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Development requires coordinated interactions between the epiblast, which generates the embryo proper; the trophectoderm, which generates the placenta; and the hypoblast, which forms both the anterior signalling centre and the yolk sac. These interactions remain poorly understood in human embryogenesis because mechanistic studies have only recently become possible. Here we examine signalling interactions post-implantation using human embryos and stem cell models of the epiblast and hypoblast. We find anterior hypoblast specification is NODAL dependent, as in the mouse. However, while BMP inhibits anterior signalling centre specification in the mouse, it is essential for its maintenance in human. We also find contrasting requirements for BMP in the naive pre-implantation epiblast of mouse and human embryos. Finally, we show that NOTCH signalling is important for human epiblast survival. Our findings of conserved and species-specific factors that drive these early stages of embryonic development highlight the strengths of comparative species studies., (© 2024. The Author(s).)

Apico-basal polarization of cells within the embryo is critical for the segregation of distinct lineages during mammalian development. Polarized cells become the trophectoderm (TE), which forms the placenta, and apolar cells become the inner cell mass (ICM), the founding population of the fetus. The cellular and molecular mechanisms leading to polarization of the human embryo and its timing during embryogenesis have remained unknown. Here, we show that human embryo polarization occurs in two steps: it begins with the apical enrichment of F-actin and is followed by the apical accumulation of the PAR complex. This two-step polarization process leads to the formation of an apical domain at the 8-16 cell stage. Using RNA interference, we show that apical domain formation requires Phospholipase C (PLC) signaling, specifically the enzymes PLCB1 and PLCE1, from the eight-cell stage onwards. Finally, we show that although expression of the critical TE differentiation marker GATA3 can be initiated independently of embryo polarization, downregulation of PLCB1 and PLCE1 decreases GATA3 expression through a reduction in the number of polarized cells. Therefore, apical domain formation reinforces a TE fate. The results we present here demonstrate how polarization is triggered to regulate the first lineage segregation in human embryos., Competing Interests: MZ, MS, AM, CZ, BS, MB, RM, RP, MM, ME, ST, RS, AC, SF, VG, HZ, KW, ZC, ES, Md, MZ No competing interests declared, (© 2021, Zhu et al.)

Research Question: During the embryo transfer procedure, to what degree of temperature drop are embryos exposed to between loading the transfer catheter and placing it into the uterus?, Design: Twenty-nine simulated embryo transfer procedures were carried out across five clinics. A thermocouple probe was used for standardized measurements inside the embryo transfer catheter to investigate the change in temperature that occurred in the time period between loading and placing the catheter in the uterus., Results: In all cases, the temperature at the loaded catheter tip fell rapidly to ambient temperature during transit from the embryo transfer workstation in the laboratory to the procedure room, even though embryo transfer procedures, ambient temperatures and embryo transfer catheter temperatures at loading varied between clinics., Conclusions: Given the sensitivity of the pre-implantation embryo to its immediate environment, the rapid and profound drop in temperature observed at the catheter tip that houses the embryo during transit from laboratory to the uterus may affect embryo viability and health. This issue should be addressed to ensure that the tight temperature control aimed for by IVF laboratories continues throughout the embryo transfer procedure, and could improve clinical outcomes., (Copyright © 2021. Published by Elsevier Ltd.)

Machine learning methods applied to large genomic datasets (such as those used in GWAS) have led to the creation of polygenic risk scores (PRSs) that can be used identify individuals who are at highly elevated risk for important disease conditions, such as coronary artery disease (CAD), diabetes, hypertension, breast cancer, and many more. PRSs have been validated in large population groups across multiple continents and are under evaluation for widespread clinical use in adult health. It has been shown that PRSs can be used to identify which of two individuals is at a lower disease risk, even when these two individuals are siblings from a shared family environment. The relative risk reduction (RRR) from choosing an embryo with a lower PRS (with respect to one chosen at random) can be quantified by using these sibling results. New technology for precise embryo genotyping allows more sophisticated preimplantation ranking with better results than the current method of selection that is based on morphology. We review the advances described above and discuss related ethical considerations.

Time-lapse imaging of the human preimplantation embryo in vitro has revealed a transient phenomenon involving the appearance of perivitelline threads, commonly observed at the two-cell stage. These threads span the perivitelline space, arising at the specific area where the cytoplasmic membrane contacts the zona pellucida, before any perivitelline space is formed. The threads persist as the cytoplasmic membrane retracts from the zona pellucida to form the first cleavage furrow. In this observational report, these structures and their incidence are described. A total of 834 time-lapse videos from IVF treatment cycles, one per patient, were retrospectively analysed for perivitelline threads, from pronuclear formation until completion of the first cell cycle. Threads were observed in 56.4% (470/834) of embryos and varied from a single to an array spanning an area of the zona pellcida. A total of 91.9% (432/470) were seen to form after cytoplasmic membrane-zona-pellucida contact. A total of 76.4% (359/470) were visible at the first cleavage furrow; 77% (362/470) were associated with cytoplasmic fragments at the two-cell-stage. Presence or absence of threads did not affect embryo development. This descriptive study is limited; further characterization of these structures is needed to elucidate their potential role in early human embryo development., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Cell-surface antigens provide invaluable tools for the identification of cells and for the analysis of cell differentiation. In particular, stage-specific embryonic antigens that are developmentally regulated during early embryogenesis are widely used as markers to monitor the differentiation of both mouse and human embryonic stem (ES) cells and their malignant counterparts, embryonic carcinoma (EC) cells. However, there are notable differences in the expression patterns of some such markers between human and mouse ES/EC cells, and hitherto it has been unclear whether this indicates significant differences between human and mouse embryos, or whether ES/EC cells correspond to distinct cell types within the early embryos of each species. We now show that human ES cells are characterized by the expression of the cell-surface antigens, SSEA3, SSEA4, TRA-1-60, and TRA-1-81, and by the lack of SSEA1, and that inner cell mass cells of the human blastocyst express a similar antigen profile, in contrast to the corresponding cells of the mouse embryo.

The survival and implantation capacity of cryopreserved cleaving (5-cell to 10-cell) human embryos and expanded blastocysts was compared. Twice as many cleaving embryos were frozen as were expanding blastocysts because of the low developmental potential of human embryos in vitro. However, significantly more expanded blastocysts survived cryopreservation than cleaving embryos, and relatively more pregnancies were established by the replacement of thawed blastocysts than by the replacement of thawed cleaving embryos. Cleaving embryos from 26 women were thawed; 17 had thawed embryos replaced, and 4 subsequently became pregnant. Expanded blastocysts were thawed from 23 other women; 15 had thawed blastocysts replaced, and 8 subsequently became pregnant. The pregnancy of one patient in each group aborted; both patients were over 40 years of age. It is estimated that by maintaining the current policy of replacing three fresh embryos and freezing any remaining embryos when they reach blastocyst stage, the total incidence of pregnancy would increase by 3%.

Changes in uptake of radioactive uridine and its incorporation into RNA were determined in preimplantation mouse embryos, from the 2-cell to the blastocyst stage, as a measure of their responsiveness to extracellular conditions. Two media were tested, one contained serum and the other contained bovine serum albumen as a control. An increase in the acid-soluble pool occurred at the 8-cell stage and a marked increase in RNA synthesis occurred at the early blastocyst stage when the embryos were incubated with serum.