Stimulation of serotonergic 5-HT 2A receptor signaling increases placental aromatase (CYP19) activity and expression in BeWo and JEG-3 human choriocarcinoma cells

Klempan, Timothy A.; Hudon-Thibeault, Andrée-Anne; Oufkir, Talal; Vaillancourt, Cathy; Sanderson, J. Thomas

doi:10.1016/j.placenta.2011.06.003

Cited by 38 publications

(21 citation statements)

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“…CYP19 is expressed and active in H295R and BeWo cells, but different tissue-specific promoters are involved in its expression in each cell type (Klempan et al 2011; Sanderson et al 2004). In the fetoplacental unit, CYP19 is mainly regulated via the PKC pathway through the major placental I.1-promoter of CYP19 (Harada et al 2003).…”

Section: Discussionmentioning

confidence: 99%

A Unique Co-culture Model for Fundamental and Applied Studies of Human Fetoplacental Steroidogenesis and Interference by Environmental Chemicals

Thibeault

Deroy

Vaillancourt

et al. 2014

Environ Health Perspect

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Background: Experimental tools for studying the complex steroidogenic interactions that occur between placenta and fetus during human pregnancy are extremely limited.Objectives: We aimed to develop a co-culture model to study steroidogenesis by the human fetoplacental unit and its disruption by exposure to environmental contaminants.Methods: We cultured BeWo human choriocarcinoma cells, representing the villous cytotrophoblast, and H295R human adrenocortical carcinoma cells, representing the fetal unit, in a carefully adapted co-culture medium. We placed H295R cells in 24-well plates and BeWo cells on transwell inserts with or without pesticide treatment (atrazine or prochloraz) and assessed CYP19 activity and hormonal production after 24 hr of co-culture.Results: The co-culture exhibited the steroidogenic profile of the fetoplacental unit, allowing a synergistic production of estradiol and estriol (but not of estrone) of 133.3 ± 11.3 pg/mL and 440.8 ± 44.0 pg/mL, respectively. Atrazine and prochloraz had cell-type specific effects on CYP19 activity and estrogen production in co-culture. Atrazine induced CYP19 activity and estrogen production in H295R cells only, but did not affect overall estrogen production in co-culture, whereas prochloraz inhibited CYP19 activity exclusively in BeWo cells and reduced estrogen production in co-culture by almost 90%. In contrast, prochloraz did not affect estradiol or estrone production in BeWo cells in monoculture. These differential effects underline the relevance of our co-culture approach to model fetoplacental steroidogenesis.Conclusions: The co-culture of H295R and BeWo cells creates a unique in vitro model to reproduce the steroidogenic cooperation between fetus and placenta during pregnancy and can be used to study the endocrine-disrupting effects of environmental chemicals.Citation: Hudon Thibeault AA, Deroy K, Vaillancourt C, Sanderson JT. 2014. A unique co-culture model for fundamental and applied studies of human fetoplacental steroidogenesis and interference by environmental chemicals. Environ Health Perspect 122:371–377; http://dx.doi.org/10.1289/ehp.1307518

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Section: Discussionmentioning

confidence: 99%

A Unique Co-culture Model for Fundamental and Applied Studies of Human Fetoplacental Steroidogenesis and Interference by Environmental Chemicals

Thibeault

Deroy

Vaillancourt

et al. 2014

Environ Health Perspect

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“…Placental stem cells from human first trimester placenta can be induced to differentiate into neurons [52], and a recent study has shown the placenta to be a source of the neurotransmitter serotonin (5HT) [53]. Whether or not serotonin can affect foetal brain development is not known, but serotonergic receptor signalling has been shown to increase placental aromatase activity [54,55]. Placental aromatase is a key enzyme controlling oestrogen synthesis, and this does have important actions on the maternal hypothalamus and placenta during pregnancy [32].…”

Section: Hypothalamic/placental Co-adaptationmentioning

confidence: 99%

Importance of the matriline for genomic imprinting, brain development and behaviour

Keverne

2013

Phil. Trans. R. Soc. B

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Mammalian brain development commences during foeto-placental development and is strongly influenced by the epigenetic regulation of imprinted genes. The foetal placenta exerts considerable influence over the functioning of the adult maternal hypothalamus, and this occurs at the same time as the foetus itself is developing a hypothalamus. Thus, the action and interaction of two genomes in one individual, the mother, has provided a template for co-adaptive functions across generations that are important for maternal care and resource transfer, while co-adaptively shaping the mothering capabilities of each subsequent generation. The neocortex is complex, enabling behavioural diversity and cultural learning such that human individuals are behaviourally unique. Retrotransposons may, in part, be epigenetic mediators of such brain diversity. Interestingly some imprinted genes are themselves retrotransposon-derived, and retrotransposon silencing by DNA methylation is thought to have contributed to the evolutionary origins of imprint control regions. The neocortex has evolved to be adaptable and sustain both short-term and long-term synaptic connections that underpin learning and memory. The adapted changes are not themselves inherited, but the predisposing mechanisms for such epigenetic changes are heritable. This provides each generation with the same ability to make new adaptations while constrained by a transgenerational knowledge-based predisposition to preserve others.

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“…In other cell types, signaling via the 5-HT 2A receptor has been shown to affect cellular differentiation, proliferation, and migration, all of which are central to the function of placental trophoblast cells in the establishment of proper placentation [75, 76]. Such a relationship becomes more relevant because serotonin is synthesized de novo in human trophoblast cells where it likely serves an important endocrine, paracrine, and autocrine role in regulating placental function [77]. Indeed, treatment of cultured trophoblasts, BeWo and JEG-3 cells, with serotonin results in increased aromatase activity; an effect which may result in altered estrogen biosynthesis [77].…”

Section: Maternal Antipsychotic Use and Altered Birth Weight: Mechmentioning

confidence: 99%

Effect of Atypical Antipsychotics on Fetal Growth: Is the Placenta Involved?

Raha

Taylor

Holloway

2012

Journal of Pregnancy

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There is currently considerable uncertainty regarding prescribing practices for pregnant women with severe and persistent psychiatric disorders. The physician and the mother have to balance the risks of untreated psychiatric illness against the potential fetal toxicity associated with pharmacological exposure. This is especially true for women taking atypical antipsychotics. Although these drugs have limited evidence for teratological risk, there are reports of altered fetal growth, both increased and decreased, with maternal atypical antipsychotic use. These effects may be mediated through changes in the maternal metabolism which in turn impacts placental function. However, the presence of receptors targeted by atypical antipsychotics in cell lineages present in the placenta suggests that these drugs can also have direct effects on placental function and development. The signaling pathways involved in linking the effects of atypical antipsychotics to placental dysfunction, ultimately resulting in altered fetal growth, remain elusive. This paper focuses on some possible pathways which may link atypical antipsychotics to placental dysfunction.

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Stimulation of serotonergic 5-HT 2A receptor signaling increases placental aromatase (CYP19) activity and expression in BeWo and JEG-3 human choriocarcinoma cells

Cited by 38 publications

References 47 publications

A Unique Co-culture Model for Fundamental and Applied Studies of Human Fetoplacental Steroidogenesis and Interference by Environmental Chemicals

A Unique Co-culture Model for Fundamental and Applied Studies of Human Fetoplacental Steroidogenesis and Interference by Environmental Chemicals

Importance of the matriline for genomic imprinting, brain development and behaviour

Effect of Atypical Antipsychotics on Fetal Growth: Is the Placenta Involved?

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