Project description:The organs of female animals can be dramatically enlarged and metabolically remodelled by reproduction. The cellular changes and genetic programmes that initiate and sustain these transformations remain largely uncharacterised. It is also unclear whether the mechanisms that drive reproductive growth are shared between organs, or with other environmental triggers of adult organ growth. We have tackled these questions in mouse mothers, whose intestines provide a striking and genetically tractable example of reproductive organ resizing. We find that intestinal remodelling during reproduction is anticipatory of reproductive needs and distinct from diet-induced intestinal resizing.
Project description:The organs of many female animals grow and are metabolically remodelled by reproduction; this process has been historically overlooked. Using the intestine of mouse mothers, a striking and genetically tractable example of reproductive organ resizing, we find that reproductive intestinal remodelling is anticipatory and distinct from diet- or microbiota-induced intestinal resizing. Reproductive remodelling involves partially irreversible elongation of the intestine and fully reversible growth of its epithelium, which ensues from an expansion of the isthmus progenitors, increased progenitor proliferation and accelerated migration of differentiated cells. Through spatiotemporal analysis of gene expression, we identify induction of the SGLT3a transporter in a subset of enterocytes as one of the earliest reproductive hallmarks within the intestinal epithelium. Electrophysiological and genetic interrogations in vivo and in organoids indicate that SGLT3a does not sustain broad digestive functions or enterocyte health. Instead, SGLT3a detects protons and sodium to extrinsically support the expansion of adjacent Fgfbp1-positive isthmus progenitors and gut epithelial growth during reproduction. Our findings reveal unanticipated molecular, cell and organ specificity to physiological organ remodelling, raising the possibility that organ- and state-specific growth programmes could be leveraged to improve pregnancy outcomes or prevent maladaptive consequences of such growth.
Project description:The organs of female animals can be dramatically enlarged and metabolically remodelled by reproduction. The cellular changes and genetic programmes that initiate and sustain these transformations remain largely uncharacterised. It is also unclear whether the mechanisms that drive reproductive growth are shared between organs, or with other environmental triggers of adult organ growth. We have tackled these questions in mouse mothers, whose intestines provide a striking and genetically tractable example of reproductive organ resizing. We find that intestinal remodelling during reproduction is anticipatory of reproductive needs and distinct from diet-induced intestinal resizing.
Project description:The organs of female animals can be dramatically enlarged and metabolically remodelled by reproduction. The cellular changes and genetic programmes that initiate and sustain these transformations remain largely uncharacterised. It is also unclear whether the mechanisms that drive reproductive growth are shared between organs, or with other environmental triggers of adult organ growth. We have tackled these questions in mouse mothers, whose intestines provide a striking and genetically tractable example of reproductive organ resizing. We find that intestinal remodelling during reproduction is anticipatory of reproductive needs and distinct from diet-induced intestinal resizing.
Project description:The organs of female animals can be dramatically enlarged and metabolically remodelled by reproduction. The cellular changes and genetic programmes that initiate and sustain these transformations remain largely uncharacterised. It is also unclear whether the mechanisms that drive reproductive growth are shared between organs, or with other environmental triggers of adult organ growth. We have tackled these questions in mouse mothers, whose intestines provide a striking and genetically tractable example of reproductive organ resizing. We find that intestinal remodelling during reproduction is anticipatory of reproductive needs and distinct from diet-induced intestinal resizing.
