(1117) ITPR1 mRNA expression is downregulated in obese placental cells

Friday, February 10, 2023

3:30 PM – 5:00 PM

Objective: Obesity during pregnancy has a critical impact not only on women’s health and fetal growth, but also later on by increasing the risk of obesity and metabolic diseases in adulthood. Inositols (INOs) regulate glycogen storage, insulin-glucose and calcium pathways. Through their interaction with Inositol 3 phosphate receptor 1 (ITPR1), they mediate the efflux of calcium ions from the endoplasmic reticulum into the cytoplasm, modulating cellular functions and gene expression. The objective of the study was to evaluate alterations in INOs pathway in placental trophoblast cells.

Study Design: In this experimental study, placentas were obtained from Obese (OB) and Normal weight (CTRL) women, undergoing elective cesarean section (breech presentation), at term (Figure). None of them reported comorbidities. Trophoblasts cells were isolated based on enzyme digestion and Density gradient separation. Expression of critical genes involved in inositol regulation and pathway including SMIT1, SMIT2, IMPA1, ISYNA1 and ITPR1 were evaluated in isolated trophoblast cells. Total mRNA was extracted using column-based purification.mRNAs were reversed transcribed into cDNA and it was analysed through quantitative PCR using taqman reagent (Life Technologies) and primers.The relative expression levels of mRNAs were calculated using the comparative ΔΔCt method.

Results: Seven placentas (3 CTR vs 4 OB) were analysed. Diluted mRNA was used for qPCR analysis. Data were normalized on gapdh mRNA levels. ITPR1 mRNA level expression was downregulated in OB group (p < 0.03) compared to lean healthy women. We did not detect significant modifications in SMIT1, SMIT2, IMPA1 and ISYNA1 expression.

Conclusion: With our data, we demonstrate an alteration in the INOs pathway in trophoblast cells induced by maternal obesity, as revealed by the significant decrease in ITPR1 expression. The identification of ITPR1 downregulation is a first step to identify potential targets and develop novel therapeutic approaches and personalized therapies to ameliorate obesity related conditions in pregnancy.

Primary Author(s)

Pierluigi Di Vinci, MSc
University of Modena and Reggio Emilia
Modena, Emilia-Romagna, Italy

Coauthor(s)

BS
Bénazir Siddeek, PhD
University of Lausanne
Lausanne, Vaud, Switzerland
US
Umberto Simeoni, MD
University of Lausanne
Lausanne, Vaud, Switzerland

Presenting Author(s)

FF
Fabio Facchinetti, MD
University of Modena and Reggio Emilia
Modena, Emilia-Romagna, Italy