(854) Inositols pathway is altered in placental tissue of obese women

Obesity in pregnancy has significant short- and long-term consequences for both women and their neonates as well for long-life metabolic disorders. Myo-Inositol (MI) has a pivotal role in Insulin/glucose metabolism interacting with Inositol 3 phosphate receptor 1 (ITPR1) in endoplasmic reticulum. This pathway influences also cellular functions. The objective was to investigate potential changes of MI pathway in placental tissue of obese women, investigating its role in cellular proliferation.


Study Design: In a non-randomized experimental study, placental explants were collected from uncomplicated obese (OB) and normal weight (CTRL) women undergoing elective cesarean section, at term. Tissues were snap frozen in liquid nitrogen. Critical proteins involved in Ins regulation and pathway including SMIT1, SMIT2, ISYNA1, MIOX, ITPR1 and CN were analyzed. Total proteins were extracted with RIPA buffer, their concentrations measured with BCA assay and quantified by Western Blot (WB). To investigate the effect of MI treatment on placental cells, a trophoblast human cell line (HTR8/SVneo) was used for proliferation assay study (Immunological science). Student’s t test was used for single comparison analysis and ANOVA for multiple comparisons. Data were significant if p< 0.05.

Results: Thirty-four placenta samples (18 OB vs 16 CTRLs) were analyzed by WB. Data were normalized on GAPDH protein level. ITPR1 was upregulated in OB group (p=0.002) compared to CTRLs, as well as the active cleaved form of calcineurin (CN) (p=0.004).  We did not observed alteration in SMITs, MIOX and ISYNA1 protein levels. “In vitro” MI treatment, in a dose-dependent way, decreased proliferation of trophoblast cells (Fig).

Conclusion: An alteration of the MI pathway within placenta tissue of OB women was demonstrated as revealed by significant increase in ITPR1 protein level and active CN. No changes instead occurred in MI cellular intake, synthesis and catabolism. MI inhibited trophoblast cell proliferation. In women with pre-pregnancy obesity up-regulation of placental MI activity could affect placenta development.