JBS BioEthics Sexual Development 2011 - 2012 Remind students about the sensitive nature of the things we will be discussing. 1 JBS BioEthics Sexual Development 2011 - 2012 sex is a biological term which refers to the functional differences between males and females and their reproductive potential male and female are biological terms sex is determined by genes in chromosomes Ususally assigned at birth sexuality is a psychological term which refers to our awareness and reaction to biological sex masculine and feminine are psychological terms which refer to a person's gender gender is determined by biological, psychological and sociological factors gender role: adoption of masculine or feminine behavioral traits that are deemed appropriate or characteristic of a particular gender – observable dress and behavior gender identity: a person's private, subjective sense of maleness or femaleness sexual orientation / preference: erotic desire for people of same or different sex 2 JBS BioEthics Sexual Development 2011 - 2012 In some cases, all of these will be typically associated with one sex. Other times, a person can have some characteristics associated with two different sexes 3 JBS BioEthics Sexual Development 2011 - 2012 According to a nature view of psychosexual differentiation, prenatal exposure to androgen influences the development of gender identity - the feeling an individual has of being a man or a woman. In contrast the nurture position holds that we are psychosexually neutral at birth and that socialization is responsible for the development of gender identity. 4 JBS BioEthics Sexual Development 2011 - 2012 Male, identical twin, Canada Accident with circumcision at 8 months (done because foreskin was not retracting); penis destroyed Parents took him to Johns Hopkins, psychologist John Money prominent proponent of the theory that gender identity was relatively "plastic" in infancy and developed primarily as a result of social learning from early childhood; most liberal academics in the late 1960s felt that all psychological and behavioral differences between males and females were learned at the age of 22 months, surgery was performed to remove his testes and construct a vagina; given the name Brenda; would be used as a test case (WHY? - identical genes, fetal environ., family environ. And no abnormal prenatal hormones) Reimer's later account, written with John Colapinto, described how, contrary to Money's reports, Brenda did not feel like a girl. She was ostracized and bullied by peers, and neither frilly dresses nor female hormones made her feel female. By the age of 13, Brenda was experiencing suicidal depression, and told her parents she would commit suicide if they made her see John Money again. In 1980, Brenda's parents told her the truth about her gender reassignment, following advice from Brenda's endocrinologist and psychiatrist. Now 15, Brenda decided to assume a male gender identity, calling himself David. After learning of the new relationship with his ex-sister, Brian began to experience a pattern of mental disturbance that would develop into schizophrenia. By 1997, David had undergone treatment to reverse the reassignment, including testosterone injections, a double mastectomy, and two penis reconstruction operations. He had married a woman, and become a stepfather to her children Although the book made David Reimer more comfortable financially, many other things went badly in his life, including a separation from his wife, severe problems for his parents, and the death of his twin brother Brian in 2002 from an overdose of schizophrenia medication. David Reimer took his own life with a sawed- off shotgun in 2004. 5 JBS BioEthics Sexual Development 2011 - 2012 6 JBS BioEthics Sexual Development 2011 - 2012 Male, identical twin, Canada Accident with circumcision at 8 months (done because foreskin was not retracting); penis destroyed Parents took him to Johns Hopkins, psychologist John Money prominent proponent of the theory that gender identity was relatively "plastic" in infancy and developed primarily as a result of social learning from early childhood; most liberal academics in the late 1960s felt that all psychological and behavioral differences between males and females were learned at the age of 22 months, surgery was performed to remove his testes and construct a vagina; given the name Brenda; would be used as a test case (WHY? - identical genes, fetal environ., family environ. And no abnormal prenatal hormones) Reimer's later account, written with John Colapinto, described how, contrary to Money's reports, Brenda did not feel like a girl. She was ostracized and bullied by peers, and neither frilly dresses nor female hormones made her feel female. By the age of 13, Brenda was experiencing suicidal depression, and told her parents she would commit suicide if they made her see John Money again. In 1980, Brenda's parents told her the truth about her gender reassignment, following advice from Brenda's endocrinologist and psychiatrist. Now 15, Brenda decided to assume a male gender identity, calling himself David. After learning of the new relationship with his ex-sister, Brian began to experience a pattern of mental disturbance that would develop into schizophrenia. By 1997, David had undergone treatment to reverse the reassignment, including testosterone injections, a double mastectomy, and two penis reconstruction operations. He had married a woman, and become a stepfather to her children Although the book made David Reimer more comfortable financially, many other things went badly in his life, including a separation from his wife, severe problems for his parents, and the death of his twin brother Brian in 2002 from an overdose of schizophrenia medication. David Reimer took his own life with a sawed- off shotgun in 2004. 7 JBS BioEthics Sexual Development 2011 - 2012 Up to the 9th week of prenatal development, sexes look alike. Week 5: All embryos develop two unspecialized gonads Week 5: gonads form near two sets of ducts -- two options Mullerian ducts -- form the female structures Wolffian ducts -- form male structures Week 6: Choice of which ducts develops Depends on which sex chromosomes present, especially on activation of the SRY gene on the Y chromosome SRY activation--> male route No SRY --> female route 8 JBS BioEthics Sexual Development 2011 - 2012 The Mullerian ducts degenerate (influenced by anti Mullerian hormone) The neutral gonad becomes a teste All the male structures, internally and externally, develop: Vas Deferens, prostrate, seminal vesicles, penis, 9 JBS BioEthics Sexual Development 2011 - 2012 No Y, no SRY gene results in female development, no anti mullerian hormone “Default” program Gonad develops into an ovary, Fallopian tubes, uterus, vagina 10 JBS BioEthics Sexual Development 2011 - 2012 Females: homogametic Males: heterogametic (Other species: reverse can be true, as in birds) 11 JBS BioEthics Sexual Development 2011 - 2012 X chromosome: 1500 genes Y chromosome: Maybe 90 protein genes Y chromosome does not have a complete homolog: How to map it? Examine men who were missing parts of the chromosome and see how they differed Now, use genome sequence: Findings: Unusual Short arm, long arm Tips: pseudoautosomal (PAR1 and PAR2) 5% - Homologous to the X chromosome 63 pseudoautosmal genes have counterparts on X chromosome Example of these genes: bone growth, cell division, immunity, signal transduction, syn. Hormones, energy met. MYS = Male-specific region (formerly called nonrecombining region) - 27 genes Does NOT recombine with the X chromomosome male fertility: SRY gene!! also has the AZF gene - codes for a protein needed to make sperm (Azoospermia factor) Azoospermia factor (AZF) refers to one of several proteins or their genes, which are coded from the AZF region on the human male Y chromosome.[1] Deletions in this region are associated with inability to produce sperm. Recall how the SRY gene was discovered (1990) - XX males (had part of Y) and XY females (missing part of the Y) 12 JBS BioEthics Sexual Development 2011 - 2012 In 95% of the chromosome that has male-specific genes, many DNA segments are palindromes “Madam I’m Adam” This destabilizes the enzymes that replicate DNA Sections of the Y chromosome attract each other,; this can loop out parts in between and account for male infertility caused by missing parts of the Y chromosome http://www.txtwriter.com/Onscience/Articles/ychromosome.html 12 JBS BioEthics Sexual Development 2011 - 2012 SRY gene discovered 1989 SRY gene codes for a transcription factor. It turns on genes located on other chromosomes 13 JBS BioEthics Sexual Development 2011 - 2012 early in week 4 primordial germ cells from the yolk sac migrate to the gonadal ridges. During week 6 the germ cells become incorporated into the gonad. SRY gene - codes for Transcription factors control expression of other genes (found on X chromosomes) Sustenacular (Seritoli) cells produce Anti-Mullerian Hormone (AMH) or Mullerian Inhibiting Substance (MIS) Sustenacular cells are cells in the semeniferous tubules The production of AMH is controlled by at least two autosomal gene loci. One codes for the hormone and one for its receptor. Appropriately, the gene is expressed only in Sertoli cells of the primordial gonad shortly before testis differentiation. The SRY gene is believed to initiate the development of the testes by repressing an X- linked gene, the "Z" gene, which would otherwise direct the fetus toward female development. [IGNORE: A complex series of