Prenatal hyperandrogenism and lipid profile during different age stages: an experimental study

Heber, María Florencia; Ferreira, Silvana Rocío; Veléz, Leandro Martín; Motta, Alicia Beatriz

doi:10.1016/j.fertnstert.2012.10.017

Cited by 16 publications

(15 citation statements)

References 69 publications

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“…In a recent study, the rats treated prenatally with testosterone had significantly lower body weights than untreated controls at postnatal 21 days; however, at 60 days of age, body weights were not different between two groups. In addition, the levels of lipids were elevated in the 60-day-old PNA rats compared with controls (Heber et al 2012). The disagreement between these studies indicates that the effects of DHT and testosterone in the intrauterine environment on body weight and the lipid profile of female offspring are indeed different.…”

Section: Discussionmentioning

confidence: 91%

Prenatal androgen excess programs metabolic derangements in pubertal female rats

Yan¹,

Dai²,

Wang³

et al. 2013

Journal of Endocrinology

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Owing to the heterogeneity in the clinical symptoms of polycystic ovary syndrome (PCOS), the early pathophysiological mechanisms of PCOS remain unclear. Clinical, experimental, and genetic evidence supports an interaction between genetic susceptibility and the influence of maternal environment in the pathogenesis of PCOS. To determine whether prenatal androgen exposure induced PCOS-related metabolic derangements during pubertal development, we administrated 5a-dihydrotestosterone (DHT) in pregnant rats and observed their female offspring from postnatal 4 to 8 weeks. The prenatally androgenized (PNA) rats exhibited more numerous total follicles, cystic follicles, and atretic follicles than the controls. Fasting glucose, insulin, leptin levels, and homeostatic model assessment for insulin resistance were elevated in the PNA rats at the age of 5-8 weeks. Following intraperitoneal glucose tolerance tests, glucose and insulin levels did not differ between two groups; however, the PNA rats showed significantly higher 30-and 60-min glucose levels than the controls after insulin stimulation during 5-8 weeks. In addition, prenatal DHT treatment significantly decreased insulin-stimulated phosphorylation of AKT in the skeletal muscles of 6-week-old PNA rats. The abundance of IR substrate 1 (IRS1) and IRS2 was decreased in the skeletal muscles and liver after stimulation with insulin in the PNA group, whereas phosphorylation of insulin-signaling proteins was unaltered in the adipose tissue. These findings validate the contribution of prenatal androgen excess to metabolic derangements in pubertal female rats, and the impaired insulin signaling through IRS and AKT may result in the peripheral insulin resistance during pubertal development. Key Words" Fetal origin of adult disease " polycystic ovary syndrome " prenatal androgen exposure " insulin resistance " insulin signaling

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Section: Discussionmentioning

confidence: 91%

Prenatal androgen excess programs metabolic derangements in pubertal female rats

Yan¹,

Dai²,

Wang³

et al. 2013

Journal of Endocrinology

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“…The amount of malondialdehyde formed from the breakdown of polyunsaturated fatty acids is taken as an index of the peroxidation reaction. The method used in this study was as that described previously (Amalfi et al 2012, Heber et al 2013. The reduced form of GSH, which comprises the bulk of cellular protein sulfhydryl groups, was quantified as described previously (Amalfi et al 2012, Heber et al 2013.…”

Section: Liver Oxidant/antioxidant Balancementioning

confidence: 99%

“…The homeostatic model assessment for IR (HOMA-IR) was determined (Yan et al 2013). The circulating lipid profile was evaluated as described previously and the TG/HDL cholesterol ratio was taken as a marker of metabolic syndrome risk (Heber et al 2013).…”

Section: General Metabolism Imbalancementioning

confidence: 99%

“…Since PCOS patients with hyperandrogenic phenotypes have a higher prevalence of developing NAFLD, it has been suggested that androgens could contribute to the development of the pathology (Vassilatou et al 2010, Vassilatou 2014. We have previously demonstrated that the levels of androgen administered in pregnant rats are directly related to the PCOS-like phenotype displayed in the female offspring during the pubertal age (Amalfi et al 2012) and that the fetal programming generated by androgens leads to metabolic alterations, particularly in lipid metabolism, which worsen through life (Heber et al 2013). Based on the above, the aim of this study was to evaluate the effect of prenatal hyperandrogenism on the liver function and lipid metabolism.…”

Section: Introductionmentioning

confidence: 99%

“…PCOS etiology remains controversial, and current theories emphasize on genetic and intrauterine origins coupled with environmental factors such as diet and altered lifestyle patterns (Franks 1995). It has been reported that prenatal androgen exposure is able to induce polycystic ovaries in rats (Demissie et al 2008, monkeys (Abbott et al 2010) and sheep (Manikkam et al 2006) and that fetal programming, mediated by prenatal hyperandrogenism, is related to hyperinsulinemia, dyslipidemia, insulin resistance (IR), cardiovascular disease and metabolic syndrome (Demissie et al 2008, Amalfi et al 2012, Heber et al 2013. However, how fetal programming impacts on different tissues is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism

Abruzzese

Heber

Ferreira

et al. 2016

Journal of Endocrinology

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Prenatal hyperandrogenism is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS patients have high risk of developing fatty liver and steatosis. This study aimed to evaluate the role of prenatal hyperandrogenism in liver lipid metabolism and fatty liver development. Pregnant rats were hyperandrogenized with testosterone. At pubertal age, the prenatally hyperandrogenized (PH) female offspring displayed both ovulatory (PHov) and anovulatory (PHanov) phenotypes that mimic human PCOS features. We evaluated hepatic transferases, liver lipid content, the balance between lipogenesis and fatty acid oxidation pathway, oxidant/antioxidant balance and proinflammatory status. We also evaluated the general metabolic status through growth rate curve, basal glucose and insulin levels, glucose tolerance test, HOMA-IR index and serum lipid profile. Although neither PH group showed signs of liver lipid content, the lipogenesis and fatty oxidation pathways were altered. The PH groups also showed impaired oxidant/antioxidant balance, a decrease in the proinflammatory pathway (measured by prostaglandin E2 and cyclooxygenase-2 levels), decreased glucose tolerance, imbalance of circulating lipids and increased risk of metabolic syndrome. We conclude that prenatal hyperandrogenism generates both PHov and PHanov phenotypes with signs of liver alterations, imbalance in lipid metabolism and increased risk of developing metabolic syndrome. The anovulatory phenotype showed more alterations in liver lipogenesis and a more impaired balance of insulin and glucose metabolism, being more susceptible to the development of steatosis. Androgen excess alters liver lipid metabolism

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Prenatally androgenized female rats develop uterine hyperplasia when adult

Ferreira

Goyeneche

Heber

et al. 2020

Molecular and Cellular Endocrinology

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Prenatal hyperandrogenism and lipid profile during different age stages: an experimental study

Cited by 16 publications

References 69 publications

Prenatal androgen excess programs metabolic derangements in pubertal female rats

Prenatal androgen excess programs metabolic derangements in pubertal female rats

Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism

Prenatally androgenized female rats develop uterine hyperplasia when adult

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