Placental exosomes and maternal inflammation in obesity

February 21, 2017 Journal Club: We’ll be discussing the following manuscript from the current issue of Placenta:

Elfeky et al. Influence of maternal BMI on the exosomal profile during gestation and their role on maternal systemic inflammation. Placenta 50: 60-69, 2017.

Click on the above link for highlights and abstract.

Summary of our discussion:

This was an interesting study on an important topic in the field.  We felt that the inflammation experiments were the strongest part of the paper. The finding that exosomes isolated from obese women had pro-inflammatory effects on endothelial cells, compared to the minor effects of exosomes isolated from lean women, supports the idea that exosomes are taken up and alter function of other tissues. This leads to further questions about whether these outcomes are due to the placental exosomes, or do all exosomes from different tissues have the same effect. Though maternal cytokine values were not measured, it would be interesting to know how maternal cytokine concentrations correlated with pro-inflammatory exosome activity. Another interesting finding, was that the exosome-induced interleukin-6 (IL-6) increase was mainly due to exosomes isolated from obese women in early pregnancy, while in late pregnancy, the differences between lean and obese women were undetectable. This supports the idea that early pregnancy is an important time for “programming” of the maternal environment.

As a lab that is concerned with the effect of maternal obesity on placental function, we were particularly interested in how maternal BMI affected exosome number. These data were, in our opinion, weak. The authors grouped women into lean, overweight and obese categories based on their body mass index (BMI) at the time of sample collection, which ranged from 10-38 weeks. A woman who is lean at the start of pregnancy, can easily gain 35 lbs, putting her into the overweight, or obese category in late pregnancy. However, as many previous studies have shown, it is maternal pre-pregnancy BMI that is most predictive of placental function and outcomes. Thus, we struggled with interpreting the data in Figures 2-4, which assessed the association between exosome number and gestational age or maternal BMI, grouped by maternal obesity. We speculated that some of the noise in the data may have been due to how these women were grouped. As such, we concluded that the question of how exosome number is affected by maternal BMI remains to be answered.

One other issue is that in the discussion, the authors mis-quoted a reference (Wallace et al., Placenta 2012). Wallace found a strong correlation between maternal BMI and placental weight, but Elfeky et al. incorrectly used this reference to support the claim that there was no association between maternal BMI and placental weight. This is important, because it is possible that as the placenta grows throughout pregnancy and is typically larger in obese women, it may be producing more exosomes, which could account for some of their associations. In this study, placental weight was not measured, so that question will require further study. The authors have previously shown that an indirect measure of placental exosomes (exosomal PLAP) was associated with placental weight in late pregnancy (Salomon et al, PlosONE, 2014).

Overall, we thought there were some very significant findings in this study, and that the authors identified a possible mechanism underlying the excessive maternal systemic inflammation in obese women.

We’d love to see your thoughts on this manuscript! Please comment below and give us your opinion.


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