Fertilization-Fetal Period PDF

Fertilization - Fetal period FERTILIZATION Fertilization is union of a sperm and ovum to form a zygote 12 - 24 hours after ovulation at ampulla of oviduct Fertilization includes the following phases: Passage of sperm through corona radiata During coitus about 200-300 million sperm...

Fertilization - Fetal period FERTILIZATION Fertilization is union of a sperm and ovum to form a zygote 12 - 24 hours after ovulation at ampulla of oviduct Fertilization includes the following phases: Passage of sperm through corona radiata During coitus about 200-300 million sperm cells are ejaculated into the vagina capacitation of germ cells occur Corona radiata is loosened by hyaluronidase enzyme 2. Penetration of zona pellucida 3. Fusion of the oocyte and sperm cell membrane 4. Completion of 2nd meiotic division of 2o oocyte female pronucleus is formed 5. Formation of male pronucleus tail degenerate 6. Fusion of male & female pronucleus results zygote (with 2n chromosomes) within 24-48 hours after fertilization EPF in maternal serum is detected  When the first sperm enters the egg, the cell depolarizes causing the release of calcium ions inside the cell. This stimulates the release of granules that cause changes in the zona pellucida to prevent entry of other sperm. Secondary oocyte completes division, and nuclei of ovum and sperm unite to form a zygote. First week of development Cleavage (Segmentation) of zygote Consists of repeated mitotic division of zygote, resulting in a rapid increase in number of cells (smaller in size) Occurs in the oviduct as zygote is still contained in the zona pellucida. It begins about 30 hrs after fertilization as it passes through the tube. The resulting daughter cells are termed as blastomeres.  At the two cell stage, they look like twins The division continues as 2, 4, 8, 16,. Cells 12 to 16 blastomeres form morula at about 3 days after fertilization.  Two factors transport zygote into uterus Peristaltic contraction of wall of uterine tube Ciliary beats of the mucosa of uterine tube Morulla is formed of two types of cells outer cell mass:- to be future trophoblast inner cell mass:- to be future embryoblast  Blastocyst formation 4 days after fertilization spaces appear b/n blastomeres of the morula Fluids pass through zona pellucida into these cavities from uterine cavity.  As fluid increases, it separates the cells into two layers outer cell layer, trophoblast inner cell mass, embryoblast Blastocele: a single cavity  The embryoblasts form the primordium of the actual embryo The trophoblasts form the primitive organ of nourishment (chorion) Trophoblasts secrete proteolytic enzymes to degenerate zona pellucida The trophoblasts also start to secrete the hormone, HCG that prepares the uterine wall for implantation  Spaces fuse to form blastocyst cavity. At the end of 4th day the late morulla contains about 100-150 cells At this stage of development, the conceptus is called blastocyst and differentiate into 2 layers an inner cytotrophoblast an outer syncytiotrophoblast  Implantation:-process of blastocyst embedding into endometrium Occur between 5 - 6 to 11. 12 days along posterior or anterior wall of uterine body. Second week of development  Completion of implantation B/n 5th & 6th day trophoblastic cells that form attachment gives polar trophoblasts Implantation begins at the end of first week, continues & is completed during second week. The erosive syncytiotrophoblast invades endometrial stroma to embed blastocyst After implantation functional endometrial layer converted to decidua  Around 8th day trophoblast in the region of attachment to the endometrium differentiate into two cell layers: 1. Inner cellular layer, cytotrophoblast (Langerhan.s layer) Secretes enzymes for degradation of endometrium during implantation 2. Outer layer consisting of multi-nucleated syncytiotrophoblasts or plasmodiotrophoblasts  Degradation of the uterine mucous membrane releases substances These substances released during degradation are absorbed by syncytiotrophoblasts & serve as nourishment of the embryo At this time endometrial stromal cell become swollen & filled with glycogen called decidual reaction  The implantation of blastocyst is completed on the 10th or 11th day Implantation should take place within 36 hours after the blastocyst contacted the endometrium After 36 hours the endometrium considers blastocyst as foreign & rejects it resulting in death of embryo  L selectin on trophoblast cells and its carbohydrate receptors on the uterine epithelium mediate initial attachment of the blastocyst to the uterus.  Sites of Implantation Most common site is upper, posterior wall of body of uterus Rarely on the anterior wall of uterus Implantation can be divided as intrauterine and extrauterine implantations Any implantation site other than the above sites is termed as abnormal (ectopic) resulting in ectopic pregnancy  Abnormal implantation 1)Placenta previa: Implantation near the internal os. The placenta over bridges the os and causes severe bleeding during later pregnancy & delivery. 2) Ectopic pregnancy implantation out side normal site mostly these pregnancies are rejected  Common Sites of Ectopic Implantations (Ectopic Pregnancies) include: 1. Tubal 2. Ovarian 3. Abdominal 4. Cervical 5. Vaginal (rare)  As implantation progress, a small space appears b/n inner cell mass and invading trophoblast (beginning of amniotic cavity) Concurrently, morphological changes occur in the inner cell mass formation of a flattened circular plate of cells called embryonic disc The disc consists of two layers: Epiblast:- upper columnar cells Hypoblast:- lower cuboidal cells  Then other cells delaminate from the cytotrophoblast & form a thin exocoelomic membrane. The cavity now surrounded by this membrane and hypoblast forming exocoelomic cavity  Further delamination of trophoblastic cells gives rise to a layer of loosely arranged cells called extraembryonic mesoderm. Now the cavity becomes primary yolk sac  At the same time, isolated spaces called lacunae appear in the syncytiotrophoblast & soon become filled with a mixture of blood (from maternal capillaries) and secretions from eroded endometrial glands This nutritive fluid passes to embryonic disc by diffusion. Aten-day conceptus is completely embedded in the endometrium Extraembryonic mesoderm increase in size & isolated coelomic spaces appear within it. These spaces rapidly fuses to form a large isolated cavity called extraembryonic coelom  Development Proliferation of Chorion of cytotrophoblast produces local masses that extend into syncytiotrophoblast This proliferation results primary chorionic villi Chorion is extraembronic mesoderm (lining trophoblast and covering amnion) and trophoblast layers. Third week of development  Formation of Trilamminar Embryo A period of rapid development of embryo from embryonic disc It is characterized by formation of primitive streak and 3 germ layers as: Ectoderm Mesoderm Endoderm  GASTRULATION Is the process by which the inner cell mass is converted into trilaminar embryonic disc It begins at the end of the first week with the formation of the hypoblast. It continues during second week completed during third week with the formation of 3 germ layers (ectoderm, mesoderm & endoderm  The appearance of three layers is known as gastrulation and the embryo at this time is known as gastrula  Amniotic cavity becomes well-developed and filled with amniotic fluid Amniotic fluid is secreted by amniotic cells at the beginning but later derived from the mother  Primitive streak  Thickened linear band of epiblast.  Becomes visible by the beginning of the 3rd wk as a narrow groove (by invagination of cells).  Has bulging regions on either side.  The cephalic end of the streak is the primitive node surrounding a 46 primitive pit.  Formation of Primitive  At the beginning of 3rd week proliferation & Streak accumulation of epiblastic cells in posterior part of the embryonic disc forms thickened linear band called primitive streak.  It elongates by addition of cells to its caudal end, and its cranial end proliferates to form primitive node 47  Primitive Streak…  Concurrently, a narrow primitive groove develops in the streak.  Shortly after primitive streak appears cells leave, its deep surface and form a loose network of tissue called mesenchyme.  Some of this tissue soon becomes embryonic mesoderm. 48 The epiblast now referred to as embryonic ectoderm and the hypoblast as embryonic endoderm. By this stage of development, it is possible to identify the embryo’s: craniocaudal axis cranial and caudal ends dorsal and ventral surfaces right and left sides  Fate of Primitive Streak  Actively forms mesoderm until the early part of 4th week  Then it starts regressing and becomes an insignificant structure in the sacrocooccygeal regions  Normally it degenerates and disappears by the end of 4th week  Remnants may persist and give rise to a large tumor called 50 Sacrococcygeal Teratomas  Notochord Is a cellular rod that develops from notochordal process. A rod of mesenchymal cells located cranially, in the midline, extending between the primitive node and the prechordal plate 51  The Notochord Steps 1. Primitive pit extends to notochordal process forming a lumen called notochordal canal 2. The floor of notochordal process fuses with the underlying embryonic endoderm. 3. The fused region undergoes degeneration. 4. Openings appear in the floor of the notochordal process 5. The openings confluent and floor of notochordal canal disappear. 6. The remains of notochordal process form a flattened grooved plate called notochordal plate 7. Beginning from the cranial end, the plate folds to 52 form notochord  Cont…. The notochord is a structure around which the vertebral column forms It degenerate & disappear when surrounded by vertebral bodies, but persists as nucleus pulposus of intervertebral disc o Notochord –induce formation of neural plate - premordium of CNS. 53 Notochordal plate folds to form the notochord. 54 55  Functions of Notochord Defines primordial axis of the embryo Provides rigidity to the embryo Serves as a basis for the development of the axial skeleton Indicates the future site of the vertebral bodies/column Regulates differentiation of surrounding structures including the overlying ectoderm (neural plate) and mesoderm (somites). Fate of Notochord Degenerates and disappears as the bodies of the vertebrae develop, but it persists as the nucleus pulposus of each intervertebral disc Remnants of notochordal tissue give rise to tumors called 56 Chordomas  Formation of the three germ layers  Cells of the epiblast migrate toward the primitive streak they become flask shaped detach from the epiblast slip beneath it This inward movement is known as invagination.  Some of the invaginated cells create:  Endoderm  Mesoderm  Ectoderm  The epiblast is the source of 57 all of the germ layers  Primitive streak… The first cells to move inward displace the hypoblast to create the definitive endoderm. Once definitive endoderm is established, 58 inwardly moving epiblast forms mesoderm.  …  By middle of third week, embryonic mesoderm separate ectoderm and endoderm completely except: 1. Oropharyngeal membrane cranially 2. Cloacal membrane caudally 3. In the middle cranial to primitive node where notochordal process extends 59  NEURULATION  Process of formation of neural plate, neural folds & their closure to form neural tube  Completed by the end of fourth week, when closure of caudal neuropore occurs 61 Neural plate and neural tube  As the notochord develops, the embryonic ectoderm over it thickens to form neural plate  It is induced by the developing notochord  Ectoderm of neural plate (neuroectoderm) gives rise to CNS (brain & spinal cord)  On about 18th day, the neural plate invaginates along its central axis to form a neural groove that has neural folds on each side.  By the end of 3rd week, the neural folds fuse converting the neural plate into a neural tube.  The neural tube soon separates from the surface ectoderm 64  The Neural Crest  As the neural folds fuse to form neural tube, some neuroectodermal cell lying along the crest of each neural fold lose their epithelial affinities & attachments to neighboring cells.  As the neural tube separates from surface ectoderm, these neuroectodermal cells (neural crest cells) migrate ventrolaterally on each side of neural tube.  They soon form an irregular flattened 65 mass called neural crest (between neural tube and surface ectoderm 66  Development of Somites  As notochord & neural tube form, the intraembryonic mesoderm on each side of them thickens to form a longitudinal column of paraxial mesoderm  Toward the end of the third week, the paraxial mesoderm begins to divide into paired cuboidal bodies called somites.  Somites, located on each side of neural tube  Somites give rise to most of the axial 68 skeleton and associated musculature and adjacent dermis of the skin The Embryonic Period 4 th _ 8 th Weeks 69  Embryonic period  All major external and internal structures are established during this period.  By the end of this organogenetic period all the main organ systems have begun develop but function of most organs is minimal.  Exposure of embryos to teratogens during this period may cause major congenital anomalies.  Teratogens are agents such as drugs and viruses that produce or increase the incidence of congenital anomalies.  It is the most critical period of development  As tissues and organs form the shape of the embryo changes, so that 70by the 8th wk the embryo ha s a distinct human appearance.  Folding  Folding changes of the Embryo the flat trilaminar embryonic disc into a cylindrical C- shaped embryo.  It is due to rapid unproportional growth of embryo.  Folding at cranial & caudal ends and folding at the sides occur simultaneously.  The two ectodermal depressions called cranial & caudal pits appear.  The cranial pit becomes the oral pit (stomodeum) & separated from gut tube by oropharyngeal membrane.  The caudal pit becomes the anal pit (proctodeum) separated from 71 caudal end of primitive gut by cloacal membrane  Folding of the trilaminar embryonic embryo… A significant event in the establishment of body form is folding of the disc in to somewhat cylindrical embryo.  Folding results from rapid growth of the embryo, particularly from the brain and SC.  Folding at the cranial and caudal ends and at the sides of the embryo occur simultaneously. Concurrently, a relative constriction occurs at the junction of the embryo and the umbilical vesicle.  Folding the ends of the embryo ventrally produces head and tail 72 folds that cause the cranial and caudal regions to move ventrally as the embryo elongates cranially and caudally.  Folding in  Occurs in head and tail region. median plane  Folding results a constriction between embryo and yolk sac and the dorsal part of the yolk sac is incorporated into the embryo and give rise to primitive gut.  The primitive gut is divided into: I. Foregut 74 II. Midgut III. Hindgut 76  GENERAL CONSIDERATIONS  By the end of the embryonic period, all major organ systems have begun to develop, although functionality may be minimal.  The development of the cardiovascular system is essential for obvious reasons, but, in particular, because diffusion of nutrients by the early uteroplacental circulation can no longer satisfy the nutritional needs of the rapidly developing embryo. 80  Germ Layer  The three germ layers (embryonic ectoderm, Derivatives mesoderm and endoderm) which arise from inner cell mass during 3rd week, differentiate into various tissue and organs.  By the end of embryonic period, the beginnings of all the main organ systems have been established.  The cells of each germ layer divide, migrate, aggregate and differentiate in precise pattern as they form various organ systems 82 Germ layer derivatives 84 85  Derivatives of Foregut,  The fore gut develops into  Midgut and Hindgut Pharyngeal gut  Part of respiratory organs  Esophagus  Stomach  Upper part of duodenum  Liver  Biliary ways  Pancreas  The midgut develops into:  parts of intestine up to right two-third of transverse colon  The hindgut develops into: 86  the rest part of intestine  part of urogenital system 87 The Fetal Period 9 Week- Birth th 88  9th -12 Week th head - half of the crown-ramp length. Primary ossification centers appear in the skeleton. External genitalia of males and females appear similar until the end of ninth week, and distinguished at 12 week. Urine formation and is excreted into the amniotic fluid.  13th -16th Weeks Growth is very rapid during this period Ossification of skeleton begins By 16 week, the ovaries are differentiated and have many primordial follicles containing oogonia  17th -20th Weeks Growth slows down Fetal movements are commonly felt by the mother The skin is covered with vernix caseosa. -fatty secretions /fetal sebaceous glands & dead epidermal cells -Protects the delicate skin from abrasions and hardening.  The body of 20-week fetus is usually completely covered with fine hair called lanugo, which help holding vernix caseosa on the skin. Brown fat forms during this period. By 18 weeks uterus of female fetus is completely formed. By 20 weeks the testes of male fetus begun their descent, but they are still located on posterior abdominal wall.  21st -25th Weeks There is a substantial weight gain By 24 week, the secretary epithelial cells or types II pneumocytes in the interalveolar walls of the lung have begun to secrete surfactant (a surface-active lipid that maintain the patency of the developing alveoli of the lungs).  26th -29th Weeks A fetus may survive if born prematurely and given intensive care because lungs are capable of breathing air. Eyes open at the beginning of this period. Considerable subcutaneous fat has formed.  30th -34th Weeks Pupillary light reflex can be elicited. Skin -pink and smooth. Fat in the body is about 8% of the body weight. Descent of testes to the scrotum continue 32 weeks and above usually survive.  35th - 38th Weeks 35 weeks have a firm grasp & exhibit a spontaneous orientation to light. Slowing of growth Fat = 16% of body weight Full term (38 weeks after fertilization or 40 weeks after LMP)  skin:- white or bluish-pink  chest:- prominent  testes:- in the scrotum (male) Twins & Multiple Pregnancies 98 Twins & Multiple Pregnancies 99  Twins & multiple  pregnancies Twinning means delivery of 2 or more embryos at the same time.  In North America (a study result shows the following descriptive figures)  Twins occur about 1 in every 90 pregnancies  Triplets occur about 1 in every 902 pregnancies  Quadruplets occur about 1 in every 903 pregnancies  Quintuplets occur about 1 in every 904 pregnancies  MULTIPLE PREGNANCIES ( Twins, Triples, Quadruples…)  May develop from multiple ova & abundant spermatozoa = Dizygotic, multizygotic or plurizygotic  May develop by splitting of the zygote, morula, or blastocyst 10 = Monozygotic 0  TWINS…  Dizygotic Twins (Fraternal Twins) Simultaneous fertilization of two different oocytes by two different sperms.  They are not more than siblings, may or may not be of the same sex  If they implant nearer to each other, their placenta may fuse.  Otherwise, they will have separate chorion & amnion  When their placenta fuse, the blood vessels may anastomose & 10 blood mixes forming blood group chimesas 1  Dizygotic twins…  Separate placenta, chorionic sac and amniotic cavity  Sometimes two placentas fuse into one.  Same or different sex; external and genetic features are no more alike than other brothers or sisters.  Have 2 amnion, 2 chorion and fused placenta or separate (some times) 10 2 10 3  Dizygotic  Same or different twins… sex.  External and genetic features are no more alike than other brothers or sisters. 10 4  Monozygotic (MZ) Twins  Resulting from a single fertilized ovum (zygote)  Splitting of zygote occurs at various stages of development  Develop by splitting at different levels of development: zygote stage, 2 cell stage, morula, blastocyst, gastrula, etc.  Identical twins occur in one- third of twins  Same sex and genetically the 10 5 same  MZ 1. Early Separation  occur at two cell stage  blastocyst separately implanted  has 2 amnion, 2 chorion & 2 placenta 2. Implanted close together  mostly takes place within one week  has 2 amnion, 1 chorion & 1 placenta 3. Late Separation  occur usually by the second week  has 1 amnion, 1 chorion & 1 placenta  usually these twins die  could be found in different forms: I. Conjoined:- attached at soft parts II. Parasitic:- one is well-developed but the other is not 10 6 III. Separate twins:- each are independent 10 7  Conjoined/Siamese  Based on the site of attachment, conjoined (Siamese) twins can be classified as: 1. Thoracopagus 2. Pygopagus 3. Craniopagus 4. Omphalopagus 5. Craniothoracopagus 6. Massive fusion 10 8 Conjoined Twins… 10 9  Monozygotic Twins  If implanted nearer to each other they may share placenta, fused placenta but mixing of blood does not occur because of the same gene for blood groups.  If they implant far away from each other, they may have separate placenta, chorion, amnion, etc. 11 0 MZ Twins 11 1 COMPARISON B/N DIZYGOTIC AND MONOZYGOTIC TWINS 11 2  Superfecundation Superfecundation is the fertilization of two or more oocytes at different times. In humans, the presence of two fetuses in the uterus caused by fertilization at different times (superfecudation) is rare. DZ human twins with different fathers have been confirmed by genetic markers. 11 3  Reading Assignments Fetal membranes Placneta Formation (placentation) Significance Barieir (BPB) Fetal circulation