Fertilization and Implantation PDF

Fertilization and Implantation Embryology Sheila Nunn Professor of Anatomy Please email me at [email protected] any questions or to set up a 1:1 TEAMS meeting No question is a stupid question. Recommended text: Langman’s Medical Embryology. 14th Edition Author T. W. Sadler. Objectives After this lec...

Fertilization and Implantation Embryology Sheila Nunn Professor of Anatomy Please email me at [email protected] any questions or to set up a 1:1 TEAMS meeting No question is a stupid question. Recommended text: Langman’s Medical Embryology. 14th Edition Author T. W. Sadler. Objectives After this lecture and associated reading and use of recommend animations, you should be able to: 1. Define the term embryology. 2. Define how long a normal pregnancy is expected to be in days and weeks post-fertilization. 3. Define when a baby is premature, at term, or overdue. 4. Describe the difference between how embryologists and clinicians classify the developmental time periods . 5. State the names and time frames for the three developmental periods. 6. Label a diagram of the female reproductive tract at the level given in this lecture. 7. Recognize the terminology used in embryology. 8. State what male and female structures meet to start the process of fertilization. 9. Define an ectopic pregnancy and explain the significance of such a condition. 10. State where fertilization normally takes place and when. 11. Describe the key events that take place during weeks 1 and 2 of development. 12. List the changing names of the zygote as it travels down the uterine tube and apply this to its morphological appearance and events that are taking place. 13. Describe implantation of a blastocyst, proliferation of the cytotrophoblast, formation of lacuna spaces and the start of placental development. 14. Have an understanding of how the bilaminar germ disc forms, including development of the oropharyngeal membrane. 15. Describe the development of the amniotic cavity, amnion, yolk sacs, extraembryonic mesoderm, chorionic cavity, connecting stalk, and pre-chordal plate. Embryology • The study of development “in utero” between the point of fertilization of the female egg (oocyte) by the male spermatozoon (single sperm) and the time of birth Coronal section through part of female reproductive tract Objectives Continued • Describe implantation of a blastocyst, proliferation of the cytotrophoblast,formation of lacuna spaces and the start of placental development. • Have an understanding of how the bilaminar germ disc forms, including development of the oropharyngeal membrane. • Describe the development of the amniotic cavity, amnion, yolk sacs, extraembryonic mesoderm, chorionic cavity, connecting stalk, and pre-chordal plate. • Relate the above objectives to the congenital abnormalities described in the lecture. How long is this time in a normal pregnancy? • Birth takes place about 266 days or 38 weeks after fertilization (length of pregnancy). MENSTRUAL CYCLE IS CONSIDERED TO BE 28 DAYS DURATION IF PREGNANT NO MENSES BEGINNING OF MENSES 1 DAY NUMBER 14 OVULATION (then fertilization < 24hours later) 28 1 How to Calculate a Woman's Due Date • This equates to 280 days (40 weeks) from the onset of the last menstrual period • A CLINICIAN WILL ASK WHEN WAS THE FIRST DAY OF YOUR LAST MENSTRUAL PERIOD NOT WHEN WAS YOUR EGG FERTILIZED! BEGINNING OF MENSES 1 DAY NUMBER FERTILIZATION 14 OVULATION (then fertilization < 24hours later) IF PREGNANT NO MENSES 28 1 Are babies always born on their due date? • The current World Health Organization definition of prematurity is a baby born before 37 weeks from the onset of the last menstrual period (LMP). • Can also be defined as baby born BEFORE 35 weeks post-fertilization (before 35 weeks of pregnancy). • IN SIMPLE TERMS, BORN THREE WEEKS BEFORE THEIR EXPECTED DUE DATE • Overdue also called post-term or post-date occurs when the baby has not been born by the forty weeks from onset of last menstrual period. This is referring only to the expected due date for the baby and is not suggesting anything about the baby or mother’s health. • Can also be defined as baby born AFTER 38 weeks post-fertilization (after 38 weeks of pregnancy). • Between 37 and just less than 40 weeks from onset of LMP is known as TERM. • Between 35 and just less than 38 weeks post-fertilization (weeks of pregnancy) is also known as TERM. A Useful Tool to Use to Determine Expected Due Date Periods of Development Embryologists divide development in utero into three periods: 1. 2. 3. Germinal (pre-embryonic): weeks 1 and 2 post-fertilization. Implantation and formation of bilaminar germ disc Embryonic Period: weeks 3-8 postfertilization. ll the major organ systems begin to develop. At the end of the embryonic period, the embryo is only about an inch long. Fetal Period: week 9 to birth. Growth and maturation Clinicians use the term trimesters! Fetal Period: Week 9 to Birth. Growth and Maturation Terminology Used in Embryology • Terminology is different to that used in gross anatomy • Development proceeds cranially to caudally The Start of Pregnancy • Pregnancy begins when the female egg (oocyte) is fertilized by the male spermatozoon (single sperm). It is then called a zygote. • Fertilization usually occurs in the ampullary region of the right or left uterine (fallopian) tube. Inside pregnancy - Sperm Fertilizing Egg: https://www.youtube.com/watch?v=BAWCrn2rwxY Cleavage of the Zygote • The zygote (fertilized egg) starts as a single cell and undergoes a series of rapid mitotic divisions leading to the 2-cell, 4cell….stage). • With each mitotic division the cytoplasm is partitioned (cleaved) to form increasingly smaller and more compacted blastomeres. • The first mitotic division occurs about 30 hours after the beginning of fertilization. • At 16-cell stage called a morula. As cleavage continues, the morula is still passing down the uterine tube towards the uterus. • Morula enters the uterine cavity end of day 4/beginning of 5. Fluid is then secreted within the morula and occupies the space found between the cells. • The morula is thus divided into 2 parts, 1. OUTER CELL MASS ( T R O P H O B L A S T ), which will give rise to the fetal portion of the placenta 2. INNER CELL MASS (EMBRYOBLAST) which will eventually become the baby • The whole structure is now called the blastocyst. (zona pellucida) (outer cell mass) • The blastocyst lies free in the uterine cavity for about a day while the zona pellucida disappears. • Just prior to implantation the trophoblast of the outer cell mass differentiates into: 1. Cytotrophoblasts and 2. Syncytiotrophoblasts ) (e) Implantation • The blastocyst normally implants on the posterior superior wall of the uterus by end of day 6 beginning of day 7 post fertilization. • https://www.youtube.com/watch ?v=PAVo16b_6j4 (coronal section) The uterus at the time of implantation is in the secretory phase, and the blastocyst implants in the functional layer of the endometrium. If fertilization does not occur, then the menstrual phase begins, and the spongy and compact endometrial layers are shed. The basal layer remains to regenerate the other layers during the next cycle. Ectopic Pregnancy • • • • • Ectopic means in wrong place. Also known as an extrauterine pregnancy. Is when a fertilized egg grows outside the uterus. Most often found in uterine tubes (tubal ectopic). An ectopic pregnancy usually cannot proceed to term. The fertilized egg and the growing tissue may cause life-threatening bleeding, if left untreated • • • Frequency of ectopic pregnancy- Occurs in approximately 2% of all pregnancies. Ectopic pregnancy is the main cause of maternal death during the first trimester Woman with tubal pregnancy has signs and symptoms of pregnancy, e.g., misses menstrual period, nausea, swelling of breasts. Early warning of ectopic pregnancy • Often, first warning signs of an ectopic pregnancy are light vaginal bleeding and pain (may mimic pain from appendicitis). • If blood leaks from the fallopian tube, patient may feel shoulder pain or an urge to have a bowel movement. Specific symptoms depend on where the blood collects and which nerves are irritated. Uterine cavity Emergency Symptoms • If the fertilized egg continues to grow in the fallopian tube, it can cause the tube to rupture. • Heavy bleeding inside the abdomen is likely. • Symptoms of this life-threatening event include extreme lightheadedness, fainting, and shock. Treatment Dependent on When Diagnosed • An early ectopic pregnancy without unstable bleeding most often treated with a medication called methotrexate, which stops cell growth and dissolves existing cells. • Late diagnosis, e.g., when fallopian tube is about to rupture/surgical. Laparoscopy: surgical procedure in which a fiber-optic instrument is inserted through the abdominal wall to view the organs in the abdomen or to permit a surgical procedure Week 2 of Development • The cytotrophoblast, syncytiotrophoblast and the EMBRYOBLAST (ICM) continue development at different rates. • In week 2 of development the bilaminar germ disc, and amnion are formed, and implantation is COMPLETE. • The easiest way to understand this process is to examine development in a stepwise fashion. • The description will be separated into further development of the A. cytotrophoblast and syncytiotrophoblast and B. the embryoblast (inner cell mass). A. Further Development of the Cytotrophoblast and Syncytiotrophoblast Layers • The cells of the cytotrophoblast undergo mitosis, and some of them are added to the syncytiotrophoblast layer. • Spaces are formed which are known as the trophoblastic lacunae. This arrangement provides nutrition for the developing embryo via diffusion. Next Stages of Development • Cells of the syncytiotrophoblast continue to penetrate deep into uterine wall. • They erode the endothelial lining of maternal capillaries (sinusoids). • The lacunae then become continuous with the sinusoids. • Result is that maternal blood enters the lacunar system, establishing the uteroplacental circulation. sinusoids • Primary villi then develop which are a proliferation of the cytotrophoblast cells surrounded by the syncytium. • These are visible at the end of week 2. B. Development of the Inner Cell Mass: Embryoblast • Cells of the inner cell mass differentiate into an epiblast and hypoblast layer. Epiblast: columnar cells Hypoblast: cuboidal cells Together these two layers form the BILAMINAR GERM DISC. • The bilaminar germ disc has now formed, but what else can we see? Look at the picture on the right; we now have an amniotic cavity. How has this formed? Formation of the Amnion and Amnionic Cavity • As the cell mass is differentiating into the epiblast and hypoblast, a small cavity appears within the epiblast layer. This cavity enlarges to become the amniotic cavity and the cells along the margin of the cavity (amnioblasts) form the amniotic membrane (amnion). • The AMNION is a protective membrane that eventually surrounds the entire embryo. • It begins to develop on the 8th day. uterine endometrium End of Implantation uterine cavity • Following formation of the bilaminar germ disc, the “pre-embryo" is completely embedded in The uterine endometrium, and the defect is closed by a fibrin plug aka fibrin coagulum on approximately day 9/10. • The bilaminar germ disc is now suspended, with the amniotic cavity above it and the primitive yolk sac below it. • Extraembryonic mesodermal layer also now formed from the epiblast/hypoblast? (https://www.sciencedirect.com/.../engineering/extraembryonic-mesoderm). • Cavities form within this layer to yield the extraembryonic cavity. • Further rearrangement results in formation of the secondary yolk sac. • Extraembryonic cavity now called the chorionic cavity. • Extraembryonic mesoderm that lines the inside of cytotrophoblast now known as the chorionic plate. (Note: You will return to this structure when you have the lecture on formation of the placenta in reproductive 1 module.) Nice summary of development so far: https://www.youtube.com/wat ch?v=bIdJOiXpp9g • The embryo is still a bilaminar germ disc, but in the future head (cephalic) region, the hypoblast is thickened. • These columnar cells are firmly attached to the overlying epiblast. • This region is called the Prechordal/Oropharyngeal Plate and with the layer above will form the OROPHARYNGEAL MEMBRANE( ).