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Title: Fructose synthesis and transport at the uterine-placental interface of pigs: cell-specific localization of SLC2A5, SLC2A8, and components of the polyol pathway

Author
item STEINHAUSER, CHELSIE - Texas A&M University
item LANDERS, MCKINSEY - Texas A&M University
item MYATT, LOUISE - Texas A&M University
item BURGHARDT, ROBERT - Texas A&M University
item Vallet, Jeff
item BAZER, FULLER - Texas A&M University
item JOHNSON, GREG - Texas A&M University

Submitted to: Biology of Reproduction
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/25/2016
Publication Date: 11/1/2016
Publication URL: https://handle.nal.usda.gov/10113/5832871
Citation: Steinhauser, C.B., Landers, M., Myatt, L., Burghardt, R.C., Vallet, J.L., Bazer, F.W., Johnson, G.A. 2016. Fructose synthesis and transport at the uterine-placental interface of pigs: cell-specific localization of SLC2A5, SLC2A8, and components of the polyol pathway. Biology of Reproduction. 95(5):108, 1-14. https://doi.org/10.1095/biolreprod.116.142174.
DOI: https://doi.org/10.1095/biolreprod.116.142174

Interpretive Summary: Pig fetal blood and fluids contain large amounts of fructose during gestation. Fructose concentrations in maternal blood are low, thus the fructose is likely synthesized from the glucose that is transported from sow to the fetus by the placenta. In the current study, the ability of the uterine lining and the placenta to synthesize fructose from glucose and then release fructose into fetal fluids was examined. The expression of genes and the production of their corresponding proteins from the polyol pathway were examined in endometrium and placenta throughout gestation. In addition, genes and proteins corresponding to the fructose transporters SLC2A5 and SLC2A8 were also examined in the same tissues. During early pregnancy (day 11 to 15), genes and proteins of the polyol pathway, which converts glucose to fructose, were present in the uterine lining. During later pregnancy, placental epithelial cells took over expression of these genes and production of these proteins. These results indicate that during early pregnancy, the enzymes needed to synthesize fructose from glucose are present in endometrium, coinciding with increased fructose concentrations within the uterus. Once the placenta becomes established at around day 30 of gestation, fructose synthesis and transport genes are expressed in the placenta for the remainder of gestation. These results indicate that the placenta is a source of the high fructose concentrations in fetal fluids during gestation.

Technical Abstract: The fetal fluids and uterine flushings of pigs contain higher concentrations of fructose than glucose, but fructose is not detected in maternal blood. Fructose can be synthesized from glucose via enzymes of the polyol pathway, aldose reductase (AKR1B1) and sorbitol dehydrogenase (SORD), transported across cell membranes by solute carriers SLC2A5 and SLC2A8, and converted to fructose-1-phosphate by ketohexokinase (KHK). SLC2A8, SLC2A5, AKR1B1, SORD, and KHK mRNAs and proteins were analyzed using quantitative PCR and immunohistochemistry or in situ hybridization in endometria and placentae of cyclic and pregnant gilts, cyclic gilts injected with estrogen, and ovariectomized gilts injected with progesterone. Progesterone up-regulated SLC2A8 protein in uterine luminal (LE) and glandular epithelia during the peri-implantation period, and expression became exclusively placental, chorion and blood vessels, after Day 30. P4 up-regulated SLC2A5 mRNA in uterine LE and glandular epithelia after implantation, and the chorion expressed SLC2A5 between Days 30 and 85. AKR1B1 and SORD proteins localized to uterine LE during the periimplantation period, but expression switched to chorion by Day 20 and was maintained through Day 85. Uterine expression of AKR1B1 mRNA was down-regulated by estrogen. KHK protein localized to trophectoderm/chorion throughout gestation. These results provide evidence that components for the conversion of glucose to fructose and for fructose transport are present at the uterine-placental interface of pigs. The shift in expression from LE to chorion during pregnancy suggests free-floating conceptuses are supported by fructose synthesized by the uterus, but after implantation, the chorion becomes self-sufficient for fructose synthesis and transport.