ArticleBiology of reproduction2018
Paternal developmental toxicant exposure is associated with epigenetic modulation of sperm and placental Pgr and Igf2 in a mouse model.
Article in Biology of reproduction, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 3 of them syntheses that pooled it.
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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.
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.
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Who cites it
26 citing papers in PubMed, 3 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- A systematic review on the role of paternal factors in human placental development, function, and pregnancy-related disorders.Journal of assisted reproduction and genetics · 2025Pooled it
- Pooled it
- Transgenerational epigenetic effects from male exposure to endocrine-disrupting compounds: a systematic review on research in mammals.Clinical epigenetics · 2020Pooled it
- A Paternal Fish Oil Diet Preconception Modulates the Gut Microbiome and Attenuates Necrotizing Enterocolitis in Neonatal Mice.Marine drugs · 2022Trial
- Dad's Diet Shapes the Future: How Paternal Nutrition Impacts Placental Development and Childhood Metabolic Health.Molecular nutrition & food research · 2025Review
- Review
- Article
- Transgenerational Epigenetic DNA Methylation Editing and Human Disease.Biomolecules · 2023Review
- Inheritance of paternal lifestyles and exposures through sperm DNA methylation.Nature reviews. Urology · 2023Review
- A Paternal Fish Oil Diet Preconception Reduces Lung Inflammation in a Toxicant-Driven Murine Model of New Bronchopulmonary Dysplasia.Marine drugs · 2023Article
- Prenatal Androgen Excess Induces Multigenerational Effects on Female and Male Descendants.Clinical medicine insights. Endocrinology and diabetes · 2023Article
- Prenatal paternal anxiety symptoms predict child DHEA levels and internalizing symptoms during adrenarche.Frontiers in behavioral neuroscience · 2023Article
- Sex differences in the intergenerational inheritance of metabolic traits.Nature metabolism · 2022Review
- Uncovering Evidence: Associations between Environmental Contaminants and Disparities in Women's Health.International journal of environmental research and public health · 2022Review
- Paternal epigenetic influences on placental health and their impacts on offspring development and disease.Frontiers in genetics · 2022Review
- A Preconception Paternal Fish Oil Diet Prevents Toxicant-Driven New Bronchopulmonary Dysplasia in Neonatal Mice.Toxics · 2021Article
- Male factor infertility and placental pathology in singleton live births conceived with in vitro fertilization.Journal of assisted reproduction and genetics · 2021Article
- Experimental Evidence of 2,3,7,8-Tetrachlordibenzo-p-Dioxin (TCDD) Transgenerational Effects on Reproductive Health.International journal of molecular sciences · 2021Review
- The Potential Relationship Between Environmental Endocrine Disruptor Exposure and the Development of Endometriosis and Adenomyosis.Frontiers in physiology · 2021Review
- Transgenerational disease specific epigenetic sperm biomarkers after ancestral exposure to dioxin.Environmental research · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Preterm birth (PTB), parturition prior to 37 weeks' gestation, is the leading cause of neonatal mortality. The causes of spontaneous PTB are poorly understood; however, recent studies suggest that this condition may arise as a consequence of the parental fetal environment. Specifically, we previously demonstrated that developmental exposure of male mice (F1 animals) to the environmental endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was associated with reduced sperm quantity/quality in adulthood and control female partners frequently delivered preterm. Reproductive defects persisted in the F2 and F3 descendants, and spontaneous PTB was common. Reproductive changes in the F3 males, the first generation without direct TCDD exposure, suggest the occurrence of epigenetic alterations in the sperm, which have the potential to impact placental development. Herein, we conducted an epigenetic microarray analysis of control and F1 male-derived placentae, which identified 2171 differentially methylated regions, including the progesterone receptor (Pgr) and insulin-like growth factor (Igf2). To assess if Pgr and Igf2 DNA methylation changes were present in sperm and persist in future generations, we assessed methylation and expression of these genes in F1/F3 sperm and F3-derived placentae. Although alterations in methylation and gene expression were observed, in most tissues, only Pgr reached statistical significance. Despite the modest gene expression changes in Igf2, offspring of F1 and F3 males consistently exhibited IUGR. Taken together, our data indicate that paternal developmental TCDD exposure is associated with transgenerational placental dysfunction, suggesting epigenetic modifications within the sperm have occurred. An evaluation of additional genes and alternative epigenetic mechanisms is warranted.
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Registered trials
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