Abstract
Hyaluronan (HA) and its receptor CD44 are expressed at the maternal-fetal interface, but its role in early pregnancy remains unclear. Here, we found that primary decidual stromal cells (DSCs) continuously secreted HA and expressed its receptor CD44. Pregnancy-associated hormones up-regulated HA synthetase (HAS) 2 transcription and HA release from DSCs. High molecular weight-HA (HMW-HA), but not medium molecular weight (MMW-HA) or low molecular weight (LMW-HA), promoted proliferation and inhibited apoptosis of DSCs in a CD44-dependent manner. The in-cell Western analysis revealed HMW-HA activated PI3K/AKT and mitogen-activated protein kinase (MAPK)/ERK1/2 signaling pathways time-dependently. Blocking these pathways by specific inhibitor LY294002 or U0126 abrogated HMW-HA-regulated DSc proliferation and apoptosis. Finally, we have found that HA content, HA molecular weight, HAS2 mRNA level, and CD44 expression were significantly decreased in DSCs from unexplained miscarriage compared with the normal pregnancy. Collectively, our results indicate that higher level and greater molecular mass of HA at maternal-fetal interface contributes to DSc growth and maintenance of DSCs in human early pregnancy.
Highlights
Decidual stromal cells (DSCs) are the major cellular component at the maternal–fetal interface, comprising 75% of decidual cells, and are important owing to their pleiotropic functions during pregnancy
The percentage of apoptotic cells was even higher than that of the control (Figure 5B). These findings indicate that High molecular weight-HA (HMW-HA) can promote growth of human DSCs through the PI3K/Akt and mitogen-activated protein kinase (MAPK)/ERK1/2 signaling pathways
We have explored the roles of HA and its predominant receptor CD44 in the DSC biological behaviors during human early pregnancy
Summary
Decidual stromal cells (DSCs) are the major cellular component at the maternal–fetal interface, comprising 75% of decidual cells, and are important owing to their pleiotropic functions during pregnancy In addition to their traditional nutrition and support to embryo in pregnancy, growing evidence suggests that DSCs are involved in immune modulation, including antigen phagocytosis and presentation, followed by cytokine production [1,2,3]. HA has a strong negative charge, and the large water volume of hydration associated with HA causes hydration and expansion of tissues, creating an environment that permits cell proliferation Both HA and CD44 are observed in the early human conceptus and in decidual stroma [17,18]. We compared HA and CD44 expression in DSCs between the normal early pregnancy and unexplained miscarriage
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