Sex for the purposes of this class refers to 4 components

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1 Sex for the purposes of this class refers to 4 components Gonadal sex Gonads or where gametes are produced by meiosis Somatic sex Somatic cells are cells that undergo mitosis. They can be divided into primary and secondary characteristics Secondary somatic sex characteristics are divided further into hair and body Sexual identification Sexual orientation

2 FOR HUMAN MALES Gonadal sex Consists of the testes where the gametes or sperm are produced Somatic sex characteristics Primary and Secondary Male primary somatic sex characteristics penis and scrotum Male secondary somatic sex characteristics Hair facial hair chest hair body hair Body pelvic build straight hips muscular build upper body Ability to generate muscle mass at a faster rate than females following puberty

3 Gonadal sex FOR HUMAN FEMALES Ovaries where eggs are produced Female primary somatic sex characteristics Clitoris, labia, vagina, cervix, uterus, fallopian tubes, and the ability to bear children Female secondary somatic sex characteristics Hair vellus rather than terminal hair Body rounded hips, breasts, ability to nurse offspring, menstrual cycle, increased body fat composition, decreased upper body strength, decreased ability to generate muscle mass at a fast rate

4 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Sex chromosomes At the cellular level the sex of an individual is determined genetically by the sex chromosomes. X and Y -> male X and X -> female 6-4 Biophoto Associates/Photo Researchers

5 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Sex chromosomes determine gender Human males are the heterogametic sex with two different sex chromosomes, (XY). Human females are the homogametic sex (XX). In other species sex determination differs: male birds ZZ female birds ZW 6-5

6 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Sexual development At the beginning of human development either male or female development is possible. Unspecialized gonads and two sets of reproductive ducts exist until 6th week of development. An embryo develops as a male or female using information from the Y chromosome. 6-6

7 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Genes on the Y chromosome Y chromosome first seen 1923 Tips of Y chromosome are pseudoautosomal regions PAR1 and PAR2 They make up 5% of the chromosome Contain 63 pseudoautosomal genes that cross over with the X chromosome Most of the Y is male specific region or MSY 6-7

8 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Genes on the Y Chromosome Y chromosome has 2 pseudoautosomal regions whose genes match genes on the X chromosome And a large central region that does not recombine with the X chromosome This non-recombining region makes up about 95% of the chromosome 6-8

9 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 3 Classes of Genes on the Y Genes shared with X chromosome define the pseudoautosomal regions (PAR) Genes similar to X chromosome genes are X- Y homologs 6-9 Genes unique to the Y including SRY gene

10 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Genes on the Y chromosome Y chromosome is small and gene poor and prone to deletion Since the Y can not recombine with X, its genes began to rot Genes decayed except for SRY and the tips The Y is degrading fast, losing genes at the rate of 5/million years May have a way out of complete degredation Many of the DNA segments are palindromes 6-10

11 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Y chromosome is highly repetitive 6-11

12 During male meiosis a synaptonemal complex forms and one chiasma will always form in this region This results in regular exchange of material between the tips of XP and YP Any genes in this region are inherited as thought they are autosomal and that is why it is called the pseudoautosomal region PAR Contains known genes including the RSP gene for making ribosomes

13 6-13 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

14 SEX REVERSAL This mutant hybrid chromosome is called an X (TDF) chromosome When it fertilizes an X bearing egg it results in a 46 XX (TDF) male When the corresponding mutant y chromosome fertilizes an egg it results in a 46 XY female

15 SEX REVERSAL Karyotype is XX but this individual will develop as an XY male because of the presence of the testes determining factor gene Remember the presence of testes, determines gonadal sex in males Even though these individual will look male they will suffer from testicular atrophy or small testes and sterility What causes the sterility?

16 SEX REVERSAL In humans if there are 2 X chromosomes in a male germ line, it acts as a poison to the germ cells and kills them during meiosis The gonadal sex of this individual will be male because they will have testes But they can not make viable sperm

17 SEX REVERSAL When a sperm carrying a Y (deltdf) chromosome fertilizes an X bearing egg the result is an XY(delTDF) zygote This individual develops as female even though the karyotype is XY Ovaries are reduced and eggs that are produced will not survive Have a female build but little pubic or underarm hair

18 6-18 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. SRY activates a cascade of developmental events

19 Sexual development

20 External genitalia differentiation

21 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Mutations in genes involved in sexual development affect gender Mutation/absence of: SRY gene Normal female development Anti-Mullerian hormone Mullerian ducts persist in male gene Testosterone gene Early development as female Masculinization at puberty DHT converting enzyme External structures lack signal and develop as female, internal structures are male. 6-21

22 HORMONES Travel in the blood stream to receptors on the target cell Receptors bind the hormone and carry it across the plasma membrane of the cell to the nucleus Once inside the nucleus the hormone binds to DNA to promote gene expression It is the protein products of these genes that lead to sexual differentiation

23 HORMONES Chemical messengers that are produced by one cell type, released into the bloodstream and received by the target cell Hormones regulate gene expression in the target cell We will look at: testosterone excreted by testes and adrenal cortex in males estrogen excreted by ovaries and adrenal cortex in females

24 HORMONE RECEPTORS AND GENE REGULATION The TDF gene is on the Y chromosome and codes for the development of testes which produce testosterone But the receptor for testosterone is regulated by a gene on the X chromosome This AR gene or androgen receptor gene codes for the testosterone receptor A mutation in this gene cause testicular feminization Individuals are XY with a normal Y chromosome with a normal TDF gene

25 HORMONE RECEPTORS AND GENE REGULATION They can not respond to testosterone s masculinizing effects because they have no receptors to transport testosterone across the cell membrane Affected individuals develop as phenotypic females who are sterile This mutation is known as the AIS mutation, androgen insensitivity syndrome

26 ANDROGEN INSENSITIVITY SYNDROME Produce testosterone This is where they differ from the XY (TDF del) individuals They have no receptors to transport testosterone across the cell membrane Referred to as AIS females Occur 1/20,000 births Taller than average External genitals are female Vagina looks normal from the outside Newborn is declared a girl and raised as such

27 ANDROGEN INSENSITIVITY SYNDROME In utero AIS females develop testes because TDF gene present so their gonadal sex is male Produce MIF and Mullerian ducts regress But the cells of the embryo cannot sense testosterone Instead they respond to the low levels of estrogen being produced by the adrenal cortex and develop as female At birth appear female No vagina, cervix, uterus or fallopian tube

28 3 WAYS TO MANIFEST TESTICULAR FEMINIZATION XY (TDF del) no testosterone XY point mutation of TDF gene no testosterone XY with normal Y but with AIS mutation so no receptors for testosterone All these individuals will be tall

29 SEX DETERMINATION IN HUMANS REQUIRES 4 ELEMENTS TO BECOME MALE Y chromosome intact TDF gene (no point mutations) Sensing mechanism in the indifferent gonad to the testes determining factor Testosterone or estrogen produced by the gonads Testosterone or estrogen receptors in the somatic tissues intact. No AIS (androgen insensitivity syndrome)

30 6-30 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. SRY activates a cascade of developmental events

31 GUEVEDOCES Born XY with female genitalia At puberty the adrenal gland begins to produce testosterone Causes masculinization voice deepens muscles develop no breast development and no menses adrenal testosterone causes clitoris to enlarge and resemble a penis

32 SEX CHROMOSOME ANEUPLOIDY Aneuploidy refers to an abnormal number of chromosomes Such anomolies occur often enough that they have been recognized and studied by medical science We will discuss 3 different cases of aneuploidy Klinefelter males XXY XYY Turner syndrome XO

33 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Nondisjunction in Sex Chromosomes X Chromosome XXX XXY Klinefelter syndrome XO Turner Syndrome 6-33

34 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. What determines gender? Number of X chromosomes, or presence of Y chromosome? Individuals with unusual chromosome combinations provide a clue: X0 XXY XY females XX males Female with Turner syndrome Male with Klinefelter syndrome SRY gene missing Small bit of Y with SRY gene present 6-34 => Y chromosome determines gender. => SRY gene on Y chromosome determines gender.

35 KLINEFELTER Klinefelter males have an extra X chromosome so they karyotype as XXY males Occurs 1/1000 live births 1940 Harry Klinefelter at Massachusetts General Hospital described a syndrome occurring in males not usually detected until after puberty

36 KLINEFELTER The testes are atrophied and do not produce much testosterone The level may be so low as to be about the same amount as the estrogen produced by the adrenal cortex Because the level is so low during puberty these individuals do not undergo normal development of male secondary sex characteristics, including muscular upper body, narrow hips and chest and facial hair

37 KLINEFELTER If treated during puberty with testosterone then breast development will stop and the hips will narrow and become more male like They will develop muscular upper bodies, broad shoulders, square jaw and deep voices Remain sterile because the undeveloped testes can not produce sperm But outwardly they will look like normal males

38 XYY MALES 1965 Jacobs in Scotland looked at the chromosomes of 197 mentally subnormal males with violent tendencies They found 7 of those males had a 47 XYY karyotype 7/197 = 1/28 a much higher ratio than among other groups of males tested XYY occurs 1/1000 live births Among tall males about 1/325 Among tall penal inmates 1/30

39 XYY MALES XYY males are over represented in mental and penal institutions Large scale study done by the Danish government suggested that tall males with lower intellectual function are more likely to be convicted of crimes regardless of their karyotype XYY karyotype is over represented in tall males 1/325 More than 95% of all XYY males are not in prison

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