title: Targeted anti-apoptosis activity for ovarian protection against chemotherapy-induced ovarian gonadotoxicity.
abstract: Chemotherapy damages the reproductive system by enhancing apoptosis, and evidence suggests that targeted anti-apoptotic therapy may preserve fertility in patients receiving chemotherapy. To investigate the protective effect of sphingosine-1-phosphate (S1P) on chemotherapeutic agent-induced ovarian gonadotoxicity, busulfan-treated female mice were pre-treated with low (0.5 mM) and high (2.0 mM) doses of S1P or vehicle 1 h before busulfan injection. In the S1P groups, each mouse was injected with low-dose S1P in one ovary and high-dose S1P in the contralateral ovary. Four weeks later, the ovaries were removed for histological and biochemical examinations. Caspase 3 immunoreactivity was greater in mice treated with busulfan compared with mice pre-treated with S1P, in which more primordial follicles were observed (P < 0.05). The mRNA level of anti-Müllerian hormone was higher in mice pre-treated with S1P than those that received busulfan only, indicating a better ovarian function in mice pre-treated with S1P. No difference was observed in the levels of growth differentiation factor-9 among all groups. In conclusion, S1P protects primordial follicles from chemotherapy-induced gonadotoxicity, and may partially preserve ovarian function.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, No.250 Wusing St., Sinyi District, Taipei 110, Taiwan; Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, No.235, Sec.2, Chenggong Rd., Neihu District, Taipei 114, Taiwan.
authors.forename: Shun-Jen
authors.initials: SJ
authors.lastname: Tan
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, National Taiwan University, No.1, Sec.1, Jen Ai Rd., Taipei 100, Taiwan.
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Lee
authors.affiliation: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Taipei Medical University Hospital, No.252, Wu Hsing St., Sinyi District, Taipei 110, Taiwan; Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, No.250, Wusing St., Sinyi District, Taipei 110, Taiwan.
authors.forename: Chii-Ruey
authors.initials: CR
authors.lastname: Tzeng
authors.affiliation: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Taipei Medical University Hospital, No.252, Wu Hsing St., Sinyi District, Taipei 110, Taiwan; Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, No.250, Wusing St., Sinyi District, Taipei 110, Taiwan.
authors.forename: Chia-Woei
authors.initials: CW
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Wan Fang Hospital, Taipei Medical University, No.111, Sec.3, Hsing-Long Rd., Taipei 116, Taiwan.
authors.forename: Ming-I
authors.initials: MI
authors.lastname: Hsu
authors.affiliation: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Taipei Medical University Hospital, No.252, Wu Hsing St., Sinyi District, Taipei 110, Taiwan; Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, No.250, Wusing St., Sinyi District, Taipei 110, Taiwan. Electronic address: d102095012@gmail.com.
authors.forename: Chi-Huang
authors.initials: CH
authors.lastname: Chen
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone / Q000378:metabolism; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects*; D002066:Busulfan / Q000009:adverse effects / Q000737:chemistry; D053148:Caspase 3 / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D006107:Granulosa Cells / Q000187:drug effects; D007150:Immunohistochemistry; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D006080:Ovarian Follicle / Q000187:drug effects; D010053:Ovary / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D008246:Lysophospholipids; D012333:RNA, Messenger; C060506:sphingosine 1-phosphate; D054304:Anti-Mullerian Hormone; D053148:Caspase 3; D002066:Busulfan; D013110:Sphingosine
keywords: anti-Müllerian hormone; anti-apoptotic therapy; caspase-3; fertility preservation; gonadotoxicity; sphingosine-1-phosphate