ALTERNATIVE METHODS USING EXPERIMENTAL ANIMALS IN ASSESSING MALE REPRODUCTIVE SYSTEM TOXICITY

Öz

Objective: This review discusses traditional in vitro methods used in male reproductive toxicity studies, innovative in vitro models, and in silico approaches integrated into toxicity assessment processes.

Result and Discussion: Male reproductive toxicity encompasses exogenous and endogenous factors that adversely affect spermatogenesis and sperm function. Key targets in this process include the seminiferous epithelium, Leydig and Sertoli cells, epididymal sperm maturation, and the endocrine system. Currently, the assessment of reproductive toxicity is predominantly conducted through in vivo methods; however, these approaches are costly, time-consuming, and ethically controversial. The need for alternative approaches has been particularly highlighted within the scope of regulations in Europe, increasing the importance of studies aimed at reducing the use of  experimental animals. The multi-stage and highly sensitive nature of the reproductive process complicates toxicity assessment, and both in vivo and in vitro methods have limited predictive capacity. Therefore, there is a pressing need for well-designed and reliable models.

Anahtar Kelimeler

• Male reproductive system toxicity
• in silico
• in vitro

ERKEK ÜREME SİSTEMİ TOKSİSİTESİNİN DEĞERLENDİRİLMESİNDE DENEY HAYVANLARINA ALTERNATİF YÖNTEMLER

Öz

Amaç: Bu derleme kapsamında erkek üreme sistemi toksisitesi çalışmalarında kullanılan geleneksel in vitro yöntemler, yenilikçi in vitro modeller ile değerlendirme süreçlerine entegre edilen in silico yaklaşımlardan bahsedilmiştir.

Sonuç ve Tartışma: Erkek üreme sistemi toksisitesi, spermatogenezis süreci ve spermatozoon fonksiyonları üzerinde olumsuz etkilere neden olan ekzojen ve endojen faktörleri kapsar. Seminifer epitel, Leydig ve Sertoli hücreleri, epididimal spermatozoa olgunlaşması ve endokrin sistem bu süreçte temel hedeflerdir. Günümüzde üreme toksisitesinin değerlendirilmesi genellikle in vivo yöntemlerle gerçekleştirilmektedir; ancak bu yöntemler yüksek maliyetli, zaman alıcı ve etik açıdan tartışmalıdır. Alternatif yaklaşımlara duyulan ihtiyaç, özellikle Avrupa’daki düzenlemeler kapsamında vurgulanmış, deney hayvanı kullanımını azaltmaya yönelik çalışmaların önemini artırmıştır. Üreme sürecinin çok aşamalı ve hassas bir yapıya sahip olması, toksisite değerlendirmesini karmaşık hale getirmektedir. Kullanılan in vivo ve in vitro yöntemler toksik etkileri öngörme konusunda sınırlı bir kapasiteye sahiptir. Daha iyi tasarlanmış, güvenilir modellere ihtiyaç duyulmaktadır.

Anahtar Kelimeler

• Erkek üreme sistemi toksisitesi
• in silico
• in vitro

Kaynakça

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