bims-reprim 2021-06-13 papers

Issue of 2021–06–13
four papers selected by
Iva Filipovic, Karolinska Institutet

Immunity. 2021 Jun 08. pii: S1074-7613(21)00215-6. [Epub ahead of print]54(6): 1102-1104

Uterine NK cell education: Learning the ropes in pregnancy.

The impact of inhibitory receptor NKG2A-mediated education on uterine NK (uNK) cell responsiveness to vascular remodeling on pregnancy outcomes has remained unclear. In this issue of Immunity, Shreeve et al. show that loss of NKG2A+ uNK cells results in deficient vascularization and restricted fetal growth.

DOI: https://doi.org/10.1016/j.immuni.2021.05.009

Commun Biol. 2021 Jun 08. 4(1): 701

Placental secretome characterization identifies candidates for pregnancy complications.

Tina Napso, Xiaohui Zhao, Marta Ibañez Lligoña, Ionel Sandovici, Richard G Kay, Amy L George, Fiona M Gribble, Frank Reimann, Claire L Meek, Russell S Hamilton, Amanda N Sferruzzi-Perri.

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.

DOI: https://doi.org/10.1038/s42003-021-02214-x

Biol Open. 2021 Jun 15. pii: bio058222. [Epub ahead of print]10(6):

RNA-Seq reveals changes in human placental metabolism, transport and endocrinology across the first-second trimester transition.

Malwina Prater, Russell S Hamilton, Hong Wa Yung, Andrew M Sharkey, Paul Robson, N Erlyani Abd Hamid, Eric Jauniaux, D Stephen Charnock-Jones, Graham J Burton, Tereza Cindrova-Davies.

The human placenta is exposed to major environmental changes towards the end of the first trimester associated with full onset of the maternal arterial placental circulation. Changes include a switch from histotrophic to hemotrophic nutrition, and a threefold rise in the intraplacental oxygen concentration. We evaluated their impact on trophoblast development and function using RNA-sequencing (RNA-Seq) and DNA-methylation analyses performed on the same chorionic villous samples at 7-8 (n=8) and 13-14 (n=6) weeks of gestation. Reads were adjusted for fetal sex. Most DEGs were associated with protein processing in the endoplasmic reticulum (ER), hormone secretion, transport, extracellular matrix, vasculogenesis, and reactive oxygen species metabolism. Transcripts higher in the first trimester were associated with synthesis and ER processing of peptide hormones, and glycolytic pathways. Transcripts encoding proteins mediating transport of oxygen, lipids, protein, glucose, and ions were significantly increased in the second trimester. The motifs of CBX3 and BCL6 were significantly overrepresented, indicating the involvement of these transcription factor networks in the regulation of trophoblast migration, proliferation and fusion. These findings are consistent with a high level of cell proliferation and hormone secretion by the early placenta to secure implantation in a physiological low-oxygen environment.

Keywords: Early placenta; Human pregnancy; Metabolism; Methylation; Transcriptome

DOI: https://doi.org/10.1242/bio.058222

J Clin Invest. 2021 Jun 08. pii: 150790. [Epub ahead of print]

The Israeli study of Pfizer BNT162b2 vaccine in pregnancy: considering maternal and neonatal benefits.

Irina Burd, Tomoshige Kino, James Segars.

Pregnant patients with COVID-19 are more likely to require intensive care and die compared with non-infected pregnant women. While the consequences of COVID-19 disease in pregnancy prompted many health care organizations to support vaccination in pregnancy, vaccine effects for mother and infant remained unclear. In this issue of the JCI, Beharier and Mayo et al. explored maternal and neonatal responses to the Pfizer BNT162b2 SARS-CoV-2 mRNA vaccine. The authors examined blood samples from women and cord blood of neonates following childbirth. Samples were stratified into three groups: vaccine recipients, unvaccinated participants with past positive SARS-CoV-2 test, and unvaccinated without prior infection. Vaccinated mothers and mothers with previous infection generated and transferred protective IgG antibodies across the placenta. This study provides evidence to support the safety and efficacy of COVID-19 vaccination in pregnancy with protection to the neonate against infection, outlining clear vaccine benefits for both maternal and child health.

DOI: https://doi.org/10.1172/JCI150790