Compensatory placental hypervascularization in a rat model of early-stage, diet-induced maternal obesity

Objective

Maternal obesity is usually associated with placental hypovascularity. This study aimed to challenge this paradigm by investigating the immediate vascular adaptations in the placental labyrinth zone in response to short-term, diet-induced obesity. The study hypothesised that there would be an initial compensatory hypervascularisation before the onset of systemic metabolic disease.

Methods

Female Wistar rats were fed either a standard control diet (CG, n = 9) or an ultra-processed, hypercaloric cafeteria diet (EG, n = 9) for eight weeks to induce obesity. On gestational day 16.5, maternal morphometric and biochemical analyses were performed alongside detailed placental histomorphometry and immunohistochemistry for CD31/α-actin, in order to quantify foetal vessel density in the labyrinth zone using ImageJ.

Results

The cafeteria diet successfully induced a significant obese phenotype (mean weight gain: 62.73 g in the experimental group (EG) versus 32.26 g in the control group (CG); P < 0.0001), but did not induce significant hyperglycaemia or dyslipidaemia (P > 0.05). Although there were no significant differences in foetal or placental weights, the labyrinth zone of the EG showed a significant increase in foetal vessel density (29.08 ± 1.91 vessels/field) compared to the CG (26.06 ± 1.80 vessels/field; P = 0.014), indicating robust vascular remodelling.

Conclusion

Short-term exposure to an ‘obesogenic’ diet triggers significant compensatory hypervascularisation in the placenta of rats, which is an adaptive response that precedes systemic metabolic dysfunction. This finding contrasts with the hypovascularity observed in chronic obesity. The discrepancy between increased vascular density and foetal growth underscores the importance of evaluating not only the quantity but also the quality and function of blood vessels when assessing placental health in cases of maternal obesity.

Highlights

• Acute cafeteria diet-induced obesity causes placental hypervascularity.

• Increased placental vasculature does not correlate with enhanced foetal growth.

• Rapid obesity develops without major pre-gestational metabolic disruption.

• A biphasic model of vascular adaptation to maternal obesity is proposed.