Sex Differentiation & Reproductive endocrine control (cell bio) Flashcards
Embryology
** Totipotent - capable of giving rise to a complete ? **
A - Oocyte
B - Mature Oocyte
- Polar body
C - 2 Cell Zygote
D - 8 cell Embryo
E - 16 cell Embryo
F - Morula
G - Blastocyst
H - Hatching Blastocyst I - Hatched Blastocyst
Early embryo development
- Several ? divisions
- Early divisions occur without an increase in cell ?
- “?” (or “Reduction Division”)
- ? support provided by ? secretions
- Zygotic protein synthesis begins at 2 to 16-cell stage depending on species (? cells)
Early embryo development
- Several mitotic divisions
- Early divisions occur without an increase in cell mass
- “Cleavage” (or “Reduction Division”)
- metabolic support provided by maternal secretions
- Zygotic protein synthesis begins at 2 to 16-cell stage depending on species (Totipotent cells)
- An important event during embryo life is the differentiation from the ? to the blastocyst stage.
- During the morula stage, the cells differentiate into #? groups of cells
- Inner cell mass (ICM) – ? cells in the “Blastocyst” that will form the ?
- Trophoblast – will develop the ? (placenta – ? portion)
- In addition, the cells from the trophoblast “pump” ? into the intracellular space and because of the osmotic pressure, the embryo is filled with “?”, which forms the “Blastocele or ?”.
- Blastocele will form the ? that will surround the embryo.
- An important event during embryo life is the differentiation from the morula to the blastocyst stage.
- During the morula stage, the cells differentiate into 2 groups of cells
- Inner cell mass (ICM) – polarized cells in the “Blastocyst” that will form the embryo
- Trophoblast – will develop the chorion (placenta – external portion)
- In addition, the cells from the trophoblast “pump” sodium into the intracellular space and because of the osmotic pressure, the embryo is filled with “?”, which forms the “Blastocele or ?”.
- Blastocele will form the cavity that will surround the embryo.
Embryology
The embryo starts as a ? of cells that eventually form layers and will differentiate into the ? proper and ?.
endoderm includes the ?, ?, ?)
mesoderm includes ?, skeleton, ?, reproductive system (MSCR)
ectoderm includes the ? system, skin and ? (HSN)
Embryology
The embryo starts as a mass of cells that eventually form layers and will differentiate into the embryo proper and placenta
endoderm includes the digestive system, lungs, endocrine system (endoderm - DLE)
mesoderm includes muscle, skeleton, cardiovascular, reproductive system (MSCR)
ectoderm includes the nervous system, skin and hair (HSN)
PLACENTAL DEVELOPMENT
- The ? is the external embryonic tissue and gives rise to the placenta.
- ? mesoderm and trophoblast constitute the (* ? *).
- Expansion of the allantois forms the ?
Embryology: Sex differentiation
* Initially ? (about 6 weeks in large domestic animals)
** ? ** cells migrate from outside the organism ( ** ? **) into the organism through the hindgut to the undifferentiated gonad just within the dorsal body wall (also known as the * ? *).
PLACENTAL DEVELOPMENT
- The trophoblast is the external embryonic tissue and gives rise to the placenta.
- extraembryonic mesoderm and trophoblast constitute the (* chorion *).
- Expansion of the allantois forms the allantochorion
Embryology: Sex differentiation
* Initially indistinguishable (about 6 weeks in large domestic animals)
** primordial germ ** cells migrate from outside the organism ( ** yolk sac **) into the organism through the hindgut to the undifferentiated gonad just within the dorsal body wall (also known as the * genital ridge*).
Embryology: sex differentiation
- The reproductive system develops at the same time as the ? system
mesonepfric = ? ducts
paramesonephric = ? ducts
Embryology: sex differentiation
- The reproductive system develops at the same time as the renal system
mesonepfric = wolffian ducts
paramesonephric = mullerian ducts
MALE
testes determining factor -> testes develop ->
sertoli cells secrete
1. AMH: causes leydig cells to differentiate
2. Degeneration of paramesonephric duct
AMH: causes Leydig cells to differentiate -> Testosterone -> development of male duct system
AMH causes leydig cells to differentiate -> dihydrotestosterone -> development of penis, scrotum and accessory sex glands
FEMALE
No TDF -> ovaries develop -> no AMH -> ? ducts become the oviducts, the ?, cervix, and part of the vagina -> complete ? tract
MALE (XY)
testes determining factor -> testes develop ->
sertoli cells secrete
1. AMH: causes leydig cells to differentiate
2. Degeneration of paramesonephric duct
AMH: causes Leydig cells to differentiate -> Testosterone -> development of male duct system
AMH causes leydig cells to differentiate -> dihydrotestosterone -> development of penis, scrotum and accessory sex glands
FEMALE (XX)
No TDF -> ovaries develop -> no AMH -> paramesonephric ducts become the oviducts, the uterus, cervix, and part of the vagina -> complete female tract
Embryology (MALE XY)
testis determining factor
-> testis development (sertoli cells)
AMH
-> Development of the Leydig cells
- testosterone - male duct system
FEMALE
absence of
- testis determining factor
- AMH
- testosterone
Embryology: Sex differentiation
Hypothalamus: Male vs. Female
- Female hypothalamus contains 2 functional areas for secretion of GnRH
-> ? (arcuate ventromedial region; ARC) and
-> ? (preoptic area; POA) centers - Hypothalamus is inherently female
-> testosterone during ? “defeminizes” the brain
- testosterone crosses blood-? barrier and is converted to ?
- estradiol defeminizes hypothalamus, ? surge center
-> fetal ovaries produce estradiol, but this doesn’t cross the blood-brain barrier bc it is bound to alpha-?
Embryology: Sex differentiation
Hypothalamus: Male vs. Female
- Female hypothalamus contains 2 functional areas for secretion of GnRH
-> tonic (arcuate ventromedial region; ARC) and
-> surge (preoptic area; POA) centers - Hypothalamus is inherently female
-> testosterone during development “defeminizes” the brain
- testosterone crosses blood-brain barrier and is converted to estradiol
- estradiol defeminizes hypothalamus, eliminating surge center
-> fetal ovaries produce estradiol, but this doesn’t cross the blood-brain barrier bc it is bound to alpha-fetoprotein (@FP)
HORMONES
Chemical messengers
* Most hormones are:
Secreted by an ? gland
Carried by the ?
Affect other organs, ?, or tissues.
Controls ? processes
Signaling molecules produced in the body that regulate the activity of certain ? and ?
HORMONES
Chemical messengers
* Most hormones are:
Secreted by an endocrine gland
Carried by the bloodstream
Affect other organs, glands, or tissues.
Controls metabolic processes
Signaling molecules produced in the body that regulate the activity of certain cells and organs
Classification of hormones
Chemical nature:
STEROID:
* Derived from ?
* ? (a male sex hormone like testosterone)
* Metabolized in the ? (first- pass)
* Ex.: Estrogens, ?, progesterone
AMINE HORMONES
* The amino acid-derived hormones are relatively small molecules that are derived from the amino acid ? and ?.
* ? metabolized
* Name of amino acid- derived ends in “-ine”
* Ex.: ?, Epinephrine
PROTEIN/PEPTIDE
* ? proteins or small/medium size peptides (chain of amino acids)
* Much larger than ? and ? hormones
* ?-soluble – membrane ?
* Short peptides – Ex.: ?
* Small proteins – Ex.: ? hormones
* ? – Ex.: FSH, LH
Eicosanoids (not produced by glands so aren’t considered real hormones)
* Derived from ? fatty acids from the cell membrane - usually ? acid (20-carbon)
* Key mediators and regulators of ? and immunity
* autocrine or paracrine?
* Ex.: ?
stomach enzymatic degradation involves:
1. amine hormones
2. protein/peptide hormones (short peptide - oxytocin, small protein - growth hormone)
3. eicosanoids
Classification of hormones
Chemical nature:
STEROID:
* Derived from cholestrol
* androgen (a male sex hormone like testosterone)
* Metabolized in the liver (first- pass)
* Ex.: Estrogens, testosterone, progesterone
AMINE HORMONES
* The amino acid-derived hormones are relatively small molecules that are derived from the amino acid tyrosine and tryptophan.
* easily metabolized
* Name of amino acid- derived ends in “-ine”
* Ex.: melatonin, Epinephrine
PROTEIN/PEPTIDE
* larger proteins or small/medium size peptides (chain of amino acids)
* Much larger than steroid and amine hormones
* water-soluble – membrane receptors
* Short peptides – Ex.: oxytocin
* Small proteins – Ex.: growth hormones
* glycoproteins – Ex.: FSH, LH
Eicosanoids (not produced by glands so aren’t considered real hormones)
* Derived from polyunsaturated fatty acids from the cell membrane - usually arachidonic acid (20-carbon)
* Key mediators and regulators of inflammation and immunity
* paracrine
* Ex.: prostaglandins
CLASSIFICATION OF HORMONES
Mechanism of action
Bind to 1. intracellular & 2. cell membrane receptors:
INTRACELLULAR receptors
* Form ?-receptor (H-R) complexes
* Biochemical function mediated by H-R complex
* ?
* Found in the circulation in association with ? proteins
* LONGER OR SHORT half-life (hours or days)
* Ex.: ?
CELL-MEMBRANE receptors
- Hormones bind the cell membrane receptors (?- protein), which induce the release of ? messengers.
- Secondary messengers perform the ? function.
- Hydrophilic or hydrophobic?
- Transported in the ?-form
- Long or Short Half-life (minutes)
Ex.: ? acid derived and ?
CLASSIFICATION OF HORMONES
Mechanism of action
Bind to intracellular receptors:
- Form hormone-receptor (H-R) complexes
- Biochemical function mediated by H-R complex
- lipophillic
- Found in the circulation in association with transport proteins
- LONGER half-life (hours or days)
- Ex.: Steroids
CELL-MEMBRANE receptors
- Hormones bind the cell membrane receptors (G- protein), which induce the release of secondary messengers.
- Secondary messengers perform the biochemical function.
- Hydrophilic so
- Transported in the free-form
- Short Half-life (minutes)
Ex.: amino acid derived and eicosanoids
Hormone control: Negative or Positive feedback
- Most endocrine hormones are regulated by + or - ? feedback loops. Negative feedback keeps the concentration of a hormone within a relatively ? range and maintains ?.
- Ex.: Testosterone is essential for spermatogenesis. However, excessive concentrations of testosterone cause ? feedback on the anterior pituitary for the release of ?, which will consequently reduce the activity of ? cells for the production of testosterone.
- Very few endocrine hormones are regulated by ? feedback loops. Positive feedback causes the concentration of a ? to become increasingly higher.
- Ex.: Estradiol produced by the pre-ovulatory follicle causes ? feedback to the anterior pituitary for the release of LH. The LH will induce the ovulation of the pre-ovulatory ?.
Hormone control: Negative or Positive feedback
- Most endocrine hormones are regulated by negative feedback loops. Negative feedback keeps the concentration of a hormone within a relatively narrow range and maintains homeostasis.
- Ex.: Testosterone is essential for spermatogenesis. However, excessive concentrations of testosterone cause NEGATIVE feedback on the anterior pituitary for the release of Leydig cells, which will consequently reduce the activity of Leydig cells for the production of testosterone.
LEYDIG CELLS -> TESTOSTERONE - Very few endocrine hormones are regulated by positive feedback loops. Positive feedback causes the concentration of a hormone to become increasingly higher.
- Ex.: Estradiol produced by the pre-ovulatory follicle causes positive feedback to the anterior pituitary for the release of LH. The LH will induce the ovulation of the pre-ovulatory follicles.
Hormones
Supraphysiological stimulation
* Exceeding what is normally found in healthy individuals
* Hormone becomes ? after long-term use
“?” of hormone receptors
Once the peptide hormones are bound to their receptors on the appropriate ? cells, they are internalized and ? by the process of receptor-mediated endocytosis
Ex.: Prolonged-release, high dose GnRH
Used as a contraceptive in dogs and horses
Physiologically, GnRH is responsible for ? growth and ?
(cells internalize their receptors which means cells can’t respond anymore so the gland stops responding to treatment and stops producing the effect we want
e..g GNRH which is imp. for cycling in females and can induce cyclists in females giving estrogen
too much GnRh then she stops cycling)
Hormones
Supraphysiological stimulation
* Exceeding what is normally found in healthy individuals
* Hormone becomes ineffective after long-term use
“ internalization ” of hormone receptors
Once the peptide hormones are bound to their receptors on the appropriate target cells, they are internalized and degraded by the process of receptor-mediated endocytosis
Ex.: Prolonged-release, high dose GnRH
Used as a contraceptive in dogs and horses
Physiologically, GnRH is responsible for follicular growth and ovulation
Hormones
Source of production Hypothalamic-pituitary-gonadal axis
- Pineal gland: ?
- Hypothalamus: ?
- Pituitary Gland: FSH, ?, Prolactin, ?Gonads:
- Ovary: Follicles - Estradiol, Inhibin, Testosterone; Corpus luteum - Progesterone, Relaxin, Oxytocin
- Testis: ?, Inhibin, ?
- Uterus: ? F2 alpha
- Placenta: ?, ?, hCG , eCG, ?, PGF2α
Hormones
Source of production Hypothalamic-pituitary-gonadal axis
- Pineal gland: melatonin
- Hypothalamus: GnRH
- Pituitary Gland: FSH, LH, Prolactin, OxytocinGonads:
- Ovary: Follicles - Estradiol, Inhibin, Testosterone; Corpus luteum - Progesterone, Relaxin, Oxytocin
- Testis: testosterone, Inhibin, estradiol
- Uterus: prostaglandin F2 alpha
- Placenta: progesterone, estradiol, hCG , eCG, Oxytocin, PGF2α
Hypothalamic-Pituitary Portal System
▪ A system of blood ? in the microcirculation at the ? of the brain, connecting the hypothalamus with the ? pituitary.
▪ Axons of hypothalamic neurons extend to blood vessels of ? system
▪ Function: quickly transport and exchange ? between the hypothalamus ? nucleus and anterior pituitary gland.
▪ Hormones: ?, GHRH (Growth hormone), CRH (corticotrophin), ? (thyrotrophin)
▪ GnRH affects the anterior pituitary ?
▪ Hypothalamic centers (FEMALE*)
▪ ? – Regulates the release of frequent low-amplitude tong GnRH pulses
▪ ? - Only in females – responsive to high levels of estradiol and release of high amplitude GnRH pulse
Regulate by levels of ? - Feedback
Hypothalamic-Pituitary Portal System
▪ A system of blood vessels in the microcirculation at the base of the brain, connecting the hypothalamus with the anterior pituitary.
▪ Axons of hypothalamic neurons extend to blood vessels of portal system
▪ Function: quickly transport and exchange hormones between the hypothalamus arcuate nucleus and anterior pituitary gland.
▪ Hormones: GnRH, GHRH (Growth hormone), CRH (corticotrophin), TRH (thyrotrophin)
▪ GnRH affects the anterior pituitary directly
▪ Hypothalamic centers (FEMALE*)
▪ TONIC – Regulates the release of frequent low-amplitude tong GnRH pulses
▪ SURGE - Only in females!! – responsive to high levels of estradiol and release of high amplitude GnRH pulse
Regulate by levels of estrogens - Feedback
adenohypophysis (anterior pituitary - non-neural tissue): release of LH, FSH, ACTH, PRL, GH, TSH
Female estrous cycle
* Period from the beginning of one estrus to the beginning of the ? (or from one ovulation to the next)
- Follicular phase - estrus (? phase in women) - estrogen
- Luteal phase - diestrus (? phase in women) - ?
- Quiescent phase – anestrus – ? hormones (when females not cycling; for seasonal animals or females that are sick - too much stress)
- Estrus is defined behaviorally
Oestrogens:
produced by developing ?
reproductive behaviours
females receptive when oestrogens are high
Progestagens
produced by ? following ovulation
supports conception and ?
females are receptive when progestagens are low (usually)
Female estrous cycle
* Period from the beginning of one estrus to the beginning of the next (or from one ovulation to the next)
- Follicular phase - estrus (proliferative phase in women) - estrogen
- Luteal phase - diestrus (secretory phase in women) - progestogen
- Quiescent phase – anestrus – NO hormones (when females not cycling; for seasonal animals or females that are sick - too much stress)
- Estrus is defined behaviorally
Oestrogens:
produced by developing follicles
reproductive behaviors
females are receptive when oestrogens are high
Progestagens
produced by the corpus luteum following ovulation
supports conception and pregnancy
females are receptive when progestagens are low (usually)
Endocrine regulation of estrous cycle Hypothalamo-hypophyseal-ovarian axis
Regulated by:
- Hypothalamus:
-> ? - Adenohypophysis/anterior pituitary:
-> ? and ? - Ovary:
-> ? (E2), ? (P4), Inhibin, and ? - Uterus:
-> ? F2α (PGF2α)
Endocrine regulation of estrous cycle Hypothalamo-hypophyseal-ovarian axis
Regulated by:
- Hypothalamus:
-> GnRH - Adenohypophysis/anterior pituitary:
-> FSH and LH - Ovary:
-> Estradiol (E2), progesterone (P4), Inhibin, and oxytocin - Uterus:
-> prostaglandin F2α (PGF2α)
FEMALE ESTROUS CYCLE
Ovary
- Medulla (intern)
-> ?, nerves, ? tissue - Cortex (extern)
-> oocytes, ?, CL
FEMALE ESTROUS CYCLE
Ovary
- Medulla (intern)
-> vasculature, nerves, connective tissue - Cortex (extern)
-> oocytes, follicles, CL
Hypothalamo-pituitary-gonadal axis
Diestrus
- progesterone (lack of E2) - no LH
-> FSH doesn’t need ? feedback. Therefore, follicles keep developing
Estrus
- Inhibin - negative feedback for FSH
-> Induce follicular ?
- estradiol - positive feedback for ? (surge center)
-> Induce ?
(estrus -> surge center -> anterior pituitary secrestes estrogen)
Hypothalamo-pituitary-gonadal axis
Diestrus
- progesterone (lack of E2) - no LH
-> FSH doesn’t need positive feedback. Therefore, follicles keep developing
Estrus
- Inhibin - negative feedback for FSH
-> Induce follicular regression
- estradiol - positive feedback for LH (surge center)
-> Induce ovulation
(estrus -> surge center -> anterior pituitary secrestes estrogen)
FEMALE ESTROUS CYCLE
Follicular dynamics
* Follicular growth occurs in ? or cohorts
- Number varies between and within ?
- Recruitment
- Selection
- Dominance
- Atresia
FEMALE ESTROUS CYCLE
Follicular dynamics
* Follicular growth occurs in waves or cohorts
- Number varies between and within species
- Recruitment
- Selection
- Dominance
- Atresia
notes:
- 1 estrus cycle is the period between 1 ovulation and the next ovulation
- UNDERSTAND THAT during the estrus cycle is not the one follicle that we develop and ovulate
- in reality, we have a recruitment of follicles so imagine we have one ovulation here so bc of that ovulation that cell will produce progesterone
- bc of that progesterone the cell doesn’t do much to the hypothalamus or to the anterior pituitary
- so the anterior pituitary, the tonic center of the hypothalamus they are still working, and then the anterior pituitary produces the hormone called FC follicular stimulating hormone.
- bc of these FSH the follicles will develop
- so most of these species will have two or three follicular waves
- so first many follicles will be recruited.
- They will develop. And then we have this second phase that’s called SELECTION.
- During this election, some follicles, they decrease, they go through ATROPHY and the other follicles they still going forward.
- After that we have 3rd phase called DOMINANCE which happens in the majority of the species that we have only one ovulation, cows, horse, sheep, goats and even humans.
- so when one follicle reaches dominance means that that follicle will be able to keep growing and other follicles will regress.
- after that we have ovulation or atresia
- most of that at the first follicular wave or second these follicles will reach dominance, but won’t ovulate due to absence of estradiol
- we need enough estradiol for the surge center to work
- in the 2nd wave everything happens again and one follicle reaches dominance.
- at this phase (ovulation - big circle on the right of potentially ovulatory) no progesterone left
- no progesterone being produced in the FSH phase so at this moment lots of estradiol and so this estradiol will cause positive feedback to the surge center
- and then we have this release of LH by the anterior pituitary and these LH will cause ovulation.
Female estrous cycle
FOLLICLES
Primordial follicle
* Oocyte surrounded by a single layer of ? cells
Primary follicle
* Oocyte surrounded by single layer of ? cells
Secondary follicle
* ? surrounded by two or more ?
* Zona ?
Antral follicle
* Fluid accumulates within a cavity formed by ? cells
Female estrous cycle
FOLLICLES
Primordial follicle
* Oocyte surrounded by a single layer of squamous cells
Primary follicle
* Oocyte surrounded by a single layer of cuboidal cells
Secondary follicle
* Oocyte surrounded by two or more layers
* Zona pellucida
Antral follicle
* Fluid accumulates within a cavity formed by follicular cells
- We have the primordial follicles that will be clearly those oocytes that are there resting.
- they will have only a single layer of hiscamo? cells that can only be seen if u do a histological section of ovary
- primary follicles when they resume that meiotic division, again, the first meiotic division, and they have a little bit of one layer of cuboid of cells here.
- similarly secondary follicles have more cells and layers of cells around oocyte but don’t have fluid
- they all are called PREANTRAL follicles and it means that they can grow and develop even tho we don’t have FSH or LH or gonadotropins so some of them even start developing right before puberty.
- but if its follicles reach the tertiary follicle stage they start to develop in the antrum which is the fluid-filled cavity inside of the follicle
and bc of this cavity has been developed at this moment
Folliculogenesis
“Resting pool”
* Pool of inactive ? follicles
* ? phase (Prophase I)
Committed follicle (four possibilities)
* Remains ?
* Die
* Begging development and ? later
* Develop and ovulate
Follicle activation is irreversible
* Finite nest
Unknown what triggers the primordial follicle activation
* Intraovarian signaling – oocyte or granulosa cells
Gonadotropin-independent growth
* Follicular development up to the formation of the antrum is independent of FSH or LH
Folliculogenesis
“Resting pool”
* Pool of inactive primordial follicles
* Dormant phase (Prophase I)
Committed follicle (four possibilities)
* Remains quiescent
* Die
* Begging development and atresia later
* Develop and ovulate
Follicle activation is irreversible
* Finite nest
Unknown what triggers the primordial follicle activation
* Intraovarian signaling – oocyte or granulosa cells
Gonadotropin-independent growth
* Follicular development up to the formation of the antrum is independent of FSH or LH
- so first we have resting pools, so all females are born with follicles which get arrested at Prophase one until puberty
- We don’t know exactly what happens that to make some of these follicles resume that to meiosis while others still resting
- when they resume meiosis, they finish meiosis I and release their first polar body and at this period are called “pre-antral follicles”
- it means that these pre-antral follicles are NOT gonadotropin-dependent hormones so they can grow during this pre-antral phase without LH or FSA
- when they reach antral phase which is when follicles start to develop in this fluid inside of the follicle, they are gonadotropin dependent so they cannot develop anymore without FSH or LH.
- bc the females have follicles that already started in meiosis these net of follicles is finished
- that’s why women go through menopause they finish them on some sites so they can’t produce oocytes for ovulation.
- another imp. thing we talk about those follicular waves, the follicles they start developing and some of them, most of them, they will go to atresia or they will regress.
- When this follicles start their development, they cannot go back so that follicles will start meiosis I if go back then die The FOLLICLE CANNOT GO BACK, then restart males again.
- so all those follicles that started will die in one or two or 3 depending on the species
Inhibin -> downregulation of FSH secretion
- Dominant follicle keeps developing bc it has enough/more receptors for ?
- produces estradiol which leads to 3.
- induces synthesis of ? which leads to 4.
- induces ?
estradiol (when it passes the threshold) -> surge center -> changes to positive feedback, to anterior pituitary to produce LH and also releases GnRH (binds to receptors on follicular wall and cause ovulation)
Inhibin -> downregulation of FSH secretion
- Dominant follicle keeps developing bc it has enough/more receptors for FSH
- produces estradiol which leads to 3.
- induces synthesis of LH which leads to 4.
- induces ovulation
estradiol (when it passes the threshold) -> surge center -> changes to positive feedback, to anterior pituitary to produce LH and also releases GnRH (binds to receptors on follicular wall and cause ovulation)
