Physiology 2 - Repro and Lactation

primordial germ cells --> oogonia

oogonia proliferate by mitosis during the first 1/3rd to 1/2 of gestation

in the late fetus, oogonia undergo mitosis to divide and then undergo meiosis in the first prophase diplotene (the "Dictyate") stage to form primary oocytes

the cell is arrested in the first diplotene ("dictyate") stage of meiosis

primordial follicle

primordial follicles become a primary oocyte by formation of cuboidal granulosa cells, basement membrane and theca

- glycoproteins secreted to form the zona pellucida
- the inner-most layer of granulosa becomes the corona radiata
- the rest of the granulosa cells become the cumulus oophorus
- during this time, the follicle starts to produce FSH receptors
- the oocyte and granulosa cells become surrounded by basement membrane: the blood-follicle barrier
- theca differentiates into the theca interna and the theca externa
- theca interna produces androgens which are transformed to estrogen by the granulosa
- estrogen stimulates LH receptor production in the theca; this causes more androgen --> estrogen production, leading to an LH spike

pre-antral phase is hormone independent, whereas the antral phase is hormone dependent

antrum

an antral follicle has an antrum, the fluid-filled capsule, whereas a pre-antral follicle is filled completely with granulosa cells and the oocyte

FSH

becomes a mature (late tertiary) follicle
- rapid increase in follicle size
- single large antrum
- resumption of metaphase I; half of the chromosomes are exocytosed as the first polar body and the other half are retained and arrested at Metaphase II to form the secondary oocyte
- cortical granules migrate to position just under the plasma membrane

LH

1. LH/FSH-induced "expansion" of cumulus granulosa via secretion of hyaluronic acid, which effectively loosens the oocyte connection from the CT wall
2. LH-induced proteases create a blister in the ovary wall
3. the release of intrafollicular pressure by outflow of antral fluid carries the cumulus-oocyte complex outside the ovary

- fertilization triggers the resumption of meiosis II
- a haploid polar body is exocytosed
- the resulting 1N sperm and 1N nucleus in the oocyte form a zygote

so that they can be quickly released upon fertilization to prevent polyspermy

(note: N refers to chromosome count here, not DNA/sister chromatid count)
1. spermatogonia (2N) divide several times by meiosis -->
2. primary spermatocytes (1N) divide by mitosis I -->
3. secondary spermatocytes divide by mitosis II (this is the last cell division) -->
4. early spermatids undergo morphological change -->
5. late spermatids -->
6. spermatozoa (aka a sperm cell)

large amorphous cells with tight junctions that surround and separate spermatogonia, spermatocytes, spermatids, and spermatozoa as they undergo spermatogenesis.

- Acts as a blood-testis barrier
- provides nourishment to developing sperm cells
- influences spermatogenesis
- resorbs droplets exocytosed from developing sperm
- secrete testicular fluid
- provide metabolites to cells in the semeniferous tubule lumen

spermatocytogenesis

spermiogenesis

spermiation

1. developing sperm from a single spermatogonia are identical genetically
2. they are connected via cytoplasmic bridges until released.

Golgi

axoneme = tail
the distal centriole

tail of a sperm

- acrosomal vesicle
- nucleus
- neck
- midpiece (mitochondrial sheath)
- annulus
- principal piece (flagellum)

acrosin - a proteolytic lysin
hyaluronidase - breaks down hyaluronic acid

stages

the stages are found in sequential order

false. The STAGES of the spermatogenic cycle are found in sequential order, which comprise sperm in various stages of development.

seminiferous tubules -->
rete testis -->
efferent ducts -->
epididymis -->
ductus deferens

1. transport - via hydrodynamic flow and muscular contractions
2. maturation of sperm
3. concentration - > 90% of tubule fluid id resorbed; compacted sperm lose their motility
4. storage

histones are replaced with protamines to make it more compact and flat

they have more S-S bonds

located in the testes, to synthesize androgens.

- LH upregulates the production of androgens
- FSH stimulates the synthesis of androgen binding protein, causing spermiation

by secretion of inhibin by the Sertoli cells, which effects a negative feedback on FSH secretion in the anterior pituitary

in the body of the epididymis (corpus epididymis)

- primates: vagina
- pigs: uterus
- rodents: vagina
- cats: vagina
- horses: cervix
- dogs: uterus
- ruminants: vagina

the cervix
(except pigs and dogs, where sperm is deposited into the uterus)

1. rapid phase: from the force of ejaculation
2. slow phase: sperm swim through channels in the cervix

they collect at the utero-tubal juncation by estrogen-induced peristaltic contractions of the uterus

to act as a sperm reservior, to gradually release sperm into the oviduct

sperm capacitation

because a capacitated sperm has a much shorter lifespan than a non-capacitated sperm; requirement for capacitation stretches out the fertilizing lifespan of an ejaculate

when it binds to the zona pellucida

epididymis - surface binding sites are free

ejaculate - vesicular secretions block surface binding sites by adding a protein called caltrin, which blocks Ca2+ transport

capacition - calitrin is removed, re-exposing the surface binding sites and allowing Ca2+ transport. Surface factors are bound to the sperm-head, including AC/cAMP modulators (calcitonin, FPP, adenosine, angiotensin II), Ca2+ influx modulators (progesterone, GABA), and adhesion molecules (e.g. SPAM1). Increased membrane fluidity by loss of cholesterol.

1. progressive motility - swimming
2. hyperactive motility

three:
1. cAMP/PKA
2. receptor tyrosine kinase pathway
3. non-receptor protein tyrosine kinase pathway

1. sperm binds to zona pellucida via ZP3
2. calcium influx into the sperm
3. F-actin converted to G-actin
4. Ca2+ induces the outer acrosomal membrane and sperm cell membrane to fuse
5. hyaluronidase is released and acrosin is exposed on the inner acrosomal membrane
6. inner acrosomal membrane binds to ZP2 on the zona pellucida

- hyaluronidase digests hyaluronic acid secreted by the cumulus cells

- acrosin digests a pathway through the zona pellucida

1. entire sperm enters the perivitelline space
2. motility diminishes or ceases
3. post-acrosomal membrane of sperm membrane binds to oocyte membrane
4. sperm ligand (fertilin) binds to oocyte surface receptor (integrin)

the post-acrosomal region (the side of the sperm)

1. depolarization of the oocyte membrane ("fast block")
2. corticle granule exocytosis changes ZP3 to ZP2 in the zona pellucide ("slow block")

after sperm-egg binding

perivitelline space

it changes the zona pellucida protein ZP3 to ZP2, which is indigestible by acrosin

the entire sperm

protamines are replaced with histones, allowing the chromatin to relax its conformation

pronuclei

both are 2N, having undergone duplication.

syngamy

4N

Metaphase and the first cleavage

blastomeres

morula

blastocyst

1. trophoblast - cells that will become placental tissues and extra-embryonic membranes
2. inner cell mass - will become the embryo
3. blastocoele - the fluid-filled cavity inside the blastocyst

by increasing pressure of the blastocoel fluid

- peptide: GnRH, oxytocin
- protein:FSH, LH
- steroid: estrogen, progesterone, testosterone
- fatty acid: prostglandin F2a

gonads, adrenal glands, placenta

arachadonic acid

- adenyl cyclase is activated in response to binding of a peptide/protein hormone to its receptor.

- AC catalyzes the conversion of ATP to cAMP

- cAMP activates protein kinase A, which stimulates gene expression and protein synthesis

1. primary reproductive regulatory system (puberty, seasonality, cyclicity)

2. balance of negative and positive feedback systems (hypothalamus, pituitary, gonads)

- GnRH is produced by the hypothalamus

- it is secreted into the pituitary via the hypophyseal portal system

- it also travels systematically to the gonads via the general circulation

- FSH and LH
- made in the anterior pituitary "gonadotroph" cells
- they are glycoproteins
- gonadotropin = "gonad" + "growth"

- Inhibin - Sertoli cells
- Testosterone - Leydig (interstitial) cells

- Estrogen - follicle
- Inhibin - follicle
- Progesterone - follicle and/or corpus luteum

LH

the follicle

- Estrogen at low levels: negative feedback on GnRH, FSH, LH
- Estrogen at high levels: positive feedback on GnRH, FSH, LH
- Inhibin: negative feedback on FSH
- Progesterone: Negative feedback on GnRH, FSH, LH

because there are different receptors that affect positive and negative feedback. The negative feedback receptor is sensitive to low levels of estergen; the positive feedback receptor needs large concentrations of estrogen, but overrides the negative feedback loop when stimulated.

Prostaglandin F2a:
- primary source: endometrium
- primary action: luteolysis
- clinical use: shorten cycle, eliminate progesterone production, evacuate the uterus (e.g. in pyometra)
- secondary action: myometrial contractions
- general action (if given systemically): systemic contraction of smooth muscle

because there are no steroid hormones being released to have a negative feedback on gonadotropin release

monestrous

polyestrous

seasonally polyestrous

short-day breeder: when days are shorter (e.g. fall)

long day breeder: when days are longer (e.g. spring)

proestrus

estrus

metestrous

diestrus

anestrus

- CL is undergoing regression/lysis (P4 levels fall below 1 ng/mL)
- female shows interest but will not stand to be bred
- follicular growth and rising estrogen levels - dominant follicles
- internel repro tract softens or becomes toned for sperm transport and fertilization

- female will stand to be bred
- follicular dominance with max estrogen production: induces LH surge (note: bitch needs estrogen and progesterone to stand to be bred)
- estrogen prepares uterus and uterine tube for sperm transport and fertilization
- the pre-ovulatory LH surge stimulates oocyte maturation and ovulation occurs 24-30 hours later
- following ovulation, LH stimulates granulosa and thecal cells from the ovulated follicle wall to become luteal cells
- following ovulation, a second increase in FSH occurs to stimulate a new wave of follicular development

1. stiumulates oocyte maturation and ovulation
2. stimulates ovulated follicle to become a CL

to stimulate follicular development

- early diestrus period where CL is developing from a corpus hemorrhagicum
- progesterone levels increase and prepare uterus for embryo and pregnancy maintenance
- embryo partially develops in uterine tube

estrogen opens the cervix; progesterone closes the cervix

- progestrone is the dominant hormone
- female will reject the male (headache)
- luteal phase: maximum CL size
- prolonged if there is pregnancy
- progesterone dominance that ends with luteal regression occurs if there is no pregnancy

- exhibits indifference to the male
- relative reproductive inactivity
- mainly seasonal breeders (exception is the bitch)
- low gonadotropin levels

1. inhibits estrus behavior (e.g. rejects male)
2. stimulates endometrial secretion of nutrients
3. closes cervix
4. inhibits myometrial contractions

> 1 ng/mL

Cow:
- Type of cycling: polyestrous
- Cycle length: 21 days
- behavior: increased riding activity
- estrus length: 7-18 hr
- time of ovulation: 28 hr after onset of estrus
- length of diestrus: 16-17 days

Mare:
- Type of cycling: seasonal polyestrous (long daylight breeder; winter anestrous); approx 20% of mares cycle year-round
- Cycle length: 21 d
- estrus length: early spring, 7-9 d; as season progresses, 3-5 d
- time of ovulation: 1-2 d before the end of estrus
- length of diestrus: 14-16 d

Ewe/Doe:
- Type of cycling: seasonal polyestrous (short-day breeder; anestrus summer)
- Cycle length: ewe 17 d; doe 21 d
- estrus length: ewe 20-48 h; doe 24-72 h
- bleeding, tail swishing, cloudy cervical mucous, seeks male

Sow:
- Type of cycling: polyestrous
- Cycle length: 21 d
- estrus length: 1-3 d
- behavior: mounting, back-pressure test in the presence of a boar
- length of diestrus: 16-18 d
- 35-45 hr after onset of estrus

Bitch:
- Type of cycling: monestrous (1-3 cycles per year)
- Cycle length: 9 day proestrus; 9 day estrus; 63 day diestrus; variable anestrus (total ~ 6 mo)
- 1-2 days after onset of estrus
- receptive to mating when progesterone and estrogen are present
- diestrus is a pseudopregnancy

Queen:
- Type of cycling: seasonal polyestrous (long day breeder: Feb - November)
- Cycle length: proestrus, 1.5 d; follicular phase every 2-3 weeks; 8-10 days if no ovulation
- estrus length: 4-7 days
- time of ovulation: 1-3 days after mating
- length of diestrus: INDUCED OVULATOR; diestrus only occurs if induced to ovulate and lasts 40-45 days as pseudopregnancy; 60 days if pregnant

conceptus

fetus

1. fertilization
2. early embryonic development
3. maternal recognition of pregnancy
4. placentation

histotrophe (uterine milk)

needs to be on the same side as (ipsilateral to the) the corpus luteum

uterine migration resulting in equidistant spacing of embryos

1. maternal recognition - prevents luteolysis
2. attachment to endometrium
3. formation of extraembryonic membranes
4. organogenesis

- cow: 278-293 (about 9 mo)
- mare: 330-345 (11 mo 11 d)
- ewe: 144-151 (about 5 mo)
- sow: 112-115 (3 mo 3 wk 3 d)
- bitch: 65 (about 2-2.5 mo)
- queen: 58-70 (about 2-2.5 mo)

- cow: 1
- mare: 1
- ewe: 1-3
- sow: 8-13
- bitch: 7 (average)
- queen: 4 (average)

- prevents natural luteolytic mechanisms
- it happens prior to the release of uterine PGF2a (myometrial contraction)
- a signal from the embryo (hormone and/or protein) is recognized by the mother

- cow: bovine interferon-τ (bovine trophoblastic protein 1)
- mare: none IDed; embryonic motility plays an important role
- ewe: ovine interferon-τ (ovine trophoblastic protein 1)
- sow: estradiol
- bitch/queen: unknown

at least four embryos are required because they must release enough estradiol to prevent intravenous passage of PGF2a

- progesterone
- ovarian (early) and placental (mid to late) origins
- closes cervix
- endometrial gland proliferation
- uterine quiescence
- mammary development

- produced by ovaries, placenta, and/or fetal gonads
- gradually increases, with peak around time or parurition
- dilates the cervix at parturition
- stimulates production of myometrial oxytocin receptors
- primer for progesterone and PRL for mammary development

- progesterone has a negative feedback on the hypothalamic secretion of LH and FSH
- low levels of LH do exist during pregnancy and are luteotropic early on.
- FSH waves may continue

the equine produces equine chorionic gonadotropin (eCG) from the endometrial cups during pregnancy, which act like LH during pregnancy. Similar hormones act like FSH in other species

luteal-dependent means that a CL of ovulation is required for the entire duration of pregnancy; luteal independent only needs the CL at the beginning of pregnancy because the placenta makes P4 later on.

Doe - dependent
Cow - independent
Bitch - dependent
Queen - dependent
Sow - dependent
Mare - independent
Ewe - independent

5 species are dependent; 3 are independent

polytocous

monotocous

nulliparous

primaparous

multiparous

- the fetus initiates its own parturition by stress-induced hormonal changes
- the dam can only control "when" it will happen, as in the morning or evening

ACTH, corticosteroids, and prostaglandin

- dilation of the cervix causes oxytocin release
- oxytocin release causes myometrial contraction (push!)
- contraction causes the cervix to dilate further and the cycle repeats until birth

relaxes the cervix and ligaments to assist with parturition

PG-E opens the cervix, and initiates parturition via the Ferguson reflex

it can be used clinically to induce labor

stimulates:
1. parturition
2. production of lung surfactant
3. liver and cardiac glycogen storage
4. maturation of insulin secretory mechanisms

5. increases conversion of T4-->T3 (higher metabolism)
6. increases deposition of brown fat
7. stimulates erythropoiesis

PRL

activates the placental enzymes that convert progesterone to estrogen

- increases myometrial oxytocin receptors
- increases prostaglandin production

- lysis of the luteal tissues in the CL-dependent species, causing a decline in progesterone levels and decreased cervical tone

- stimulates uterine contractions

1. pelvic limbs soften (estrogens and relaxin)
2. cervix softens and secretes mucus (estrogens and relaxin)
3. vulva relaxes (collagenase)
4. udder swells (first edema, then with milk)
5. fetus moves into proper position (in cow sternal recumbancy with front limbs extended and head facing cervix)

1. Dilation of the cervix
2. Expulsion of the fetus
3,. Expulsion of the fetal membranes

Stage I - dilation of the cervix

- variable clinical signs
- entry of fetus into cervical canal --> Fergusson's reflex
- ends with rupture of the chorioallantois (water breaks)

Stage II - expulsion of the fetus

- active labor
- Fergusson's reflex
- peak oxytocin --> forceful contractions
- abdominal contractions - the PUSH
- amnion ruptures to lubricate the birth canal
- ends with delivery of the fetus(es)

Stage III - expulsion of the fetal membranes

- variable in duration
- continued uterine contractions
- passage of placenta
- in polytocous species, placentas are usually passed during labor or shortly after birth of the first offspring
- mare: 3 hours; ruminants: 12 hours

puerperium or postpartum period

- uterine involution
- first estrus after parturition

- mare - first heat at 7-9 days; best fertility of ovulation >/= day 10
- cow - lochia passed after 1-2 weeks; 1st ovulation 10-20 days; low fertility; 45 day mandatory waiting period in dairy cattle; lactational anestrus in beef cattle
- small ruminants: not until next season
- sow: 5-7 days after weaning
- queen: 5-7 days after weaning
- bitch: long cycle length

chorion and allantois

allantois

- gases: simple diffusion
- urea: simple diffusion
- iron: facilitated diffusion
- glucose: non-insulin-dependent glucose transporters
- amino acids - primary active transport (and secondary)

- the primary gestational hormone
- promotes endometrial growth
- suppresses myometrial contraction
- promotes alveolar development in the mammary glands
- once established, makes enough to maintain pregnancy

alveolar growth: progesterone
ductal growth: estrogen

fetal gonads

causes increased Na (and water) reabsorption

- increases glucose delivery to the fetus
- maybe lactogenic

1. by degree of uterine tissue at implantation
2. by presence or absence of fusion of amnion and chorion
3. gross shape
4. histological structure

superficial - no loss of maternal tissue after parturition. pigs, horses, part of ruminant's placenta

interstitial - fetal tissues fuse with maternal, so there is loss of maternal tissue after parturition. most carnivores, rodents, primates, part of ruminant's placenta

- does not fuse: carnivores, horses; these species may be born covered with amnion

- does fuse: ruminants; may be born free of amnion

1. diffuse: modified area covers entireplacenta (horse, pig)
2. cotyledonary: plecentomes in ruminants
3. zonary: ring shaped (dog and cat)
4. discoid: disc shaped (primates, rodents)

- maternal endothelium
- maternal connective tissue
- maternal epithelium
- fetal epithelium
- fetal connective tissue
- fetal endothelium

the three maternal layers can be lost depending on placenta type. The three fetal layers are maintained.

1. water
2. fat (emusified)
3. protein (colloidal)
4. milk sugar (dissolved)
5. minerals and vitamins (dissolved)

- cow: 2 pairs, inguinal area
- pig: 4-8 pairs, thoracic and abdominal wall
- rabbit: 4-8 pairs, thoracic and abdominal wall
- small ruminants: one pair, inguinal region
- carnivores: 4-8 pairs, thoracic and abdominal wall
- mare: one pair, inguinal region
- rodent: 4-8 pairs, thoracic and abdominal wall
- deer: 2 pairs, inguinal area
- guinea pig: one pair, inguinal region

galactophore

(functional openings per teat)
- cow: 1
- bitch: 8-20
- queen: 4-7
- pig: 2-4
- mare: 2-4 (usually 2)
- small ruminant: 1
- mouse: 1
- rabbit: 8-20

1. arteriole
2. myoepithelial cells
3. capillaries
4. venules
5. lumen
6. epithelial cells
7. ducts

alveolus

alveoli

lobule

lobe

1. alveolus
2. alveoli
3. lobule
4. lobe

travels through the mammary ducts and is stored in the gland cistern

cricoid fold

passes through the streak canal.

the streak canal has smooth muscle to keep it closed, keratin, and antibacterial secreting cells to prevent microbes from entering the udder

approximately 1/3rd, 1/3rd, and 1/3rd

suckling intervals and physiological maturity. Those that suckle less frequently will tend to have more concentrated milk

casein

- casein is curdled out
- beta lactalbumin and alpha lactoglobulin remain dissolved

glucose

- high: Ca, P, K, I
- moderate: Na, Cl
- low to deficient: Fe (pigs), Se, other microminerals

dog and cat

- globulins and other protein
- vitamin A and beta carotene
- vitamin E
- some B vitamins

IgG1 and IgM

antitrypsin activity

atrophic ducts

1. atrophic ducts --(estrogen + somatotropin + corticoids)-->
2. duct growth --(estrogen + PRL + somatotropin + corticoids)-->
3. lobule-alveolar growth --(PRL + corticoids)-->
4. milk secretion

1. mammary duct growth only (rodents, cat)
2. mammary duct growth and loubuloalveolar system (ruminants)
3. no mammary growth (dogs)

estrogen and progesterone

glactopoiesis

production - PRL
letdown - oxytocin

rises and peaks between 30-60 days for most species and tails off until weaning.

- contraction of myoepithelial cells of the alveolus
- concurrent relaxation of the muscle surrounding the large alveolar ducts

cows will produce the most milk when allowed to dry off, the least milk when continuously milked, and somewhere in between these two values if not completely dried off.

increases. 3x per day results in a 10-20% increase versus 2x per day

the body temperature drops at night

males have paired testes
females have only one functional ovary, usually on the left

male: ZZ (homogamete)
female: ZW (heterogamete)

1. vocalization
2. courtship
3. aggression
4. nest building

extreme bone loss in the female bird to produce her eggs

cloacal protuberance or ejaculatory papilla

anseriformes (ducks and geese) and rattites

1. infundibulum
2. magnum
3. isthmus
4. uterus
5. vagina

magnum

isthmus

uterus

in spermatic fossulae at the junction between the uterus and vagina

altricial - immature and requires nursing by parents

precocial - self-reliant shortly after hatch

light passes through the skull and directly hits the pineal gland. Also the eye plays a role.

growth of seminiferous tubules

promotes testosterone secretion by the Leydig cells

- gas (O2, CO2)
- slow water loss

- nourishment
- maternal antibodies

the chick breathes in the air in the air cell, which is high in CO2. This stimulates breathing. To get its first real breath, the bird needs to poke through the egg shell.