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.

Keywords: Cell junctions; Compaction; Human embryo; Polarization; Trophectoderm biopsy.

Fig. 1

Schematic description of some unanswered questions on both the safety of the TE biopsy and the clinical value of PGT-A. (a) Assisted hatching: potential rescue of abnormal embryos. (b) Uncertain number of biopsied TE cells. (c) Higher number of biopsied TE cell: impaired HCG and VEGF secretion and increased risk of implantation failure. (d) Tight junction disruption and developmental compromise. (e) Focally biopsied TE cells do not necessarily reflect the ploidy of the ICM. (f) The developmental fate of TE cells is uncertain at the time of biopsy. (g) Impaired ICM cell load following TE cell extraction. (h) Cell communication system disruption. ICM, inner cell mass; TE, trophectoderm; ZP, zona pellucida; HCG, human chorionic gonadotropin; VEGF, vascular endothelial growth factor; AH, assisted hatching; TJ, tight junction; PGT-A, pre-implantation genetic testing for aneuploidy