title: The antibiotic streptomycin assessed in a battery of in vitro tests for reproductive toxicology.
abstract: Streptomycin is one of the most widely used antibiotics and is frequently added to cell culture media to prevent bacterial growth. We tested streptomycin in a battery of in vitro assays for assessment of reproductive toxicity. The follicle bio-assay (FBA) is a multiparametric long-term follicle culture system mimicking ovarian function; in vitro fertilisation (IVF) of exposed oocytes enables gamete quality determination through fecundability; the mouse embryo assay (MEA) analyses pre-implantation embryo development whereas the embryonic stem cell test (EST) studies post-implantation embryotoxicity. The FBA revealed a concentration-dependent decrease in oocyte nuclear maturation during continuous exposure from 50 microg/ml streptomycin onwards, characterised by a significantly reduced polar body-rate (40% vs. 92% in the control group). Oocytes that remained arrested in metaphase I (germinal vesicle breakdown) had aberrant spindle formation. IVF of long-term exposed oocytes in the FBA to 50 microg/ml streptomycin resulted in a significantly lower fertilisation rate of 23% vs. 74% in the control group and were unable to develop to the blastocyst stage. The MEA revealed no effect at pre-implantation embryo development and quality. Furthermore, no embryo-toxic effects of streptomycin were observed in the EST. In conclusion, oocytes are vulnerable to streptomycin treatment. Long-term exposure might cause fertility problems in the female and caution should be taken using streptomycin in cell culture media for assisted reproductive technology (ART).
authors.affiliation: EggCentris NV, Z.1 Researchpark 310, B-1731 Zellik, Belgium. kelly.lemeire@eggcentris.com
authors.forename: K
authors.initials: K
authors.lastname: Lemeire
authors.forename: V
authors.initials: V
authors.lastname: Van Merris
authors.forename: R
authors.initials: R
authors.lastname: Cortvrindt
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D004622:Embryo, Mammalian / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro; D007247:Infertility, Female / Q000139:chemically induced; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009865:Oocytes / Q000187:drug effects*; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects*; D013307:Streptomycin / Q000633:toxicity*; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents; D013307:Streptomycin