Experimental method for modeling polycystic ovary syndrome in rats: a cross-sectional study

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Abstract

BACKGROUND: Existing rodent models of polycystic ovary syndrome (PCOS) have several limitations: they do not match the hormonal profile of the human disease, do not fully reproduce metabolic disturbances, or are difficult to implement. This study describes a PCOS modeling methodology suitable for preclinical research.

AIM: To validate an experimental model of polycystic ovary syndrome in rats with the assessment of hormonal and histological parameters.

METHODS: The animals were divided into three groups: intact (n = 22, saline), PCOS model (n = 30), and PCOS + therapy model (n = 10, pathology induction + combined oral contraceptives [COCs]). PCOS modeling was carried out for 10 days via intramuscular injections of human chorionic gonadotropin (300 U/animal) and increasing doses of isophane insulin (from 1.5 to 3.5 U/animal). The PCOS + therapy group received COCs (drospirenone + ethinyl estradiol) orally for 14 days. Body weight dynamics and glucose levels were measured as indicators of metabolic disorders. Hormone levels, including anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), estradiol, and sex hormone-binding globulin (SHBG) were measured by ELISA. Morphological analysis was also performed.

RESULTS: In modeling the pathology, PCOS model group showed a significant increase in body weight (295.2 ± 20.2 g) compared with the intact group (267.3 ± 22.4 g; p < 0.05) and the PCOS + therapy group (273.9 ± 18.5 g; p < 0.05). In the PCOS model group, levels of free testosterone, AMH, and estradiol increased, while SHBG decreased compared with the intact group (p < 0.05). The LH/FSH ratio on day 12 was significantly higher in the PCOS + therapy group (16.6 ± 7.6) than the intact group (6.9 ± 4.8; p < 0.05). Histological examination confirmed an increase in the number of cysts, atretic follicles, and corpora lutea in the ovaries of animals with induced PCOS. COCs therapy significantly reduced ovarian mass coefficients and glucose levels compared with the PCOS model group.

CONCLUSION: The presented PCOS model, based on the combined administration of hCG and insulin in Wistar rats, successfully reproduces the key features of the disease: an increased LH/FSH ratio, hyperandrogenemia, elevated AMH and estradiol, decreased SHBG, polycystic ovarian morphology with multiple functional and retention cysts, and metabolic disorders such as weight gain. Furthermore, the model demonstrates sensitivity to standard COCs therapy.

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About the authors

Denis A. Borozdenko

The Russian National Research Medical University named after N.I. Pirogov; PeptidPRO

Author for correspondence.
Email: borozdenko@phystech.edu
ORCID iD: 0000-0002-6797-9722
SPIN-code: 7351-6661

MD

Russian Federation, Moscow; Moscow

Sofya A. Stislavskaya

The Russian National Research Medical University named after N.I. Pirogov

Email: sstislav@gmail.com
ORCID iD: 0009-0009-1315-1610

MD

Russian Federation, Moscow

Oksana V. Pyrkova

The Russian National Research Medical University named after N.I. Pirogov

Email: oksanapyrkovaa@yandex.ru
ORCID iD: 0009-0002-7091-4580

MD

Russian Federation, Moscow

Dmitriy N. Lyakhmun

The Russian National Research Medical University named after N.I. Pirogov

Email: lyahmun@mail.ru
ORCID iD: 0000-0002-0760-0899
SPIN-code: 4286-7041

MD

Russian Federation, Moscow

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2. Fig. 1. Experimental design. hCG — human chorionic gonadotropin; LH — luteinizing hormone; COC — combined oral contraceptives; * on day 12, 10 rats were selected from the "PCOS Model" group to form the "PCOS Model + Therapy" group; # event from the "PCOS Model" group after euthanasia of 10 rats on day 12 and transfer of 10 animals to the "PCOS Model + Therapy" group.

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3. Fig. 2. Hormone concentrations in rat blood plasma on the 26th day of the experiment, M±SD: a — concentration of free testosterone in blood plasma, pg/ml; b — concentration of anti-Müllerian hormone in blood plasma; c — concentration of sex hormone-binding globulin; d — concentration of estradiol in blood plasma; * statistically significant differences from the intact group (Tukey's test, p < 0.05).

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4. Fig. 3. Eviscerated ovaries: a — multiple follicles, including those with cystic transformation (arrow); b — multiple follicles, hemorrhagic cyst (arrow).

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