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bioRxiv · 10.1101/2023.06.18.545206

The extension of mammalian pregnancy required taming inflammation; independent evolution of extended placentation in the tammar wallaby

Dudley, J. S.·Renfree, M. B.·Wagner, G. P.·Griffith, O. W.
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Abstract

In the first live bearing mammals, it is assumed that pregnancy was short and ended with a brief period of inflammatory maternal-fetal interaction. This mode of reproduction has been retained in many marsupials. While inflammation is key to successful implantation in eutherians, a key innovation in eutherians is the ability to switch off this inflammation after it has been initiated. This extended period, in which inflammation is suppressed, likely allowed for an extended period of placentation. One lineage of marsupials, the macropodids (wallabies and kangaroos), have extended placentation beyond the 2-4 days seen in other marsupial taxa, which allows us to test whether a moderated inflammation response after attachment is a general pattern associated with the extension of placentation in mammals. We show that during tammar wallaby pregnancy, some inflammatory genes are expressed at key time points of gestation, including IL6, before attachment, IL12A and LIF throughout the period of placentation and prostaglandins before birth. However, we did not see evidence of a complete inflammatory response at any time point. We argue that genes involved in a moderated inflammation reaction may have been co-opted into roles for placentation, facilitating the establishment and maintenance of extended fetal-maternal contact. Whilst the absence of other key mediators of inflammation may prevent prolonged damage to the uterus. We argue the moderation of inflammation following maternal-fetal contact is a convergently evolved key innovation that allowed for the extension of placentation in different mammalian lineages. Significance statementOur data suggest that moderation of the inflammatory reaction to embryo attachment allows for extension of pregnancy in mammals. The ancestor of all mammals likely experienced an ancestral inflammatory reaction in response to embryo attachment. In contrast, eutherians and some marsupials, such as macropodids, have an extended period of fetal-maternal contact. During this period of placentation many inflammatory genes are silenced while a few others are still expressed. This moderated expression of inflammatory genes suggests that some genes of inflammation were coopted into establishing and maintaining the placenta. This challenges the perspective of inflammation as being detrimental to pregnancy, instead suggesting that fetal-maternal interactions are based on a modified inflammation response necessary for maintaining pregnancy over an extensive period of time.

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Dudley, J. S., Renfree, M. B., Wagner, G. P., Griffith, O. W.. 2023-06-21. The extension of mammalian pregnancy required taming inflammation; independent evolution of extended placentation in the tammar wallaby. https://doi.org/10.1101/2023.06.18.545206

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