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PLoS One. 2015 Mar 26;10(3):e0120736. doi: 10.1371/journal.pone.0120736. eCollection 2015.

Orthotopic transplantation of cryopreserved mouse ovaries and gonadotrophin releasing hormone analogues in the restoration of function following chemotherapy-induced ovarian damage.

Author information

1
Department of Oncology, the 452nd hospital of People's Liberation Army, Sichuan, Chengdu, People's Republic of China; West China School of Medince, Sichuan University, Sichuan, Chengdu, People's Republic of China.
2
Department of Molecular and Clinical Cancer Medicine, Royal Liverpool University Hospital, University of Liverpool, Liverpool, United Kingdom.
3
West China School of Medince, Sichuan University, Sichuan, Chengdu, People's Republic of China.
4
Department of Thoracic Oncology, West China Hospital, Sichuan University, Sichuan, Chengdu, People's Republic of China.
5
Department of Chemotherapy, Sichuan Cancer Hospital, Sichuan, Chengdu, People's Republic of China.
6
Department of Oncology, the 452nd hospital of People's Liberation Army, Sichuan, Chengdu, People's Republic of China.
7
Department of Medical Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, Chengdu, People's Republic of China.
8
Department of IVF of West China Second Hospital, Sichuan University, Sichuan, Chengdu, People's Republic of China.

Abstract

Therapy advances are constantly improving survival rates of cancer patients, however the toxic effects of chemotherapy drugs can seriously affect patients' quality of life. In women, fertility and premature ovarian endocrine dysfunction are of particular concern. It is urgently we find methods to preserve or reconstruct ovarian function for these women. This study compares GnRHa treatment with ovarian tissue cryopreservation and orthotopic transplantation in a chemotherapy-induced ovarian damage murine model. 56 inbred Lewis rats were divided into 4 treatment groups: Saline control (group I); cyclophosphamide only (group II); cyclophosphamide plus GnRHa (group III); cyclophosphamide and grafting of thawed cryopreserved ovaries (group IV). Body weight, estrous cycle recovery time, ovarian weight, morphology and follicle count, as well as breeding and fertility were compared among groups. Only group IV was able to restore to normal body weight by the end of the observation period and resumed normal estrous cycles in a shorter time compared to other treatment groups. There was a decrease in primordial follicles in all treatment groups, but group III had the greatest reduction. Although, there was no difference in pregnancy, only one animal littered normal pups in group II, none littered in group III and four littered in group IV. Thus, cryopreservation and orthotopic transplantation of ovarian tissue can restore the fertility of rats subjected to chemotherapy in a manner that is superior to GnRHa treatment. We also observed increased rates of hepatic, splenic and pulmonary haemorrhage in group III, suggesting there may be synergistic toxicity of GnRHa and cyclophosphamide.

PMID:
25811681
PMCID:
PMC4374936
DOI:
10.1371/journal.pone.0120736
[Indexed for MEDLINE]
Free PMC Article

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