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

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Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in women, leads to reduced reproductive potential and infertility. Rodent models, including those induced by dehydroepiandrosterone (DHEA), are used to study PCOS. However, they have not been sufficiently studied, including in terms of ovulation stimulation in PCOS rats by luteinizing hormone (LH) agonists, and this complicates their use in developing approaches for the treatment of PCOS. The aim of the work was to comparatively study and characterize the morphological and biochemical parameters in animals with two most commonly used models of PCOS, induced by six-week treatment of immature (23–25 days) and three-week treatment of prepubertal (45–47 days) female rats with DHEA, and to evaluate the effectiveness of ovulation stimulation in PCOS rats using TP03, a low-molecular-weight LH receptor agonist developed by us. Six-week treatment of immature female rats with DHEA resulted in the development of polycystic ovary morphology, decreased blood progesterone levels, and decreased expression of ovarian genes encoding key steroidogenic proteins (CYP11A1, CYP17A1) and the metalloproteinase ADAMTS-1, a marker of ovulation. Treatment with TP03 increased progesterone levels, enhanced expression of the Cyp11a1, Cyp17a1, and Adamts-1 genes, and led to the formation of corpora lutea (CL), but a significant proportion of these were luteinized unruptured follicles. Three-week treatment of prepubertal female rats with DHEA also resulted in the characteristic features of PCOS, but had a lesser effect on Adamts-1 gene expression and did not induce the formation of defective CL upon stimulation with TP03. In this case, two subgroups were identified among PCOS rats – those with relatively low and those with high progesterone levels. They differed significantly in Cyp17a1 gene expression and in the efficiency of new cycle adipose tissue formation after TP03 treatment. Thus, the longer-term DHEA-induced PCOS model in immature female rats is well suited for studying functional impairments in severe forms of PCOS, while the PCOS model generated in prepubertal rats by three-week DHEA treatment is more suitable for studying moderate forms of PCOS and optimizing the choice of ovulation stimulants effective in this disease.

作者简介

A. Pechalnova

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Saint Petersburg, Russia

K. Derkach

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: derkatch_k@list.ru
Saint Petersburg, Russia

I. Morina

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Saint Petersburg, Russia

I. Zorina

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Saint Petersburg, Russia

L. Bayunova

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Saint Petersburg, Russia

I. Romanova

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Saint Petersburg, Russia

E. Chernenko

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Saint Petersburg, Russia

A. Shpakov

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Saint Petersburg, Russia

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