Uterine glycogen metabolism in mink during estrus, embryonic diapause and pregnancy

Abstract

We have determined uterine glycogen content, metabolizing enzyme expression and activity in the mink, a species that exhibits obligatory embryonic diapause, resulting in delayed implantation. Gross uterine glycogen concentrations were highest in estrus, decreased 50% by diapause and 90% in pregnancy (P ≤ 0.05). Endometrial glycogen deposits, which localized primarily to glandular and luminal epithelia, decreased 99% between estrus and diapause (P ≤ 0.05) and were nearly undetectable in pregnancy. Glycogen synthase and phosphorylase proteins were most abundant in the glandular epithelia. Glycogen phosphorylase activity (total) in uterine homogenates was higher during estrus and diapause, than pregnancy. While glycogen phosphorylase protein was detected during estrus and diapause, glycogen synthase was almost undetectable after estrus, which probably contributed to a higher glycogenolysis / glycogenesis ratio during diapause. Uterine glucose-6-phosphatase 3 gene expression was greater during diapause, when compared to estrus (P ≤ 0.05) and supports the hypothesis that glucose-6-phosphate resulting from phosphorylase activity was dephosphorylated in preparation for export into the uterine lumen. The relatively high amount of hexokinase-1 protein detected in the luminal epithelia during estrus and diapause may have contributed to glucose trapping after endometrial glycogen reserves were depleted. Collectively, our findings suggest to us that endometrial glycogen reserves may be an important source of energy, supporting uterine and conceptus metabolism up to the diapausing blastocyst stage. As a result, the size of uterine glycogen reserves accumulated prior to mating may in part, determine the number of embryos that survive to the blastocyst stage, and ultimately litter size.

Hexokinase 2 drives glycogen accumulation in equine endometrium at day 12 of diestrus and pregnancy

“…In mink, protein expression of HK1 and PYGM was greatest during estrus and diapause, whereas GYS protein expression was barely detectable after estrus [6]. Furthermore, G6PC3 gene expression was highest during diapause, suggesting that progesterone is glycogenolytic in the mink endometrium, as opposed to glycogenic in the human endometrium [6]. In the current study, HK2 was significantly upregulated during diestrus and pregnancy.…”

“…In human endometrium, expression of GSK3B is suggested to be regulated by progesterone, with higher expression of phosphorylated GSK3B (inactive) in secretory versus proliferative phases [23]. In mink, protein expression of HK1 and PYGM was greatest during estrus and diapause, whereas GYS protein expression was barely detectable after estrus [6]. Furthermore, G6PC3 gene expression was highest during diapause, suggesting that progesterone is glycogenolytic in the mink endometrium, as opposed to glycogenic in the human endometrium [6].…”

“…Glycogen, a storage form of glucose molecules, is one of the endometrial secretions that comprise histotroph and contribute to a successful pregnancy in a variety of species, including mink and human [6, 19]. In the equine endometrium, glycogen content is highest during diestrus, lower during estrus, but almost absent during anestrus.…”

“…In human endometrium, activity of GSK3B is regulated by progesterone [23]. Glycogen degradation, glycogenolysis, is catalyzed by glycogen phosphorylase (PYGM), releasing glucose-1-phosphate, that can be converted into glucose-6-phosphate, that can enter the glycolytic pathway [6] or be hydrolyzed by glucose 6-phosphatase (G6PC3) to form glucose.…”

“…More recently, uterine glycogen metabolism has been investigated in mink [6, 22]. However, the presence and expression of glycogen-metabolizing enzymes in the equine endometrium have not been as well characterized.…”