Maternal microbiota regulate glucocorticoids levels and placental development in mice

The gut microbiota contributes to postnatal development and maturation by influencing barrier functions of the intestinal wall, the development of the immune system, and the utilisation of nutrients. Recent studies have also implicated a role in the prenatal period since the maternal gut microbiota is altered during pregnancy with a potential role in the regulation of glucose homeostasis and protection against preterm birth. Using as a model system germ-free mice that have never encountered a live bacterium and pathogen-free mice that were reared in an environment free of monitored mouse pathogens, we demonstrated that lack of gut microbiota is associated with an altered hypothalamic-pituitary-adrenal axis (HPA) and impaired placental development. Germ-free (GF) mice displayed elevated serum glucocorticoids and reduced levels of glucocorticoid regulated insulin-like growth factor 2 (IGF2) and peroxisome proliferator-activated receptor (PPAR) β and γ compared to specific pathogen-free (SPF) dams, which correlated with an impairment of placenta development. Morphological analysis revealed reduced labyrinth size, inhibited vascularization and reduced expression of the tight junction proteins in the placenta from GF dams compared to SPF dams. Permeability test using a 1-kDa tracer showed an increased permeability in GF placental barrier. We conclude that the maternal microbiome can influence placental development and we propose that mammalian development, known to have the capacity to modulate placenta size and morphology to ensure the development of the growing offspring, is under the influence of the maternal microbiome, the forgottenThis work was supported by grants from Qatar University, VR, Cancerfonden, EU-project TORNADO, and the Singapore Millennium Foundation