Anti-Müllerian Hormone Is a Marker for Chemotherapy-Induced Testicular Toxicity

Author:

Levi Mattan1,Hasky Noa1,Stemmer Salomon M.2,Shalgi Ruth1,Ben-Aharon Irit2

Affiliation:

1. Department of Cell and Developmental Biology (M.L., N.H., R.S.), Davidoff Center, Rabin Medical Center, Beilinson Campus, Petah-Tiqva 49100, and Sackler Faculty of Medicine, Tel-Aviv University, Israel

2. Sackler Faculty of Medicine, Tel Aviv University, Israel and Institute of Oncology (S.M.S., I.B-A.), Davidoff Center, Rabin Medical Center, Beilinson Campus, Petah-Tiqva 49100, and Sackler Faculty of Medicine, Tel-Aviv University, Israel

Abstract

Due to increased numbers of young cancer patients and improved survival, the impact of anticancer treatments on fertility has become a major health concern. Despite mounting research on ovarian toxicity, there is paucity of data regarding reliable biomarkers of testicular toxicity. Our aim was to evaluate anti-Müllerian hormone (AMH) as a marker for chemotherapy-induced testicular toxicity. Serum AMH and a panel of gonadal hormones were measured in male cancer patients at baseline and after chemotherapy. In the preclinical setting, mice were injected with diverse chemotherapies and were killed 1 week or 1, 3, or 6 months later. We evaluated spermatogenesis by AMH as well as qualitative and quantitative sperm parameters. Nineteen patients were enrolled, the median age was 38 years (21–44 y). Serum AMH was correlated with increased FSH and T and decreased inhibin-B in gonadotoxic protocols (cisplatin or busulfan) and remained unchanged in nongonadotoxic protocols (capecitabine). AMH expression had the same pattern in mice serum and testes; it was negatively correlated with testicular/epididymal weight and sperm motility. The increase in testicular AMH expression was also correlated with elevated apoptosis (terminal transferase-mediated deoxyuridine 5-triphosphate nick-end labeling) and reduced proliferation (Ki67, proliferating cell nuclear antigen; all seminiferous tubules cells were analyzed). Severely damaged mice testes demonstrated a marked costaining of AMH and GATA-4, a Sertoli cell marker; staining that resembled the pattern of the Sertoli cell-only condition. Our study indicates that the pattern of serum AMH expression, in combination with other hormones, can delineate testicular damage, as determined in both experimental settings. Future large-scale clinical studies are warranted to further define the role of AMH as a biomarker for testicular toxicity.

Publisher

The Endocrine Society

Subject

Endocrinology

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