Early postnatal genistein administration permanently affects nitrergic and vasopressinergic systems in a sex-specific way
Open accessAbstract
Genistein (GEN) is a natural xenoestrogen (isoflavonoid) that may interfere with the development of estrogen-sensitive neural circuits. Due to the large and increasing use of soy-based formulas for babies (characterized by a high content of GEN), there are some concerns that this could result in an impairment of some estrogen-sensitive neural circuits and behaviors. In a previous study, we demonstrated that its oral administration to female mice during late pregnancy and early lactation induced a significant decrease of nitric oxide synthase-positive cells in the amygdala of their male offspring. In the present study, we have used a different experimental protocol mimicking, in mice, the direct precocious exposure to GEN. Mice pups of both sexes were fed either with oil, estradiol or GEN from birth to postnatal day 8. Nitric oxide synthase and vasopressin neural systems were analyzed in adult mice. Interestingly, we observed that GEN effect was time specific (when compared to our previous study), sex specific, and not always comparable to the effects of estradiol. This last observation suggests that GEN may act through different intracellular pathways. Present results indicate that the effect of natural xenoestrogens on the development of the brain may be highly variable: a plethora of neuronal circuits may be affected depending on sex, time of exposure, intracellular pathway involved, and target cells. This raises concern on the possible long-term effects of the use of soy-based formulas for babies, which may be currently underestimated.
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GEN alters AVP and OT neuron numbers and innervation of sexually dimorphic regions associated with social and aggressive behaviors in multiple species, and is anxiogenic in males of multiple species.
“Altered AVP and OT neuron numbers and innervation of sexually dimorphic regions associated with social and aggressive behaviors in multiple species; anxiogenic in males of multiple species”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [74]
The Paraventricular nucleus results (page unavailable) report that genistein increased AVP-positive cell numbers in female mice and decreased them in males; the figure caption also reports increased AVP immunoreactivity in the female bed nucleus of the stria terminalis. The paper does not establish changes in OT neurons or effects across multiple species. Its Introduction mentions altered anxiety behavior in male mice from an earlier study, but does not specify an anxiogenic effect or establish one in multiple species. (LLM, conf=0.89)
Experimental — accuracy not yet measuredPostnatal GEN eliminated the sexually dimorphic density of AVP-ir neurons in the medial parvicellular part of the PVN (PaMP), with higher numbers in females and lower numbers in males.
“Notably, the sexually dimorphic density of AVP-ir neurons in the medial parvicellular part of the PVN (PaMP) was eliminated by postnatal GEN, with higher numbers in females and lower numbers in males.”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [74]
The Paraventricular nucleus results report that postnatal GEN increased AVP-positive cell numbers in female PaMP and decreased them in male PaMP; the Discussion describes an inverted phenotype. But the paper does not establish a pre-treatment PaMP sex dimorphism that GEN eliminated, and the difference between GEN-treated females and males fell just short of significance (p=0.054). (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn CD1 mice, oral intake of 50 μg/kg GEN in the first week of life slightly but significantly increased AVP-ir in the female BnST but did not impact sexually dimorphic AVP innervation of the LS.
“For example, in CD1 mice, oral intake of 50 µg/kg GEN in the first week of life slightly, but significantly increased AVP-ir in the female BnST but did not impact the sexually dimorphic AVP innervation of the LS (74).”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [74]
The Animals and treatment sections (page unavailable) describe CD-1 mice fed GEN from postnatal day 1 to 8. The AVP results report a significant increase in female BST AVP immunoreactivity and no treatment effect on sexually dimorphic LS innervation. However, the treatment section specifies 50 mg/kg GEN, not the claimed 50 µg/kg; 50 µg/kg was the estradiol dose. (LLM, conf=0.93)
Experimental — accuracy not yet measuredNO endocrine disruption by GEN, BPA, and other EDCs has been found in parvocellular aspects of AVP signaling.
“Concomitant work focused on the parvocellular aspects of AVP signaling has also found evidence of NO endocrine disruption by GEN, BPA, and other EDCs (39, 74, 151).”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [74]
The Results (Paraventricular nucleus; page unavailable) report that genistein changed AVP-positive cell numbers in the medial parvicellular region, increasing them in females and decreasing them in males. The paper also reports effects on nNOS, a marker of nitric-oxide-producing neurons, but does not show that nitric oxide disruption caused the parvocellular AVP changes. BPA and other EDCs appear to be covered by the sentence’s other citations, not this study’s experiment. (LLM, conf=0.81)
Experimental — accuracy not yet measured
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Cites
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Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice
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Endocrine Disruption of Vasopressin Systems and Related Behaviors
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- Authors
- Ponti, G., Rodriguez-Gomez, A., Farinetti, A., Marraudino, M., Filice, F., Foglio, B., Sciacca, G., Panzica, G. C., & Gotti, S.
- Affiliations
- Neuroscience Institute Cavalieri Ottolenghi (IT)
- University of Turin (IT)
- Corresponding author
- Ponti, G.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 346
- Pages
- 203-215
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2580642877
- Cited by
- 21
- References
- 7
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2021: 4 · 2020: 2 · 2019: 8 · 2017: 1
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by-nc-nd
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- genistein, xenoestrogens, isoflavonoids, nitric oxide synthase, vasopressin, nitrergic system, sex differences, early postnatal exposure, soy-based infant formula, estradiol, amygdala, brain development
- MeSH terms
- Animals, Brain, Estradiol, Female, Male, Sex Characteristics, Vasopressins, Genistein, Phytoestrogens, Mice, Nitric Oxide Synthase Type I
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