Prenatal Androgenization of Ewes as a Model of Hirsutism in Polycystic Ovary Syndrome

Santos, Joabel Tonellotto dos; Nóbrega, J. E.; Mujica, Lady Katerine Serrano; Amaral, Carolina dos Santos; Machado, Fabrício Amadori; Manta, M. W.; Rizzetti, Tiele Medianeira; Zanella, Renato; Fighera, Rafael A.; Antoniazzi, Alfredo Q.; Gonçalves, Paulo Bayard Dias; Comim, Fábio Vasconcellos

doi:10.1210/en.2018-00781

Cited by 7 publications

(6 citation statements)

References 54 publications

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“…However, treatment with LA did not change the androgens levels (data not shown). 29 Interestingly, despite higher weights at 12 months of age, PA sheep exhibited a proportionally lower ratio of visceral to SC fat (estimated by 3D CT) and lower total cholesterol. These features were similar to those described by Veiga-Lopez et al who reported an increased total amount of visceral fat and reduced ratio of visceral to SC fat in sheep treated with high levels of bisphenol A during gestation.…”

Section: Discussionmentioning

confidence: 92%

“…Insulin resistance estimated by the intravenous glucose tolerance test was increased in PA and LA sheep at 16 months of age, as previously reported. 29…”

Section: Resultsmentioning

confidence: 99%

“…However, as recently described, PA and LA sheep showed significantly elevated insulin levels in an intravenous glucose tolerance test, suggesting insulin resistance in both androgenized groups. 29 Androgen levels or the presence of hyperandrogenemia also reflects changes in the oxidative stress status, as gender is thought to influence disruptions in the oxidative/antioxidative balance. However, treatment with LA did not change the androgens levels (data not shown).…”

Section: Discussionmentioning

confidence: 99%

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Oxidative stress and biochemical markers in prenatally androgenized sheep after neonatal treatment with GnRH agonist

Nóbrega¹,

Santos²,

Serrano-Mujica³

et al. 2019

JIR

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Background Disruption of the balance between the production of ROS and their removal through enzymatic and non-enzymatic (antioxidant) processes has been proposed as a new mechanism in the pathology of polycystic ovary syndrome (PCOS). Evidence from animal models of PCOS (prenatally androgenized sheep) has suggested that treatment with insulin sensitizers, but not antiandrogens, can reduce increases in ROS. Materials and methods In the present study, we investigated the effects of neonatal treatment with a gonadotropin-releasing hormone (GnRH) agonist (leuprolide acetate) on prenatally androgenized sheep with testosterone propionate to determine its impact on oxidative stress molecules (ferric reducing antioxidant power [FRAP], advanced oxidation protein product [AOPP], nitric oxide [NOx], albumin) at 8, 12, and 18 months of age. Results Androgenized ewes (but not leuprolide-treated ewes) showed reduced total cholesterol levels associated with a decrease in the ratio of visceral to subcutaneous adiposity (adjusted to abdominal area) as determined by computed tomography. In androgenized ewes at 12 months of age, an increase in subcutaneous fat and relative decrease in the visceral fat compartment did not affect the expression of REDOX markers. At 18 months of age, however, the levels of NOx metabolites decreased in androgenized animals, but remained close to normal in ewes subjected to neonatal treatment with leuprolide acetate. Other oxidative stress parameters (FRAP, AOPP, albumin) did not vary among groups. Conclusion Our results demonstrate that the GnRH agonist leuprolide (as a single dose after birth) had weak effects on markers of the oxidative stress balance.

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Section: Discussionmentioning

confidence: 92%

“…Insulin resistance estimated by the intravenous glucose tolerance test was increased in PA and LA sheep at 16 months of age, as previously reported. 29…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Oxidative stress and biochemical markers in prenatally androgenized sheep after neonatal treatment with GnRH agonist

Nóbrega¹,

Santos²,

Serrano-Mujica³

et al. 2019

JIR

Self Cite

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“…The research also shows that there are no differences in the expression of the AR, SRD5A1, and HSD17B2 genes between the group of sheep who underwent prenatal androgens and the control group. This research has some limitations, such as a limited number of animals and a limited time of research [21].…”

Section: Androgenolmentioning

confidence: 99%

Experimental animal models for polycystic ovarian syndrome (methods, effects, and implications)

Kurniawati,

Pramono,

Hidayat

et al. 2024

Livest. Anim. Res.

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Many studies have replicated the clinical and genetic features of polycystic ovarian syndrome (PCOS) using a range of experimental animal models to improve treatment outcomes. This article aims to present an overview of the various experimental animal models that have been used in PCOS research. In this study, we conducted a systematic review of relevant research articles on the induced animal model PCOS. We searched research articles in Indonesian and English published over the last five years through three databases: PubMed, ScienceDirect, Google Scholar. We use established inclusion and exclusion criteria to select suitable articles. Out of 19 research articles included in our systematic review, we found the animal model PCOS based Rotterdam criteria, PCOS-IR model, PCOS-Inflammation model, PCOS-Gut microbiota model and PCOS-syndrome metabolic model. Androgen agents such as testosterone propionate, free testosterone, DHEA, and letrozole, as well as sodium valproate, are effective in the induction of PCOS phenotypes based on the Rotterdam criteria (oligo/amenorrhea, hyperandrogenic, and polycystic ovaries).

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“…Because sheep and monkeys are similar to humans in terms of physiology and hormone regulation, several researchers have used these large animals to simulate human PCOS and to explore possible pathogenesis in recent years ( Table 3 ). In a study by Tonellotto Dos Santos et al (2018) , the possible causes of the hypertrichosis symptoms caused by PCOS were investigated by injecting pregnant ewes with androgens to make them androgenic. It was found that increased 5-a-reductase type 1 (SRD5A1) activity may be a cause of hirsutism due to PCOS.…”

Section: Polycystic Ovary Syndromementioning

confidence: 99%

Large animal models in the study of gynecological diseases

Cui

Liu²,

Men³

et al. 2023

Front. Cell Dev. Biol.

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Gynecological diseases are a series of diseases caused by abnormalities in the female reproductive organs or breast, which endanger women’s fertility and even their lives. Therefore, it is important to investigate the mechanism of occurrence and treatment of gynecological diseases. Animal models are the main objects for people to study the development of diseases and explore treatment options. Large animals, compared to small rodents, have reproductive organs with structural and physiological characteristics closer to those of humans, and are also better suited for long-term serial examinations for gynecological disease studies. This review gives examples of large animal models in gynecological diseases and provides a reference for the selection of animal models for gynecological diseases.

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Prenatal Androgenization of Ewes as a Model of Hirsutism in Polycystic Ovary Syndrome

Cited by 7 publications

References 54 publications

<p>Oxidative stress and biochemical markers in prenatally androgenized sheep after neonatal treatment with GnRH agonist</p>

<p>Oxidative stress and biochemical markers in prenatally androgenized sheep after neonatal treatment with GnRH agonist</p>

Experimental animal models for polycystic ovarian syndrome (methods, effects, and implications)

Large animal models in the study of gynecological diseases

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