The effects of recombinant klotho in cisplatin‐induced ovarian failure in mice

Abstract

Aim To investigate whether recombinant klotho given concomitantly with cisplatin is effective in preventing cisplatin‐induced ovarian damage. Methods Thirty‐two adult female mice were divided into four groups. Saline was given to the first group, cisplatin to the second group, recombinant mouse klotho to the third group, and recombinant mouse klotho + cisplatin to the fourth group. The removed ovarian tissues were examined and groups were compared histologically and immunohistochemical examination for antimullerian hormone (AMH), superoxide dismutase (SOD) and catalase expression were done. Glutathione peroxidase (GPx) and glutathione reductase (GR) activities were measured by ELISA. Results Ovarian tissue weight, primary and secondary follicle counts were higher in cisplatin + recombinant klotho group compared to cisplatin group in our study (respectively p < 0.0001, p < 0.0001, and p = 0.010). Injury scores (stromal congestion, edema and infiltration, follicular degeneration scores and edema in corpus luteum scores) were similar between cisplatin and cisplatin + recombinant klotho groups (all p > 0.05). AMH staining intensities were similar between cisplatin and cisplatin + recombinant klotho groups (p = 0.925). There was no difference between the groups in terms of SOD, GPx, and GR (p > 0.05). Conclusions The recombinant klotho administered before cisplatin could partially protect the ovarian tissue from cisplatin‐induced ovarian damage considering that there was no difference in histologic injury score parameters, AMH staining intensity and oxidative stress markers between cisplatin and cisplatin plus klotho groups except that klotho preserved follicules to some extent. The antioxidant mechanism of action of klotho may not be the primary protection mechanism in cisplatin induced ovarian injury.

Paeoniflorin Alleviates Cisplatin-Induced Diminished Ovarian Reserve by Restoring the Function of Ovarian Granulosa Cells via Activating FSHR/cAMP/PKA/CREB Signaling Pathway

“…The pathogenesis of DOR is complex, and no unified animal model could be used on the study of DOR. Chemotherapy for oncological reasons is one of the common causes of DOR [19]; thus, cisplatin (CDDP, a chemotherapeutic drug) has been reported to be one of the most common methods to induce DOR with a shorter modeling cycle and typical pathological changes [33,34]. In the study, 1.0 mg/kg/day CDDP treatment for 5 consecutive days could cause an estrous cycle disorder, a decrease in the number of antral follicles and corpora lutea, an increase in the serum FSH level, and a decrease in the serum E 2 and AMH levels in mice, which were largely consistent with the clinical features of DOR patients, indicating that the in vivo model was successfully established and suitable to be used on the study of DOR.…”

Mechanism of Thymopentin Alleviating Cisplatin-Induced Premature Ovarian Failure by Reducing Endoplasmic Reticulum Stress in Granulosa Cells

“…In addition, many studies in this field in recent years have pointed out that the induction and development of endoplasmic reticulum pressure in ovarian GC go hand in hand in the ubiquitination course of specific molecules in cells [12] . GC cells play a vital role in biological course, but the role of TP5 in GC has not been thoroughly studied [13,14] . In this study, we found that TP5 was helpful to maintain the steady state of GCs endoplasmic reticulum and provide a stationary internal environment for follicular advancement.…”