Sphingosine-1-phosphate prevents chemotherapy-induced human primordial follicle death

Li, Fang; Turan, Volkan; Lierman, Sylvie; Cuvelier, Claude; Sutter, Petra De; Oktay, Kutluk

doi:10.1093/humrep/det391

Cited by 149 publications

(119 citation statements)

References 29 publications

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“…These advances occurred mainly in the investigation of pharmacological agents to protect ovarian reserve during chemotherapy. Cytotoxic agents have different mechanisms of damage to the various cell populations within the ovaries, providing different targets for potential attenuating agents [70,71]. Most of these protective agents are in preliminary stages of study and future developments in these areas will depend on accurate evaluation of the effictiveness of each potential pharmacological agent.…”

Section: Future Perspectivementioning

confidence: 99%

Chemotherapy-Induced Damage to Ovary: Mechanisms and Clinical Impact

2016

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Cancer is a major public health problem around the world. Currently, about 5% of women diagnosed with cancer are of reproductive age. These young survivors may face compromised fertility. The effects of chemotherapeutic agents on ovarian reserve and its clinical consequences are generally inferred from a variety of surrogate markers of ovarian reserve, all aiming to provide prognostic information on fertility or the likelihood of success of infertility treatment. Until recently, the mechanisms that are responsible for chemotherapy-induced ovarian damage were not fully elucidated. The understanding of these mechanisms may lead to targeted treatments to preserve fertility. In this manuscript, we will review the current knowledge on the mechanism of ovarian damage and clinical impact of chemotherapy agents on fertility. Cancer is a major public health problem around the world and is the second leading cause of death in the USA [1]. In 2016, approximately 844,000 new cases of cancer will be diagnosed in women in the USA [1]. In recent years, the remarkable screening, diagnostic and therapeutic advances in oncology practice improved the prognosis for many cancer patients, adding years to their anticipated survival. In fact, all these measures have resulted in a 23% drop in the cancer death rates from 1991 to 2012 [1].Currently, about 5% of cancers affects women younger than 50 years [1]. As young patients with these once-fatal malignancies become long-term survivors, many must face the potentially devastating complications of the treatment. Young survivors will likely face compromised fertility that is now recognized as among the most prevalent long-term side effects of cancer therapy. The prospect of partial or total infertility can significantly add to anxiety and emotional strain during disease management, and may also compromise quality of life [2]. To offset these risks, women can be offered several options for fertility preservation, including conservative cancer management, and cryopreservation of oocyte, embryo or ovarian tissue. Embryo and oocyte cryopreservation are considered established fertility preservation techniques and have been widely applied across the world [3,4]. On the other hand, ovarian tissue cryopreservation is still considered an experimental technique, despite advances in recent years [5].Studies exploring the mechanisms behind the actions of the different chemotherapy agents are providing greater information as to the specific effects of each agent on the different cell types of the ovary. The effects of antineoplastic agents on the ovaries are clinically inferred from a variety This article will review all the mechanism and clinical impact of chemotherapy on ovarian reserve. Ovarian agingThe ovary has a finite endowment of primordial follicles that is established during the second half of intrauterine life, followed by a steady decline until menopause. Each primordial follicle consists of an immature oocyte surrounded by a single layer of granulosa cells. The primordial follicles constit...

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Section: Future Perspectivementioning

confidence: 99%

Chemotherapy-Induced Damage to Ovary: Mechanisms and Clinical Impact

2016

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“…54 In addition to GnRH agonists, fertoprotective adjuvant therapies that inhibit apoptosis and prevent germ cell loss in response to gonadotoxic exposures (sphingosine-1-phosphate, FTY720, and imatinib) have shown promise in several preclinical rodent and primate models of radiation and chemotherapy-induced damage. [55][56][57][58] An important limitation of emerging technologies, which rely on anti-apoptotic agents, is that the surviving germ cells may have significant DNA damage. This would restrict the usefulness of these protected germ cells to providing endocrine support rather than also restoring fertility.…”

Section: Figmentioning

confidence: 99%

Pediatric and Teen Ovarian Tissue Removed for Cryopreservation Contains Follicles Irrespective of Age, Disease Diagnosis, Treatment History, and Specimen Processing Methods

Duncan

Pavone

Gunn

et al. 2015

Journal of Adolescent and Young Adult Oncology

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“…We understand and appreciate the commitment of Dr. Blumenfeld in seeking for a simpler approach to fertility preservation. Our laboratory is also committed to the same and showed that a ceramideinduced cell death inhibitor sphingosine-1-phosphate maybe a promising candidate [13] as it may directly block the chemotherapy-induced damage to DNA.…”

Section: Declaration Of Interestmentioning

confidence: 97%

Comment on: sexual and fertility adverse effects associated with chemotherapy treatment in women

Blumenfeld

2014

Expert Opinion on Drug Safety

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Sphingosine-1-phosphate prevents chemotherapy-induced human primordial follicle death

Abstract: This research is supported by NIH's NICHD and NCI (5R01HD053112-06 and 5R21HD061259-02) and the Flemish Foundation for Scientific Research (FWO-Vlaanderen, grant number FWO G0.065.11N10). The authors have no conflicts of interest to disclose.

Cited by 149 publications

References 29 publications

Chemotherapy-Induced Damage to Ovary: Mechanisms and Clinical Impact

Chemotherapy-Induced Damage to Ovary: Mechanisms and Clinical Impact

Pediatric and Teen Ovarian Tissue Removed for Cryopreservation Contains Follicles Irrespective of Age, Disease Diagnosis, Treatment History, and Specimen Processing Methods

Comment on: sexual and fertility adverse effects associated with chemotherapy treatment in women

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