Evidence map›Paper›PMID 33511402›Full record

ArticleBiology of reproduction2021

Environmentally relevant mixtures of phthalates and phthalate metabolites differentially alter the cell cycle and apoptosis in mouse neonatal ovaries†.

Genoa R Warner, Daryl D Meling, Kathy M De La Torre, Karen Wang, Jodi A Flaws

Open access · greenAbstract read
In one paragraph

Article in Biology of reproduction, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.6field-weighted citation impact, top 20% 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

17 citing papers in PubMed, 23 citations in OpenAlex.

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  6. Single-cell RNA-seq reveals that granulosa cells are a target of phthalate toxicity in the ovary.Toxicological sciences : an official journal of the Society of Toxicology · 2025
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  14. Chronic exposure to a mixture of phthalates shifts the white and brown adipose tissue phenotypes in female mice.Toxicological sciences : an official journal of the Society of Toxicology · 2023
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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

5 authors at 1 institution in 1 country.

Genoa R WarnerDepartment of Comparative Bioscience, University of Illinois, Urbana, IL, USA.
Daryl D MelingDepartment of Comparative Bioscience, University of Illinois, Urbana, IL, USA.
Kathy M De La TorreDepartment of Comparative Bioscience, University of Illinois, Urbana, IL, USA.
Karen WangDepartment of Comparative Bioscience, University of Illinois, Urbana, IL, USA.
Jodi A FlawsDepartment of Comparative Bioscience, University of Illinois, Urbana, IL, USA.
University of Illinois Urbana-Champaign · US

Funding

Research Training Program in Toxicology and Environmental HealthT32ES007326 · NIEHS · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI Jodi A. Flaws · 2000 to 2026
$8.7M
Phthalates and Ovarian ToxicityR01ES028661 · NIEHS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI FLAWS, JODI A. · 2018 to 2022
$1.8M
Mechanisms of Phthalate Toxicity in the OvaryR00ES031150 · NIEHS · NEW JERSEY INSTITUTE OF TECHNOLOGY · PI WARNER, GENOA R · 2022 to 2024
$1.1M
Mechanisms of Phthalate Toxicity in the OvaryK99ES031150 · NIEHS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI WARNER, GENOA R · 2020 to 2021
$194k
NIEHS NIH HHS K99 ES031150NIEHS NIH HHS R00 ES031150NIEHS NIH HHS R01 ES028661NIEHS NIH HHS T32 ES007326
6 · The paper itself

Abstract

Phthalates are a group of chemicals used as additives in various consumer products, medical equipment, and personal care products. Phthalates and their metabolites are consistently detected in humans, indicating widespread and continuous exposure to multiple phthalates. Thus, environmentally relevant mixtures of phthalates and phthalate metabolites were investigated to determine the effects of phthalates on the function of the ovary during the neonatal period of development. Neonatal ovaries from CD-1 mice were cultured with dimethyl sulphoxide (DMSO; vehicle control), phthalate mixture (0.1-100 μg/mL), or phthalate metabolite mixture (0.1-100 μg/mL). The phthalate mixture was composed of 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. The phthalate metabolite mixture was composed of 37% monoethyl phthalate, 19% mono(2-ethylhexyl) phthalate, 15% monobutyl phthalate, 10% monoisononyl phthalate, 10% monoisobutyl phthalate, and 8% monobenzyl phthalate. After 96 h of culture, ovaries were harvested for histological analysis of folliculogenesis, gene expression analysis of cell cycle and apoptosis regulators, and immune staining for cell proliferation and apoptosis. The metabolite mixture significantly decreased the number and percentage of abnormal follicles (100 μg/mL) compared to controls. The metabolite mixture also significantly increased the expression of cell cycle inhibitors (100 μg/mL) and the antiapoptotic factor Bcl2l10 (10 μg/mL) compared to controls. The phthalate mixture did not significantly alter gene expression or follicle counts, but ovaries exposed to the phthalate mixture (0.1 μg/mL) exhibited marginally significantly increased apoptosis as revealed by DNA fragmentation staining. Overall, these data show that parent phthalates and phthalate metabolites differentially impact ovarian function.

Indexed as

AnimalsAnimals, NewbornApoptosisCell CycleCells, CulturedEndocrine DisruptorsEnvironmental PollutantsFemaleGene Expression Regulation, DevelopmentalMiceOvaryPhthalic AcidsPregnancyEndocrine DisruptorsEnvironmental PollutantsPhthalic Acidsapoptosiscell cycleendocrine disruptionfolliculogenesismixturesneonatal ovaryovaryphthalatestoxicology

Identifiers

PMID33511402
PMCPMC8023422
OpenAlexW3121967743

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.