Evidence map›Paper›PMID 23077170›Full record

ArticleBiology of reproduction2012

Mono-(2-ethylhexyl) phthalate induces oxidative stress and inhibits growth of mouse ovarian antral follicles.

Wei Wang, Zelieann R Craig, Mallikarjuna S Basavarajappa, Katlyn S Hafner, Jodi A Flaws

Open access · bronzeAbstract read
In one paragraph

Article in Biology of reproduction, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 1 pooled it
5.2field-weighted citation impact, top 4% 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

86 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Ovarian toxic effects of micro- and nanoplastics (Review).Experimental and therapeutic medicine · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Mechanistic study on the role of multi-pathway autophagy in ovarian aging: literature review.Apoptosis : an international journal on programmed cell death · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. 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
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

26 more citing papers are in PubMed but not listed here.

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.

Wei WangDepartment of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, USA.
Zelieann R Craig
Mallikarjuna S Basavarajappa
Katlyn S Hafner
Jodi A Flaws
University of Illinois Urbana-Champaign · US

Funding

Endocrine disrupting chemicals and ovotoxicityR01ES019178 · NIEHS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI FLAWS, JODI A. · 2010 to 2014
$1.9M
Mechanisms of phthalate-induced ovarian follicle toxicityK99ES021467 · NIEHS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI CRAIG, ZELIEANN RIVERA · 2012 to 2013
$164k
NIEHS NIH HHS K99 ES021467NIEHS NIH HHS R01 ES019178NIEHS NIH HHS R01ES019178
6 · The paper itself

Abstract

Mono-(2-ethylhexyl) phthalate (MEHP) is the active metabolite of the most commonly used plasticizer, di-(2-ethylhexyl) phthalate, and is considered to be a reproductive toxicant. However, little is known about the effects of MEHP on ovarian antral follicles. Thus, the present study tested the hypothesis that MEHP inhibits follicle growth via oxidative stress pathways. The data indicate that MEHP increases reactive oxygen species (ROS) levels and inhibits follicle growth in antral follicles, whereas N-acetylcysteine (NAC; an antioxidant) restores ROS levels to control levels and rescues follicles from MEHP-induced inhibition of follicle growth. To further analyze the mechanism by which MEHP induces oxidative stress and inhibits follicle growth, the expression and activities of various key antioxidant enzymes (copper/zinc superoxide dismutase [SOD1], glutathione peroxidase [GPX], and catalase [CAT]) and the expression of key cell-cycle regulators (Ccnd2, Ccne1, and Cdk4) and apoptotic regulators (Bcl-2 and Bax) were compared in control and MEHP-treated follicles. The data indicate that MEHP inhibits the expression and activities of SOD1 and GPX; does not inhibit Cat expression; inhibits the expression of Ccnd2, Ccne1, Cdk4, and Bcl-2; but increases the expression of Bax compared to controls. Furthermore, NAC blocks these toxic effects of MEHP. Collectively, these data suggest that MEHP induces oxidative stress by disrupting the activities of antioxidant enzymes. This may lead to decreased expression of cell-cycle regulators and antiapoptotic regulators and increased expression of proapoptotic factors, which then may lead to inhibition of follicle growth.

Indexed as

AcetylcysteineAnimalsApoptosis Regulatory ProteinsCell Cycle ProteinsDiethylhexyl PhthalateDown-RegulationEndocrine DisruptorsFemaleFree Radical ScavengersInfertility, FemaleMiceMice, Inbred StrainsOvarian FollicleOxidative StressOxidoreductasesPlasticizersAcetylcysteineApoptosis Regulatory ProteinsCell Cycle ProteinsDiethylhexyl PhthalateEndocrine DisruptorsFree Radical Scavengersmono-(2-ethylhexyl)phthalateOxidoreductasesPlasticizersReactive Oxygen SpeciesRNA, Messenger

Identifiers

PMID23077170
PMCPMC4435432
OpenAlexW2156651118

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.