# Assessing the mechanism by which fetal glucagon inhibits placental nutrient transfer

> **NIH NIH F32** · UNIVERSITY OF COLORADO DENVER · 2024 · $74,284

## Abstract

PROJECT SUMMARY
The goal of this proposal is to identify the mechanistic link between fetal glucagon and placental
nutrient delivery as a novel, adaptive mechanism for matching nutrient supply to fetal metabolic
demand under adverse uterine conditions. Pregnancies complicated by intrauterine acidosis, hypoxia,
and growth restriction are often characterized by elevated fetal glucagon. While fetal metabolic
hormones have historically been considered for their function in regulating fetal growth, recent
evidence from the Rozance laboratory has suggested glucagon may be regulating maternal nutrient
delivery via placental signaling. In nine-day fetal glucagon infusions in sheep, we observed
dramatically reduced uterine blood flow which resulted in decreased placental transfer of amino acids,
glucose, and oxygen to the fetus. This decrease was accompanied by a robust reduction in maternal
placental lactogen (CSH) concentrations, which we have previously demonstrated results in lower
uterine blood flow and placental nutrient delivery in an in vivo model of placental CSH RNAi in sheep.
Thus, we hypothesize that fetal glucagon regulates placental nutrient delivery by inhibiting placental
trophoblast CSH secretion and uterine blood flow. This proposal will demonstrate that fetal glucagon
acts by matching placental nutrient delivery to fetal growth and metabolic demands by regulating
maternal CSH secretion and NO-mediated vasodilation to alter blood flow. Aim 1 will establish the
mechanism by which fetal glucagon inhibits CSH secretion by the trophoblast. Aim 2 will identify the
link between fetal glucagon, CSH, and uterine blood flow, and how this relationship regulates
vasoactivity and placental nutrient delivery. Expected outcomes: This proposal will be the first
mechanistic physiological investigation into fetal glucagon as an inhibitor of trophoblast CSH
production, regulating uterine blood flow and placental nutrient transfer. Furthermore, it will also
demonstrate the novel vasodilatory role of CSH in uterine circulation. Lastly, this proposal will provide
me critical training in fetal physiology, improve the translatability of my research by working with
human samples, augment my grantsmanship and scientific writing skills, and cultivate key
professional relationships to establish successful future collaborations as a tenure-track, assistant
professor specializing in fetal-placental-maternal communication. Impact: The research outlined by
this proposal will identify a previously unknown mechanism for matching nutrient delivery to fetal
metabolic demand to increase survival during pregnancy complications.

## Key facts

- **NIH application ID:** 10995887
- **Project number:** 1F32HD116431-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Amelia Ruth Tanner
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,284
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10995887

## Citation

> US National Institutes of Health, RePORTER application 10995887, Assessing the mechanism by which fetal glucagon inhibits placental nutrient transfer (1F32HD116431-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10995887. Licensed CC0.

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