-EMBRYO- 02 First Week of Development- Ovulation to Implantation.pdf

ANA 11: EMBRYOLOGY FIRST WEEK OF DEVELOPMENT: OVULATION TO IMPLANTATION DRA. MARIA CONSTANCIA CELINA C. FERRARIS | AUGUST 24, 2023 Figure 2. Role of Hypothalamus and...

ANA 11: EMBRYOLOGY FIRST WEEK OF DEVELOPMENT: OVULATION TO IMPLANTATION DRA. MARIA CONSTANCIA CELINA C. FERRARIS | AUGUST 24, 2023 Figure 2. Role of Hypothalamus and Pituitary Gland in regulating the TABLE OF CONTENTS Ovarian Cycle. I. Ovarian Cycle IV. Blastocyst Formation Retrieved from Langman’s Medical Embryology (13th ed.) (2015). A. Follicular Phase V. Uterus at Time of 3 Phases of the Ovarian Cycle B. Ovulation Implantation 1. Follicular (proliferative phase) C. Luteal Phase 2. Ovulation D. Oocyte Transport 3. Luteal phase E. Corpus Albicans II. Fertilization A. FOLLICULAR PHASE A. Fertilization Follicle-stimulating hormone B. Phases of Fertilization → rescues and stimulates 15-20 primary-stage (preantral) follicles C. Main Results of from a continuous pool of primary follicle formation Fertilization → NOT responsible for the development of primordial to primary D. Clinical Correlates follicles but without it the follicles die and become atretic III. Cleavage Only 1 follicle reaches maturity and 1 oocyte is discharged. Others degenerate and become atretic I. OVARIAN CYCLE → Corpus atreticum-formed by a connective tissue which replaced (Ovarian Cycle and Menstrual Cycle) the atretic follicle and the surrounding follicular cells and oocyte → Fertilization-usually takes place at the ampullary region of the which degenerated uterine tube (ampulla) Hormonal Functions Follicle-stimulating hormone (FSH) → stimulates maturation of follicular (granulosa) cells surrounding the oocyte → growth differentiation factor 9 ▪ a member of the transforming growth factor-β (TGF-β) family ▪ mediates the growth of the granulosa cells Estrogen → produced by theca interna and granulosa cells: ▪ Theca interna-produces androstenedione and testosterone ▪ Granulosa cells-convert the hormones (androstenedione and testosterone) into Estrone and 17β-estradiol (estrogen) → prepares the uterine endometrium to enter into proliferative phase → allows the thinning of cervical mucus to allow passage of sperm Figure 1. Parts of the Uterus Retrieved from Encyclopedia Britannica (2012), → anterior lobe of the pituitary gland is stimulated to secrete LH (https://cdn.britannica.com/05/55705-050-DE695AC2/uterus-bladder-system LH surge at mid-cycle -rectum-child-egg.jpg) → elevates concentrations of maturation-promoting factor, → Spermatozoa may remain viable in the female reproductive tract causing oocytes to complete meiosis I and initiate meiosis II for 48-72 hours → stimulates Luteinization- production of progesterone by follicular → Ovum only lasts for 24-48 hours stromal cells Hypothalamus → Causes follicular rupture and ovulation → small area in the center of the brain which controls the sexual Progesterone cycles necessary to prepare the reproductive system for → brings secretory changes in the uterine endometrium pregnancy → prepares the uterus for implantation of embryo Gonadotropin-releasing hormone (GnRH) B. OVULATION → produced by the hypothalamus the release of secondary oocyte → acts on cells of the anterior lobe (adenohypophysis) of the Prior to ovulation pituitary gland Mature Vesicular (Graafian) follicle Adenohypophysis (pituitary gland) → formed when the vesicular follicle grows rapidly to a diameter of → produce the gonadotropins: follicle-stimulating hormone 25 mm under the influence of FSH AND LH (FSH) and luteinizing hormone (LH) that stimulate and control Abrupt increase in LH causes: cyclic changes in the ovary. → primary oocyte to complete meiosis I → follicle enters the preovulatory mature vesicular stage → Meiosis II is also initiated, but the oocyte is arrested in metaphase approximately 3 hours before ovulation Process of Ovulation 1. Increase in volume & pressure of follicular fluid 2. Overlying ovarian cortex become thin & translucent 3. Stigma (avascular) formation-surface of ovary bulge locally at the apex 4. LH surge/High concentration of LH results to: increased collagenase activity-digests collagen fibers around follicle increased prostaglandin (PG) levels-cause local muscular contractions of ovarian wall oophorus) break free (ovulation is done ) 🙂 5. Due to contractions, oocyte along with granulosa cells (cumulus Corona radiata-formed when some cumulus oophorus cells are rearranged around the zona pellucida (ZP) Trans # 2 Group 6: Ibuyat, Inoc, Madrid, Maminta, Molina TC: Maminta TH: Madrid 1 of 6  Figure 5. Relation of fimbriae and ovary. (Fimbriae collect the oocyte and Figure 3. Recording of Surgeons Performing Hysterectomy that Elucidated sweep it into the uterine tube.) Spontaneous Ovulation Retrieved from Langman’s Medical Embryology (13th ed.) (2015). Retrieved from Langman’s Medical Embryology (13th ed.) (2015). Before ovulation: fimbriae of the uterine tube sweep over the surface Note: Ovulation was not an explosive event but a 15-min long and of the ovary, and the tube itself begins to contract rhythmically smooth release of an egg oocyte is carried into the tube thru: → sweeping movements of the fimbriae Ovulation symptoms → motion of cilia on the epithelial lining Mittelschmerz Oocyte in the uterine tube → German for middle pain → cumulus cells withdraw their cytoplasmic processes from the zona → Slight pain normally occurs near the middle of the menstrual cycle pellucida and lose contact with the oocyte → Caused by prostaglandins → propelled by peristaltic muscular contractions of the tube and by → Relieved by taking NSAIDs cilia in the tubal mucosa Basal Temperature rise In humans, the fertilized oocyte reaches the uterine lumen in → By 1 degree Celsius a day before ovulation approximately 3 to 4 days. → can be monitored to aid couples in becoming pregnant, or to Note: Ectopic pregnancy occurs if the rhythmic muscular prevent pregnancy contraction of the tube or fimbriae fails to catch the oocyte and the C. LUTEAL PHASE egg will stay at the ampulla and then it will be fertilized E. CORPUS ALBICANS Latin for “whitening body” Table 1. Fate of the Corpus Luteum Fertilization does not occur Oocyte is fertilized Absence of human chorionic Degeneration of the corpus gonadotropin (HCG) luteum is prevented by human Recognized as yellowish chorionic gonadotropin, projection on the surface of the secreted by the ovary (9 days after ovulation). syncytiotrophoblast of the Corpus luteum shrinks because developing embryo. of degeneration of lutein cells The corpus luteum continues to (luteolysis) and forms a mass grow and forms the corpus Figure 4. Luteal Phase leading to the formation of Corpus Luteum. of fibrotic scar tissue (Corpus luteum of pregnancy (corpus Retrieved from Langman’s Medical Embryology (13th ed.) (2015). albicans). luteum graviditatis). After ovulation, follicle is ruptured and collapsed Progesterone production Progesterone secretion Granulosa cells and theca interna cells hypertrophied, luteinized, decreases, precipitating continues until end of 4th month and vascularized by surrounding vessels. menstrual bleeding. and it regresses slowly as the Corpus luteum trophoblastic component of the placenta becomes adequate for → formed by lutein cells from the vascularized cells (granulosa, pregnancy wall of ruptured follicle, theca interna cells) by developing a Removal of the corpus luteum of yellowish pigment pregnancy before the 4th month → secrete estrogens and progesterone, causing the uterine mucosa usually leads to abortion to enter the progestational or secretory stage in preparation for Corpus luteum → Corpus Corpus luteum → Corpus luteum implantation of the embryo. albicans gravidatis D. OOCYTE TRANSPORT II. FERTILIZATION A. FERTILIZATION The process by which male and female gametes fuse, occurs in the ampullary region of the uterine tube Trans # 2 Group 6: Ibuyat, Inoc, Madrid, Maminta, Molina TC: Maminta TH: Madrid 2 of 6  Figure 7. A. Scanning electrón micrograph of sperm binding to the zona pellucida. B. The three phases of oocyte penetration. In phase 1, spermatozoa pass through the corona radiata barrier; in phase 2, one or more spermatozoa penetrate the zona pellucida; and in phase 3, one spermatozoon penetrates the oocyte membrane while losing its own plasma membrane. Inset shows normal spermatocyte with acrosomal head cap. Retrieved from Langman’s Medical Embryology (13th ed.) (2015) B. PHASES OF FERTILIZATION Phase I - Penetration of the Corona Radiata Only one out of all spermatozoa deposited in the female genital tract fertilizes the egg Capacitated sperm pass freely through corona cells Phase II: Penetration of the Zona Pellucida Zona pellucida - glycoprotein shell surrounding the egg that Figure 6. Relation of fimbriae and ovary. Fimbriae collect the oocyte and facilitates and maintains sperm binding and induces the acrosome sweep it into the uterine tube. reaction (both mediated by the ligand ZP3, a zona protein) Retrieved from Langman’s Medical Embryology (13th ed.) (2015) Release of acrosomal enzymes (acrosin) allows sperm to penetrate Movement of sperm from the cervix to the uterine tube occurs by the zona, thereby coming in contact with the plasma membrane of muscular contractions of the uterus the oocyte Travel of sperm from cervix to oviduct may take 30 minutes to 6 This contact changes the permeability of the zona pellucida due to days release of lysosomal enzymes (from cortical granules lining the After reaching the isthmus, sperm become less motile and cease plasma membrane of the oocyte) that alter properties of the zona their migration. At ovulation, sperm again become motile, due to pellucida (zona reaction) to prevent sperm penetration and chemoattractants produced by cumulus cells, and swim to the inactivate species-specific receptor sites for spermatozoa on the ampulla zona surface To fertilize the oocyte, the spermatozoa must undergo: (1) Results in only one spermatozoon penetrating the oocyte capacitation and (2) the acrosome reaction Capacitation A period of conditioning in the female reproductive tract which lasts approx. 7 hours Involves epithelial interactions between the sperm and the mucosal surface of the uterine tube A glycoprotein coat and seminal plasma proteins are removed from the plasma membrane that overlies the acrosomal region of the spermatozoa Only capacitated sperm can pass through the corona cells (corona radiata) and undergo the acrosome reaction Acrosome Reaction Occurs after binding to the zona pellucida and is induced by zona proteins Figure 8. A. Oocyte immediately after ovulation, showing the spindie of the Results in the release of enzymes needed to penetrate the zona second meiotic división. B. A spermatozoon has penetrated the oocyte, pellucida, including acrosin- and trypsin-like substances which has finished its second meiotic division. Chromosomes of the oocyte are arranged in a vesicular nucleus, the female pronucleus. Heads of several sperm are stuck in the zona pellucida. C. Male and female pronuclei. D,E. Chromosomes become arranged on the spindle, split longitudinally, and move to opposite poles. F. Two-cell stage. Retrieved from Langman’s Medical Embryology (13th ed.) (2015). Phase III: Fusion of the Oocyte and Sperm Cell Membranes After adhesion, plasma membranes of the sperm and egg fuse Both the head and the tail of the spermatozoon enter the cytoplasm of the oocyte, but the plasma membrane is left behind As soon as the spermatozoon has entered the oocyte, the egg responds in three ways: 1. Cortical and zona reactions - Oocyte membrane becomes impenetrable to other spermatozoa - Zona pellucida alters its structure and composition to prevent sperm binding and penetration, preventing polyspermy (polyspermy is the penetration of more than one spermatozoon into the oocyte) 2. Resumption of the second meiotic division - The second meiotic division resumes, giving rise to the second polar body and the definitive oocyte - The chromosomes (22 plus X) arrange themselves into a vesicular nucleus known as the female pronucleus Trans # 2 Group 6: Ibuyat, Inoc, Madrid, Maminta, Molina TC: Maminta TH: Madrid 3 of 6  Emergency contraceptive pills ➔ may prevent pregnancy if taken 120 hours after sexual intercourse ➔ may be administered as high doses of progestin alone or in combination with estrogen ➔ other ECPs acts as antihormonal agents or as abortifacients Sterilization ➔ Vasectomy (men) prevents the release of sperm by blocking the ductus deferens, the tube that trans- ports sperm from the Figure 9. A. Phase contrast view of the pronuclear stage of a fertilized testes to the penis human oocyte with male and female pronuclei. B. Two-cell stage of human ➔ Tubal sterilization (women) in which the uterine tubes are zygote. blocked or ligated. 3. Metabolic activation of the egg ➔ May be reversed in some cases - Encompasses the initial cellular and molecular events associated with early embryogenesis Infertility Spermatozoon moves closer to the female pronucleus as its nucleus 15% to 30% of couples becomes swollen and forms the male pronucleus while the tail Male infertility may be a result of insufficient numbers of sperm detaches and degenerates and/or poor motility The male and female pronuclei (indistinguishable) come into close Female infertility may be due to occluded uterine tubes (most contact and lose their nuclear envelopes commonly caused by pelvic inflammatory disease), hostile cervical Both male and female pronuclei (haploid) must replicate its DNA mucus, immunity to spermatozoa, absence of ovulation, etc. Chromosomes organize on the spindle in preparation for a normal Clomiphene citrate (Clomid) mitotic division Drug used to increase FSH concentrations to stimulate ovulation The 23 maternal and 23 paternal (double) chromosomes split given to women who do not ovulate or ovulate irregularly longitudinally at the centromere, sister chromatids move to opposite Used to stimulate egg development for use in in vitro fertilization poles, thus providing each cell of the zygote with the normal diploid procedures number of chromosomes and DNA Assisted Reproductive Technology (ART) Offspring from these conceptions show increases in prematurity, low C. MAIN RESULTS OF FERTILIZATION or very low birth weight, and some types of birth defects Restoration of the diploid number of chromosomes Some of the approaches used for ART include the following: ➔ The zygote contains 23 maternal and 23 paternal ➔ In vitro fertilization [IVF] chromosomes, giving a new combination different from both - Follicle growth in the ovary is stimulated by parents administration of gonadotropins Determination of the sex of the new individual - Oocytes are recovered by laparoscopy ➔ The sperm carries either an X or Y sex chromosome to - Egg is placed in a simple culture medium, and produce either a female (XX) or male (XY) embryo, sperm are added immediately or a single sperm is respectively injected into an egg’s cytoplasm (intracytoplasmic Initiation of Cleavage sperm injection (ICSI) to circumvent male infertility ➔ The two-cell stage begins - Fertilized eggs are monitored to the eight-cell stage NOTE: The oocyte degenerates after 24 hours if unfertilized and then placed in the uterus NOTE: D. CLINICAL CORRELATES Success rate depends on maternal age; associated with a higher rate of birth defects Contraceptive Methods To increase chances of a successful pregnancy, 4 or 5 ova Barrier methods are used increasing frequency of multiple births but with high ➔ Examples: rates of morbidity and mortality Male condom – made of latex; often contains spermicides Female condom – made of polyurethane, lines the vagina ➔ Intracytoplasmic Sperm Injection (ICSI) Diaphragm - A single sperm is injected into the cytoplasm of the Cervical cap egg Contraceptive sponge - Increased risk for fetuses to have Y chromosome Hormonal methods deletions and is associated with a higher incidence ➔ Provide the female hormones estrogen and/or progestin of birth defects than standard IVF techniques (progesterone analogue) which inhibit ovulation (by NOTE: preventing the release of FSH and LH from the pituitary Oligozoospermia: ejaculate has very few live sperm gland), change uterine lining, thicken cervical mucus, making Azoospermia: no live sperm it difficult for sperm to enter the uterus ➔ Examples: Birth control pills (estrogen + progestin or progestin only) III. CLEAVAGE Skin patch Vaginal ring Injection Implant Male “pill” ➔ Contains a synthetic androgen that prevents both LH and FSH secretion and either stops sperm or reduces it to a level of infertility Intrauterine device (IUD) ➔ a small T-shaped unit and there are two types: a. Hormonal - releases progestin that causes thickening of cervical mucus; may make sperm less Figure 10. Development of two-cell stage to late morula stage. Retrieved from Langman’s Medical Embryology (13th ed.) (2015) active and both eggs and sperm less viable b. Copper - releases copper into the uterus that The zygote undergoes a series of mitotic divisions, resulting in an prevents fertilization or inhibits attachment of the increase in the number of cells. fertilized egg to the uterine wall; helps prevent ➔ Two-cell stage - 30 hours after fertilization sperm from entering ➔ Four-cell stage - 40 hours after fertilization Trans # 2 Group 6: Ibuyat, Inoc, Madrid, Maminta, Molina TC: Maminta TH: Madrid 4 of 6  ➔ 12- to 16-cell stage - approximately 3 days after fertilization ➔ Outer cell mass - now called as trophoblast; flatten and ➔ Late morula stage - 4 days after fertilization form the epithelial wall of the blastocyst Blastomeres (Fig. n) - terminology used for cells that have become Zona pellucida disappears which will allow implantation to begin smaller with each cleavage division On about 6th day - trophoblastic cells on the embryoblast pole will begin to penetrate the epithelial cells of the uterine mucosa L-selectin (located on the trophoblast cells) and its carbohydrate receptors (located on the uterine epithelium) mediate the initial attachment of the blastocyst to the uterus. By the end of 1st week of development, the human zygote has passed through the morula and blastocyst stages and has begun implantation in the uterine mucosa. V. UTERUS AT THE TIME OF IMPLANTATION A. LAYERS OF UTERINE WALL Endometrium - mucosa lining the inside wall Myometrium - thick layer of smooth muscle Perimetrium - peritoneal cover lining the outside wall Figure 11. (A) photo of a zygote before the 8-cell stage, loosely B. CHANGES IN THE ENDOMETRIUM arranged. (B) after cleavage of the 8-cell stage, blastomeres become From puberty (11 to 13 years) until meno- pause (45 to 50 years), more compacted through the process of compaction. the endometrium undergoes changes in a cycle of approximately 28 days under hormonal control by the ovaries. Morula - 16-cell stage; usually occurs 3 days after fertilization. During this menstrual cycle, the uterine endometrium passes through constitutes of inner cell mass surrounding it would be the outer cell three stages: mass 1. Follicular or proliferative phase ➔ Inner cell mass - will give rise to tissues of the embryo 2. Secretory or progestational phase proper 3. Menstrual phase ➔ Outer cell mass - will form the trophoblast and later on, the placenta. IV. BLASTOCYST FORMATION Figure 13. Events during the first week of human development Retrieved from Langman’s Medical Embryology (13th ed.) (2015) Follicular or proliferative phase begins at the end of the menstrual phase under the influence of estrogen, and parallels growth of the ovarian follicles. Secretory or progestational phase begins approximately 2 to 3 days after ovulation in response to progesterone produced by the corpus luteum. If fertilization does occur, the endometrium assists in implantation and contributes to formation of the placenta. At the time of implantation, the mucosa of the uterus is in the secretory phase, during which time uterine glands and arteries become coiled and the tissue becomes succulent. Three distinct layers can be recognized in the endometrium: 1. Superficial compact layer Figure 12. 2. Intermedíate spongy layer (A) Section of Human blastocyst 3. Thin basal layer. (B) Schematic diagram of human blastocyst. Blue-colored cells Normally, the human blastocyst implants in the endometrium along represent embryoblast; green-colored cells represent the anterior or posterior wall of the body of the uterus, where it trophoblast becomes embedded be- tween the openings of the glands (C) Schematic representation of trophoblast penetrating the Later in gestation, the placenta assumes the role of hormone uterine mucosa on the sixth day of development. production, and the corpus luteum degenerates. Retrieved from Langman’s Medical Embryology (13th ed.) (2015) Fluid begins to penetrate through the zona pellucida into the intercellular spaces of the inner cell mass. Blastocoele - single cavity formed as the intercellular spaces become confluent At this time, the embryo is called as blastocyst ➔ Inner cell mass - now called as embryoblast; located at one pole Trans # 2 Group 6: Ibuyat, Inoc, Madrid, Maminta, Molina TC: Maminta TH: Madrid 5 of 6  Figure 14. Changes in the uterine mucosa correlated with those in the ovary. Retrieved from Langman’s Medical Embryology (13th ed.) (2015) Menstrual phase If fertilization does not occur, shedding of the endometrium Figure 15. Changes in the uterine mucosa [endometrium] and (compact and spongy layers) marks the beginning of the corresponding changes in the ovary during a regular menstrual cycle menstrual phase. without fertilization. Venules and sinusoidal spaces gradually become packed with blood Retrieved from Langman’s Medical Embryology (13th ed.) (2015). cells, and an extensive diapedesis of blood into the tissue is seen. When the menstrual phase begins, blood escapes from superficial arteries, and small pieces of stroma and glands break away. III. REVIEW QUESTIONS During the following 3 or 4 days, the compact and spongy layers are 1. In the absence of pregnancy, corpus luteum expelled from the uterus, and the basal layer is the only part of the a. Becomes active, secretes FSH and LH endometrium that is retained. This layer, which is supplied by its b. Produces lot of relaxin and oxytocin own arteries, the basal arteries, functions as the regenerative layer c. Degenerates after some time in the rebuilding of glands and arteries in the proliferative phase. d. Is maintained by progesterone 2. Which is responsible for increasing the ovarian wall contractions? a. Estrogen b. Progesterone c. Luteinizing Hormone (LH) d. Prostaglandin 3. Which of the following is produced when the degenerated lutein cells generates a mass of fibrous tissues? a. Corona Radiata b. Corpus Luteum c. Corpus Albicans d. Corpus Luteum Gravidatis 4. The four-cell stage is reached at approximately ___ hours after fertilization. a. 30 b. 40 c. 50 d. 60 5. The inner cell mass of the blastocyst is called. a. blastocele b. trophoblast c. embryoblast d. embryo proper Answers: 1C, 2D, 3C, 45, 5C III. REFERENCES Batch Namnama Trans. (August 25, 2022). First week of development. Ferraris, M.C.C. (2023). Powerpoint Presentation. Sadler, T.W. (2015). Langman’s medical embryology (13th ed.). Wolters Kluwer Health. The Editors of Encyclopaedia Britannica. (2023, July 14). Uterus | Definition, Function, & Anatomy. Encyclopedia Britannica. https://www.britannica.com/science/uterus Trans # 2 Group 6: Ibuyat, Inoc, Madrid, Maminta, Molina TC: Maminta TH: Madrid 6 of 6