Recurrent spontaneous miscarriages from sperm after ABVD chemotherapy in a patient with Hodgkin's lymphoma: sperm DNA and methylation profiling.

Gwendoline LECUYER; Antoine D ROLLAND; Anne-Sophie NEYROUD; Bertrand EVRARD; Nathan ALARY; Clemence GENTHON; Nathalie DEJUCQ-RAINSFORD; Célia RAVEL; Jessika MOREAU; Nathalie MOINARD; Mohamed Hadi Mohamed ABDELHAMID; Christophe KLOPP; Louis BUJAN; Frédéric CHALMEL

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Recurrent spontaneous miscarriages from sperm after ABVD chemotherapy in a patient with Hodgkin's lymphoma: sperm DNA and methylation profiling.

Author: Gwendoline LECUYER ¹ ; Antoine D ROLLAND ¹ ; Anne-Sophie NEYROUD ¹ ; Bertrand EVRARD ¹ ; Nathan ALARY ¹ ; Clemence GENTHON ² ; Nathalie DEJUCQ-RAINSFORD ¹ ; Célia RAVEL ¹ ; Jessika MOREAU ³ ; Nathalie MOINARD ⁴ ; Mohamed Hadi Mohamed ABDELHAMID ³ ; Christophe KLOPP ³ ; Louis BUJAN ⁴ ; Frédéric CHALMEL ¹
Author Information

1. Univ Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, Rennes F-35000, France.
2. Institut National de Recherche pour l'agriculture, l'alimentation et l'environnement (INRAE), Unité Service 1426 (US1426), Transcriptome Plateforme Technologique (GeT-PlaGe), Genotoul, Castanet-Tolosan 31326, France.
3. ToxAlim (Research Center in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse F-31027, France.
4. Service de Biologie de la Reproduction et CECOS, Hôpital Paule de Viguier, CHU Toulouse, 330 Avenue de Grande Bretagne, Toulouse 31059, France.
Publication Type:Case Reports
Keywords: chemotherapy; embryo loss; methylation; miscarriage; sperm DNA; whole-genome sequencing
MeSH: Humans; Male; Hodgkin Disease/drug therapy*; Adult; DNA Methylation/drug effects*; Bleomycin/therapeutic use*; Spermatozoa/metabolism*; Vinblastine/therapeutic use*; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*; Abortion, Habitual/genetics*; Doxorubicin/therapeutic use*; Dacarbazine/therapeutic use*; Female; Pregnancy
From: Asian Journal of Andrology 2025;27(5):598-610
CountryChina
Language:English
Abstract: Lymphomas represent one of the most common malignant diseases in young men and an important issue is how treatments will affect their reproductive health. It has been hypothesized that chemotherapies, similarly to environmental chemicals, may alter the spermatogenic epigenome. Here, we report the genomic and epigenomic profiling of the sperm DNA from a 31-year-old Hodgkin lymphoma patient who faced recurrent spontaneous miscarriages in his couple 11-26 months after receiving chemotherapy with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). In order to capture the potential deleterious impact of the ABVD treatment on mutational and methylation changes, we compared sperm DNA before and 26 months after chemotherapy with whole-genome sequencing (WGS) and reduced representation bisulfite sequencing (RRBS). The WGS analysis identified 403 variants following ABVD treatment, including 28 linked to genes crucial for embryogenesis. However, none were found in coding regions, indicating no impact of chemotherapy on protein function. The RRBS analysis identified 99 high-quality differentially methylated regions (hqDMRs) for which methylation status changed upon chemotherapy. Those hqDRMs were associated with 87 differentially methylated genes, among which 14 are known to be important or expressed during embryo development. While no variants were detected in coding regions, promoter regions of several genes potentially important for embryo development contained variants or displayed an altered methylated status. These might in turn modify the corresponding gene expression and thus affect their function during key stages of embryogenesis, leading to potential developmental disorders or miscarriages.