Remdesivir impairs mouse preimplantation embryo development at therapeutic concentrations.

Remdesivir (RDV) is the first antiviral drug to be approved by the US Food and Drug Administration for the treatment of COVID-19. While the general safety of RDV has been studied, its reproductive risk, including embryotoxicity, is largely unknown. Here, to gain insights into its embryotoxic potential, we investigated the effects of RDV on mouse preimplantation embryos cultured in vitro at the concentrations comparable to the therapeutic plasma levels. Exposure to RDV (2-8 µM) did not affect the initiation of blastocyst formation, although the maintenance of the cavity failed at 8 µM due to increased cell death. While exposure to 2-4 µM permitted the cavity maintenance, expressions of developmental regulator genes associated with the inner cell mass (ICM) lineage were significantly diminished. Adverse effects of RDV depended on the duration and timing of exposure, as treatment between the 8-cell to early blastocyst stage most sensitively affected cavity expansion, gene expressions, and cell proliferation, particularly of the ICM than the trophectoderm lineage. GS-441524, a major metabolite of RDV, did not impair blastocyst formation or cavity expansion, although it altered gene expressions in a manner differently from RDV. Additionally, RDV reduced the viability of human embryonic stem cells, which were used as a model for the human ICM lineage, more potently than GS-441524. These findings suggest that RDV is potentially embryotoxic to impair the pluripotent lineage, and will be useful for designing and interpreting further in vitro and in vivo studies on the reproductive toxicity of RDV.

Ex uno, plures-From One Tissue to Many Cells: A Review of Single-Cell Transcriptomics in Cardiovascular Biology.

Recent technological advances have revolutionized the study of tissue biology and garnered a greater appreciation for tissue complexity. In order to understand cardiac development, heart tissue homeostasis, and the effects of stress and injury on the cardiovascular system, it is essential to characterize the heart at high cellular resolution. Single-cell profiling provides a more precise definition of tissue composition, cell differentiation trajectories, and intercellular communication, compared to classical bulk approaches. Here, we aim to review how recent single-cell multi-omic studies have changed our understanding of cell dynamics during cardiac development, and in the healthy and diseased adult myocardium.

Human Oocytes Express Both ACE2 and BSG Genes and Corresponding Proteins: Is SARS-CoV-2 Infection Possible?

In addition to a number of scientific and medical questions about SARS-CoV-2 infection that still need to be answered, there is also the question of how this highly virulent virus and COVID-19 disease affect gametogenesis in humans. Even more important is the question of whether the virus can also enter and infect oocytes and possibly alter them in an unknown way, which could also affect the development and status of the human embryo. The answers to these questions are still poorly known, so we reviewed the human oocyte transcriptome and proteome obtained in our previous studies and found that human oocytes from the in vitro fertilization program expressed both the ACE2 and BSG genes and the corresponding ACE2 and BSG proteins. This means that human oocytes possess the molecular 'machinery' to facilitate SARS-CoV-2 entrance and infection. According to various studies, especially in animal models, different viruses can infect oocytes, so infection of the oocyte with SARS-Cov-2 cannot be completely ruled out. A hypothetical model of human oocyte infection with this virus has been proposed.