Estrogen (via androgen secretion)

* Theca interna of the Secondary/Antral Follicle

* Theca leutin of the corpus luteum

Progesterone

* Granulosa cells of the corpus luteum

Primordial Follicle: Contain primary oocytes (arrested in Pro I of Meiosis I) ard are present at birth. During each menstrual cycle a batch mature to primary follicles but only one will mature fully. Primordial follicles that do not mature degenerate to form atretic follicles.

Growing Follicles: Primary Follicle: Simple Cuboidal follicular cells, a primary oocyte and a homogenous zona pellucida.

Late Primary Follicle: Follicular cells form Membrana granulosa (stratified epi) and stromal cells form Theca Folliculi.

Secondary/Antral Follicle: Antrum develops surrounded by granulosa cells. Theca folliculi differentiates into Theca externa and Theca Interna (interna produces androgens which the granulosa can convert to estrogen).

Mature/Graffian Follicle: Antrum becomes hores-shoe shaped and there is a Secondary oocyte (arrested in Meta II) Cumulus oophorus and corona radiata appear.

Secondary oocyte surrounded by its corona radiata is expelled from the ruptured follicle.

Occurs when...

When ovulation has taken place and the secondary oocyte has been expelled the follicle surroundeing it collapses forming the Corpus Luteum.

If fertilization/implantation does not occur the corpus luteum is the CL of Menstruation and is active for 14 days.

If fertilization/implantation does occur it becomes the CL of Pregnancy and lasts for 8 weeks during which time its continued presence is promoted by hCG which is secreted by throphoblasts (specialized cells of the placenta).

Atretic Follicle: the degradation of the follicle at any point during the growing follicle stage that does not form the final mature follicle. Mediated by apoptosis of granulosa cells . Glassy membrane forms bw follicular cells and the theca interna.

Degenerated corpus luteum forms a white scar known as the Corpus Albicans.

FSH/LH levels spike just prior to ovulation (day 14)

Estrogen levels peak similarly to FSH/LH just before ovulation but remian high throughout the rest of the cycle.

Progesterone levels peak later in the cycle, after Day 14 and after the estrogen peak. Peak occurs int he secretory phase.

Cervical Endometrium does not have spiral arteries and is not sloughed off during menstruation.

Endocervix is the innermost portion of the cervix (simple columnar epi) with two openings: External os and Internal os. Contains glands that produce large amounts of mucus (visable in sections).

Ectocervix opens into the vagina (stratified squamous epi)

Inner Mucosal layer has transferse folds (stratified, squamous, non-K epi) with no muscularis mucosa.

Intermediate Musuclar Layer.

OUter Adventita.

Unlike the vagina, the esophagus has a very thick muscularis mucosa*

The breast is a modified sweat gland made up of ~20 lobes of branched tubuloalveolar glands which lie in subQ tissue.

Each gland ends in a lactiferous duct which opens into a nipple. Each duct has a dilation known as a lactiferous sinus.

Inactive Mammary Gland has sparce glands and is made mainly of ducts (lined by columnar epi), CT and fat. Myoepithelial cells are present.

Active Mammary Gland duct system proliferates, secretory alveoli appear as secretory products accumulate. CT and fat components decrease through myoepi cells are still visable.

Plasma cells, lymphocytes and eosinophils infultrate.

Produces gametes and steroid hormones.

Each ovary is attached to the broad ligament via the Mesovarium. The Mesothelium (lining of the peritoneum) is continuous with the lining of the ovary (the germinal epithelium). Germinal Epithelium surrounds each ovary, simple cuboidal epi. Deep to the germinal epithelium is the Tunica albugenia (dense CT,). Inside the Tunica Albugenia is the Cortex which contains Ovarian Follicles and CT. Deep to the Cortex is the medulla which does not contain follicles but does contain loose CT, vessels, lymphatics, and nerves.

The reminants of the collapsed follicle after ovulation.

Granulosa Cells are lare cells that are fat and have a yellow pigmentation. Granulosa cells secrete Progesterone.

Theca leutin cells are derrived from theca interna. Are smaller cells that stain deeply. Theca leutin cells secrete Androgens (that are converted to estrogen).

After ~8 weeks, the corpus luteum degenerates leaving a white scar called the corpus albicans.

4 Segments: Infundibulum, Ampulla (*Fertilization usually occurs here, near where it meets the isthmus), Isthmus, and the Intramural part.

Perimetrium: Outer, serous layer.

Myometrium: a thick middle, muscular layer. Is made of three layers itself. The central stratum vasculare contains the large blood vessels and the inner and outer layers, whose muscle cells increase in length during pregnancy.

Endometrium: Innermost, mocosal layer. Proliferates and generates. 2 zones: Stratum basale (maintained during menstration and supplied by straight arteries) and the Stratum functionale (sloughed off during menstruation, supplied by spiral arteries)

Proliferative Phase (reg by Estrogen, Days 1-14) Epithelum migrages to cover endometral surface and spiral arteries lengthen, stromal cells proliferate and glands are straight with a narrow lumen.

Secretory Phase (reg by Progesterone) Changes in the stratum functionale, lengtheinging and coiling of spiral arteries, enlargement of stromal cells and glands. glands become corkscrew in shape.

Menstrual Phase (result of a decline in Progesterone and Estrogen from the ovary) occurs if fertilization does not. Sloughing off of the functional layer is caused by periodic, then extended periods of spiral arterial contractions which disrupt the fuctional layer.

In the cervix, where the columnar epi of the endocervix abruptly meets the stratified epi of the ectocervix at the External Os.

Ectropin occurs when there is growth of the columanr epithelum beyond the exocervical os.

Remodling occurs continuously in the transformation zone which makes this the location of precancerous cervial lesions.

It is this region that is sampled in a Pap smear looking for cervical neoplasims.

Terminal Duct Lobular Unit

Consists of a Terminal Duct whose epithelum becomes the acini of the lactating breast, Intralobular collecting duct and intralobular stroma.

Most breast cancers arise in TDLU*

Presence or absence of Estrogen/Progesterone Receptors (ER/PR)

Overexpression of HER2/NEU

The side of the developing embryo/morula where the Inner Cell Mass remains in contact with the trophoblast layer.

It is here that the embryo will develop.

The cells of the blastocyst that form the outermost layer of the developing blastocyst, surruounding the blasotcyst cavity and the embryoblast.

Cytotrophoblasts begin to invade the uterine endometrial epithelium and will give rise the the synctiotrophoblasts.

~7 days post-fertilization (dpf)

Invading cytotrophoblast cells begin to fuse with one another and lose their individula cell membranes, giving rise to the synctotrophoblast.

A mass of synctial cells. Trophoblastic lacunae within the synctotrophoblast will connect with vessels and glands.

At this point in development the embryoblast hs formed a bilaminar disc (epiblasts and hypoblasts) and an amniotic cavity has developed in a cleft in the epiblast layer. Cells migrating out of the hypoplast form the primitive yolk sac.

The primary villus is a core of cytotrophoblast surrounded by synctiotrophoblast.

As the villus develops there is a mesodermal core that fills the center and is surrounded by a layer of cytotrophoblast surrounded by a layer of synctiotrophoblast.

Eventually the mesodermal core will develop villous capillaries.

Villi are surroudned by maternal blood so they function to bick up oxygen and nutrients (returning them to the fetus via the umbilical vein) and give off fetal carbon dioxide.

The chorion is the fetal part of the placenta; a membrane layer that surrounds the developing embryo and the other membranes.

It is made of an outer synctiotrophoblast, a middle layer of cytotrophoblastic cells and an inner layer of extrembryonic somatoplueric mesoderm.

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What makes up the maternal part of the placenta?

The fetal part?

Inner layer surrounding the exocoelomic cavity (the primitive yolk sac).

Is formed when the chorionic cavity develops dividing the extraembryonic mesoderm into somatic and splanchnic.

Decidua

Name its regions and the fate of each.

From the mother, the decidua cells form from stromal cells in the maternal functionalis that enlarge and gain lots of lipid and glycogen. This is when the maternal functionalis becomes the decidua.

Decidua basalis is the maternal part of the placenta.

Decidua capsularis is the protion of the decidua that encapsulates the embryo itself (over the chorion laeve)

Decidua parietalis is everywhere else, lining the uterine cavity.

Eventually the capsularis and paritalis fuse and the capsularis degenerates leaing an enlarged amniotic cavity with the parietalis directly on the chorion laeve.

Chorion laeve

vs.

Chorion frondosum

Chorion laeve is the portion of the developed chorion that does not have villi (villi were compressed as the fetus grew and those in teh decidua capsularis degenerated)

Chorion frondosum is the portion of the chorion that still has villi (the portion associated with the decidua basalis).

Describe the placental septa.

What are cotyledons?

The placental septa are wedge-shaped areas of maternal decidua that have erroded into intervillous spaces. Enables better transfer of blood from mother to fetus.

Cotyledons are the compartments that are created by the septal divisions of the placenta. They appear as bulges that can be seen deep to the decidua basalis.

Structures passing through the umbilical ring at 5 wk = A connecting stalk (contains umbilical vessels and the allantois) + the yolk stalk/vitelline duct (has the yolk sac on its distal end) + canal connecting intra and extraembryonic coelom called the chorionic cavity.

The amnion expands and envelops the youlk sac and connecting stalk fusing them together to form the primitive umbilical cord (loops of intestine, yolk sac, umbilical vessels, and allantois).

Amniochorionic membrane is formed when the somatic extraembryonic mesoderm lining the chorion and the somatic extra meso of the amnion fuse.

Definitive umbilical cord is formed when the intestinal loops are drawn back into the body and the yolk sac and stalk are obliterated. Contains umbilical vessels embeded in CT and the whole cord is covered with amnion.

Amniotic fluid= fluid from maternal blood transported across the amnion in intervillous spaces/decidua parietalis+fluid from fetal and urinary tracts.

Water content turns over every three hours and much of it goes back into the maternal blood (through some is swallowed by the fetus.

Umbilical vessels allow corssing of the placental membrane into the mother's blood in the intervillous spaces.

Functions in exchange in maternal oxygen and nutrients for fetal waste products.

Can also pass on drugs, many infectious agents and antibodies (such as anti-Rh+ Abs from an Rh- mother to her second Rh+ child).

Placenta is vital in the production of hormones: Progesterone, Estrogen, hCG (to keep the corpus lutuem around) and placental lactogen (a GH that gives the fetus priority on maternal blood glucose).

How many amnions, chorions and umbilical cords would be present in:

a. dizygotic twins

b. normal monozygotic twins

c. monozygotic twins with complete seperation of the inner cell mass.

a. 2 seperate placentas, 2 chorions, and 2 umbilical cords.

b. Common placenta but seperate chorions and seperate umbilical cords.

c. Common placenta and common chorionic/amnioti cavity. Still have seperate umbilical cords.

Tunica albugenia (outer, thick CT capsule), tunica vasculosa (just deep to albugenia, contains blood vessels), lobules (~250/testis). Mediastinum testis (thickend albugenia along the posterior surface of the testis)

Inside each lobule there are 1-4 seminiferous tubule clusters and each lobule is separated by a septum of tunica albugenia called the tunica propria.

Strait portion of the seminiferous tubules open into the rete testis in the mediastinum testis.

Divides the basal and luminal compartments by sertoli cell to sertoli cell junctional complexes.

This barrier is important because it isolates spermatogenic cells from the immune system.

Sidenote* 95% of testicular cancers occur in germ cells.

Spermatogonal Phase: Spermatogonia → 1° spermatocyte (Mitosis)

Spermatocyte Phase: 1° spermatocyte →Spermatid (Meiosis)

*From 1° spermatocyte to 2° spermatocyte cells go from 2n to n*

Spermatid Phase Spermatids →Mature sperm (Spermiogenesis)

Columnar epithelial cells that rest on basal lamina.

Have an oval or triangular nucleus that sits in the basal portion of the cell.

Sertoli cells do not replicate.

Sertoli cell:Sertoli cell junctional complexes make up the blood-testis barrier.

Key functions inculde nursing the developing gametes and phagocytose abnormal germ cells.

Secrete:Androgen-binding protein (ABP) which binds testosterone and Inhibin (which inhibits FSH and stimulates ABP secretion).

Hormones of the testis

(include cells of origin and actions)

Spermatogenesis

vs

Spermiogenesis

Spermatogenesis is the entire process from spermatogonium to mature sperm.

Speriogenesis is the last step of the process whereby sperm mature.

What are the major divisions of a spermatozoon?

Where are the mitochondria located in each?

One leaves each of the ejaculatory ducts and travels down the spermatic cord carrying the sperm to the epididymis.

Psudostratified columnar epithelium

Tall columnar cells with microvilli.

Mucus membrane with logitudinal folds and irregular lumen due to contractions of the vas.

Lamina propria is a CT layer between the epi and muscle layers.

A smooth muscle coat is uniquely arranged: Inner longatudinal, middle circular, and outer longatudinal layers.

A crescent-shaped strucutre that is made up of the efferent ductle and the duct of epididymis.

Lined with pseudostratified columnar epithelum.

Principal cells are tall with stereocilia (microvilli)

Smooth muscle coat with increasing thickness near the tail.

Epididymal duct has epi cells that reabsorb fluid from the seminiferous tubules and phagocytize remaning residual bodies. They also produce secretions which aid in sperm maturation (sperm gain teh latent ability to move and to fertilize an egg).

Terminal epididymis is the principal resevoir of mature sperm.

A pair of elongated, convoluted, tubular glands which have a short duct that joins with the vas deferens to form the ejaculatory duct.

Mucosa (folded and branched, Psudostratified columnar epithelium), a thin smooth muscle layer, and a fibrous coat.

Secretion: whitish-yellow, viscous, alkaline, fructose-rich secretion. Contains a substance that makes semen clot and comprises 60% of the volume of semen.

Where are the efferent ducts located?

How could you distinguish them form the epididymal duct in a histological section?

Corpora cavernosa

Two dorsal masses of erectile tissue

Enclosed (along with the single, ventral corpus spongiosum containign the urethra) in a layer of tunica albugenia.

Corpra cavernosa contain wide, endothelial-lined vascular sinuses surrounded by trabecular smooth muscle and supplied by thick-walled helicine arteries.

Key in erection.

How does an erection occur?

What is the role of tunica albuginea?

CNS-initiates and it is maintained by an interplay between the vascular and neurological imputs.

Parasympathetic stimulation causes erection by relaxing trabecular smooth muscle and dilating the helicine arteries leading to explansion of the corpra cavernosa.

Blood accumulates in the erectile tissues and compreses veins against the rigid tunica albugenia causing rigidity.

Sympathetic stimulation terminates teh penile erection by causing contraction of the trabecular muscles after mediating ejaculation.

aka Inerstitial cells

Large, polygonal cells with an elaborate sER.

Are found in clusters between seminiferous tubules.

Secrete Testosterone*

Stratified epithelium with 2 key cell types:

Sertoli cells (supporting cells)

Spermatogenic cells that will replicate and differentiate into mature sperm.

From the outside of the tubule in is how sperm mature within the seminiferous tubules (Spermatogonia→1° spermatocyte→Early spermatid→late spermatid; from the outside in)

Secreted by the sertoli cells.

Inhbits FSH release from the pituitary.

Inhibin therefore acts to inhibit the FSH-induced Sertoli cell secretion of ABP.

Provides multiple entries into the epididymus from the ?

Psudostratified columnar epithelium with tall, ciliated cells and Basal cells (epithelial stem cells).

An outer, smooth muscle layer has visible elastic fibers.

Contains the key structures passing to and from the testis.

Vas deferens, testicular artery, pampiniform venous plexus, lymphatics, nerves, and the cremaster muscle.

A collection of ~40 tubuloalveolar glands lined with pseudostratified epithelum and surrounded by a fibroelastic stroma. A fibromuscula stroma is present between the glands.

Epithelial islands are present in tangential cut as dark areas between clear/white spaces. Prostatic concretions are lighter than epithelial islands and consist fo epi cells and secretions.

Zones of the Prostate: Periurethral, transitional, central, and peripheral.

Peripheral zone contains most of the glandular tissue and is the most commons ite of prostate cancer.

Integument=an organ

Epithelium, CT, glands and sensory receptors.

aka Skin + Nails, hairs, glands, and sensory receptors.

Acts as a barrier and a protective covering.

Plays a key role in homeosasis, preventing water loss and regulating temperature.

Also key in touch, pain, and temperature sensation

Dermal-Epidermal Junction

Dermal Papillae: Protrusions from the dermis up into the epidermis. DPs interdigitate with Interpapillary Pegs of the epidermis which protrude down into the dermis.

DP underlie Primary Epidermal Ridges which are made deeper by mechanical stress and are the souce of fingerprints.

The D-E Junction is along the DP and IPs and is strengthened by Hemidesmosomes.

D-E junctions are present in both thick and thin skin.

Thick Skin

vs.

Thin Skin

All skin has 2 layers: Epidermis: Keratinized, stratified squamous epithelium and Dermis: CT (note that the hypodermis is not part of the skin but cushions and insulates)

Thin Skin

Has no surface ridges, a thinner stratum corneum, ususally no granulosum layer, and no pigment.

Dermis of thin skin has fewer and shorter dermal papillae. Has hair and sebaceous glands!

Thick Skin

Has surface ridges, an obvious corneum, and a granule layer. Has pigment but no hair and no sebacous glands*

Stratum Basale: a single layer of cuboidal/low columnar cells that are mitotically active. Interconnected by desmosomes and connected to the basal lamina by hemidesmosomes. Synthesis of lamellar bodies (that will be secreted by keratinocytes) begins here.

Stratum Spinosum: (Prickle cell layer). Is several cells thicks with spine-like desmosomes that connect adjacent cells.

Stratum Granulosum: several cells thick, is the site of specialized apoptosis. Cells here contian Keratohyalin Granules (contain Cys and His-rich aa's and precursors for filaggrin and trichohylin, all elements that help in keratinization).

Stratum Corneum: The outermost, surface layer of the skin containing flattened, dried, anucleate cells which are keratinized and full of keratin filaments.

Distinct from Merkel's!!!

Located in dermal papillae of thick skin (fingers/toes).

Sensitive to light touch and surface roughness.

Each contains 1-2 unmylinated nerve fibers take a circuitous route through stacks of flat Schwann cells.

(Encapsulated nerve endings)

Encapsulated receptors in the deep dermis/hypodermis.

Abundant in fingertips

Very sensitive to light touch.

Fluid-filled, concentric outer layers and a core of fibroblasts and collagen fibers. Concentric inner layers of Schwan cells (form a swirled pattern).

A single nerve fiber penentrates to the center of the corpuscle.

Cells that migrate from neural crest to the basal layer to form epidermal-melanin units.

Produce skin pigmentation and provide UV protection.

Have dendritic processes that extend from s. basale to s. spinosum.

Melanin is found in membrane-bound melaosomes which are fomred in the Golgi as pre-melanosomes which become melanized when they reach the dendrites of melanocytes (which project into the s. spinosum).

Formed by the oxidation of Tyr→DOPA→→Melanin (tyrosinase) which is stimulated by MSH.

Melanocytes secrete melanosomes at their dendritic tips and keratinocytes ingest them to protect the cells from UV radiation.

*Note that melanocytes are Clear cells on H and E due to lack of desmosomal connections to adjacent cells.

Dark Skin: due to more melanin being produced and transfered to keratinocytes and the productionof larger, more numerous and more stable melaonosomes.

Tanning causes a rapid darkening of existing pigment and the eventual increase in tyrosinase activity leading to increased melanin production.

Dendrites of the epidermis!

Located in s. spinosum

Derived from stem cells in BM

Are the APCs of the skin which migrate from the epidermis to nearby lymphnodes to present Ag to T cells.

Contain HIV vius in AIDs patients.

Modifiedy sensory receiving epidermal cells located in teh s. basale (epidermal origin).

Have an expalnded nerve terminal ending which is apposed to the a nerve fiber

Fiber + epi cell=Merkel's corpuscle

Tactile sensory receptors.

Clear cells in H&E.

Eccrine

vs

Apocrine Sweat Glands

Eccrine

Present all over the body (except lips/ext genitalia)

Watery, hypotonic sweat (low in protein with varied amts of NaCl, urea, ammonia)

Colied tubular duct (with stratified, cuboidal epi) and a secretory segment (has clear cells that produce watery component, dark segements-glycoprotein, and myoepi cells-excretion)

Duct discharges onto the skin surface.

Play a role in temperature regulation.

Innervated by the Parasympathetic nervous system.

Responds to heat and stress.

Apocrine

Only in axillia, areola, nipple, anus, ext genetalia.

Become functional @ puberty

Made of a straight duct (stratified cuboidal epi) and a coiled terminus with duct and secretory segments.

Larger lumen than Eccrine.

Viscous secretion with protein, carb, ammonia, lipid, and organic compouds.

Odorless until it mixes with surface bacteria.

Duct discharges into the hair follicle

Innervated by the Sympathetic nervous system.

Responds to emotional and sensory stimuli.

Develop from invaginations of the epidermis into the dermis/hypodermis.

Epidermis→External Root Sheath and the follicle expands at its base to form the Bulb (invaginated by dermal papilla and the cells surrounding the bulb are called matrix cells which differentiate into the Internal Root Sheath (IRS) and the Hair)

IRS is keratinized just above the bulb in the Keratogenous zone and IRS cells have trichohyalin that help this. IRS is broken down at teh sebacous gland canal and does not exit the follicle.

Hair has a cortex and a medulla.

Dermal Sheath is a dense, irregular CT encapsulation of the follicle.

Sebaceous glands are ususally but not always associated with hair follicles via Pilosebacous canals. Gland is an outgrowth from the external root sheath of the hair follicle.

Sebum is the fatty holocrine secretion (contains whole cells) from these glands. Cells of the gland migrate away from the basal lamina, making sebum as they go. Undergo apoptosis after sebum is made and the whole thing is dischaged into the pilosebacous canal.

Acts as a vapor barrier, possibly bacteriostatic, ↑ production at puberty, squeezed upon contraction of arrector pili m.

Associated with hair follicles.

Contraction causes hairs to rais,e sebacous glands to be squeezed and goose bumps.

An attempt to preserve heat.

1st Degree: restricted to the epidermis.

2nd Degree: epidermis and upper dermis

3rd degree: extends down to hypodermis and req. grafts.

1st and 2nd degree burns can heal whith hair follicles and sweat glands providing foci for epidermal regeneration. Requires a lot of calories to regenerate skin.

Consequences of burns: Loss of fluids (proteins, and electrolytes)=key concern, must replace fluids asap.

Renal shutdown, circulatory shock

Infection is a concern after 24h.

Key in homeostasis and pervention of water loss.

2 key components:

Cell Envelope: made by crosslinked, insoluble proteins (small Pro-rich and loricrin) in the intracellular membrane of keratinized s. corneum cells.

and a

Lipid envelope: produced by exocytosis of lamellar bodies from graulosum cells (sits between graulosum and corneum). Lipid cells are ester-bonded to the outer surface of S. Corneum cells.

CT, sits below the Epidermis, is one of the 2 key components of skin.

Papillary layer: is loose CT. Contains thin collagen I and III, elastic fibers, capillaries, nerves, sensory receptors.

Reticular Layer: is dense, irregular CT. Has courser collagen and elastic fibers and larger blood vessels.

The most predominant cell type in the epidermis (85%)

Of epidermal origin.

Continually regenerate, synthesize keratin and proteins that aid in keratinization + lipids and prteins for the water barrier.

Provides protection against the elements and is a barrier to water loss.

Hard, keratinized plates.

Nail Bed: continuous with s. basale and s. spinosum (note there is no granulosum in the nail bed).

Root: is the proximal part of the nail, convers the matrix/germinative zone.

Matrix: germinative zone, contains the 4 cell types of the epidermis.

Lunula: partially keratinized cells that underlie the matrix right at the cuticle.

Eponychium: (Cuticle) the edge of skin that folds over to cover the root.

Hyponychium: thickened epi layer on the free, under edge of the nail plate.