Sex-specific Impact of Maternal Obesity on Fetal Placental Macrophages and Cord Blood Triglycerides
Key findings
- This study examined whether maternal obesity is characterized by alterations in Hofbauer cells (fetal placental macrophages) in the placenta at term and whether those alterations are associated with changes in placental lipid transport to the fetus
- Differences in Hofbauer cell morphology were observed in response to maternal obesity that may suggest a pro-inflammatory activation state, with greater effects observed in male placentas
- Expression of placental genes involved in fatty acid binding and transport (FABPPM, FATP4 and FATP6) and umbilical cord plasma triglycerides were decreased in females and increased in males in the setting of maternal obesity
- Umbilical cord plasma triglycerides were significantly correlated with Hofbauer cell density in the placenta, suggesting a connection between placental immune activation and lipid transport to the fetus
- The findings suggest that maternal obesity affects offspring cardiometabolic programming in a sex-specific manner through placental immune activation
Large epidemiologic studies have established that in utero exposure to maternal obesity increases the risk of childhood obesity, as well as the odds of diabetes and other diseases that develop later in life. Sex differences have been observed in these outcomes.
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Research at Massachusetts General Hospital has uncovered sex-specific placental immune activation and alterations in placental lipid transport that may explain the sex differences in offspring cardiometabolic programming. Lydia L. Shook, MD, and Andrea G. Edlow, MD, MSc, investigators in the Vincent Center for Reproductive Biology and maternal–fetal medicine specialists in the Department of Obstetrics and Gynecology, and colleagues published their data in Placenta.
Background
Maternal obesity is a chronic inflammatory state that stimulates immune activation in the placenta and fetus. The number and phenotype of fetal placental macrophages called Hofbauer cells (HBCs), which are critical for antimicrobial defense, placental nutrient transport, and tissue repair, have been observed to be abnormal in maternal obesity.
Like other macrophages, HBCs can exist in both pro- and anti-inflammatory states, or intermediate phenotypes, although variations are common. Lipid metabolism, a key function of tissue-resident macrophages, may be deranged in inflammation/immune activation.
Methods and Results
The researchers analyzed umbilical cord blood and samples of placental tissue from 34 women (15 with body mass index ≥30 kg/m2) who underwent Cesarean delivery at term.
The principal observations were:
- Maternal obesity was associated with a significantly increased density of HBCs, and greater effect size was observed in male placentas
- Obesity-exposed male placentas had the highest: HBC density; expression of placental genes involved in fatty acid binding and transport (FABPPM, FATP4, and FATP6); and expression of genes encoding the beta and gamma subunits of AMPK, a protein involved in cellular energy homeostasis and sensing of intracellular energy depletion
- When HBC morphology was examined as a proxy for the immune activation state, male HBCs were significantly larger and rounder than female HBCs in the setting of maternal obesity
- Obesity-exposed male placentas had the highest levels of cord triglycerides, which were positively correlated with CD163+ HBC density and placental FATP1 expression
Research Implications
These findings support further exploration of the connection between maternal obesity, placental immune activation, and cardiometabolic programming, with fetal sex an important potential effect modifier to consider.
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