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GnRH antagonist cetrorelix inhibits mitochondria-dependent apoptosis triggered by chemotherapy in granulosa cells of rats.
Gynecol Oncol 2010; 118(1):69-75GO

Abstract

OBJECTIVE

Exposure to chemotherapy causes various adverse effects on the ovaries including premature ovarian failure and infertility. GnRH antagonist cetrorelix could reverse the ovarian damage during chemotherapy, but the mechanism remains unclear. The objectives of this study were to examine the role of the cetrorelix for prevention of mitochondria-dependent apoptosis in granulosa cells of rats during the treatment with cyclophosphamide(Cy), if the mitochondria-dependent apoptotic process was involved.

METHODS

Female SD rats were injected with cetrorelix before and after administration of saline, or Cy. Main outcome measures were the apoptotic indexes, serum hormones, ultrastructure of granulosa cells, mitochondrial membrane potential, the kinetics of cytochrome c (Cyt-c) processing in cells, and apoptotic markers.

RESULTS

The ovarian apoptotic indexes as shown by TUNEL assay were reduced by cetrorelix pretreatment and the rats regained normal hormonal profile. The ultrastructure and JC-1 fluorescence intensity assessments showed cetrorelix pretreatment inhibited mitochondrial dysfunction in granulosa cells induced by chemotherapy. Western blot analysis showed that cetrorelix suppressed the release of Cyt-c from mitochondria to cytoplasm. Meanwhile, cetrorelix pretreatment expressed less Bax, caspase-3 and Cyt-c in granulosa cells compared with chemotherapy alone.

CONCLUSION

Cetrorelix could reduce the apoptosis in granulosa cells through inhibiting mitochondria-dependent apoptosis triggered by chemotherapy.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, Xi'jing Hospital, 4th Military Medical University, Xi'an, Shaanxi 710033, PR China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20417958

Citation

Zhao, Xue-Jing, et al. "GnRH Antagonist Cetrorelix Inhibits Mitochondria-dependent Apoptosis Triggered By Chemotherapy in Granulosa Cells of Rats." Gynecologic Oncology, vol. 118, no. 1, 2010, pp. 69-75.
Zhao XJ, Huang YH, Yu YC, et al. GnRH antagonist cetrorelix inhibits mitochondria-dependent apoptosis triggered by chemotherapy in granulosa cells of rats. Gynecol Oncol. 2010;118(1):69-75.
Zhao, X. J., Huang, Y. H., Yu, Y. C., & Xin, X. Y. (2010). GnRH antagonist cetrorelix inhibits mitochondria-dependent apoptosis triggered by chemotherapy in granulosa cells of rats. Gynecologic Oncology, 118(1), pp. 69-75. doi:10.1016/j.ygyno.2010.03.021.
Zhao XJ, et al. GnRH Antagonist Cetrorelix Inhibits Mitochondria-dependent Apoptosis Triggered By Chemotherapy in Granulosa Cells of Rats. Gynecol Oncol. 2010;118(1):69-75. PubMed PMID: 20417958.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GnRH antagonist cetrorelix inhibits mitochondria-dependent apoptosis triggered by chemotherapy in granulosa cells of rats. AU - Zhao,Xue-Jing, AU - Huang,Yan-Hong, AU - Yu,Yue-Cheng, AU - Xin,Xiao-Yan, Y1 - 2010/04/24/ PY - 2010/01/26/received PY - 2010/03/19/revised PY - 2010/03/28/accepted PY - 2010/4/27/entrez PY - 2010/4/27/pubmed PY - 2010/6/23/medline SP - 69 EP - 75 JF - Gynecologic oncology JO - Gynecol. Oncol. VL - 118 IS - 1 N2 - OBJECTIVE: Exposure to chemotherapy causes various adverse effects on the ovaries including premature ovarian failure and infertility. GnRH antagonist cetrorelix could reverse the ovarian damage during chemotherapy, but the mechanism remains unclear. The objectives of this study were to examine the role of the cetrorelix for prevention of mitochondria-dependent apoptosis in granulosa cells of rats during the treatment with cyclophosphamide(Cy), if the mitochondria-dependent apoptotic process was involved. METHODS: Female SD rats were injected with cetrorelix before and after administration of saline, or Cy. Main outcome measures were the apoptotic indexes, serum hormones, ultrastructure of granulosa cells, mitochondrial membrane potential, the kinetics of cytochrome c (Cyt-c) processing in cells, and apoptotic markers. RESULTS: The ovarian apoptotic indexes as shown by TUNEL assay were reduced by cetrorelix pretreatment and the rats regained normal hormonal profile. The ultrastructure and JC-1 fluorescence intensity assessments showed cetrorelix pretreatment inhibited mitochondrial dysfunction in granulosa cells induced by chemotherapy. Western blot analysis showed that cetrorelix suppressed the release of Cyt-c from mitochondria to cytoplasm. Meanwhile, cetrorelix pretreatment expressed less Bax, caspase-3 and Cyt-c in granulosa cells compared with chemotherapy alone. CONCLUSION: Cetrorelix could reduce the apoptosis in granulosa cells through inhibiting mitochondria-dependent apoptosis triggered by chemotherapy. SN - 1095-6859 UR - https://www.unboundmedicine.com/medline/citation/20417958/GnRH_antagonist_cetrorelix_inhibits_mitochondria_dependent_apoptosis_triggered_by_chemotherapy_in_granulosa_cells_of_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0090-8258(10)00282-9 DB - PRIME DP - Unbound Medicine ER -