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Unformatted text preview: PSL302: Lecture 33, by Prof. French! Friday, Dec. 3, 2010 Female Reproductive System
Lecture Outline 1. How are oocytes produced? 2. What are the components of the menstrual cycle? 3. How is the menstrual cycle regulated? 4. What is the fxn of estrogens and progesterone? 5. How do birth control pills work? 6. What causes menopause? Suggested textbook reading: 844-851, 854 (5E); 836-844, 847 (4E) Female Reproductive Female Reproductive System Overview of lecture
1. Formation of oocyte 2. 2 Function of cells surrounding oocyte 3. Preparation of uterus for embryo p y 4. Regulation by hypothalamus and pituitary g y yp p y System Figure 26.12b How are oocytes produced? Oogenesis - During fetal life: oogonia (2n) develop in ovaries - Born w/ ~1-2 mil 1 oocytes - At puberty: ~ 300,000 left (quality over quantity!) - Undergo mitosis, and - Enter (but don't complete) meiosis I = primary oocytes (2n) - After puberty: 1 primary oocyte completes meiosis I - First meiotic division = 2n -> n - Enters (but does not complete) meiosis II = secondary oocyte (n) - Released at ovulation - Completes meiosis II (-> second meiotic division) only if it is fertilized = zygote (2n) Diffces btwn oogenesis & spermatogenesis - Asymmetric cell division: 1 secondary oocyte produced per oogonium - During meiotic division, majority of cytoplasm goes into 1 cell = 2 polar bodies - Limited duration: no oocyte pdc after menopause (avg age 51) - Limited # of primary oocytes: fixed at birth? - No continuous pdc of oocytes
1 of 11 PSL302: Lecture 33, by Prof. French! How are oocytes produce Oogenesis
Friday, Dec. 3, 2010 During fetal life develop, which complete, meio Born with ~1 oocytes. At pub remain After puberty, o completes meio meiosis II to be i i b oocyte The secondary ovulation The secondary y meiosis II only
Fecundity decreases a te t e age o 30 yea s ecu d ty dec eases after the of years
Fecundity after the age of 30 years - Ability to go thru pregnancy past age 30 - Fecundity risk of birth defects as age at pregnancy - Oocytes in suspended animation (paused at metaphase) - Spindle fibers have been attached to chromosomes for years = becomes disorganized w/ age 2 of 11
Broekmans et al. (2009) Endocrine Reviews 30(5):465493 PSL302: Lecture 33, by Prof. French! Friday, Dec. 3, 2010 Meiotic Meiotic spindle becomes spindle becomes disorganized with age p g g disorganized w/ age -Top: chromosomes (shown in red) are organized inside oocytes from younger women -Bottom: spindles are disorganized in older women = messy placement of chromosomes
Broekmans et al. (2009) Endocrine Reviews 30(5):465493 What are the components of the menstrual cycle? What are the components of the menstrual cycle? Ovarian cycle Uterine cycle Two components: -Ovarian & uterine cycles -Combo of both is ~28 days long = menstrual cycle Uterus has 2 layers: -Myometrium: consists of smooth muscle, can stretch during pregnancy -Endometrium: most will shed every month during menstruation Figure from Stanfield and Germain (2009) Principals of Human Physiology ~Fig. 26.12 - Uterine cycle is timed according to what is needed in uterus based on ovarian cycle (devlpt of oocyte w/ surrounding cells) Ovarian O i cycle Overview of Menstrual Cycle - Day 1: start of menses (menstrual phase) Uterine - Loss of endometrial cycle lining: arteries constrict -> region lacks oxygen = endometrium sloughed - ~50-150mL blood & Figure from Stanfield and Germain (2009) Principals cellular debris lost of Human Physiology ~Fig. 26.13 - Lasts for ~5 days - Days 5-13: Proliferative phase (replenish endometrium) - Day 14: Ovulation of 2 oocyte into Fallopian tube - Cells that remain in ovaries after ovulation change biochemistry - Form yellow structure that produces hormones = corpus luteum - Day 15-28: Secretory phase (endometrium is thickest) - If sperm is present: fertilization -> implantation of embryo into endometrium - If sperm is absent: endometrium undergoes menstruation 3 of 11 PSL302: Lecture 33, by Prof. French!
Ovarian cycle Friday, Dec. 3, 2010 Closer look: Ovarian cycle Follicular phase: - 1 follicles start to devlp - Cells surrounding it grow larger - Oocyte also gets larger - Surroundings cells produce hormones, esp. estrogen - 1 follicle devlps into mature follicle (or Graafian or tertiary follicle) - Contains fluid-filled cavity + hormonepdcing cells + oocyte Ovulation: mature follicle ruptures Luteal phase: - Remaining cells = corpus luteum - Regress if fertilization doesn't occur Follicular phase Luteal phase Figure 26.12d Cells of the mature follicle Hormone-producing cells surround the devlping oocyte - In image: oocyte not visible - Basement membrane: cxtive tissue - Antral fluid: fills cavity (antrum) of mature follicle -- respond to LH and make androgens esp. androstendione - Thecal & granulosa cells work together to produce estrogen & estrogen-like hormones - Thecal cells: outside of follicle - Responds to LH & secrete androgens, esp. -- respond to FSH and make estrogens from androstendione Figure 26.12e androstendione released from theca - Like Leydigs cells (respond to LH & secrete testosterone) - Androstendione diffuses into... - Granulosa cells: inner side of follicle - Responds to FSH & produce estrogen from androstendione Steps in the Ovarian Cycle ! Follicular phase: 1. Small # of primordial follicles develop into primary follicles - Born w/ these = 1 oocytes have 1 layer of granulosa cells 2. Become a primary follicle (thecal + granulosa cells) - Thecal cells synthesize androgens => estrogens in granulosa cells - As follicle devlps, granulosa cells secrete fluid that fills antrum 3. An antrum (fluid-filled cavity) forms - Fluid contains hormones (esp. estrogen) + enzymes - From granulosa cells & nearby capillaries - Structure now called a secondary follicle 4. A dominant follicle develops = called Graafian (tertiary) follicle - The other devlping follicles & assoc oocyte degenerate 5. The Graafian follicle ruptures = ovulation occurs - 2 oocyte released Total time: 1 year - Group of primary follicles begin to develop in an ovary - But only some per month develop a bit more and one becomes a dominant follicle 4 of 11 PSL302: Lecture 33, by Prof. French! Friday, Dec. 3, 2010 ! Luteal phase: 6. Follicular cells left behind (thecal & granulosa cells) in ovary = corpus luteum ("yellow body" - Change biochemistry = releases estrogen but also progesterone 7. - 9. If fertilization does not occur, corpus luteum degenerates (after ~14 days) - The scar tissue remaining = corpus albicans ("the white body") - If fertilization does occurs, corpus luteum continues to make progesterone + estrogen until the end of 1st trimester of pregnancy (1st three months) Uterine Cycle - Endometrium (in purple) - Has spiral arteries - Myometrium (smooth muscle, in red) - Contracts during labour Uterine cycle Figure 26.12c, f 5 of 11 Proliferative phase: Endometrium develops in response
PSL302: Lecture 33, by Prof. French! to estrogen. The endometrial lining thickens as the blood Friday, Dec. 3, 2010 supply to the tissue is re-established and cells proliferate. Figure 26.13 Uterine cycle, in detail Menses - Initiated by progesterone + estrogen - Blood vessels (spiral arteries) supplying endometrium undergo constriction - Causes shedding of endometrial lining Proliferative phase - Endometrium develops in response to estrogen - Endometrial lining thickens as blood supply to tissue is re-established = cells proliferate Secretory phase - Glands in endometrium secrete more viscous fluid - Endometrial cells deposit lipid + glycogen in cytoplasm - Make lining more attractive to embryo, i.e. nutrients - Under influence of progesterone + estrogen y Summary of estrogen + progesteroneSummary release
- During follicular phase (menstrual & proliferative) - Estrogen made by granulosa cells (converted from androstendione from thecal cells) in ovaries - During luteal phase (secretory phase) - Progesterone + estrogen made by corpus luteum Review question #1: Which statement re: luteal phase of ovarian cycle is correct? A) Estrogen + progesterone lvls are low. B) It starts after ovulation of the secondary oocyte. C) It occurs during the proliferative phase of the uterine cycle. D) It is named for the yellow colour of the secondary oocyte. of estrogen and progestrone release g p g Figure 26.13 6 of 11 PSL302: Lecture 33, by Prof. French! Friday, How is the menstrual cycle regulated? Dec. 3, 2010 Recall: H R ll Hypothalamic/pituitary control of reproduction th l i / it it t l f d ti
How is the menstrual cycle regulated? Hypothalamic/ant pituitary control of reproduction GnRH = gonadotropinreleasing hormone LH = Luteinizing hormone FSH = Folliclestimulating hormone - Recall: with males -> GnRH released from hypothalamus -> trigger release of LH & FSH from Figure 26.7 ant.pit. -> act on gonads - How do LH & FSH act to stimulate the same process in females? Overview O i Figure 26.14
7 of 11 PSL302: Lecture 33, by Prof. French! Friday, Dec. 3, 2010 Overview - At diff parts of the cycle, the regulation is completely different! - 4 diff phases of the cycle (a) Early to mid-follicular phase (b) Late follicular phase & ovulation (c) Early to mid-luteal phase (d) Late luteal phase Regulation of Menstrual Cycle, in detail (a) Early to mid-follicular phase - Day 0 = start of menses - Just before day 0 - GnRH (pulsatile): pulses occur every 1.5h -> cause LH & FSH release - Thecal cells: LH stimulates androgen release - FSH stimulates conversion into estrogens by granulosa cells - Estrogens exert +ve feedback on granulosa cells - # estrogen receptors proliferation - Leads to estrogen release - Estrogens exert -ve feedback at pituitary + hypothalamus - Principally on cells that release FSH - LH lvls remain about same, FSH Two-cell, two-gonadotropin regulation of estrogen synthesis th regulation of estrogen synthesis - Diagram: two-cell,t two-gonadotropin i (i)LH binds to thecal cells = produce androstendione (ii)Androstendione crosses into granulosa cells
Estradiol = converted to estradiol via FSH binding Figure modified from: http://www.endotext.org/female/female3/femaleframe3.htm (b) Late follicular phase + ovulation - Tertiary follicle present - Follicular cells begin to secrete inhibin (inhibits FSH secretion) + progesterone + estrogen - +ve feedback: estrogens freqcy of GnRH pulses (from 1 pulse/1.5h -> 1/65min) - LH surge = triggers completion of meiosis I + ovulation - Progesterone pituitary sensitivity to GnRH ! Ovulation - Follicle secretes collagenase -> breaks down connective tissue ! = allows release of oocyte + cumulus cells - Tissue breakdown stimulates inflammatory rxn w/ release of prostaglandins ! = smooth muscle contraction - Ovulation triggered by tissue breakdown + smooth muscle contraction 8 of 11 PSL302: Lecture 33, by Prof. French! Friday, Dec. 3, 2010 - Fallopian tube & ovaries not sewn together - Cilia of tubes draw oocyte in - When cell is ovulated, some granulosa cells come with it (corona irradiata) Late follicular phase and Early to mid-lu ovulation Corpus l C luteum un
Tertiary follicle present and FSH releases inhibin and estrog Follicular cells begin to secrete inhibin g exert negative fee and progesterone along with estrogen hypothalamus and High estrogens increase frequency of Progesterone inhi GnRH pulses to 1 / 65 min (positive1 every 3-4 h (now feedback) Progesterone also increases pituitary P t l i it it sensitivity to GnRH Causes LH surge, which triggers surge completion of meiosis I and ovulation (c) Early to mid-luteal phase Figure 26.14c Figure under - Corpus luteum 26.14b influence of LH + FSH = releases progesterone + inhibin + estrogen - Respond to lvls of LH - Exert -ve feedback at hypothalamus + pituitary - [progesterone] inhibits GnRH pulses (now 1/3-4h) (d) Late luteal phase - Intrinsic life-span of the corpus luteum: 12 days - If fertilization does not take place: corpus luteum undergoes apoptosis - Progesterone + estrogen lvls - Reduced -ve feedback at hypothalamus + pituitary = GnRH pulses return to 1/1.5h 9 of 11 PSL302: Lecture 33, by Prof. French! Friday, Dec. 3, 2010 Overview of the Menstrual Cycle view What is the fxn of estrogens and progesterone? Secondary sex characteristics + steroid hormones Estrogens: Devlpt + maintenance of 2 sex characteristics ! I.e. Breast devlpt, fat distribution on hips + upper thighs + narrow waist Androgens (from adrenal cortex): Pubic + axillary (on arms) hair, sex drive Figure 10 of 11 PSL302: Lecture 33, by Prof. French! Friday, Dec. 3, 2010 How do birth control pills work? Review question #2: Birth control pills often contain a combo of estrogens + progesterone that are taken continuously for 3 weeks/cycle. What effect do you think this has on plasma FSH + LH lvls for these 3 weeks? A) Both remain low (-ve feedback on GnRH release = prevent ovulation) B) Both remain elevated C) FSH would be high, LH would be low D) LH would be low, FSH would be high What causes menopause? Menopause = cessation of the reproductive cycle Ovaries causes menopause? What lose their ability to respond to FSH and LH Menopause: cessation of reproductive cycle Estradiol- Estradiolprogesterone levels fall and + progesterone lvls - Lack of -ve feedback on GnRH = & Lack of negativetheir ability to respond to FSHLHLH FSH and LH to rise - Ovaries lose feedback causes FSH +
- Probably b/c not many follicles left at this age Broekmans et al. (2009) Endocrine Reviews 30(5):465493 11 of 11 ...
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This note was uploaded on 03/27/2012 for the course PSL PSL300 taught by Professor Mackayfrench during the Fall '11 term at University of Toronto- Toronto.
- Fall '11