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Marek Glezerman, MD
Department of Obstetrics and Gynecology
Helen Schneider Hospital for Women, Rabin Medical Center
IL-49100 Petah Tiqwa (Israel)
Tel. +972 3 6952443, E-Mail [email protected]
Social and Biological Determinants in Health and Disease
Schenck-Gustafsson K, DeCola PR, Pfaff DW, Pisetsky DS (eds): Handbook of Clinical Gender Medicine.
Basel, Karger, 2012, pp 52–67
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Pierre D.E. Mouriquanda · Justine M. Schoberb
aDepartment of Pediatric Urology, Hôpital Mère-Enfants - Groupement Hospitalier Est, Bron, France; bDepartment of Urology, UPMC Hamot, Erie, Pa., USA
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Abstract
Developmental biology discoveries have advanced our understanding of anatomic details of the process and influences of genital formation. Although all malformations of the urinary and genital tracts are not yet explained by embryology, some malformations can be related to stages of development and hormonal or genetic factors. We continue to elucidate genes, proteins, and pathways related to sexual differentiation and organotypic features. Understanding the androgen and estrogen receptor status of genital tissue is critical to medical and surgical therapy considerations impacting the surface integrity of urogenital epithelium. Continuing elucidation of the embryology and immunohistochemistry of urogenital tissue may be a step toward the development of molecular tools to treat urogenital abnormalities. This chapter outlines the embryology, known causes, diagnostic categorization, and considerations for ambiguous genitalia.
Copyright © 2012 S. Karger AG, Basel
Sex Determination
Chromosomes, Embryology, Hormones, and Receptors
Sex differentiation can be divided into 3 phases. Chromosomal sex is established at fertilization. Male sex differentiation almost always occurs if a functioning sex-determining region of the Y chromosome (SRY) gene is present. Two functional X chromosomes are necessary for reproductive females. Deletions from Xp or Xq, or from both, have indicated that genes from both arms of the X chromosome are involved in ovarian differentiation and maturation. On Xq in the paracentromeric region there is a location for androgen receptor protein and for X inactivation. In female mammals this is important for dosage inactivation of one X chromosome. Random inactivation is fixed for each cell, and its progeny, so that each female is a mosaic of paternal and maternal active X chromosomes.
The second step is differentiation of the gonads. Development of the reproductive tract begins in the embryo and is sex independent. In the human, the embryonic period spans weeks 2-8 of gestation. Until the fetus reaches 50 mm in CR length (9 weeks), the genitalia in both sexes look identical. Germ cells appear in the epiblast and migrate through the primitive streak and then to the base of the allantois. Along the wall of the hindgut, they migrate to the urogenital ridge. In the primitive gonad, primitive sex cords displaying corticomedullary architecture are formed by the end of the 6th week. The third
