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Maternal androgen excess and obesity induce sexually dimorphic anxiety-like behavior in the offspring

Published on Aug 1, 2018in The FASEB Journal 5.59
· DOI :10.1096/fj.201701263RR
Maria Manti1
Estimated H-index: 1
(Karolinska Institutet),
Romina Fornes5
Estimated H-index: 5
(Karolinska Institutet)
+ 6 AuthorsElisabet Stener-Victorin43
Estimated H-index: 43
(Karolinska Institutet)
Abstract
Maternal polycystic ovary syndrome (PCOS), a condition associated with hyperandrogenism, is suggested to increase anxiety-like behavior in the offspring. Because PCOS is closely linked to obesity, we investigated the impact of an adverse hormonal or metabolic maternal environment and offspring obesity on anxiety in the offspring. The obese PCOS phenotype was induced by chronic high-fat–high-sucrose (HFHS) consumption together with prenatal dihydrotestosterone exposure in mouse dams. Anxiety-like behavior was assessed in adult offspring with the elevated-plus maze and open-field tests. The influence of maternal androgens and maternal and offspring diet on genes implicated in anxiety were analyzed in the amygdala and hypothalamus with real-time PCR (n = 47). Independent of diet, female offspring exposed to maternal androgens were more anxious and displayed up-regulation of adrenoceptor α 1B in the amygdala and up-regulation of hypothalamic corticotropin-releasing hormone (Crh). By contrast, male offspring e...
  • References (43)
  • Citations (4)
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References43
Newest
Published on May 1, 2017in Molecular Psychiatry 11.64
Rong Zhang2
Estimated H-index: 2
,
Masato Asai4
Estimated H-index: 4
+ 4 AuthorsJoseph A. Majzoub47
Estimated H-index: 47
Loss of hypothalamic corticotropin-releasing hormone markedly reduces anxiety behaviors in mice
20 Citations Source Cite
Published on May 1, 2017in Human Reproduction 4.99
Cooney Lg1
Estimated H-index: 1
(Hospital of the University of Pennsylvania),
Lee I1
Estimated H-index: 1
(Hospital of the University of Pennsylvania)
+ 1 AuthorsDokras A1
Estimated H-index: 1
(Hospital of the University of Pennsylvania)
Abstract Do women with polycystic ovary syndrome (PCOS) have an increased prevalence of moderate and severe depressive and anxiety symptoms compared with control women, and do these symptoms correlate with age, BMI, testosterone, hirsutism or insulin resistance (IR)? Women with PCOS have significantly increased odds of moderate and severe depressive and anxiety symptoms, independent of obesity, and the symptoms are weakly associated with age, BMI, elevated testosterone, hirsutism and IR. Previou...
48 Citations Source Cite
Published on Mar 1, 2017in Human Reproduction 4.99
Yingchen Wu1
Estimated H-index: 1
(Sun Yat-sen University),
Guangzheng Zhong1
Estimated H-index: 1
(Sun Yat-sen University)
+ 3 AuthorsMeiqing Xie2
Estimated H-index: 2
(Sun Yat-sen University)
15 Citations Source Cite
Published on Nov 1, 2016in Psychoneuroendocrinology 4.73
Carolyn E. Cesta3
Estimated H-index: 3
(Karolinska Institutet),
Mattias Månsson4
Estimated H-index: 4
(Karolinska Institutet)
+ 3 AuthorsMikael Landén47
Estimated H-index: 47
(Karolinska Institutet)
Abstract Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting 5–15% of reproductive-aged women and characterized by high levels of circulating androgens. Given that androgens have been implicated in the aetiology of several psychiatric disorders, it was hypothesized that women with PCOS have high risk for psychiatric comorbidity. We aimed to investigate this risk amongst women with PCOS, as well as in their siblings, to elucidate if familial factors underlie any potential associat...
31 Citations Source Cite
Published on Dec 1, 2015in Clinical Endocrinology 3.08
Elisabeth A. Lambert15
Estimated H-index: 15
(Monash University),
Helena Teede48
Estimated H-index: 48
(Monash University)
+ 10 AuthorsBarbora de Courten27
Estimated H-index: 27
(Monash University)
SummaryObjective Polycystic ovary syndrome (PCOS) is a common endocrine condition underpinned by insulin resistance and associated with increased risk of obesity, type 2 diabetes and adverse cardiovascular risk profile. Previous data suggest autonomic imbalance [elevated sympathetic nervous system (SNS) activity and decreased heart rate variability (HRV)] as well as endothelial dysfunction in PCOS. However, it is not clear whether these abnormalities are driven by obesity and metabolic disturban...
21 Citations Source Cite
Min Hu6
Estimated H-index: 6
(Karolinska Institutet),
Jennifer E. Richard9
Estimated H-index: 9
(University of Gothenburg)
+ 8 AuthorsKarolina P. Skibicka29
Estimated H-index: 29
(University of Gothenburg)
During pregnancy, women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring. This study investigated whether maternal androgen excess causes anxiety-like behavior in offspring mimicking anxiety disorders in PCOS. The PCOS phenotype was induced in rats following prenatal androgen (PNA) exposure. PNA offspring displayed anxiety-like behavior in the elevated plus maze, which was reversed by flu...
36 Citations Source Cite
I.B. Ressler3
Estimated H-index: 3
(University of Cincinnati),
Bernadette E. Grayson23
Estimated H-index: 23
(University of Mississippi Medical Center)
+ 1 AuthorsRandy J. Seeley87
Estimated H-index: 87
(University of Michigan)
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. Although a comorbidity of PCOS is obesity, many are lean. We hypothesized that increased saturated fat consumption and obesity would exacerbate metabolic and stress indices in a rodent model of PCOS. Female rats were implanted with the nonaromatizable androgen dihydrotestosterone (DHT) or placebo pellets prior to puberty. Half of each group was maintained ad libitum on either a high-fat diet (...
14 Citations Source Cite
Published on Apr 1, 2015in International Journal of Obesity 5.16
Adelheid Soubry11
Estimated H-index: 11
,
Susan K. Murphy43
Estimated H-index: 43
+ 8 AuthorsJoellen M. Schildkraut59
Estimated H-index: 59
BACKGROUND: Several epidemiologic studies have demonstrated associations between periconceptional environmental exposures and health status of the offspring in later life. Although these environmentally related effects have been attributed to epigenetic changes, such as DNA methylation shifts at imprinted genes, little is known about the potential effects of maternal and paternal preconceptional overnutrition or obesity. OBJECTIVE: We examined parental preconceptional obesity in relation to DNA ...
141 Citations Source Cite
Published on Feb 17, 2015in Frontiers in Neuroscience 3.88
Peter Celec27
Estimated H-index: 27
,
Daniela Ostatníková16
Estimated H-index: 16
(Comenius University in Bratislava),
Július Hodosy17
Estimated H-index: 17
(Comenius University in Bratislava)
Testosterone influences the brain via organizational and activational effects. Numerous relevant studies on rodents and a few on humans focusing on specific behavioral and cognitive parameters have been published. The results are, unfortunately, controversial and puzzling. Dosing, timing, even the application route seem to considerably affect the outcomes. In addition, the methods used for the assessment of psychometric parameters are a bit less than ideal regarding their validity and reproducib...
49 Citations Source Cite
Published on Nov 1, 2014in British Journal of Psychiatry 5.87
Quetzal A. Class12
Estimated H-index: 12
,
Martin E. Rickert17
Estimated H-index: 17
+ 2 AuthorsBrian M. D’Onofrio44
Estimated H-index: 44
Background It is unclear whether associations between fetal growth and psychiatric and socioeconomic problems are consistent with causal mechanisms. Aims To estimate the extent to which associations are a result of unmeasured confounding factors using a sibling-comparison approach. Method We predicted outcomes from continuously measured birth weight in a Swedish population cohort ( n = 3 291 773), while controlling for measured and unmeasured confounding. Results In the population, lower birth w...
33 Citations Source Cite
Cited By4
Newest
Published on Apr 1, 2019in Chemosphere 4.43
W. Wang5
Estimated H-index: 5
(Ocean University of China),
Xiaona Zhang7
Estimated H-index: 7
(Ocean University of China)
+ 4 AuthorsShaoguo Ru10
Estimated H-index: 10
(Ocean University of China)
Abstract Bisphenol S (BPS), as a substitute for bisphenol A, was frequently detected in human urine and blood. It has been reported that BPS could disrupt fat metabolism in vivo and vitro although mechanisms remain unclear. Additionally, there is no study that the disruptive effect of BPS on parental fat metabolism indirectly interferes with the lipid metabolism of offspring. Here, after 120-d exposure to 1, 10, 100, and 1000 μg/L BPS, the transcription level of genes involved in lipid metabolis...
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Published on Mar 1, 2019in Biology of Reproduction 3.18
Danielle L Peecher (Central Washington University), April K. Binder7
Estimated H-index: 7
(Central Washington University),
Kara I. Gabriel3
Estimated H-index: 3
(Central Washington University)
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Published on Jan 22, 2019in International Journal of Obesity 5.16
Romina Fornes5
Estimated H-index: 5
(Karolinska Institutet),
Maria Manti1
Estimated H-index: 1
(Karolinska Institutet)
+ 9 AuthorsMattias Carlström22
Estimated H-index: 22
(Karolinska Institutet)
Maternal obesity together with androgen excess in mice negatively affects placental function and maternal and fetal liver function as demonstrated by increased triglyceride content with dysfunctional expression of enzymes and transcription factors involved in de novo lipogenesis and fat storage. To identify changes in molecular pathways that might promote diseases in adulthood, we performed a global proteomic analysis using a liquid-chromatography/mass-spectrometry system to investigate total an...
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Published on Dec 1, 2018
Lisa Lindheim2
Estimated H-index: 2
(University of Graz),
Maria Manti1
Estimated H-index: 1
(Karolinska Institutet)
+ 8 AuthorsBarbara Obermayer-Pietsch43
Estimated H-index: 43
(University of Graz)
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