So, is it a girl or a boy? This is the first
question parents ask at the birth of an infant.
Though the answer is obvious, the mechanism of sex
determination is much less so. Researchers at the
University of Geneva (UNIGE) attempt to shed light
on this complex process by identifying the crucial
role played by insulin and IGF1 and IGF2 growth
factors, a family of hormones known for its role in
metabolism and growth.
In the absence of these factors at the time of sex
determination, embryos do not differentiate into
either male or female and have no adrenal glands.
The results of this study, published in the journal
PLOS Genetics, allow us to better understand sexual
development and will eventually improve diagnosis
and genetic counseling practices for individuals
with disorders of sex development.
In mammals, sexual development is a long process
beginning at conception when the sperm's
transmission of an X or Y sex chromosome will
determine the genetic sex of the embryo. The
following developmental stages will translate this
genetic sex into gonadal sex, that is, either
ovaries or testes, which will secrete hormones that
will masculinise or feminise the foetus. The
intention of the study conducted by Serge Nef,
Professor at the Department of Genetic Medicine and
Development at UNIGE, is to better understand the
first stages of sexual development.
The researchers were interested in the role of a
class of hormones, insulin-like growth factors (IGFs),
and their receptors in cells. These factors, known
to be involved in the regulation of metabolism and
growth, also have a key role in the regulation of
reproductive capacities of the individual, whether
male or female. Reproductive function is, in fact,
closely linked to metabolism and growth. This is
actually quite logical: the growth of an individual
cannot progress normally without adequate energy
intake and there is no point in reproducing if this
caloric intake is insufficient. This may explain why
some women with anorexia have anovulatory cycles and
may suffer from infertility.
Conversely, people with morbid obesity also have
significant disturbances in their fertility. Though
it is now recognized that the interactions between
metabolism, growth and reproductive capacity are
regulated by common factors such as insulin and IGFs,
Professor Nef's study shows that these interactions
are even more important than previously believed
because the insulin and IGF receptors are also
essential for primary sex determination in mammals.
To analyze the impact of these hormones on sex
determination, Professor Nef's group used
genetically modified mice. The scientists
genetically inactivated the receptors for insulin
and IGFs in mouse embryos. They then discovered that
in the absence of these factors, at the time of sex
determination, the gonads of mutant embryos were
unable to develop into testes or ovaries. As such,
the embryo and its gonads remained stuck in a fully
undifferentiated state for several days
demonstrating the essential role of these hormones
and growth factors in sexual differentiation.
In humans, cases of disorders of sex development are
relatively common with about 1 newborn in every 3000
births being affected. Unfortunately, in the
majority of cases, the genetic causes of such
alterations remain unexplained. "This study provides
a better understanding of the basic mechanisms of
sexual development and is a step forward towards a
better understanding of the causes of sexual
ambiguities, which often remain unknown," states
Professor Nef. "The research we are conducting will
provide the opportunity to refine and improve
clinical diagnosis of individuals with disorders of
sex development."
For more information
Université de Genève
http://www.plosgenetics.org/
(MDN)
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