Growth of the maternal intestine during reproduction

Tomotsune Ameku; Anna  Laddach; Hannah Beckwith; Iain Tough; Helen Cox; Vassilis Pachnis; Nicholas Bellono; Irene Miguel-Aliaga

doi:10.1016/j.cell.2025.02.015

Growth of the maternal intestine during reproduction

Tomotsune Ameku, Anna Laddach, Hannah Beckwith, Iain Tough, Helen Cox, Vassilis Pachnis, Nicholas Bellono, Irene Miguel-Aliaga^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

The organs of many female animals are remodeled by reproduction. Using the mouse intestine, a striking and tractable model of organ resizing, we find that reproductive remodeling is anticipatory and distinct from diet- or microbiota-induced resizing. Reproductive remodeling involves partially irreversible elongation of the small intestine and fully reversible growth of its epithelial villi, associated with an expansion of isthmus progenitors and accelerated enterocyte migration. We identify induction of the SGLT3a transporter in a subset of enterocytes as an early reproductive hallmark. Electrophysiological and genetic interrogations indicate that SGLT3a does not sustain digestive functions or enterocyte health; rather, it detects protons and sodium to extrinsically support the expansion of adjacent Fgfbp1-positive isthmus progenitors, promoting villus growth. Our findings reveal unanticipated specificity to physiological organ remodeling. We suggest that organ- and state-specific growth programs could be leveraged to improve pregnancy outcomes or prevent maladaptive consequences of such growth.

Original language	English
Article number	e22
Pages (from-to)	2738-2756
Journal	Cell
Volume	188
Issue number	10
Early online date	19 Mar 2025
DOIs	https://doi.org/10.1016/j.cell.2025.02.015
Publication status	Published - 15 May 2025

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Growth of the maternal_AMEKU_Publishedonline19March2025_GOLD VoR (CC-BY)Final published version, 25.5 MBLicence: CC BY

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abstract = "The organs of many female animals are remodeled by reproduction. Using the mouse intestine, a striking and tractable model of organ resizing, we find that reproductive remodeling is anticipatory and distinct from diet- or microbiota-induced resizing. Reproductive remodeling involves partially irreversible elongation of the small intestine and fully reversible growth of its epithelial villi, associated with an expansion of isthmus progenitors and accelerated enterocyte migration. We identify induction of the SGLT3a transporter in a subset of enterocytes as an early reproductive hallmark. Electrophysiological and genetic interrogations indicate that SGLT3a does not sustain digestive functions or enterocyte health; rather, it detects protons and sodium to extrinsically support the expansion of adjacent Fgfbp1-positive isthmus progenitors, promoting villus growth. Our findings reveal unanticipated specificity to physiological organ remodeling. We suggest that organ- and state-specific growth programs could be leveraged to improve pregnancy outcomes or prevent maladaptive consequences of such growth.",

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AU - Ameku, Tomotsune

AU - Laddach, Anna

AU - Beckwith, Hannah

AU - Tough, Iain

AU - Cox, Helen

AU - Pachnis, Vassilis

AU - Bellono, Nicholas

AU - Miguel-Aliaga, Irene

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N2 - The organs of many female animals are remodeled by reproduction. Using the mouse intestine, a striking and tractable model of organ resizing, we find that reproductive remodeling is anticipatory and distinct from diet- or microbiota-induced resizing. Reproductive remodeling involves partially irreversible elongation of the small intestine and fully reversible growth of its epithelial villi, associated with an expansion of isthmus progenitors and accelerated enterocyte migration. We identify induction of the SGLT3a transporter in a subset of enterocytes as an early reproductive hallmark. Electrophysiological and genetic interrogations indicate that SGLT3a does not sustain digestive functions or enterocyte health; rather, it detects protons and sodium to extrinsically support the expansion of adjacent Fgfbp1-positive isthmus progenitors, promoting villus growth. Our findings reveal unanticipated specificity to physiological organ remodeling. We suggest that organ- and state-specific growth programs could be leveraged to improve pregnancy outcomes or prevent maladaptive consequences of such growth.

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Growth of the maternal intestine during reproduction

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