The Difference between the Sexes - From Biology to Behaviour

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Eric Vilain

UCLA, USA

Biography

Eric Vilain, M.D., Ph.D., was born in Paris, France, and earned his M.D. from the Paris Children’s Hospital Necker, his Ph.D. from the Pasteur Institute in Paris, France, then completed a post-doctoral fellowship in Medical Genetics at the University of California, Los Angeles. He is Professor of Human Genetics, Pediatrics and Urology in the David Geffen School of Medicine at UCLA, the Chief of Medical Genetics in the Department of Pediatrics and the Director of the Center for Gender-Based Biology. His laboratory explores the genetics of sexual development, focusing on the molecular mechanisms of gonad development, as well as on the genetic determinants of brain sexual differentiation. He has identified a large number of mutations in sex-determining genes, developed animal models with atypical sexual development, and identified genes differentially expressed between male and female fetal mouse brains. He currently works at three projects: the genetics of Disorders of Sex Development (intersexuality), the genetics of sexual orientation and gender identity, and the biological bases of sex differences in susceptibility to diseases, particularly for Parkinson’s disease and hypertension. His research program has been continuously supported by several grants from the NIH, and he has published extensively in the field of sexual development. He is a Fellow of the American College of Medical Genetics, and a member of numerous professional committees, including those related to the care of intersex individuals.

Abstract

Pink Genes or Blue Genes? A Biological Perspective on Sexual Development

Sex matters! Men and women differ considerably in their anatomy, their metabolism, their life span, their behavior and their susceptibility to diseases. Our research efforts have focused on the origin of sex differences in the development of the reproductive organs, including the brain.

Sex determination refers to the developmental decision that directs the orientation of the bipotential, undifferentiated embryo into a sexually dimorphic individual. In mammals, and in humans in particular, this decision occurs during the development of the gonads.

The molecular mechanisms of human sex determination are poorly understood as known genetic defects have been identified in only a minority of patients with disorders of sex development (DSD). These disorders encompass a large spectrum of phenotypes, from minor malformations of the genitalia (hypospadias, cryptorchidism, hypertrophy of the clitoris) to genital ambiguity, and taken together, have an estimated frequency of about 1%. They can have severe consequences in terms of behavioral health, infertility, risk of cancer and quality of life. For families, the birth of a child with a DSD, and the accompanying uncertainty about the child’s future psychological and sexual development, is believed to be extraordinarily stressful. Recently, the debate about the management of intersex patients has intensified over issues of gender assignment and the indication for early genital surgery; yet the scientific data on patient outcomes have remained poor. Major obstacles to the optimal management of DSD include gaps in understanding of pathophysiology, preventing precise diagnostic categorization of patients, along with the absence of prospective longitudinal studies of health and quality of life outcomes. We will present the most recent genetic discoveries in sex determination, and discuss the current burning controversies in the field.

Research on patients with DSD has also led us to investigate sexual differentiation of the human brain and its behavioral consequences. The traditional view that all meaningful sex differences in the brain are exclusively influenced by gonadal secretions has been recently challenged. The accumulated evidence from animal and human models provides strong arguments for a role – whether isolated or in concert with gonadal hormones - of sex chromosomes and of sex-specific genes. Behavioral traits such as sexual orientation and gender identity are also highly sexually dimorphic, and we will present the biological approaches that have been used to determine the role of genetics, hormones and environment in the development of these complex traits.