Micronuclei and developmental abnormalities in 4‐day mouse embryos after paternal treatment with acrylamide

The developmental consequences of paternal exposure to acrylamide (50 mg/kg i.p. for 5 days) were assessed in preimplantation embryos. There was a significant increase in the proportion of morphologically abnormal embryos after postmeiotic treatment during spermatogenesis (88.7% vs. 14.8% in control). Abnormal embryos had an average of 1.8 ± 3.5 cells and >80% had at least one fragmented nucleus. In addition, morphologically normal embryos were significantly delayed (34.3 ± 12.8 cells per embryo vs. 57.6 ± 15.7 in control, P < 0.001). Acrylamide caused 10‐ and 20‐fold increases in frequencies of cells with micronuclei (MN) in morphologically normal and abnormal embryos, respectively (41 and 93 MN per 1,000 cells). Both centromere‐negative (M−) and centromere‐positive (M+) were induced. Nuclei of abnormal embryos were significantly larger (900 μm2 vs. 250 μm2) than controls. In addition, MN of abnormal embryos were larger than those of normal embryos (21.2 μm2 vs. 6.5 μm2, P < 0.01). Among control embryos, M+ were significantly larger than M− (P < 0.05). These findings suggest that the preimplantation embryo is a sensitive indicator of paternally transmitted effects on early development. Multiple mechanisms appear to be involved, including cytogenetic damage, proliferation arrest/delay, and fertilization failure. Future studies are needed to establish how induced cytological defects in preimplantation embryos contribute to birth defects and other postimplantation abnormalities. Environ. Mol. Mutagen. 31:206–217, 1998 © 1998 Wiley‐Liss, Inc.

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