Evidence map›Paper›PMID 41055590›Full record

ArticleBiology of reproduction2025

Uterine histotroph and conceptus development. V. Comparative analyses of arginine-mediated transcriptomic reprogramming in conceptus trophectoderm of pigs and sheep†.

Sudikshya Paudel, Xiukun Wang, Hongyao Yu, Tianyuan Wang, Xinxia Peng, Fuller W Bazer, Robert C Burghardt, Guang Hu, Xiaoqiu Wang

Abstract readComparative Study
In one paragraph

Article in Biology of reproduction, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. 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

9 authors.

Sudikshya PaudelDepartment of Animal Science, North Carolina State University, Raleigh, NC, USA.
Xiukun WangEpigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Hongyao YuEpigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Tianyuan WangIntegrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.ORCID 0000-0002-3970-0771
Xinxia PengDepartment of Molecular Biomedical Sciences and Bioinformatics Research Center, North Carolina State University, Raleigh, NC, USA.ORCID 0000-0002-0117-3582
Fuller W BazerDepartment of Animal Science, Texas A&M University, College Station, TX, USA.ORCID 0000-0002-5823-5086
Robert C BurghardtDepartment of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA.ORCID 0000-0003-1021-8444
Guang HuEpigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Xiaoqiu WangDepartment of Animal Science, North Carolina State University, Raleigh, NC, USA.ORCID 0000-0001-9660-528X

Funding

Deciphering molecular mechanisms controlling age-associated uterine adaptabilityto pregnancyR01HD111463 · NICHD · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI Xiaoqiu Wang · 2023 to 2026
$2.5M
TET2 as a novel epigenetic regulator for uterine function and fertilityR03HD112581 · NICHD · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI WANG, XIAOQIU · 2023 to 2023
$152k
Agriculture and Food Research Initiative Competitive 2022-67015-36491NICHD NIH HHS R01 HD111463NICHD NIH HHS R03 HD112581NIH HHS R01HD111463NIH HHS R03HD112581North Carolina Agricultural Foundation 665143North Carolina Agricultural Foundation 665163North Carolina State UniversityU.S. Department of Agriculture National Institute of Food and Agriculture
6 · The paper itself

Abstract

In ungulates such as pigs and sheep, blastocyst elongation is essential for implantation, driven by coordinated trophoblast proliferation, cytoskeletal remodeling, and nutrient signaling. L-arginine (Arg), a conditionally essential amino acid enriched in uterine histotroph during early pregnancy, plays a key role in conceptus development; however, its genomic effects on the trophectoderm are poorly defined. Therefore, we investigated Arg-responsive transcriptomic changes in porcine (pTr2) and ovine (oTr1) trophectoderm cells using RNA-seq and integrative pathway analyses. Arg significantly stimulated proliferation in both cell types in a non-linear, dose-dependent manner, with maximal effects at 0.2 mM, consistent with physiological levels. Transcriptomic profiling identified 2723 and 5369 differentially expressed genes in pTr2 and oTr1 cells, respectively, encompassing genes involved in cell proliferation, metabolism, cytoskeletal remodeling, and implantation. Canonical pathway and upstream regulator analyses revealed both conserved and species-specific responses to Arg, including shared activation of actin cytoskeleton and adrenomedullin signaling and suppression of p53 signaling. Species-specific enrichment of cholesterol biosynthesis (pigs) and interferon signaling (sheep) further highlighted divergent strategies for pregnancy recognition. Comparative analyses identified 615 commonly regulated differentially expressed genes and highlighted O-linked N-acetylglucosamine transferase as a conserved upstream regulator, implicating nutrient-responsive O-GlcNAcylation in trophectoderm function. Arg promoted gene programs supporting mitosis, oxidative phosphorylation, and extracellular matrix remodeling while repressing pathways related to apoptosis and pluripotency. These results advance understanding of how Arg activates conserved transcriptional networks to support trophectoderm proliferation and differentiation, while also fine-tuning species-specific pathways aligned with pregnancy recognition and implantation of conceptuses in sheep and pigs.

Indexed as

ArginineEmbryonic DevelopmentTranscriptomeTrophoblastsUterusAnimalsFemalePregnancySheepSwineArginineargininepigssheeptranscriptometrophectoderm cells

Identifiers

PMID41055590
PMCPMC12706476

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Registered trials

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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 OpenQuestion graph.