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CC BY 4.0 · Rev Bras Ginecol Obstet 2019; 41(11): 668-672
DOI: 10.1055/s-0039-3399551
Original Article
Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil

Thalidomide Reduces Cell Proliferation in Endometriosis Experimentally Induced in Rats

A talidomida induz diminuição da proliferação celular em endometriose experimentalmente induzida em ratas
Luana Grupioni Lourenço Antônio 
1   Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Julio Cesar Rosa-e-Silva
1   Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Deborah Juliani Machado
1   Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Andrezza Telles Westin
1   Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Sergio Britto Garcia
1   Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Francisco José Candido-dos-Reis
1   Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Omero Benedicto Poli-Neto
1   Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Antonio Alberto Nogueira
1   Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
› Author Affiliations
Further Information

Publication History

18 April 2019

02 October 2019

Publication Date:
19 November 2019 (online)

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Abstract

Objective To analyze the effect of thalidomide on the progression of endometriotic lesions experimentally induced in rats and to characterize the pattern of cell proliferation by immunohistochemical Proliferating Cell Nuclear Antigen (PCNA) labeling of eutopic and ectopic endometrium.

Methods Fifteen female Wistar rats underwent laparotomy for endometriosis induction by resection of one uterine horn, isolation of the endometrium and fixation of a tissue segment to the pelvic peritoneum. Four weeks after, the animals were divided into 3 groups: control (I), 10mg/kg/day (II) and 1mg/kg/day (III) intraperitoneal thalidomide for 10 days. The lesion was excised together with the opposite uterine horn for endometrial gland and stroma analysis. Eutopic and ectopic endometrial tissue was submitted to immunohistochemistry for analysis of cell proliferation by PCNA labeling and the cell proliferation index (CPI) was calculated as the number of labeled cells per 1,000 cells.

Results Group I showed a mean CPI of 0.248 ± 0.0513 in the gland and of 0.178 ± 0.046 in the stroma. In contrast, Groups II and III showed a significantly lower CPI, that is, 0.088 ± 0.009 and 0.080 ± 0.021 for the gland (p < 0.001) and 0.0945 ± 0.0066 and 0.075 ± 0.018 for the stroma (p < 0.001), respectively. Also, the mean lesion area of Group I was 69.2 mm2, a significantly higher value compared with Group II (49.4 mm2, p = 0.023) and Group III (48.6 mm2, p = 0.006). No significant difference was observed between Groups II and III.

Conclusion Thalidomide proved to be effective in reducing the lesion area and CPI of the experimental endometriosis implants both at the dose of 1 mg/kg/day and at the dose of 10 mg/kg/day.

Resumo

Objetivo Analisar o efeito da talidomida na progressão de lesões endometrióticas induzidas experimentalmente em ratas e caracterizar o padrão de proliferação celular pela marcação imunohistoquímica de Antígeno Nuclear de Célula Proliferativa (PCNA) no endométrio eutópico e ectópico.

Métodos Quinze ratas Wistar foram submetidas a laparotomia para indução de endometriose por ressecção de um corno uterino, isolamento do endométrio e fixação de um segmento do tecido ao peritônio pélvico. Após quatro semanas, os animais foram divididos em 3 grupos: controle (I), 10 mg/kg/dia (II) e 1 mg/kg/dia (III) de talidomida intraperitoneal por um período de 10 dias. As lesões foram resseccionadas juntamente com o corno uterino oposto para análise da glândula endometrial e do estroma. O tecido endometrial eutópico e ectópico foi submetido à imunohistoquímica para análise da proliferação celular por marcação com PCNA e o índice de proliferação celular (CPI) foi calculado como o número de células marcadas por 1.000 células.

Resultados O grupo I apresentou média de CPI de 0,248 ± 0,0513 na glândula e de 0,178 ± 0,046 no estroma. Em contraste, os grupos II e III apresentaram CPI significativamente menor, isto é, 0,088 ± 0,009 e 0,080 ± 0,021 para a glândula (p < 0,001) e 0,0945 ± 0,0066 e 0,075 ± 0,018 para o estroma (p < 0,001), respectivamente. Além disso, a área de lesão média do Grupo I foi de 69,2 mm2, valor significativamente maior em relação ao Grupo II (49,4 mm2, p = 0,023) e Grupo III (48,6 mm2, p = 0,006). Não houve diferença estatisticamente significante entre os Grupos II e III.

Conclusão A talidomida mostrou-se eficaz na redução da área da lesão e CPI dos implantes de endometriose experimental tanto na dose de 1 mg/kg/dia quanto na dose de 10 mg/kg/dia.

Keywords

experimental endometriosis - cell proliferation - PCNA - thalidomide - rat

Palavras-chave

endometriose experimental - proliferação celular - PCNA - talidomida - rata

Contributions

All of the authors of the present article contributed to the design, data collection, analysis, and interpretation of data, the writing of the article or critical review of the intellectual content and to the final approval of the version to be published.


 

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