Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCB344

Poster Communications

Hypoxia and ischemia regulate placental syndecan expression and shedding

E. M. George1

1. Physiology, U of MS Medical Center, Jackson, Mississippi, United States.


Preeclampsia, a hypertensive disorder of gestation, affects ~5% of the population, and is a leading cause of fetal and maternal morbidity and mortality. While the origins of the disease are unclear, it is commonly accepted that placental ischemia/hypoxia is a central causative factor. In response, the placenta secretes soluble factors which cause the maternal manifestation of the disorder. Among the pathways believed to be important in this response is activation of innate immune mechanisms, such as inflammatory cytokines. It has been widely reported in sepsis that vascular inflammation induces remodeling and shedding of the endothelial glycocalyx, in particular cleavage and shedding of members of the integral membrane syndecan family. It is now known that these shed fragments have biological activity and act as potent inducers of the innate immune and inflammatory response. What is less well known is the presence of a functional glycocalyx in the placenta. Here we hypothesize that hypoxia will induce changes in syndecan production and shedding in vitro, and that chronic placental ischemia will cause syndecan shedding from the placenta in vivo. To examine the effects of hypoxia on placental cells, we cultured BeWo cytotrophoblast cells in oxygen tensions mimicking healthy (8%) and ischemic (1%) placentas, and examined syndecan1-4 mRNA and soluble SDC1 in the media. In response to hypoxia, SDC1, 2, and 4 mRNA increased significantly (14, 6.5, and 2.5 Fold, respectively, p<0.05 each), as assayed by TaqMan qRT-PCR. SDC3, in contrast, exhibited no significant difference in expression. Soluble SDC1 in the media, meanwhile was significantly increased by ~50% compared to normoxic control as measured by ELISA (41 ± 4 vs 63 ± 4 pg/ml, p<0.05). To determine the effects of chronic placental hypoxia/ischemia on SDC, we utilized the reduced uterine perfusion pressure (RUPP) rodent model. RUPP rats exhibited significantly increased blood pressure on gestational day 19 when compared to their control counterparts (105 ± 4 vs 122 ± 6 mmHg, p<0.05). Interestingly, soluble circulating SDC1 in the maternal circulation was significantly increased in RUPP rats when compared to their control counterparts (11 ± 4 vs 99 ± 20 pg/ml, p<0.05). These data suggest that hypoxia/ ischemia differentially regulate SDC isoforms in vitro. Furthermore it is possible that isoform specific or pan-syndecan circulating levels of syndecans could serve as a biomarker for preeclampsia. The importance of syndecan fragments in the inflammatory cascade during preeclampsia remains to be determined, as do the mechanisms regulating syndecan production and cleavage in these tissues.

Where applicable, experiments conform with Society ethical requirements