Abstract
Pregnancy is a unique situation, in which two (or more) individuals are in intimate contact, with development of the foetus supported by a specialised structure called the placenta. The placenta transports nutrients and waste, and provides a physical barrier between the maternal and foetal circulation. Importantly for this chapter, the placenta functions as an endocrine organ, synthesising hormones that flood the maternal circulation, inducing and maintaining the critical adaptations required for a successful pregnancy. While mammals have adopted different strategies to synthesise hormones in sufficiently high concentrations, and there are considerable variations in the nature of placental hormone gene families, the adaptations driven by placental hormones are conserved at a fundamental level. These adaptations include changes in behaviour of the mother to ensure that offspring receive appropriate care and nutrition. Experimental studies in rodents have identified placental hormones that contribute to the priming of this maternal behaviour. Studies in humans suggest that aberrant expression of placental hormones may contribute to the higher incidence of mood disorders associated with pregnancy. Hormones synthesised by, or dependent on, the placenta may also act directly on the foetal brain influencing neurodevelopment. Through this bi-directional signalling of hormones, the placenta has potential to influence both maternal and offspring behaviour. For these reasons, studies on placental endocrine lineage development are fundamentally important for our understanding of brain health.
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Acknowledgements
With thanks to members of Preg_lab past and present, and Hannah Tyson for her comments on the chapter. Research relevant to this chapter was funded by Medical Research Council (MR/M013960/1) and Biotechnology and Biological Sciences Research Council (BB/J015156; BB/P002307/1; BB/P008623/1).
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Key References: See Main List for Reference Details
Key References: See Main List for Reference Details
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Bridges and Freemark (1995). First report that (human) placental lactogen induces maternal behaviour in non-pregnant rats.
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Simmons et al. (2008). Characterisation of the spatial and temporal expression of prolactin family members in the mouse placenta. This work identified the spongiotrophoblast as a major endocrine lineage.
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Tunster et al. (2016a). First demonstration that the maternally expressed imprinted gene Phlda2 is a key negative regulator of the mouse spongiotrophoblast lineage, which is the major endocrine lineage of the mouse placenta. Loss-of-function of Phlda2 increased the size of this lineage and the global expression of key placental hormones, including mouse placental lactogen.
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Creeth et al. (2018). First demonstration that maternal behaviour is modulated by the dosage of Phlda2 in the mouse foetus. Genetically wild type dams exposed to higher levels of Phlda2 in their offspring (lower placental hormones) were more focused on nest building while those exposed to lower levels of Phlda2 in their offspring (higher placental hormones) were more focused on nurturing and grooming their pups.
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Bonnin et al. (2011). First experimental demonstration that the mouse placenta is a source of serotonin for the foetal brain, with the potential to influence foetal brain development and later-life behaviour.
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Sumption et al. (2020). Reported low placental lactogen associated with symptoms of postnatal depression and anxiety.
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John, R.M. (2024). The Placenta as a Neuroendocrine Organ. In: Brunton, P.J., Grattan, D.R. (eds) Neuroendocrine Regulation of Mammalian Pregnancy and Lactation. Masterclass in Neuroendocrinology, vol 15. Springer, Cham. https://doi.org/10.1007/978-3-031-51138-7_2
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