Increasing levels of estradiol are deleterious to embryonic implantation because they directly affect the embryo

Citation
D. Valbuena et al., Increasing levels of estradiol are deleterious to embryonic implantation because they directly affect the embryo, FERT STERIL, 76(5), 2001, pp. 962-968
Citations number
27
Categorie Soggetti
Reproductive Medicine","da verificare
Journal title
FERTILITY AND STERILITY
ISSN journal
00150282 → ACNP
Volume
76
Issue
5
Year of publication
2001
Pages
962 - 968
Database
ISI
SICI code
0015-0282(200111)76:5<962:ILOEAD>2.0.ZU;2-E
Abstract
Objective: To investigate whether the deleterious effect of E-2 on embryoni c implantation is due to a direct effect on the endometrium, on the embryo, or both. Design: Prospective, controlled in vitro study. Setting: Tertiary infertility center. Patient(s): Fertile patients in the luteal phase with histologically normal endometrium who were attending the infertility clinic as oocyte donors (n = 14). Intervention(s): 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 per-formed in an in vitro embryo adhesion assay composed of human polarized endometrial e pithelial cells obtained from fertile patients and mouse embryos. Main Outcome Measure(s): Blastocyst formation rate and embryo adhesion rate . Results: Monolayers of polarized endometrial epithelial cells expressed ER alpha at the mRNA level. The E-2 dose response of blastocysts with polarize d endometrial epithelial cells (n = 235) demonstrated a progressive reducti on in embryonic adhesion that was statistically significant at 10(-6) M. Wh en polarized endometrial epithelial cells were treated alone with increasin g 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 con centrations until day 5, the rate of M, and embryonic adhesion decreased bl astocyst formation significantly decreased at a concentration greater than or equal to 10(-6) when blastocysts (n = 400) were obtained at a concentrat ion greater than or equal to 10(-7) M. Time course experiments of embryos c ultured for 2 days with polarized endometrial epithelial cells (n = 426) sh owed 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). Conclusion(s): High E-2 levels are deleterious to embryo adhesion in vitro, mainly because they have a direct toxic effect on the embryo that may occu r at the cleavage stage. (C) 2001 by American Society for Reproductive Medi cine.