High-quality human preimplantation embryos actively influence endometrial stromal cell migration

R P Berkhout,C B Lambalk,S Repping,G Hamer,V Mijatovic,S Mastenbroek,J Huirne

doi:10.1007/s10815-017-1107-z

Abstract

PurposeThe purpose of this paper is to study whether human preimplantation embryos regulate endometrial stromal cell (hESC) migration.MethodsPrimary hESCs were isolated from fertile patients undergoing hysterectomy for benign conditions (uterine scar niche n = 3, dysmenorrhea n = 2; no hormonal treatment). Migration and proliferation assays were performed by culturing decidualized or non-decidualized hESCs in the presence of embryo conditioned medium (ECM) from high-quality embryos (fragmentation ≤ 20%) or from low-quality embryos (fragmentation > 20%) or in non-conditioned medium from the same dishes (control). ECM samples from 425 individually cultured human embryos were used in this study.ResultsECM from high-quality embryos, i.e., with a low percentage of fragmentation, actively stimulated decidualized hESC migration (p < 0.001). This effect was consistent throughout embryonic development from cleavage stage embryos with 2–7 cells (high quality vs. control; p = 0.036), 8–18 cells (high quality vs. control; p < 0.001) to morulae (high quality vs. control; p = 0.003). Additionally, linear regression analysis showed that hESC migration was influenced by embryo quality (fragmentation, β − 0.299; p = 0.025) and not developmental stage (cell number, β 0.177; p = 0.176) or maternal age (β − 0.036; p = 0.78). Opposite to decidualized hESCs, the migration response of non-decidualized hESCs was inhibited by ECM from high-quality embryos (p = 0.019). ECM from low-quality embryos, i.e., with a high percentage of fragmentation, did not cause an altered migration response in decidualized hESCs (p = 0.860) or non-decidualized hESCs (p = 0.986). Furthermore, ECM of both high- and low-quality human embryos did not influence the number of proliferating cells (p = 0.375) and the cell cycle time (p = 0.297) of non-decidualized or decidualized hESCs.ConclusionThis study reveals a mechanism by which high-quality human preimplantation embryos actively interact with the endometrium to increase their chances of successful implantation.

Highlights

Implantation failure is still common in treatments for subfertility such as IVF/ICSI
Decidualization of human preimplantation embryos regulate endometrial stromal cell (hESC) was confirmed by expression of Prolactin (PRL) and Insulin-like growth factor-binding protein 1 (IGFBP1) by using Real-Time PCR
Decidualized hESCs were incubated with embryo conditioned medium (ECM) from lowquality embryos with 2–7 blastomeres, highquality embryos with eight or more blastomeres or non-conditioned medium from the same dishes and migration assays were performed

Summary

Introduction

Implantation failure is still common in treatments for subfertility such as IVF/ICSI. More than half of all embryo transfers are not followed by a pregnancy resulting in live birth [1]. Improving the chances of implantation is considered an attractive strategy to improve ongoing pregnancy rates in IVF/ICSI [2]. A synchronous interplay has been suggested to take place between the embryo and the receptive endometrium [3]. Little is known about the precise interaction between the embryo and the endometrium. An acknowledged predictor for successful implantation in IVF/ICSI is the morphology of the transferred embryo [4].

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