Detrimental effects of hyperandrogenism on uterine functions

Dehydroepiandrosterone to induce murine models for the study of polycystic ovary syndrome

“…For this reason, we designed experiments to study the mechanisms involved in the injurious action of the excess of androgens on uterine functions. We demonstrated that hyperandrogenism induces uterine morphological changes closely related to the development of pre-cancerous structures, concomitantly with an increased incidence of uterine endometrial tissue apoptosis [46]. We also found an enhanced proinflammatory stage (shown by increased PGF2␣ and decreased uterine PGE levels) and a negative feedback mechanism that regulates the expression of uterine cyclooxygenase 2 (COX2) [46,47].…”

“…We demonstrated that hyperandrogenism induces uterine morphological changes closely related to the development of pre-cancerous structures, concomitantly with an increased incidence of uterine endometrial tissue apoptosis [46]. We also found an enhanced proinflammatory stage (shown by increased PGF2␣ and decreased uterine PGE levels) and a negative feedback mechanism that regulates the expression of uterine cyclooxygenase 2 (COX2) [46,47]. In addition, the excess of androgens promoted a pro-oxidant status since it increased nitric oxide synthase (NOS) activity and decreased SOD and CAT activities and the content of the antioxidant metabolite GSH [46].…”

Link between metformin and the peroxisome proliferator-activated receptor γ pathway in the uterine tissue of hyperandrogenized prepubertal mice

“…We had previously reported that the excess of androgens induced the development of uterine structures closely related to the development of precancerous structures (7,8). These adverse effects are mediated by a proinflammatory status characterized by an increased production of prostaglandins by the uterus (7,8).…”

“…The animal model (7)(8)(9)(10)(11) consisted of female prepubertal (25-dayold) mice of the BALB/c strain. The dehydroepiandrosterone (DHEA) group consisted of animals injected daily with DHEA (6 mg/100 g body weight, dissolved in 0.10 mL sesame oil) for 20 consecutive days, and the DHEA þ M group consisted of animals injected with DHEA and given metformin orally (50 mg/100 g body weight in 0.05 mL of water, given orally with a cannula) for 20 days.…”

“…These adverse effects are mediated by a proinflammatory status characterized by an increased production of prostaglandins by the uterus (7,8). We also found that metformin partially prevented these adverse effects (7,8). These findings, together with the fact that the activation of the PPAR system is related to the uterine function (26,29), the synergistic action of metformin þ PPAR treatment described in PCOS (27,28,30,31), and the role of PPAR in regulating the prostaglandin pathway (32), led us to evaluate the action of metformin and the PPARg system on hyperandrogenized uteri.…”