Embryology LC2&3 First and Second Week of Development PDF

the mature follicle or graafian follicle. The FSH together with the LH will help the growing follicle to m...

the mature follicle or graafian follicle. The FSH together with the LH will help the growing follicle to mature until a woman reaches her OUTLINE ovulation period. I. FIRST WEEK OF DEVELOPMENT II. OVULATION A. Step 1 III. FERTILIZATION A. Step 2 IV. FERTILIZATION TO IMPLANTATION A. Step 3 B. The Ovarian Cycle V. IMPLANTATION A. Step 4 VI. SECOND WEEK OF DEVELOPMENT A. 8th Day of Development B. 9th Day of Development C. 11th and 12th Day of Development D. 13th Day of Development E. Menstrual Cycle I. FIRST WEEK OF DEVELOPMENT First week of development: ovulation → fertilization → implantation. Ovulation: one of the ovaries releases a mature egg Fertilization: sperm cell from male combine with mature egg to form a fertilized egg Implantation: fertilize egg lodges itself into the endometrial lining of the uterus. II. OVULATION FIGURE 1. The Ovulation Process STEP 1 In ovulation, the mature egg is released from the ovary, moving Making the egg (oogenesis) and sperm (spermatogenesis). down to the fallopian tube and staying there for 12-24 hours, where Male testes produce new sperm cells a day. it can be fertilized. Egg is only released one at a time, once per menstrual cycle. In the ovarian cycle, it is a release of an oocyte from a mature follicle. Sperm cells stick around for 3-4 days. It is triggered by a surge of LH production. Eggs are more short-lived, surviving only around 24 hours after ovulation. ○ The female, for the whole menstrual cycle of 28 days, usually ovulates on the 14th day. Overall fertile window is only the day of ovulation and the several days leading up to it. ○ It is usually an allowance or the fertile window a few days before the peak of the ovulation and also a few days after ovulation. It includes the fertile period of the female and male. For females, it starts during adolescent period (about the time when a woman starts to menstruate, at least about the age of 11-15). It does not start from the reproductive organ, but from the brain. FIGURE 2. Primordial Follicle, Growing Follicle, and Vesicular follicles. Every day The hypothalamus secretes the Gonadotropin-releasing hormone from the pool of primordial follicles [A], some begin to develop into growing (GnRH) that stimulates the anterior pituitary gland to release follicles [B], and this growth is independent of FSH. Then, as the cycle gonadotropins. The gonadotropins are the follicle-stimulating progresses, FSH secretion recruits growing follicles to begin development into hormone (FSH) and luteinizing hormone (LH). vesicular [antral] follicles [C]. During the last few days of maturation of vesicular The FSH stimulates the ovary to release follicles. The ovary will follicles, estrogens, produced by follicular and thecal cells, stimulate increased release several follicles, but only one of these will mature to become production of LH by the pituitary gland, and this hormone causes the follicle to Page 1 of 10 [EMBRYOLOGY] 1.02&3 FIRST AND SECOND WEEK OF DEVELOPMENT – Dr. La Paz L. Peredo, MD enter the mature vesicular [graafian] stage, to complete meiosis I, and to enter Once the egg is fertilized, it will travel down the body of the uterus meiosis II, where it is arrested in metaphase approximately 3 hours before where it will be implanted. The uterus is lined with endometrium. ovulation. STEP 2 The primordial follicle will start to grow day by day, forming the Sperm released in ejaculation travel through the cervix and into the vesicular follicle. The growing follicle is surrounded by granulosa cells uterus where they make way to the fallopian tube where the egg lies and theca cells. in wait. Together, the FSH and granulosa cells produce prostaglandin and ○ Only 1% of sperm deposited in the vagina enter the estrogen. The prostaglandin stimulates the ovary causing a vascular cervix, where they may survive for many hours. spasm, causing the follicle to come out, thereby leading to ovulation. Movement of sperm from the cervix to the uterine tube At the time of ovulation, the LH takes charge and prepares the occurs by muscular contractions of the uterus and uterine corpus luteum. The theca cells and blood vessels become the corpus tube and very little by their own propulsion. The trip from luteum. It is vascularized in preparation if after ovulation and cervix to oviduct can occur as rapidly as 30 minutes or as fertilization takes place, this will be the place where implantation slow as 6 days. takes place. When the sperm enters through the cervix, it goes to the uterus, If fertilization does not take place, this corpus luteum will travels to the fallopian tube, then meets the egg cell to the ampulla degenerate. which is the widest part and where the follicles grow forming the If no pregnancy takes place, progesterone decreases and the corpus corpus luteum and where ovulation and fertilization take place. luteum is maintained by LH which also produces progesterone. ○ Spermatozoa are not able to fertilize the oocyte immediately upon arrival in the female genital tract but must undergo (1) capacitation and (2) the acrosome reaction to acquire this capability. Thus, speeding to the ampulla is not an advantage because capacitation has not yet occurred, and such sperm are not capable of fertilizing the egg. When the egg is fertilized, it travels down to the fallopian tube and goes down the uterus where it will be embedded and implantation takes place. Before a sperm can travel into the cervix, the normal volume for sperm is 500. The male normally produces 200-300 million sperm cells per ejaculation, but only 500 of these are active, normal, and considered fertile. ○ Normal seminal volume during ejaculation is 2-6ml ○ Semen liquifies in 30 minutes. FIGURE 3. Mature Vesicular Follicle, Ovulation and Corpus Luteum When a patient comes in for a fertility test, ask the patient to get a sample within the vicinity of the hospital if he is an hour or longer The oocyte, in metaphase of meiosis II, is discharged from the ovary away from the hospital. To have a good amount of sample, ask the together with a large number of cumulus oophorus cells. patient to abstain from any sexual activity before the testing. Follicular cells remaining inside the collapsed follicle differentiate To know if the problem of infertility is from the male or female, the into lutein cells. first testing is done with the male, but can be done at the same time as the female. Note: The large size of the corpus luteum, caused by hypertrophy and accumulation of lipid in granulosa and theca interna cells. The remaining cavity of the follicle is filled with fibrin. III. FERTILIZATION FERTILIZATION: when the sperm cell from male combines with a mature egg to form a fertilized egg. Occurs in the ampullary region of the uterine tube (ampulla). Ampulla - the widest part of the tube and is close to the ovary. Sperm may remain viable in the female reproductive tract for several days. The movement of sperm from the cervix to the uterine tube can be as fast as 30 minutes, or as slow as 6 days. ○ The movement of the sperm is assisted by the muscular contractions of the uterus and the uterine tube; the FIGURE 4. Relation of Fimbriae and ovary. Fimbriae collect the oocyte and sperm alone moves through propulsion. sweep it into the uterine tube. Page 2 of 10 [EMBRYOLOGY] 1.02&3 FIRST AND SECOND WEEK OF DEVELOPMENT – Dr. La Paz L. Peredo, MD Phases of Oocyte Penetration the oocyte, the corona radiata. Only one of these sperms After reaching the isthmus, sperm cells become less motile and cease will fertilize the egg. their migration. At ovulation, they only become active again due to: ○ Chemoattractants produced by the cumulus cells Phase 2: Penetration of zona pellucida surrounding the egg. ○ After successfully penetrating the zona radiata, the The sperm must first undergo capacitation and acrosome reaction sperms will now penetrate the zona pellucida. before it can penetrate an oocyte. ○ Zona pellucida: a glycoprotein shell that surrounds the ○ Capacitation: conditioning period of the sperm in the egg. female reproductive tract. This usually lasts for 7 hours in Facilitates sperm binding, induces acrosome humans. During the capacitation period, epithelial reaction. interactions between the sperm and mucosal surface of ○ Release of acrosomal enzyme (acrosin) makes it possible the uterine tube occur. The glycoprotein coat and seminal for the sperms to penetrate zona pellucida → contact of plasma proteins of the sperm are removed from the the sperm with the oocyte’s plasma membrane. plasma membrane, which will then expose its acrosomal ○ Cortical granules: structures lining the plasma membrane region. of the oocyte. They release lysosomal enzymes which will ○ Acrosome reaction: occurs after the sperm binds to the change the properties of zona pellucida (zona reaction); zona pellucida. This will cause the release of enzymes this prevents sperm penetration and inactivate needed to penetrate the zona pellucida. species-specific receptor sites for spermatozoa on the These enzymes include acrosin- and zona surface. trypsin-like substances. ○ Other spermatozoa have been found embedded in the zona pellucida, but only one seems to be able to penetrate the oocyte. Phase 3: Fusion of the oocyte and sperm cell membranes ○ After penetrating the zona pellucida, the sperm will now adhere to the oocyte. The adhesion is mediated by the interaction of the oocyte’s integrin and the sperm’s disintegrins. ○ The adhesion of the successful sperm to the oocyte results in the fusion of their plasma membrane. In humans, both the head and the tail of the sperm enters the oocyte’s cytoplasm, but the plasma membrane is left behind on the oocyte surface. The Results of Fertilization Restoration of the diploid number (from 23 → 46) ○ Haploid numbers are from the father’s and mother’s gametes. Determination of the sex of the new individual ○ Chromosomal sex of the embryo is determined at fertilization ○ X-carrying sperm → female (XX) ○ Y-carrying sperm → male (XY) Initiation of cleavage ○ If the oocyte is not fertilized, it will degenerate 24 hours after ovulation. FIGURE 5. A. scanning electron micrograph of sperm binding to the zona DEVELOPMENT OF ZYGOTE FROM THE TWO-CELL STAGE TO THE LATE MORULA pellucida. B. The three phases of oocyte penetration. In phase 1, spermatozoa STAGE pass through the corona radiata barrier; in phase 2, one or more spermatozoa Once the zygote reaches the two-cell stage, it will continue to divide penetrate the zona pellucida; and in phase 3, one spermatozoon penetrates the through a series of mitotic divisions, thereby increasing the number oocyte membrane while losing its own plasma membrane. Inset shows normal of cells. spermatocyte with acrosomal head cap. As these cells undergo cleavage division, they will decrease in size, and are now called blastomeres. Until the eight-cell stage, they form Three Phases of Fertilization a loosely arranged clump. Phase 1: Penetration of the corona radiata After the third cleavage, blastomeres maximize their contact with ○ Of all the sperm deposited in the female reproductive each other and form a compact ball of cells, held tightly big tight tract, only 300 to 500 reach the site of fertilization. These junctions. sperms will now aid in the penetration of the barrier of ○ Compaction: segregation of the inner cells from the outer cells Page 3 of 10 [EMBRYOLOGY] 1.02&3 FIRST AND SECOND WEEK OF DEVELOPMENT – Dr. La Paz L. Peredo, MD 3 days after fertilization, the cells of the compacted embryo divide into a morula (16 cells), also termed as mulberry. ○ Inner cells (inner cell mass) → embryo proper ○ Outer cells (outer cell mass) → trophoblast → placenta ○ Fluid cavity amniotic cavity FIGURE 6. Development of the zygote from the two-cell stage to the late morula stage. The two-cell stage is reached ~30 hours after fertilization; the four-cell stage is reached at approximately 40 hours; the 12- to 16-cell stage is reached at approximately 3 days; and the late morula stage is reached at approximately 4 days. During this period, blastomeres are surrounded by the zona pellucida, which disappears at the end of the fourth day. FORMATION OF BLASTOCYST FIGURE 8. A. Section of a 107-cell human blastocyst showing inner cell mass and When the morula enters the uterine cavity, fluid begins to penetrate trophoblast cells. B. Schematic representation of a human blastocyst recovered through the zona pellucida into the intercellular spaces of the inner from the uterine cavity at approximately 4.5 days. Blue, inner cell mass or cell mass. embryoblast; green, trophoblast. C. Schematic representation of a blastocyst at The intercellular spaces become confluent, and form a single cavity the sixth day of development showing trophoblast cells at the embryonic pole of called blastocoele. The embryo is now a blastocyst. the blastocyst penetrating the uterine mucosa. The human blastocyst begins to Now, penetrate the uterine mucosa by the sixth day of development. ○ Inner cells → mass embryoblast ○ Trophoblast → wall of the blastocyst IV. FERTILIZATION TO IMPLANTATION ○ Blastocyst cavity (blastocoele) STEP 3 In fertilization, one sperm is eventually able to make it through and combine with the egg to form a ZYGOTE. The fertilized egg begins to divide into clamps of cells as it travels through the fallopian tube towards the uterus. After 4-6 days of cell division, it matures into a BLASTOCYST, and it is ready to be implanted into the uterus. The wall of the uterus has three layers: ○ Perimetrium - peritoneal covering lining the outside wall ○ Myometrium - a thick layer of smooth muscle ○ Endometrium - mucosa lining the inside wall and also has three layers: The endometrium has 3 layers: 1. Basal layer (stratum basalis) - highly FIGURE 7. Layers of a blastocyst. vascular 2. Spongy layer (stratum spongiosum) - vascular and with associated glands 3. Upper layer / Compact layer (stratum compactum) - usual part that degenerates if no fertilization takes place Page 4 of 10 [EMBRYOLOGY] 1.02&3 FIRST AND SECOND WEEK OF DEVELOPMENT – Dr. La Paz L. Peredo, MD The basal layer is the only part that is retained. If fertilization takes place, the blastocyst implants into the uterus, and in between uterine glands at the level of the compact and spongy layer. FIGURE 9. Changes in the uterine mucosa correlated with those in the ovary. Implantation of the blastocyst has caused development of a large corpus luteum of pregnancy. Secretory activity of the endometrium increases gradually as a result of the large amount of progesterone produced by the corpus luteum of pregnancy. FIGURE 10. Changes in the uterine mucosa [endometrium] and corresponding changes in the ovary during a regular menstrual cycle without fertilization. THE OVARIAN CYCLE A regular 28-day cycle Depends on hormonal activity V. IMPLANTATION ○ Hypothalamus: secretes gonadotropin releasing hormone ○ Pituitary glands: secretes follicle stimulating hormone STEP 4 Has three phases: During OVULATION, ovaries release the eggs. When the sperm enters ○ Follicular or proliferative phase the fallopian tube, it fertilizes the egg within 12-24 hours of Begins at the end of the menstrual phase ovulation. Under the influence of estrogen; parallels the o During the peak period (14th day) growth of follicles Fertilized egg, known as ZYGOTE, travels down the fallopian tube. ○ Secretory or progestational phase Zygote multiplies several times to form a BLASTOCYST which enters Begins 2-3 days after ovulation in response to the uterine cavity in 5-6 days after fertilization – implants in a day or progesterone produced by corpus luteum 2. If fertilization does not occur: ○ In the peak of fertilization/ fertility. The compact and spongy layers of Whole process from fertilization to implantation takes 6-10 days. the endometrium shed the Implantation occurs between the 20th and 24th day of the regular menstrual phase. menstrual cycle. If fertilization occurs: The endometrium assists in IMPLANTATION implantation and contributes to the Fertilized egg (BLASTOCYST) attached to the lining of the uterus to formation of the placenta. grow and develop. Later in gestation, the placenta will assume the o Endometrium – lining of the uterus role of hormone production, and the corpus Happens a week after ovulation, in an early stage of pregnancy, and luteum degenerates. an entirely a natural process. o Implantation happens after the ovulation that is on the 14th ○ Menstrual phase or gravid phase day. If the oocyte is not fertilized, venules and Most cases, it takes place around 9 days after ovulation, but sinusoidal spaces gradually become packed sometimes it can occur as early as 7 days or as late as 12 days. with blood cells, and an extensive diapedesis o It depends if it is a 28-day cycle, 24-day cycle or even less. of blood into the tissue is seen. o At the time of implantation, the mucosa of the uterus is in Blood, and small pieces of stroma the secretory phase, during which time uterine glands and and glands break away and are arteries become coiled, and the tissue becomes succulent. expelled from the uterus. As a result, three distinct layers can be recognized in the endometrium: a superficial compact layer, an intermediate Page 5 of 10 [EMBRYOLOGY] 1.02&3 FIRST AND SECOND WEEK OF DEVELOPMENT – Dr. La Paz L. Peredo, MD spongy layer, and a thin basal layer. Normally, the human “middle pain” which usually occurs during the middle of menstrual blastocyst implants in the endometrium along the anterior cycle or ovulation. or posterior wall of the body of the uterus, where it becomes embedded between the openings of the glands. Mittelschmerz (German for “middle pain”) o Normally occurs near the middle of the menstrual cycle. Remember: Ovulation period occurs on the 14th day – pain usually occurs – different from dysmenorrhea – a little bit painful. ○ 1st day of menstruation is day 1 ○ Under ultrasound, follicles are observed in the reproductive organ – indicating ovulation – fertile period. ○ Suitable time to conceive a child. WHY IS THERE MITTELSCHMERZ (fertility pain or ovulation pain)? During ovulation, LH is released as well as a little of progesterone and Gonadotropins – that causes spasms thereby causing pain (ovulation pain). The hypothalamus stimulates the ovarian cycle (starts at the age of puberty) – it specifically stimulates the anterior pituitary gland to release gonadotropins, FSH, and LH. FIGURE 11. Events during the first week of human development. 1) oocyte Important Events in the Cycle (refer to Figure 12): immediately after ovulation; 2) fertilization, approximately 12 to 24 hours after Follicular Phase (before the 14th day): ovulation; 3) stage of the male and female pronuclei; 4) spindle of the first ○ FSH is being released (green), responsible for growing and mitotic division; 5) two-cell stage (approximately 30 hours of age); 6) morula maturing the follicles – peak of FSH and Estradiol – containing 12 to 16 blastomeres (approximately 3 days of age; 7) advanced FOLLICULAR PHASE. morula stage reaching the uterine lumen (approximately 4 days of age); 8) early blastocyst stage (approximately 4.5 days of age; the zona pellucida has Ovulation (starts at the 14th day): disappeared); 9) early phase of implantation (blastocyst approximately 6 days of ○ LH peaks (blue) which stimulate the release of egg. age). The ovary shows stages of transformation between a primary follicle and a ○ Progesterone also starts to peak which prepares preovulatory follicle as well as a corpus luteum. The uterine endometrium is (thickens) the endometrium (becomes succulent, shown in the pregestational stage. produces more arteries, more blood that can be used during pregnancy). Blastocyst begins to wedge itself into the endometrial lining of the uterus – this takes about 5 days to complete. Luteal Phase (Progestational Phase):· After implantation, cell division begins to specialize, forming what ○ Progesterone peaks; corpus luteum changes color due to will become the embryo’s body and the placenta. more blood vessels (more lectin). ○ Body temp also peaks - from the normal temp 37°C Stages of Implantation becomes 38°C (basal temp rises) – females become hotter 1st Stage - embryo attaches to the uterine wall (endometrium), during ovulation – in “heat”. embryo is about 5-6 days old, adplantation. Ovulation is generally accompanied by a rise in 2nd Stage - fertilized egg penetrates the uterine wall so it is secured basal temperature – can be monitored to aid in the uterus, adhesion of blastocyst to the endometrium. couples in becoming pregnant or preventing 3rd Stage - embryo embeds deeply inside the uterine wall, ovum pregnancy. located in the endometrial cavity, the endometrium grows and the cavity is wrapped better. If fertilization takes place within the 28-day cycle: o As the stages progress, the egg adheres more ○ The corpus luteum of pregnancy will take over so that the blastocyst will be implanted there – no abortion takes Summary: place. Blastocyst is caught in the crevice of zona pellucida (ovulation) It If no fertilization takes place: then rolls to the surface of the epithelium deepens into the ○ The endometrium will degenerate as well as the corpus endometrium attached deeply into the endometrium gets deeper luteum – the corpus albicans will then take place. into the uterus Clinical Significance: Importance of Ovulation: During consultation with a patient or couple that have a problem Sometimes women complain on Hypogastric pain (slight pain on the with child conception, the doctor should examine this cycle. hypogastric area) – might be appendicitis / uterine infection (must be ○ Check the ovulation (is the patient ovulating?) ruled out) – because during early pregnancy, women complain about If not ovulating: Give the patient a medication slight pain (usually at the hypogastric area) – try to ask their history that can increase the anterior pituitary of menstruation because there is this called mittelschmerz or hormone – which could induce ovulation. Page 6 of 10 [EMBRYOLOGY] 1.02&3 FIRST AND SECOND WEEK OF DEVELOPMENT – Dr. La Paz L. Peredo, MD Clomiphene citrate [Clomid] is a drug given VI. SECOND WEEK OF DEVELOPMENT: early in the menstrual cycle used to increase BILAMINAR GERM DISC FSH concentrations to stimulate ovulation in women who do not ovulate or to those who INTRODUCTION ovulate irregularly. Also, it is given to stimulate egg development for use in in vitro fertilization This chapter gives a day-by-day account of the major events of the second week procedures. of development; however, embryos of the same fertilization age do not ○ Check the hormone concentration necessarily develop at the same rate. Indeed, considerable differences in rate of Some women fail to ovulate because of low growth have been found even at these early stages of development. concentration of gonadotropins. An agent to stimulate gonadotropin release is 8TH DAY OF DEVELOPMENT therefore administered in order for ovulation to be employed. The trophoblast consists of an inner layer with mononuclear cells, Although such drugs are effective, they often the cytotrophoblast, and an outer layer without distinct cell produce multiple ovulations, so that the boundaries, the syncytiotrophoblast. The embryoblast is formed by likelihood of multiple pregnancies is 10 times the epiblast and hypoblast layers. The amniotic cavity appears as a higher in these women than in the general small cleft. population. At the eight day of development, the blastocyst (or the zygote) is ○ Check the body temperature (is the body temperature partially embedded in the endometrial stroma. rising?) Endometrium is the columnar cells at the bottom, going up with ○ Is the endometrium developed? – give supplemental blood vessels. progesterone In the area over the embryoblast, the TROPHOBLAST (future ○ Check the male partner placenta; described as ring; the body of the ring) has differentiated If a patient does not want to get pregnant, into two layers: advise them of contraceptive pills. There are ○ Cytotrophoblast - an inner layer of mononucleated cells pills that contain FSH or only LH. Others (single layer cell) contain estradiol or estrogen and others have ○ Syncytiotrophoblast - an outer multinucleated zone progesterone hormone alone. without distinct cell boundaries. Mitotic figures are found in the cytotrophoblast but not in the syncytiotrophoblast. Thus, cells in the cytotrophoblast divide and migrate into the syncytiotrophoblast, where they fuse and lose their individual cell membranes. EMBRYOBLAST (future embryo) or inner cell mass differentiates into two layers: ○ Hypoblast layer - adjacent to blastocyst cavity ○ Epiblast layer - amniotic cavity Together, the layers form a flat disc. At the same time, a small cavity appears within the epiblast. This cavity enlarges to become the amniotic cavity. Epiblast cells adjacent to the cytotrophoblast are called amnioblasts; together with the rest of the epiblast, they line the amniotic cavity (refer to Fig. 13). FIGURE 12. Phases of the first week of development along with the changes in ovarian cycle, body temperature, anterior pituitary hormones, ovarian hormones, and uterine or endometrial cycle. FIGURE 13. A 7.5-day human blastocyst, partially embedded in the endometrial stroma. Page 7 of 10 [EMBRYOLOGY] 1.02&3 FIRST AND SECOND WEEK OF DEVELOPMENT – Dr. La Paz L. Peredo, MD FIGURE 14. Section of a 7.5-day human blastocyst (x100). Note: The multinucleated appearance of the syncytiotrophoblast, large cells of FIGURE 15. A 9-day human blastocyst. the cytotrophoblast, and slit-like amniotic cavity. The syncytiotrophoblast shows a large number of lacunae. Flat cells form the exocoelomic membrane. The bilaminar disc consists of a layer of columnar 9TH DAY OF DEVELOPMENT epiblast cells and a layer of cuboidal hypoblast cells. The original surface defect The blastocyst is more deeply embedded in the endometrium, and is closed by a fibrin coagulum. the penetration defect in the surface epithelium is closed by a fibrin coagulum. 11th and 12th DAY OF DEVELOPMENT The trophoblast shows considerable progress in development, particularly at the embryonic pole, where vacuoles appear in the Mid of the second week: formation of your lacunar and maternal syncytium. site. When these vacuoles fuse, they form large lacunae, and this phase The blood vessels from the mother side enter the lacunar space - of trophoblast development is known as the LACUNAR STAGE (very formation of fetal and maternal circulation. significant during day 9). By the 11th and 12th day of development, the blastocyst is completely At the abembryonic pole, meanwhile, flattened cells probably embedded in the endometrial stroma. originating from the hypoblast forms a thin membrane that lines the And the surface epithelium almost entirely covers the original defect inner surface of the cytotrophoblast. in the uterine wall. This membrane, together with the hypoblast, forms the lining of the The blastocyst now produces a slight protrusion into the lumen of exocoelomic cavity, or primitive yolk sac. the uterus. The trophoblast is characterized by lacunar spaces in the syncytium that form an intercommunicating network. The hypoblast with the continuation of cells lining the This network is particularly evident at the embryonic pole, the cytotrophoblast is your exocoelomic membrane. trophoblast still consists mainly of cytotrophoblastic cells. Cytotrophoblast (light green in color shown in Fig. 15), invades some Concurrently, cells of the syncytiotrophoblast penetrate deeper into villi and syncytiotrophoblast. the stroma and erode the endothelial lining of the maternal During the 8th day, syncytiotrophoblast is the outer layer and is capillaries. These capillaries, which are congested and dilated, are multinucleated, but during the 9th day, it forms vacuoles. known as SINUSOIDS. Epiblast near the amniotic cavity together with hypoblast is called As the trophoblast continues to erode more and more sinusoids, bilaminar germ disc. maternal blood begins to flow through the trophoblastic system, Blood vessels and enlarged and engorged. establishing the UTEROPLACENTAL CIRCULATION. Page 8 of 10 [EMBRYOLOGY] 1.02&3 FIRST AND SECOND WEEK OF DEVELOPMENT – Dr. La Paz L. Peredo, MD Bleeding occurring near or at the 27-28th day of fertilization is an implantation bleeding due to an extra position of capillaries of blood coming from the maternal side going to lacunar spaces. The trophoblast is characterized by a villous structure. Cells of the cytotrophoblast proliferate locally and penetrate into the syncytiotrophoblast forming cellular columns surrounded by syncytium. Cellular columns with the syncytial covering are known as primary villi. Secondary yolk sac (definitive yolk sac) - a new cavity within the exocoelomic cavity as a result of proliferation and migration of additional cells produced by hypoblast to the inside of the exocoelomic membrane; much smaller than the original exocoelomic cavity (primitive yolk sac). Exocoelomic cysts - large portions of the exocoelomic cavity that are pinched off and are often found in the extraembryonic coelom. Chorionic cavity (extraembryonic coelom) - the result of extraembryonic coelom expansion, forming a large cavity. The extraembryonic mesoderm lining the inside of the cytotrophoblast is FIGURE 16. Human blastocyst of approximately 12 days. then known as the chorionic plate. The trophoblastic lacunae at the embryonic pole are in open connection with Connecting stalk - the place where extraembryonic mesoderm maternal sinusoids in the endometrial stroma. Extraembryonic mesoderm traverses the chorionic cavity. With development of blood vessels, proliferates and fills the space between the exocoelomic membrane and the the stalk becomes the umbilical cord. inner aspect of the trophoblast. FIGURE 17. Fully implanted 12-day human blastocyst (x100). Note: Maternal blood cells in the lacunae, the exocoelomic membrane lining the primitive yolk sac, and the hypoblast and epiblast. FIGURE 18. A 13 - day human blastocyst. Trophoblastic lacunae are present at Extraembryonic mesoderm- derived from yolk sac cells, form a fine, the embryonic as well as the abembryonic pole, and the uteroplacental loose connective tissue, splits into 2: circulation has begun. ○ Somatic mesoderm - lining the cytotrophoblast (and amnion) The second week of development is known as the week of 2's: ○ Splanchnic mesoderm - lining covering the primitive yolk ○ The trophoblast differentiates into two layers: sac (exocoelomic cavity). cytotrophoblast and syncytiotrophoblast. Syncytiotrophoblast is responsible for hormones especially 13th DAY OF DEVELOPMENT the Human Chorionic Gonadotropin (Perfect time to take Surface defect in endometrium healed. pregnancy test) - as early as second week and that can be Bleeding occurs at the implantation site as a result of increased detected. blood flow into the lacunar spaces, and occurs near the 28th day of By day 9, lacunae develop in the menstrual cycle. syncytiotrophoblast. Subsequently, maternal Because this bleeding occurs near the 28th day of the menstrual sinusoids are eroded by the syncytiotrophoblast, cycle, it may be confused with normal menstrual bleeding, therefore maternal blood enters the lacunar network, and by causing inaccuracy in determining the expected date of delivery. the end of the second week, a primitive uteroplacental circulation begins. Page 9 of 10 [EMBRYOLOGY] 1.02&3 FIRST AND SECOND WEEK OF DEVELOPMENT – Dr. La Paz L. Peredo, MD The cytotrophoblast, meanwhile, forms cellular until ovulation. During this time, body temperatures are lower and columns penetrating into and surrounded by the the development of ovarian follicles begins. syncytium. These columns are primary vili. By the After the peak in LH stimulating ovulation, there is a drop in estrogen end of the second week, the blastocyst is levels. The next phase- the luteal phase, is dominated by completely embedded, and the surface defect in progesterone. The luteal phase is typically 14 days long. Following the mucosa has healed. ovulation, the remaining cells that are not released at ovulation ○ The embryoblast forms two layers: the epiblast and become enlarged. This eventually forms the corpus luteum. The hypoblast. This will be your bilaminar germ disk. corpus luteum is a transient (short lived) endocrine organ that ○ The extraembryonic mesoderm (cells extending from primarily secretes progesterone. hypoblast) splits into two layers: the somatic and splanchnic layers. Splanchnic lines trophoblast going to primitive yolk sac. REFERENCES Somatic lining trophoblast. Extraembryonic mesoderm lining the 1. Sadler, T. W. (2015). Langman’s medical embryology. Wolters Kluwer. cytotrophoblast and amnion is extraembryonic 2. Moore K. & Torchia M. (2016), The Developing Human, Clinically somatic mesoderm; the lining surrounding the yolk Oriented Embryology 10th Edition, Elsevier Inc. sac is extraembryonic splanchnic meso- derm. 3. Gateway Natural Medicine & Diagnostic Center (2020). How Does the ○ The cavities form: the amniotic adjacent to epiblast and yolk Female Menstrual Cycle Work? sac cavities adjacent to trophoblast. https://gatewaynaturalmedicine.com/how-does-the-female-menstru Extra-embryonic mesoderm cells migrate between al-cycle-work/. the cytotrophoblast and yolk sac and amnion. 4. Tagnawa Trans At the end of the second week, it is possible to distinguish the dorsal (amniotic cavity) from the ventral (yolk sac) side of the embryo. MENSTRUAL CYCLE FIGURE 19. The Menstrual Cycle. The average menstrual cycle is 28 days. Day 28 of the ending cycle is the same as day zero of the cycle that is about to start. The normal range for a menstrual cycle is 25 to 35 days. The typical amount of blood lost during menstruation is 30 mL. Relation of body temperature whether having an ovulation. Anterior pituitary hormone - produces Follicle-stimulating hormone (FSH) and Luteinizing hormone (LH) Ovarian hormones - estrogen and progesterone A woman's menstrual cycle is regulated by several hormones: estrogen, progesterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH). The menstrual cycle can be divided into 2 phases: the follicular or proliferative cycle and the luteal or secretory phase. Day 1 of the menstrual cycle is marked by the first day of bleeding. This also marks the beginning of the follicular phase which persists Page 10 of 10