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Handbook of Clinical Gender Medicine


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Tel Aviv, Israel

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      Abstract

      In his book‘Life in the Womb’, Nathanielisz aptly states that’…how we are ushered into life, determines how we leave…’. This, in essence, is the basic idea of fetal programming, namely the understanding that during intrauterine life the stage is set for future health and disease. During fetal life, epigenetic changes aim to prepare the fetus for his future life, and if this preparation turns out to be inadequate the risk of various diseases increases. In this chapter, hormonal and genetic aspects of fetal sex determination will be presented, the effects of exogenous toxins on the fetal environment will be discussed, and the effects of the hormonal milieu on the development of the fetus will be reviewed, including the sexual dimorphous brain. Fetal programming of adult disease will be exemplified by maternal nutrition and stress, and the concept of the pregnant mother as an information window to the outside world will be discussed. Other topics like the impact of the intrauterine environment on future IQ and sexuality will be mentioned, and obstetric implications of fetal programming will be considered.

      Copyright © 2012 S. Karger AG, Basel

      What Is Fetal Programming?

      Hormonal and Genetic Aspects of Fetal Sex Determination

      One of the most crucial time windows which the human embryo faces occurs during a few hours sometime between 41 and 44 days after conception (in obstetrical terms during the 6th week of pregnancy). During these few fateful hours in that narrow time window, nature determines whether the developing fetus will be phenotypically male or female. Of course, chromosomal sex determination has already taken place during fertilization but, phenotypically, all odds are still open. If nothing happens during this time window, the embryo will by default develop into a phenotypic female. However, if a Y chromosome is present and a very specific single gene which is located on the short arm of that Y chromosome is activated, then the primitive gonad develops into a testicle and soon begins to secrete large amounts of testosterone and the embryo begins its development to become a phenotypic male. This sex-determining gene is named after its location on the Y chromosome, hence sex-determining region on the Y chromosome, in short SRY. The ensuing enormous testosterone production of the fetal testes will have a crucial impact on the subsequent development of intrauterine and extrauterine gender differences.

      The chromosomal makeup and the hormonal environment and the appropriate functional receptors for various hormones thus determine the phenotypic sex.

      Exogenous Effects on the Intrauterine Environment

      It is now common understanding that prenatal life is no safe haven for the fetus and that the environment in which the pregnant mother lives has a direct impact on the development of the fetus. In effect, there is no other time throughout the life span of an individual where it is so intimately exposed to the environment. Whatever affects the pregnant mother may well affect her growing embryo and fetus, in many cases in a greatly amplified manner. The impact of exogenous toxins on the developing fetus is dependent on qualitative and quantitative factors and also on when they occur during the development of the fetus. First trimester exposure will generally have teratogenic effects while second and third trimester exposure will more often be expressed in growth restriction and organ failure.