Abstract
Treosulfan (L-treitol-1,4-bis-methanesulfonate) has been increasingly incorporated as a main conditioning protocol for hematopoietic stem cell transplantation in pediatric malignant and non-malignant diseases. Treosulfan presents lower toxicity profile than other conventional alkylating agents containing myeloablative and immunosuppressive traits such as busulfan. Yet, whereas busulfan is considered highly gonadotoxic, the gonadal toxicity profile of treosulfan remains to be elucidated. To study the gonadotoxicity of treosulfan, pubertal and prepubertal male and female mice were injected with treosulfan or busulfan and sacrificed one week, one month or six months later. Testicular function was assessed by measurements of sperm properties, testes and epididymides weights as well as markers for testicular reserve, proliferation and apoptosis. Ovarian function was assessed by measurements of ovary weight and markers for ovarian reserve, proliferation and apoptosis. Treosulfan testicular toxicity was milder than that of busulfan toxicity; possibly by sparing the stem spermatogonia in the testicular sanctuary. By contrast, ovarian toxicity of both treosulfan and busulfan was severe and permanent and displayed irreversible reduction of reserve primordial follicles in the ovaries. Our data indicate that treosulfan exerts a different gonadal toxicity profile from busulfan, manifested by mild testicular toxicity and severe ovarian toxicity.
Highlights
Hematopoietic stem cell transplantation (HSCT)HSCT conditioning regimen usually comprises a combination of immunosuppressive and myeloablative drugs with the goal of suppressing the host immune system to allow donor cell acceptance, and, if applicable, eliminate the underlying malignancy
Our data indicate that treosulfan exerts a different gonadal toxicity profile from busulfan, manifested by mild testicular toxicity and severe ovarian toxicity
The first part of our study was devoted to examine the effect of treosulfan on conventional indicators of testicular function in comparison to busulfan that served as reference in pubertal male mice
Summary
HSCT conditioning regimen usually comprises a combination of immunosuppressive and myeloablative drugs with the goal of suppressing the host immune system to allow donor cell acceptance, and, if applicable, eliminate the underlying malignancy. The immunosuppressive and myeloablative chemotherapeutic drugs busulfan (1,4-butanediol-dimethylsulfonate) and treosulfan (L-threitol 1,4-bismethanesulphonate) are the cornerstone conditionings of pediatric HSCT [1]. The need for chemotherapy is clear, the longterm consequences of chemotherapy observed on nontarget tissues, such as testis and ovaries, are substantial, raising concern and potential health risks for surviving patients after chemotherapy treatments. With increasing survival rates after HSCT, long-term effects represent a major concern especially in pediatric HSCT recipients. Toxicity profiles of the two alkylating agents, treosulfan and busulfan appear to be different
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
