Evidence map›Paper›PMID 40121545›Full record

ArticleBiology of reproduction2025

Developmental programming: mechanisms of early exposure to real-life chemicals in biosolids on offspring ovarian dynamics†.

Yiran Zhou, Katherine M Halloran, Michelle Bellingham, Richard G Lea, Neil P Evans, Kevin D Sinclair, Peter Smith, Vasantha Padmanabhan

Abstract read
In one paragraph

Article in Biology of reproduction, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
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.

Yiran ZhouDepartment of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
Katherine M HalloranDepartment of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
Michelle BellinghamSchool of Biodiversity One Health and Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, UK.
Richard G LeaSchools of Biosciences and Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire LE12 5RD, UK.
Neil P EvansSchool of Biodiversity One Health and Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, UK.
Kevin D SinclairSchools of Biosciences and Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire LE12 5RD, UK.
Peter SmithAgricultural Systems and Reproduction, Animal Science, Invermay Agricultural Centre, AgResearch Ltd, Mosgiel, Otago, New Zealand.
Vasantha PadmanabhanDepartment of Pediatrics, University of Michigan, Ann Arbor, MI, USA.

Funding

Strategic Vision & Impact on Environmental HealthP30ES017885 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Dana Dolinoy · 2011 to 2026
$21.3M
ENVIRONMENTAL TOXICOLOGY PRE/POST DOCTORAL RES.TRAININGT32ES007062 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Justin Adam Colacino · 1985 to 2026
$10.5M
Transgenerational consequences of pre-conceptional and in utero exposure to real-life chemical mixtures on fertility and metabolic healthR01ES030374 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI EVANS, NEIL PRICE, LEA, RICHARD · 2020 to 2024
$2.3M
National Institute of Environmental Health Sciences of the National Institutes of Health T32ES007062NIEHS NIH HHS P30 ES017885NIEHS NIH HHS R01 ES030374NIEHS NIH HHS T32 ES007062
6 · The paper itself

Abstract

Female reproductive capacity is shaped by ovarian reserve and patterns of follicle development. Ovarian reserve depletion occurs by follicle activation and atresia, which are affected by environmental chemicals (ECs). Because humans are simultaneously exposed to hundreds of ECs, real-life exposure models are essential to assess patterns of atresia after EC exposure. Previous findings demonstrate maternal preconceptional and gestational EC exposure via biosolids increases activation rate and reduces primordial follicle pool in juvenile, but not adult sheep. We hypothesized that this shift involves changes in death and proliferative pathways that impact follicle atresia from juvenile to adult life. Ovaries were collected from juvenile (9.5 weeks) and adult (2.5 years) offspring from ewes grazed on biosolids-treated pasture (BTP) or inorganic fertilizer-treated pasture (Control). Follicular atresia was assessed through morphological characteristics and molecular death pathways, including expression of markers for apoptosis (CASP3), autophagy (LC3), ferroptosis (GPX4), and proliferation (Ki67). There were higher levels of apoptosis and autophagy, and lower proliferation, in juvenile BTP offspring compared to controls. In adult BTP offspring, apoptosis and proliferation were similar, autophagy was lower, and ferroptosis was higher compared to controls. Apoptosis was lower and ferroptosis was higher in adults than juveniles, regardless of treatment. Adult BTP offspring had lower autophagy and similar proliferation levels than juvenile BTP offspring. These findings suggest that lower autophagy and lack of decrease in proliferation contribute to normalization of activation rate and ovarian pool in BTP adult offspring and supportive of lasting impacts of gestational EC exposure on offspring follicular health.

Indexed as

Environmental PollutantsMaternal ExposureOvaryPrenatal Exposure Delayed EffectsAnimalsApoptosisAutophagyFemaleFollicular AtresiaOvarian FollicleOvarian ReservePregnancySheepEnvironmental Pollutantsbiosolidsenvironmental chemical mixturesfollicular atresiaovarian follicles

Identifiers

PMID40121545
PMCPMC12191645

What OpenQuestion holds

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Registered trials

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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.