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

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Abstract Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in women, leads to a reduction in reproductive potential and infertility. To study PCOS, rodent models are used, including those induced by dehydroepiandrosterone (DHEA). However, they are not sufficiently studied, including in terms of ovulation stimulation in PCOS rats with luteinizing hormone (LH) agonists, and this complicates their use for developing approaches to treat this pathology. This work was aimed to comparatively study and characterize morphological and biochemical parameters in animals using the two most popular PCOS models, induced by a six-week treatment of immature (aged 23–25 days) and a three-week treatment of prepubertal (aged 45–47 days) female rats with DHEA, as well as to assess the effectiveness of ovulation stimulation in PCOS rats using TP03, a low-molecular-weight LH receptor agonist developed in our laboratory. A six-week DHEA treatment of immature female rats led to the development of polycystic ovary morphology, a decrease in blood progesterone levels and the expression of ovarian genes encoding key steroidogenic proteins (CYP11A1, CYP17A1) and the metalloproteinase ADAMTS-1, a marker of ovulation. TP03 treatment increased progesterone levels, enhanced the expression of the Cyp11a1, Cyp17a1, and Adamts-1 genes, and led to the formation of corpora lutea (CL), with a significant proportion of them being represented by luteinized unruptured follicles. A three-week DHEA treatment of prepubertal females also led to characteristic features of PCOS, but had a lesser effect on Adamts-1 expression and did not cause the formation of defective CL upon TP03 stimulation. In this case, two subgroups were identified among PCOS rats c with relatively low and high levels of progesterone. They differed significantly in Cyp17a1 expression and the effectiveness of new cycle’s CL formation after TP03 treatment. Thus, the longer-term PCOS model induced by DHEA in immature female rats is well suited for studying functional disorders in severe forms of PCOS, while the shorter-term PCOS model generated in prepubertal rats by a three-week DHEA treatment is more suitable for studying moderately severe forms of PCOS and optimizing the choice of ovulation stimulants effective for this disease.

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