Life-long brain function and mental health are critically determined by developmental processes occurring before birth. During mammalian pregnancy, maternal cells are transferred to the fetus. They are referred to as maternal microchimeric cells (MMc). Among other organs, MMc seed into the fetal brain, where their function is unknown. Here, we show that, in the offspring’s developing brain in mice, MMc express a unique signature of sensome markers, control microglia homeostasis and prevent excessive presynaptic elimination. Further, MMc facilitate the oscillatory entrainment of developing prefrontal-hippocampal circuits and support the maturation of behavioral abilities. Our findings highlight that MMc are not a mere placental leak out, but rather a functional mechanism that shapes optimal conditions for healthy brain function later in life.

Subsequent pregnancies are generally less prone to obstetric complications. A successful pregnancy outcome requires pivotal immunological adaptation to ensure immune tolerance towards the foetus. Thus, the lower risk for pregnancy complication during subsequent pregnancies may be attributable to immune memory mounted during first pregnancies. Here we identify higher frequencies of fetal-antigen-specific CD4⁺ regulatory T (Treg) cells both postpartum and in subsequent pregnancies in mice which are partly originating from trans-differentiated Th17 cells. Our functional experiments demonstrate that these CD4⁺ Treg cells have memory functions (CD4⁺ mTreg) and account for an improved fetal development and pregnancy outcome, also during adverse conditions, such as gestational sound stress. Using a high-throughput single-cell quantification method, we identify candidate markers for the detection of CD4⁺ mTreg cells, which include CXCR4 and CD274. Our findings thus contribute to the improved understanding of pregnancy-induced immune memory and foster the identification of immune targets aiming to reduce the risk for immune-mediated pregnancy complications.

This review evaluates in-vitro models for studying how maternal influences during pregnancy impact the development of offspring microglia, the immune cells of the central nervous system. The models examined include primary microglia cultures, microglia cell lines, iPSC-derived microglia, PBMC-induced microglia-like cells, 3D brain organoids derived from iPSCs, and Hofbauer cells. Each model is assessed for its ability to replicate the in-vivo environment of the developing brain, with a focus on their strengths, limitations, and practical challenges. Key factors such as scalability, genetic and epigenetic fidelity, and physiological relevance are highlighted. Microglia cell lines are highly scalable but lack genetic and epigenetic fidelity. iPSC-derived microglia provide moderate physiological relevance and patient-specific genetic insights but face operational and epigenetic challenges inherent to reprogramming. 3D brain organoids, derived from iPSCs, offer an advanced platform for studying complex neurodevelopmental processes but require extensive resources and technical expertise. Hofbauer cells, which are fetal macrophages located in the placenta and share a common developmental origin with microglia, are uniquely exposed to prenatal maternal factors and, depending on fetal barrier maturation, exhibit variable epigenetic fidelity. This makes them particularly useful for exploring the impact of maternal influences on fetal programming of microglial development. The review concludes that no single model comprehensively captures all aspects of maternal influences on microglial development, but it offers guidance on selecting the most appropriate model based on specific research objectives and experimental constraints.

To assess maternal mental health during the first weeks after birth including birth experience, postpartum adjustment to early motherhood and the perception of newborn behaviour, and how this may b...

Cold-water exposure has gained increasing popularity as a self-applied intervention for improving mental health and psychological well-being. While anecdotal evidence and popular media suggest potential benefits for reducing stress, anxiety, and depressive symptoms, the scientific evidence supporting these claims remains fragmented. This protocol outlines the methodology for a systematic review and meta-analysis aiming to critically appraise and synthesize the available evidence on the effects of CWE on mental health outcomes in adult populations, including both healthy individuals and those with clinical conditions. The review will examine both psychological variables and physiological stress markers in response to cold-water exposure interventions. Following PRISMA 2020 guidelines, a systematic search will be conducted in PubMed, PsycINFO, Embase, and Web of Science. Eligible studies will include randomized controlled trials, controlled clinical trials without randomization, cohort studies, and case-control studies. Risk of bias will be assessed using RoB1 for randomized controlled trials, ROBINS-I for non-randomized intervention studies, and ROBINS-E for observational studies. Random-effects meta-analyses will be conducted where sufficient data are available. The review will provide a structured quantitative synthesis of cold-water exposure’s effects on mental health, helping to bridge the gap between popular claims and empirical evidence. The findings will inform future research, public health guidelines, and the development of safe and effective cold-water exposure protocols for clinical and wellness applications.