Evidence map›Paper›PMID 36189433›Full record

ArticleCurrent research in toxicology2022

Interaction between mono-(2-ethylhexyl) phthalate and retinoic acid alters Sertoli cell development during fetal mouse testis cord morphogenesis.

Maha A Alhasnani, Skylar Loeb, Susan J Hall, Zachary Caruolo, Faith Simmonds, Amanda E Solano, Daniel J Spade

Abstract read
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In one paragraph

Article in Current research in toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. In vitro models of the male reproductive system: applications for developmental and reproductive toxicology.Toxicological sciences : an official journal of the Society of Toxicology · 2025
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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

7 authors.

Maha A AlhasnaniDepartment of Pathology and Laboratory Medicine, Brown University, Box G-E5, Providence, RI 02912, USA.
Skylar LoebDepartment of Pathology and Laboratory Medicine, Brown University, Box G-E5, Providence, RI 02912, USA.
Susan J HallDepartment of Pathology and Laboratory Medicine, Brown University, Box G-E5, Providence, RI 02912, USA.
Zachary CaruoloDepartment of Pathology and Laboratory Medicine, Brown University, Box G-E5, Providence, RI 02912, USA.
Faith SimmondsDepartment of Pathology and Laboratory Medicine, Brown University, Box G-E5, Providence, RI 02912, USA.
Amanda E SolanoDepartment of Pathology and Laboratory Medicine, Brown University, Box G-E5, Providence, RI 02912, USA.
Daniel J SpadeDepartment of Pathology and Laboratory Medicine, Brown University, Box G-E5, Providence, RI 02912, USA.

Funding

Retinoic Acid Signaling Disruption by Phthalates in Human and Rodent Fetal TestisR00ES025231 · NIEHS · BROWN UNIVERSITY · PI SPADE, DANIEL JAMES · 2018 to 2020
$725k
NIEHS NIH HHS R00 ES025231
6 · The paper itself

Abstract

Phthalic acid esters (phthalates) are a class of industrial chemicals that cause developmental and reproductive toxicity, but there are significant gaps in knowledge of phthalate toxicity mechanisms. There is evidence that phthalates disrupt retinoic acid signaling in the fetal testis, potentially disrupting control of spatial and temporal patterns of testis development. Our goal was to determine how a phthalate would interact with retinoic acid signaling during fetal mouse testis development. We hypothesized that mono-(2-ethylhexyl) phthalate (MEHP) would exacerbate the adverse effect of all-trans retinoic acid (ATRA) on seminiferous cord development in the mouse fetal testis. To test this hypothesis, gestational day (GD) 14 C57BL/6 mouse testes were isolated and cultured on media containing MEHP, ATRA, or a combination of both compounds. Cultured testes were collected for global transcriptome analysis after one day in culture and for histology and immunofluorescent analysis of Sertoli cell differentiation after three days in culture. ATRA disrupted seminiferous cord morphogenesis and induced aberrant FOXL2 expression. MEHP alone had no significant effect on cord development, but combined exposure to MEHP and ATRA increased the number of FOXL2-positive cells, reduced seminiferous cord number, and increased testosterone levels, beyond the effect of ATRA alone. In RNA-seq analysis, ATRA treatment and MEHP treatment resulted in differential expression of genes 510 and 134 genes, respectively, including 70 common differentially expressed genes (DEGs) between the two treatments, including genes with known roles in fetal testis development. MEHP DEGs included RAR target genes, genes involved in angiogenesis, and developmental patterning genes, including members of the homeobox superfamily. These results support the hypothesis that MEHP modulates retinoic acid signaling in the mouse fetal testis and provide insight into potential mechanisms by which phthalates disrupt seminiferous cord morphogenesis.

Indexed as

ATRA, All-trans retinoic acid. CAS # 302-79-4DMSO, dimethyl sulfoxideFetal testis developmentGD, gestational dayGO, Gene OntologyIPA, Ingenuity Pathway AnalysisITCN, Image-based Tool for Counting NucleiMEHP, mono-(2-ethylheyxl) phthalate. CAS # 4376-20-9MNGs, multinucleated germ cellsPhthalate toxicityPVC, polyvinyl chlorideRetinoic acidSertoli cellTDS, testicular dysgenesis syndrome

Identifiers

PMID36189433
PMCPMC9520016

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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.