Placental programming of anxiety in adulthood revealed by Igf2-null models

Mikaelsson, Mikael Allan; Constância, Miguel; Dent, Claire L.; Wilkinson, Lawrence S.; Humby, Trevor

doi:10.1038/ncomms3311

Cited by 67 publications

(64 citation statements)

References 58 publications

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“…Placental specific deletion of the Igf2-P0 transcript in mice was associated with intrauterine growth restriction, an imbalance between fetal requirement and placental delivery of nutrients, and curiously, anxiogenic effects later in life (103). Although the results support a linkage between placental responses and later behavioral alterations, the study did not examine for potential sex differences.…”

Section: Placental-brain Axismentioning

confidence: 89%

Sex-Specific Placental Responses in Fetal Development

2015

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The placenta is an ephemeral but critical organ for the survival of all eutherian mammals and marsupials. It is the primary messenger system between the mother and fetus, where communicational signals, nutrients, waste, gases, and extrinsic factors are exchanged. Although the placenta may buffer the fetus from various environmental insults, placental dysfunction might also contribute to detrimental developmental origins of adult health and disease effects. The placenta of one sex over the other might possess greater ability to respond and buffer against environmental insults. Given the potential role of the placenta in effecting the lifetime health of the offspring, it is not surprising that there has been a resurging interest in this organ, including the Human Placental Project launched by the National Institutes of Child Health and Human Development. In this review, we will compare embryological development of the laboratory mouse and human chorioallantoic placentae. Next, evidence that various species, including humans, exhibit normal sex-dependent structural and functional placental differences will be examined followed by how in utero environmental changes (nutritional state, stress, and exposure to environmental chemicals) might interact with fetal sex to affect this organ. Recent data also suggest that paternal state impacts placental function in a sex-dependent manner. The research to date linking placental maladaptive responses and later developmental origins of adult health and disease effects will be explored. Finally, we will focus on how sex chromosomes and epimutations may contribute to sex-dependent differences in placental function, the unanswered questions, and future directions that warrant further consideration.

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Section: Placental-brain Axismentioning

confidence: 89%

Sex-Specific Placental Responses in Fetal Development

2015

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“…The use of a bi-transgenic mouse model shows that IGFI plays a significant role in programming growth as well as sustaining postnatal development and reproductive function (Stratikopoulos et al 2008). In contrast, IGFII modulates fetal and placental growth (Constancia et al 2002) and appears to influence the placental programming of anxiety in the adult offspring (Mikaelsson et al 2013).…”

Section: Insulin-like Growth Factor I and Ii (Igfi And Igfii)mentioning

confidence: 97%

Female Tract Cytokines and Developmental Programming in Embryos

Robertson

Chin

Schjenken

et al. 2015

Advances in Experimental Medicine and Biology

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In the physiological situation, cytokines are pivotal mediators of communication between the maternal tract and the embryo. Compelling evidence shows that cytokines emanating from the oviduct and uterus confer a sophisticated mechanism for 'fine-tuning' of embryo development, influencing a range of cellular events from cell survival and metabolism, through division and differentiation, and potentially exerting long-term impact through epigenetic remodelling. The balance between survival agents, including GM-CSF, CSF1, LIF, HB-EGF and IGFII, against apoptosis-inducing factors such as TNFα, TRAIL and IFNg, influence the course of preimplantation development, causing embryos to develop normally, adapt to varying maternal environments, or in some cases to arrest and undergo demise. Maternal cytokine-mediated pathways help mediate the biological effects of embryo programming, embryo plasticity and adaptation, and maternal tract quality control. Thus maternal cytokines exert influence not only on fertility and pregnancy progression but on the developmental trajectory and health of offspring. Defining a clear understanding of the biology of cytokine networks influencing the embryo is essential to support optimal outcomes in natural and assisted conception.

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“…14 The specific importance of placental expression of the imprinted gene IGF2 has also been demonstrated through placental specific disruption in mice, resulting in increased reactivity to stress stimuli; this phenotype was not observed in total knockouts. 7 A better understanding of molecular mechanisms underlying the regulation of neurodevelopment could aid in identifying individuals who may benefit from early life interventions, when such interventions may be most successful. Our group has previously explored the role of placental imprinted gene expression in neurodevelopmental outcomes.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4] Alterations in DNA methylation at imprinted sites, suggestive of altered imprinting status, have been linked to greater risk for the development of schizophrenia in humans, 5 as well as with general cognitive and behavioral defects in mice. [6][7][8] The placenta is an important mediator in the communication between the developing fetus and the maternal environment. This organ regulates nutrient and waste exchange, facilitates interactions with the maternal immune system, and acts as a neuroendocrine organ by producing important hormones and growth factors.…”

Section: Introductionmentioning

confidence: 99%