# The Role of Uterine Glycogen in Establishing a Successful Pregnancy

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2023 · $327,507

## Abstract

Project Summary
Infertility is a significant public health problem with substantial medical, psychosocial, and economic costs.
Maximal fertility in women is 30% per cycle. In most cases, the oocyte is fertilized, but the resulting embryo
dies before or during implantation. During this time, embryos depend on glucose secretions into the uterine
lumen. From fertilization until the morula stage, glucose uptake is low. As embryos approach the blastocyst
stage, glucose uptake increases 50-fold. Similarly, endometrial decidualization is a glucose-intense process.
Inhibition of the pentose phosphate pathway impairs decidualization and reduces litter size. After
decidualization, the endometrium switches to Warburg metabolism to generate ATP. Defects in glucose
secretion into the lumen or uptake by the decidua are linked to pregnancy complications. How the uterus
meets the changing needs of the embryos and endometrium for glucose in a spatiotemporal manner is poorly
understood. Our preliminary data show that the uterine endometrium can store glucose as the macromolecule
glycogen in the mouse. We show that glycogen reserves in the uterine epithelium peak at proestrus and
decline during the preimplantation period. The uterine epithelium expressed glucose-6-phosphatase, which is
necessary for the section of glucose released from glycogen. Conversely, the glycogen content of the stroma
was low and unchanging from proestrus to day post coitum (DPC) 3.5. At DPC 5.5, the glycogen content of the
stroma increased 7-fold at the implantation site but remained low at the inter-implantation site. We confirmed
that the decidua stores large amounts of glycogen by inducing artificial decidualization. These data indicate
that the endometrium stores two distinct pools of glycogen that may serve as essential sources of glucose
during pregnancy. Therefore, Aim 1 of this project is to determine if glycogen stored in the endometrium is
necessary for a successful pregnancy. Using glycogen synthase 1 (GYS1) floxed mice, we will knock out
glycogen synthase in the uterus using progesterone receptor (PRCre) Cre mice. After confirming a successful
knockout of GYS1 and a corresponding decrease in glycogen, we will determine if these mice have regular
reproductive cycles and glucose tolerance. Next, we will evaluate their fertility and determine if the lack of
uterine glycogen synthase impairs the embryo's ability to establish a successful pregnancy. The pregnancy-
dependent changes in glycogen content of the uterine epithelium suggest that ovarian hormones regulate
glycogen in this tissue. We have already shown that estradiol-stimulated IGF1 induces glycogenesis in the
uterine epithelium in vitro. Our preliminary data indicate that progesterone directly stimulates glycogen
breakdown via membrane progesterone receptors. Aim 2 will elucidate the pathway by which activation of
membrane progesterone receptors leads to glycogenolysis. We will then confirm the effects of estradiol and
prog...

## Key facts

- **NIH application ID:** 10725894
- **Project number:** 1R21HD112772-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Matthew J Dean
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $327,507
- **Award type:** 1
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10725894

## Citation

> US National Institutes of Health, RePORTER application 10725894, The Role of Uterine Glycogen in Establishing a Successful Pregnancy (1R21HD112772-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10725894. Licensed CC0.

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