The Secret Life of Uterine Glycogen: How It Impacts Fertility
"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
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.
- 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.
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.