K. Asimaki , P. Vazakidou , H.T.A. van Tol , M.B.M. van Duursen , B.M. Gadella
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引用次数: 0
Abstract
Ketoconazole (KTZ) is widely used as a fungicide, but it is also known to target steroid hormone formation which may affect female reproductive health. Our study aims to investigate the effects of KTZ on in vitro matured bovine cumulus-oocyte complexes (COCs), as a model for female reproductive toxicity. Cumulus cells of in vitro maturing COCs produce progesterone and pregnenolone, but exposure to 10−6 M KTZ effectively blocked the synthesis of these hormones. Exposure to lower concentrations of KTZ (i.e. 10−7 M and 10−8 M) had no such effect on steroidogenesis compared to the 0.1 % v/v DMSO vehicle control. Classical parameters of in vitro COC maturation, such as oocyte nuclear maturation to the metaphase II stage and expansion of the cumulus investment, were not affected by any KTZ concentration tested. Apoptosis and necrosis levels were also not altered in cumulus cells or oocytes exposed to KTZ. Moreover, oocytes exposed to KTZ during maturation showed normal cleavage and early embryo development up to day 8 post fertilization; albeit a statistically significant decrease was observed in day 8 blastocysts produced from oocytes exposed to the lowest concentration of 10−8 M KTZ. When unexposed mature oocytes were fertilized, followed by embryo culture for 8 days under KTZ exposure, no adverse effects in embryo cleavage and blastocyst formation were observed. In conclusion, KTZ has no major impact on in vitro bovine oocyte maturation and blastocyst formation in our study, even at concentrations blocking steroidogenesis.
期刊介绍:
Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine.
All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.