Endometrial glycogen metabolism during early pregnancy in mice

Abstract

Glucose is critical during early pregnancy. The uterus can store glucose as glycogen but uterine glycogen metabolism is poorly understood. This study analyzed glycogen storage and localization of glycogen metabolizing enzymes from proestrus until implantation in the murine uterus. Quantification of diastase‐labile periodic acid–Schiff (PAS) staining showed glycogen in the glandular epithelium decreased 71.4% at 1.5 days postcoitum (DPC) and 62.13% at DPC 3.5 compared to proestrus. In the luminal epithelium, glycogen was the highest at proestrus, decreased 46.2% at DPC 1.5 and 63.2% at DPC 3.5. Immunostaining showed that before implantation, glycogen metabolizing enzymes were primarily localized to the glandular and luminal epithelium. Stromal glycogen was low from proestrus to DPC 3.5. However, at the DPC 5.5 implantation sites, stromal glycogen levels increased sevenfold. Similarly, artificial decidualization resulted in a fivefold increase in glycogen levels. In both models, decidualization increased expression of glycogen synthase as determine by immunohistochemistry and western blot. In conclusion, glycogen levels decreased in the uterine epithelium before implantation, indicating that it could be used to support preimplantation embryos. Decidualization resulted in a dramatic increase in stromal glycogen levels, suggesting it may have an important, but yet undefined, role in pregnancy.

Endometrial glucose metabolism during early pregnancy

“…Confirming this, the glycogen-synthesizing enzyme, i.e. glycogen synthase, is highly expressed in the uterine epithelium of humans, mink, mice, and cows ( Dean et al 2014 , Jones et al 2015 , Sandoval et al 2021 , Chen et al 2022 ).…”

“…Little is known about factors controlling flux through glycolysis in the uterine epithelium. The uterine epithelium expresses high levels of hexokinase 1, which phosphorylates glucose, yielding G6P ( Sandoval et al 2021 , Chen et al 2022 ). However, G6P is a substrate for all the major pathways that use glucose.…”

“…Glycogen has been observed in the luminal and glandular epithelium of cows, mink, humans, and mice via histological staining and transmission electron microscopy ( Demir et al 2002 , Dean et al 2014 , Jones et al 2015 , Sandoval et al 2021 , Chen et al 2022 ). Confirming this, the glycogen-synthesizing enzyme, i.e.…”

“…In mice and mink, glycogen content of luminal and glandular epithelium was high during proestrus/estrus than during pregnancy ( Dean et al 2014 , Chen et al 2022 ). In cows, the glycogen content of the uterine epithelium was higher near estrus than during the luteal phase ( Sandoval et al 2021 ).…”

gys1 regulates maternal glycogen reserve essential for embryonic development in zebrafish

“…During embryogenesis, glycogen is one of the main sources of ATP and intermediate substrates required for the progression of embryonic development. In viviparous animals, the glucose is stored as glycogen in placenta to support the high energy demand of development and growth of the fetus, especially before implantation [ [6] , [7] , [8] , [9] ].Reduced placental glycogen content is frequently associated with fetal development and growth retardation [ 10 ]. Distinct from vivipara, oviparous animals like insect and fish, their eggs become closed and isolated from the environment after egg laying with all energy conversion taking place during embryogenesis [ 11 ].…”