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Abstract <p>Polycystic ovary syndrome (PCOS), one of the most common endocrinedisorders in women, leads to a reduction in reproductive potentialand infertility. To study PCOS, rodent models are used, includingthose induced by dehydroepiandrosterone (DHEA). However, they arenot sufficiently studied, including in terms of ovulation stimulationin PCOS rats with luteinizing hormone (LH) agonists, and this complicatestheir use for developing approaches to treat this pathology. Thiswork was aimed to comparatively study and characterize morphologicaland biochemical parameters in animals using the two most popularPCOS models, induced by a six-week treatment of immature (aged 23–25&#xa0;days)and a three-week treatment of prepubertal (aged 45–47 days) femalerats with DHEA, as well as to assess the effectiveness of ovulationstimulation in PCOS rats using TP03, a low-molecular-weight LH receptor agonistdeveloped in our laboratory. A six-week DHEA treatment of immaturefemale rats led to the development of polycystic ovary morphology,a decrease in blood progesterone levels and the expression of ovariangenes encoding key steroidogenic proteins (CYP11A1, CYP17A1) andthe metalloproteinase ADAMTS-1, a marker of ovulation. TP03 treatmentincreased progesterone levels, enhanced the expression of the <i>Cyp11a1</i>, <i>Cyp17a1</i>,and <i>Adamts-1</i> genes, and ledto the formation of corpora lutea (CL), with a significant proportionof them being represented by luteinized unruptured follicles. Athree-week DHEA treatment of prepubertal females also led to characteristicfeatures of PCOS, but had a lesser effect on <i>Adamts-1</i> expressionand did not cause the formation of defective CL upon TP03 stimulation.In this case, two subgroups were identified among PCOS rats c withrelatively low and high levels of progesterone. They differed significantlyin <i>Cyp17a1</i> expression and theeffectiveness of new cycle’s CL formation after TP03 treatment. Thus,the longer-term PCOS model induced by DHEA in immature female ratsis well suited for studying functional disorders in severe formsof PCOS, while the shorter-term PCOS model generated in prepubertalrats by a three-week DHEA treatment is more suitable for studyingmoderately severe forms of PCOS and optimizing the choice of ovulationstimulants effective for this disease.</p>

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A Comparative Study of Dehydroepiandrosterone-Induced Polycystic Ovary Syndrome Models in Immature and Prepubertal Female Rats

  • 期刊论文

  • 发表日期：

    2025年12月19日

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  • A. S. Pechalnova,
  • K. V. Derkach,
  • I. Yu. Morina,
  • I. I. Zorina,
  • L. V. Bayunova,
  • I. V. Romanova,
  • E. E. Chernenko,
  • A. O. Shpakov

摘要

Abstract

Polycystic ovary syndrome (PCOS), one of the most common endocrinedisorders in women, leads to a reduction in reproductive potentialand infertility. To study PCOS, rodent models are used, includingthose induced by dehydroepiandrosterone (DHEA). However, they arenot sufficiently studied, including in terms of ovulation stimulationin PCOS rats with luteinizing hormone (LH) agonists, and this complicatestheir use for developing approaches to treat this pathology. Thiswork was aimed to comparatively study and characterize morphologicaland biochemical parameters in animals using the two most popularPCOS models, induced by a six-week treatment of immature (aged 23–25 days)and a three-week treatment of prepubertal (aged 45–47 days) femalerats with DHEA, as well as to assess the effectiveness of ovulationstimulation in PCOS rats using TP03, a low-molecular-weight LH receptor agonistdeveloped in our laboratory. A six-week DHEA treatment of immaturefemale rats led to the development of polycystic ovary morphology,a decrease in blood progesterone levels and the expression of ovariangenes encoding key steroidogenic proteins (CYP11A1, CYP17A1) andthe metalloproteinase ADAMTS-1, a marker of ovulation. TP03 treatmentincreased progesterone levels, enhanced the expression of the Cyp11a1, Cyp17a1,and Adamts-1 genes, and ledto the formation of corpora lutea (CL), with a significant proportionof them being represented by luteinized unruptured follicles. Athree-week DHEA treatment of prepubertal females also led to characteristicfeatures of PCOS, but had a lesser effect on Adamts-1 expressionand did not cause the formation of defective CL upon TP03 stimulation.In this case, two subgroups were identified among PCOS rats c withrelatively low and high levels of progesterone. They differed significantlyin Cyp17a1 expression and theeffectiveness of new cycle’s CL formation after TP03 treatment. Thus,the longer-term PCOS model induced by DHEA in immature female ratsis well suited for studying functional disorders in severe formsof PCOS, while the shorter-term PCOS model generated in prepubertalrats by a three-week DHEA treatment is more suitable for studyingmoderately severe forms of PCOS and optimizing the choice of ovulationstimulants effective for this disease.