Cell‐cycle alterations underlie cyclophosphamide‐induced teratogenesis in the chick embryo

Abstract

CP-induced cytotoxicity manifested by dose-dependent disturbance of cell-cycle resulted in an overall depression of proliferation activity clearly associated with the occurrence of malformations and embryonic death. Although a non-significant depression of mitotic activity appeared sufficient to produce malformations on Day 2, remarkably deeper disturbance was needed to interfere with the development of the embryos in more advanced stages. Changes in proliferation rate appear to be a primary and most important event in teratogenesis induced by general toxic agents.

Cell cycle proteins in normal and chemically induced abnormal secondary palate development: a review

“…Early exposure resulted in malformations even when the rate of proliferation was reduced only mildly, whereas later exposure required a greater effect on cell cycle to induce malformations. 15 A large body of evidence has accumulated in support of a role for perturbation of cell cycle in the induction of developmental toxic effects of many agents for which cell cycle is not the primary target for their non-developmental effects. For example, the developmental neurologic effects of methyl mercury, an agent known to induce CP in animals and defects in neural development in both animals and human beings, are likely due to an inhibition of proliferation of relevant cells secondary to its inhibition of their entry into, and progression of, the cell cycle.…”

Multiple Sclerosis and Pregnancy: Maternal Considerations

“…It has been used off label to treat active relapsing and progressive forms of MS [83]. CPA is shown to be teratogenic in animal studies when given to rats, mice, chicks and rabbits, producing similar CNS and skeletal anomalies [86][87][88][89] as well as craniofacial malformations in rhesus monkeys [90]. Human data are scarce with no available prospective observational studies of CPA exposure in pregnancy and its effect on fetal outcome.…”