Farelere Uygulanan Paklitaksel’in Testis Dokusu Üzerine Etkileri

Abstract

Amaç: Kemoterapötik ilaçlar, sperm kalitesini ve erkek fertilitesini etkileyerek üreme bozukluklarına neden olabilir. Birçok kanser türünün tedavisinde aktif olarak kullanılan paklitaksel (PTS), dokularda oksidatif stresin artmasına neden olarak toksik etki gösterir. Mevcut çalışmada, farelere PTS uygulaması yapılarak PTS'nin erkek üreme sistemi üzerindeki hasar verici etkilerinin ortaya konulması amaçlandı. Araçlar ve Yöntem: Çalışmada 8-10 haftalık erkek Balb/c cinsi fareler kullanıldı. Her bir grupta n:5 olacak şekilde hayvanlar rastgele seçildi. 1, 3 ve 5. günlerde intraperitoneal olarak kontrol grubu farelerine serum fizyolojik, PTS grubu farelerine ise 2 mg/kg PTS uygulandı. Hayvanlar, deneyin sonunda (7. gün) sakrifiye edildi, testis dokuları toplandı ve histopatolojik incelemeler (Hematoksilen-eozin, Masson trikrom, Periyodik asit schiff) yapıldı. Ayrıca farelerden sperm örnekleri toplandı, yayma preparatlar hazırlandı ve DNA kromatin bütünlüğü Toluidin mavisi boyama ile değerlendirildi. Bulgular: PTS grubunda testis histolojik yapısında bozulmalar gözlendi. Seminifer tübüllerde bozulma, germinal epiteldeki spermatojenik seri hücrelerinde azalma, seminifer tübüllerin bazal membranında bozulma, interstisyel bağ dokuda azalma, ödem ve hemoraji gözlendi. Ayrıca, PTS grubunda zayıf bir peritübüler interstisyel doku reaksiyonu ve leydig hücrelerinde azalma mevcuttu. Gruplar DNA kromatin bütünlüğü bakımından karşılaştırıldığında, PTS grubunda DNA bütünlüğünde bozulmanın yüksek düzeyde olduğu ve gruplar arasında istatistiksel olarak anlamlı bir farklılık belirlendi (p=0.009). Sonuç: Elde ettiğimiz bulgular, PTS'nin fare testis dokusunda toksisiteye neden olabileceğini ve sperm DNA integritesini olumsuz olarak etkileyerek erkek infertilitesine neden olabileceğini göstermektedir.

Keywords

• Fertilite
• infertilite
• DNA
• kromatin

Effects of Paclitaxel Administered to Mice on Testicular Tissue

Abstract

Purpose: Chemotherapy drugs can cause reproductive disorders by affecting sperm quality and male fertility. Paclitaxel (PTS), which is actively used in the treatment of many types of cancer, exhibits toxic effects by causing an increase in oxidative stress in tissues. In the present study, PTS was administered to mice to investigate its damaging effects on the male reproductive system. Materials and Methods: Male Balb/c mice aged 8-10 weeks were used in the study. Animals were randomly selected as n:5 in each group. On days 1, 3 and 5, saline was administered intraperitoneally to control group mice and 2 mg/kg Paclitaxel to PTS group mice. Animals were sacrificed at the end of the experiment (day 7), testicular tissues were collected and histopathological examinations (Haematoxylin-eosin, Masson trichrome, Periodic acid schiff) were performed. In addition, sperm samples were collected from mice, smear preparations were prepared and DNA chromatin integrity was evaluated by Toluidine blue staining. Results: Testicular histology was abnormal in the PTS group. The seminiferous tubules had abnormalities, a decrease in germinal epithelial spermatogenic series cells, damage to the basal membrane, a decrease in interstitial connective tissue, oedema, and haemorrhage. PTS group also had a limited peritubular interstitial tissue reactivity and fewer leydig cells. High DNA chromatin integrity damage was reported in the PTS group, with a significant difference between the groups (p=0.009). Conclusion: Our findings indicate that PTS may cause toxicity in mouse testicular tissue and may cause male infertility by adversely affecting sperm DNA integrity.

Keywords

• Fertility
• infertility
• DNA
• chromatin

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