Untitled Quiz

• This study material covers the female reproductive system including anatomy and physiology of the ovaries
• Includes development of follicles, corpus luteum, hormone production, the cyclical changes in the ovaries and the endometrium

Female Internal Sex Organs

• The uterine wall is composed of the endometrium (inner layer), myometrium (middle and thickest layer), and perimetrium (outer layer).
• The perimetrium is a peritoneal covering

Ovaries

• Almond-shaped bodies which are approximated 3-cm long, 1.5-cm wide, and 1-cm thick
• Each ovary is covered by a simple cuboidal epithelium (surface or germinal epithelium) which overlies the tunica albuginea (dense connective tissue capsule)

Ovary Makeup

• The cortex is a region with a stroma of highly cellular connective tissue and many ovarian follicles.
• The medulla contains loose connective tissue and blood vessels.
• There is no distinct border between the ovarian cortex and the medulla

Ovary - Functions

• Major functions include production of gametes and steroid hormones such as estrogens and progesterone.

Estrogens

• Promote the growth and maturation of internal and external sex organs
• Responsible for the female sex characteristics that develop at puberty.
• Act on mammary glands, which promotes breast development by stimulating ductal and stromal growth and accumulation of adipose tissue

Progesterone

• Prepares the uterus for pregnancy by promoting secretory changes in the endometrium.
• Prepares the mammary gland for lactation by promoting lobular proliferation

Primordial Follicles

• Contain a primary oocyte surrounded by an outer layer of flat follicular or granulosa cells.
• They are generated at fetal life and retained in the resting phase for 12-50 years.
• Each egg starts oogenesis in fetal life as a primary oocyte, but meitoic division is blocked at prophase by OMI (oocyte maturation inhibitor secreted by follicular cells)

Secondary Oocyte

• Starts as the the developing egg being released during ovulation each month from puberty (menarche) until menopause
• Accounts for a total of 400-500 eggs per life

Ovarian and Menstruation Cycle

• Are accompanied by endometrial cycles that occur in repeating rhythmic phases
• The ovarian cycle phases are only interrupted by pregnancy, and continue from menarche until menopause

Ovarian Cycle

• Typically lasts 28 days and is initiated by an increase of blood FSH level.
• FSH is secreted by basophil cells of the adenohypophysis, which are stimulated by GnRH released by hypothalamic neurons.
• FSH stimulates the release of estrogens into blood from granular cells of ovarian follicles and lutein cells of corpus luteum.

Ovulatory phase

• Secondary oocyte is released from the Graafian (mature) follicle
• Ovulation is caused by a high increase of blood LH level.
• LH is secreted by basophil cells of the adenohypophysis, which are stimulated by hypothalamic GnRH.

Luteal Phase

• Luteal = secretory phase where phase is dominated by the corpus luteum (yellow body) which secretes progesterone, estrogens, and other hormones.
• The ovary produces and releases female gametes (ova = eggs), 400,000 potential eggs are already present at birth.

Ovary Hormones

• Secretes female sex hormones: Estradiol (plus estron & estriol) and Progesterone.

Relaxin

• Produced by both the ovary and the placenta.
• Induces relaxation of the pelvic ligaments and softens the cervix to facilitate childbirth

Oxytocin

• Increases contractions of uterus during parturition.

Inhibin

• Secreted by Graafian follicle and blocks FSH secretion.

Germinal Epithelium/Surface of the Ovary

• The surface of the ovary is covered by the germinal epithelium which is a single layer that mainly is cubodial cells
• Continuous with mesothelium that covers the mesovarium

Germinal Epithelium - Past and Present

• Used to be termed as site of germ cell formation during embryonic development, but primordial germ cells migrate from the embryonic yolk sac into the cortex of the embryonic gonad.

Tumors

• Arises from the epithelial surface of the ovary and accounts for more than 70% of ovarian cancers
• Origin may be related to repeated disruption and repair of the germinal epithelium, which occurs during ovulation.

Primordial follicles

• Contain a primary oocyte surrounded by an outer layer of flat follicular or granulosa cells.
• Primordial follicles originate during fetal life and are retained in the resting phase for 13-50 years.

Oogenesis

• Each egg begins this process in fetal life as a primary oocyte, but its 1st meiotic division is blocked at prophase by OMI (oocyte-maturation inhibitor secreted by follicular cells)
• Release of the secondary oocyte occurs during ovulation monthly from puberty (menarche) to menopause with a total of 400-500 eggs per life

Primordial (non-growing) follicles

• Have a primary oocyte (25-30 µm)
• The nucleoplasm contains uncoiled chromosomes.
• There is a large amount of organelles with few ribosomes

Unique Cell Characteristics

• Balbiani body
• Annulate lamellae
• Cortical granules

Primordial Follicle - Squamous Follicular Cells

• Supported by basal lamina
• Has a single layer of the squamous follicular cells connected by desmosomes
• Early growth of the follicles does not depend on FSH

Balbiani Body in Primordial Follicles

• Accumulation of Golgi membranes and vesicles, endoplasmic reticulum, centrioles, numerous mitochondria, and lysosomes.
• Human oocytes contain annulate lamellae, resembling stacks of nuclear envelope profiles
• Each layer includes pore structures that are morphologically comparable to nuclear pores.
• Vesicles are scattered throughout the cytoplasm, along with small, spherical mitochondria.

Primary Follicle vs Resting State

• Follicules leaving resting state are called PRIMARY Follicles
• At least one layer of cuboidal follicular cells identifies the primary Follicle
• Oocyte is ca. 100 µm big
• Has single Balbiani body in primordial oocyte which then transforms into multiple, dispersed Golgi elements.

Primary Follicle - Cellular Elements

• An increase in free ribosomes, mitochondria, small vesicles, multivesicular bodies, and the amount of RER
• Occasional lipid droplets and lipochrome pigment masses are typically present
• Exhibit cortical granules just beneath the oolemma, contains proteases released during cortical reaction when sperm cell reacts with zona pellucida proteins to block against polyspermia.

Numerous Microvilli

• Projects out oocytes into the perivitelline area
• This lies between the oocyte and the granulosa cells as the zona pellucida is deposited.

Filopodia

• From granulosa cells develop and project towards the oocyte, intermingling with oocyte microvilli.

Primary Follicle: Morpholigical Stages

• Stage 1: First primary oocyte

• This stage means proliferation of follicular cells is in the granulosa cell layer and connexin is 43 in the gap junctions

• Has basal lamina

• Stage 2: Zona pellucida contains 4 glycoproteins: ZP-1, -2, -3, -4

• Connexin 37 is between the oolema and granola cells

• Stage 3: Theca interna, is a inner cellular layer thats richly vascularized

• Stage 4: Theca externa is the outside fibrous layer of stromal CT with myocytes

• Stage 5: Single layer of cuboidal follicular cells

• Stage 6: Basal lamina separates the follicle from the CT stroma

Zona Pellucida

• Composed of glycoproteins that bind to capacitated spermatozoa and induce acrosomeal reaction
• ZP-3 and ZP-4 are the receptors present in acrosomal cap

ZP-1 and ZP-2

• Act as secondary spermatozoa-binding proteins that interact mainly with the equatorial segment of the spermatozoon head
• Are responsible for acrosomal reaction in capacitated spermatozoa
• ZP glycoproteins are cleaved by metalloproteases which are released from cortical granules in oolemma
• This make ZP proteins unrecognizable for binding with other spermatozoa

PCOS

• A section of the cortex of the ovary has sections from a person with polycystic ovary disease
• A bidirectional oocyte-granulosa cell breaks down in polycystic ovary syndrome (PCOS) Characterized by disruption in folliculogenesis associated with ovarian hyperandrogenism (excess androgen), insulin resistance (causing high blood sugar) and potential infertility The combination of endocrine and paracrine abnormalities affecting granulosa cell-oocyte communication are regarded as a possible cause of PCOS.

Enlarged ovaries/cysts

• Ovaries are often described as being enlarged and containing numerous cysts
• These are diagnosed with ultrasound tests
• Main clinical aspects are infrequent or prolonged menstral periods, excess hair growth and acne

Secondary Follicle

• Proliferation of granulosa cells and follicle is dependent on FSH, growth factors (EGF, IGF-1), estrogens and Ca++.
• Primary oocyte enlarges to 125 m: its microvilli extend into zona pellucida with contact filipodia of granulosa cells via gap junctions

Key Cell Layers

• Granulosa Layer
• Basal Lamina
• Theca Interna
• Thick Zona Pellucia

Formation of An Antrum

• Antrum occurs when Fluid begins to accumulate between granulosa cells in structures with 6-12 cell layers

Granulosa Cells

• Narrow Processes extend into zona pellucida while cells contact each other and oolema via gap junctions

Fluid-Filled Antrum

• Occurs in the secondary follicle, which arisies from the cell cavaties of granulosa
• Shaped as relationship of granulosa cells (GC), basal lamina, and the theca interna (TI) and theca externa

Theca Interna

• Cells differentiate into highly vascularized, steroid-producing cells.

Theca Externa

• An outer layer stromal cells that surrounds the theca interna called

Basal Lamina

• Separates granulosa cells from the theca interna separating them

• The large antrum in Graafian follicles contains an oocyte embeded in cumulus oophorus (CO)

• Corona radiata are the cells surrounding the oocyte after ovulation from the cumulus oophorus

Membrana Granulosa

• (stratum granulosum, SG) from the follicle cell wall makes up the lumen of the antrum

Corona Radiata

• One layer of granulosa cells attached to the zona Pellucida that also encompasses oocyte
• Most larger antral follicules have oocytes located at an edge (excentrically) at the cumulus oophorus

Liquor Folliculi

• A collection of theca interna, hyaluronic acid and proteoglycans, steroid-binding protiens, estrogens
• Also includes progesterone, inhibin, activin which all stimulate oocyte function

Other Key Contributors

• Follistatin
• FSH
• OMI (oocyte maturation factor)
• Granulosa Cells

Follistatin

• An extracellular layer
• Its an antagonist of activin

Synthesis of Estrogen's

• Granulosa and theca intera must be in constant direct communication

Paracrine

• Also requires autocrine interactions between theca cells, granulosa cells and also the occyte itself

Graafian Follicule

• Measures 20MM to 25MM in the average mature formation
• Creates a 2nd Oocyte and polar body
• Requires hormones to produce follicle cells

Ovulation Prerequisites

• Blood Estrogen
• The cell release

The Oocyte's Pathway (Ovulation)

• The blood flow stops in the stigmata and leads through the stigma
• Its fimbriae attach to cumulus mass from the oocyte

Ovulation Process

• A process where a secondary oocyte is released from a Graafian follicle, as the follicle passes through the germinal epithelium

Key steps

• An increase in pressure
• Proteolysis
• Smooth muscle cell activation

CL Fates

• Corpus Luteum is the result of reorganized granulosa and theca which form a larger endocrine gland

Granulosa

• 80% Cell mass location, secretes hormone which makes the egg and oestrogen work appropriately
• the innermost lining of the follicle of the mammalian ovary that secretes female sex hormones and a fluid that provides nutrition to the ovum

Lutein Process

• Follows right after cell folding, after which clotted fluid is formed
• Creates hemorragicum
• The process is known as Ovulation
• 20% outer layer of the ovarium which is then transformed by hormones and blood vessels

Corpus Luteum

• This structure can be best described as a temporal endocrine grand which can create cell secretions of cholesterol in the form of FSH

Progesterone/Androstenedione

• They are transported by blood carriers from the ovaries granulosa by aid of lutein cells

Oocyte

• The ovarian oocyte fates are sealed by the presence of fertilized fluids, after which they secrete more eggs and develop a membrane

CL Hormonal Balance

• Balances LH and FSH to create progesterone which keeps the uterus from destroying the blastocyst

hCS Process

• Supports lutenium growth

• Albnicans is a 14day cycle which degenerates the CL scar tissues

CL Degeneration Process

• Once not enough fluids are secreted, the 10-12 day cycle in the CL degenerates the stroma

CL Structure

• Mostly collagen that aids fibers as white bloods in the ovarium dissolve it

Ovarium cell function

• Destroy tissues through a variety of different apoptosis mechanisms, which require the TNF hormones

Oviduct

• Fallopian, Uterine tube, four chambers
• All transport oocytes which may or may not involve actions from cillia

Cell Structure

• Cillia
• Lamina
• Muscularis folds

Mucosa - Fold structure

• Branching with smooth mucus which may or may not contain a embryo at all
• Thick muscle fibers
• Mucus fibers which line the top of the oviduct

Cytokine

• Cytokines are released by cells and affect the behavior of other cells, and the term cytokine has been used to distinguish these immunoregulatory proteins from other cell regulatory molecules such as hormones

Uterus cell structure

• Serosa
• Fibromusclar (connective) Tissue
• The layers are composed of Endometrium (Mucous) and myometrium cells

Endometrium

• Simple column shape connected by epitheme