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Geneva, Switzerland (SPX) Jan 08, 2013
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.
Growth, metabolism and reproduction
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."
Universite de Geneve
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