Below is the outline for study. You can find discussions of female anatomy in many and various sources from GYN textbooks, to CD ROM programs to the World Wide Web. Think of anatomy from a clinical point of view. What do you need to know to understand a patients symptoms or disease process or functional anatomy? Think of what you will be seeing and palpating as you perform your examination. I will give you some hints and Study Questions along the way to help you. Study Questions will be in GREEN
For example, what muscles are used to do Keegle's exercises? What happens anatomically during sex to the internal and external genitals? Why are adolescents more prone to Chlamydia? What does PID do the fallopian tubes?
Sexual differentiation - Occurs in a sequential order.
1. Sex determination
a. Genetic sex is determined at fertilization, but for awhile the gonads and external genitals are undifferentiated.. At fertilization all eggs are alike chromosomally e. g. 22 autosomes and one X chromosome. Spermatozoa are of two varieties e.g. 22 autosomes and either one X or one Y chromosome.
b. There remains a great deal to be learned about the entire cascade of events that begins with an undifferentiated gonad and ends with an ovary or testis and both internal and external genitalia of matching sex. Sex differentiation is a continuum of successive, overlapping embryologic events.
c. Sexual differentiation of the genital system occurs in a sequential order: genetic, gonadal (the testis-determining factor (TDF) which produces an antimullerian hormone and testosterone to stimulate maleness), genital ducts, external genitalia. Testosterone influences the persistence and differentiation of the male mesonephric (wolffian) duct system and anti-mulliarian hormone influences regression of the female paramesonephric (mullerian) duct system. "Thus, the inherent pattern of differentiation of the genital system can be viewed as one directed toward somatic "femaleness" unless the system is dominated by certain factors for "maleness.." (DeCherney & Pernoll, 1994, p. 71). .
2. Gonadal
a. Indifferent stage. This stage temporally overlaps metanephrogenesis (kidney) and interacts with tissues of the mesonephric system. Lasts until 8-9 or so weeks. The testis and ovary are derived from the same primordial tissue but histological differentiation toward a testis occurs earlier than that toward an ovary. Primordial germ cells are originally near the yolk sac and traverse to the genital ridge for development into an ovary or testis.
3. Ductal
a. Both the female paramesonephric (Mullerian) ducts and the mesonephric (Wolffian) ducts are present during the indifferent stage. Remnants in the female of the male ducts system include Gartner's duct cysts. Failure of ducts to fuse may lead to anomalies of the uterus such as bicornate uterus or "heart shaped" uterus.
See Development of Urogential System Before Sexual Differentiation Graphic
See Development of Female Reproductive System Graphic
See Development of Male Reproductive System Graphic
See Mesonephric (Wolffian) Remnants Graphic
4. Genital. Analogous systems
Genital tubercle: glans penis of male; glans clitoris of female.
Urogenital folds: Urogenital folds around urethra in male; labia minora in female.
Genital swellings: scrotum in male; labia majora in female
Urogenital sinus: bladder, urethra, prostate, blubo-urethral glands of male: bladder, urethra, lower vagina and Bartholin's glands of female.
Study Questions
What is the name of the duct system that develops into fallopian tubes and uterus?
How does a bicornate uterus occur?
What is the embryologic structure that develops into the male penis and female clitoris?
Study Question:
What is the vulva, perineum, pudendum, vestibule, fourchette, introitus?
External Genital Anatomy
A.Vulva - What does this area encompass?
- Mons pubis - What is a Tanners score? What relationship does Tanners scoring have to pubic hair? What is the usual female pattern?
- Labia majora - This structure contains the corpora cavernosa which engorges during sexual arousal. It also contains fibers of the round ligament
- Labia minora
- Clitoris - This also contains corpora cavernosa which engorges during sexual arousal. The dorsal vein (only vein) is blocked by the ishiocavernosis and bulbocavernosus muscle to create erection. Where is the prepuce? What is the male homologue? What do you know about the action of the new drug Viagra? How does it work? Would it work with women?
- Urethra
- Anus
B. Vestibular glands
- Periurethral - What is another name for these glands?
- Bartholin's - What pathology can occur relative to these glands? How do we chart that there was no pathology?
Internal Genital Anatomy
A. Vagina -
Role of lactobacilli (Doderleins) (pH 3.8-4.8)
Estrogen effect
Study Questions:
What is the role of lactobacilli?
What is another for these organisms?
What effect does estrogen have on the vagina?
B. Fornices
C. Cul-de-Sac of Douglas
Squamous cells
Columnar cells
Squamocollumar junction
Transformation zone
Squamous metaplasiaStudy Question:
What is the relationship to STD's particularly HPV?
E. Uterus
Myometrium
EndometriumF. Adenexa:
Ovary (2 x 3 x 1/2) (Function: hormones and eggs.)
Tube, vessels
Muscular Support
A. Upper (superior)
Endpelvic Fascia
Levator ani muscles includes the levator aniB. Lower (inferior)
Urogenital diaphragm
Sphincter musclesIschiocavenosus muscle
Bulbocavernosus muscle
Superficial transverse perinealPelvic floor
Pubococcygeus
Levator ani
Iliococcygeus
Ishiococcygeus
(Keegal exercises)
Ligament Support
Round ligaments
Uterosacral ligaments
Broad ligament (Cardinal ligament)
Bones
Symphasis
Keegal exercises
Hypothalamic Anatomy
A. Hypothalamic-Pituitary anatomy and feedback
See External Genitalia Graphic
See Pelvic Organs - Sagittal View Graphic
See Pelvic Floor Organs - Coronal View Graphic
See Perineum Structure Graphic
See Pubococcygeus Muscle Graphic
A. Bladder, detrusor muscles
Multilayered contractile muscle.
- Cholinergic nerves cause the detrusor muscle to contract
- Also contains prostaglandin's, hence NSAIDS may have an effect.
- Calcium dependent, CCB's may have an effect
B. Urethra and sphincter
Internal and external sphincters
Alpha-adrenergic activity causes the urethral sphincter to contract. Alpha blockers may contribute to incontinence (terazosin(Hytrin)); beta blockers (propranalol (Inderal)) may increase urethral tone; alpha agonist may contribute to sphincter closure (pseudoephedrine).
- Posterior urethral vesicle angle and continence
Dear Students:
This is a very important section. It is really important that you understand menstrual physiology so that you can understand dysfunctional uterine bleeding, Polycystic Ovarian Disease, PMS, natural family planning methods, etc.
There is a very good chart of the interacting events in Hatcher, et al (1994) on page 41 and 42. It is unfortunate that the authors did not reproduce this chart in the 1998 edition.
Menarche
Puberty Girls 8 - 13
First sign is accelerated growth.
Prior to puberty, GNRH is not pulsitile, LH and FSH are at very low levels and begin to rise and pulse with a GNRH pulse. This initially happens at night. Reason is still unknown.
As gonadal estrogen increases (gonarche), breast development, female fat distribution, vaginal and uterine growth occur. Skeletal growth rapidly increases as a Result of initial gonadal secretion of low levels of estrogen, which increases the secretion of growth hormone.
Ovary has 1-2 million germ cells at birth; drops to 300,000 at puberty; all gone by menopause
Terms
Thelarche. Development of breasts
Pubarche. Development of pubic and axillary hair
Menarche. First menstrual period.
Usually anovulatory for about a year.
Adrenarche. Increase in secretion of adrenal androgensPulsitile GNRH and FSH lead to pulses of estradiol and the menarche, but not yet ovulation.
As gonadal estrogen increases (gonarche), breast development, female fat distribution, vaginal and uterine growth occur. Skeletal growth rapidly increases as a result of initial gonadal secretion of low levels of estrogen, which increases the secretion of growth hormone.
Ovary has 1-2 million germ cells at birth; drops to 300,000 at puberty; all gone by menopause
Tissue response
A. Ovary
Phases of the menstrual cycle.
Follicular Phase In the Ovary (Two cell, two gonadotropin theory of the menstrual cycle.) (Speroff, 1994).
Follicular development
At the beginning of a normal ovulatory menstrual cycle, the outer theca cells can only be stimulated by LH, the inner ganulosa cells can only be stimulated by FSH.
FSH receptors are present on the granulosa cells
FSH receptors are induced by FSH itself
LH receptors are present on the theca cells and initially absent on the granulosa cells, but as the follicle grows, FSH induces the appearance of LH receptors on the granulosa cells where progesterone is produced.
FSH induces aromatase enzyme activity in granulosa cells. All the gonadal hormones are made from the cholesterol molecule. Androgens are the common precursors of estrogens (androstenedione and testosterone). They are aromatized to estradiol.
Note: Availability of hormones depends on amount of SHBG.
Dominant follicle selection
Many germ cells begin (18-20) development each cycle, one becomes the dominant follicle; the rest become atretric. The dominant follicle is better at inducing more FSH receptors and thus has more receptors to respond when FSH decreases (in response to increase to estrogen) and able to produce more estradiol than the other follicles.
For ovulation to occur, estradiol must be above 200 picograms and remain up for 50 hours. This causes or induces the LH surge.
Selection of the dominant follicle is established during days 5-7 of the menstrual cycle. This follicle is the most effective in producing estradiol.
Atrophy of the corpus luteum from the previous cycle leads to a fall in estradiol levels. It is this fall in estradiol levels which is recognized by the hypothalamic pituitary system and leads to the production of FSH. There is always a tonic level of LH to stimulate the outer theca cells. It is the new stimulus of FSH which starts the new cycle by stimulating the inner ganulosa cells.
FSH induced aromatization of androgen in the granulosa results in the production of estrogen.
FSH and estrogen increase the FSH receptor content of the follicle.
Ovulation
Rising estradiol directs a decline in FSH and a positive effect increasing LH receptors on the granulosa cell. LH surge is associated with ovulation. Estradiol levels peak 4-36 hours prior to ovulation.
The mid-cycle peak of estradiol must be above 200 picograms and must remain up for at least 50 hours for ovulation to occur.
The LH surge causes a change in the granulosa cell. It is luteinized and produces progesterone. There is a small amount of progesterone produced prior to ovulation.
Progesterone enhances the activity of proteolytic enzymes responsible for digestion and rupture of the follicular wall.
LH surge initiates the resumption of meiosis which is not complete until the sperm enters the oocyte.
Luteal Phase in the Ovary
Luteal phase is fairly constant at 14 days
Corpus luteum rapidly declines 9-11 days after ovulation. (reason unknown)
In early pregnancy, the HCG maintains Luteal function until the placenta takes over.
The demise of the corpus luteum results in a nadir in the circulating levels of estradiol progesterone and inhibin.
B. Uterus
Proliferative
Secretory
MenstrualC. Cervix
Mucous
D. Vagina
E. Breasts
Fertilization and Early Pregnancy Events
Menstrual Cycle Regulation
Hypothalamic-pituitary-ovarian axis
Hormones
Hypothalamus: Pulsitile Gonadotropin releasing hormone (GNRH) at 90 minute pulses. Made in the supraoptic nuclei.
Pituitary.
Anterior-FSH, LH
Posterior- oxytocin, Prolactin & VasopressonOvarian
Two cell, two gonadotropin theory of the menstrual cycle. (Speroff).
Study Questions:
What is a hormone?
- Explain the hypothalamic-pituitary-ovarian axis?
Production of estrogen
Estrogens are secreted by theca interna and granulosa cells of the ovarian follicles, corpus luteum, placenta and adrenal cortex.Types of estrogens.
Natural Estrogens
Estradiol - Most potent estrogen. Highest level in reproductive years. Two peaks during a menstrual cycle. One just prior to ovulation; the second mid luteal phase. Must have 200 for ovulation. Need 40 to protect bones and have positive effects on bone.
Estrone - In equilibrium with estradiol in serum.
Estriol - Produced as major estrogen post menopausal. Produced in ovary and adrenals and fat cells. Least potent estrogen.Synthetic Estrogens
Ethinyl estradiol - Derivative of estradiol is a potent estrogen that can be given orally and is metabolized in the liver.
Mestranol - Less potent that EE by about 1/3. Used in a few 50ug birth control pills.Dosage
The gold standard for dosage of estrogen in medication is .625 mg of conjugated estrogens. About 20 mcg of ethinyl estradiol is the equivalent. This is also the estrogen dose of the lowest dose oral contraceptive pills.
Effects of Estrogens
Estrogens are steroid hormones that involve entry of the steroid into the cell, binding to a receptor, transformation of the receptor to expose a DNA-binding domain, binding of the steroid-receptor complex, bringing about the changes in the cell function.
Stimulates growth of duct system in breast,
female fat distribution,
proliferation of the endometrium,
ferning pattern of cervical mucous,
probably PMS symptoms,
edema,
cholasma,
vascular headaches,
hypercoagulation (promote thrombosis by altering hepatic production of clotting factors.),
increases plasma glucose,
growth of ovarian follicles,
increases tubal motility,
increases uterine blood flow,
increase amount of uterine muscle and the content of contractile proteins,
FSH secretion,
increases secretion of angiotensinogen and thyroid-binding globulin,
increases libido,
stimulates growth of thick, folded vaginal epithelium that is resistant to trauma and infections (cells accumulate glycogen which is acted on by Doderleins bacilli to produce acidic vaginal secretions),
acts on cervical glands to produce clear, watery secretion which facilitates sperm passage,
favorable effect on bones (favors osteoblastic activity),Estrogen action on the cardiovascular system. 8/1/01 Note: This has become a controversy. What is the current research indicating? What would you advise a patient regarding HRT and heart disease?
Favorable impact on lipids and lipoproteins. LDL declines and HDL (protective) increases.
Direct antiathrosclerotic effects. Effects arterial wall, reducing the tendency to produce atherosclerosis independent of lipid values.
Endothelium-dependent vasodilatation and antiplatelet aggregation. Endothelial derived peripherally and in the coronary arteries. Also reduces platelet adhesion decreasing incidence of clotting.
Endothelium-independent vasodilatation. Estrogen causes relaxation in coronary arteries that are denuded of epithelium.
Inotropic Actions on the Heart. Estrogen increases left ventricular diastolic filling and stroke volume.
Improvement of glucose metabolism. Decreases tendency to develop central body fat. This is associated with a decrease in insulin resistance. This decreases hyperinsulinism.
Inhibition of lipoprotein oxidation. Estrogen is an antioxidant. Oxidation of LDL is associated with development of atherosclerosis.
Favorable impact on the clotting mechanism. No increase with low doses of estrogen of thrombus.
Adrenal
Ovulation
Estradiol must reach a level of 200-300 picograms/ml in order for ovulation to occur.
Production of progesterone - Secreted by corpus luteum and placenta.
Types of progesterone. Essentially only one.
Synthetic Progestins
Medroxyprogesterone acetate Provera/ Cycrine 2.5 mg
5mg
10 mgNorethindrone Aygestin 0.35 mg
5 mgMicronized progesterone (made from yams) Prometria (note name! pro or for the endometrium) 100 mg
200 mg
400 mgAction of progesterone
Simulates lobules and alveoli of the breast
Secretory endometrium
Gain (anabolic effect)
Effects the brain
Increases sensitivity to oxytocin in the uterus
Thermogenic
Stimulates respiration
Can produce diuresis in large amounts
Reduces motility of tubes
Uses cervical mucous to become viscous
Production of androgens
Secreted by adrenals (5 types) and ovary
Types of androgens
Ovary and adrenals: testosterone and androstenedione
- Adrenal: Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS)
Action of androgens
Most androgens are bound to SHBG and inactive
Androgens are pulsitile and vary with the time of day and menstrual cycle
Increase libido
Increase LDL, decrease HDL, increase total cholesterol
SHBG (Sex Hormone Binding Globulin)
Production of SHBG
Action of SHBG
Unbound hormones are active.
SHBG binds hormones.
SHBG is decreased by testosterone and insulin and obesity (like Type II diabetes)
SHBG is increased by estrogen
In some states such as polycystic ovarian disease, SHBG is reduced. Therefore there is more free androgen which leads to hirsutusm, acne, abdominal adiposity, possible clitoral enlargement and anovulation.
Gonadotropin Releasing Hormone (GnRH) From the Hypothalmus
Released in a pulsitile manner from the hypothalmus
Follicular stage. One pulse every 70-90 minutes. Release FSH
- The pulse is important to fertility. Women with pulses that are too slow or too rapid can fail to ovulate.
- Question? Could alterations in the pulse lead to infertility? Do you think that the pulse could be altered to promote ovulation and fertility.
- Luteal stage. One pulse every 100-200 minutes. Release FSH & LH
Peptide Hormones Produced in the Ovary
Types of peptide hormones
Inhibin
Synthesized in granulosa and theca cells
Suppresses FSH secretion
Secreted by Dominent follicle, has a negative feedback on FSH secretion.
Regulates androgen and estrogen productionActivin
Enhances FSH secretion
Regulates androgen and estrogen productionFollistatin
Suppresses FSHInsulin-like growth factor-1 (IGF-1)
Oocyte maturation inhibitor (OMI)
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