 4.68 vs. 118 ± 2.16). HEnSCs significantly decreased the percentage of TUNELpositive cells in the cell group compared with model and PBS groups (20.37 ±. 3.37 vs. 33.67 ± 1.79, 31.53 ± 1.05 in glomeruli and 15.10 ± 1.47 vs. 42.33 ± 1.72, 39.23 ± 1.61 in tubules). In addition, HEnSCs resulted in upregulation of Bcl-2 and downregulation of Tnf-α in the cisplatin-induced AKI. CONCLUSION: Our results showed that injection of hEnSCs may improve AKI through lowering the amount of apoptosis in renal cells.