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孕期单次暴露于睾酮对成年雌性大鼠后代胰岛素抵抗、糖耐量和血脂水平的影响。

The impact of prenatal exposure to a single dose of testosterone on insulin resistance, glucose tolerance and lipid profile of female rat's offspring in adulthood.

作者信息

Noroozzadeh M, Ramezani Tehrani F, Sedaghat K, Godini A, Azizi F

机构信息

Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

J Endocrinol Invest. 2015 May;38(5):489-95. doi: 10.1007/s40618-014-0198-y. Epub 2014 Dec 21.

DOI:10.1007/s40618-014-0198-y
PMID:25527160
Abstract

PURPOSE

In our previous study, we introduced a rat model of polycystic ovary syndrome (PCOS) induced by prenatal exposure to a single dose of testosterone on embryonic day 20. In the current study, we aimed to investigate whether prenatal exposure to a single dose of testosterone could also induce metabolic disturbances, especially insulin resistance in adulthood (100-110 days of age) and also to make it as an appropriate rat model of PCOS (exhibiting both reproductive and metabolic disturbances with minimum morphological disorders in reproductive system) for further studies in PCOS.

METHODS

Pregnant rats in the experimental group were subcutaneously injected with 5 mg free testosterone on the gestational day 20, while controls received only the solvent. Female offspring of both groups, prenatally androgenized (PNA) rats (PCOS models of rats) and controls were examined.

RESULTS

Body weight measures showed significant increase in the PNA rats compared to controls on days 30, 45, 60 of age and in adulthood (P < 0.05). PNA rats showed insulin resistance compared to controls. Impaired glucose tolerance was not observed in the PNA rats compared to controls. There were no significant differences in lipid profile between the PNA and control rats (P > 0.05).

CONCLUSION

Our study suggests that metabolic disturbances in PCOS and their severity during adult life probably depend on the particular time and levels of prenatal androgen exposure.

摘要

目的

在我们之前的研究中,我们引入了一种多囊卵巢综合征(PCOS)大鼠模型,该模型通过在胚胎第20天产前单次暴露于睾酮诱导产生。在当前研究中,我们旨在调查产前单次暴露于睾酮是否也会诱发代谢紊乱,尤其是成年期(100 - 110日龄)的胰岛素抵抗,并且使其成为一种合适的PCOS大鼠模型(表现出生殖和代谢紊乱,同时生殖系统形态紊乱最小),用于PCOS的进一步研究。

方法

实验组的怀孕大鼠在妊娠第20天皮下注射5毫克游离睾酮,而对照组仅接受溶剂。对两组的雌性后代,即产前雄激素化(PNA)大鼠(大鼠PCOS模型)和对照组进行检查。

结果

体重测量显示,与对照组相比,PNA大鼠在30日龄、45日龄、60日龄及成年期体重显著增加(P < 0.05)。与对照组相比,PNA大鼠表现出胰岛素抵抗。与对照组相比,未在PNA大鼠中观察到糖耐量受损。PNA大鼠和对照大鼠之间的血脂谱无显著差异(P > 0.05)。

结论

我们的研究表明,PCOS中的代谢紊乱及其在成年期的严重程度可能取决于产前雄激素暴露的特定时间和水平。

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Exp Physiol. 2014 May 1;99(5):792-801. doi: 10.1113/expphysiol.2014.078055. Epub 2014 Feb 14.
2
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J Endocrinol. 2013 Mar 19;217(1):119-29. doi: 10.1530/JOE-12-0577. Print 2013 Apr.
3
Prenatal hyperandrogenization induces metabolic and endocrine alterations which depend on the levels of testosterone exposure.
成年多囊卵巢综合征的产前雄激素化大鼠模型中卵巢滤泡刺激素和激活素受体基因的表达。
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Association between maternal polycystic ovary syndrome and early childhood growth: a continuous observation from 3 months to 6 years of age.多囊卵巢综合征与儿童早期生长的关系:3 个月至 6 岁连续观察。
J Assist Reprod Genet. 2022 Feb;39(2):461-471. doi: 10.1007/s10815-021-02378-9. Epub 2022 Jan 20.
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Increased Skeletal Muscle Fiber Cross-Sectional Area, Muscle Phenotype Shift, and Altered Insulin Signaling in Rat Hindlimb Muscles in a Prenatally Androgenized Rat Model for Polycystic Ovary Syndrome.多囊卵巢综合征的产前雄激素化大鼠模型中,大鼠后肢肌肉的骨骼肌纤维横截面积增加、肌肉表型转变和胰岛素信号改变。
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产前雄激素化会引起代谢和内分泌的改变,这些改变取决于睾酮暴露的水平。
PLoS One. 2012;7(5):e37658. doi: 10.1371/journal.pone.0037658. Epub 2012 May 24.
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PCOS Forum: research in polycystic ovary syndrome today and tomorrow.多囊卵巢综合征论坛:今日与明日的多囊卵巢综合征研究。
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