Cyclophosphamide treatment prior to implantation: the effects on embryonic development

  • H. Spielmann
  • H.-G. Eibs
  • Ursula Jacob-Müller
Part of the Advances in the Study of Birth Defects book series (ASBD, volume 2)


Research in teratology usually focuses on the period of organogenesis, because this is the most sensitive period for the induction of malformations in mammals1,2. Attempts to study drug actions on earlier periods of pregnancy have not been very successful, because the preimplantation embryo is remarkably resistant to teratogens. In the earliest study of this problem the treatment of cleaving rabbit eggs with purine analogues in vivo 3 has no effect on development until at or after implantation. Investigations on the effects of X-irradiation4 during the first days of pregnancy in the rat increased neither gross congenital malformations nor fetal growth retardation at the end of pregnancy. There is, furthermore, no indication for an increased rate of abnormalities among the offspring from embryos cultured in vitro in the presence of various teratogens during the preimplantation period and subsequently transferred to foster mothers5. Additionally the fetuses from transplanted preimplantation mouse embryos on which different kinds of microsurgery had been performed6 or which had been frozen to -269 °C for up to one year7 never showed an increased malformation rate at term. The effect of teratogens on embryos during the preimplantation period, therefore, has been explained by Austin8 as follows: ‘The effect of teratogens on the cleavage embryo depends on the number of cells killed or inhibited: above a certain portion, the embryo dies; below that figure, the remaining cells multiply to replace those lost and subsequent development is essentially normal.’


Inner Cell Mass Preimplantation Embryo Resorption Rate Mouse Blastocyst Preimplantation Mouse Embryo 
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Copyright information

© MTP Press Limited 1979

Authors and Affiliations

  • H. Spielmann
  • H.-G. Eibs
  • Ursula Jacob-Müller

There are no affiliations available

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