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Define sex determination and sex differentiation
- Sex Determination - gender of the individual set by genetic inheritance. (involves genetic, cellular, and hormonal factors)
- Established at the moment of fertilization.
- Determined by inheritance of 2 chromosomes—sex chromosomes, X and Y; Males XY; Females XX
- Sex Differentiation -
- process by which specific gene products result in a gonad whose products make possible a male or female phenotype.
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Gonads and what they secrete:
- Gonads are source of steroid hormones:
- Males - testosterone/androgen
- Females - estrogen aka estradiol and progesterone
which determines external and internal genitalia ( phenotypic sex)
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When are primordial germ cells generated
in embryogenesis
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What gene is expressed on the Y chromosome?
- gene SRY on chromosome Y results in testes
- - gene SRY differentiates the developing embyo of male
You can have an XY gene, but an inactive/no SRY gene: individual will have a phenotype of a female
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Important of testosterone receptors
- have individuals that are XY, make testes (b/c active SRY gene), are producing testosterone, but testosterone not functioning within the body b/c they don't have testosterone receptors
- Receptor resistance as if not making testosterone
- So genetically male, but phenotypically female
- In absence of testosterone you will retain the female ducts
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Gonadal sex:
gonadal sex (XX or XY) determines whethere there is testes or ovaries
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What occurs after 7 weeks of gestation
- Male phenotype is induced after 8 weeks of gestation; prior to the 8th week, sex of embryo is not recognized (indifferent state aka indeterminant sex) - both ducts are present up to 8 weeks
- if no Y chromosome, or SRY gene expression then testes doesn't develop...instead, ovaries begin to develop at week 11
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Duct used for male embryo at week 8
will have a regression of Mullerian ducts in male due to Mullerian Inhibitory hormone (MIF) --> secreted by Sertoli cells (from testes); so in addition to needing MIF males also need testosterone present AND testosterone receptors for Mullerian ducts to regress
this means you need a functional testes to make MIF --> regression of mullerian duct will than form ale ductal systems
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duct in females:
what is a hemaphrodite
In female (absence of testosterone) --> Wolferian ducts regress
hemaphrodite - have both ductal systems
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Definition of sexual Identity, sexual preference, and sexual functioning
Sexual Identity = refers to whether individuals consider themsevles male or female (doesn't always correlate with genotype)
Sexual preference = refers to whether individual is attracted to the same sex or opposite sex
Sexual Functioning = refers to whether an individual has testes, ovaries, or gonads with both features (hermaphroditism)
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Wolferian ducts differentiate into:
- Epididymis
- Van deferens
- Ejaculatory duct
- Seminal vesicles
- DHT produced from testosterone forms penis and scrotum.
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Mullerian system develops into:
- Fallopian tubes
- Uterus
- Vagina and external genitalia develops from previous Wolferian ducts.
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Common Axis - describe it
- Hypothalmus (responds to levels of circulating steroid hormones) --> GnRH --> Pituitary --> gonadotropins: LH (luteinizing hormone) and FSH (follicle stimulating hormones)
- LH and FSH regulate the development and function of the gonads in males and females (so act upon the gonads)
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LH and FSH
- LH works on cell type secreting androgen --> theca cells in females and Leydig cells in males
- FSH regulates the actual cells which are surrounding the developing spirmor cells surounding the developing egg in the female (follicle cells - Granulosa) or sertoli cells in the male
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Androgen
Androgen is made locally and is critical to making eggs or sperm (under control of LH)
Androgen - testosterone is converted to estrogen by aromatase
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Long loop negative feedback and short negative feedback loop
- estrogen made by ovary --> ovary will take that locally made testosterone and convert it into estrogen which is done by the follicle cells and done with aromatase (in non gonadal tissue)
- -this feeds back negatively to regulate both pituitary and hypothalamus
FSH acts on granulosa/sertoli cells and secrete Inhibin which acts as a negative feedback on FSH --> critical point
so FSH is tightly regulated
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GnRH secretion in males vs females
in males secretion is continuous and pulsatile
in females secretion is cyclic (monthly pattern)
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How does hypothalamus change during development?
Hypothalamus is very sensitive to feedback from testosterone and estrogen à highly suppressed hypothalamus until puberty, than axis changes and matures à now have pulsatility (so don’t down regulate receptors in pituitary from GnRH) and circadian rhythm for males (peak androgen output 2x/day)
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Male Reprodcutve system glands
- Glands:
- seminal vesicle - adding fructose rich fluid to ejaculate b/c sperm uses this as there main energy use
- Prostate gland - adds bicarbonate (buffer) b/c female reproductive tract is acidic
- bulbourethral gland - adds another 10% to the fluid
ejaculate = 5mL; have 200-400 million sperm per 5mL
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sperm movement through organs
- Have testes and with testes have seminiferous tubules --> takes sperm 64 days to get out of seminiferous tubules
- then goes into epididymis and takes sperm 90 days to get to end of epididymis
- then enters vas deferens which conducts sperm to penile urethra
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Describe spermatogenesis and spermatogonia
Spermatogenesis (sperm formation) occurs in the testes where the stem cell population
- · Spermatogonia (stem cells) divide via mitosis to create 2 daughter cells (each have 46 chrom)
- · Primary Spermatocytes—resulting from final mitotic division, beginning of differentiation
- * Meiotic division=Secondary Spermatocytes (each have 23 chrom).
- · Meiotic division=Spermatids
- · Differentiation=Spermatazoa
- Each primary spermatocyte produces 4 sperm.
- · Sperm are then released from Sertoli cells but are immotile until they mature in the epididymis.
- · Spermatogonia can divide continuously throughout the life of the male. One of the clone cells drop out at the mitosis-differentiation stage to ensure this can continue.
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Describe roll of different cell types in spermatogenesis
- Sertoli cells surround the developing sperm and create a barrier around the sperm to protect it from the blood (immune system)—Blood-Testes barrier.
- o The # of Sertoli cells determines the # of sperm he can make.
- o Secretes androgen-binding protein (ABP)—
- Binds testosterone secreted by Leydig cells and is able to cross the B-T barrier.
- Presents high concentration of testosterone to developing sperm.
- o Secretes inhibin and paracrine agents which influence Leydig cell function.
- o Converts testosterone to estradiol through aromatase
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Hormones that affect spermatogenesis
testosterone
- Testosterone
- -Produced by Leydig cells
- -Androgen
- - Promotes Sertoli cell function
- -Needed for maturation of the sperm.
- -Prevents degeneration at Stage VII.
- -Essential for spermatid elongation.
- -Decreases GnRH via negative feedback.
- -Inhibits LH secretion via negative feedback.
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Hormones that affect spermatogenesis
Estradiol and inhibin
Estradiol - Produced by Sertoli cells via androgen converted to estradiol by aromatase
- Inhibin - Produced by Sertoli cells
- FSH levels in males is decreased by inhibin
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Hormones that affect spermatogenesis
FSH
- FSH—follicle stimulating hormone
- Produced by anterior pituitary
- Required to initiate sperm differentiation.
- FSH regulates the mitotic divisions and efficiency of spermatogonia development.
- FSH controls entry of stem cell spermatogonia into proliferating pool
- The yield of spermatozoa is increased by FSH by preventing the degeneration of differentiating spermatogonia.
- Partially restores spermatogenesis through meiosis.
- FSH is necessary during development: required to establish Sertoli cell function
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Hormones that affect spermatogenesis
LH and GnRH
- LH—lutenizing hormone
- Produced by anterior pituitary
- Increases testosterone production by Leydig cells
- GnRH—gonadotropic releasing hormone
- Hypothalamic hormone that controls release of anterior pituitary hormones (LH and FSH)
- Once the Sertoli function is developed, testosterone alone will maintain spermatogenesis
- The yield of spermatozoa is increased if FSH is present
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Sperm cell differentiation
spermatocyte --> spermatid --> sperm --> released from sertoli cell
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List the target organs for testosterone
- o Seminal vesicles—provides fructose rich liquid which is 60% semen volume. Sperm use fructose as energy source.
- o Muscle—increased muscle mass.
- o Bone—length of bone determined by estrogen (converted via aromatase)
- o Prostate
- o Libido
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List the target organs for DHT
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o Testosterone to DHT through 5 alpha reductase.
- o More potent than testosterone.
- o Drives the secondary sex characteristics in men.
- o Most important for external virilization and secondary sex characteristics.
- o Drives growth of prostate.
- o Other organs: adrenal glands, hair follicles, testes
- o Causes male pattern baldness—promotes hair loss from scalp.
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o If exogenous testosterone is given, we down regulate the axis and will not make sperm. It takes the sperm 90 days to get through the epididymis, so it will take 90 days to lose sperm. It will reverse if the oral contraceptives are removed, but it will take at least another 90 days to get counts back up. 100million sperm per 5mL is considered infertile, and it is nearly impossible to get the system to reverse above 100 million. This contraceptive will also cause him to begin to grow breast tissue, testes to shrink, etc.
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Sertoli Cells
so hyptothalmus --> GnRH --> Anteritory pituitary --> FSH and LH
- protecting sperm from immune system - androgen binding protein - on surface of sertoli cells - allow developing sperm to see high concentrations of testosterone --> bind testosterone to the ABP
- inhibin - feedback in a negative manner to regulate FSH
- convert testosterone to estrogen (estradiol) --> bind testosterone to the ABP (presenting very high conc. of testoerone to sperm)
FSH --> sertoli cell (in seminiferous tubules)
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Leydig cells
so hyptothalmus --> GnRH --> Anteritory pituitary --> FSH and LH
LH --> Leydig cells -->
- testosterone - made locally and acts in a paracrine manor which is bound to ABP --> so giving testosterone exogenous to male does not give them this function
- testosterone - also enters into blood stream and in negative feedback manner to regulate LH and FSH and also GnRH (long neg. feedback loop)
DHT - high octane from testoerone which is a conversion (testosteorne --> DHT) this is done by 5 alpha reductase (enzyme) --> DHT drives all of the secondary sex characteristics (beard, deep voice, etc)
so exogenous testosterone --> testes shrink and prostate grows
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Sperm Production
- FSH requires to initiate sperm differentiation
- # of sperm depends on how many sertoli cells and frquency of ejaculation
testosterone needed for maturation of sperm
maturation and storage in epididymus - 90 days to complete
capacitation - requires contact with female oviduct epithelium
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