Disruption of gap junctions reduces biomarkers of decidualization and angiogenesis and increases inflammatory mediators in human endometrial stromal cell cultures
J Yu, J Wu, IC Bagchi, MK Bagchi, N Sidell… - Molecular and cellular …, 2011 - Elsevier
Molecular and cellular endocrinology, 2011•Elsevier
CONTEXT: Uterine decidualization is critical to embryonic implantation and sustained
pregnancy. OBJECTIVE: To evaluate the role of gap junction intercellular communications
and connexin (Cx) proteins in the morphological and biochemical differentiation of
decidualized human endometrial stromal cell (ESC) cultures. DESIGN: Translational cell
biological study. SETTING: Academic medical center. PATIENTS: Endometrial tissue was
provided by five healthy reproductive age women on no hormonal medication, undergoing …
pregnancy. OBJECTIVE: To evaluate the role of gap junction intercellular communications
and connexin (Cx) proteins in the morphological and biochemical differentiation of
decidualized human endometrial stromal cell (ESC) cultures. DESIGN: Translational cell
biological study. SETTING: Academic medical center. PATIENTS: Endometrial tissue was
provided by five healthy reproductive age women on no hormonal medication, undergoing …
CONTEXT
Uterine decidualization is critical to embryonic implantation and sustained pregnancy.
OBJECTIVE
To evaluate the role of gap junction intercellular communications and connexin (Cx) proteins in the morphological and biochemical differentiation of decidualized human endometrial stromal cell (ESC) cultures.
DESIGN
Translational cell biological study.
SETTING
Academic medical center.
PATIENTS
Endometrial tissue was provided by five healthy reproductive age women on no hormonal medication, undergoing laparoscopy in the early proliferative phase of the menstrual cycle.
INTERVENTIONS
Endometrial biopsy under general anesthesia, establishment and decidualization of ESC with 10nM 17β-estradiol, 100nM progesterone and 0.5mM dibutyryl-cAMP (E/P/c), and manipulation of gap junctions in vitro via a combination of pharmacological or transgenic approaches.
MAIN OUTCOME MEASURES
Decidualized ESC evaluated morphologically for epithelioid transformation, gap junctions by dye diffusion and Cx43, prolactin, VEGF and IL-6 expression by RT-PCR, Western and ELISA methods.
RESULTS
Cx43 accumulation and functional gap junctions between decidualized ESC increase concomitantly with morphological differentiation following E/P/c treatment. Disruption of gap junctions using pharmacological inhibitors or Cx43 shRNA prevents morphological differentiation and inhibits prolactin and VEGF secretion. By contrast, IL-6 secretion from decidualized ESC is augmented by both approaches.
CONCLUSIONS
The findings suggest that decidualized ESC function as a coordinated secretory organ to regulate embryonic implantation via intercellular cooperation mediated by gap junctions. When adjacent cells can communicate through these junctions, decidual prolactin and VEGF secretion appears to be optimized for vascular development of the placental bed. Conversely, when intercellular communications are disrupted, angiogenesis is impaired and an inflammatory state is induced.
Elsevier
