2-Methoxyoestradiol impairs mouse embryo implantation via F-spondin
Emanuel Guajardo-Correa A B , Denisse Mena-Silva A B , Patricia Diaz A B , Carlos Godoy-Guzmán C , Hugo Cardenas A B and Pedro A. Orihuela
A B D
+ Author Affiliations
- Author Affiliations
A Laboratorio de Inmunología de la Reproducción, Facultad de Química y Biología, Universidad de Santiago de Chile.
B Centro para el Desarrollo en Nanociencia y Nanotecnología-CEDENNA.
C Centro de Investigación Biomédica y Aplicada (CIBAP), Escuela de Medicina, Facultad de Ciencias Médicas, Universidad de Santiago de Chile, Casilla 40, Correo 33, Chile.
D Corresponding author. Email: pedro.orihuela@usach.cl
Reproduction, Fertility and Development 31(4) 689-697 https://doi.org/10.1071/RD18114
Submitted: 24 March 2018 Accepted: 17 October 2018 Published: 19 November 2018
Abstract
The anti-implantation effects of high oestradiol (E2) concentrations could be mediated by E2 metabolites. Herein, we examined whether 2-methoxyoestradiol (2ME) impairs embryo implantation via its target protein F-spondin. Mice on Day 3 of pregnancy were treated with E2 concomitantly with the cathecol-O-methyl transferase inhibitor OR486 and the number of implanted embryos was recorded 5 days later. The effect of 2ME or 4-methoxyoestradiol (4ME) on embryo implantation was also investigated. Plasma and uterine levels of 2ME were measured 0.5, 1 or 3 h after E2 treatment while the mRNA for spondin 1 (Spon1) and F-spondin were determined in the uterus 3, 6, 12 or 24 h after 2ME treatment. Finally, the effect of a neutralising F-spondin antibody on the anti-implantation effect of 2ME was explored. OR486 blocked the anti-implantation effect of E2; 2ME, but not 4ME, affected embryo implantation. The 2ME concentration was increased after 0.5 and 1 h in plasma and 3 h in uterine fluid following E2 treatment. 2ME increased levels of Spon1 at 12 and 24 h although F-spondin was increased at 12 h. F-spondin antibody blocked the effect of 2ME on embryo implantation. We conclude that 2ME impairs mouse embryo implantation via activation of F-spondin in the uterus.
Additional keywords: blastocyst, cathechol-O-methyltransferase, hyperoestrogenic, oestradiol, oestrogen metobolites, uterine fluid.
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