Evidence map›Paper›PMID 39739409›Full record

ArticleEnvironmental health perspectives2024

Two Hits of EDCs Three Generations Apart: Evaluating Multigenerational Anxiety-Like Behavioral Phenotypes in Female Rats Exposed to Aroclor 1221 and Vinclozolin.

Emily N Hilz, Ross Gillette, Lindsay M Thompson, Lexi Ton, Timothy Pham, M Nicole Kunkel, David Crews, Andrea C Gore

Abstract read
In one paragraph

Article in Environmental health perspectives, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. 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

8 authors.

Emily N HilzDivision of Pharmacology & Toxicology, The University of Texas at Austin, Austin, Texas, USA.ORCID 0000-0002-1380-4919
Ross GilletteDivision of Pharmacology & Toxicology, The University of Texas at Austin, Austin, Texas, USA.
Lindsay M ThompsonDivision of Pharmacology & Toxicology, The University of Texas at Austin, Austin, Texas, USA.
Lexi TonDivision of Pharmacology & Toxicology, The University of Texas at Austin, Austin, Texas, USA.
Timothy PhamDivision of Pharmacology & Toxicology, The University of Texas at Austin, Austin, Texas, USA.
M Nicole KunkelDivision of Pharmacology & Toxicology, The University of Texas at Austin, Austin, Texas, USA.
David CrewsDepartment of Integrative Biology, The University of Texas at Austin, Austin, Texas, USA.
Andrea C GoreDivision of Pharmacology & Toxicology, The University of Texas at Austin, Austin, Texas, USA.

Funding

Functional and epigenetic effects of preconceptional EDCs on the female HPG axisR01ES029464 · NIEHS · UNIVERSITY OF TEXAS AT AUSTIN · PI GORE, ANDREA C · 2019 to 2023
$3.2M
Environmental Epigenetics of EDCs: From Germline to BrainR35ES035024 · NIEHS · UNIVERSITY OF TEXAS AT AUSTIN · PI Andrea C Gore · 2023 to 2026
$3.1M
Ancestral Exposures/Modern Responses to EDCsR01ES023254 · NIEHS · UNIVERSITY OF TEXAS AT AUSTIN · PI CREWS, DAVID P, GORE, ANDREA C · 2013 to 2017
$1.9M
NIEHS NIH HHS R01 ES023254NIEHS NIH HHS R01 ES029464NIEHS NIH HHS R35 ES035024
6 · The paper itself

Abstract

backgroundEndocrine-disrupting chemicals (EDCs) are exogenous chemical compounds that interfere with the normal function of the endocrine system and are linked to direct and inherited adverse effects in both humans and wildlife. Legacy EDCs such as polychlorinated biphenyls (PCBs) are no longer used yet remain detectable in biological specimens around the world; concurrently, we are exposed to newer EDCs like the fungicide vinclozolin (VIN). This combination of individuals' direct environmental chemical exposures and any heritable changes caused by their ancestors' chemical exposures leads to a layered pattern of both direct and ancestrally inherited exposures that might have cumulative effects over generations.

objectivesWe assessed consequences of both direct and ancestral exposure to EDCs over six generations, examining anxiety-like behaviors in maternal and paternal lines of female rats. We used the "two hits, three generations apart" multigenerational exposure model to explore how two distinct EDCs-the weakly estrogenic PCB mixture Aroclor 1221 (A1221) and the antiandrogenic VIN-interact on behavior across generations. We also explored serum hormones as a potential mechanism.

methodsRats were prenatally exposed to A1221, VIN, or vehicle (DMSO) in the F1 generation, and a second exposure (same or different) was administered to the F4 generation. Anxiety-like behavior was measured in the Open Field test, Light:Dark box, and Elevated Plus Maze in the F1, F3, F4, and F6 generations. Serum concentrations of estradiol and corticosterone were analyzed.

resultsBehavioral effects were not detectable in the F1 generation but emerged and became more robust across generations. Rats with ancestral VIN exposure demonstrated less anxiety-like behavior in the F3 paternal line in comparison with controls. Rats exposed to ancestral then prenatal A1221/VIN and VIN/A1221 had more anxiety-like behavior in the F4 maternal line, and those with two ancestral hits of VIN/VIN had more anxiety in the F6 paternal line, in comparison with controls. DISCUSSION: Our findings suggest that anxiety-like behavioral phenotypes can manifest in rats following germline exposure to EDCs and that subsequent exposures across generations can intensify these effects in a lineage-dependent manner. https://doi.org/10.1289/EHP15621.

Indexed as

AnxietyAroclorsBehavior, AnimalEndocrine DisruptorsOxazolesAnimalsEnvironmental PollutantsFemaleFungicides, IndustrialMalePhenotypePregnancyRatsaroclor 1221AroclorsEndocrine DisruptorsEnvironmental PollutantsFungicides, IndustrialOxazolesvinclozolin

Identifiers

PMID39739409
PMCPMC11687612

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.