Protective Effect of Mesenchymal Stem Cells and Melatonin on Testicular Torsion-Induced Infertility

Abstract

We aimed to explore the effects of systemic melatonin and intratesticular Adipose tissue-derived mesenchymal stem cells (AdMSCs) administration on rats with acute unilateral testicular torsion. Rats were randomized into Sham group (S) (n=8), torsion/detorsion group (T/D by torsion of right testis with rotated 720° counter clockwise for 3 h, then detorsion) (n=8), Melatonin group given 25 mg/kg after torsion/detorsion (M) (n=8), Adipose tissue-derived mesenchymal stem cell-treated group after torsion/detorsion (MSC) (n=8), Adipose tissue-derived mesenchymal stem cell-treated group with melatonin after torsion/detorsion (MSC+M) (n=8). We measured MDA, Testosterone, FSH and LH levels, performed histopathological analyses in testicles, and identified SOX, VASA and Caspas-3 reactions immunohistochemically. Testosterone, FSH, LH values did not yield any significant difference between the groups. While the Johnson score in the right testis remained the lowest in T/D, the highest score was noted in the S. The T/D manifested some degenerative seminiferous tubules, abnormal spermatogenesis and maturation arrest. The degenerative appearance monitored in M, MSC and MSC+M groups persisted in some tubules, while markedly reduced degeneration was observed in some other tubules. The highest Caspase-3 expression in T/D, whereas SOX-9 expression remained significantly higher in the treatment groups. Another aspect deserving attention is that MSC were characterized by low VASA expression. Our experimental trial suggests that the torsion-induced degeneration in testicular tissue was ameliorated in all the treatment groups. Although MSC, MSC+M and M administrations decreased the torsion-induced degeneration in the testicular tissue, these treatments did not prove to be superior to each other.

Keywords

• Testicular Torsion-Detorsion
• Stem cell
• Melatonin
• Apoptosis

Testiküler Torsiyonun İndüklediği Kısırlığa Mezenkimal Kök Hücrenin ve Melatoninin Koruyucu Etkisi

Abstract

Sistemik melatonin ve intratestiküler adipoz doku kaynaklı mezenkimal kök hücrelerin (AdMSCs) uygulamasının akut tek taraflı testis torsiyonu olan sıçanlar üzerindeki etkilerini araştırmayı amaçladık. Sıçanlar, Sham grubu (S) (n=8), torsiyon/detorsiyon grubu (sağ testisin 3 saat boyunca saat yönünün tersine 720° döndürülerek torsiyonu ve ardından detorsiyonu ile T/D) (n=8), torsiyon/detorsiyon sonrası 25 mg/kg melatonin verilen grup (M) (n=8), torsiyon/detorsiyon sonrası adipoz doku kaynaklı mezenkimal kök hücre ile tedavi edilen grup (MSC) (n=8), torsiyon /detorsiyon sonrası melatonin ile adipoz dokusu kaynaklı mezenkimal kök hücre ile tedavi edilen grup (MSC+M) (n=8) olarak randomize edildi. MDA, Testosteron, FSH ve LH düzeyleri ölçüldü. Testislerde histopatolojik analizler yapıldı ve SOX, VASA ve Caspas-3 reaksiyonları immünohistokimyasal olarak incelendi. Testosteron, FSH, LH değerleri gruplar arasında anlamlı bir fark göstermedi. Sağ testiste Johnson skoru T/D'de en düşük seviyede kalırken, en yüksek skor S grubunda kaydedildi. T/D grubunda bazı dejeneratif seminifer tübüller, anormal spermatogenez ve olgunlaşma durması görüldü. M, MSC ve MSC+M gruplarında izlenen dejeneratif görünüm bazı tübüllerde devam ederken, diğer bazı tübüllerde belirgin şekilde azalmış olduğu gözlendi. En yüksek Kaspaz-3 ekspresyonu T/D'de görülürken, SOX-9 ekspresyonu tedavi gruplarında anlamlı derecede yüksek kalmıştır. Dikkat edilmesi gereken bir diğer husus da MSC'nin düşük VASA ekspresyonu ile karakterize olmasıdır. Deneysel çalışmamız, testis dokusunda torsiyona bağlı dejenerasyonun tüm tedavi gruplarında iyileştiğini göstermektedir. MSC, MSC+M ve M uygulamaları testis dokusunda torsiyona bağlı dejenerasyonu azaltmış olsa da, bu tedavilerin birbirlerine üstünlüğü kanıtlanmamıştır.

Keywords

• Testiküler Torsiyon-Detorsiyon
• Kök hücre
• Melatonin
• Apoptozis

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