A Rat Model of Maternal Polycystic Ovary Syndrome Shows that Exposure to Androgens In Utero Results in Dysbiosis of the Intestinal Microbiota and Metabolic Disorders of the Newborn Rat
Open accessAbstract
BACKGROUND Intestinal dysbiosis, or dysbacteriosis, is an abnormal interaction between the intestinal microbiota and the host cells due to altered microbial diversity. This study aimed to investigate the metabolic effects and changes in the intestinal microbiota in newborn rats following exposure to increased levels of maternal androgens in a rat model of maternal polycystic ovary syndrome (PCOS). MATERIAL AND METHODS The administration of androgen developed the rat maternal PCOS model during pregnancy. Maternal rat ovarian follicles were counting and assessed by histology. The metabolic phenotype of newborn rats was evaluated and included an insulin tolerance test, a glucose tolerance test, and measurement of serum levels of triglyceride, insulin, cholesterol, adiponectin, and leptin. Expression of pro-inflammatory cytokines was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), serum levels were measured by enzyme-linked immunosorbent assay (ELISA), and proteins associated with adipose tissue remodeling and adipocyte differentiation were measured by Western blot. RESULTS Markers of systemic inflammation were significantly increased in the female offspring but not in the male offspring born to rat in the PCOS model. Following birth, newborn rats that received antibiotics showed an improved metabolic phenotype, with reduced serum lipid levels, insulin resistance, body weight, inflammation of adipose tissue, and serum levels of inflammatory cytokines compared with controls. Probiotics had no significant effects on these parameters in newborn rats. CONCLUSIONS In a rat model of maternal PCOS, exposure to androgens in utero resulted in dysbiosis of the intestinal microbiota and metabolic disorders of the newborn female rats.
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In female offspring, excess androgen exposure changes the size of WAT adipocytes and increases chemokine and pro-inflammatory cytokine expression and dysregulated adiponectin expression, depending on the timing of exposure and WAT depot.
“There is a change in the size of WAT adipocytes [132, 136] and an increase in chemokine and pro-inflammatory cytokine expression and dysregulated adiponectin expression, depending on the timing of the androgen exposure and WAT depot in female offspring [132, 137].”
From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [137]
The Results section on adipose-tissue inflammation reports increased inflammatory cytokine expression in white adipose tissue of androgen-exposed female offspring. The Results section on serum hormones reports reduced circulating adiponectin and increased MCP-1, but not their expression in WAT. Our copy does not establish changes in adipocyte size or effects that depend on exposure timing or WAT depot. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAndrogen-exposed female offspring have an additional increase in pro-inflammatory cytokines when fed an obesogenic diet postnatally.
“Androgen exposed female offspring also seem to have an additional increase in pro-inflammatory cytokines when fed an obesogenic diet postnatally [137].”
From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [137]
The Results section reports elevated pro-inflammatory cytokines in androgen-exposed female rats fed a high-fat diet. It also reports elevated cytokines in androgen-exposed offspring fed normal chow, but does not establish a direct increase caused by the high-fat diet relative to normal chow. Thus, the claimed additional diet-related increase is not fully supported. (LLM, conf=0.82)
Experimental — accuracy not yet measuredAndrogen-exposed female offspring have greater sensitivity to increase their body weight with an obesogenic diet postnatally.
“There is also a greater sensitivity of androgen exposed female offspring to increase their body weight with an obesogenic diet postnatally [137].”
From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [137]
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- Authors
- Gulan, T., Yeernuer, T., Sui, S., & Mayinuer, N.
- Affiliations
- People's Hospital of Xinjiang Uygur Autonomous Region (CN)
- Corresponding author
- Gulan, Tuohetimulati
- ORCID
- Sui, Shuang
- Venue
- Medical Science Monitor
- Published
- 2019-12-09
- Volume
- 25
- Pages
- 9377-9391
- ISSN
- 1234-1010 (ISSN-L)
- 1643-3750
- PMC
- PMC6921696
- OpenAlex
- W2996245450
- Cited by
- 16
- References
- 30
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 6 · 2020: 2
- FWCI
- 0.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Medical Science Monitor (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- gut dysbiosis, gut microbiota, insulin resistance, systemic inflammation, adipose tissue inflammation, adipogenesis, adipose tissue remodeling, sex differences, probiotics, antibiotics
- MeSH terms
- Gastrointestinal Microbiome, Adipose Tissue, Androgens, Animals, Animals, Newborn, Body Weight, China, Disease Models, Animal, Female, Glucose, Glucose Tolerance Test, Ovarian Follicle, Insulin, Insulin Resistance, Male, Metabolic Diseases, Obesity, Polycystic Ovary Syndrome, Pregnancy, Prenatal Exposure Delayed Effects, Rats, Sprague-Dawley, Leptin, Rats, Dysbiosis
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