Y1S1 MHSBLEC Gametogenesis PDF

(MICRO LEC) – (MICROSCOPIC HUMAN STRUCTURAL BIOLOGY 1A) (GAMETOGENESIS & Dr. Mariemids I. Borlaza) (Y1S1_Week 3_August/2024) DIMAYACYAC - SALAMANCA - SALAS - SAMSON - SANCHEZ - SANTIAGO - SAROCA - SICAT - TABBILOS - TALO...

(MICRO LEC) – (MICROSCOPIC HUMAN STRUCTURAL BIOLOGY 1A) (GAMETOGENESIS & Dr. Mariemids I. Borlaza) (Y1S1_Week 3_August/2024) DIMAYACYAC - SALAMANCA - SALAS - SAMSON - SANCHEZ - SANTIAGO - SAROCA - SICAT - TABBILOS - TALOSIG - TAWASIL - TEOPENGCO - ULANG - UMALI - VENDIVIL Conceptus OUTLINE Embryology ○ includes all structures that develop from the zygote, both Terminologies embryonic and extraembryonic Stages of Human Development Embryo ○ Prefertilization Primordial Germ Cells ○ end of 8th week Chromosomes Fetus Mitosis ○ 9th week to birth Meiosis Clinical Correlation ○ Chromosomal Abnormalities STAGES OF HUMAN DEVELOPMENT Trisomy 21 Trisomy 18 Klinefelter’s Syndrome Turner’s Syndrome ○ Structural Abnormalities Cri-du-chat Syndrome Spermatogenesis Spermatogenic Cells Spermiogenesis Clinical Correlation ○ Male Factor Infertility Oogenesis In Utero Before Puberty At Puberty During Ovulation Under the Microscope Week 1 of Human Development ○ Fertilization Phases of Fertilization Results of Fertilization Cleavage Prefertilization Events Morula Inside the Uterus ○ Spermatogenesis Ovulation ○ Oogenesis Implantation Fertilization Week 2 of Human Development Embryonic ○ Week 1 of human development Fetal Period ○ Week 2 of human development REFERENCES Embryonic Period Gametogenesis PPT Fetal Period Langman's Medical Embryology 14th ed Prefertilization EMBRYOLOGY Why Study Embryology? Provide knowledge essential for creating health care strategies for better reproductive outcomes Improvements in prenatal diagnoses and treatments, therapeutic procedures and mechanisms to prevent birth defects TERMINOLOGIES Embryology ○ Study of the DEVELOPMENTAL changes from fertilization up to birth (single cell - ZYGOTE to a baby in 9 months) Fertilization ○ union of sperm and egg cells to form zygote PAGE 1 OF 20  MICRO LEC – GAMETOGENESIS DEVELOPMENT BEGINS WITH FERTILIZATION: CHROMOSOMES ○ Male gamete (sperm) + female gamete (oocyte) = Humans have approximately 23,000 genes on 46 zygote chromosomes ○ Gametes derived from PRIMORDIAL GERM CELLS 23 homologous pairs to form diploid number of 46 Autosomes: 22 pairs of matching chromosomes (PGC) Sex chromosomes: 1 pair ○ XX - genetically female PRIMORDIAL GERM CELLS (PGC) ○ XY - genetically male ○ One chromosome derived from oocyte and Formed in the epiblast during the second week sperm each containing haploid of 23 Eventually it will move to the primitive streak during gastrulation chromosomes and migrate to the wall of the yolk sac. Union of the gametes will restore the 46 chromosomes Fourth week, these cells begin to migrate from the yolk sac toward the developing gonads, where they arrive by the end MITOSIS of the fifth week. Process whereby one cell divides giving rise to 2 Mitosis to increase the number of cells daughter cells that are genetically identical to the parent In the gonad, these germ cells will undergo gametogenesis cell. ○ Meiosis - reduce the number of chromosomes For cell repair and regeneration Phases: Prophase, Metaphase, Anaphase, and Primordial germ cells (PGCs) give rise to spermatogonial stem Telophase (PMAT) cells. At regular intervals, cells emerge from this stem cell population to form type A spermatogonia, and their production marks the initiation of spermatogenesis. Type A cells undergo a MITOSIS limited number of mitotic divisions to form clones of cells. The last cell division produces type B spermatogonia, which then divides to form four primary spermatocytes. From the multiplication of Mitosis to eventually Meiosis in the gonads which will cause reduction on the number of chromosomes and cytodifferentiation to be able to complete their maturation. PRIMORDIAL GERM CELLS (PGC) Various stages of mitosis. In Prophase, chromosomes are visible as slender threads. Doubled chromatids become clearly visible as individual units during Metaphase. At no time during do members of a chromosome pair unite. Blue, paternal chromosomes; Red, maternal chromosomes An embryo at the end of the third week, showing the position of primordial germ cells (PGCs) in the wall of the yolk sac, close to the attachment of the future umbilical cord. From this location, these cells migrate to the developing gonad. PAGE 2 OF 20  MICRO LEC – GAMETOGENESIS MITOSIS of two chromatids. C. Intimately paired homologous chromosomes interchange fragments [crossover]. Note the chiasma. D. Double-structure chromosomes pull apart. E. Anaphase of the first meiotic division. F, G. During the second meiotic division, the double-structured chromosomes split at the centromere. At completion of division, chromosomes in each of the four daughter cells are different from each other. Cross overs: ○ Critical event in Meiosis I ○ Interchange of chromatid segments between paired homologous chromosomes ○ Genetic variability is enhanced because there is redistribution of genetic material. MEIOSIS MEIOSIS Phases: Prophase, Metaphase, Anaphase, and Telophase Cell division that takes place in the germ cells to generate male and female gametes (sperm and egg respectively) ○ Spermatogenesis - Male ○ Oogenesis - Females Requires 2 cell divisions, to reduce number of chromosomes to haploid number 23 ○ Meiosis I - results to formation of 2 secondary gametocytes (23 pairs chromosomes, 2N) ○ Meiosis II - results to formation of 4 gametes (23 chromosomes, 1N) The main purpose of the meiosis is to eventually form the gametes. Clinical Correlation MEIOSIS CHROMOSOMAL ABNORMALITIES Numerical or structural Important cause of birth defects and spontaneous abortions Most common chromosomal abnormalities in abortuses: ○ 45, X (Turner’s Syndrome) ○ Triploidy ○ Trisomy 16 First and second meiotic divisions. A. Homologous chromosomes approach each other. B. Homologous chromosomes pair, and each member of the pair consists PAGE 3 OF 20  MICRO LEC – GAMETOGENESIS Trisomy 18 (Edward Syndrome) MECHANISM BEHIND CHROMOSOMAL ANOMALIES Common cause of early pregnancy loss (10 weeks AOG) Those born alive usually die in 2 months and only 5% live beyond 1-year-old Clinical features: ○ Intellectual disability ○ Congenital heart defects ○ Low set of ears, flexion of fingers and hands, syndactyly ○ Micrognathia ○ Renal abnormalities TRISOMY 21 VS TRISOMY 18 In normal meiosis, disjunction occurs - as a result, gametes with 23 single chromosomes are produced. In nondisjunction - abnormal gametes are produced; either 24 or 22 single chromosomes are produced Fertilization between normal gamete and abnormal gamete ○ Example: 23 + 24 = 47 (Trisomy) 23 + 22 = 45 (Monosomy) Klinefelter’s Syndrome NUMERICAL ABNORMALITIES ONLY in MALES Detected by amniocentesis Trisomy 21 (Down Syndrome) We get samples transabdominal ultrasound guided aspiration of Extra copy of chromosome 21 amniotic fluid Results from meiotic nondisjunction (95%), nondisjunction occurs in oocyte formation 47, XXY Increase risk with increasing maternal age, >/40yo (1 in Nondisjunction of XX homologue 100) Pathognomonic: presence of Barr bodies (condensation Clinical features: of inactivated X chromosome) ○ Growth retardation Clinical features: ○ Intellectual disability ○ Sterility ○ Craniofacial abnormalities (upward slanting ○ Testicular atrophy eyes, epicanthal, ○ gynecomastia ○ flat facies and small ears 1 in 500 males ○ Cardiac defects ○ Hypotonia ○ increased risk: leukemia, infections, thyroid dysfunctions and premature aging PAGE 4 OF 20  MICRO LEC – GAMETOGENESIS KLINEFELTER’S SYNDROME TURNER’S SYNDROME KLINEFELTER’S SYNDROME VS. TURNER’S SYNDROME STRUCTURAL ABNORMALITIES Involve one or more chromosomes Turner’s Syndrome Results from breakage of chromosome secondary to environmental factors and drugs 45, X Deletions of chromosomes ONLY in FEMALES Most common cause: nondisjunction in male gamete Cri-du-chat Syndrome Paternal naman siya. Kapag sobrang tanda nung father yun yung nagiging problema. Partial deletion of the short arm of chromosome 5 Absence of ovaries, short stature, webbed neck, skeletal Cat-like cry, microcephaly, intellectual disability and congenital heart disease. deformities, broad chest with widely spaced nipples The only monosomy compatible with life PAGE 5 OF 20  MICRO LEC – GAMETOGENESIS CRI-DU-CHAT SYNDROME SPERMATOGENESIS Once a male begins developing secondary sex characteristics, Begins at puberty his brain starts to develop further. The hypothalamus produces Transformation of spermatogonia to spermatozoa gonadotropin-releasing hormone (GnRH), which influences the anterior pituitary gland to produce luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Spermatogenesis is regulated by LH production by the pituitary gland. LH binds to receptors on Leydig cells and stimulates testosterone production, which in turn binds to Sertoli cells to promote spermatogenesis. Follicle-stimulating hormone is also Spermatogenesis, which begins at puberty, includes all of the essential because its binding to Sertoli cells stimulates testicular events by which spermatogonia are transformed into fluid production and synthesis of intracellular androgen receptor spermatozoa. At birth, germ cells in the male infant can be proteins, all of which will help in development of recognized in the sex cords of the testis as large, pale cells. spermatogenesis. PAGE 6 OF 20  MICRO LEC – GAMETOGENESIS Two secondary spermatocytes (meiosis II) – four spermatids Take Note: Primordial cells remain dormant until puberty Maturation of sperm begins at puberty One primary spermatocyte gives rise to four (4) daughter cells = all four (4) develop into mature gametes Testosterone, along with follicle-stimulating hormone, stimulates the Sertoli cells of the testes, leading to the production of inhibin and the upregulation of testosterone-binding globulin (TBG) receptors. This upregulation of the receptors allows further stimulation of these cells by testosterone, resulting in the activation of spermatogenesis. The PGCs or Primordial germ cells give rise to spermatogonial stem cells and then at regular intervals, these cells will emerge from these stem cell populations to eventually form your type A spermatogonia. Their production will mark the initiation of spermatogenesis. These type A cells will undergo a limited number of mitotic divisions to form clones of cells. The last cell division will produce this type B spermatogonia which will, then, divide to form 4 primary spermatocytes. These primary spermatocytes will undergo prolonged prophase - 22 days followed by meiosis I and formation of secondary spermatocytes. SPERMATOGENESIS Process by which spermatogonia develop into sperm (approximately 64-72 days) Primordial germ cells-gonad (week 4): remain dormant Contains 3 phases: until puberty ○ Spermatogonial Phase At puberty, differentiate into spermatogonia: Primary spermatocytes (meiosis I) PAGE 7 OF 20  MICRO LEC – GAMETOGENESIS stem cells divide to replace In the Epididymis themselves and provide a population of committed spermatogonia When fully formed, Spermatozoa enters the ○ Spermatocyte Phase seminiferous tubules and pushed toward the epididymis Primary spermatocytes undergo to obtain full motility meiosis to reduce both the ○ Although initially only slightly motile, chromosome and amount of DNA spermatozoa obtain full motility in the ○ Spermatid Phase (spermiogenesis) epididymis Final stage of maturation of spermatocytes occurs Spermatogenic Cells post-ejaculation Post capacitation, spermatocytes are not able to SPERMATOGONIA fertilize a secondary oocyte Stem cell, diploid chromosomes (46 chromosomes or 44 xy) Primary spermatocyte ○ 44 xy Secondary spermatocyte ○ 22 x / 22 y or haploid Spermatid (22 x / 22 y) Sperm Cell (22 x / 22 y) Spermiogenesis Series of changes resulting in the transformation of spermatids into spermatozoa Changes includes: ○ Formation of acrosome (very important during fertilization; covers half of the nucleus surface): contains enzymes to assist in penetration of egg during fertilization ○ Condensation of nucleus ○ Formation of neck, middle piece, and tail ○ Shedding of most of the cytoplasm as residual bodies that are phagocytized by Sertoli cells The time required for a spermatogonium to develop into a mature spermatozoon is approximately 74 days The testes are responsible for making the testosterone (primary male sex hormone and necessary for the production of sperm). Note: 300 million sperm cells are produced daily after the 74 days Within the testes are coiled masses of tubes called the seminiferous tubules. These tubules are responsible for producing the sperm cells through a process called spermatogenesis. PAGE 8 OF 20  MICRO LEC – GAMETOGENESIS LPO view of the Seminiferous tubules. Inside these tubules are different stages of spermatogenic cells. At birth, the germ cells in the male infant can be recognized in the sex cord of the testis which you can see in figure A, as large pale cells surrounded by supporting cells. These supporting cells which are derived from the surface epithelium of the testis, are actually in the same manner as the follicular cells. They become sustentacular cells or what we call the sertoli cells. As you can see here this is a cross section of the seminiferous tubules at puberty. You have to take note of the different stages of spermatogenesis and the developing cells embedded in the cytoplasmic processes supporting sertoli cells which you can see here. Testis Each lobule of testis consists of 1 to 4 seminiferous tubules Connective tissue stroma – Interstitial tissue containing Leydig cells TESTIS SPERMATOGENIC CELLS Spermatogonia Primary spermatocyte Secondary spermatocyte Spermatid Sperm cell The sertoli cells are actually the blood barrier, these are the different spermatogenic cells PAGE 9 OF 20  MICRO LEC – GAMETOGENESIS Infertile as long as they do not use any form or method of protection. Mostly female factors ang cause ng infertility. 10-15% are male factors. Infertility Problems in the Philippines ○ Common causes: Male factor (25%) Ovulatory dysfunction Tubal factor ○ Peritoneal factor Pelvic endometriosis Pelvic adhesive diseases ○ Uncommon causes: Cervical or interactive factor Endometrial or uterine factor ○ Male causes: Genetic abnormalities: Varicocele SERTOLI CELLS Cigarette smoking Oxidative stress Columnar cells; supporting cell Note: If the patient comes into the clinic, we also work up the male. Important in the formation or in collecting substances to affect the developing sperm. These products may include hormones which are toxic to your developing sperms. Physical Examination and Work Up: MALE SEMEN ANALYSIS SEMINIFEROUS TUBULE You have to have at least 300 million produced sperm daily. Abnormalities in semen analysis: 20% of infertile couples 2-3 days of abstinence before semen collection In order to have proper or appropriate number/sample of semen WHO REFERENCE VALUES FOR HUMAN SEMEN CHARACTERISTICS (2010) Semen volume (mL) 1.5 Sperm concentration 15 (million/mL) Total number 39 (million/ejaculate) Total motility (%) 40 HPO view of the Seminiferous tubules. Normal forms (%) 4 A. Spermatogonium occupying the base of the tubules B. Primary spermatocytes are marked by the presence of mitotic figures What we look into semen analysis is the morphology which is an C. Spermatids near the lumen important parameter which is correlated to fertilized capability. D. Leydig cells or supporting cells Morphology would include the tail and head. The degree of sperm motility should be determined which usually occurs 15-20 minutes after ejaculation. All of the listed items above are important to be Clinical Correlation able to fertilize an egg. MALE FACTOR - INFERTILITY Infertility is a disease of the reproductive system defined as failure to achieve a clinical pregnancy after 12 months or more of unprotected intercourse Affects 10-15 % of reproductive - aged couples PAGE 10 OF 20  MICRO LEC – GAMETOGENESIS Oogenesis IN UTERO Once PGCs have arrived in the gonad of a genetic female, they differentiate into oogonia Mitotic divisions, and by the end of the third month, they are arranged in clusters surrounded by a layer of flat epithelial cells Majority of oogonia continue to divide by mitosis, but some of them arrest their cell division in prophase of meiosis I and form primary oocytes 5th month AOG: total number of germ cells in the ovary reaches its maximum, estimated at 7 million. At this time, cell death begins, and many oogonia as well as primary oocytes degenerate and become atretic. 7th month: majority of oogonia have degenerated except for a few near the surface. All surviving primary oocytes have entered prophase of meiosis I, and most of them are individually surrounded by a layer of flat follicular epithelial cells MUST KNOW!! Maturation of Oocytes begins before birth Process of oogonia differentiating into mature oocytes. Maturation of Oocytes at puberty One primary oocyte gives rise to four (4) daughter cells Maturation happens in but only one will develop into a mature gamete - Males = During puberty - Females = Usually starts in the utero PAGE 11 OF 20  MICRO LEC – GAMETOGENESIS BEFORE PUBERTY In male, the involvement of hypothalamus, pituitary gland, are important anatomical landmarks to be able to fully understand Primary oocytes remain arrested in prophase and do not these. finish their first meiotic division before puberty is reached Total number of primary oocytes at birth is estimated to vary from 600,000 to 800,000. During childhood, most oocytes become atretic; only approximately 40,000 are present by the beginning of puberty, and fewer than 500 will be ovulated. This is why we sometimes associate that a female has body clock, because to uterus from utero to menopause, nagbabawas ng nagbabawas ang ovarian follicles Primary oocytes ○ 7 millions at 5 months of fetal life ○ 2 millions at birth ○ 40,000 at puberty Secondary oocytes – 12 are ovulated /year; 480 over the entire reproductive life ( 40 yrs x 12 ) ○ number of time that a female can possibly get pregnant Again, the hypothalamus will produce the gonadotropin hormone. Th gonadotropin hormone will stimulate the pituitary gland to produce luteinizing hormone and follicle stimulating hormone. This luteinizing hormone will cause production of theca cells, production of androgens and testosterones (influences the granulosa cells). Follicle stimulating hormone will influence the granulosa cells to convert androstenedione to estrogen. Luteinizing hormone and the production of estrogen will cause ovulation. Ovulation is important to be able to release an egg that will eventually be fertilized by a sperm. Ovarian Endometrial Cycle and Follicular development Ovarian - Menstrual Cycle PAGE 12 OF 20  MICRO LEC – GAMETOGENESIS As follicles continue to grow, secondary to the These are the days/cycle of a woman (1st pic) continuous production of LSH and FSH, the cells of the These are the different hormones produced (2nd and 3rd theca folliculi will organize into: pic) ○ Theca interna- an inner layer of secretory cells As well as what is happening in the endometrial lining ○ Theca externa - outer fibrous capsule (4th pic) this stratification is very important in converting Follicular development and endometrial thickening are your androstenedione into estrogen both important in pregnancy/fertilization in order to have a good egg and a good bed for the zygote/blastocyst to implant in. Any problem that concerns your hypothalamus, acranial mass or pituitary gland, thyroid has similar molecular sub-unit to FSH and LSH that can affect your normal menstrual cycle, production of hormones, affect the follicular development and endometrium which will affect the possibility of pregnancy. AT PUBERTY AT PUBERTY: PRIMORDIAL FOLLICLES ANATOMY OF GRAAFIAN CELL Granulosa Cells surrounding the oocyte remain intact and form the cumulus oophorus. At maturity, the mature vesicular (graafian) follicle may be 25 mm or more in diameter. ○ pinakamagandang egg to look into via ultrasound to see if responsive sa ovulating agents yung mga patients for infertility, tinitignan yung egg via ultrasound if they have formed the Graafian follicle pool of growing follicles is established and continuously maintained from the supply of primordial follicles. DURING OVULATION Primordial follicles begin to grow, surrounding follicular cells change from flat to cuboidal and proliferate to produce a stratified epithelium of granulosa cells ○ Primary follicle - unit for stratified epithelium of granulosa cells. With each ovarian cycle, a number of follicles begin to develop, but usually, only one reaches full maturity. Surge in LH induces the preovulatory growth phase. Meiosis I is completed, resulting in formation of two daughter cells of unequal size, each with 23 double structured chromosomes The cell then enters meiosis II but arrests in metaphase approximately 3 hours before ovulation. PAGE 13 OF 20  MICRO LEC – GAMETOGENESIS Meiosis II is completed, only if the oocyte is fertilized; UNDER THE MICROSCOPE: Otherwise, the cell degenerates approximately 24 hrs after ovulation. Binabantayan namin is the mature Graafian follicle because of the LH surge there will be ruptured and will release isang magandang matured egg. The mature egg will go to the fallopian tube and will be fertilized by the sperm cell. DIFFERENT STAGES OF FOLLICULAR DEVELOPMENT cross section of the ovary Shown here is the different phases of follicular development From primary follicle to flatten cells of primordial follicles to the growing follicles to the mature Graafian follicles to be influenced already by the luteinizing hormone to be able to release the egg with secondary oocyte because of ovulation. If there is no pregnancy, it will become corpus albicans and then the cycle again. The different stages of follicular development, different hormones, as well as the primary and secondary oocyte. Iba yung nasa loob ng follicular development ( what will call the oocyte; its either the primary or secondary oocyte) Under the microscope: On the developing follicles, you must observe the cortex area. Here you would be able to appreciate the different developing follicles. medulla- containing only connective tissues and blood vessels PAGE 14 OF 20  MICRO LEC – GAMETOGENESIS Eventually, it will form zona pellucida. Then there will be already a stratification to become the antral follicle. This antral follicle will further cause a maturation of cells to be able to be stratified into your theca externa and theca interna to eventually produce mature Graafian follicle. Now with continuous development and secretion of different hormones, it will now become Primary Unilaminar follicle. PAGE 15 OF 20  MICRO LEC – GAMETOGENESIS SPERMATOGENESIS VS OOGENESIS FERTILIZATION Mature Graafian Follicle Fusion of male and female gametes Most commonly occurring in the ampullary part of the fallopian tube ○ The Ampullary part is the widest area of the fallopian tube hence it is the most common site of fertilization. PAGE 16 OF 20  MICRO LEC – GAMETOGENESIS WHAT HAPPENS TO THE SPERM? MALE AND FEMALE PRONUCLEI FUSE FORMING A ZYGOTE The sperm is made up of the head and the tail. In the head, theres a Capacitation. Capacitation Period of conditioning in the female reproductive tract Lasts approximately 7 hours Involves epithelial interaction between the sperm and mucosal surface of the tube Glycoprotein coat and plasma membrane at the acrosomal region (of the sperm) is removed Acrosome reaction Binding to the zona pellucida The head will try to penetrate the mature egg and it will first come into contact with the zona pellucida ZP3 and ZP4 enzymes produced by the zona pellucida ○ They are the ones necessary for the head of RESULTS OF FERTILIZATION the sperm to penetrate into the zona pellucida Restoration of the diploid number of chromosomes ○ Half from the father and half from the mother Determination of the sex of the new individual PHASES OF FERTILIZATION ○ X-carrying sperm produces female embryo (XX) ○ Y-carrying sperm produces male embryo (XY) Initiation of cleavage Remember… Chromosomal and Genetic sex of an embryo is determined at fertilization by the kind of sperm that fertilizes the ovum but the male and female morphological characteristics do not begin to develop until the 7th week Early genital systems in the two sexes are similar = indifferent stage of sexual development CLEAVAGE Penetration of the corona radiata Penetration of the zona pellucida ○ Only one sperm can penetrate and eventually the membrane will close off so that other sperm cells will not be able to penetrate the zone pellucida Fusion of the oocyte and sperm cell membranes ○ Cortical and zona reactions to prevent polyspermy (the closure so that other sperms will not penetrate) There will be fusion of the oocyte and the sperm cell membranes. ○ Resumption of the 2nd meiotic division forming the female pronucleus Form a 2-cell stage, undergoes series of mitotic division ○ Metabolic activation of the egg to increase the number of cells. Blastomeres: product of each cleavage division PAGE 17 OF 20  MICRO LEC – GAMETOGENESIS MORULA OVULATION TO IMPLANTATION Blastomeres form a MORULA (16 cell) by undergoing compaction Morula enters the uterine cavity Once it implants in the uterine cavity, it is already called morula. INSIDE THE UTERUS After ovulation.. ○ Fertilization – 12 – 24 hrs after ovulation BLASTOCYST FORMATION WITH THE FOLLOWING ○ 2 cell stage – 30 hrs after fertilization PARTS ○ Morula – 3 days of age ○ Blastocyst – 5 days of age IMPLANTATION Inner cell mass positioned at one end of pole called as embryonic pole also called as Embryoblast = Embryo Outer cell mass is called as Trophoblast = Placenta Blastocyst cavity Penetration of embryoblast pole in the uterine mucosa Day 7 after fertilization on about the 6th day Within the posterior superior wall of the uterus Functional layer of endometrium during the secretory phase of the menstrual cycle Zona pellucida must degenerate for implantation to occur There would be follicular rupture causing ovulation, it will release the mature egg. What goes out from the mature graafian follicle is actually the cumulus oophorus together with the zona pellucida PAGE 18 OF 20  MICRO LEC – GAMETOGENESIS together with the primary oocyte. Once it ruptures, it becomes be two-celled, four-cells, eight-celled, and then becoming a your secondary oocyte already. morula, to blastocyst and implanted blastocyst, 6 days after fertilization. STAGES OF HUMAN DEVELOPMENT What would be the most common clinical correlation that you can account for when we talked about fertilization? One would be the ectopic pregnancy. Triad symptoms of ectopic pregnancy would include severe hypogastric pain, amenorrhea, spotting, and a positive pregnancy test. CASE: ECTOPIC PREGNANCY Now after that of course, there would already be formation of embryonic period and fetal period. Like what we have defined a while ago, the embryonic period is until the 8th week age of gestation. Fetal period will be until the 9th week and until the term or what we called 37 weeks and above until the 42nd week of gestation. OVULATION TO IMPLANTATION When we say ectopic pregnancy, it is a pregnancy outside of the uterus. Most commonly in the fallopian tube, specifically at the ampullary part because it is the most common site of fertilization. Ectopic pregnancy can also happen in other areas, like the ovaries, cervix, previous cesarean scar, even in the abdominal area, anywhere within the pelvic cavity. But the most common is in the ampullary part of the fallopian tube. What happens in ectopic pregnancy? – There is a failure of the morula to go into the uterine cavity to be implanted. Doon lang siya naka-implant sa area ng fallopian tube. That’s why it will not grow there. Eventually because of the diameter of the fallopian tube and the growing zygote, it will not be able to accommodate. Eventually it will rupture. Sometimes, patient comes in in severe pain, hypotensive, anemic because of hemoperitoneum already. The most common thing that we do especially in ruptured ectopic pregnancy is to do exploration, open up the abdomen, do laparotomy and remove the fallopian tube. If the fallopian tube is So this one is just an illustration, telling you the ovulation to removed, there is still a chance for the patient to be pregnant implantation. As you can see here, we have the ovary, we have because she has another fallopian tube. Unfortunately, for this the maturing follicle, you have your corpus luteum and then this patient, the risk of another ectopic pregnancy is higher already, one the maturing follicle, it will eventually replace a mature egg because she has a previous history of ectopic pregnancy already. and then, carrying the secondary oocyte, it will go into the widest area of the fallopian tube. The sperm will come from here of course with sexual contact, and then it will go up to meet in the fallopian tube the mature egg. And then once they combine, meaning there is already fertilization, to form the zygote. here will PAGE 19 OF 20  MICRO LEC – GAMETOGENESIS EMBRYONIC TO FETAL PERIOD Ovarian - Menstrual Cycle EMBRYONIC PHASE YOUTUBE VIDEOS Continues growth of the embryo Formation of bilaminar germ disc Differentiation to: ○ Cytotrophoblast ○ Syncitiotrophoblast Implantation and formation of placenta Establishment of uteroplacental blood flow For the embryonic phase, it’s just actually the stage for embryogenesis. FETAL PERIOD For the fetal period, I will not expound so much on the development or embryogenesis or fetal development mismo because it is not part of the learning outcome. But just an overview, this is the stages from implantation, to organogenesis to the fetal period. So those are the structures that will be formed depending on the age of gestation. So in this line you will see the different age of gestation (pointed at horizontal line above yung may 1,2,3,4) PAGE 20 OF 20