Placental secretome characterization identifies candidates for pregnancy complications.
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Springer Nature
https://doi.org/10.1038/s42003-021-02214-x
https://doi.org/10.1038/s42003-021-02214-x
Abstract
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Alterations in maternal physiological adaptation during pregnancy lead to complications, including abnormal birthweight and gestational diabetes. Maternal adaptations are driven by placental hormones, although the full identity of these is lacking. This study unbiasedly characterized the secretory output of mouse placental endocrine cells and examined whether these data could identify placental hormones important for determining pregnancy outcome in humans. Secretome and cell peptidome analyses were performed on cultured primary trophoblast and fluorescence-activated sorted endocrine trophoblasts from mice and a placental secretome map was generated. Proteins secreted from the placenta were detectable in the circulation of mice and showed a higher relative abundance in pregnancy. Bioinformatic analyses showed that placental secretome proteins are involved in metabolic, immune and growth modulation, are largely expressed by human placenta and several are dysregulated in pregnancy complications. Moreover, proof-of-concept studies found that secreted placental proteins (sFLT1/MIF and ANGPT2/MIF ratios) were increased in women prior to diagnosis of gestational diabetes. Thus, placental secretome analysis could lead to the identification of new placental biomarkers of pregnancy complications.
This work was supported by a Royal Society Dorothy Hodgkin Research Fellowship, Academy of Medical of Sciences Springboard Grant, Isaac Newton Trust Grant and Lister Institute Research Prize grant to ANSP (grant numbers DH130036 / RG74249, SBF002/1028 / RG88501, RG97390 and RG93692, respectively). TN was supported by an EU Marie Skłodowska-Curie Fellowship (PlaEndo/703160) and an Early Career Grant from the Society for Endocrinology. CLM is supported by the Diabetes UK Harry Keen Intermediate Clinical Fellowship (DUK-HKF 17/0005712) and the EFSD-Novo Nordisk Foundation Future Leader’s Award (NNF19SA058974). Work in the FR/FMG laboratory was supported by the Wellcome Trust (106262/Z/14/Z,106263/Z/14/Z), the MRC (MRC_MC_UU_12012/3 and MRC -Enhancing UK clinical research grant MR/M009041/1) and the Cambridge Biomedical Research Centre (NIHR-BRC Gastrointestinal Diseases theme).
This work was supported by a Royal Society Dorothy Hodgkin Research Fellowship, Academy of Medical of Sciences Springboard Grant, Isaac Newton Trust Grant and Lister Institute Research Prize grant to ANSP (grant numbers DH130036 / RG74249, SBF002/1028 / RG88501, RG97390 and RG93692, respectively). TN was supported by an EU Marie Skłodowska-Curie Fellowship (PlaEndo/703160) and an Early Career Grant from the Society for Endocrinology. CLM is supported by the Diabetes UK Harry Keen Intermediate Clinical Fellowship (DUK-HKF 17/0005712) and the EFSD-Novo Nordisk Foundation Future Leader’s Award (NNF19SA058974). Work in the FR/FMG laboratory was supported by the Wellcome Trust (106262/Z/14/Z,106263/Z/14/Z), the MRC (MRC_MC_UU_12012/3 and MRC -Enhancing UK clinical research grant MR/M009041/1) and the Cambridge Biomedical Research Centre (NIHR-BRC Gastrointestinal Diseases theme).