Physio Female Reproduction I & II (23/24)

  1. Once secreted from the anterior pituitary, on what cells in the female reproductive system does LH act?
    • Theca cells
    • which produce androgens (go to the granulosa cells) & progestins (significant for the reproductive tract)
  2. theca interna cells
    • express receptors for LH & when signaled they synthesize androgens (androstenedione & testosterone) using cholesterol
    • these male hormones diffuse INTO the follicle for conversion by granulosa cells…
  3. Once secreted from the anterior pituitary, on what cells in the female reproductive system does FSH act?
    • Granulosa cells
    • also produces progestin
    • estrogens: works in the reproductive tract; is made in the granulosa cells from androgens supplied by the theca cells
    • inhibins: for feedback inhibition to the anterior pituitary
    • activins: for positive feedback to the anterior pituitary (*NOT seen in males)
  4. granulosa cells
    located more internally than the theca cells, are stimulated by FSH make aromatase, which converts the male hormones into estrogens (estradiol & estrone)
  5. Can the granulosa cells produce estrogens directly?
    • no, they do not have the capacity to do so
    • aromatase, a granulosa cell enzyme, converts male hormones secreted by theca interna cells to estrogens to foster oocyte growth
  6. FSH's Effects in the Testes & Ovaries
    • targets Sertoli cells & Granulosa cells
    • both target cell types are in DIRECT contact w/ the respective developing germ cells (Sertoli cells support Spermatogonia; Granulosa cells surround the zona pellucida surrounding the oocyte)
    • both target cell types that function to convert testosterone into estrogen
  7. LH's Effects in the Testes & Ovaries
    • targets Leydig cells (testis) & Theca cells (ovary)
    • both target cell types synthesize androgen that is passed over to the respective Sertoli & Granulosa cells for conversion to estrogen
  8. When are the most oocytes present for females?
    • their peak is at week ~15 of gestation: there are 10^7 oocytes arrested in meiosis I
    • by birth, the number has decreased to 10^6 primordial oocytes arrested in prophase of meiosis I
  9. How many ovulations are there in a typical life-span?
    • ~500
    • in each cycle a cohort of several follicles are
    • recruited for development
    • all but one (the dominant follicle) is lost by atresia
  10. Atresia
    • a process undergone by follicles that don't mature & instead degenerate at various stages & undergo apoptosis
    • can happen to follicles at any stage of development
    • it begins in intrauterine life, becomes prominent at birth & shortly before puberty
  11. Follicle Order
    primordial → unilaminar primary → multilaminar primary → secondary/antral → mature/graäfian
  12. What defining event initiates ovulation, aka the release of an oocyte from a mature/graäfian follicle into the abdominal cavity to be sucked up by the fallopian tube infundibulum fimbriae?
    the LH surge
  13. Corpus Leuteum
    • what remains of the follicle structure in the ovary cortex after the ovum is released
    • it becomes a highly vascularized endocrine body who's granulosa cells produces progesterone in order to support a possible fertilization event & a subsequent pregnancy
  14. Luteal Phase
    • ruptured follicle fills w/ blood which is replaced by lipid-rich lipid cells to form the corpus luteum
    • the corpus luteum degenerates after ~10 days if no fertilization/pregnancy occurs
    • however it persists after fertilization & functions to produce estrogen & progesterone (which helps prevent further periods from occurring)
  15. What happens to the corpus luteum IF an oocyte is fertilized?!
    • it becomes the corpus luteum of pregnancy, fortified by increased progesterone production
    • this corpus luteum of pregnancy is functional for 20 weeks
    • after this 20 weeks the placenta makes enough estrogen & progesterone to support the pregnancy
  16. What prevents the corpus luteum from degenerating and where is the source of this prevention?
    • human chorionic gonadotropin (hCG) prevents the corpus luteum from degrading
    • hCG comes from the implanted blastocyst (embryo)
  17. Corpus Albicans ('white body')
    • what a corpus luteum eventually degenerates into - a dense CT scar
    • the scar is larger for a corpus luteum of pregnancy than that of a corpus luteum of menstruation (when the leuteum forms a scar more quickly because no pregnancy occurred)
  18. How is it determined which oocyte progresses to become the mature/graäfian follicle?
    • based on the one with the most FSH receptors on their surface
    • FSH stimulates granulosa cells which make aromatase which converts androgens to estrogen
    • estrogen is essential for the development of the oöcyte
  19. Or according to his slide: how does the dominant follicle achieve dominance?
    • due to estrogen induced events: estrogen causes proliferation of cells that support the oocyte as well as development of the oocyte itself
    • FSH & LH support estrogen synthesis
    • less mature follicles make less estrogen due to FSH decline in that there are just fewer cells for it to act on - a buildup of androgens → atresia
    • more mature follicles have MORE FSH receptors → therefore MORE aromatase (synthesized in response to FSH stimulation) → more estrogen synthesis → more granulosa cell proliferation…
  20. Two-cell, two-gonadotropin model
    • communication between theca & granulosa cells
    • theca cell converts cholesterol into various compounds, one of which, progesterone, is supplemented by progesterone from the granulosa cells as well
    • when androstenedione is made, the theca cell can no longer do anything w/ it but make testosterone, which is unnecessary, so it sends androstenedione to the granulosa cells where aromatase converts it into (among other things) estradiol
    • must account for differences in sex hormone production during follicular & luteal phases of cycle
  21. Phases
    • proliferative (uterine) ~ follicular (ovary)
    • secretory (uterine) ~ luteal (ovary)
    • same phase, different organs (happening at the same time)
    • the proliferative phase in the uterus represents the restoration of the epithelium from the preceding menstrual shedding - is supported by estrogen
    • during the secretory phase in the uterus the endometrium becomes highly vascularized & slightly edematous under the combined influences of the estrogen & progesterone produced by the corpus luteum; uterine glands begin to secrete a clear fluid; purpose is to make the endometrium receptive to implantation of a blastocyst (fertilized ovum)
    • Image Upload 1
  22. Hormonal Changes During the Menstrual Cycle
    Image Upload 2
  23. LH Levels During the Menstrual Cycle
    • LH surge at the end of the follicular/proliferative phase signals ovulation (will occurs w/in 24 hrs)
    • LH levels DROP after ovulation & stay low until anterior pituitary receives GnRH signals from the hypothalamus around the end of menses
    • PEAK: end of the follicular/proliferative phase
  24. FSH Levels During the Menstrual Cycle
    • FSH has a similar trajectory, although it's a little bit higher at the beginning of menses than LH
    • FSH also peaks right before ovulation (same time as LH surge) then DROPS then actually levels increase slightly toward the end of the secretory/luteal phase (which accounts for why it's slightly higher than LH at the start of menses)
    • PEAK: end of the follicular/proliferative phase
  25. Estrogen Levels During the Menstrual Cycle
    • estradiol (prominent form of estrogen) slowly increases during the follicular/proliferative phase, reaches peak slightly before LH/FSH, then drops after ovulation
    • has a second rise (lower than it's 1st though) during the secretory/luteal phase as it supports the secretory function of the uterine endometrium
  26. When are estradiol levels highest (PEAKS) during the menstrual cycle?
    • during the proliferative (follicular) phase
    • it's second peak in the secretory (luteal) phase is less marked
  27. Progesterone Levels During the Menstrual Cycle
    • progesterone is low during menses & for beginning of the follicular/proliferative phase however late in the follicular/proliferative phase its levels begins to rise
    • then its levels significantly go up with the formation of the corpus luteum during the secretory/luteal phase
    • here progesterone & estrogen work together to support the secretory function of the uterine endometrium
    • as the corpus luteum begins to degenerate toward the end of the luteal phase, progesterone levels drop
    • however IF PREGNANCY OCCURS, progesterone (& estrogen) levels will remain elevated & continue to go up to support the pregnancy
    • PEAK: secretory/luteal phase
  28. Inhibin Levels During the Menstrual Cycle
    • not very active at all in the follicular/proliferative phase but then increases (PEAKS) during the secretory/luteal phase
    • PEAK: secretory/luteal phase
  29. What two types of arteries supply the uterine endometrium?
    • coiled spiral arteries supply the stratum functionale (which is shed) of the endometrium
    • short, straight, basilar arteries supply the stratum basale
    • as the corpus luteum regresses & the endometrium thins, spiral arteries become more coiled
    • endometrial necrosis is accompanied by spasm & degeneration of spiral artery walls → menstruation
  30. What probably mediates the vasospasm of spiral artery walls?
    • a local released prostaglandins
    • large amounts of prostaglandins are present in the secretory endometrium & in menstrual blood & experimental infusions of prostaglandin F2α produce endometrial necrosis & bleeding
  31. What happens to the spiral arteries during pregnancy?
    • they form the blood supply for the placenta
    • (in pre-eclampsia there is significant evidence of abnormal hypertension of the spiral arteries, reducing blood supply to the placenta which usually results in some degree of fetal growth restriction due to limited access to nutrients)
  32. How does the cervical mucous change during the menstrual cycle?
    • it thins & becomes more alkaline in response to estrogen during the follicular/proliferative phase + a ferning pattern can be observed when looking at the mucous under a slide
    • it THICKENS in response to progesterone during luteal/secretory phase & in contrast no ferning
    • pattern is observed
  33. Ferning
    • can look at cervical mucous under a slide & depending on the pattern, can determine which hormone is predominant/at high levels & from that can determine where in the menstrual cycle a woman is
    • eg. ~ 14th day of a normal cycle, the follicular/proliferative phase would be just ending therefore estrogen levels would be high(est), progesterone would be low → ferning
    • Image Upload 3
    • during the middle of the luteal/secretory phase progesterone would be at its peak → no ferning (mucous is really thick)
    • Image Upload 4
  34. What would cervical mucous look like during an anovulatory cycle?
    • because the follicular/proliferative phase proceeded normally in preparation for ovulation, estrogen levels are high
    • without the release of a mature oocyte during ovulation (anovulation) there is no luteal phase for a follicle & therefore no progesterone is secreted to support the secretory phase in the uterus
    • cervical mucus WOULD exhibit ferning as it is only influenced by estrogen, not progesterone
    • Image Upload 5
  35. What diagnostic usefulness does the presence of ferning of cervical mucous have when evaluating a pregnancy for possible rupture of the amniotic membranes?
    in the presence of amniotic fluid after membrane rupture, cervical fluid regains the ability to demonstrate ferning (usually doesn't during pregnancy)
  36. How does the vaginal epithelium change during the menstrual cycle?
    • it cornifies with estrogen
    • thicker vaginal mucous is produced in response to
    • progesterone
  37. What breast changes occur during the menstrual cycle?
    • mammary ducts proliferate in response to estrogen
    • lobules & alveoli grow in response to progesterone
    • there is swelling & tenderness in the late luteal/secretory phase
  38. During sexual arousal in women what causes fluid to be secreted onto the vaginal walls?
    the release of vasoactive intestinal peptide (VIP) from vaginal nerves
  39. Why is it clinically important to know when during the menstrual cycle ovulation occurs?
    • in order to promote family planning, i.e. increase the chances of a successful pregnancy
    • an easily monitored & reasonable indicator of the timing of ovulation is a rise in basal body temperature (occurs 1-2 days after ovulation due to the increase in progesterone production as the corpus starts producing progesterone, which is thermogenic)
  40. How long does an ovum lives after extrusion from the follicle?
    • for approximately 72 hours
    • however it is fertilizable for a much shorter time than 72 hours
    • some sperms can survive in the female genital tract & fertilize an ovum for up to 120 hours before ovulation, but the most fertile period is the 48 hours before ovulation & immediately afterward
  41. In what diseases would pulsatile vs. continuous GnRH administration be used as a therapeutic intervention?
    • pulsatile: Kallmann Syndrome
    • continuous: Endometriosis & Leiomyomas
  42. Gonadotropin-releasing Hormone (GnRH) Agonist
    • agonists do not quickly dissociate from the GnRH receptor, therefore initially there is an increase in FSH & LH secretion ("flare effect")
    • after ~10 days a profound hypogonadal effect is achieved through receptor down-regulation by internalization of receptors
    • this induced & reversible hypogonadism (decrease in FSH & LH) is the therapeutic goal
  43. Kallmann Syndrome
    • disordered migration of GnRH cells during embryonic development
    • results in loss of sense of smell & no menstrual cycle in females
    • the pituitary & gonads can function normally w/ pulsatile administration of GnRH analogues
  44. Endometriosis
    • a common condition caused by aberrant presence of endometrial tissue OUTSIDE the uterus
    • the tissue responds to estrogens during menstrual cycle which produces pain & other problems
    • treatment w/ continuous GnRH diminishes gonadotropin & estrogen production which causes involution & diminution of endometriotic tissue
  45. Leiomyomas
    • smooth muscle tumor of the uterus (uterine “fibroid”) who's growth is dependent on estrogen
    • treatment w/ continuous GnRH reduces proliferation of these lesions
  46. Menopause
    • the termination of reproductive function in a female
    • physiologic changes caused by a loss of functional ovarian follicles & the steroids produced by them have a major impact on health
    • characteristic changes associated w/ menopause are due primarily to reduced circulating levels of ESTROGENS
    • hormonal replacement therapy w/ combinations of estrogens & progestins is controversial (HD) but can be used in some cases to alleviate effects of estrogen deficiency
    • Image Upload 6
  47. What did the 8 year WHI study show about the effects of estrogen PLUS progestin in post-menopausal women?
    • estrogen plus progestin vs. placebo was used in women who still had a uterus (no hysterectomy)
    • showed a higher incidence of breast cancer, heart disease, & stroke than the placebo group
    • showed a lower incidence of colorectal cancer, endometrial cancer, & hip fracture (osteoporosis) than the placebo group
    • Image Upload 7
  48. What did the 8 year WHI study show about the effects of estrogen alone in post-menopausal women?
    • estrogen alone vs. placebo was used in women who did not have a uterus (had undergone hysterectomy)
    • showed a higher incidence of stroke than the placebo group (same)
    • a lower incidence of hip fracture (same)
    • shows a somewhat lower incidence of breast cancer & heart disease* (HD = different)
    • Image Upload 8
  49. Gestational/Menstrual Age
    • the age of a pregnancy starting from the first day of the woman's last normal menstrual period (LMP) b/c it's difficult to discern when fertilization occurred
    • commonly used
    • ~2 weeks between menses followed by ovulation; that 2 weeks is included in this age
  50. Ovulation Age
    • the age of a pregnancy starting from the hypothesized day of ovulation to delivery
    • can be predicted by LH levels (surge happens right before), basal body temperature, etc.
    • ovulation age is 1-2 days longer than post-conceptional age
  51. Post-conceptional Age
    • the age of a pregnancy starting from the moment a sperm fertilizes an ovum
    • almost impossible to know unless undergoing IVF
    • Image Upload 9
  52. What several successive phases of development can be identified during the 1st 2 weeks after ovulation?
    • 1. fertilization
    • 2. formation of a free blastocyst
    • 3. implantation of the blastocyst
    • primitive chorionic villi are formed soon after implantation
    • it is conventional to refer to the products of conception as an embryo during the development of chorionic villi (instead of fertilized ovum or zygote)
  53. Where does normal fertilization take place?
    • in the ampulla of the fallopian tube
    • sperm must be present in the fallopian tube within a short time window: nearly all pregnancies result from sexual intercourse between 2 days before through the day of ovulation
  54. zygote
    • the fertilized ovum, a diploid cell with (normally) 46 chromosomes
    • it goes through several stages of cell division that ultimately give rise to cell lineages for the placenta & the embryo proper
    • two cell blastomere → slow cell division over the next 3 days → morulla → blastocyst
  55. Morulla
    • the early blastocyst, a compact multi-cellular body
    • during its formation, the zygote moves from the site of fertilization into the uterus, a process which takes about 3 days, at which time the morulla has reached the 8 - 16 cell stage
    • Image Upload 10
  56. At what cell stage has the zygote formed the trophectoderm?
    • at the ~50-52 cell stage
    • the trophectoderm is the outer cell layers which surrounds the inner cells & can be distinguished from the cells of the embryo proper
    • trophoblasts are cells that form the outer layer of a blastocyst, provide nutrients to the embryo, & develop into a large part of the placenta
    • after gastrulation the layer = the trophectoderm b/c it's then contiguous w/ the ectoderm of the embryo
  57. Gastrulation
    • a phase early in the embryonic development during which the single-layered blastula is reorganized into a trilaminar (3-layered) structure known as the gastrula
    • 3 germ layers: ectoderm, mesoderm, & endoderm
  58. What's one thing that happens before the embryo implants into the endometrium?
    • it receives nourishment from the uterine secretions in
    • the form of steroid dependent proteins, cholesterol, steroids, iron, & fat-soluble vitamins
  59. human chorionic gonadotropin (hCG)
    • substance secreted by the blastocyst that is required for implantation
    • is closely related to LH & SUSTAINS the corpus luteum in the face of rapidly falling levels of maternal LH
    • acts as an immunosuppressive agent, growth- promotor, & an autocrine growth factor that promotes placental development
  60. Steps in Zygote → Embryo Implantation
    • 1. Hatching
    • 2. Apposition
    • 3. Adhesion
    • 4. Invasion
  61. Hatching
    • plasmin + other lytic factors are activated by unknown factors released by blastocyst
    • lytic factors serve to break down the zona pellucida
    • Image Upload 11
  62. Apposition
    • now w/ the zona pellucida disintegrated, a loose connection is formed between the blastocyst wall & endometrial epithelium
    • blastocyst orientation is important: the inner cell mass must be adjacent to the uterine endothelial lining
    • Image Upload 12
  63. Adhesion
    • involves ligand-receptor interactions mediated by the integrin family of receptors on the trophoblast
    • integrins bind initially to laminin around cells on surface of endometrium, then to fibronectin in decidual basement membrane
    • Image Upload 13
  64. Invasion
    • cells in the blastocyst rapidly proliferate & differentiate
    • trophoblast differentiates into 2 layers:
    • 1. inner cytotrophoblast
    • 2. outer syncytiotrophoblast (multinucleated mass w/o cellular boundaries)
    • syncytiotrophoblast creates projections that "eat" their way into the uterine endometrium by releasing factors (eg. TNF-α) that dissociate endometrial cells & degrade ECM → anchoring of the blastocyst
    • Image Upload 14
  65. Syncytiotrophoblast
    • the outer layer the trophoblast proliferates & differentiates into ~6 days after fertilization
    • is a thick layer that lacks cell boundaries & erodes the uterine endometrium, allowing the blastocyst to implant
    • secretes hCG in order to maintain progesterone secretion & sustain pregnancy
    • think of this as the maternal component of the placenta
  66. Cytotrophoblast
    • the inner layer the trophoblast proliferates & differentiates into ~6 days after fertilization
    • play an important role in the implantation of a zygote in the uterus & are known as the trophoblastic stem cells
    • think of this as the fetal component of the placenta
  67. When does implantation occur?
    • ~1 week after fertilization
    • at the initiation of implantation the blastocyst is in the ~100-250 cell stage
  68. Implantation
    • begins by the blastocyst adhering loosely to the endometrium in the dorsal uterine wall
    • requires a decidua (receptive endometrium) prepared by post-ovulatory estrogen & progesterone from the corpus luteum & hCG (human chorionic gonadotrophin) from the embryo
    • involves the release of leukemia inhibitory factor & colony-stimulating factor-1 which cause the trophoblast to produce proteases (esp matrix metalloproteinase 9) that break down the endometrial tissue
  69. Fetal Fibronectin (fFN)
    • acts as a trophoblast glue that binds the trophoblasts (fetal sack) to the decidua (uterine lining)
    • a unique glycopeptide of the fibronectin molecule & therefore its presence in cervical or vaginal fluid is frequently used as a prognostic indicator for impending preterm labor or that it's in its early stage
  70. # days after fertilization
    • 8: the invading syncytiotrophoblast starts developing lacuna (spaces)
    • 12-15: syncytiotrophoblast begins to make contact w/ & break down uterine blood vessels; as it does so, lacuna start to fill w/ maternal blood
    • also the cytotrophoblast starts to send projections into the syncytiotrophoblast
    • 20 days: both invasions have reached mature stages; fetal blood vessels will start to develop w/in the cytotrophoblast invasions into the syncytiotrophoblast
    • Image Upload 15
  71. Chorionic Villi
    emerge from the chorion (membrane made from the extraembryonic mesoderm & the 2 layers of trophoblast) & invade the endometrium, allowing the transfer of nutrients from maternal blood to fetal blood
  72. Placenta
    • primary function is the exchange of materials between fetal & maternal blood
    • *occurs at the interface between chorionic villus & intervillous space
    • there is no direct contact between the fetal blood (contained in the fetal capillaries in the intrAvillous space of the chorionic villi) & the maternal blood (located in the intErvillous space)
    • basically fetal blood is contained in the mature chorionic villus which is covered by the syncytiotrophoblast & those structures are bathed in maternal blood - gasses diffuse, bringing newly oxygenated fetal blood back to the fetus through the umbilical vein (vein b/c it carries blood BACK to the fetus' heart)
    • Image Upload 16
  73. At what point in a pregnancy does the placenta become the major source of progesterone & estrogens?
    • by 8 weeks
    • early in pregnancy these hormones are supplied by the corpus luteum
    • high levels of progesterone & estrogens are required for pregnancy
  74. Estrogen Functions during Pregnancy
    • aids in breast development, specifically the development of milk secreting ducts
    • facilitates the deposition of fatty tissue
    • promotes prolactin production by anterior pituitary
  75. Progestins Functions during Pregnancy
    • aids in breast development, specifically the development of development of glandular tissue
    • suppresses uterine contractions so the uterus doesn't pump out the growing mass that is the fetus (↓ uterine responsiveness)
  76. What effect do high levels of both estrogens & progestins have on the hypothalamic-pituitary-gonadal axis?
    they negatively feedback to inhibit the HPG axis in order to prevent new follicle development & the menstrual cycle
  77. Parturition (the process of birth)
    • during most of pregnancy the uterus is relatively quiescent, however during the last month of pregnancy weak & irregular contractions begin to occur
    • eventually, these contraction develop into a series of regular, rhythmic, & forceful contractions (labor) that may last for several hours, a day, or even longer & eventually result in the expulsion of the fetus & placenta
    • endocrine, paracrine, & mechanical stretching of the uterus all play a role in the initiation of labor (not all are known)
    • once labor is initiated, it is sustained by a series of positive feedback mechanisms
  78. Key Endocrine Mediators of Parturition
    • 1. Prostaglandins: possibly initiate labor
    • 2. Oxytocin: sustains labor by stimulating uterine
    • contractions
    • 3. Relaxin: dilates the cervix & relaxes ligaments of the pubic symphysis
  79. What are the 3 major effects of prostaglandins during parturition?
    • 1. strongly stimulate the contraction of uterine smooth-muscle cells
    • 2. PGF (& estradiol) potentiate contractions produced by oxytocin by promoting the formation
    • of gap junctions between uterine smooth muscle cells; these gap junctions permit a synchronous contraction of the uterus (needed to move the fetus out)
    • 3. cause softening, dilatation, & thinning out (“effacement”) of the cervix early in labor
    • *b/c of these effects (esp. the 1st 2) prostaglandins are used to INDUCE labor & delivery
  80. Role of Oxytocin (OT) in Parturition
    • released in bursts once labor is initiated which ↑ in frequency as labor progresses
    • stimulates of myometrial contraction late in labor
    • stimulates prostaglandin release later in labor, aiding in the expulsion of the fetus
    • induces uterine contractions during the final stages of labor that constrict uterine BVs at the site where the placenta used to be, promoting hemostasis (aka blood coagulation)
    • *oxytocin is clinically used to augment labor AFTER labor's been initiated but isn't progressing well
  81. What is the the primary stimulus for the release of maternal oxytocin during parturition?
    distension of the cervix, called the Ferguson reflex, that comes from the baby's head pushing against the cervix
  82. The Positive Feedback Loop of Parturition
    • when the fetus drops lower in the uterus during labor it causes the cervix to stretch
    • cervical stretch promotes OT release from the posterior pituitary
    • this stimulates uterine contractions & the release of prostaglandins from uterine wall
    • the released prostaglandins go on to also stimulate uterine contractions
    • uterine contractions cause the baby to drop down further, promoting further cervical stretch, potentiating the cyce
    • Image Upload 17
  83. Endocrine Changes Following Delivery
    • stimulation of uterine smooth muscle cells stops & the cells decrease in size as estrogen levels decrease b/c of removal of the placenta
    • uterus vasculature regresses → reduced blood flow to → further uterus involution
    • this happens in the mother almost immediately after newborn birth
  84. Breast Changes Throughout Pregnancy
    • rising estrogen, progesterone, & prolactin levels increase breast water, electrolyte, & protein content
    • hyperplasia of ductal, epithelial, & myoepithelial components (they enlarge)
    • breasts gains up to 1/3 Kg in volume
    • blood supply increases 2-fold
    • nipples & Montgomery glands enlarge & nipple pigmentation increases
    • colostrum production begins in 3rd trimester
  85. Colostrum (20 ccs at most)
    • 1st milk produced right after birth [yellowish, thick, clear] high in fat & PROTEIN, antibodies (IgA), carbohydrates, vitamins, solutes, & minerals
    • is a source of active lymphocytes & monocytes, interferon (which facilitates meconium
    • passage), & Bifidus Factor (probiotic protein that stimulates Lactobacillus bifidus colonization of intestinal tract)
  86. Hormone Functions in the Breast During Pregnancy
    • estrogen → prolactin → ductal proliferation
    • estrogen → progesterone → acinar epithelial differentiation → inhibits lactation (high levels of both hormones inhibit lactation)
  87. Events in Development of Lactation
    • progesterone & estrogen levels drop after delivery (placenta removal)
    • cortisol & prolactin become able to act on acinar epithelium & promote milk production
    • acinar epithelium changes from pre-secretory → secretory
    • initial secretion is colostrum (made during last
    • trimester & 1st few days post-partum)
    • milk production takes 2-5 days post-partum
    • prolactin, cortisol, & oxytocin are necessary for the initiation & maintenance of breast milk production
  88. Prolactin Neural Pathways
    afferent (breast → hyopothalamus) through T4, 5, 6 decreases dopamine levels → prolactin synthesis & release from anterior pituitary
  89. Oxytocin Neural Pathways
    • afferent to mesencephalon → stimulates release of oxytocin from posterior pituitary
    • Sheehan Syndrome is when there's necrosis of the posterior pituitary & oxytocin release fails to occur upon stimulation via this cycle
  90. Breast Milk
    • maintains proper gut flora through antimicrobial factors (lactoferrin, transferrin) + bifidus factor
    • low casein high whey content facilitates digestion
    • lipase + more finely emulsified lipids facilitate
    • digestion
    • also contains immunologic factors
    • provides optimum amounts of vitamin A, C, & sort of D (mother is usually lacking to start with - newborns given supplements)
    • has EGF & IGF-1 important growth factors for intestinal growth & barrier function, + overall infant growth
  91. Galactopoiesis
    • maintenance of milk production once lactogenesis is successfully established
    • requires low maternal stress levels & adequate dietary intake
    • requires regular & frequent nursing (milk removal) which stimulates galactopoiesis by ~3 mechanisms
    • 1. synthesis & release of prolactin & oxytocin
    • 2. promotes blood supply to deliver nutrients to the breast so milk can be continuously synthesized
    • 3. matches output to demands
Card Set
Physio Female Reproduction I & II (23/24)
Exam 2