阿霉素对大鼠睾丸细胞分化和增殖的影响。
Effects of adriamycin on cell differentiation and proliferation in rat testis.
发表日期:2023 Sep 01
作者:
Ali Tugrul Akin, Ayse Toluk, Saim Ozdamar, Serpil Taheri, Emin Kaymak, Ecmel Mehmetbeyoglu
来源:
Cellular & Molecular Immunology
摘要:
尽管多种癌症使用了丽珠单抗(ADR)进行治疗,但它对包括睾丸在内的健康器官可能具有毒性。我们研究了ADR对大鼠睾丸多能性的影响。在雄性Wistar白化率参鼠中,通过累积剂量或单剂量给予ADR,诱导睾丸损伤。鼠被随机分为三组:未经处理的对照组,累积剂量ADR组(每隔三天给予2 mg/kg ADR,共30天)和单剂量ADR组(15 mg/kg,单剂量ADR)。通过光学显微镜评估睾丸损伤,并测量附睾小管直径。采用免疫组织化学和实时PCR评估Oct4、Sox2、Klf4、c-Myc、Utf1和Dazl的表达水平。使用ELISA法测量血清睾酮水平。与ADR组相比,组织病理学分数低,平均附睾小管直径较小。与对照组相比,累积剂量和单剂量ADR组的精子发生细胞中Oct4、Sox2、Klf4和Utf1表达显著下降。我们发现,与对照组相比,累积剂量ADR组和单剂量ADR组的精子发生和莱迪格细胞中c-Myc表达显著上升。与对照组相比,累积剂量ADR组的Dazl表达下降,而单剂量ADR组的Dazl表达增加,并且单剂量ADR组的Dazl表达高于对照组和累积剂量ADR组。ADR组的血清睾酮水平较对照组下降。我们的发现表明,ADR有害于大鼠睾丸多能性的调控和维持。
Although adriamycin (ADR) is used to treat many cancers, it can be toxic to healthy organs including the testis. We investigated the effects of ADR on pluripotency in rat testis. Testicular damage was induced by either cumulative or single dose single dose administration of ADR in Wistar albino rats. Rats were divided randomly into three groups: untreated control, cumulative dose ADR group (2 mg/kg ADR every three days for 30 days) and single dose ADR group (15 mg/kg, single dose ADR). Testicular damage was evaluated and seminiferous tubule diameters were measured using light microscopy. Expression levels of Oct4, Sox2, Klf4, c-Myc, Utf1 and Dazl were assessed by immunohistochemistry and real time PCR. Serum testosterone levels were measured using ELISA assay. Histopathologic scores were lower and mean seminiferous tubule diameters were less compared to the ADR groups. Oct4, Sox2, Klf4 and Utf1 expressions were decreased significantly in spermatogenic cells of both cumulative and single dose ADR groups compared to the control group. We found that c-Myc expression in spermatogenic and Leydig cells were increased significantly in both ADR groups compared to the control group. Dazl expression was decreased in the cumulative adriamycin group compared to the control group, but increased in the single dose ADR group compared to both the control and cumulative ADR groups. Serum testosterone levels were decreased in both ADR groups compared to the control group. Our findings suggest that ADR is detrimental to regulation and maintenance of pluripotency in rat testis.