Growth-Restricted Fetuses and Offspring Reveal Adverse Sex-Specific Metabolic Responses in Preeclamptic Mice Expressing Human sFLT1

Rebekka Vogtmann, Mian Bao, Monia Vanessa Dewan, Alina Riedel, Rainer Kimmig, Ursula Felderhoff-Müser, Ivo Bendix, Torsten Plösch, Alexandra Gellhaus*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
51 Downloads (Pure)

Abstract

Fetal adaptations to harmful intrauterine environments due to pregnancy disorders such as preeclampsia (PE) can negatively program the offspring’s metabolism, resulting in long-term metabolic changes. PE is characterized by increased circulating levels of sFLT1, placental dysfunction and fetal growth restriction (FGR). Here we examine the consequences of systemic human sFLT1 overexpression in transgenic PE/FGR mice on the offspring’s metabolic phenotype. Histological and molecular analyses of fetal and offspring livers as well as examinations of offspring serum hormones were performed. At 18.5 dpc, sFLT1 overexpression resulted in growth-restricted fetuses with a reduced liver weight, combined with reduced hepatic glycogen storage and histological signs of hemorrhages and hepatocyte apoptosis. This was further associated with altered gene expression of the molecules involved in fatty acid and glucose/glycogen metabolism. In most analyzed features males were more affected than females. The postnatal follow-up revealed an increased weight gain of male PE offspring, and increased serum levels of Insulin and Leptin. This was associated with changes in hepatic gene expression regulating fatty acid and glucose metabolism in male PE offspring. To conclude, our results indicate that sFLT1-related PE/FGR in mice leads to altered fetal liver development, which might result in an adverse metabolic pre-programming of the offspring, specifically targeting males. This could be linked to the known sex differences seen in PE pregnancies in human.

Original languageEnglish
Article number6885
Number of pages23
JournalInternational Journal of Molecular Sciences
Volume24
Issue number8
DOIs
Publication statusPublished - 7-Apr-2023

Keywords

  • fetal growth restriction
  • fetal programming
  • liver
  • obesity
  • placenta
  • preeclampsia
  • sex differences
  • sFLT1

Fingerprint

Dive into the research topics of 'Growth-Restricted Fetuses and Offspring Reveal Adverse Sex-Specific Metabolic Responses in Preeclamptic Mice Expressing Human sFLT1'. Together they form a unique fingerprint.

Cite this