ArticleToxicology and applied pharmacology2022
Perfluorooctanoic acid (PFOA) promotes follicular growth and alters expression of genes that regulate the cell cycle and the Hippo pathway in cultured neonatal mouse ovaries.
Article in Toxicology and applied pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Time-Dependent Effects of PFAS and Their Mixtures on Ovarian Epithelial Cell Proliferation and Chemotherapeutic Response.International journal of molecular sciences · 2026Article
- Investigating ovarian effects of perfluorooctanoic acid in postpubertal pigs during thermal neutral and heat stress conditions.Journal of animal science · 2026Article
- From algorithm to verification: based on network toxicology and machine learning, the immunomodulatory role of IGFBP1/MKI67/C9 in perfluorooctanoic acid-induced osteoarthritis was discovered, and a diagnostic model was constructed.Frontiers in immunology · 2026Article
- Living in a chemical cocktail: real-world mixture exposures and their impact on ovarian function.The Journal of reproduction and development · 2026Review
- PFAS exposure and reproductive dysfunction: implications for outcomes in assisted reproductive technologies.Frontiers in endocrinology · 2026Review
- SOD1, A Crucial Protein for Neural Biochemistry: Dysfunction and Risk of Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2025Review
- Distribution of perfluorooctanoic acid in exposed female postpubertal pigs in thermal neutral or heat-stressed conditions.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Early-life exposure to PCBs and PFAS exerts negative effects on the developing central nervous system.Journal of hazardous materials · 2025Review
- Sex differences in ischemic heart disease and evidence gathering related to exposure risk, prevention, and treatment of per- and poly-fluoroalkyl substances.Frontiers in public health · 2025Article
- Adolescent exposure to a mixture of per- and polyfluoroalkyl substances (PFAS) depletes the ovarian reserve, increases ovarian fibrosis, and alters the Hippo pathway in adult female mice.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- An environmentally relevant mixture of per- and polyfluoroalkyl substances (PFAS) impacts proliferation, steroid hormone synthesis, and gene transcription in primary human granulosa cells.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Review
- Perfluorooctanoic acid (PFOA) inhibits steroidogenesis and mitochondrial function in bovine granulosa cells in vitro.Environmental pollution (Barking, Essex : 1987) · 2023Article
- FHL2 deficiency impairs follicular development and fertility by attenuating EGF/EGFR/YAP signaling in ovarian granulosa cells.Cell death & disease · 2023Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Perfluorooctanoic acid (PFOA) is a synthetic chemical resistant to biodegradation and is environmentally persistent. PFOA is found in many consumer products and is a major source of water contamination. While PFOA has been identified as a contaminant of concern for reproductive health, little is known about the effects of PFOA on ovarian follicular development and growth. Recent evidence indicates that the Hippo pathway is an important regulator of ovarian physiology. Here, we investigated the effects of PFOA on ovarian folliculogenesis during the neonatal period of development and potential impacts on the Hippo signaling pathway. Post-natal day 4 (PND4) neonatal ovaries from CD-1 mice were cultured with control medium (DMSO <0.01% final concentration) or PFOA (50 μM or 100 μM). After 96 h, ovaries were collected for histological analysis of folliculogenesis, gene and protein expression, and immunostaining. Results revealed that PFOA (50 μM) increased the number of secondary follicles, which was accompanied by increases in mRNA transcripts and protein of marker of proliferation marker Ki67 with no impacts on apoptosis markers Bax, Bcl2, or cleaved caspase-3. PFOA treatment (50 μM and 100 μM) stimulated an upregulation of transcripts for cell cycle regulators Ccna2, Ccnb2, Ccne1, Ccnd1, Ccnd2, and Ccnd3. PFOA also increased abundance of transcripts of Hippo pathway components Mst1/2, Lats1, Mob1b, Yap1, and Taz, as well as downstream Hippo pathway targets Areg, Amotl2, and Cyr61, although it decreased transcripts for anti-apoptotic Birc5. Inhibition of the Hippo pathway effector YAP1 with Verteporfin resulted in the attenuation of PFOA-induced follicular growth and proliferation. Together, these findings suggest that occupationally relevant levels of PFOA (50 μM) can stimulate follicular activation in neonatal ovaries potentially through activation of the Hippo pathway.
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