The placenta goes viral: Retroviruses control gene expression in pregnancy - PMC
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PLoS Biol<br>. 2018 Oct 9;16(10):e3000028. doi: 10.1371/journal.pbio.3000028
The placenta goes viral: Retroviruses control gene expression in pregnancy
Edward B Chuong<br>Edward B Chuong
1BioFrontiers Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado, United States of America
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1,*
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1BioFrontiers Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado, United States of America
The author has declared that no competing interests exist.
✉* E-mail: edward.chuong@colorado.edu
Collection date 2018 Oct.
© 2018 Edward B. Chuong
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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PMCID: PMC6177113 PMID: 30300353
See "Anthropoid primate–specific retroviral element THE1B controls expression of CRH in placenta and alters gestation length", e2006337.
Abstract
The co-option of endogenous retroviruses (ERVs) is increasingly recognized as a recurrent theme in placental biology, which has far-reaching implications for our understanding of mammalian evolution and reproductive health. Most research in this area has focused on ERV-derived proteins, which have been repeatedly co-opted to promote cell–cell fusion and immune modulation in the placenta. ERVs also harbor regulatory sequences that can potentially control placental gene expression, but there has been limited evidence to support this role. In a recent study, Dunn-Fletcher and colleagues discover a striking example of an ERV-derived enhancer element that has been co-opted to regulate a gene important for human pregnancy. Using genomic and experimental approaches, they firmly establish that a primate-specific ERV functions as a placenta-specific enhancer for corticotropin-releasing hormone (CRH), a hormone linked to the control of birth timing in humans. Their findings implicate an extensive yet understudied role for retroviruses in shaping the evolution of placental gene regulatory networks.
The rapidly evolving placenta
The ancestral form of our placenta emerged roughly 130 million years ago, marking a key evolutionary innovation that enabled live birth in mammals [1]. In mammalian development, the fetal placenta is the first organ to form and is responsible for anchoring the embryo to the uterus and mediating physiological exchange with the mother. The placenta sustains the fetus throughout pregnancy, and defects in placentation are at the root of many pregnancy complications. Yet despite its significance for evolution, development, and reproductive health, the placenta is arguably the least understood of all mammalian organs.
One of the unique challenges to studying the placenta is the fact that it exhibits unexpectedly wide variation in form and function across species, despite performing a conserved role supporting fetal development. The mammalian placenta shows great diversity across species in its morphology and tissue organization, mechanisms of implantation and invasion, and physiological regulation [2,3]. Even trophoblast cells, the cellular building blocks of the placenta, bear little morphological or molecular resemblance across species [4]. Current theories suggest that life history changes and/or parent–offspring conflicts over maternal resources promoted rapid evolution of the placenta [5,6]. The diverse array of placental shapes and sizes has complicated efforts to model human placentation in other animals but also underscores its unusual biology and evolutionary history [7].
What fueled the explosive evolutionary diversification of the mammalian placenta? Addressing this question is crucial for understanding mammalian reproductive biology and human-specific conditions of pregnancy [1,8]. Intriguingly, a mounting body of evidence suggests that the evolution of the placenta had significant assistance from ancient retroviruses.
Placenta's little helpers
Retroviruses, which include...