When bovine life begins in a petri dish: transcriptomic insights from embryos to calves conceived in vitro

Abstract

Gamete plasticity enables fertilization and embryo development under laboratory conditions through procedures commonly known as in vitro production (IVP). While this technology is primarily used in humans to treat infertility, it also enables the propagation of high-quality genetic material at relatively low cost in cattle, supporting sustainable animal production. However, IVP has inherent limitations. The artificial environment in which gamete maturation, fertilization, and embryo development occur may induce permanent epigenomic modifications, thereby altering the individual's transcriptome. This review synthesizes studies describing recurrent phenotypes observed across life stages in IVP-derived cattle compared with in vivo counterparts, from embryonic development through postnatal life, and outlines associated transcriptomic alterations and their potential prediction based on transcriptomic data. Collectively, the evidence indicates that increased pregnancy losses following the transfer of IVP embryos, predominantly after implantation, represent the principal limitation of the technology. When IVP embryos survive, early molecular perturbations may manifest as fetal overgrowth, increased birth weight, stillbirth, and a greater predisposition to reproductive disorders later in life. At the molecular level, transcriptomic alterations are already detectable in the 16-cell IVP embryo if embryonic genome activation occurs in vitro; IVP blastocysts exhibit dysregulated expression of genes involved in energy homeostasis; key developmental genes are deregulated in the embryonic disc of elongated IVP embryos prior to implantation; and transcriptomic alterations due to IVP persist in metabolically relevant organs during fetal and postnatal stages. These findings, together with future research, may enhance understanding of how IVP influences developmental outcomes in cattle and other species, including humans.