title: The Tyrosine Kinase Inhibitor Sunitinib Affects Ovulation but Not Ovarian Reserve in Mouse: A Preclinical Study.
abstract: The aim of the study was to evaluate ovarian toxicity of tyrosine kinase inhibitor (TKI) sunitinib, since only scarce data are available on gonadal function after this treatment. Six-week-old female mice received orally, once daily, vehicle or sunitinib (50 mg/kg/d) during 5 weeks. Fertility parameters were analyzed from ovulation to litter assessment. Sunitinib exposure significantly reduced (i) corpora lutea number per ovary (1.1 ± 0.38 in sunitinib group versus 4 ± 0.79 in control group, p<0.01) and (ii) serum Anti Müllerian hormone (AMH) levels in sunitinib treated mice (12.01 ± 1.16) compared to control mice (14.33 ± 0.87 ng/ml, p< 0.05). However, primordial and growing follicles numbers per ovary were not different in both groups. After treatment withdrawal, female mice in both groups were able to obtain litters. These data could be helpful to counsel clinicians and patients, when fertility preservation methods are discussed, before TKI treatment in girls and young women.
authors.affiliation: Inserm U1185, Univ. Paris-Sud, Université Paris Saclay, Le Kremlin-Bicêtre, 94276, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bernard
authors.affiliation: Inserm U1185, Univ. Paris-Sud, Université Paris Saclay, Le Kremlin-Bicêtre, 94276, France.
authors.forename: Justine
authors.initials: J
authors.lastname: Bouilly
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Piet
authors.initials: P
authors.lastname: Kramer
authors.affiliation: Inserm U1185, Univ. Paris-Sud, Université Paris Saclay, Le Kremlin-Bicêtre, 94276, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Carré
authors.affiliation: Institut Gustave Roussy, Département de Médecine nucléaire et Oncologie endocrinienne, Université Paris-Sud, Villejuif, 94800, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Visser
authors.affiliation: Inserm U1185, Univ. Paris-Sud, Université Paris Saclay, Le Kremlin-Bicêtre, 94276, France.|Service d'Endocrinologie et des Maladies de la Reproduction, Assistance Publique des Hôpitaux de Paris, Univ. Paris-Sud, Faculté de Médecine Paris-Sud, Le Kremlin Bicêtre, 94276, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Young
authors.affiliation: Inserm U1185, Univ. Paris-Sud, Université Paris Saclay, Le Kremlin-Bicêtre, 94276, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Binart
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D051379:Mice; D065851:Ovarian Reserve / Q000187:drug effects*; D010060:Ovulation / Q000187:drug effects*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000494:pharmacology*; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib