Evidence map›Paper›PMID 29571896›Full record

ArticleToxicology letters2018

Validation of an automated counting procedure for phthalate-induced testicular multinucleated germ cells.

Daniel J Spade, Cathy Yue Bai, Christy Lambright, Justin M Conley, Kim Boekelheide, L Earl Gray

Erratum issuedOpen access · greenAbstract readValidation Study
In one paragraph

Article in Toxicology letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.2field-weighted citation impact, top 26% 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

8 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. Phthalates toxicityHeliyon · 2025
    Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Daniel J SpadeDepartment of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA. Electronic address: daniel_spade@brown.edu.
Cathy Yue BaiDepartment of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA. Electronic address: yue_bai@brown.edu.
Christy LambrightReproductive Toxicology Branch, Toxicity Assessment Division, National Health and Environmental Effects Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA, USA. Electronic address: lambright.christy@epa.gov.
Justin M ConleyReproductive Toxicology Branch, Toxicity Assessment Division, National Health and Environmental Effects Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA, USA. Electronic address: conley.justin@epa.gov.
Kim BoekelheideDepartment of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA. Electronic address: kim_boekelheide@brown.edu.
L Earl GrayReproductive Toxicology Branch, Toxicity Assessment Division, National Health and Environmental Effects Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA, USA. Electronic address: gray.earl@epa.gov.
Brown University · USEnvironmental Protection Agency · US

Funding

Vapor Pressures and Thermodynamic Properties of Complex Organic MixturesP42ES013660 · NIEHS · BROWN UNIVERSITY · PI BOEKELHEIDE, KIM · 2005 to 2020
$37.7M
TRAINING IN ENVIRONMENTAL PATHOLOGYT32ES007272 · NIEHS · BROWN UNIVERSITY · PI ZHITKOVICH, ANATOLY · 1992 to 2021
$7.5M
Retinoic Acid Signaling Disruption by Phthalates in Human and Rodent Fetal TestisK99ES025231 · NIEHS · BROWN UNIVERSITY · PI SPADE, DANIEL JAMES · 2016 to 2017
$200k
NIEHS NIH HHS K99 ES025231NIEHS NIH HHS P42 ES013660NIEHS NIH HHS T32 ES007272
6 · The paper itself

Abstract

In utero exposure to certain phthalate esters results in testicular toxicity, characterized at the tissue level by induction of multinucleated germ cells (MNGs) in rat, mouse, and human fetal testis. Phthalate exposures also result in a decrease in testicular testosterone in rats. The anti-androgenic effects of phthalates have been more thoroughly quantified than testicular pathology due to the significant time requirement associated with manual counting of MNGs on histological sections. An automated counting method was developed in ImageJ to quantify MNGs in digital images of hematoxylin-stained rat fetal testis tissue sections. Timed pregnant Sprague Dawley rats were exposed by daily oral gavage from gestation day 17 to 21 with one of eight phthalate test compounds or corn oil vehicle. Both the manual counting method and the automated image analysis method identified di-n-butyl phthalate, butyl benzyl phthalate, dipentyl phthalate, and di-(2-ethylhexyl) phthalate as positive for induction of MNGs. Dimethyl phthalate, diethyl phthalate, the brominated phthalate di-(2-ethylhexyl) tetrabromophthalate, and dioctyl terephthalate were negative. The correlation between automated and manual scoring metrics was high (r = 0.923). Results of MNG analysis were consistent with these compounds' anti-androgenic activities, which were confirmed in an ex vivo testosterone production assay. In conclusion, we have developed a reliable image analysis method that can be used to facilitate dose-response studies for the reproducible induction of MNGs by in utero phthalate exposure.

Indexed as

AnimalsDibutyl PhthalateDose-Response Relationship, DrugFetusGerm CellsMalePhthalic AcidsRatsRats, Sprague-DawleyTestisTestosteronebutylbenzyl phthalateDibutyl Phthalatediethyl phthalatedimethyl phthalatePhthalic AcidsTestosteroneMultinucleated germ cellsPhthalate estersQuantitative pathology

Identifiers

PMID29571896
PMCPMC5921076
OpenAlexW2791522975

What OpenQuestion 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 OpenQuestion graph.