`Battle of the sexes' begins in womb as father and mother's genes tussle
over nutrition

Date:
December 27, 2021
Source:
University of Cambridge
Summary:
Scientists have identified a key signal that the fetus uses to
control its supply of nutrients from the placenta, revealing a
tug-of-war between genes inherited from the father and from the
mother. The study, carried out in mice, could help explain why
some babies grow poorly in the womb.



FULL STORY ========================================================================== Cambridge scientists have identified a key signal that the fetus uses to control its supply of nutrients from the placenta, revealing a tug-of-war between genes inherited from the father and from the mother. The study,
carried out in mice, could help explain why some babies grow poorly in
the womb.


==========================================================================
As the fetus grows, it needs to communicate its increasing needs for
food to the mother. It receives its nourishment via blood vessels in
the placenta, a specialised organ that contains cells from both baby
and mother.

Between 10% and 15% of babies grow poorly in the womb, often showing
reduced growth of blood vessels in the placenta. In humans, these blood
vessels expand dramatically between mid and late gestation, reaching a
total length of approximately 320 kilometres at term.

In a study published today in Developmental Cell, a team led by scientists
at the University of Cambridge used genetically engineered mice to show
how the fetus produces a signal to encourage growth of blood vessels
within the placenta. This signal also causes modifications to other
cells of the placenta to allow for more nutrients from the mother to go
through to the fetus.

Dr Ionel Sandovici, the paper's first author, said: "As it grows in the
womb, the fetus needs food from its mum, and healthy blood vessels in
the placenta are essential to help it get the correct amount of nutrients
it needs.

"We've identified one way that the fetus uses to communicate with the
placenta to prompt the correct expansion of these blood vessels. When this communication breaks down, the blood vessels don't develop properly and
the baby will struggle to get all the food it needs." The team found
that the fetus sends a signal known as IGF2 that reaches the placenta
through the umbilical cord. In humans, levels of IGF2 in the umbilical
cord progressively increase between 29 weeks of gestation and term:
too much IGF2 is associated with too much growth, while not enough IGF2
is associated with too little growth. Babies that are too large or too
small are more likely to suffer or even die at birth, and have a higher
risk to develop diabetes and heart problems as adults.



==========================================================================
Dr Sandovici added: "We've known for some time that IGF2 promotes the
growth of the organs where it is produced. In this study, we've shown
that IGF2 also acts like a classical hormone -- it's produced by the
fetus, goes into the fetal blood, through the umbilical cord and to
the placenta, where it acts." Particularly interesting is what their
findings reveal about the tussle taking place in the womb.

In mice, the response to IGF2 in the blood vessels of the placenta is
mediated by another protein, called IGF2R. The two genes that produce IGF2
and IGF2R are 'imprinted' -- a process by which molecular switches on the
genes identify their parental origin and can turn the genes on or off. In
this case, only the copy of the igf2gene inherited from the father is
active, while only the copy of igf2rinherited from the mother is active.

Lead author Dr Miguel Consta^ncia, said: "One theory about imprinted
genes is that paternally-expressed genes are greedy and selfish. They
want to extract the most resources as possible from the mother. But maternally-expressed genes act as countermeasures to balance these
demands." "In our study, the father's gene drives the fetus's demands
for larger blood vessels and more nutrients, while the mother's gene in
the placenta tries to control how much nourishment she provides. There's
a tug-of-war taking place, a battle of the sexes at the level of the
genome." The team say their findings will allow a better understanding
of how the fetus, placenta and mother communicate with each other during pregnancy. This in turn could lead to ways of measuring levels of IGF2
in the fetus and finding ways to use medication to normalise these levels
or promote normal development of placental vasculature.



==========================================================================
The researchers used mice, as it is possible to manipulate their genes
to mimic different developmental conditions. This enables them to study
in detail the different mechanisms taking place. The physiology and
biology of mice have many similarities with those of humans, allowing researchers to model human pregnancy, in order to understand it better.

The lead researchers are based at the Department of Obstetrics and
Gynaecology, the Medical Research Council Metabolic Diseases Unit, part
of the Wellcome-MRC Institute of Metabolic Science, and the Centre for Trophoblast Research, all at the University of Cambridge.

The research was largely funded by the Biotechnology and Biological
Sciences Research Council, Medical Research Council, Wellcome Trust and
Centre for Trophoblast Research.

========================================================================== Story Source: Materials provided by University_of_Cambridge. The original
text of this story is licensed under a Creative_Commons_License. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Ionel Sandovici, Aikaterini Georgopoulou, Vicente Pe'rez-Garci'a,
Antonia
Hufnagel, Jorge Lo'pez-Tello, Brian Y.H. Lam, Samira N. Schiefer,
Chelsea Gaudreau, Fa'tima Santos, Katharina Hoelle, Giles
S.H. Yeo, Keith Burling, Moritz Reiterer, Abigail L. Fowden, Graham
J. Burton, Cristina M. Branco, Amanda N. Sferruzzi-Perri, Miguel
Consta^ncia. The imprinted Igf2-Igf2r axis is critical for matching
placental microvasculature expansion to fetal growth. Developmental
Cell, 2021; DOI: 10.1016/ j.devcel.2021.12.005 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211227154328.htm

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