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Mice exposed to maternal androgen excess and diet-induced obesity have altered phosphorylation of catechol-O-methyltransferase in the placenta and fetal liver

Published on Jan 22, 2019in International Journal of Obesity 5.16
· DOI :10.1038/s41366-018-0314-8
Romina Fornes5
Estimated H-index: 5
(Karolinska Institutet),
Maria Manti1
Estimated H-index: 1
(Karolinska Institutet)
+ 9 AuthorsElisabet Stener-Victorin43
Estimated H-index: 43
(Karolinska Institutet)
Abstract
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 and phosphorylated proteins in the placenta and fetal liver in a mouse model that combines maternal obesity with maternal androgen excess. After ten weeks on a control diet (CD) or high fat/high sugar-diet, dams were mated with males fed the CD. Between gestational day (GD) 16.5 and GD 18.5, mice were injected with vehicle or dihydrotestosterone (DHT) and sacrificed at GD 18.5 prior to dissection of the placentas and fetal livers. Four pools of female placentas and fetal livers were subjected to a global proteomic analysis. Total and phosphorylated proteins were filtered by ANOVA q < 0.05, and this was followed by two-way ANOVA to determine the effect of maternal obesity and/or androgen exposure. In placenta, phosphorylated ATP-citrate synthase was decreased due to maternal obesity, and phosphorylated catechol-O-methyltransferase (COMT) was differentially expressed due to the interaction between maternal diet and DHT exposure. In fetal liver, five total proteins and 48 proteins phosphorylated in one or more sites, were differentially expressed due to maternal obesity or androgen excess. In fetal liver, phosphorylated COMT expression was higher in fetus exposed to maternal obesity. These results suggest a common regulatory mechanism of catecholamine metabolism in the placenta and the fetal liver as demonstrated by higher phosphorylated COMT expression in the placenta and fetal liver from animals exposed to diet-induced maternal obesity and lower expression of phosphorylated COMT in animals exposed to maternal androgen excess.
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Published on Aug 1, 2018in The FASEB Journal 5.59
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)
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...
4 Citations Source Cite
Published on Dec 1, 2017in Scientific Reports 4.12
Romina Fornes5
Estimated H-index: 5
(Karolinska Institutet),
Manuel Maliqueo20
Estimated H-index: 20
(Karolinska Institutet)
+ 8 AuthorsAnna Benrick15
Estimated H-index: 15
(University of Skövde)
Pregnant women with polycystic ovary syndrome (PCOS) are often overweight or obese. To study the effects of maternal androgen excess in obese dams on metabolism, placental function and fetal growth ...
5 Citations Source Cite
Published on Nov 1, 2017in Biological Psychiatry 11.98
Kyriaki Kosidou10
Estimated H-index: 10
(Karolinska Institutet),
Christina Dalman35
Estimated H-index: 35
(Karolinska Institutet)
+ 4 AuthorsRenee M. Gardner19
Estimated H-index: 19
(Karolinska Institutet)
Abstract Background Attention-deficit/hyperactivity disorder (ADHD) is the most common childhood neurodevelopmental disorder, and boys are two to three times more likely to develop ADHD. Maternal polycystic ovary syndrome (PCOS), a common metabolic disorder associated with excess circulating androgens, has been associated with increased risk for autism spectrum disorder in the offspring. In this study, we aimed to investigate whether maternal PCOS increases the risk for ADHD in the offspring. Me...
13 Citations Source Cite
Published on May 1, 2017in Physiology 5.95
Joanna James13
Estimated H-index: 13
(University of Auckland),
Lawrence W. Chamley41
Estimated H-index: 41
(University of Auckland),
Alys R. Clark12
Estimated H-index: 12
(University of Auckland)
The utero-placental circulation links the maternal and fetal circulations during pregnancy, ensuring adequate gas and nutrient exchange, and consequently fetal growth. However, our understanding of this circulatory system remains incomplete. Here, we discuss how the utero-placental circulation is established, how it changes dynamically during pregnancy, and how this may impact on pregnancy success, highlighting how we may address knowledge gaps through advances in imaging and computational model...
7 Citations Source Cite
Published on Apr 1, 2017in Current Opinion in Lipidology 3.85
Amy C. Burke6
Estimated H-index: 6
,
Murray W. Huff45
Estimated H-index: 45
Purpose of reviewATP-citrate lyase (ACLY) has re-emerged as a drug target for LDL cholesterol (LDL-C) lowering. We review ACLY as a therapeutic strategy, its genetics, its molecular and cellular biology, and also its inhibition.Recent findingsACLY is a critical enzyme linking glucose catabolism to l
15 Citations Source Cite
Published on Feb 1, 2017in Reproduction 3.09
Beatriz Piquer1
Estimated H-index: 1
(University of Chile),
Jose L Fonseca1
Estimated H-index: 1
(University of Chile),
Hernán E. Lara27
Estimated H-index: 27
(University of Chile)
6 Citations Source Cite
Published on Dec 1, 2016in Genes and Nutrition 3.21
Z. C. T. R. Daniel8
Estimated H-index: 8
(University of Nottingham),
Angelina Swali8
Estimated H-index: 8
(University of Nottingham)
+ 1 AuthorsSimon C. Langley-Evans51
Estimated H-index: 51
(University of Nottingham)
Background Fetal exposure to a maternal low protein diet during rat pregnancy is associated with hypertension, renal dysfunction and metabolic disturbance in adult life. These effects are present when dietary manipulations target only the first half of pregnancy. It was hypothesised that early gestation protein restriction would impact upon placental gene expression and that this may give clues to the mechanism which links maternal diet to later consequences.
7 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 Oct 1, 2016in Molecular Psychiatry 11.64
Kyriaki Kosidou10
Estimated H-index: 10
,
Christina Dalman35
Estimated H-index: 35
+ 4 AuthorsRenee M. Gardner19
Estimated H-index: 19
Maternal polycystic ovary syndrome and the risk of autism spectrum disorders in the offspring: a population-based nationwide study in Sweden
36 Citations Source Cite
Published on Sep 1, 2016in Molecular and Cellular Endocrinology 3.56
Romina Fornes5
Estimated H-index: 5
(Karolinska Institutet),
Min Hu6
Estimated H-index: 6
(Karolinska Institutet)
+ 7 AuthorsElisabet Stener-Victorin43
Estimated H-index: 43
(Karolinska Institutet)
Abstract Women with polycystic ovary syndrome (PCOS) have elevated circulating androgens during pregnancy and are at an increased risk of adverse pregnancy outcomes. Here we tested the hypotheses that maternal androgen excess decrease placental and fetal growth, and placental expression of markers of steroidogenesis, angiogenesis and sympathetic activity, and that acupuncture with low-frequency electrical stimulation prevents these changes. Pregnant rats were exposed to vehicle or testosterone o...
9 Citations Source Cite
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