Natural Selection of Human Embryos: Decidualizing Endometrial Stromal Cells Serve as Sensors of Embryo Quality upon Implantation

Abstract

BackgroundPregnancy is widely viewed as dependent upon an intimate dialogue, mediated by locally secreted factors between a developmentally competent embryo and a receptive endometrium. Reproductive success in humans is however limited, largely because of the high prevalence of chromosomally abnormal preimplantation embryos. Moreover, the transient period of endometrial receptivity in humans uniquely coincides with differentiation of endometrial stromal cells (ESCs) into highly specialized decidual cells, which in the absence of pregnancy invariably triggers menstruation. The role of cyclic decidualization of the endometrium in the implantation process and the nature of the decidual cytokines and growth factors that mediate the crosstalk with the embryo are unknown.Methodology/Principal FindingsWe employed a human co-culture model, consisting of decidualizing ESCs and single hatched blastocysts, to identify the soluble factors involved in implantation. Over the 3-day co-culture period, approximately 75% of embryos arrested whereas the remainder showed normal development. The levels of 14 implantation factors secreted by the stromal cells were determined by multiplex immunoassay. Surprisingly, the presence of a developing embryo had no significant effect on decidual secretions, apart from a modest reduction in IL-5 levels. In contrast, arresting embryos triggered a strong response, characterized by selective inhibition of IL-1β, -6, -10, -17, -18, eotaxin, and HB-EGF secretion. Co-cultures were repeated with undifferentiated ESCs but none of the secreted cytokines were affected by the presence of a developing or arresting embryo.ConclusionsHuman ESCs become biosensors of embryo quality upon differentiation into decidual cells. In view of the high incidence of gross chromosomal errors in human preimplantation embryos, cyclic decidualization followed by menstrual shedding may represent a mechanism of natural embryo selection that limits maternal investment in developmentally impaired pregnancies.

Standardisation of uterine natural killer (uNK) cell measurements in the endometrium of women with recurrent reproductive failure

“…Further work is required to determine what constitutes a 'high' uNK cell density and the timing of the biopsy will be an 435 important aspect of this work. In addition, it still needs to be determined whether the increased uNK cell numbers reflects a causative role in recurrent miscarriage and recurrent implantation failure or rather is a marker of a more generalised endometrial dysfunction that contributes to these conditions (Salker et al 2010;Teklenburg et al 2010). 440…”

Prediction of embryo implantation potential by mass spectrometry fingerprinting of the culture medium

“…This result is reasonable as implantation is known to involve an intricate dialog between the embryo and the endometrium, which is supposed to be receptive (Achache & Revel 2006, Teklenburg et al 2010, Mastenbroek et al 2011. We are aware that the ideal experimental design for the evaluation of embryo viability would involve only single-embryo transfers.…”

The role of immunological markers in assessment of implantation uterus receptivity - clinical implications.

“…Reakcja doczesnowa zapewnia wrażliwość endometrium na rozpoznawanie prawidłowych i nieprawidłowych zarodków i szybką eliminację zarodków nieprawidłowych, jeszcze w czasie okołoimplantacyjnym [4,9]. Do czynników wydzielanych przez endometrium macicy w czasie implantacji i wczesnej ciąży zalicza się m.in.…”