bims-mamemb 2026-10-18 papers

Genome Res. 2026 Oct 13.

Parental genome reprogramming drives allelic convergence while preserving parent-of-origin memory during human early embryonic development.

Fanqing Xu, Qian Liu, Zhengrong Du, Yuwen Xiu, Qianying Guo, Jie Qiao, Peng Yuan, Liying Yan.

Human sperm and oocytes carry highly distinct DNA methylation landscapes, yet parental DNA methylation ultimately converges to a largely equivalent state, raising the question of when and how the allelic DNA methylome is reprogrammed toward convergence. Here, we present an integrated allelic analysis of DNA methylation and transcriptome dynamics throughout human pre- to peri-implantation development, a stage that lays the foundation for future development. We find that oocyte-specific hypermethylated regions retain maternal-biased DNA methylation asymmetry throughout early development, whereas paternal hypermethylation at sperm-specific regions is erased after fertilization and re-established during peri-implantation. Whole-genome parental DNA methylation levels converge across all lineages at embryonic days 8 to 12, prior to gastrulation, although the timing of this equilibrium differs among genomic elements. Notably, a subset of transposable elements, including SVAs and LTR12 elements, remains persistently maternally hypermethylated. Finally, we identify parent-of-origin-biased genes involved in early human embryonic development and find that these genes are enriched for dosage-sensitive genes. We further show that epiblast-specific parental expression bias is associated with genes implicated in neurodevelopmental disorders. These findings highlight the developmental and clinical relevance of allele-specific DNA methylation and transcription regulation during the earliest stages of human development.

DOI: https://doi.org/10.1101/gr.281969.126

Anim Reprod. 2026 ;23(4): e20260065

Modelling mammalian implantation in vitro.

Delanyo Kpeglo, Parisa Noohi, Haidee Tinning, Ella E Proudly, Rohan M Lewis, Virginia Pensabene, Niamh Forde.

Embryo implantation is a major reproductive bottleneck, requiring precise spatiotemporal coordination between the embryo and the maternal endometrium. This intricate communication is governed by synchronised molecular signalling, mechanical cues, and endocrine regulation. Although some of these mechanisms are conserved across mammals, marked species differences in the degree of invasiveness of implantation, decidualisation, and placental morphology, as well as in embryonic developmental milestones, limit comparative understanding of early pregnancy across species. Moreover, ethical restrictions on human embryo research, the need to reduce animal use in research, and the oversimplified nature of 2D cultures, which cannot replicate the 3D, multicellular organisation of the implantation site, have further constrained progress. Recent advances in 3D in vitro technologies, including organoids, blastoids, and biomaterial-based cultures, provide more physiologically relevant platforms for studying embryo-endometrium interactions. When integrated with organ-on-a-chip systems, these models enable dynamic control of hormonal gradients, paracrine signalling, and fluid flow, closely mimicking the native implantation microenvironment, unlike static cultures. These systems have yielded key insights into epithelial-stromal crosstalk, immune regulation, and vascular remodelling at the maternal-foetal interface. However, challenges remain regarding reproducibility and rigorous biological validation. This review explores the biological principles of implantation across mammalian species. It evaluates in vivo animal models and 2D and 3D in vitro models for their ability to recapitulate species-specific implantation strategies. Furthermore, we highlight how integrating cellular diversity, biomechanical forces, and species-specific tissue architecture into bioengineered 3D platforms, together with advanced imaging, can bridge the gap between in vitro approaches and complex in vivo physiology. The convergence of these technologies is poised to transform implantation research and ultimately improve reproductive outcomes.

Keywords: 3D imaging; 3D in vitro models; embryo implantation; embryo-maternal interactions; species-specific physiology

DOI: https://doi.org/10.1590/1984-3143-AR2026-0065

Nat Rev Genet. 2026 Oct 12.

Gene regulation at the early human maternal-fetal interface.

Ana Paredes, Christina E Kim, Roser Vento-Tormo.

Pregnancy is a distinct physiological context in which the mother hosts and nurtures the development of a genetically distinct fetus. Healthy pregnancy outcomes rely on successful placental development, during which specialized placental cells with fetal genotype, known as trophoblasts, drive the establishment of the maternal-fetal interface, a balanced tissue ecosystem that supports fetal development while safeguarding maternal well-being. Advances in single-cell, single-nuclei and spatial genomics technologies, along with data science, are now providing an unprecedented view of trophoblast regulation, which drives their differentiation into diverse cell subtypes that dynamically transform the maternal niche. More specifically, these cells modulate the immune system and remodel the vasculature to facilitate communication with maternal cells, leading to the successful formation of the maternal-fetal interface. These advances, when combined with in vitro modelling, hold promise for inferring causality in mechanisms that govern genome regulation, cellular behaviour and ultimately pregnancy homeostasis and maladaptive responses.

DOI: https://doi.org/10.1038/s41576-026-01014-5