Female Reproductive System Flashcards
What is the fundamental reproductive unit?
Single ovarian follicle
What is an ovarian follicle composed of?
Oocyte (germ cell)
Surrounded by endocrine cells
What is menarche?
beginning of menstrual cycle around 11-13 years of age
What is the female monthly sexual cycle?
One ovum is released from ovaries/month
uterine endometrium is prepared for implantation of fertilized ovum
What are the three phases of the ovarian cycle?
Follicular phase
Ovulation
Luteal Phase
What releases hCG?
embryo trophoblasts
What does FSH do?
stimulates follicle to grow durign follicular stage
Where does estrogen come from and what does it do?
Comes from follicles
Causes female sexual chracteristics and thickening of endometrium
What doe luteinizing hormone do?
produces progesterone
What does progesterone do?
Maintains thickness of endometrium and keeps uterus from contracting too early in pregnancy
What causes ovulation?
LH surge at day 14
What is oogenesis?
Germ cells in the ovary differentiate into oogonia, which divide by mitosis, and mature into primary oocyte enclosed in primordial follicles
What happens to the primary oocyte during puberty?
It becomes a secondary oocyte by completing Meiosis I
When is Meiosis II completed?
After fertilization of ovum by sperm
Where does fertilization occur?
fallopian tube
What is estrogen?
a steroid hormone that is derived from androgenic precursors androstenedione and testosterone by means of aromatization
What are the three naturally occurring estrogens?
17 beta-estradiol (E2)
Estrone (E1)
Estriol (E3)
What is E2?
primarily produced by theca and granulosa cells of the ovary
Predominant form of estrogen found in PREMENOPAUSAL WOMEN
What is E1?
Predominant form of circulating estrogen after menopause
What is E3?
Estrogen the placenta secretes during pregnancy
What are the three estrogen receptors?
ER-alpha
ER-beta
GPER
Where is ER-alpha found?
Uterus Mammary gland Testis Pituitary Liver Kidney Heart Skeletal Muscle
What does ER-alpha activation do?
Increases the risk and/or the progression of various cancers, including cancers in the breast and endometrium
Where is ER-beta found?
Ovary
Prostate
What does ER-beta activation do?
activates antiproliferative and pro-apoptotic pathways in many cancer cells
What does G-protein coupled estrogen receptor activation do?
mediates rapid estrogen signaling via stimulation of adenylyl cyclase
Expressed in normal ovary
Regulates physiological processes such as follicle maturation
What is endometriosis?
a chronic, hormone-dependent, inflammatory disease
What is endometriosis characterized by?
presence and growth of endometrial tissue outside the uterine cavity
What is endometriosis frequently associated with?
Moderate to severe pain
Dysmenorrhea
Low back pain
Infertility
What are the most common sites that endometriosis occurs?
Ovaries
Anterior and Posterior cul-de-sac
Broad Ligaments
What is the pathogenesis of Endometriosis?
Ectopic endometrial tissue Altered immunity and inflammation Imbalanced cell proliferation and apoptosis Angiogenesis Genetic factors
What is Sampson’s theory of retrograde menstruation?
states that endometrial cells flow backwards through the fallopian tubes and into the peritoneal cavity during menses and that this is what causes endometriosis
What is Pre-menarcheal endometriosis?
Undifferentiated cells of mullerian origin in the peritoneal cavity can differentiate to endometrial tissue
What is MCP-1?
Monocyte chemotactic protein 1 that comes from ectopic endometrium and causes peritoneal macrophages to produce: Inflammatory cytokines Growth factors Angiogenic factors Oxidative stress
What are the three things that cause endometriotic pain?
Endometriotic lesions
Innate immune system
Peripheral nervous system
How is endometriotic pain caused?
Endometrial lesions produce mediators that activate Innate immune system
Innate immune system releases NGF which stimulates sensory nerve endings to generate nociceptive pain
What are uterine Leiomymomas (Fibroids)?
benign tumors arising from the smooth muscle cells of the myometrium
Most common pelvic tumor in women
What is the clinical significance of fibroids?
Effects the function and structure of the endometrium causing pathogenesis of excessive bleeding in uterus
How do fibroids form?
Transformation of normal myocytes into abnormal myocytes
Growth of abnormal myoctyes into clinically apparent tumors
What should you associate Uterine Leiomymomas with?
Fibrotic process with lots of ECM production
What is the pathogenesis behind uterine leiomymomas?
Genetics
Steroid Hormones
Vascular abnormalities
Fibrotic factors
What genetics cause Uterine Leiomymomas?
Abnormal karyotypes casing dysregulation of specific genes
Point mutation in regulatory genes
What steroid hormones cause Uterine Leiomymomas?
Estradiol and Progesterone induce mature leiomymoma cells to release mitogenic stimuli to adjacent immature cells
What vascular abnormalities cause Uterine Leiomymomas?
Increased numbers of arterioles and venules
Venular Ectasia (dilation)
What fibrotic factors cause Uterine Leiomymomas?
Increase in extracellular matrix components and collagen
Fibrotic growth factors are also dysregulated
What is Polycystic Ovarian Syndrome (PCOS)?
A disorder of intraovarian androgen excess
Closely associated with insulin resistance
What does PCOS predispose patients to?
metabolic dysfunction
Increased risk of type 2 diabetes
What are the clinical symptoms of PCOS?
Hirsutism due to the function of hypersecretion of ovarian androgens
Menstrual Irregularity and Infertility due to infrequent or absent ovulation
What is the etiology of PCOS?
arises as a congenitally programmed predisposition = first hit
this becomes manifest in the presence of a provocative factor = second hit
What are the congenital factors that cause PCOS?
Hereditary
Acquired = maternal drugs or nutritional deficits affecting the fetus
What are the postnatal provocative factors that cause PCOS?
Insulin resistant hyperinsulinism
What is the two-gonadotropin, two cell model of ovarian steroidogenesis?
- Theca cells, under the control of LH, produce androgens that diffuse into the granulosa cells
- in mature follicles, FSH acts on granulosa cells to stimulate conversion of androgens to estrogens
What is the connection between ovarian steroidogenesis and PCOS?
Down-regulation of thecal androgen production is flawed
Ovaries are hypersensitive to LH stimulation
Excess intraovarian androgen causes the granulosa cell dysfunction
What is the minimal model for the pathogenesis of PCOS?
- Ovarian Hyperandrogenism
- Insulin-resistant hyperinsulinism
- LH excess
- Obesity
What is PMS/PMDD?
characterized by physical and/or behavioural symptoms in the second half of the menstrual cycle
What are the physical manifestations of PMS/PMDD?
abdominal bloating
breast tenderness
headaches
What are the risk factors for PMS/PMDD?
genetic factors
environmental influences
What is the pathogenesis of PMS/PMDD?
Ovarian steroids = normal serum levels, but there is an abnormal neurotransmitter response to normal hormonal changes
Serotonin is low
What processes contribute to decline ovarian function and development of menopause?
Hypthalamic and ovarian aging
Environmental, genetic, and lifestyle factors
Systemic diseases
What does hypothalamic aging do?
leads to desynchronized GnRH production and an impaired surge of LH
What is menopause?
CNS changes + ovarian aging + anovulation = cycle irregularities and FSH upregulation
