Evidence map›Paper›PMID 38537412›Full record

ArticlePlacenta2024

High-throughput mRNA sequencing of human placenta shows sex differences across gestation.

Amy E Flowers, Tania L Gonzalez, Yizhou Wang, Chintda Santiskulvong, Ekaterina L Clark, Allynson Novoa, Caroline A Jefferies, Kate Lawrenson, Jessica L Chan, Nikhil V Joshi and 7 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Placenta, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
20.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 2 institutions in 1 country.

Amy E FlowersDepartment of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Tania L GonzalezDepartment of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Yizhou WangComputational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Chintda SantiskulvongCS Cancer Applied Genomics Shared Resource, CS Cancer, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Ekaterina L ClarkDepartment of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Allynson NovoaDepartment of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Caroline A JefferiesDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Kate LawrensonDepartment of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Jessica L ChanDepartment of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Nikhil V JoshiDepartment of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Yazhen ZhuDavid Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Hsian-Rong TsengCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Erica T WangDepartment of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Mariko IshimoriDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
S Ananth KarumanchiDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
John WilliamsDepartment of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Margareta D PisarskaDepartment of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA. Electronic address: Margareta.Pisarska@cshs.org.
Cedars-Sinai Medical Center · USCalifornia NanoSystems Institute · US

Funding

Non-Invasive Prenatal Diagnostics Based on Circulating TrophoblastsU01EB026421 · NIBIB · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PISARSKA, MARGARETA, TSENG, HSIAN-RONG · 2019 to 2023
$4.0M
Training Program in Endocrinology, Diabetes, and MetabolismT32DK007770 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI MELMED, SHLOMO · 1999 to 2022
$3.4M
Sex and gender differences in lupus - intersection between immunometabolism, epigenetic remodeling and cardiac involvementR01AI164504 · NIAID · CEDARS-SINAI MEDICAL CENTER · PI JEFFERIES, CAROLINE · 2021 to 2024
$2.3M
The impact of sex and gender on disease progression, from developmental originsR01AI154535 · NIAID · CEDARS-SINAI MEDICAL CENTER · PI PISARSKA, MARGARETA · 2020 to 2024
$2.3M
Placental Organoids to Model PreeclampsiaR01HL167268 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI S. Ananth Karumanchi · 2023 to 2026
$1.7M
Noncoding RNA regulation of the human placental transcriptome among the sexesR01HD091773 · NICHD · CEDARS-SINAI MEDICAL CENTER · PI PISARSKA, MARGARETA · 2017 to 2018
$900k
NHLBI NIH HHS R01 HL167268NIAID NIH HHS R01 AI154535NIAID NIH HHS R01 AI164504NIBIB NIH HHS U01 EB026421NICHD NIH HHS R01 HD091773NIDDK NIH HHS T32 DK007770
6 · The paper itself

Abstract

introductionFetal sex affects fetal and maternal health outcomes in pregnancy, but this connection remains poorly understood. As the placenta is the route of fetomaternal communication and derives from the fetal genome, placental gene expression sex differences may explain these outcomes.

objectivesWe utilized next generation sequencing to study the normal human placenta in both sexes in first and third trimester to generate a normative transcriptome based on sex and gestation. STUDY

designWe analyzed 124 first trimester (T1, 59 female and 65 male) and 43 third trimester (T3, 18 female and 25 male) samples for sex differences within each trimester and sex-specific gestational differences.

resultsPlacenta shows more significant sexual dimorphism in T1, with 94 T1 and 26 T3 differentially expressed genes (DEGs). The sex chromosomes contributed 60.6% of DEGs in T1 and 80.8% of DEGs in T3, excluding X/Y pseudoautosomal regions. There were 6 DEGs from the pseudoautosomal regions, only significant in T1 and all upregulated in males. The distribution of DEGs on the X chromosome suggests genes on Xp (the short arm) may be particularly important in placental sex differences. Dosage compensation analysis of X/Y homolog genes shows expression is primarily contributed by the X chromosome. In sex-specific analyses of first versus third trimester, there were 2815 DEGs common to both sexes upregulated in T1, and 3263 common DEGs upregulated in T3. There were 7 female-exclusive DEGs upregulated in T1, 15 female-exclusive DEGs upregulated in T3, 10 male-exclusive DEGs upregulated in T1, and 20 male-exclusive DEGs upregulated in T3. DISCUSSION: This is the largest cohort of placentas across gestation from healthy pregnancies defining the normative sex dimorphic gene expression and sex common, sex specific and sex exclusive gene expression across gestation. The first trimester has the most sexually dimorphic transcripts, and the majority were upregulated in females compared to males in both trimesters. The short arm of the X chromosome and the pseudoautosomal region is particularly critical in defining sex differences in the first trimester placenta. As pregnancy is a dynamic state, sex specific DEGs across gestation may contribute to sex dimorphic changes in overall outcomes.

Indexed as

High-Throughput Nucleotide SequencingPlacentaSex CharacteristicsAdultFemaleHumansMalePregnancyPregnancy Trimester, FirstPregnancy Trimester, ThirdRNA, MessengerSequence Analysis, RNATranscriptomeRNA, MessengerAbbreviations: CVSBenjamini-Hochberg false discovery rateChorionic villus samplingDEGsDifferentially expressed genesFCFDRFirst trimesterFold changeGestational differencesHigh-throughput mRNAseqHuman placentaIngenuity pathway analysisIPANext generation sequencingNormative atlasPARPCAPrincipal components analysisPseudoautosomal regionSex differencesT1T3Third trimesterTPMTranscriptomeTranscripts per million

Identifiers

PMID38537412
PMCPMC11262790
OpenAlexW4393029450

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.