Loss of Endometrial Sodium Glucose Cotransporter SGLT1 is Detrimental to Embryo Survival and Fetal Growth in Pregnancy

Sci Rep. 2017 Oct 3;7(1):12612. doi: 10.1038/s41598-017-11674-3.

Madhuri S Salker ¹ ², Yogesh Singh ³, Ni Zeng ³, Hong Chen ³, Shaqiu Zhang ³, Anja T Umbach ³, Hajar Fakhri ³, Ursula Kohlhofer ⁴, Leticia Quintanilla-Martinez ⁴, Ruban R Peter Durairaj ⁵, Flavio S V Barros ⁵, Pavle Vrljicak ⁶, Sascha Ott ⁶, Sara Y Brucker ⁷, Diethelm Wallwiener ⁷, Ivana Vrhovac Madunić ⁸, Davorka Breljak ⁸, Ivan Sabolić ⁸, Hermann Koepsell ⁹, Jan J Brosens ⁵, Florian Lang ¹⁰

Affiliations

1 Department of Physiology I, Eberhard-Karls Universität Tübingen, Tübingen, D-72076, Germany. [email protected].
2 Obstetrics, Gynecology, Eberhard-Karls Universität Tübingen, Tübingen, D-72076, Germany. [email protected].
3 Department of Physiology I, Eberhard-Karls Universität Tübingen, Tübingen, D-72076, Germany.
4 Institute of Pathology and Comprehensive Cancer Centre, Eberhard-Karls Universität Tübingen, Tübingen, D-72076, Germany.
5 Division of Biomedical Sciences, Warwick Medical School, and Tommy's National Centre for Miscarriage Research, University Hospitals Coventry and Warwickshire NHS Trust, Clifford Bridge Rd, Coventry, CV2 2DX, UK.
6 Warwick Systems Biology Centre, University of Warwick, Coventry, CV4 7AL, UK.
7 Obstetrics, Gynecology, Eberhard-Karls Universität Tübingen, Tübingen, D-72076, Germany.
8 Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, 10000, Zagreb, Croatia.
9 Department of Molecular Plant Physiology and Biophysics, Julius-von-Sachs-Institute, University of Würzburg, Würzburg, D-97082, Germany.
10 Department of Physiology I, Eberhard-Karls Universität Tübingen, Tübingen, D-72076, Germany. [email protected].

PMID: 28974690 DOI: 10.1038/s41598-017-11674-3

Abstract

Embryo implantation requires a hospitable uterine environment. A key metabolic change that occurs during the peri-implantation period, and throughout early pregnancy, is the rise in endometrial glycogen content. Glycogen accumulation requires prior cellular uptake of glucose. Here we show that both human and murine endometrial epithelial cells express the high affinity Na⁺-coupled glucose carrier SGLT1. Ussing chamber experiments revealed electrogenic glucose transport across the endometrium in wild type (Slc5a1 ^+/+) but not in SGLT1 deficient (Slc5a1 ^-/-) mice. Endometrial glycogen content, litter size and weight of offspring at birth were significantly lower in Slc5a1 ^-/- mice. In humans, SLC5A1 expression was upregulated upon decidualization of primary endometrial stromal cells. Endometrial SLC5A1 expression during the implantation window was attenuated in patients with recurrent pregnancy loss when compared with control subjects. Our findings reveal a novel mechanism establishing adequate endometrial glycogen stores for pregnancy. Disruption of this histiotrophic pathway leads to adverse pregnancy outcome.

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