Vitamin D Supplementation Improves Mitochondrial Function and Reduces Inflammation in Placentae of Obese Women.
Level 5 - mechanism / opinion, no new human data
Bench and ex vivo cell culture study using human tissue samples
PubMed 35712242 · doi:10.3389/fendo.2022.893848
What was done
Placental samples, maternal blood, and cord blood were collected at term Cesarean section from normal-weight (BMI < 25) and obese (BMI > 30) women with uncomplicated pregnancies, as well as women with gestational diabetes and preeclampsia. Plasma 25(OH)D3 was measured by ELISA. Placental expression of CYP27B1 and vitamin D receptor (VDR) was assessed. Cytotrophoblasts isolated from normal-weight and obese placentae were treated ex vivo with calcitriol (10 nM and 100 nM) to assess mitochondrial respiration via Seahorse bioanalysis and inflammatory markers (NLRP3, IL-18) via Western blot.
What was found
Cord blood vitamin D inversely correlated with pre-pregnancy BMI (r = -0.55, p = 0.004) and positively correlated with maternal vitamin D (r = 0.83, p < 0.00) and placental efficiency (r = 0.69, p < 0.00). In maternal blood from obese women, the correlation with BMI was r = -0.50 (p < 0.1). Placental VDR expression was reduced by 50% in obese vs. normal-weight women (p < 0.03), with no difference in CYP27B1 or in cases of gestational diabetes or preeclampsia relative to BMI-matched controls. In trophoblasts from obese women, calcitriol dose-dependently increased VDR expression and improved mitochondrial respiration (p < 0.05). Baseline two-fold elevations in NLRP3 and IL-18 in obese trophoblasts (p < 0.05) were mitigated, with IL-18 expression reversed by 100 nM calcitriol.
Why it matters
This mechanistic study indicates that reduced placental vitamin D signaling contributes to the mitochondrial dysfunction and inflammatory state seen in maternal obesity, and that direct active vitamin D exposure can rescue these pathways in vitro.
Limits
The abstract does not report the sample size (n) of women or placental donors. Findings rely on in vitro calcitriol treatment of isolated cytotrophoblasts, which does not demonstrate whether oral maternal vitamin D supplementation achieves clinical or in vivo placental improvements.
Cited by
- supports Vitamin D has beneficial effects on mitochondrial function and immune cells.