Bortezomib-Induced Ovarian Toxicity in Mice

MUTLUAY D., YÜCEL TENEKECİ G., Monsef Y. A.

TOXICOLOGIC PATHOLOGY, cilt.50, sa.3, ss.381-389, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 50 Sayı: 3
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1177/01926233221083527
  • Dergi Adı: TOXICOLOGIC PATHOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, EMBASE, Environment Index, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.381-389
  • Anahtar Kelimeler: bortezomib, cancer, chemotherapy, ovary, proteasome inhibitor, PROTEASOME INHIBITION, CYCLOPHOSPHAMIDE, CHEMOTHERAPY, ALPHA, CELL, ACTIVATION, EXPRESSION, RESISTANCE, APOPTOSIS, EXPOSURE
  • Ankara Üniversitesi Adresli: Evet

Özet

Cancer survivors may experience long-term adverse effects of cancer treatments such as premature ovarian failure and infertility. We aimed to investigate the potential effects and toxicity of bortezomib (BTZ) as an effective anticancer drug on ovaries, raise awareness to the negative consequences of the treatment, and help increase the quality of life after treatment. Mice were distributed into bortezomib (BTZ1, BTZ2) and saline-injected control groups (C1, C2) at a dose of 1 mg/kg twice per week for 6 weeks. We sacrificed C1, BTZ1 groups at day 1 and C2, BTZ2 groups at 4 weeks after the last injection. Ovary samples were examined using histopathological and immunohistochemical methods. Ovarian follicle impairment was detected on BTZ-treated mice and was associated with a statistically significant decreased population of primordial and antral follicles compared with control groups. In experimental groups, Caspase-3 and Ki67 expressions were increased, whereas estrogen receptor alpha (ER alpha) and progesterone receptor (PR) expressions were decreased in various developmental stages of follicles. BTZ specifically targets granulosa cells by inducing granulosa cell apoptosis and may have long-term effects on follicles. Bortezomib treatment may adversely affect ovarian function by accelerating ovarian reserve depletion and changing ER alpha and PR hormone levels that can cause fertility problems in the long term.