Deleterious reproductive effects of nilotinib in mouse model


ÖZKAVUKCU İ. S., KUŞCU N., ADIGÜZEL D., CENGİZ SEVAL G., ÇELİK ÖZENCİ Ç.

REPRODUCTION, cilt.161, sa.3, ss.295-306, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 161 Sayı: 3
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1530/rep-20-0548
  • Dergi Adı: REPRODUCTION
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.295-306
  • Ankara Üniversitesi Adresli: Evet

Özet

Nilotinib is a second-generation tyrosine kinase inhibitor (TKI) that is widely used to treat patients with Philadelphia chromosome-positive chronic myeloid leukaemia (CML). TKIs provided a significant improvement in terms of survival rates and disease-free period in CML; however, there is insufficient knowledge about their side effects, including reproductive toxicity. Since nearly half of the CML patients are in their reproductive age, and newly announced indications cover the treatment of the paediatric age groups, concerns arise about the effects of these drugs on the reproductive system, as there are no controlled preclinical studies. We investigated acute and long-term gonadotoxic and teratogenic effects of nilotinib, utilising a mouse model that simulates various clinical scenarios. We observed significant testicular damage in mice receiving nilotinib according to Johnsen's score analysis. Alterations were observed in female mice's number of follicles, as the primordial follicle numbers significantly decreased. Proliferating cell number in both genders' gonads decreased and apoptosis rate increased significantly. The nilotinib-received female and male mice's pregnancy rates were low compared to controls. A significant decrease in the thickness of the spongiotrophoblast and decidual layers of the placenta was detected in pregnancies consisting of male and/or female mice treated with nilotinib. The results of this study establish a critical point of view for clinical translation and indicate the importance of consulting patients for directing them to fertility preservation and contraception options for both genders before nilotinib treatment.