Experimental Models: a contribution to understand the intraovarian component of PCOS pathogenesis.

ORTEGA HH ; SALVETTI NR; REY F; BARBEITO CG; GIMENO EJ

Ovarian Cysts: Symptoms, Causes and Treatment

Nova Science Publishers, Inc.

Año: 2010; p. 1 - 30

Several hypotheses have been proposed about the pathogenesis of the polycystic ovarian syndrome (PCOS). However, intraovarian alterations, as causes that contribute to the follicular persistence, have not been clearly established. In this sense, several experimental models have been developed in order to study this syndrome in the rat, contributing to understand specific aspect related to the pathogenesis of PCOS. The following hormonal substances, among others, have been employed to induce that syndrome: estradiol valerate, dehydroepiandrostenerone (DHEA), and neonatal androgenization. An additional simple method to induce polycystic ovaries consists on exposing mature rats to constant light. The procedure induces cysts gradually, similar to the human PCOS and is the least invasive method developed until now. Recently, a new animal model, based on the use of a non-steroidal aromatase inhibitor (letrozole), has been described which in several features is similar to the human PCOS. Ovaries of rats with PCOS exhibited an altered steroid receptor expression and subtype balance, increased expression of steroidogenic enzymes, changes in the ovarian regional concentration of growth factors and aberrant expression of cytoskeletal proteins and adhesion molecules.  The combination of weak proliferation indices and low apoptosis observed in follicular cysts, could explain the gradual growth of cystic follicles and the maintenance of a static condition without degeneration, which leads to their persistence. Alterations described may be caused by structural and functional modifications occurring in these cells and could be related to hormonal changes in animals with this condition. These observations indicate that cystogenesis, in some experimental models, is characterized by changes in numerous cellular components that may be essential to a suitable ovarian functioning, in agreement with similar modifications reported in women with PCOS. Although experimental models could be improved, they are valuable tools to study several aspects of cystogenesis that might be targets for the development of future treatments for PCOS.