Reproductive immunology and tolerance across vertebrates

Successful reproduction presents a fundamental evolutionary paradox: the immune system must tolerate genetically foreign sperm and embryos while maintaining effective defense against pathogens. This balance is achieved through reproductive immunomodulation — a dynamic recalibration of immune activity at the maternal-fetal or parental-embryo interface. While research has traditionally focused on uterine immunology in placental mammals, a broader evolutionary perspective reveals that immune tolerance is a universal prerequisite for reproductive success across vertebrates. From the maternal-fetal immune dialog in eutherian mammals to paternal brooding adaptations in teleost fish and mucosal remodeling in oviparous species, diverse mechanisms have evolved to dampen harmful inflammation without causing systemic immunosuppression. Comparative analyses have identified shared regulatory pathways — including Treg expansion, cytokine modulation, and local immune checkpoint control — with wide implications for reproductive medicine, aquaculture seed production, and comparative immunology. Beyond the immediate gestation, appropriate immunomodulation during early pregnancy has lasting consequences for offspring fitness and may exert transgenerational effects through epigenetic modifications, shaping immune competence and disease resilience across generations.Despite major progress in placental mammal research, crucial knowledge gaps remain regarding how non-mammalian vertebrates regulate immune recognition during reproduction. In mammals, immune suppression is largely transient, whereas some teleost fishes exhibit permanent genomic adaptations — such as modification or functional loss of the MHC class II pathway — linked to male pregnancy and internal gestation. Reproductive tolerance also entails trade-offs with pathogen resistance, as gravid and brooding animals often display localized immunomodulation that heightens infection susceptibility. Priority areas include mapping the immune microenvironment at the parent–embryo interface, determining how reproductive investment modifies systemic immunity, and elucidating transgenerational protection via epigenetic and trained innate immunity mechanisms. Emerging technologies — including single-cell transcriptomics, comparative genomics, and epigenetic profiling — enable unprecedented resolution of these adaptations, providing new opportunities to enhance reproductive success and disease resilience across vertebrate taxa.This Research Topic explores the molecular, cellular, and evolutionary basis of reproductive immunomodulation across mammals and non-mammalian vertebrates, aiming to build a comparative framework for understanding how immune systems adapt to reproduction while maintaining defense against infection. Interdisciplinary submissions integrating immunology, reproductive biology, genomics, endocrinology, and ecology are strongly encouraged.We welcome manuscripts addressing, but not limited to, the following themes:o Specialized immune cell populations and reproductive interface barrierso Cytokine signaling, immune checkpoints, and regulation of local inflammationo Trade-offs between immune defense and reproductive toleranceo Genetic and epigenetic adaptations associated with internal incubation and parental careo Parental immune transfer and trained innate immunityo Impacts of climate change, pollution, and environmental stressors on reproductive immunityWe invite original research articles, reviews, mini-reviews, perspectives, and methodological papers on these topics across human, animal, and fish models. Topic editors: Dhanashree Jagtap, Irfan Ahmad Bhat, Ruben Dario Motrich, Irshad Ahmad Source: https://www.frontiersin.org/research-topics/82641/reproductive-immunology-and-tolerance-across-vertebrates