Sphingolipids, apoptosis, cancer treatments and the ovary: investigating a crime against female fertility.
Premature ovarian failure and infertility are well-known side-effects observed in young girls and reproductive-age women treated for cancer. Although the need for tumor eradication in these patients is clear, the long-term consequences of chemotherapy and radiation on non-target tissues, such as the ovaries where large numbers of germ cells (oocytes) are also killed off, are substantial. Unfortunately, the mechanism mediating the undesirable toxicity of cancer therapies in the female gonads has only recently been explored. Nevertheless, some important insights into the role of ceramide and sphingosine-1-phosphate (S1P) as a mediator and suppressor, respectively, of cancer therapy-induced oocyte apoptosis have emerged over the past few years. Such findings are exciting in that a better understanding of the crime--how radiation and chemotherapy kill off this irreplaceable population of innocent cells in the ovaries--may finally allow for the development of novel lipid-based strategies to combat infertility and premature menopause in female cancer patients.
Tilly
Jonathan L
JL
Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical School, 55 Fruit Street, VBK137E-GYN, Boston, MA 02114-2696, USA. jtilly@partners.org
Kolesnick
Richard N
RN
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D017209:Apoptosis / Q000502:physiology*; D002518:Ceramides / Q000378:metabolism; D005260:Female; D006801:Humans; D007246:Infertility / Q000209:etiology* / Q000517:prevention & control; D008565:Membrane Proteins; D009865:Oocytes / Q000187:drug effects / Q000528:radiation effects; D010053:Ovary / Q000187:drug effects / Q000503:physiopathology / Q000528:radiation effects; D010744:Phosphoric Monoester Hydrolases / Q000627:therapeutic use; D011837:Radiation-Protective Agents / Q000627:therapeutic use; D011878:Radiotherapy / Q000009:adverse effects*; D013107:Sphingolipids / Q000502:physiology*
D000970:Antineoplastic Agents; D002518:Ceramides; D008565:Membrane Proteins; D011837:Radiation-Protective Agents; D013107:Sphingolipids; C498527:SGPP1 protein, human; C401298:sphingosine-1-phosphate phosphatase; D010744:Phosphoric Monoester Hydrolases