Surreal illustration of a mink uterus with glowing glycogen deposits sustaining dormant embryos.

The Secret Life of Uterine Glycogen: How It Impacts Fertility

Avery Sinclair in Science & Nature August 2025 • 4 min read.

"Unlocking the mysteries of uterine glycogen metabolism in mink and its implications for embryonic development and fertility."

For successful embryonic growth and implantation, the uterus has to get nutrients from glandular secretions, known as histotroph. These include glucose, glycogen, proteins, amino acids, and fats. Getting enough glucose and using it for energy are vital for the early stages of development, like blastulation and hatching. Also, glucose helps the endometrium, which is the inner lining of the uterus, get ready for pregnancy.

Although the uterus doesn't make new glucose, it stores it as glycogen. Scientists know that in rodents, glycogen levels in the uterus are highest during the estrus phase (when the female is receptive to mating) and then drop as implantation and early pregnancy progress. In women, the uterus builds up a lot of glycogen in the lining of the uterus during the first half of the menstrual cycle, but it's used up later. It's not fully understood how important glycogen is for a successful pregnancy, but women who struggle with infertility often have very low levels of glycogen in the uterine lining.

Glycogen synthesis begins with a critical step: the phosphorylation of glucose by hexokinase (Hk), creating glucose-6-phosphate. This molecule is then converted into glucose-1-phosphate and subsequently into uridine diphosphate glucose. Glycogen synthase (Gys) then transfers glucosyl units from uridine diphosphate glucose to growing glycogen chains. Glycogen breakdown, or glycogenolysis, is initiated by glycogen phosphorylase (Pyg), which releases glucose-1-phosphate. This product can either enter glycolysis for energy production or be dephosphorylated by glucose-6-phosphatase (G6pc) to yield free glucose, potentially for export into the uterine environment.

Mink Reproduction: A Unique Model

Surreal illustration of a mink uterus with glowing glycogen deposits sustaining dormant embryos.

Mink exhibit a reproductive strategy known as obligatory embryonic diapause, where as many as 17 blastocysts can remain in a state of suspended development for up to 50-60 days after mating, resulting in delayed implantation. This unique characteristic makes mink an interesting species to study uterine glycogen reserves. It’s thought that uterine glycogen is crucial for pre-embryonic growth and implantation in these animals. Past research has found glycogen in the uterine lining of mink during diapause. However, detailed studies of glycogen metabolism in the mink uterus, particularly across estrus, embryonic diapause, and pregnancy, have been lacking.

A new study sought to address these gaps by investigating: (1) glycogen content in different parts of the uterus (endometrium, glandular and luminal epithelia, stroma, and myometrium), (2) the location of key proteins like Gys, Pyg, and Hk within uterine cells, and (3) Pyg activity in uterine tissue during various reproductive stages (estrus, embryonic diapause, and pregnancy).

Estrous Stage: Uterine glycogen levels are at their peak, primarily concentrated in the glandular and luminal epithelia.
Diapause Stage: Glycogen levels decrease significantly, with a marked reduction in the endometrium.
Pregnancy Stage: Glycogen reserves are minimal, indicating their consumption to support the developing embryos.
Enzyme Dynamics: Glycogen synthase and phosphorylase proteins are predominantly found in the glandular epithelia, with phosphorylase activity higher during estrus and diapause.

The research revealed a detailed picture of how glycogen is stored and used in the mink uterus during different stages of reproduction. Overall glycogen levels in the uterus were highest during estrus, decreased by about 50% during diapause, and plummeted by 90% during pregnancy. The endometrial glycogen deposits, mainly found in the glandular and luminal epithelia, showed an even more dramatic decrease, dropping by 99% between estrus and diapause and becoming almost undetectable during pregnancy.

Implications for Fertility

These findings suggest that endometrial glycogen reserves may serve as a critical energy source, sustaining uterine and conceptus metabolism until the blastocyst stage during diapause. The amount of glycogen stored before mating could influence the number of embryos that survive to the blastocyst stage, and ultimately, litter size. Further studies in other species could reveal broader implications for understanding and improving fertility outcomes.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1262/jrd.2014-013, Alternate LINK

Title: Uterine Glycogen Metabolism In Mink During Estrus, Embryonic Diapause And Pregnancy

Subject: Animal Science and Zoology

Journal: Journal of Reproduction and Development

Publisher: Japanese Society of Animal Reproduction

Authors: Matthew Dean, Jason Hunt, Lisa Mcdougall, Jack Rose

Published: 2014-01-01

Everything You Need To Know

Why is uterine glycogen important for fertility?

Uterine glycogen serves as a vital energy reservoir, particularly crucial for sustaining uterine and conceptus metabolism during the blastocyst stage in species exhibiting embryonic diapause, like mink. The amount of glycogen stored in the endometrium before mating can directly impact the number of embryos that survive to the blastocyst stage, subsequently affecting litter size. Understanding the dynamics of glycogen metabolism, including synthesis and breakdown pathways involving key enzymes like glycogen synthase and glycogen phosphorylase, provides insights into optimizing conditions for successful embryonic development and implantation.

Can you explain the process of glycogen synthesis in the uterus and why it matters for embryonic development?

Glycogen synthesis is a process where glucose is converted and stored as glycogen. It begins with hexokinase phosphorylating glucose into glucose-6-phosphate, which is then converted to glucose-1-phosphate and subsequently to uridine diphosphate glucose. Glycogen synthase then adds glucosyl units from uridine diphosphate glucose to create the growing glycogen chains. Understanding this process is crucial because sufficient glycogen storage is essential for providing energy to the developing embryo, especially during stages like embryonic diapause where development is temporarily suspended. Disruptions in glycogen synthesis could lead to reduced glycogen reserves, potentially affecting embryo survival and implantation.

What is glycogenolysis, and how does it contribute to uterine energy balance during early pregnancy?

Glycogenolysis is the breakdown of glycogen, initiated by glycogen phosphorylase, which releases glucose-1-phosphate. This product can then enter glycolysis for energy production or be dephosphorylated by glucose-6-phosphatase to yield free glucose, which can be exported into the uterine environment. The regulation of glycogenolysis is critical for providing energy when it is needed, such as during the transition from diapause to active development or during periods of high energy demand in the endometrium. Imbalances in glycogenolysis, leading to either excessive or insufficient glucose release, can disrupt the energy balance in the uterus and negatively impact embryonic development and implantation.

Why are mink used as a model to study the impact of uterine glycogen on fertility?

Mink exhibit a unique reproductive strategy known as obligatory embryonic diapause, where blastocysts remain in a state of suspended development for an extended period after mating. During this diapause, the embryos rely on uterine secretions, including glycogen, for sustenance. Understanding how glycogen reserves are managed during diapause, including the activity of enzymes like glycogen synthase and glycogen phosphorylase, can provide insights into optimizing conditions for embryo survival and successful implantation once diapause ends. The study of glycogen metabolism in mink can help unlock strategies for improving fertility outcomes in other species, including humans.

How do uterine glycogen levels change throughout the estrus, diapause, and pregnancy stages, and what does this tell us about its role?

The study highlights the dynamic changes in uterine glycogen levels across different reproductive stages: estrus, diapause, and pregnancy. During estrus, glycogen levels are highest, particularly in the glandular and luminal epithelia. As the animal enters diapause, glycogen levels decrease significantly, especially in the endometrium. By the time pregnancy is established, glycogen reserves are minimal, indicating their consumption to support the developing embryos. These findings suggest that endometrial glycogen serves as a critical energy source until the blastocyst stage and its availability can impact embryo survival and ultimately, litter size. Understanding these fluctuations and the factors that regulate them is crucial for optimizing reproductive success.