A combination of stereological methods, biochemistry and electron microscopy for the investigation of drug treatment effects in experimental animals.
Some chemotherapeutic agents used for breast cancer (BC) treatment can induce severe side effects in the ovarian tissue. The combination of cyclophosphamide and docetaxel (TC) is widely used for BC treatment; however, its late effects in the ovary are not completely understood. The main purpose of this study was to evaluate the structural and ultrastructural alterations in the ovarian stroma induced by TC treatment. Wistar rats were divided into two groups: a control group and a TC group. They were euthanized 5 months after the end of treatment, and their plasma and ovaries were collected. Important alterations were noted. The serum estradiol level was significantly reduced in the TC group compared with the control group. Additionally, the number of apoptotic nuclei was higher in the TC group. The role of the inflammatory response in the development of ovarian damage was investigated, and we found an increased number of mast cells and increased expression of TNF-α in the TC group. The involvement of fibrosis was also investigated. The results showed that the TC group had increased expression levels of TGF-β1, collagen type I (col-I) and collagen type III (col-III) compared with the control group. Ultrastructural analysis revealed the presence of collagen fibrils in the treated group and illustrated that the ovarian tissue architecture was more disorganized in this group than in the control group. The results from this study are important in the study of chemotherapy-induced ovarian failure and provide further insight into the mechanisms involved in the development of this disease.
Laboratório de Pesquisas em Células-Tronco, Departamento de Histologia e Embriologia, Instituto de Biologia Roberto Alcântara Gomes, UERJ, Rio de Janeiro, RJ, Brazil.
Alan C N
AC
De Moraes
Laboratório de Cardiologia Celular e Molecular, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, UFRJ, Rio de Janeiro, Brazil.
Cherley B V
CB
Andrade
Laboratório de Ciências Radiológicas, Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcântara Gomes, UERJ, Rio de Janeiro, RJ, Brazil.
Camila
C
Salata
Laboratório de Ultraestutura e Biologia Tecidual, Departamento de Histologia e Embriologia, Instituto de Biologia Roberto Alcântara Gomes, UERJ, Rio de Janeiro, RJ, Brazil.
Ana L R
AL
Nascimento
Laboratório de Cardiologia Celular e Molecular, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, UFRJ, Rio de Janeiro, Brazil.
Isalira P
IP
Ramos
Laboratório de Cardiologia Celular e Molecular, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, UFRJ, Rio de Janeiro, Brazil.
Regina C S
RC
Goldenberg
Laboratório de Ultraestutura e Biologia Tecidual, Departamento de Histologia e Embriologia, Instituto de Biologia Roberto Alcântara Gomes, UERJ, Rio de Janeiro, RJ, Brazil.
Jorge J
JJ
Carvalho
Laboratório de Pesquisas em Células-Tronco, Departamento de Histologia e Embriologia, Instituto de Biologia Roberto Alcântara Gomes, UERJ, Rio de Janeiro, RJ, Brazil.
Ana C S
AC
Machado
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000627:therapeutic use; D000077143:Docetaxel; D004958:Estradiol / Q000097:blood; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy*; D046529:Microscopy, Electron, Transmission; D010053:Ovary / Q000187:drug effects* / Q000648:ultrastructure*; D051381:Rats; D017208:Rats, Wistar; D043823:Taxoids / Q000009:adverse effects* / Q000627:therapeutic use; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014599:Uterus / Q000187:drug effects*
D000970:Antineoplastic Agents; D024042:Collagen Type I; D024061:Collagen Type III; D043823:Taxoids; D053773:Transforming Growth Factor beta1; D000077143:Docetaxel; D004958:Estradiol; D003520:Cyclophosphamide
Breast cancer; CIOF; cyclophosphamide; docetaxel; ovarian fibrosis