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

Motta, Alicia Beatriz

doi:10.1016/j.jsbmb.2010.02.015

Cited by 51 publications

(33 citation statements)

References 112 publications

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“…S1A). The dose of metformin used in this study was equivalent to that used in the treatment of PCOS patients (Elia et al, 2009, Motta, 2010). After the animals were anesthetized, trunk blood was collected and the uteri were removed, stripped of fat and connective tissue, and weighed.…”

Section: Methodsmentioning

confidence: 99%

Metformin Ameliorates Uterine Defects in a Rat Model of Polycystic Ovary Syndrome

Zhang

Meng

et al. 2017

EBioMedicine

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Adult rats treated concomitantly with insulin and human chorionic gonadotropin exhibit endocrine, metabolic, and reproductive abnormalities that are very similar to those observed in polycystic ovary syndrome (PCOS) patients. In this study, we used this rat model to assess the effects of metformin on PCOS-related uterine dysfunction. In addition to reducing androgen levels, improving insulin sensitivity, and correcting the reproductive cycle, metformin treatment induced morphological changes in the PCOS-like uterus. At the molecular and cellular levels, metformin normalized the androgen receptor-mediated transcriptional program and restored epithelial–stromal interactions. In contrast to glucose transport, uterine inflammatory gene expression was suppressed through the PI3K–Akt–NFκB network, but without affecting apoptosis. These effects appeared to be independent of AMPK subunit and autophagy-related protein regulation. We found that when metformin treatment partially restored implantation, several implantation-related genes were normalized in the PCOS-like rat uterus. These results improve our understanding of how metformin rescues the disruption of the implantation process due to the uterine defects that result from hyperandrogenism and insulin resistance. Our data provide insights into the molecular and functional clues that might help explain, at least in part, the potential therapeutic options of metformin in PCOS patients with uterine dysfunction.

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Section: Methodsmentioning

confidence: 99%

Metformin Ameliorates Uterine Defects in a Rat Model of Polycystic Ovary Syndrome

Zhang

Meng

et al. 2017

EBioMedicine

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“…The Ob/Ob mouse lacks biologically active leptin due to a mutation in the leptin gene. This model develops severe insulin resistance and marked hyperinsulinemia with gross obesity, extensive β -cell hyperplasia, and mild-to-moderate hyperglycemia [18, 65, 66, 84]. Thus, ob/ob mouse provides an especially challenging test for any potential treatment against insulin resistance.…”

Section: Spontaneous and Transgenic Animal Modelsmentioning

confidence: 99%

Animal Models as Tools to Investigate Antidiabetic and Anti-Inflammatory Plants

Eddouks

Chattopadhyay

Zeggwagh

2012

Evidence-Based Complementary and Alternative Medicine

106

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Plants have been historically used for diabetes treatment and related anti-inflammatory activity throughout the world; few of them have been validated by scientific criteria. Recently, a large diversity of animal models has been developed for better understanding the pathogenesis of diabetes mellitus and its underlying inflammatory mechanism and new drugs have been introduced in the market to treat this disease. The aim of this work is to review the available animal models of diabetes and anti-inflammatory activity along with some in vitro models which have been used as tools to investigate the mechanism of action of drugs with potential antidiabetic properties and related anti-inflammatory mechanism. At present, the rigorous procedures for evaluation of conventional antidiabetic medicines have rarely been applied to test raw plant materials used as traditional treatments for diabetes; and natural products, mainly derived from plants, have been tested in chemically induced diabetes model. This paper contributes to design new strategies for the development of novel antidiabetic drugs and its related inflammatory activity in order to treat this serious condition which represents a global public health problem.

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“…Hyperandrogenism impairs maturation of developing follicles in ovaries and consequently leads to developing cystogenesis [13]. Extensive animal experimentations have indicated that prepubertal or pubertal exposure of low doses of androgens via aromatization to estrogen results in long-term reproductive consequences including constant estrous cycles, hyposteroidogenesis, anovulation, and development of cystic follicles at adulthood [14]. Moreover, exposure to exogenous estrogen in adulthood has been determined by having deleterious effects on the ovarian physiology and endocrinology which may ultimately lead to cystogenesis, loss of follicle pool, and early senescence [15].…”

Section: Introductionmentioning

confidence: 99%

Ovarian Aging-Like Phenotype in the Hyperandrogenism-Induced Murine Model of Polycystic Ovary

Rezvanfar

Saadi

Gooshe

et al. 2014

Oxidative Medicine and Cellular Longevity

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There are prominently similar symptoms, effectors, and commonalities in the majority of characteristics between ovarian aging and polycystic ovarian syndrome (PCOS). Despite the approved role of oxidative stress in the pathogenesis of PCOS and aging, to our knowledge, the link between the PCO(S) and aging has not been investigated yet. In this study we investigated the possible exhibition of ovarian aging phenotype in murine model of PCO induced by daily oral administration of letrozole (1 mg/kg body weight) for 21 consecutive days in the female Wistar rats. Hyperandrogenization showed irregular cycles and histopathological characteristics of PCO which was associated with a significant increase in lipid peroxidation (LPO) and reactive oxygen species (ROS) and decrease in total antioxidant capacity (TAC) in serum and ovary. Moreover, serum testosterone, insulin and tumor necrosis factor-alpha (TNF-α) levels, and ovarian matrix metalloproteinase-2 (MMP-2) were increased in PCO rats compared with healthy controls, while estradiol and progesterone diminished. Almost all of these findings are interestingly found to be common with the characteristics identified with (ovarian) aging showing that hyperandrogenism-induced PCO in rat is associated with ovarian aging-like phenotypes. To our knowledge, this is the first report that provides evidence regarding the phenomenon of aging in PCO.

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

Cited by 51 publications

References 112 publications

Metformin Ameliorates Uterine Defects in a Rat Model of Polycystic Ovary Syndrome

Metformin Ameliorates Uterine Defects in a Rat Model of Polycystic Ovary Syndrome

Animal Models as Tools to Investigate Antidiabetic and Anti-Inflammatory Plants

Ovarian Aging-Like Phenotype in the Hyperandrogenism-Induced Murine Model of Polycystic Ovary

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