Novel insights into the pathophysiology of chemotherapy-induced damage to the ovary

Panminerva Med. 2019 Mar;61(1):68-75. doi: 10.23736/S0031-0808.18.03494-8. Epub 2018 Jun 28.

Abstract

Cancer is the second leading cause of death in the USA and is considered a public health issue worldwide. Early diagnosis and advancement of treatment modalities contributed to declining mortality rates. Consequently, survival rates increased, leading to a greater interest in maintaining the quality of life after cancer treatment. Overall survival and disease-free survival rates are improved with the use of adjuvant chemotherapy. However, chemotherapy treatment might cause short and long-term side effects for cancer survivors. A special concern of young women diagnosed with cancer is their reproductive potential after chemotherapy. Chemotherapy drugs act by distinct mechanisms in the ovaries. DNA damage of primordial follicle oocytes, leading to chemotherapy-induced apoptosis, was recognized as the principal mechanism responsible for the irreversible decline of the ovarian reserve. The oocyte first attempts to repair DNA damage via the DNA damage repair pathway mediated by ataxia-telangiectasia mutated. Elimination through apoptosis occurs in cells in which DNA damage could not be repaired. In this review, the clinical impact and the major mechanisms of ovarian damage from chemotherapy treatment will be briefly described.

Publication types

  • Review

MeSH terms

  • Anti-Mullerian Hormone / metabolism
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • DNA Damage
  • Disease-Free Survival
  • Female
  • Humans
  • Infertility, Female / complications
  • Neoplasms / complications
  • Neoplasms / drug therapy*
  • Oocytes / physiology
  • Ovarian Follicle
  • Ovarian Reserve
  • Ovary / drug effects*
  • Ovary / pathology
  • Quality of Life
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Anti-Mullerian Hormone
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins