Pharmacological administration of recombinant human AMH rescues ovarian reserve and preserves fertility in a mouse model of chemotherapy, without interfering with anti-tumoural effects

H. Roness, I. Spector, Y. Leichtmann-Bardoogo, A. M. Savino, Sanaz Dereh-Haim, Dror Meirow

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To determine whether pharmacological administration of recombinant human anti-Mullerian hormone (rAMH) protects the ovarian reserve and preserves fertility without interfering with anti-tumoural cytotoxic action of chemotherapy. Methods: Intraperitoneal delivery of rAMH and ovarian post-receptor activity were assessed with immunohistochemistry and western blot. Differential follicle counts and reproductive outcomes were assessed after cyclophosphamide (Cy) administration, with/without concurrent administration of rAMH. Interference of rAMH with Cy chemotoxicity was assessed on a human breast cancer cell line and an in vivo mouse model of human leukaemia. Results: rAMH reached the ovary after intraperitoneal injection and demonstrated post-receptor bioactivity. Cy administration in mice caused primordial follicle activation, as shown by a decrease in primordial follicle population accompanied by an increase in early growing follicles and granulosa cell proliferation. Co-administration of rAMH reduced follicle activation, thereby protecting the primordial follicle reserve, and improving long-term fertility and reproductive outcomes. rAMH co-administration did not interfere with the cytotoxic actions of Cy in vitro on breast cancer cell line or in vivo in a model of human leukaemia. Conclusion: This study demonstrates that rAMH is bioactive in the ovary for a limited time, and that pharmacological administration of rAMH during chemotherapy treatment reduces follicle activation and primordial follicle loss and significantly improves reproductive outcomes in a mouse model, and does not interfere with the therapeutic actions of the treatment. Further investigation is necessary to determine whether it has similar protective effects in the human ovary.

Original languageEnglish
Pages (from-to)1793-1803
Number of pages11
JournalJournal of Assisted Reproduction and Genetics
Volume36
Issue number9
DOIs
StatePublished - 1 Sep 2019

Keywords

  • Anti-Mullerian hormone
  • Chemotherapy
  • Fertility preservation
  • Follicle activation

Fingerprint

Dive into the research topics of 'Pharmacological administration of recombinant human AMH rescues ovarian reserve and preserves fertility in a mouse model of chemotherapy, without interfering with anti-tumoural effects'. Together they form a unique fingerprint.

Cite this