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A. Normal Uterus navigator

  1. Normal Zones of the Uterus
    1. Endometrium divided into basalis and functionalis
    2. Myometrium
    3. Outer Stroma
  2. For the first 2 weeks of the cycle, uterus is Proliferative and dependent on Estrogen
    1. Estrogen from granulosa cells following FSH stimulation
    2. Functionalis layer exhibits tubular to coiled glands
    3. Glands secrete alkaline watery solution which promotes sperm motility
    4. Spiral arteries are narrow and inconspicuous
    5. Many mitoses seen in the glandular tissue
  3. Ovulation occurs ~14 days due to FSH and LH surge (GnRH controlled)
    1. Progesterone, made by granulosa cells, begins to accumulate
    2. Second estrogen peak also occurs
    3. Endometrial glands become enlarged and more coiled due to progesterone
    4. Gland cells store glycogen in vacuoles (days 17-19)
  4. Gland cells in Secretory Phase
    1. Copious secretions to bathe implanted zygote
    2. Glands become enlarged and much more coiled (saw-tooth)
    3. Stromal cells develop vacuolar and eosinophilic changes = predecidualization
  5. By day 27 the entire stroma has become predecidualized
  6. The uterus is supported by progesterone (progestational hormone)
    1. Progesterone synthesis by granulosa lutein cells stimulated by FSH and LH
    2. Towards end of menstrual cycle, LH levels decrease
    3. Note that in pregnancy, trophoblasts make hCG, which serves LH function
  7. In the absence of pregnancy (HCG), newly formed corpus luteum degenerates
    1. Progesterone levels fall
    2. Endometrium undergoes collapse and breakdown
    3. Menses commences on day 28 for 3-7 days

B. Pregnancy [1] navigator

  1. Maximum fecundity (probability of conception during one menstrual cycle) ~30%
  2. Fertilization
    1. Occurs in fallopian tube within 24-48 hours after ovulation
    2. Sperm binds to egg and egg induces head of sperm to disolve (acrosome reaction)
    3. Both zona pellucida and progesterone can induce acrosome reaction
    4. Defective zona pellucida induced acrosome reaction (DZPIAR) can lead to infertility [2]
    5. Fertilized ovum is called zygote
    6. Zygote divides to mass of 12-16 cells called morula
    7. Morula is encased in nonadhesive protective coating called zona pellucida
    8. Passes through fallopian tubes, entering uterus 2-3 days after fertilization
  3. Blastocyst
    1. Morula develops fluid-filled cavity within mass of cells and is called blastocyst
    2. Surface cells of blastocyst become the trophoblast
    3. Trophoblast develops into placenta and other extraembryonic structures
    4. Inner cell mass of blastocyst gives rise to embryo
    5. Within 3 days of entering uterine cavity, embryo hatches from zona pellucida
    6. This leads to exposure of of outer covering of trophoblast
    7. Cells in this trophoblast layer have fused to form syncytial (multinucleate) trophoblasts
  4. Uterine Implantation
    1. Implantation occurs 6-7 days after conception
    2. Likely involves 3 stages
    3. Initial adheions of blastocyst to uterine wall, apposition, is unstable
    4. Microvilli on apical surface of syncytiotrophoblasts interdigitate with uterine wall
    5. Uterine epithelial apical structures involved in binding are called pinopodes
    6. Binding of microvilli to pinopodes leads to stable adhesion
    7. Last stage, invasion, involved syncytiotrophoblasts penetrating uterine epithelium
    8. By 10 days after conception, blastocyst is completely embedded in stromal tissue
    9. Uterine epithelium regrows over invasion site, completely embedding embryo
    10. Implantation usually occurs in upper posterior (fundal wall) of uterus
  5. Biochemical Requirements for Implantation
    1. Preovulatory increase in 17ß-estradiol secretion
    2. Synthesis of prostaglandins (PGs)
    3. Progesterone and estrogen both stimulate cyclooxygenase I (Cox-1)
    4. Cox-2 expression is steroid independent and occurs at site of implantation
    5. Interleukin 1 (IL-1) is required and induces Cox-2 expression
    6. PG-I2 (prostacyclin) is a ligand for nuclear receptor PPAR delta
    7. Matrix metalloproteinase 9 contributes to invasion of cytotrophoblasts
    8. Tissue inhibitors of metalloproteinases help contain activity of proteases
  6. Uteroplacental Circulation
    1. Mononuclear cytotrophoblasts stream out of trophoblast layer and invade endometrium
    2. These cytotrophoblasts invade the entire endometrium and inner third of myometrium
    3. They also invade uterine vasculature (endovascular invasion)
    4. This establishes uteroplacental circulation
    5. Thus, cytotrophoblast are in direct contact with maternal blood
  7. 50-60% of all conceptions progress beyond 20 weeks of pregnancy
  8. Uterine Structures
    1. Corpus luteum production of progesterone leads to endometrial stromal changes
    2. Maintenance of corpus luteum and progesterone depends on trophoblast HCG
    3. Gestational endometrium has widely dilated glands, stimulated by 17ß-estradiol
    4. Cells have abundant glycogen
    5. Uterine receptivity is state during which blastocyst can become implanted
    6. Typically, days 20 to 24 of normal 28 day menstrual cycle are optimal for implantation

C. Maintenance of Early Pregnancy navigator

  1. Pregnancy loss after implantation estimated at 25-40%
  2. Oocyte quality, rather than uterine factors, probably determine success of implantation
  3. Causes of Pregnancy Loss
    1. Genetic abnormalities
    2. Hormonal factors
    3. Prostaglandin Insufficiency
    4. Immunologic factors
  4. Placental development and maintenance

D. Related Topicsnavigator

  1. Labor
  2. Complications
  3. Trophoblastic Disease
  4. Heart Disease
  5. Prematurity
  6. Bleeding during pregnancy

Resources navigator

calcApgar Score

References navigator

  1. Norwitz ER, Schust DJ, Fisher SJ. 2001. NEJM. 345(19):1400 abstract
  2. Barratt CLR and Publicover SJ. 2001. Lancet. 358(9294):1661