{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T09:50:22Z","timestamp":1791798622304,"version":"4.3.4"},"reference-count":217,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001665","name":"French National Research Agency","doi-asserted-by":"publisher","award":["ANR-21-CE014-0085-21"],"award-info":[{"award-number":["ANR-21-CE014-0085-21"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University Hospital Federation PREMA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"Abstract<\/jats:title>\n \n BACKGROUND<\/jats:title>\n Infertility is a growing global challenge, with ARTs significantly improving birth rates for infertile couples. However, ART conceptions are associated with a higher risk of negative obstetrical and perinatal outcomes, with potential long-term effects on offspring health. Many pre-implantation embryos exhibit abnormal morphokinetics, implantation failure, or arrested development. ART procedures and parental factors are suspected to perturb the embryonic transcriptome, potentially affecting molecular and epigenetic events during gametogenesis and early development. The timing and mechanisms of these perturbations remain unclear. Genome-wide transcriptomic misregulation in ART-conceived human pre-implantation embryos may provide important insights into observed differences between ART and naturally conceived offspring.<\/jats:p>\n <\/jats:sec>\n \n OBJECTIVE AND RATIONALE<\/jats:title>\n This narrative review aims to explore how the transcriptome of the human pre-implantation embryo is influenced by parental characteristics, ART conditions, and embryonic factors, with the characterization of the temporal sequence of acquisition of lineage-specific markers at the blastocyst stage serving as a prerequisite. The primary objective is to compile changes in gene expression resulting from parental and intrinsic characteristics or from ART-specific interventions. A secondary aim is to identify common dysregulated molecular pathways across all factors studied.<\/jats:p>\n <\/jats:sec>\n \n SEARCH METHODS<\/jats:title>\n A comprehensive PubMed search (up to December 2024) was conducted to identify studies assessing transcriptomic profiles in human blastocysts. Studies were included based on parental infertility characteristics (e.g. age, polycystic ovary syndrome (PCOS), endometriosis, diminished ovarian reserve (DOR), sperm alterations, unexplained infertility (UI), and obesity), ART interventions (e.g. hormonal stimulation, IVM, IVF, culture conditions, and vitrification), and intrinsic embryo factors (e.g. morphology, ploidy, sex, and developmental arrest). Differentially expressed genes between different embryo groups were compared across studies, and Gene Ontology analysis identified common or specific pathways. Single-cell RNA sequencing data were used to map lineage-specific transcriptomic patterns in human blastocysts, categorizing expression changes by cell lineages (epiblast, primitive endoderm, and trophectoderm). Where human data on blastocysts were limited, animal studies or other cleaved stages were discussed.<\/jats:p>\n <\/jats:sec>\n \n OUTCOMES<\/jats:title>\n Maternal age was the most significant contributor to misregulated gene expression in human blastocysts, affecting metabolic and developmental processes. Variations in culture medium impacted cell cycle regulation, carbohydrate metabolism, and RNA biosynthesis. Blastocyst morphology mostly influenced metabolic process changes. Blastocyst aneuploidy induced significant changes in developmental pathways and pluripotency gene expression in the epiblast. Evidence on the effects of PCOS, endometriosis, DOR, sperm alterations, UI, and ART technologies remains limited. Dysregulated pathways commonly involve metabolic, cellular, reproductive, and developmental processes. Dysregulation of genomic imprinting and chromatin-modifier genes was also observed across at least two conditions.<\/jats:p>\n <\/jats:sec>\n \n WIDER IMPLICATIONS<\/jats:title>\n This review highlights the complexity of interpreting gene expression in human pre-implantation embryos due to diverse influences, including parental age, ART conditions, developmental stage, and embryo sex. ART procedures may have cumulative effects on the blastocyst transcriptome. Modifiable factors, such as culture conditions, offer opportunities for improving IVF outcomes. Epigenetic modifications may also be sensitive to these diverse influences and involved in observed transcriptomic changes, opening further research investigation to clarify long-term health effects.<\/jats:p>\n <\/jats:sec>\n \n REGISTRATION NUMBER<\/jats:title>\n n\/a.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/humupd\/dmaf022","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T11:55:30Z","timestamp":1754049330000},"page":"33-57","source":"Crossref","is-referenced-by-count":9,"title":["Transcript profiling and gene regulation of the human pre-implantation embryo: parental effects and impact of ARTs"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4822-9176","authenticated-orcid":false,"given":"Lucile","family":"Ferreux","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Paris Cit\u00e9 University , Paris,","place":["France"]},{"name":"Department of Reproductive Biology-CECOS, Assistance 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