To investigate whether the deleterious effect of E(2) on embryonic implantation is
due to a direct effect on the endometrium, on the embryo, or both.
Prospective, controlled in vitro study.
Tertiary infertility center.
Fertile patients in the luteal phase with histologically normal endometrium who were
attending the infertility clinic as oocyte donors (n = 14).
E(2) dose-response (0, 10(-8), 10(-7), 10(-6), 10(-5), and 10(-4) M) and time course
(day 2 vs. day 5) experiments were performed in an in vitro embryo adhesion assay
composed of human polarized endometrial epithelial cells obtained from fertile patients
and mouse embryos.
Blastocyst formation rate and embryo adhesion rate.
Monolayers of polarized endometrial epithelial cells expressed ERalpha at the mRNA
level. The E(2) dose response of blastocysts with polarized endometrial epithelial
cells (n = 235) demonstrated a progressive reduction in embryonic adhesion that was
statistically significant at 10(-6) M. When polarized endometrial epithelial cells
were treated alone with increasing doses of E(2) for 3 days and E(2) was then removed
and blastocysts added (n = 410), embryonic adhesion was not significantly reduced,
except at 10(-4) M. When 2-day mouse embryos (n = 609) were treated with increasing
E(2) concentrations until day 5, the rate of blastocyst formation significantly decreased
at a concentration >or= 10(-6) M, and embryonic adhesion decreased when blastocysts
(n = 400) were obtained at a concentration >or= 10(-7) M. Time course experiments
of embryos cultured for 2 days with polarized endometrial epithelial cells (n = 426)
showed that the adhesion rate was higher at E(2) levels of 10(-7), 10(-6) and 10(-5)
M compared with embryos cultured for 5 days (n = 495).
High E(2) levels are deleterious to embryo adhesion in vitro, mainly because they
have a direct toxic effect on the embryo that may occur at the cleavage stage.