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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\u2010\u03b1 in the TC group. The involvement of fibrosis was also investigated. The results showed that the TC group had increased expression levels of TGF\u2010\u03b21, collagen type I (col\u2010I) and collagen type III (col\u2010III) 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\u2010induced ovarian failure and provide further insight into the mechanisms involved in the development of this disease.<\/jats:p>","DOI":"10.1111\/jmi.12329","type":"journal-article","created":{"date-parts":[[2015,10,20]],"date-time":"2015-10-20T18:40:35Z","timestamp":1445366435000},"page":"267-276","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A combination of stereological methods, biochemistry and electron microscopy for the\u00a0investigation of drug treatment effects in experimental animals"],"prefix":"10.1111","volume":"261","author":[{"given":"ALAN CN DE","family":"MORAES","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Pesquisas em C\u00e9lulas\u2010Tronco, Departamento de Histologia e Embriologia Instituto de Biologia Roberto Alc\u00e2ntara Gomes  UERJ Rio de Janeiro RJ Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CHERLEY BV","family":"ANDRADE","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Cardiologia Celular e Molecular, Instituto de Biof\u00edsica Carlos Chagas Filho Centro de Ci\u00eancias da Sa\u00fade  UFRJ Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CAMILA","family":"SALATA","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ci\u00eancias Radiol\u00f3gicas, Departamento de Biof\u00edsica e Biometria Instituto de Biologia Roberto Alc\u00e2ntara Gomes  UERJ Rio de Janeiro RJ Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ANA LR","family":"NASCIMENTO","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ultraestutura e Biologia Tecidual, Departamento de Histologia e Embriologia Instituto de Biologia Roberto Alc\u00e2ntara Gomes  UERJ Rio de Janeiro RJ Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ISALIRA P","family":"RAMOS","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Cardiologia Celular e Molecular, Instituto de Biof\u00edsica Carlos Chagas Filho Centro de Ci\u00eancias da Sa\u00fade  UFRJ Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"REGINA CS","family":"GOLDENBERG","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Cardiologia Celular e Molecular, Instituto de Biof\u00edsica Carlos Chagas Filho Centro de Ci\u00eancias da Sa\u00fade  UFRJ Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JORGE J","family":"CARVALHO","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ultraestutura e Biologia Tecidual, Departamento de Histologia e Embriologia Instituto de Biologia Roberto Alc\u00e2ntara Gomes  UERJ Rio de Janeiro RJ Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ANA CS","family":"MACHADO","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisas em C\u00e9lulas\u2010Tronco, Departamento de Histologia e Embriologia Instituto de Biologia Roberto Alc\u00e2ntara Gomes  UERJ Rio de Janeiro RJ Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,10,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1933719111426599"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070479"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.04.003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/626319"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21385"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.119.3.493"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2014.03.011"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acra.2011.10.003"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1139\/Y10-086"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.02.063"},{"key":"e_1_2_8_12_1","volume-title":"Unbiased Stereology: Three\u2010Dimensional Measurement in Microscopy","author":"Howard C.V.","year":"2005"},{"key":"e_1_2_8_13_1","first-page":"2571","article-title":"Risk of ovarian failure and fertility after intravenous cyclophosphamide. 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