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Protective effects ROS up-regulation on premature ovarian failure by suppressing ROS-TERT signal pathway
1Department of Obstetrics, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. ganyapingya@163.com.
Objective:
Premature ovarian failure (POF) refers to the condition of pre-onset ovarian function failure, and is one commonly occurred disease in gynecology. Its pathogenic mechanism, however, is still unclear. Early study found decreased activity of telomerase reverse transcriptase (TERT). As an important factor to suppress TERT, oxidative stress has not been studied in POF. We, thus, investigated the role of reactive oxygen species (ROS)-TERT in POF.
Materials And Methods:
Rat POF model was induced by a single intraperitoneal injection of cyclophosphamide plus 12 mg/kg busulfan. Level of follicle stimulating hormone (FSH) and inhibin B was measured by enzyme-linked immunosorbent assay (ELISA), along with hematoxylin and eosin (HE) staining to confirm successful generation of models. Western blot was applied to measure TERT expression, and N-acetyl-cysteine (NAC) or TERT small interfere RNA (siRNA) was injected to suppress ROS or TERT level, followed by HE staining to observe POF condition.
Results:
In POF model, ovary tissues showed atrophy, less follicles, and more follicular atresia, plus mesenchymal hyperplasia. FSH and inhibin B level were significantly up-regulated and down-regulated, respectively (p<0.05). In POF rat, ROS level was elevated (p<0.05) whilst TERT level was decreased. NAC inhibited ROS level and enhanced TERT expression. In contrast, TERT siRNA further aggravated POF condition.
Conclusions:
ROS up-regulation inhibits TERT expression, suppresses TERT activity and facilitates POF. The ROS-TERT pathway may work as the target for treating POF.
Insights
Reactive oxygen species (ROS) elevate in premature ovarian failure (POF), inhibiting telomerase reverse transcriptase (TERT) and worsening the condition. Targeting the ROS-TERT pathway may offer a new treatment for POF.
Area of Science:
- Gynecology
- Reproductive Biology
- Cellular Biology
Background:
- Premature ovarian failure (POF) is a gynecological condition with unclear pathogenic mechanisms.
- Decreased telomerase reverse transcriptase (TERT) activity has been observed in POF.
- The role of oxidative stress, a suppressor of TERT, in POF remains understudied.
Purpose of the Study:
- To investigate the involvement of reactive oxygen species (ROS) and TERT in the pathogenesis of POF.
- To explore the potential of targeting the ROS-TERT pathway for POF treatment.
Main Methods:
- A rat model of POF was established using cyclophosphamide and busulfan.
- Hormone levels (FSH, inhibin B) and ovarian histology were assessed.
- Western blot was used to measure TERT expression.
- N-acetyl-cysteine (NAC) was used to reduce ROS, and TERT small interfering RNA (siRNA) was used to suppress TERT.
Main Results:
- POF models exhibited ovarian atrophy, reduced follicles, increased follicular atresia, and elevated FSH and decreased inhibin B levels.
- Elevated ROS and decreased TERT levels were observed in POF rats.
- NAC treatment reduced ROS and increased TERT expression, ameliorating POF.
- TERT siRNA exacerbated the POF condition.
Conclusions:
- Increased ROS inhibits TERT expression and activity, contributing to POF.
- The ROS-TERT pathway is implicated in POF pathogenesis.
- Modulating the ROS-TERT pathway presents a potential therapeutic strategy for POF.
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