Development

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Development Anatomy of theReproductive System

• Anatomy of the Reproductive System
• Development Genotypic Sex (Gonad)
• Hormonal Regulation of Sex Differentiation
• Puberty
• Sexual Differentiation of the Brain

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Anatomy of the Reproductive System

• Gonads ovary (female), testis (male)
• Associated ducts
• - male epididymis, ductus deferens, ejaculatory
  duct, penile urethra
• - female uterine tubes, uterus, vagina
• Other structures
• - male seminal vesicle, prostate gland,
  bulbourethral glands, external genitalia
• - female external genitalia, mammary glands
• Hypothalamus, pituitary
• Brain

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Epididymis and Ductus Deferens

• Epididymis connection between the testis and
  ductus deferens
• Three parts head (cauda), body, and tail
• Ductus deferens (vas deferens) connects tail of
  epididymis to ejaculatory duct
• Ascends within scrotum in the spermatic cord,
  into the pelvic region.

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Seminal Vesicles and Prostate

• Seminal vesicles enlarged, sac-like structures
  which open into ejaculatory ducts.
• Prostate lobular structure at base of bladder.

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Male External Genitalia

• Penis male copulatory organ (also excretion
  elimination of urine)
• Composed of three columns of erectile tissue,
  each enclosed by connective tissue
• Scrotum two separate compartments, each
  containing a testis.
• Wall of scrotum skin, superficial loose
  connective tissue, smooth muscle (dartos).

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Male Accessory Sex Organs the Penis

• Three columns of erectile tissue
• - corpus spongiosum one column, includes glans
  penis, and contains the spongy (penile) urethra
• - two corpora cavernosa lateral columns,
  forming the dorsum and sides of the penis

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Secondary Sex Characteristics in the Male

• Increased skeletal growth.
• Increased muscular development.
• Enlargement of larynx and thickening of vocal
  cords.
• Increased facial and body hair.

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Female Reproductive Organs

• Ovary female gonad
• Uterine Tubes (fallopian tube, oviduct)
• - three parts infundibulum, ampulla, isthmus

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Uterus

• Uterus site of implantation of developing embryo
• Three parts fundus, body, and cervix
• Uterine wall has three layers
• - perimetrium serous connective tissue layer
• - myometrium smooth muscle layer
• - endometrium epithelial layer

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Female Accessory Sex Organs Uterus

• Uterine endometrium has two layers
• - basal layer
• - functional layer built up and shed each cycle

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Female Accessory Sex Organs Vagina

• Connects uterus/uterine tubes to outside body
• Female copulatory organ
• Birth canal
• Menstrual flow

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External Genitalia

• Labia majora and labia minora
• Clitoris, prepuce

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Mammary Glands

• Organs of milk production
• Composed of adipose tissue and glandular duct
  system
• Milk produced in glands, accumulates in
  lactiferous sinus
• From sinus, milk flows through lactiferous duct
  to exit from nipple

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Female Secondary Sex Characteristics

• Mammary development
• Little facial/body hair
• Decreased capacity for muscular development
• Increased percentage of body fat
• Smaller larynx, thinner vocal cords

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Development of the Reproductive System

• Development of the reproductive system is
  dependent upon a genetic influence and subsequent
  endocrine influences.
• Genetic Influence Sex chromosomes (XX or XY),
  which determine gonadal development
• Endocrine Influence Hormones produced from the
  gonad, which result in all other phases of sexual
  differentiation.

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Genetic Basis of Structure Function

• Genes DNA encoding a single protein
• Genes are contained on chromosomes
• DNA is transcribed into messenger RNA
• Messenger RNA is translated into protein
• Proteins contribute to the characteristic
  structure and function of cells, tissues, organs,
  organ systems, and organisms

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Chromosomal DNA

• Genes are located on chromosomes (strands of DNA)
• Humans have 46 chromosomes (two different copies
  of 23 different chromosomes)
• One copy of 23 chromosomes is from mother
  (maternal)
• One copy of 23 chromosomes is from father
  (paternal)

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Types of Chromosomes

• Of the 23 chromosomes, 22 are autosomes and 1
  pair are called sex chromosomes (X and Y)
• The sex chromosomes determine the genetic sex of
  the individual
• Females XX
• Males XY

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Sex Chromosomes

• Development of the testis is dependent upon a Y
  chromosome (genetic sex).
• The Y chromosome has a region of DNA (SRY gene)
  which causes development of the testes.
• Development of duct systems and secondary sex
  characteristics is dependent upon hormonal
  factors secreted by the testis.

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Development of the Reproductive System

• We all develop from embryos which at one point
  are neither male nor female (indeterminant
  stage).
• Recall these adult structures
• male testis, epididimis, ductus deferens,
  seminal vesicles
• female ovary, uterine tubes, uterus, vagina
• During the indeterminant stage, there are two
  duct systems and an indifferent gonad.

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Gonadal Development

• Early (indifferent) Gonad
• Genital ridge (mesoderm) proliferates and is
  invaded by epithelial cells, forming the primary
  sex cords
• Primordial germ cells migrate from yolk sac.

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Gonadal Development (cont.)

• In testis, the primary sex cords continue to
  proliferate deep into the medulla of the gonad to
  form testis cords.
• Testis cords develop into seminiferous tubules.
• The surface epithelium develops as a fibrous
  covering, the tunica albuginea.

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Gonadal Development (cont.)

• In the ovary, the primary sex cords degenerate.
• Secondary sex cords form from the surface
  epithelium, and associate with primordial germ
  cells to form follicles containing oogonia.
• All subsequent sexual differentiation is
  dependent upon factors secreted from the
  developed gonad.

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Sexual Determination of Duct Systems

• In the indifferent embryo, there are both duct
  systems
• Mesonephric Duct male duct system (Wolfian
  duct), gives rise to the epidydimis, ductus
  deferens, and seminal vesicles. (Prostate
  develops as an outgrowth of the urogenital sinus,
  not mesonephric duct).
• Paramesonephric Duct female duct system
  (Mullerian Duct), gives rise to the oviduct,
  uterus, and the superior portion of the vagina.

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Factors Influencing Duct Formation

• If Y chromosome present, testis develops
• - testis produces testosterone
• - testis produces Mullerian Inhibiting Substance
  (MIS)
• Testosterone supports growth of mesonephric duct.
• MIS inhibits paramesonephric (Mullerian) duct

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Factors Influencing Duct Formation

• If no Y chromosome present (XX), ovary develops
• No testosterone and MIS production
• Mesonephric duct fails to develop (no
  testosterone)
• Paramesonephric duct develops (no MIS)

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Development of External Genitalia

• The external genitalia are at some point also
  indifferent.
• Androgens cause development of male genitalia.

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Masculinization of External Genitalia

• The specific androgen required is
  dihydrotestosterone (DHT).
• Testosterone is converted to DHT locally in the
  genital tissues by the enzyme 5 alpha reductase.

5a reductase
T
T
DHT
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Development of External Genitalia in Absence of
DHT Action

• In females, absence of androgens leads to
  development of female genitalia.

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Effects of Puberty on Sexual Development

• Puberty completion of sexual maturation due to
  increased activity of the gonads.
• The onset of puberty occurs earlier in girls than
  boys.
• Age of puberty varies in different countries, and
  is influenced by body fat content in girls.
• The limiting factor appears to be maturation of
  the neuroendocrine mechanisms regulating GnRH
  release from the hypothalamus.
• Increased GnRH secretion results in increased
  gonadotropin release, followed by gonadal
  activity (steroidogenesis, gametogenesis).

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Effects of Puberty in Males

• Increased testosterone production during puberty
  leads to several changes
• - enlargement of prostate, testes, scrotum, and
  penis
• - enlargement of the larynx, thickening of vocal
  cords
• - increased muscle mass and skeletal growth
• - growth of pubic, facial, and body hair
• - increased libido and aggressive behavior

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Roles of Testosterone versus DHT

• Effects of androgens on aggressive behavior,
  increased libido, muscle development, voice
  deepening, spermatogenesis, and axillary and
  pubic hair growth are due to testosterone itself.
• Effects of androgens on prostate growth,
  development of the external genitalia, and
  increased facial and body hair require conversion
  of T to DHT.

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Roles of Testosterone versus DHT

• During aging, male pattern baldness is caused by
  DHT, not testosterone.
• Blocking conversion from T to DHT can prevent
  baldness.
• DHT has a higher affinity for the androgen
  receptor than T.

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Effects of Puberty in Females

• Increased steroid production during puberty leads
  to several changes in females
• - breast development
• - growth of pubic and axillary hair (adrenal
  androgens)
• - enlargement of labia majora and minora
• - increased hip width
• - increased skeletal growth
• - increased body fat deposition

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Other Differences Between the Sexes

• A number of other differences between males and
  females (sexual dimorphisms) have been
  identified
• - neuroendocrine response to estradiol (positive
  feedback)
• - differences in aggressive behavior/libido
• - differences in spatial skills
• - differences in verbal skills
• - differences in navigational strategies
• - differences in toy preference

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Why do Sex Differences Exist?

• Are these differences the result of nature or
  nurture?
• Are there sex differences in structure/functioning
  of the brain?

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Sexual Dimorphism of Neuroendocrine Function

• Earlier you learned that low levels of estradiol
  exert a negative feedback effect, decreasing
  release of LH and FSH.
• During the ovulatory cycle in females, high
  estradiol levels exert a positive feedback effect
  on LH and FSH, resulting in the preovulatory
  gonadotropin surges.

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Positive Feedback in Females

• If you inject a female rat with a high dose of
  estradiol, you will induce an LH surge (positive
  feedback response).
• If you castrate a male rat and inject it with a
  high dose of estradiol, you will NOT induce an LH
  surge.
• The male hypothalamus does not display a positive
  feedback response to estradiol.

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Mating Behavior in the Rat A Model for Sexual
Differentiation?

• Female rats exhibit female mating behavior
  (receptivity to the male) only under the
  influence of high levels of estradiol.
• Male rats exhibit male mating behavior (mounting,
  intromission, ejaculation) only under the
  influence of testosterone.
• If you castrate an adult female rat and treat
  with testosterone, it will not show (much) male
  mating behavior.
• If you castrate an adult male rat and treat with
  estradiol, it will not show female mating
  behavior.

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Hormonal Determination of Mating Behavior as an
Adult

• If you castrate a male rat right after birth, you
  can treat it with testosterone as an adult and it
  will not show male mating behavior.
• However, you can treat these rats with estradiol
  as adults, and they will show female mating
  behavior.
• Conversely, if you inject testosterone into
  female rats right after birth, they do not show
  female mating behavior in response to estradiol
  as adults.
• Instead, they show male mating behavior if
  treated with testosterone as adults.

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Hormonal Determination of Mating Behavior as an
Adult
Treatment Response to T Response to E2 at
Birth as adult as adult

• male intact male behavior none
• male castrate none female behavior
• male castrate
• T male behavior none
• female intact none female behavior
• female castrate none female behavior
• female T male behavior none

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Effect of Steroid Hormones on Masculinization of
Mating Behavior

• During early development (embryonic day 19 - day
  6 of life), androgens result in masculinization
  of mating behavior as adults (in rats!)
• Actually it turns out that the masculinizing
  hormone is estradiol, not testosterone, since
  treating males or females with E2 also results in
  masculinization.
• Testosterone is peripherally converted to E2 in
  the brain by brain aromatase.
• Circulating estradiol is prevented from acting on
  the brain of females due to high levels of an
  estrogen binding protein during this stage of
  development.

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Do Steroids also Masculinize Brain Structures?

• What is the basis of the effects of T/E2 on
  masculinization of mating behavior?
• Gorski discovered a size difference in the medial
  preoptic area of the hypothalamus (larger in
  males than females).
• This area is called the sexually dimorphic
  nucleus of the medial preoptic area (SDN-POA).
• Interestingly, treatments in newborn rats that
  cause masculinization of mating behavior increase
  the size of the SDN-POA, while treatments
  resulting in female behavior as adults decrease
  the size of the SDN-POA.
• Thus, steroid hormones can influence the
  structure of the brain (but we dont know what
  the SDN-POA does).

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Are there Sexual Dimorphisms in Brain Structure
in Humans?

• Several structures in the human brain (number of
  neurons, corpus callosum, anterior commissure,
  bed nucleus of stria terminalis, interstitial
  nuclei of the hypothalamus, cortex) are sexually
  dimorphic.
• Males have more neurons, but lose them quicker
  during aging.
• Are these differences responsible for differences
  in behavior, spatial ability, etc., observed
  between men and women?

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Does Early Exposure to Elevated Androgens Have an
Influence in Human Females?

• Congenital Adrenal Hyperplasia Results in high
  androgen levels during fetal development,
  masculinizing the external genitalia.
• One study examined 17 female patients (4 - 19
  years old) treated for CAH (early surgical repair
  of genitalia, replacement glucocorticoids),
  compared to their unaffected sisters (n 11)

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Does Early Exposure to Elevated Androgens Have an
Influence in Human Females?

• Findings indicated that CAH patients had
  significant differences in the following
  categories
• - preferred boys as playmates, and were more
  aggressive in play
• - had little interest in infant care, idea of
  motherhood and marriage, and dolls
• - little interest in make-up, jewelry, dress
  clothes
• - increased tomboyishness (60)

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Does Early Exposure to Elevated Androgens Have an
Influence in Human Females?

• A separate study examined sexual orientation of
  30 women treated for CAH.
• While 40 were exclusively heterosexual, 37 were
  bisexual or homosexual (compared with Kinsey
  report of 10 homosexual).
• Are there hormonal determinants of sexual
  preference?
• Are there differences in brain structure between
  heterosexuals and homosexuals? (Cause or result?)

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Relationship between Gender Identity/Preference
and Brain Structure

• Studies have reported differences in some brain
  structures (anterior commissure, interstitial
  nuclei of the hypothalamus) between heterosexual
  and homosexual men.
• One study reports a difference in the size of the
  bed nucleus of the stria terminalis between
  heterosexual men and transsexuals (male to
  female). Transsexuals had BNST sizes more
  similar to women.
• Sample sizes are small, and some reports are
  inconsistent.
• What would such observations, if true, mean?

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NEXT LECTURE....

• Reproductive Endocrinology in the Male