High Rates of Placental Inflammation Among Samples Collected by the MOMI Consortium.

chorionic villi chronic villitis inflammation parturition placenta pregnancy prematurity preterm birth transcriptomics

Journal

American journal of obstetrics and gynecology
ISSN: 1097-6868
Titre abrégé: Am J Obstet Gynecol
Pays: United States
ID NLM: 0370476

Informations de publication

Date de publication:
30 Apr 2024
Historique:
received: 02 11 2023
revised: 18 04 2024
accepted: 24 04 2024
medline: 3 5 2024
pubmed: 3 5 2024
entrez: 2 5 2024
Statut: aheadofprint

Résumé

The Multi-Omics for Mothers and Infants (MOMI) consortium aims to improve birth outcomes. Preterm birth is a major obstetric complication globally causing significant infant and childhood morbidity and mortality. We analyzed placental samples (basal plate, placenta/chorionic villi and/or the chorionic plate) collected by the 5 MOMI sites: The Alliance for Maternal and Newborn Health Improvement (AMANHI) Bangladesh, AMANHI Pakistan, AMANHI Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) Bangladesh and GAPPS Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births. The teams provided biopsies from 166 singleton preterm (<37 weeks) and 175 term (≥37 weeks) deliveries. They were formalin-fixed and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphological analyses. Other placental biopsies (n = 35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics. The morphological analyses revealed a surprisingly high rate of inflammation involving the basal plate, placenta/chorionic villi and/or the chorionic plate. The rate in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs. the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes as differentially expressed (DE) between placentas from preterm vs. term births (123 upregulated, 144 downregulated). Mapping the DE genes onto single cell RNA-seq data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathological findings, GO (Gene Ontology) analyses highlighted leukocyte infiltration/activation and inflammatory responses in both the fetal and maternal compartments. The relationship between placental inflammation and preterm birth is appreciated in developed countries. Here, we show that this link also exists in developing geographies. Also, among the participating sites, we found geographic- and/or population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

Sections du résumé

BACKGROUND BACKGROUND
The Multi-Omics for Mothers and Infants (MOMI) consortium aims to improve birth outcomes. Preterm birth is a major obstetric complication globally causing significant infant and childhood morbidity and mortality.
OBJECTIVES OBJECTIVE
We analyzed placental samples (basal plate, placenta/chorionic villi and/or the chorionic plate) collected by the 5 MOMI sites: The Alliance for Maternal and Newborn Health Improvement (AMANHI) Bangladesh, AMANHI Pakistan, AMANHI Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) Bangladesh and GAPPS Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births.
STUDY DESIGN METHODS
The teams provided biopsies from 166 singleton preterm (<37 weeks) and 175 term (≥37 weeks) deliveries. They were formalin-fixed and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphological analyses. Other placental biopsies (n = 35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics.
RESULTS RESULTS
The morphological analyses revealed a surprisingly high rate of inflammation involving the basal plate, placenta/chorionic villi and/or the chorionic plate. The rate in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs. the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes as differentially expressed (DE) between placentas from preterm vs. term births (123 upregulated, 144 downregulated). Mapping the DE genes onto single cell RNA-seq data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathological findings, GO (Gene Ontology) analyses highlighted leukocyte infiltration/activation and inflammatory responses in both the fetal and maternal compartments.
CONCLUSION CONCLUSIONS
The relationship between placental inflammation and preterm birth is appreciated in developed countries. Here, we show that this link also exists in developing geographies. Also, among the participating sites, we found geographic- and/or population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

Identifiants

DOI: 10.1016/j.ajog.2024.04.034 PMID: 38697337
pubmed: 38697337
pii: S0002-9378(24)00560-X
doi: 10.1016/j.ajog.2024.04.034
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Auteurs

Joshua F Robinson (JF)

Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA 94143, USA.

Sayan DAS (S)

Public Health Laboratory-IdC, Wawi, Chake, Pemba, Zanzibar, Tanzania.

Waqasuddin Khan (W)

Biorepository and Omics Research Group, Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi-74800, Pakistan; Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi-74800, Pakistan.

Rasheda Khanam (R)

Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.

Joan T Price (JT)

UNC Global Projects - Zambia; Lusaka, Zambia; Department of Obstetrics and Gynecology, University of North Carolina School of Medicine; Chapel Hill, NC, USA.

Anisur Rahman (A)

Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh.

Salahuddin Ahmed (S)

Projahnmo Research Foundation. Bangladesh.

Said Mohammed Ali (S)

Public Health Laboratory-IdC, Wawi, Chake, Pemba, Zanzibar, Tanzania.

Saikat Deb (S)

Public Health Laboratory-IdC, Wawi, Chake, Pemba, Zanzibar, Tanzania; Center for Public Health Kinetics, 214A, Vinoba Puri, Lajpatnagar-2, New Delhi, India.

Brian Deveale (B)

Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA 94143, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA; Department of Urology, University of California, San Francisco, San Francisco, CA 94143, USA.

Arup Dutta (A)

Center for Public Health Kinetics, 214A, Vinoba Puri, Lajpatnagar-2, New Delhi, India.

Matthew Gormley (M)

Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA 94143, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA; Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco, San Francisco, California 94143, USA.

Steven C Hall (SC)

Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA 94143, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA; Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco, San Francisco, California 94143, USA.

A S M Tarik Hasan (ASMT)

Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh.

Aneeta Hotwani (A)

Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi-74800, Pakistan.

Mohamed Hamid Juma (MH)

Public Health Laboratory-IdC, Wawi, Chake, Pemba, Zanzibar, Tanzania.

Margaret P Kasaro (MP)

UNC Global Projects - Zambia; Lusaka, Zambia; Department of Obstetrics and Gynecology, University of North Carolina School of Medicine; Chapel Hill, NC, USA; Department of Gynaecology and Obstetrics, University of Zambia School of Medicine; Lusaka, Zambia.

Javairia Khalid (J)

Biorepository and Omics Research Group, Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi-74800, Pakistan; Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi-74800, Pakistan.

Pallavi Kshetrapal (P)

Maternal and Child Health, Translational Health Science and Technology Institute, Faridabad, India.

Michael T McMaster (MT)

Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA 94143, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA; Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, California 94143, USA.

Usma Mehmood (U)

Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi-74800, Pakistan.

Imran Nisar (I)

Biorepository and Omics Research Group, Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi-74800, Pakistan; Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi-74800, Pakistan.

Jesmin Pervin (J)

Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh.

Sayedur Rahman (S)

Projahnmo Research Foundation. Bangladesh.

Rubhana Raqib (R)

International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) Dhaka, Bangladesh.

Ali San (A)

Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA 94143, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.

Protim Sarker (P)

Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh.

Sami T Tuomivaara (ST)

Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA 94143, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA; Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco, San Francisco, California 94143, USA.

Ge Zhang (G)

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA; Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center and March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Yan Zhou (Y)

Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA 94143, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.

Shaki Aktar (S)

Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh.

Abdullah H Baqui (AH)

Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.

Fyezah Jehan (F)

Biorepository and Omics Research Group, Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi-74800, Pakistan; Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi-74800, Pakistan.

Sunil Sazawal (S)

Center for Public Health Kinetics, 214A, Vinoba Puri, Lajpatnagar-2, New Delhi, India.

Jeffrey S A Stringer (JSA)

Department of Obstetrics and Gynecology, University of North Carolina School of Medicine; Chapel Hill, NC, USA.

Susan J Fisher (SJ)

Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA 94143, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA; Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco, San Francisco, California 94143, USA. Electronic address: Susan.Fisher@ucsf.edu.

Classifications MeSH