Factors of importance for decreased early embryo survival in female mice treated neonatally with diethylstilboestrol.

Abstract

Neonatal female mice of the NMRI strain were treated s.c. with 5 micrograms of the synthetic oestrogen diethylstilboestrol (DES) or vehicle only (olive oil; controls) for the first 5 days after birth. Embryos at the two-cell stage from control females were transferred to the oviducts of control females or DES-treated females (6-8-weeks-old). Immediately after transfer, the oviducts were removed and incubated in vitro for 6 h. After incubation, slightly fewer embryos were recovered from oviducts exposed to DES compared with control oviducts (81% versus 92%; 0.05 > P > 0.01). When the recovered embryos were cultured in vitro, 64% of the embryos from control oviducts reached the blastocyst stage in contrast to only 24% of those from oviducts of DES-treated mice; slightly fewer of the latter showed trophoblastic outgrowth (76% versus 93%; 0.05 > P > 0.01). Oviductal transport and uterine attachment was studied by introduction of blue-stained dextran microspheres into the oviduct. The microspheres appeared earlier in the uteri of DES-treated females than in the uteri of controls. Moreover, the spheres were not captured in the uterus in most DES-treated females, but they were trapped when a piece of Spongostan was placed in the uterine lumen. Scanning electron microscope studies showed differences between controls and DES-treated females in uterine mucosal lining of possible importance for embryo attachment to the surface epithelium. These studies showed that neonatal DES treatment caused changes in the adult reproductive tract as revealed by a detrimental effect upon embryo development, more rapid oviductal transport and loss of embryos from the uterus.