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It is thanks to viruses that humans (and other mammals) no longer lay eggs

EVOLUTION – Discover, every day, an analysis of our partner The Conversation. Today, a cell biology professor explains why mammals no longer hatch from an egg

While plastic microparticles have just been detected in human placentas, let’s come back to the formation of this organ with essential functions in mammals.

Mammals do not lay eggs. Finally, not all mammals since theornithorynque and the echnidae are original by persisting in laying eggs, with an embryonic development that takes place in the shelter of a shell.

The short-nosed echidna, or Australian echidna, is one of the rare oviparous mammals © Penny Ash / Pixabay

How did so-called eutherian or placental mammals lose their shells?

The story is said to be over 150 million years old: the ancestors of mammals, which laid eggs, caught “a virus”. The genetic material of these ancestors integrated genetic sequences of viruses. The integrations of these viral sequences are reproduced and repeated over time: proteins essential to cell fusion are thus incorporated into the genome of mammals. These viral sequences allowed the production of proteins that spelled the death knell for the shell and the advent of a new organ: the placenta. These animals have become viviparous: the development of the embryo no longer takes place outside the maternal organism, but in the uterus.

Of both maternal and embryonic origin, the placenta performs metabolic roles essential to the development of the embryo. It is made up of both maternal cells from the uterus and embryonic cells. It constitutes a body in its own right. The placenta is a place of exchange: it allows the fetus to draw from the mother’s body the elements necessary for embryonic development, such as nutrients or oxygen. It flushes out urea and carbon dioxide produced by the fetus. It is considered as a place of immunological tolerance allowing the maintenance of the fetus in the maternal organism. It also produces hormones that support fetal development as well as lactation. Finally, the placenta also forms a protective barrier for the fetus against most parasites and bacteria, but certain viruses or compounds, such as alcohol, pass through this organ and affect fetal development.

The invention of the placenta: syncytins

How is a placenta formed? A few days after fertilization, the mammalian embryo is made up of two populations of cells: the embryonic button and the trophoblaste.

Blastocyst. The mammalian embryo is a hollow sphere, the circumference of which is formed by the cells of the trophoblast. They will participate in the formation of the placenta. The cells that will organize the embryo constitute a modest cell mass, shaped like a “button” © Medical Graphics, CC BY-NC-ND

The embryonic button will make up all of the organs of the embryo, while the peripheral trophoblast cells will be responsible for building extraembryonic structures like the placenta. Part of the trophoblast, called a syncytiotrophoblast, forms a layer of fused cells. When several cells merge, a giant cell is formed. Possessing several nuclei, this structure is called syncytium. These fused cells “attack” the maternal tissues, puncture them and allow anchoring (called implantation) of the embryo.

The fusion of trophoblast cells is an essential step for the implantation of the embryo in the uterus and for the proper course of development. It is provided by specific proteins: syncytins. Syncytin-like proteins are expressed in the placentas of almost all mammals. The simultaneous loss of the two types of syncytins expressed in mice prevents the development of a placenta and causes the early death of embryos, emphasizing their crucial role in development.

Retroviral nudges: exhilarating exaptation

The viral origin of syncytines has been demonstrated by paleovirologists, who are able to detect in a genome “fossil viruses” or sequences resulting from the integration, in the past, of viral genetic material. This viral origin provides an amazing example of the phenomenon called exaptation.

By the term exaptation, Stephen J. Gould and Elizabeth Vrba illustrated how complex functions can arise from simple structures or elements. For example, selected because they ensured temperature regulation, the feathers would then have allowed adaptation to flight.

The genes called Env, which belong to a family of genes encoding proteins forming the viral envelope, provide another example of exaptation. At the retrovirus, the proteins Env, encoded by these genes, are envelope proteins by which viral particles fuse their membranes with those of target cells. This fusion allows infection of the cell by bypassing the host’s immune system. Integrated and transmitted to progeny in mammals, these Env genes have evolved into syncytin-like proteins.

Is the appearance of the placenta a unique event?

It is astonishing to note that the domestication of these genes was not done only once, but derives from at least ten independent infections by different retroviruses, during the evolution of mammals. The acquisition of a placenta would therefore be a convergent development. The oldest known type of syncytin has been identified in carnivores. Integration of the conserved syncytin-1 gene in humans is believed to have occurred 30 million years ago, while syncytin genes integrated in mice more than 25 million years ago.

Different retroviral infections have therefore repeatedly favored cell fusion mechanisms leading to the formation of syncytium at the interface between fetal and maternal tissues and contributing to the development of original intrauterine development, thanks to the formation of a “retroviral envelope”. The cell fusion and immunosuppressive properties of syncytins would have favored the maintenance and development of this new structure.

The HIV virus is released from the cell membrane of a T lymphocyte © NTB scanpix, CC BY-NC-ND

The diversity of syncytin genes may reflect the morphological diversity of placentas in mammals. Depending on the species, the placenta juxtaposes the embryonic and maternal structures or anchors the embryo deeply in the uterine tissues. Mammals would not be the only ones to have captured syncytins. The latter have been detected in a few rare placental vertebrates distant from mammals, such as the Mabuya lizard. This same mechanism would therefore have played a crucial role in the appearance and development of placentas in vertebrates.

Vulnerability

Embryonic development within a uterus does not make this development less sensitive and vulnerable. The placenta, which creates intimacy between mother and offspring, is an organ that both protects and exposes the fetus. The active or passive properties and mechanisms that allow the exchanges essential to development also allow the passage of substances with harmful effects. Viruses such as those of rubella, chickenpox, HIV or parvovirus, as well as infectious agents such as toxoplasms, turn this place of exchange to their advantage to invade it and contaminate the embryo. Certain pharmaceutical agents, metals or alcohol have sinister reputations, due to the deleterious effects which it causes in the embryo.

Our “Pregnancy” file

Very recently, plastic microparticles have been detected in human placentas. These particles are said to have been inhaled or ingested by the mothers. The effects of these particles remain unknown but the detection of this type of plastic is worrying for several reasons: can they alter the essential functions of the placentas such as immune regulation? Can they upset the development of fetuses? These observations remind us of the vulnerability of embryonic development.

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