Animal models of hyperandrogenism and ovarian morphology changes as features of polycystic ovary syndrome: a systematic review

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting 9–18% of women in reproductive age that causes hyperandrogenism and infertility due to dysfunctional follicular maturation and anovulation. The etiology of PCOS is still poorly known, and information from experimental animal models may help improve current understanding of the mechanisms of PCOS initiation and development. Therefore, we conducted a systematic review of currently available methods for simulation of PCOS in experimental models, focusing on two main endocrine traits: ovarian morphology changes and circulating levels of sex hormones and gonadotropins.We searched the MEDLINE database for articles in English or Spanish published until October 2016. Of 933 studies identified, 39 were included in the systematic review. One study compared interventions with androgens versus estrogens, 18 used androgen-induced stimulation, 9 used estrogens or drugs with estrogen action, including endocrine disruptors, to induce PCOS-like models, and 12 used miscellaneous interventions. Broad differences were found among the studies concerning hormonal interventions, animal species, and developmental stage at the time of the experiments, and most models resulted in ovarian morphology changes, mainly increases in the number of cystic and antral follicles and decreases in the corpus luteum. Hyperandrogenism was produced by using androgens and other drugs as the stimulatory agent. However, studies using drugs with estrogenic effect did not observe changes in circulating androgens.In conclusion, medium- or long-term testosterone administration in the pre- and postnatal periods performed best for induction of a PCOS-like phenotype, in rhesus macaque and rat models respectively. In rats, postnatal exposure to androgens results in reprogramming of the hypothalamic-pituitary-ovarian-axis. Thus, comparisons between different intervention models may be useful to define the timing of reproductive PCOS phenotypes in experimental animal models.

Berberine Ameliorates Prenatal Dihydrotestosterone Exposure-Induced Autism-Like Behavior by Suppression of Androgen Receptor

“…Thus, we hypothesize that prenatal androgen exposure may trigger ASD development. The DHT treatment was used to mimic PCOS conditions during the in vivo rat experiments (Mannerås et al, 2007;Noroozzadeh et al, 2017;Paixão et al, 2017). Our results show that prenatal DHT exposure induces ALB in offspring with suppressed expression of ERβ and SOD2 in the amygdala Li et al, 2018;Xie et al, 2018).…”

“…Further investigation shows that DHT/BBR-mediated gene suppression is due to hypermethylation on the related gene promoters. We further established an in vivo PCOS rat model by DHT administration (Mannerås et al, 2007;Paixão et al, 2017) and found that maternal PCOS induces autism-like behavior (ALB) in offspring through ERβ/SOD2 suppression and subsequent oxidative stress and mitochondrial dysfunction. Prenatal treatment of AR knockdown restores this effect, indicating that prenatal DHT exposure induces ALB through the AR signaling pathway; interestingly, both prenatal and postnatal treatment of BBR partly restores this effect.…”

Effects of Stachys sylvatica hydroalcoholic extract on the ovary and hypophysis-gonadal axis in a rat with polycystic ovary syndrome

“…1 Weight difference of animals before and after treatment in the groups (mean ± SEM). ++ P < 0.01 PCO and 100 mg/kg of extract versus control, * P < 0.05, extract versus PCO (2) polycystic ovary [2,4]. Therefore, biochemical markers and ovarian biopsy are usual evidence for PCOS diagnosis.…”

“…For the first time, PCOS was described by Stein and Leventhal in the mid-1930s, but the exact cause of PCOS is unclear yet [3]. Both genetic and environmental factors (obesity and lack of physical exercise) can be significantly involved, and most treatments of PCOS are palliative which focuses on the symptoms of this disease and cannot completely cure PCOS [4].…”

Myo‐inositol and D‐chiro‐inositol (40:1) reverse histological and functional features of polycystic ovary syndrome in a mouse model

“…Androgens are considered the main culprit of PCOS, and therefore the most common experimental model makes use of androgen administration to induce symptoms and alterations that represent a good paradigm of hyperandrogenism-dependent PCOSlike syndrome (Paixão, Ramos, Lavarda, Morsh, & Spritzer, 2017). An alternative experimental model for PCOS induction in rodents is provided by exposing them to a regimen of continuous light.…”