Glycogen in the uterus and fallopian tubes is an important source of glucose during early pregnancy†

Abstract

Pregnancy loss is common during the peri-implantation period in mammals when glucose is required for both embryonic development and decidualization of the endometrium. As the uterus cannot synthesize glucose, all glucose must come directly from maternal circulation as needed or transiently stored as the macromolecule glycogen. Glycogen acts as a glucose reservoir, storing up to 55 000 glucose moieties per molecule. Endometrial glycogen concentrations are correlated with fertility in humans, indicating that glycogen is an essential source of glucose during early pregnancy. In humans and primates, endometrial glycogen concentrations peak during the luteal phase due to progesterone. In contrast, in rats and mink, estradiol triggers an accumulation of uterine glycogen during proestrus and estrus. In mated rats, the glycogen content of the endometrium increases again after implantation due to high levels of glycogen stored in the decidua. In mink, endometrial glycogen reserves are localized in the uterine epithelia at estrus. These reserves are mobilized before implantation, suggesting they are used to support embryonic growth. Uterine glycogen concentrations continue to decrease after implantation in mink, probably due to a lack of decidualization. How ovarian steroids stimulate glycogenesis in the endometrium is unclear, but current evidence suggests that estradiol/progesterone interacts with insulin or insulin-like growth factor signaling. In summary, endometrial glycogen is an essential source of glucose during the peri-implantation period. More work is needed to characterize differences among species, elucidate the fate of the glucose liberated from glycogen, and understand how ovarian steroids regulate glycogen metabolism in the uterus.

Metabolomic Profile of Oviductal Extracellular Vesicles across the Estrous Cycle in Cattle

“…It is of note that levels of maltose and glucose-1-phosphate in oEVs paralleled those of P4 and were in opposition with those of E2 as previously reported in the bovine OF [19] and circulating plasma [39]. The hormonal regulation of glycogen metabolism in the oviduct remains unclear, but reproductive cycle-dependent changes in oviductal glycogen have been evidenced [36]. In pigs and rabbits, reserves of glycogen in the oviducts were highest near ovulation and decreased during the following luteal phase [40,41].…”

“…Maltose is usually the product of starch digestion, after alpha-amylase enzymatic action [35]. Although starch is not present in the oviduct, a large amount of glycogen was reported in the mammalian oviduct, where it acts as a glucose mobilized reservoir, storing up to 55,000 glucose moieties per molecule [36]. In the bovine oviduct epithelium, glycogen was quantified at around 60 µg/mg protein [37].…”

“…Most of the glucose residues in glycogen macromolecules are linked by α-1,4-glycosidic bonds while about one tenth of glucose residues are linked by α-1,6-glycosidic bonds. The enzymes alpha-amylase (AMY2B) and glycogen phosphorylase (PYGL, liver form and PYGB, brain form), all able to cut α-1,4-linkages, are produced in oviduct epithelial cells in mammals [30,36] and were reported at high abundance in the bovine OF [18,38]. Thus, it is likely that maltose and glucose-1-phosphate are products of glycogen catabolism in the oviduct epithelium.…”

“…In pigs and rabbits, reserves of glycogen in the oviducts were highest near ovulation and decreased during the following luteal phase [40,41]. Furthermore, the hormonal control of endometrial glycogen has been well studied in rats, rabbits, and mink, where P4 promotes glycogen catabolism while E2 stimulates uterine glycogen synthesis and storage [36,42,43]. Altogether, these data suggest that the products of glycogen catabolism in the oviduct epithelium are abundantly released in oEVs under P4 action during the luteal phase and that this process is inhibited by E2 during estrus.…”

Regulation of Pregnancy: Evidence for Major Roles by the Uterine and Placental Kisspeptin/KISS1R Signaling Systems

“…Decidualized stromal cells store glycogen and along with small amounts of maternal blood derived from ruptured capillaries they provide glucose needed to support the growth of the conceptus during early pregnancy. 60 Decidualized stromal cells also express a wide array of growth factors and cytokines and thereby exert developmental effects on the conceptus. 61 Immune cells of the decidua protect the embryo from being attacked by maternal immune cells and together with decidualized stromal cells regulate the development of the trophoblast lineage.…”