Premature Induction of the Decidual Reaction after Cyclophosphamide Treatment in the Rat

Abstract

After treatment of pregnant rats or mice during the preimplantation period with cyclophosphamide (CPA), the embryos are retarded and die during organogenesis. Previous studies using both in vivo and in vitro approaches have shown that the embryos are affected by CPA-treatment of the mother already before implantation (J. Embryol. exp. Morph. 41, 65, 1977; Nature 270, 54, 1977). The same investigations indicated an inhibition of the decidual reaction of the uterus during organogenesis after CPA-treatment before implantation. — To elucidate to what extent effects of the early CPA-treatment on the decidualization of the uterus are involved in the delayed embryolethal effect, the course of the decidual reaction was investigated during the implantation period after CPA-application. On day 3 of gestation rats were treated with a single s.c. injection of 60 mg/kg CPA. Between days 4 and 7 the uteri were examined light microscopically. In addition, the labelling index of the stroma cells on day 4 (preimplantation) and day 6 (postimplantation) was determined after a ³H-thymidine pulse, On day 4 the increase in the labelling index of the uterine stroma cells 24 h after CPA-application on day 3 (40% as compared to 7% in controls) as well as the light microscopical findings of an increased cell number and a reduction in the size of the intercellular spaces underneath the uterine epithelium suggest a premature decidual reaction. On day 6 of gestation the percentage of stroma cells which had differentiated into decidual cells was increased after CPA-treatment when compared to untreated controls. It is, therefore, concluded that the transformation of stroma cells into decidual cells is induced prematurely by CPA-application before implantation. Furthermore, the percentage of necrotic stroma cells increased between days 4 and 7 in CPA-treated animals, eventually leading to a reduction in the amount of decidual tissue.