Thursday, December 14, 2017

GDF15, "morning sickness," and angiogenesis

Last month, researchers at Cambridge announced that they had found a correlation between the protein GDF15 and nausea and vomiting in pregnancy. ( Here's the abstract from their prepublication paper:

Nausea and vomiting in pregnancy (NVP) affects 70-90% of all pregnant women, but its pathogenesis is unknown. Growth and Differentiation Factor 15 (GDF15), secreted from the trophoblast and decidual stromal cells, is present at high levels in the blood of pregnant women. The receptor for GDF15 has recently been identified and is specifically expressed in the hindbrain where it transmits aversive signals including nausea and conditioned taste aversion. We explored the relationship between GDF15 concentrations in maternal serum during pregnancy and self-reported NVP. In a study of 791 women from the Cambridge Baby Growth Study maternal GDF15 concentrations were higher in women who reported vomiting in the 2nd trimester (geometric mean: 11,670 pg/mL; 95% confidence interval 11,056-12,318) and were even higher in the eleven women who reported taking anti-emetics during pregnancy (13,376 (10,821-16,535) compared to those who reported no nausea or vomiting during pregnancy (10,657 (10,121-11,222); P=0.02 and P=0.04, respectively, adjusted for gestational age at sampling and maternal BMI). In conclusion serum GDF concentrations early in the second trimester are significantly and positively associated with second trimester vomiting and with maternal anti-emetic use. In the context of the recently revealed biology of GDF15 this data suggests that antagonism of GDF15 may have some potential for therapeutic benefit in NVP.

I am both delighted and worried by this paper, and the cause for both feelings is the same: GDF15 promotes ( and has an essential role in angiogenesis (, the creation of new blood vessels from existing ones. Around 18 months ago, I published my hypothesis that sulfite, a metabolic product of endogenous H2S used in angiogenesis, is the primary culprit behind NVP and that molybdenum supplementation can help the body more quickly break down that sulfite to sulfate via sulfite oxidase.* ( So naturally I'm very pleased to see this recent finding that connects an angiogenesis promoter to NVP. What worries me is the paper's suggestion that antagonism of GDF15 might be a therapy to treat NVP.

We do not want to interfere with angiogenesis during early pregnancy. That's exactly what went wrong with thalidomide. Thalidomide inhibits angiogenesis, leading to truncated limbs and other awful consequences.

I found the lead author's professional Facebook page and posted my appreciation of his findings and concern about the proposal to antagonize GDF15. I hope he takes it seriously despite my lack of biology credentials. Whether I have a piece of paper from the proper college is irrelevant to the copious evidence of the necessity of proper angiogenesis in pregnancy.

* And if you've been reading my blog, you know that molybdenum ended up surprising me by being good for more than just NVP!

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