Abstract
Podophyllotoxin (PPT) is a kind of lignans extracted from the roots and stems of the genus Podophyllum from the tiller family, and it has been widely used in the treatment of condyloma acuminatum, multiple superficial epithelioma in the clinics. However, PPT has been reported to be toxic and can cause liver defects and other organ poisoning. In addition, emerging evidences also indicate that PPT has reproductive toxicity and causes female reproduction disorders. In this study, we used fertilized oocytes and tried to explore the effects of PPT on the early embryonic development with the mouse model. The results showed that exposure to PPT had negative effects on the cleavage of zygotes. Further analysis indicated that PPT could disrupt the organization of spindle and chromosome arrangement at the metaphase of first cleavage. We also found that PPT exposure to the zygotes induced excessive reactive oxygen species (ROS), suggesting the occurrence of oxidative stress. Moreover, in the PPT-exposed embryos, there was positive γH2A.X and Annexin-V signals, indicating that PPT induced embryonic DNA damage and early apoptosis. In conclusion, our results suggested that PPT could affect spindle formation and chromosome alignment during the first cleavage of mouse embryos, and its exposure induced DNA damage-mediated oxidative stress which eventually led to embryonic apoptosis, indicating the toxic effects of PPT on the early embryo development.
Highlights
The early embryonic development quality of mammals is very important for the successful implantation (Teh et al, 2016)
Our results suggest that PPT could reduce the first cleavage competence to the two-cell stage in early mouse embryos. 1 nM PPT treatment was used for the following experiments
Since previous studies showed that DNA damage increases the level of reactive oxygen species (ROS) in somatic cells, we investigated whether PPT exposure could induce oxidative stress in early mouse embryos
Summary
The early embryonic development quality of mammals is very important for the successful implantation (Teh et al, 2016). The mammalian embryo development begins with the entry of sperm into oocytes and the formation of fertilized oocytes (Duan et al, 2014). When the sperm enters the oocyte, the oocyte completes the second meiosis and forms a zygote (Teh et al, 2016). The embryo undergoes continuous cleavage to form a morula, and the embryo differentiates into trophoblast ectoderm and inner cell mass, and forms a blastocyst (Marikawa and Alarcon, 2009). During this process, important morphological changes such as cell proliferation, compaction, and blastocyst formation occur (Oestrup et al, 2009).
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