Increased risk of primary ovarian insufficiency by high-fructose diet consumption: a 90-day study in female rats

In: Environmental Science and Pollution Research · 2022 · vol. 30(3) , pp. 7415–7426 · doi:10.1007/s11356-022-22258-8 · PMID:36040692 · W4293660791
article OA: closed CC0
AI-generated summary by qwen3.7-flash, 2026-09-02

A 90-day study in female rats found that high-fructose diet consumption induced reproductive toxicity, characterized by hormonal imbalances and uterine changes, suggesting an increased risk of primary ovarian insufficiency.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

AI-generated deep summary by qwen3.7-flash, 2026-09-02 · read from full text

This 90-day study in female Wistar rats investigated the reproductive toxicity of a high-fructose corn syrup diet compared to sucrose and control groups. The researchers observed significant hormonal disruptions, including elevated FSH and LH levels alongside decreased testosterone and estradiol, accompanied by histopathological changes such as squamous metaplasia in uterine tissue and ovarian congestion. These findings indicate that high fructose consumption deteriorates ovarian and endometrial health, potentially increasing the risk of primary ovarian insufficiency. Relevance to endometriosis: listed as one indication for GnRH antagonists, though the paper's main focus is uterine fibroids.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

There is ambiguous evidence that high-fructose diet can induce toxicity in different organ systems but its endocrine disrupting effects by abnormal changes in female reproductive organs is poorly evidenced. This study aimed to address the reproductive safety of high fructose diet through clinical, biochemical, hormonal, histopathological, and immunohistochemical analysis. For this purpose, 5-6 weeks mature female Wistar rats were divided in three groups and each five animals/group exposed to standard chow + water + HFCS-55, standard chow + water + sucrose 75%w/v and standard chow + water for 90 days. Remarkable increase in most lipid profile factors and total body weights of HFCS-55 fed rats and sucrose fed rats were detected in similar pattern compared to control. At the same time, a battery of differential signs and symptoms in HFCS-fed groups including squamous metaplasia in the uterine tissue and ovarian congestion, significant increase in FSH and LH levels, meaningful decreased serum testosterone and 17β-estradiol levels, and strong androgen receptor expression in ovaries and uterine of HFCS group of animals were recorded compared to other two study groups. These thought-provoking signs and signals of fructose induced reproductive toxicity in this model emphasis the contribution of HFCS-55 to deteriorated ovarian and endometrial health and increased risk primary ovarian insufficiency (POI) in women.
Full text 8,787 characters · extracted from oa-doi-fallback · 3 sections · click to expand

Abstract

There is ambiguous evidence that high-fructose diet can induce toxicity in different organ systems but its endocrine disrupting effects by abnormal changes in female reproductive organs is poorly evidenced. This study aimed to address the reproductive safety of high fructose diet through clinical, biochemical, hormonal, histopathological, and immunohistochemical analysis. For this purpose, 5–6 weeks mature female Wistar rats were divided in three groups and each five animals/group exposed to standard chow + water + HFCS-55, standard chow + water + sucrose 75%w/v and standard chow + water for 90 days. Remarkable increase in most lipid profile factors and total body weights of HFCS-55 fed rats and sucrose fed rats were detected in similar pattern compared to control. At the same time, a battery of differential signs and symptoms in HFCS-fed groups including squamous metaplasia in the uterine tissue and ovarian congestion, significant increase in FSH and LH levels, meaningful decreased serum testosterone and 17β-estradiol levels, and strong androgen receptor expression in ovaries and uterine of HFCS group of animals were recorded compared to other two study groups. These thought-provoking signs and signals of fructose induced reproductive toxicity in this model emphasis the contribution of HFCS-55 to deteriorated ovarian and endometrial health and increased risk primary ovarian insufficiency (POI) in women. Similar content being viewed by others Data availability All data and materials are available upon journal request.

References

Akarca-Dizakar SÖ, Erdoğan D, Peker T, CoşkunAkçay N, Türkoğlu I, Eşmekaya MA, Ömeroğlu S (2020) Effects of co-administered melatonin, fructose and bisphenol A (BPA) on rat epididymis and sperm characteristics. Biotech Histochem 95(1):18–26 Bhat SF, Pinney SE, Kennedy KM, McCourt CR, Mundy MA, Surette MG, Sloboda DM, Simmons RA (2021) Exposure to high fructose corn syrup during adolescence in the mouse alters hepatic metabolism and the microbiome in a sex-specific manner. J Physiol 599(5):1487–1511 Bidgoli SA, Karimi M, Asami Z, Baher H, DjamaliZavarhei M (2011) Association between testicular Aryl hydrocarbon Receptor levels and idiopathic male infertility: a case-control study in Iran. Sci Total Environ 409(18):3267–3273 Bidgoli SA Ahmadi R, Zavarhei MD (2010) Role of hormonal and environmental factors on early incidence of breast cancer in Iran. Sci Total Environ 408 (19)- pp. 4056–61. Bidgoli SA, Arabshahi P, Ramezan Y (2022) Ovarian toxicity of plant-derived edible oils: a 28 days hormonal and histopathological study in Wistar rat. Environ Sci Pollut Res Int 29(6):9153-9163. https://doi.org/10.1007/s11356-021-13279-w Chenxia Dai TM, Hai J, Xiao Y, Li Y, Zhao J, Qiu H, Bo Xu (2020) A novel glucose isomerase from Caldicellulosiruptor bescii with great potentials in the production of high-fructose corn syrup. Biomed Res Int 2020:1871934 Collison KS, Saleh SM, Bakheet RH, Al-Rabiah RK, Inglis AL, Makhoul NJ, Maqbool ZM, Zaidi MZ, Al-Johi MA, Al-Mohanna FA (2009) Diabetes of the liver: the link between nonalcoholic fatty liver disease and HFCS-55. Obesity (silver Spring) 17(11):2003–2013 de Melo GB, Soares JF, Costa TCL, Benevides ROA, Vale CC, Paes AMA, Gaspar RS (2021) Early exposure to high-sucrose diet leads to deteriorated ovarian health. Front Endocrinol (lausanne) 12:656831 DeChristopher LR, Auerbach BJ, Tucker KL (2020) High fructose corn syrup, excess-free-fructose, and risk of coronary heart disease among African Americans- the Jackson Heart Study. BMC Nutr 6(1):70 Goncalves MD Lu C, Tutnauer J, Hartman TE, Hwang SK, Murphy CJ, Pauli C, Morris R, Taylor S, Bosch K, Yang S, Wang Y, Van Riper J, Lekaye HC, Roper J, Kim Y, Chen Q, Gross SS, Rhee KY, Cantley LC, Yun J (2019) High-fructose corn syrup enhances intestinal tumor growth in mice. Science 363 (6433)1345–1349 Ishikawa H, Hashimoto S, Ohashi K (2018) Maternal fructose intake disturbs ovarian 17β-estradiol synthesis in rats. Life Sci 202:117–123 Marzieh Rostami Dovom, Mahsa Noroozzadeh, Nariman Mosaffa, Azita Zadeh–Vakili, Abbas Piryaei, Fahimeh Ramezani Tehrani (2019) Induced premature ovarian insufficiency by using D galactose and its effects on reproductive profiles in small laboratory animals: a systematic review. J Ovarian Res. - Vol. 12. - p. 96. Marzieh Rostami Dovom, Razieh Bidhendi-Yarandi, Kazem Mohammad, Maryam Farahmand, Fereidoun Azizi, Fahimeh Ramezani Tehrani (2021) Prevalence of premature ovarian insufficiency and its determinants in Iranian populations: Tehran lipid and glucose study. BMC Womens Health 21:79 Michael I, Goran Ashley A, Martin Tanya L, Alderete Hideji Fujiwara, David A (2017) Fields Fructose in breast milk is positively associated with infant body composition at 6 months of age. Nutrients 9(2):146 Paige K, Berger David A, Fields Ellen W, Demerath Hideji Fujiwara, Goran Michael I (2018) High-fructose corn-syrup-sweetened beverage intake increases 5-hour breast milk fructose concentrations in lactating women. Nutrients 10(6):669 Rizk MG, Thackray VG (2020) Intersection of polycystic ovary syndrome and the gut microbiome. J Endocr Soc 5(2):bvaa177 Rossetti R, Ferrari I, Bonomi M, Persani L (2017) Genetics of primary ovarian insufficiency. Clin Genetx 91(2):183–198 Sadowska J, Rygielska M (2019) The effect of high fructose corn syrup on the serum insulin and leptin concentration, body weight gain and fat accumulation in rat. Adv Clin Exp Med 28(7):879–884 Santoro N, Randolph JF Jr (2011) Reproductive hormones and the menopause transition. Obstet Gynecol Clin North Am 38(3):455–466 Semnani-Azad Z, Khan TA, Blanco Mejia S, de Souza RJ, Leiter LA, Kendall CWC, Hanley AJ, Sievenpiper JL (2020) Association of major food sources of fructose-containing sugars with incident metabolic syndrome: a systematic review and meta-analysis. JAMA Netw Open 3(7):e209993 Tkachenko OY, Shayakhmetova GM, Matvienko AV, Kovalenko VM (2020) Reproductive disorders in male rats induced by high-fructose consumption from juvenile age to puberty. Arh Hig Rada Toksikol 71(1):78–86 Tsiligiannis S, Panay N, Stevenson JC (2019) Premature ovarian insufficiency and long-term health consequences. Curr Vasc Pharmacol 19(6):604–609 Vercellini P, Viganò P, Somigliana E, Fedele L (2014) Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol 10(5):261–275 Zargaraan A, Kamaliroosta L, SeyedYagoubi A, SeyedYagoubi L, Mirmoghtadaie L (2016) Effect of substitution of sugar by high fructose corn syrup on the physicochemical properties of bakery and dairy products: a review. Nutr Food Sci Res 3(4):3–11 Zhou Y, Chi J, Lv W, Wang Y (2021) Obesity and diabetes as high-risk factors for severe coronavirus disease 2019 (Covid-19). Diabetes Metab Res Rev 37(2):e3377

Acknowledgements

The authors are thankful from Zar Fructose Co., Ltd., Tehran, Iran, for providing our study samples. The authors also acknowledge Dr. Hasti Azar Abad as the veterinary pathologist of the present study for her excellent supports of histopathological studies. We acknowledge cancer Institute of Iran for supporting immunohistochemical analysis. Author information Authors and Affiliations Contributions RM performed all animal studies and lab as part of her PhD thesis. She read and approved the manuscript before submission. SAB is the main supervisor of this study who planned, designed the work, conducted, performed the statistical analysis, and provided the manuscript. RK was the second supervisor of this PhD study who suggested the main topic and contributed in planning and study design execution of HFCS-55. SS and HAA were co-advisors of this PhD program who were contributed to all parts of this study. Corresponding author Ethics declarations Ethical approval This study was approved by the ethics committee of Islamic Azad University, Tehran Medical Sciences (IAUTMU) under the number of IR. IAU. TMU REC.1399.216. Consent to participate Not applicable. Consent for publication The authors ensure that this Journal and the Publisher have the Author’s permission to publish the relevant contribution. Competing interests The authors declare no competing interests. Additional information Responsible Editor: Mohamed M. Abdel-Daim Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Mirzaei, R., Bidgoli, S.A., Khosrokhavar, R. et al. Increased risk of primary ovarian insufficiency by high-fructose diet consumption: a 90-day study in female rats. Environ Sci Pollut Res 30, 7415–7426 (2023). https://doi.org/10.1007/s11356-022-22258-8 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s11356-022-22258-8

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood (sparse)

Too few in-corpus citations on either side for a chart; here are the lists.

Cites (1)

References (23)

SciLite annotations

chemicals 9
fructose fructose fructose water sucrose lipid sucrose testosterone estradiol
organisms 6
rattus sp. zitter rats multicellular animals rattus sp. rattus sp. noordeloos 2009062

Source provenance

openalex
last seen: 2026-06-10T17:14:06.276822+00:00
scilite
last seen: 2026-05-18T04:26:01.642840+00:00
unpaywall
last seen: 2026-09-11T06:32:28.951138+00:00
License: CC0 · commercial use OK