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Repro 1 Flashcards

1
Q

“Sex” vs “Gender”

Sex: ________ determined

“Sex differences” refer to _____ inherent differences

(Differences that are biologically innate as a result of ____ differences)

Gender: _______ determined

  • usually related to appearance: ____ and ___
A

Sex: biologically determined

  • “sex differences” refer to biologically inherent differences, differences that are biolically innate as a result of genetics

Gender: socially determined:

  • usually related to appearance: genatalia and secondary sex characteristics
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2
Q

Describe the hierarchy of determinants of sexual differentiation:

1>>>>>2>>>>>3>>>>> 4

A

Hierarchy:

(1) chromosome > (2)gonad development >>>>
* these are both due to genetics
(3) genitalia > (4) gender identity
* due to hormones, internal and external structures, and social behavior

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3
Q

Sexual Determination:

Genotype (chromosomal sex);

46 ____ : female sex

46 ____: male sex

A

Sexual Determination:

Genotype (chromosomal sex):

46, XX : female sex

46, XY : male sex

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4
Q

Sexual Determination:

Gonadal sex is determined by _____

_ chromosome determines male gonads (testes)

_____ gene is a transcription factor whose major target is _______ (this determines whether or not testes develops)

A

Sexual Determination:

Gonadal sex is determined by chromosome:

Y chromosome determines male gonads (testes)

SRY gene (also called TDF) is a transcription factor, major target is SOX 9

These gene is on the short arm of the Y chromosome, and having it creates the development of a testes

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5
Q

Draw the sexual determination ginormous graph:

Gonadal sex is determined by chromosome (or SRY gene):

First, you start out as an indifferent gonad, then:

XY: develops into which gonad? what three cells are then created? what do those cells do

XX: develops into which gonad? what three cells are made, and what do those cells do?

A

Gonadal sex is determined by chromosome (or SRY)

XY: develops testes for gonads

  • spermatogonia (germ cell)
  • Sertoli cells (antimullerian hormone or AMH)
  • Leydig cells (produce androgens, aka testosterone)

XX: develops ovaries for gonads:

  • oogenia (germ cells)
  • granulosa cells (NO AMH)
  • Theca cells (no androgens)

NOTE: it is the absence of testes NOT the presence of an ovary that gives female genetalia

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6
Q

It is the ______ of a _____ NOT the ____ of an ____ that gives rise to female genitalia

A

It is the ABSENCE of a testes and NOT the presence of an ovary that gives rise to female genatalia

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7
Q

Early Development:

Primordial germ cells (PGCs): migrate to the ______ at ___ weeks gestation

Indifferent gonad (“primodial gonad”): has _____ for becoming a testes or an ovary

A

Early Development:

Primordial Germ Cells (PGCs): migrate to the gonadal ridge (5-6 weeks gestation)

Primordial (indifferent gonad) has bipotential for testes or ovary (can go either way depending on which genes the chromosomes are expressing)

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8
Q

Early Development:

______ cells direct the specific development of the gonad

Specific gene expression patterns lead to gonad differentiation:

  • Male: ____ + _____
  • Female: ____ + _____
A

Early Development:

Germ cells direct the specific development of the gonad

Specific gene expression patterns lead to gonad differentiation:

  • Male: Sry + Sox9
  • Female: Rspo1 + Wnt4
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9
Q

Migration of Germ Cells to gonadal ridges:

_________ develops into female internal genitalia

_________ develops into male internal genitalia

A

Germ cells are migrating to the gonadal ridge (within the fifth week)

CORTEX develops into female internal genitalia

MEDULLA develops into male internal genitalia

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10
Q

Embryonic Development of the Male Gonad:

  1. Indifferent gonad = primitive sex cords
  2. Proliferation of sex cords due to ___ and ___ genes
  3. Penetration of ____ by sex cords
  4. Differentiation of ____ cords - becomes the ____
A

Embryonic Development of the Male Gonad:

  1. Indifferent gonad = primitive sex cords
  2. Proliferation of sex cords due to Sry and Sox 9
  3. Penetration of medulla by sex cords
  4. Differentiation of medullary cords - becomes testes
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11
Q

Embryonic Development of Female Gonad:

  1. Indifferent gonad = primitive sex cords
  2. Sex cords ______ (epithelial cells proliferate due to the absense of ____)
  3. _______ develop from the cortical epithelium
  4. Cells form clusters around germ cells - epithelial cells become _____ cells - ovary develops
A

Embryonic Development of Female Gonad:
1. Indifferent gonad = primitive sex cords

  1. Sex cords disorganize - epithelial cells proliferate (due to the absence of SRY they never penetrate medulla)
  2. Cortical cords develop from cortical epithelium
  3. Cells form clusters around germ cells - epithelial cells become follicular cells - ovary develops
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12
Q

What’s In a Gonad?

Testes: (explain the three types of cells and what they do)

Ovaries:

Follicular maturation results in formation of:

  • *
A

What is in a Gonad?

Testes:

  • Gametes (sperm)
  • Sertoli Cells (secrete AMH, anti-mullerian hormone)
  • Leydig Cells- synthesize and secrete testosterone

Ovaries:

  • gametes (ova)
  • follicular cells

Follicular materation results in formation of:

  • Granulosa cells - secrete and synthesize estrogens and progesterone
  • Thecal cells
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13
Q

Internal Genitalia:

Sexually Indifferent Duct System:

At the indifferent stage: there are general gonads, mesenephros, ______ duct, and _____ duct

A

Sexually Indifferent Duct System:

At the indifferent stage: there are general gonads, mesenephros (transient kidneys), mullerian ducts, and wollfian ducts

SO, at the indifferent stage there are both mullerian and wolffian ducts

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14
Q

Male Internal Genitalia:

Testes:

Stertoli cells make ____ and _____ to induce what?

Leydig cells make ______

Explain what testosterone and DHT do at the embryonic stage

A

Male Internal Genitalia:

Testes:

Stertoli cells make AMH and inhibin B to induce regression of the mullerian duct

Leydig cells make androgens: testosterone and when it gets coverted to DHT

Testosterone stimulates internal genitalia:

  • top = epidymis
  • middle: ductus deferens
  • base: seminle vesicle and ejaculatory duct

DHT stimulates formation of prostate and external genitalia

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15
Q

Female Internal Genitalia:

_______ of _____ NOT _____ of ____ induces regression of Wolffian Ducts

There are no androgens and no AMH

Mullerian Ducts differentiate:

  • Top:
  • Middle:
  • Bottom:
A

Female Internal Genitalia:
Absence of testes NOT presence of an ovary induces regression of Wolffian Ducts

There is no DHT, and NO AMH so mullerian duct stays

Mullerian Ducts differentiate:

  • Top: fallopian tubes
  • Middle: fuses to become utereus
  • Bottom: cervix and upper 1/3 of vagina
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16
Q

Explain the following structures within males and females:

  1. Genital Tubercle
  2. Urogenital Folds
  3. Urogenital Sinus
  4. Labrioscrotal Folds

The _____, _____ and ____ require DHT

“Propecia” drug inhibits _______

What happens if that enzyme is inhibited during early development

A

Check chart for structures

The prostate, penis, and scrotum require DHT

“Propecia” inhibits 5-alpha reductase enzyme, which is necessary for testosterone—–> DHT

If you inhibit that enzyme during early embryonic development, you will not have male external genitals (internal genitals would be male though), but external would not

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17
Q

Mitosis vs Meiosis

Mitosis: somatic cells only, daughter cells are gentically identical

Meiosis I - germ cells

  • Duplication of DNA
  • _________ = genetic diversity
  • Chromosomes ___ in meiosis I

Meiosis II:

  • NO ______
  • chromatids ____
  • how many daughter cells?
A

Mitosis vs Meiosis:

Mitosis: somatic cells only, daughter cells genetically identical

Meiosis I - germ cells:

  • Duplication of DNA
  • Recombination = genetic diversity
  • Chromosomes split in meiosis I

Meiosis II:

  • No duplication
  • Chromatids Split
  • 4 daughter cells
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18
Q

Male Gametogenesis: Spermatogenesis:;

Male meiosis begings when ___- axis is initiated

Spermatagonium is ____

Primary spermatocyte is ____

Secondary spermatocyte is ___

Final sperm cell is called _____

there are ____ daughter cells per germ cell

A

Male Gametogenesis:

Spermatogenesis

Male meiosis begins when HPG axis initiated

Spermatogonium: diplod

Primary spermatocyte: diplod

Secondary spermatocyte: haploid

Spermatozoa (one with tail)

There are 4 daughter cells per germ cell

19
Q

Female Gametogenesis: Oogenesis:
Meiosis I is initiated in ____ but arrested at what stage until when?

Meiosis then resumes only in _____ in response to an ___ surge (meiosis I completes and meiosis II begins)

Then Meiosis II is arrested in _____ until fertilization

A

Female Oogenesis:
Meiosis I is initiated in utero but is arrested at the diplotene stage of prophase until puberty

Meiosis then resumes only in the dominant follice in response to an LH surge (meiosis I completes and meiosis II begins)

Then Meiosis II is arrested in metaphase until fertilization

20
Q

Disorders of Sexual Development:

  1. Disorders of sexual determination = _______
    * Examples?
  2. Disorders of gonadal dysgenesis = _____
    * Examples?
  3. Disorders of Sexual differentiation = _____
    * Examples?
A

Disorders of Sexual Development:

  1. Disorders of sexual determination = sex chromosome aneuploidy
    * Examples: Turner’s (XO), Klinefelter (XXY)
  2. Disorders of gonadal dysgenesis = abnormal testis formation in utero
    * androgen resistance due to loss of X liked androgen receptor
  3. Disorders of sexual differentiation = defects in internal or external genitalia
    * Examples: enzyme deficiencies, androgen excess
21
Q

Explain the following:
Normal Male and Normal Female:

Normal Male (XY): gonad is ______, (___ and ___ cells) release ____ and _____, causing ____ duct regression and developed ______ duct, androgens get converted to ____ to make male external genitalia

Normal Female (XX):

A

Normal Male (XY): gonad is a testes (w/ Stertoli and Leydig cells) which release testosterone and AMH, causing mullerian duct regression and development of the wolffian duct AND androgens get converted to DHT to make external male genitalia

Normal Female (XX): gonad is ovary, because there is no AMH the mullerian duct stays and develops, and because there are no androgens, the wolfian duct regresses and external genitalia becomes female

22
Q

Define the various terms

Chromosomal Abnormalities:

Structural Errors

  • Translocations:
  • Inversions:
  • Deletions, Duplications:
  • Rings

Chimerism

Mosaicism

Aneuploidy

A

Chromosomal Abnormalities:
Structural Errors:

  • Translocations - equal or unequal exchange of chromosomal materia
  • Inversions - piece of chromosome gets inserted upside down
  • Deletions or duplications- loss or addition of part of chromosome
  • Rings - two ends of chromosome join to form a ring

Chimerism: genetically distinct cells

Mosaicism - cell specific chromosome differences (X inactivation)

Aneuploidy = abnormal number of chromosomes, most famous is triploidy 21 or down syndrome

23
Q

Chromosomal Abnormalities:
Part of the Y chromosome gets translocated to the X

XY genotupe with female phenotype due to a mutation in the ____ gene

A

Part of Y chromosome gets translocated to the X

XY genotype with female phenotype due to a mutation in the SRY gene

24
Q

Turner’s Syndrome: (___) Karyotype

Example of disorder of ______ (chromosomal abnormalities)

Both X chromosomes are required for ___ development, therefore the gonad becomes a _____

Systemic phenotypic issues with aneuploidy, such as _____, ____, ____, _____, etc)

A

Turner’s Syndrome: XO karotype

Example of disorder of sexual determination (chromosomal abnormalities)

Both X chromosomes are required during development, gonad becomes a “streak” gonad (aka just fibrous tissue, so pt w/ turner’s syndrome is infertile

Systemic phenotypic issues with aneuploidy: web neck, wide set nipples, low ears, SHORT, elbows turn out (cubitus vulgus)

25
Klinefelter Syndrome 47 (\_\_\_\_) Example of a disorder of \_\_\_\_\_ Y chromosome present: testes present but \_\_ Testosterone is \_\_\_, \_\_\_\_penis "Eunuchoid body": lower segment is ___ than upper segment by more than 2 inches, short arms They have ______ estradiol levels Systemic phenotypic issues due to aneuploidy
Klinefelter Syndrome 47 (XXY) Example of disorder of sexual determination (chromosomal abnormality) Y chromosome is present (smal), infertile Testosterone is low (due to testicular dysfunction), micropenis Lower half of body is longer than upper half (short torso) They have elevated estradiol levels Note: pt's with klinefelter have low testosterone but high estradiol
26
Disorders of Gonadal Dysgenesis: **Complete Androgen Resistance, XY** Complete loss of X-linked AR gene Hormones: androgens are ___ (lack of feedback), estrogen levels are _____ (for a male) Phenotype? Y chromosome: induces mullerian duct \_\_\_\_\_, testes (but undescended), lack of adrogen effects ( __ wollfian duct development, ___ male genitalia) High _____ induce development of ____ genitalia
**Complete Androgen Resistance, XY** Complete loss of X-linked AR gene Hormones: androgens are high (lack of feedback), estrogen levels are high (for a male) Phenotype: female with blind vaginal pouch Y chromosome: induces mullerian duct regression, testes (undescended), lack of androgen effects (no wolffian duct development, no male external genitalia) High estrogens induce developnent of female body characteristics
27
Partial Androgen Resistance 46, XY Partial AR mutation - partionally functional Hormones: ____ are high, _____ are high Phenotype? Y chromosome: induces mullerian duct \_\_\_\_\_, testes (undescended), wollfian dut \_\_\_\_\_
Partial Androgen Resistance 46, XY Partial AR mutation - partionally function Hormones: androgen levels are high, estrogen levels are high (for a male) Phenotype: ambigous with blind vaginal pouch Y chromosome induces mullerian duct regression, testes, wolffian duct develops
28
Presence of both gonads in an XY individual: XX historically raised as females, possible ____ translocation or loss of ___ gene No ______ because other Y genes not present Differentiation of external genitalia is \_\_\_\_\_
Presence of BOTH gonads in an XY individual Possible due to SRY translocation and loss of RSPo1 gene (testes repressor) Nor spermatogenesis because other Y genes not present Differentiation of external genitalia is highly variable/ambigous
29
Disorders of Sexual Differentiation: Excess Androgens in Utero: Exposure after the 12th fetal week leads to clitoral \_\_\_\_\_ Exposure at earlier stages leads to retention of _____ and ______ fusion If exposure occurs early enough, ____ will fuse to form penile urethra Commonly caused by: * *
DIsorders of Sexual Differentiation: Excess Androgens in Utero: Exposure after the 12th fetal week leads to clitoral hypertrophy Exposure at progressively earlier stages of differentiation leads to retention of urogenital sinus and labioscrotal fusion If exposure occurs early enough, labia will fuse to form penile urethra Common causes of excess androgens in utero: * Fetal congenital adrenal hyperplasia (most common) * Maternal androgen excess * adrenal or ovarian tumors * progestational drugs
30
Excess Androgens in Utero: - retention of \_\_\_\_\_\_\_\_ -Fusion of the \_\_\_\_\_\_ Virilization by androgens: advanced \_\_\_\_\_, clitiromegaly and other \_\_\_\_\_\_\_ This can also be caused by _____ during pregnancy How to test for this?
Excess Androgens in Utero: - Retention of urogenital sinus - Fusion of the labia Virilization by androgens - advanced skeletal age, clitoromegaly and other ambiguities of genital anatomy This can also be caused by controceptive use during pregnancy How to test for this: * 17 ketosteroids (urine test for excess androgens) * Pregnanetriol - inactive metabolite of progesterone, measure if its coming from something else
31
HPG Axis: Major hypothalamic hormone: \_\_\_\_\_\_ * absolutely required for _____ (without it you would be infertile) * released in a pulsatile manner (fast pulse: ___ and slow pulse: \_\_\_) Major pituitary hormones: ___ and \_\_\_\_ * LH: stimulates ____ in ovaries and testes * FSH: stimulates _____ in ovaries and testes
HPG Axis: Major hypothalamic hormone: GnRH * absolitely required for reproduction (without it you would be infertile) * released in a pulsatile manner (fast pulse: LH, slow fulse: FSH) Major pituitary hormones: LH and FSH * LH stimulates steroidogenesis in ovaries and testes * FSH stimulates gametogenesis (egg and sperm materiation in ovaries and testes)
32
Regulation of GnRH: Kisspeptin: require to ____ increased GnRH release at time of puberty * presumed signal for \_\_\_\_\_ * mutations in KISS1 receptor cause \_\_\_\_\_\_ Gonadal steroid hormones (androgens/estrogens) - exert ______ feedback on GnRH Prolactin _____ GnRH
Regulation of GnRH: Kisspeptin: required to initiate increased GnRH release at the time of puberty * presumed signal for pubertal onset * mutations in KISS1 receptor cause hypogonadotropic hypogonadism (low FSH and LH, causing low sex steroid hormones) Gonadal steroid hormones (androgens/estrogens) exert negative and positive feedback on GnRh (note, estrogen exerts both negative and positive feedback) Prolactin INHIBITS GnRH release
33
Explain the roles of Inhibin B and Activin within the HPG Axis, but on the **pituitary** ## Footnote **Inhibin B:** **Activin:**
Inhibin B: specific inhibitor for FSH release in pituitary * produced by stertoli cells (expressed in gonads) * inhibits FSH beta subunit synthesis in gonadotropes Activin: expressed in pituitary and gonads * stimulates FSH beta, LH beta, and GnRH receptor synthesis in the pituitary
34
Pituitary Gonadotropins (FSH and LH): Large glycoproteins Share a common _____ subunit \_\_\_ subunits specify the hormone IN GENERAL FOR BOTH SEXES: * LH does what? * FSH does what?
Pituitary Gonadotropins (FSH and LH): Large glycoproteins Share a common alpha subunit Beta subunits specify the hormone IN GENERAL FOR BOTH SEXES: * LH stimulates steroidogenesis * FSH stimulates gametogenesis
35
Male Reprodudction: FSH \_\_\_\_\_\_ cells have high affinity FSH receptors and forms the blood\_\_\_ barrier FSH: * stimulates spermato\_\_\_\_\_\_ * increases sperm \_\_\_\_\_ * stimulates growth of ______ (primary determinant of testes size) * stimulates ________ (maintaining high local T) * stimulates _____ (enzyme) * stimulates \_\_\_\_\_\_ * stimulates \_\_\_\_\_
Male Reproduction: FSH Sertoli Cells have high affinity FSH receptors and form the blood-testes barrier FSH: * stimulates spermatogenesis * increases sperm motility * stimulates growth of seminiferous tubules - primary determinant of testes size * stimulates androgen binding protein (ANP) to maintain high local T in testes * Stimulates aromatase * stimulates inhibin * stimulates Growth factors
36
Male Reproduction LH: \_\_\_\_\_ cells have high LH receptors LH: * stimulates ________ from cholesterol * androgens = __ carbon steroids * Stimulates _____ protein (rate limiting) * stimulates leydig cell growth
Male Reproduction: LH: Leydig cells have high affinity LH receptors LH: * stimulates steroidogenesis from cholesterol * Androgens = 19 carbon steroids * Stimulates StAR protein: rate limiting step to turn cholesterol ----\> prenenolone * Stimulates leydig cell growth
37
Testosterone: Testosterone precursors are made in _____ tissues \_\_\_\_\_\_ is the primary source of circulating T In plasma circulation, testosterone is bound to \_\_\_ Intracellular: converted to ____ or \_\_\_\_ Metabolized: \_\_ and ___ both bind androgen receptors (nuclear steroid receptor) \_\_\_\_\_ has a higher affinity for AR
Testosterone: Testosterone precursors are made in extragonadal tissues (brain, adrenal gland, skin, adipose tissue) Testes - primary source of circulating T Intracellular: converted to estrogen or DHT Metabolized - -diols and -triols T and DHT both bind to the androgen receptor DHT has higher affinity than T for AR
38
Androgens: \_\_\_\_, \_\_\_\_, \_\_\_\_, \_\_\_\_ Explain the progression and the major enzymes in for T: * CYP 17 * 17BHSD * 5 alpha reductase * aromatase
Androgens include DHEA, Androstenedione, Testosterone, DHT Major enzymes: star protein takes cholesterol out of one compartment to make it to pregnenolone Then **CYP 17** turns progesterone into 17 oh progesterone (first step in the conversion) Two steps later, Androstenedione is turned into testosterone by **17B HSD** (so this enzyme is required to make testosterone) **5** **alpha** **reductase** turns testosterone into DHT **Aromatase** turns testosterone into estradiol
39
Excretion of Testosterone: \_\_\_ of daily testosterone is excreted as free testosterone Remained is converted to _____ and ____ (conjugated to water soluble forms and then excreted)
Excretion of Testosterone: \<2% of daily testosterone is excreted as free testosterone Remainder is converted to 17-ketosteroids and DHT (conjugated to water soluble forms and then excreted)
40
Masculinization of the brain requires __ to ___ conversion
Masculinization of the brain requires T to E conversion
41
Comparison of Testosterone and DHT Actions in Fetal Development and During Puberty Testosterone * during fetal development: * during puberty DHT: * during fetal development * during puberty
Comparison of Testosterone and DHT Actions in Fetal Development during Puberty: **Testosterone**: * during fetal development: (internal genitalia is developed from the wolffian duct: Epididymis, Vans deferens and Seminal Vesicles) * During puberty: growth of seminal vesicles, musculature growth, voice deeper, skeleton bones age, spermatogenesis **DHT**: * during fetal development: development of external genitalia (penis, penile urethra, scrotum, prostate development) * during puberty: scrotum, prostate, male pattern hair distribution aka beard, subcutaneous glands that cause acne
42
What is the "coolidge effect"?
Coolidge Effect: After copulation: testosterone levels in males decline However, if male is paired with a novel female, testosterone levels rise again
43
Explain what the "fan effect" on testosterone in males is
Fan Effect: testosterone levels fall in supporters of the losing team

FHB II (14 decks)

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