The Notch Family Transcription Factor, RBPJκ, Modulates Glucose Transporter and Ovarian Steroid Hormone Receptor Expression During Decidualization

Published on 2018-09-13T12:00:00Z (GMT) by
<div><p>During decidualization, endometrial stromal cells differentiate into a secretory phenotype to modulate the uterine microenvironment and promote embryo implantation. This highly metabolic process relies on ovarian steroid receptors and glucose transporters. Canonical Notch signaling is mediated by the transcription factor Recombination Signal Binding Protein for Immunoglobulin Kappa J Region (RBPJ). Loss of RBPJ in the mouse uterus (<i>Pgr<sup>cre/+</sup>Rbpj<sup>flox/flox</sup> </i>; <i>Rbpj</i> c-KO) results in subfertility in part due to an abnormal uterine–embryonic axis during implantation and, as described herein, decidualization failure. Induced in vivo decidualization in <i>Rbpj</i> c-KO mice was impaired with the downregulation of decidual markers and decreased progesterone receptor (Pgr) signaling. Consistent with in vivo mouse data, <i>RBPJ</i> knockdown during in vitro Human uterine fibroblast (HuF) cell decidualization results in the reduced expression of decidual marker genes along with <i>PGR</i>. Expression of the glucose transporter, <i>SLC2A1</i>, was decreased in the RBPJ-silenced HuF cells, which corresponded to decreased Slc2a1 in the secondary decidual zone of <i>Rbpj</i> c-KO mouse uteri. Exogenous administration of pyruvate, which bypasses the need for glucose, rescues <i>PRL</i> expression in <i>RBPJ</i>-deficient HuF cells. In summary, Notch signaling through RBPJ controls both ovarian steroid receptor <i>PGR</i> and glucose transporter <i>SLC2A1</i> expression during decidualization, and this dysregulation likely contributes to embryo implantation failure.</p></div>

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Strug, Michael R; Su, Ren-Wei; Hoon Kim, Tae; Jeong, Jae-Wook; Fazleabas, Asgerally (2018): The Notch Family Transcription Factor, RBPJκ, Modulates Glucose Transporter and Ovarian Steroid Hormone Receptor Expression During Decidualization. SAGE Journals. Collection.