Induction of polycystic ovary by testosterone in immature female rats: Modulation of apoptosis and attenuation of glucose/insulin ratio

Beloosesky, Ron; Gold, Richard M.; Almog, Benny; Sasson, Ravid; Dantes, Ada; Land-Bracha, Abigail; Hirsh, Liron; Itskovitz‐Eldor, Joseph; Jb, Lessing; Homburg, Roy; Amsterdam, Abraham

doi:10.3892/ijmm.14.2.207

Cited by 44 publications

(49 citation statements)

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“…Owing to the heterogeneity of PCOS, it is difficult to create a single-animal model that expresses the main PCOS characteristics. Common models of PCOS include female rats exposed to testosterone (Beloosesky et al 2004) or the aromatase inhibitor letrozole (Kafali et al 2004, Manneras et al 2007) to cause cystic follicles and endocrine features similar to human PCOS. However, these induced models do not develop many of the metabolic disturbances (e.g.…”

Section: Introductionmentioning

confidence: 99%

The New Zealand obese mouse model of obesity insulin resistance and poor breeding performance: evaluation of ovarian structure and function

Radavelli-Bagatini

Blair²,

Proietto³

et al. 2011

Journal of Endocrinology

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Infertility, associated with oligo/anovulation, increased ovarian volume, numerous follicular cysts, and metabolic disturbances such as obesity and insulin resistance (IR) are characteristics common to polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age. Here, we show that New Zealand obese (NZO) mice display similar metabolic characteristics such as obesity, leptin insensitivity, glucose intolerance, and IR. Importantly, NZO mice are poor breeders; however, the mechanism for this has not been investigated. The aim of this study was to assess the ovarian structure/morphology and sex hormone levels in female NZO and lean C57BL/6J control mice. Twenty-five NZO and twenty female control mice were studied at three different ages (young, adult, and aged). The animals were weighed, an insulin tolerance test was carried out, and blood was collected for measurement of hormone levels. The ovaries were removed for histological analysis. As expected, NZO mice presented higher body weights (PZ0 . 001), increased basal plasma glucose (PZ0 . 007), and insulin levels (PZ0 . 001) as well as IR, compared with control mice. NZO mice showed an increased ovarian volume, reduced numbers of corpora lutea, and higher total follicle numbers (PZ0 . 0001). The number of primordial follicles increased (PZ0 . 02) at the young stage, as well as the amount of atretic follicles (PZ0 . 03), in NZO compared with control mice. NZO mice also displayed reduced plasma LH and increased estradiol levels. In conclusion, NZO mice show a poor breeding performance due to decreased ovulation, increased number of primordial and atretic follicles, and ovarian size. Given that NZO mice are obese, hyperinsulinemic and insulin resistant, they are suitable for investigating pathophysiological mechanisms linking metabolic alterations with reproductive defects.

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Section: Introductionmentioning

confidence: 99%

The New Zealand obese mouse model of obesity insulin resistance and poor breeding performance: evaluation of ovarian structure and function

Radavelli-Bagatini

Blair²,

Proietto³

et al. 2011

Journal of Endocrinology

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“…PCOS is characterized by clinical and/or biochemical hyperandrogenism. In female rats and humans, exogenous exposure to testosterone or dihydrotestosterone (DHT) leads to insulin resistance and obesity (4,14,17,22,50,58). The insulin resistance in women with PCOS is associated with a dyslipidemia characterized by low levels of high-density lipoprotein (HDL) cholesterol and high levels of low-density lipoprotein (LDL) and triglycerides (TG) (49).…”

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confidence: 99%

Intense electroacupuncture normalizes insulin sensitivity, increases muscle GLUT4 content, and improves lipid profile in a rat model of polycystic ovary syndrome

Johansson

Feng

Shao

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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Intense electroacupuncture normalizes insulin sensitivity, increases muscle GLUT4 content, and improves lipid profile in a rat model of polycystic ovary syndrome. Am J Physiol Endocrinol Metab 299: E551-E559, 2010. First published July 27, 2010; doi:10.1152/ajpendo.00323.2010.-Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and insulin resistance, possibly reflecting defects in skeletal muscle and adipocyte insulin signaling. Low-frequency (2 Hz) electroacupuncture (EA) increases insulin sensitivity in female rats with dihydrotestosterone (DHT)-induced PCOS, but the mechanism is unclear. We hypothesized that low-frequency EA regulates mediators involved in skeletal muscle glucose uptake and metabolism and alters the lipid profile in rats with DHT-induced PCOS. To test this hypothesis, we implanted in prepubescent female rats 90-day continuousrelease pellets containing DHT (PCOS). At 70 days of age, the rats were randomly subdivided into two groups: one received lowfrequency EA (evoking muscle twitches) for 20 -25 min five times/wk for 4 -5 wk; the other did not. Controls were implanted with pellets containing vehicle only. All three groups were otherwise handled similarly. Lipid profile was measured in fasting blood samples. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp, soleus muscle protein expression of glucose transporter 4 (GLUT4), and phosphorylated and nonphosphorylated Akt, and Akt substrate of 160 kDa was determined by Western blot analysis and GLUT4 location by immunofluorescence staining. PCOS EA rats had normalized insulin sensitivity, lower levels of total high-density lipoprotein and low-density lipoprotein cholesterol, and increased expression of GLUT4 in different compartments of skeletal muscle compared with PCOS rats. Total weight and body composition did not differ in the groups. Thus, in rats with DHT-induced PCOS, low-frequency EA has systemic and local effects involving intracellular signaling pathways in muscle that may, at least in part, account for the marked improved insulin sensitivity.acupuncture; glucose transporter 4; insulin resistance; muscle contraction; skeletal muscle HYPERANDROGENEMIA IS THE MOST PROMINENT endocrine phenotype in women with polycystic ovary syndrome (PCOS) (56) in addition to ovulatory dysfunction and polycystic ovary morphology (3). The main metabolic phenotype is hyperinsulinemia and insulin resistance, which are independent of body weight (19,40). Other metabolic abnormalities associated with insulin resistance are obesity, dyslipidemia, and increased risk for type 2 diabetes.The mechanisms for the association between endocrine and metabolic abnormalities in PCOS are unclear (13, 18). PCOS is characterized by clinical and/or biochemical hyperandrogenism. In female rats and humans, exogenous exposure to testosterone or dihydrotestosterone (DHT) leads to insulin resistance and obesity (4,14,17,22,50,58). The insulin resistance in women with PCOS is associated with a dyslipidemia characterized by low levels of high...

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“…Experimental and clinical experience indicated that exogenous LH administration plays an important role in completing maturation of the follicle. 3 Experimentally, androgen which is produced in response to LH have been shown to stimulate early follicular development and reduce the incidence of apoptosis in rat model 4 and androgen receptor stimulation is necessary to promote the action of growth differentiation factor (Gdf)9, to stimulate granulosa cell division and progesterone synthesis in porcine model. 5 Clinical studies using recombinant FSH (rFSH) in hypogonadotropic women have demonstrated that only FSH can induce follicular growth at the preovulatory stage but estradiol (E 2 ) concentrations were extremely low.…”

Section: Introductionmentioning

confidence: 99%

Effects of Urinary and Recombinant Gonadotropins on In Vitro Maturation Outcomes of Mouse Preantral Follicles

Park

Ku²,

Jung

et al. 2013

Reprod. Sci.

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Gonadotropins including follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play a crucial role in human-assisted reproduction techniques. Despite wide use of recombinant gonadotropins in clinical practice, the efficacy of urinary gonadotropins and the dosage of LH component have not yet been elucidated. This study was designed to investigate the difference of follicle culture outcomes according to various compositions of gonadotropins during in vitro culture of mouse preantral follicles. Ovaries were obtained from the 14-day-old C57BL/6 mice, and preantral follicles were isolated and cultured in culture media supplemented with human menopausal gonadotropin (hMG) 200 mIU/mL (group 1), recombinant FSH and LH (rFSH þ rLH) 200 mIU/mL each (group 2), rFSH 200 mIU/mL þ rLH 100 mIU/mL (group 3), or rFSH 200 mIU/mL þ rLH 20 mIU/mL (group 4). Follicle survival rate was significantly lower in group 4. Antral follicles in lower doses of LH (groups 3, 4) showed a statistically significant larger diameter and tended to have a higher antral formation rate. However, follicles in group 1 tended to have a higher oocyte maturation rate. Estradiol concentration from conditioned media from 2:1 FSH/LH (group 3) was significantly higher than those from 1:1 FSH/LH (group 2) or 10:1 FSH/LH (group 4). Half dose of rLH to rFSH facilitated upregulation of growth differentiation factor 9 (Gdf9) expression in granulosa cells when compared to 1:1 FSH/LH or 10:1 FSH/LH. Conclusively, recombinant gonadotropins provided a comparable condition to hMG, and half dose of rLH to rFSH seems to be more suitable for follicular development during in vitro culture.

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Induction of polycystic ovary by testosterone in immature female rats: Modulation of apoptosis and attenuation of glucose/insulin ratio

Cited by 44 publications

References 0 publications

The New Zealand obese mouse model of obesity insulin resistance and poor breeding performance: evaluation of ovarian structure and function

The New Zealand obese mouse model of obesity insulin resistance and poor breeding performance: evaluation of ovarian structure and function

Intense electroacupuncture normalizes insulin sensitivity, increases muscle GLUT4 content, and improves lipid profile in a rat model of polycystic ovary syndrome

Effects of Urinary and Recombinant Gonadotropins on In Vitro Maturation Outcomes of Mouse Preantral Follicles

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