Overlapping but distinct effects of genistein and ethinyl estradiol (EE2) in female Sprague–Dawley rats in multigenerational reproductive and chronic toxicity studies
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Genistein and ethinyl estradiol (EE(2)) were examined in multigenerational reproductive and chronic toxicity studies that had different treatment intervals among generations. Sprague-Dawley rats received genistein (0, 5, 100, or 500 ppm) or EE(2) (0, 2, 10, or 50 ppb) in a low phytoestrogen diet. Nonneoplastic effects in females are summarized here. Genistein at 500 ppm and EE(2) at 50 ppb produced similar effects in continuously exposed rats, including decreased body weights, accelerated vaginal opening, and altered estrous cycles in young animals. At the high dose, anogenital distance was subtly affected by both compounds, and a reduction in litter size was evident in genistein-treated animals. Genistein at 500 ppm induced an early onset of aberrant cycles relative to controls in the chronic studies. EE(2) significantly increased the incidence of uterine lesions (atypical focal hyperplasia and squamous metaplasia). These compound-specific effects appeared to be enhanced in the offspring of prior exposed generations.
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EE2-treated rats exhibited a significantly lower proportion of days in diestrus and a higher percentage of extended estrus transitions, similar to that reported for dietary EE2 treatment in rats and DES treatment in mice.
“Here, EE 2 -treated rats exhibited a significantly lower proportion of days in diestrus and a higher percentage of extended estrus transitions, similar to that reported for dietary EE 2 treatment in rats (Delclos et al., 2009) and PNDs 15-18 DES treatment in mice (Nikaido et al., 2005) as well as similar but chronic EE 2 treatment (Delclos et al., 2014).”
From Developmental Treatment with Ethinyl Estradiol, but Not Bisphenol A, Causes Alterations in Sexually Dimorphic Behaviors in Male and Female Sprague Dawley Rats (2014) · cites this paper as Delclos et al., 2009
Administration of EE2 during development can affect a variety of reproductive anatomical and physiological endpoints in mice and rats.
“administration of EE2 during development can affect a variety of reproductive anatomical and physiological endpoints in mice and rats [20, 36–46]”
From Developmental exposure to low levels of ethinylestradiol affects social play in juvenile male rats (2020) · cites this paper as [36]
Lactational exposure was as effective or more effective than gestational exposure.
“In general, lactational exposure was as effective or more effective than gestational exposure, which is in contrast with studies reviewed by Delclos et al. [36] reporting a limited transfer of EE2 to newborns via milk in humans and rats.”
From Developmental exposure to low levels of ethinylestradiol affects social play in juvenile male rats (2020) · cites this paper as [36]
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Use of Ranks in One-Criterion Variance Analysis
Kruskal, W. H., & Wallis, W. A. (1952) · Journal of the American Statistical Association · doi:10.1080/01621459.1952.10483441 · Cited by 13,912 · see citing works
Metabolic fuels and reproduction in female mammals
Wade, G. N., & Schneider, J. E. (1992) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(05)80183-6 · Cited by 686 · see citing works
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- Authors
- Delclos, K. B., Weis, C. C., Bucci, T. J., Olson, G., Mellick, P., Sadovova, N., Latendresse, J. R., Thorn, B., & Newbold, R. R.
- Affiliations
- National Center for Toxicological Research (US)
- National Institute of Environmental Health Sciences (US)
- Corresponding author
- Delclos, K. Barry
- ORCID
- Delclos, K. Barry
- Venue
- Reproductive Toxicology
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 27
- Issue
- 2
- Pages
- 117-132
- ISSN
- 0890-6238 (ISSN-L)
- PMC
- PMC2706590
- OpenAlex
- W2022165854
- Cited by
- 77
- References
- 3
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 2 · 2020: 6 · 2019: 2 · 2018: 6 · 2017: 4 · 2016: 7 · 2015: 7 · 2014: 10 · 2013: 4 · 2012: 4
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Reproductive Toxicology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- genistein, ethinyl estradiol, phytoestrogens, chronic toxicity, female reproductive tract, estrous cycle, vaginal opening, anogenital distance, litter size, uterine lesions, squamous metaplasia, offspring effects, treatment interval
- MeSH terms
- Animals, Body Weight, Dose-Response Relationship, Drug, Eating, Endometrial Hyperplasia, Estrus, Ethinyl Estradiol, Female, Litter Size, Metaplasia, Pregnancy, Reproduction, Sexual Behavior, Animal, Sexual Maturation, Time Factors, Uterus, Vagina, Rats, Sprague-Dawley, Genistein, Rats, Endocrine Disruptors
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