Experimental study for the establishment of a chemotherapy-induced ovarian insufficiency model in rats by using cyclophosphamide combined with busulfan

Regul Toxicol Pharmacol. 2021 Jun:122:104915. doi: 10.1016/j.yrtph.2021.104915. Epub 2021 Mar 9.

Abstract

With an improvement in the survival rate of cancer patients, chemotherapy-induced premature ovarian insufficiency (POI) is increasingly affecting the quality of life of female patients. Currently, there are many relevant studies using mice as an animal model. However, a large coefficient of variation for weight in mice is not appropriate for endocrine-related studies, compared with rats; therefore, it is necessary to identify an appropriate experimental model in rats. In this study, cyclophosphamide combined with busulfan was used to establish an animal model. We compared several common modeling methods using chemotherapeutic drugs, cisplatin, cyclophosphamide, and 4-vinylcyclohexene diepoxide (VCD), and we found that the combination of cyclophosphamide and busulfan was more effective in establishing a POI model in rats with few side effects by analyzing general physical conditions, pathological tissue sections of heart, liver, lung, spleen, kidney, uterus, and ovary, serum hormone levels, and follicle counts; thus, providing a more reliable model basis for subsequent studies.

Keywords: Busulfan; Chemotherapy; Cyclophosphamide; Premature ovarian insufficiency; Rat model.

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Busulfan / pharmacology*
  • Cyclophosphamide / pharmacology*
  • Disease Models, Animal*
  • Female
  • Ovary / drug effects
  • Primary Ovarian Insufficiency / chemically induced*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • Cyclophosphamide
  • Busulfan