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New Insights on HLA-G in Preeclampsia Revealed – Benthic Genomics
Benthic Genomics/benthic.bio
Nov 19, 2025, 01:28

New Insights on HLA-G in Preeclampsia Revealed – Benthic Genomics

Benthic Genomics shared a post on LinkedIn about a paper by Satu Wedenoja et al. published in EBioMedicine:

“Fetal HLA-G: The master regulator of pregnancy success that affects even the sex of your baby.

A study of 1.79 million births by Satu Wedenoja et al. reveals that fetal HLA-G isn’t just about immune tolerance – it may actually influence whether pregnancies result in boys or girls.

Key findings from this landmark research:

  •  Male fetuses are underrepresented in preeclamptic births, especially those delivered preterm
  •  HLA-G expression is significantly downregulated in preeclamptic placentas
  •  Specific HLA-G genetic variants are associated with both pregnancy complications and offspring sex ratios
  • Balancing selection at the HLA-G locus promotes genetic diversity as an evolutionary trade-off

HLA-G creates immune tolerance at the maternal-fetal interface, preventing the mother’s immune system from rejecting the fetus. When this system fails, it can lead to:

  • Increased risk of preeclampsia
  • Higher rates of stillbirth
  • Altered sex ratios in affected pregnancies

The study found that placental HLA-G and IFNA1 expression distinguished preeclamptic pregnancies better than current biomarkers (FLT1 and PlGF), suggesting new diagnostic possibilities.

This research demonstrates how evolution has shaped pregnancy success through immune regulation, with HLA-G heterozygosity providing advantages for fetal survival.

Link to the full paper.

What role might HLA-G testing play in future prenatal care?”

Title: Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia

Authors: Satu Wedenoja, Masahito Yoshihara, Hindrek Teder, Hannu Sariola, Mika Gissler, Shintaro Katayama, Juho Wedenoja, Inka M. Häkkinen, Sini Ezer, Nina Linder, Johan Lundin, Tiina Skoog, Ellika Sahlin, Erik Iwarsson, Karin Pettersson, Eero Kajantie, Mikael Mokkonen, Seppo Heinonen, Hannele Laivuori, Kaarel Krjutškov, Juha Kere

Benthic Genomics

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