The unknown human trophectoderm: implication for biopsy at the blastocyst stage

Abstract

Trophectoderm biopsy is increasingly performed for pre-implantation genetic testing of aneuploidies and considered a safe procedure on short-term clinical outcome, without strong assessment of long-term consequences. Poor biological information on human trophectoderm is available due to ethical restrictions. Therefore, most studies have been conducted in vitro (choriocarcinoma cell lines, embryonic and pluripotent stem cells) and on murine models that nevertheless poorly reflect the human counterpart. Polarization, compaction, and blastomere differentiation (e.g., the basis to ascertain trophectoderm origin) are poorly known in humans. In addition, the trophectoderm function is poorly known from a biological point of view, although a panoply of questionable and controversial microarray studies suggest that important genes overexpressed in trophectoderm are involved in pluripotency, metabolism, cell cycle, endocrine function, and implantation. The intercellular communication system between the trophectoderm cells and the inner cell mass, modulated by cell junctions and filopodia in the murine model, is obscure in humans. For the purpose of this paper, data mainly on primary cells from human and murine embryos has been reviewed. This review suggests that the trophectoderm origin and functions have been insufficiently ascertained in humans so far. Therefore, trophectoderm biopsy should be considered an experimental procedure to be undertaken only under approved rigorous experimental protocols in academic contexts.

Polygenic risk score for embryo selection—not ready for prime time

“…Therefore, to undertake fertility treatment for the sole purpose of selecting an embryo that has marginally lower risk of developing a late-onset polygenic condition appears counterproductive and is likely to result in an overall reduced chance of a healthy life. A similar argument can be made in relation to trophectoderm biopsy, which itself appears to produce higher risks of adverse outcomes in an offspring ( Cimadomo et al , 2016 ; Zacchini et al , 2017 ; Tocci, 2020 ). Therefore, an offspring that is born as a result of PRS-ES, where ART is undertaken for the singular purpose of embryo selection based on this technology, may end up having a less healthy life, compared to a naturally conceived individual.…”

Epidermal growth factor induces a trophectoderm lineage transcriptome resembling that of human embryos during reconstruction of blastoids from extended pluripotent stem cells

“…To further characterize TE‐like cells derived from human EPSCs, naive hPSCs, primed hPSCs and hTSCs, we analysed the expression of all genes with upregulated expression in the TE lineage 44 . The expression levels of TE‐like cells derived from human EPSCs and 2iLGöY 30 and PXGL 9 naive hPSCs were much higher than those of other cells, even compared with those of hTSCs (Figure 2A).…”

Current Advancements in Noninvasive Profiling of the Embryo Culture Media Secretome

“…The current gold standard methods require a biopsy to obtain genetic material from the developing embryo. Potential risk of compromising embryo development, long-term consequences [ 3 , 4 ] and associated high costs with the biopsy procedure have encouraged scientists to investigate options for a noninvasive PGT (niPGT), correlating genetic material found in blastocoele fluid (BF) and spent blastocyst media (SBM) to the one in trophectoderm (TE) following the biopsy. A recent review was published on the current advancements in the field niPGT testing for the identification of embryo ploidy.…”