Preimplantation exposures of murine embryos to estradiol or methoxychlor change postnatal development

Abstract

Long-term effects of in vivo exposures to proestrogen methoxychlor (MXC) or estradiol-17beta (E) were studied during early pregnancy (preimplantation) in ICR mice. Pregnant dams received either subcutaneous injections of 1 microg of E on Day 2 of pregnancy only (vaginal plug = Day 1), or 5.0mg of MXC on Days 2-4 of pregnancy in sesame oil. Pregnant control mice were treated with the vehicle only. Litter size, postnatal survival, sex ratio at birth, and anogenital distance (AGD) in offspring of both sexes were examined, as well as vaginal opening in female offspring. High mortality rate was recorded in MXC-exposed offspring due to infanticide. Exposures to either E or MXC did not change sex ratio at birth, but the litter size was smaller in the former group. On postnatal Day 21, male pups exposed to either E or MXC at preimplantation stage exhibited shorter AGD than the controls, with the change most pronounced after MXC treatments. AGD in female offspring was unaffected after MXC exposures, but E treatments produced longer AGD in the females than that recorded in the controls. Preimplantation exposures to E or MXC also accelerated sexual maturation as significantly more females exhibited precocious vaginal opening at weaning. Our study shows that exposures to MXC or E at preimplantation stages cause long term alteration of sexual development during weaning in offspring of both sexes. Also, MXC treatments retarded both growth and weight of both sexes of offspring, in comparison to controls.