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1. Gametogenesis: Spermatogenesis - Begins at puberty Before puberty a. Primordial Germ Cells (PGC’s) (46, 4n) gametes i. 2nd week: formed in the epiblast ii. 4th week: migrate to gonads iii. Remain dormant till puberty Puberty b. PGC’s at puberty differentiate into spermatogonia A (stem cell) in the sex cords i. Spermatogonia A undergo series of mitotic division to create clones of cell. ii. The last division of spermatogonia A creates spermatogonia B c. Spermatogonia B (46, 2n) mitosis 1° spermatocytes (46, 4n) d. 1° Spermatocytes meiosis I 2° spermatocytes (23, 2n) e. 2° Spermatocyte (23, 2n) meiosis II spermatids (23, n) 2. Spermiogenesis: Morphology of the spermatozoon a. Four steps for transformation of spermatids into spermatozoa (takes 64 days) i. Formation of acrosome from Golgi 1. Covers half the nuclear surface 2. Contains acrosin assisting penetration of the egg (zona pellucida) ii. Condensation of the nucleus iii. Formation of neck, middle piece, and tail 1. Same structure as kinocilia (9 + 2 arrangement) iv. Shedding of most of the cytoplasm b. Morphology i. Head 1. Acrosome and nucleus ii. Neck 1. Proximal and Distal Centrioles iii. Midpiece 1. Microtubules 2. Outer dense fibers 3. Mitochondria Page |1 4. Annulus iv. Tail 1. Main piece a. Microtubules b. Outer dense fibers c. Fibrous Sheath 2. End piece a. Microtubules c. The mature spermatozoa enters the lumen of the seminiferous tubules and then ‘squeezed’ towards the epididymis i. Gain full motility in the epididymis ii. 2-3 mm/min swim speed 3. Gametogenesis: Oogenesis a. Prenatal maturation i. 3rd week: PGC’s enter ovary and differentiates into oogonia ii. Until end of 3rd Month: undergoes number of mitotic divisions iii. Become arranged in clusters surrounded by flat epithelial cells (follicle cells) iv. The majority of oogonia continue to divide by mitosis but 1. Some stop in prophase I and form 1° oocytes v. 5th Month: Rapid oogonia production, germ cells in the ovary reach maximum (about 7 million) vi. After: Cell death begins vii. 7th Month: The majority of oogonia have degenerated except for a few near the surface viii. All surviving 1° oocytes (46 4n) are stopped in prophase I and most are individually surrounded by follicular cells = primordial follicle ix. Near birth: all 1° oocytes enter into diplotene stage (end of prophase) 1. 1° oocytes remain in prophase and do not finish the meiotic division before puberty is reached. b. Postnatal maturation i. At birth: there are 700 000 – 2 000 000 1° oocytes 1. <500 will be ovulated 2. Can last for 40 years or more ii. Each ovarian cycle: 15-20 primordial follicles begin to mature only 1 matures through all 3 stages – Primary or Preantral Secondary or Antral Preovulatory Page |2 Preantral 1. As 1° oocyte grows, follicular cells change from flat to cuboidal and then proliferate to produce stratified epithelium of granulosa cells. (It is now a primary follicle). 2. Granulosa cells rest on a basement membrane separating them from surrounding stromal cells that form the Theca folliculi. 3. Granulosa cells and oocytes secrete glycoprotein’s on the surface of oocytes = zona pellucida. 4. As growth continues: Theca follculi organize into theca interna (secretory cells) and theca externa (fibrous capsule) Antral 5. A fluid filled space forms between the granulose cells making the antrum. It is now a secondary follicle / Grafian follicle(25 mm diameter) a. Granulosa cells surrounding the oocyte becomes cumulus oophorus 6. A surge in LH causes the mature secondary follicle to undergo the Preovulatory growth phase Preovulatory 7. Meiosis I completed and two unequal daughter cells (each 23, 2n) are formed a. Secondary oocyte (23, 2n) receives most of the cytoplasm b. First Polar body receives no cytoplasm and lies between zona pellucida and cell membrane 8. The cell enters meiosis II but stops in metaphase II 3 hours before ovulation a. Meiosis II completed only if fertilized b. Cell degenerates 24 hours after ovulation if not fertilized 4. Ovulation and Fertilization Ovulation - process in the menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum (also known as an oocyte, female gamete, or casually, an egg) Periovulatory phase Preceding ovulation, under the influence of LH & FSH, an increase in cumulus cell number causes an increase in antrum fluid volume that can swell the follicle to over 20mm in diameter. It forms a pronounced bulge at the surface of the ovary called the blister. Page |3 Ovulatory phase Through a signal transduction cascade initiated by LH, proteolytic enzymes are secreted by the follicle that degrades the follicular tissue at the site of the blister, forming a hole called the stigma. High concentration of LH increases collagenase activity. Prostaglandin also increases in response to the LH surge and cause local muscular contractions in the ovarian wall. These contractions extrude the ovum-cumulus complex via the ruptured follicle and out into the peritoneal cavity through the stigma, where it is caught by the fimbriae at the end of the fallopian tube (also called the oviduct). After entering the oviduct, the ovum-cumulus complex is pushed along by cilia, beginning its journey toward the uterus. Some of the cumulus oophorus cells rearrange themselves around the zona pellucida to form the corona radiate. a. Corpus Luteum i. After ovulation, the ruptured follicle together with cells from the theca interna forms the corpus luteum by LH influence ii. The corpus luteum secretes progesterone iii. Progesterone + Estrogen causes the uterine wall to enter the progestational stage which prepares for embryo implantation b. If no fertilization then… i. Corpus Luteum reaches maximum development 9 days after ovulation ii. It shrinks and forms the Corpus Albicans iii. Progesterone production decreases and menstrual bleeding occurs c. If fertilization occurs then… i. Human chorionic gonadotropin (HCG) prevents degeneration of corpus luteum ii. Corpus luteum continues to secrete progesterone until the end of 4th month iii. After 4th month: placenta takes over progesterone secretion d. Fertilization i. Occurs in the ampullary region of the fallopian tube (widest part and close to ovary) ii. Spermatazoa must undergo capacitation (to pass through corona cells) and acrosome reaction 1. Capacitation is the conditioning period in the uterine tube where the glycoprotein coat and seminal plasma proteins are removed from the plasma membrane covering the acrosome 2. The acrosome reaction is induced by zona proteins (zona pellucid). This causes the release of enzymes to penetrate the zona pellucida (e.g. acrosin) iii. 3 Phases of fertilization 1. Penetration of Corona Radiata Page |4 a. Capacitated sperm passes through the corona radiata 2. Penetration of Zona Pellucida a. Aided by acrosomal enzymes 3. Cortical reaction: once one sperm comes in contact with the oocyte surface, the zona pellucida releases lysosomal enzymes from the cortical granules -> oocyte membrane becomes impermeable to other spermatozoa (Prevention of polyspermy). a. Plasma membranes of egg and sperm fuse nucleus from head of spermatozoa enter the cytoplasm of oocyte, but tail & plasma membrane is left behind b. Spermatozoa nucleus male pronucleus (22 + X or Y) c. Oocyte completes meiosis II i. The result is second polar body ii. And the definitive oocyte forms female pronucleus (22 + X) d. Each pronucleus replicates its own DNA before they fuse together and form a zygote Main result of Fertilization: 1. Diploid chromatid number restored. 2. Determination of sex. 3. Initiation of cleavage. 5. Cleavage of the fertilized egg, morula, formation of the blastocyst (First week of intrauterine life) a. Cleavage i. After 2 cell stage zygote increases number of cells by mitotic divisions (NOT increase in mass) ii. These cells which become smaller with each cleavage are known as blastomeres iii. The third cleavage (1 2 4 8 cells) causes the cells to maximize contact with each other forming a compact ball (compaction process) held by tight junctions iv. After 3 days, the compacted 16 cell morula has an inner cell mass and outer cell mass 1. Inner cell mass embryo proper 2. Outer cell mass trophoblast which later contributes to the placenta b. Blastocyst formation i. Formed when zygote enters uterine cavity ii. Fluid begins to penetrate zona pellucida into intercellular spaces of the inner cell mass Page |5 iii. iv. v. vi. The spaces gradually become one singel cavity called the blastocele Inner mass located on one pole = embryooblast Outer mass flattens to form wall of blastocyst= trophoblast Zona pellucida disappears ready for implantation 6. Implantation: Changes in the uterus and on the surface of the blastocyst a. Wall of uterus consists of 3 layers i. Endometrium – mucosa lining the inside wall ii. Myometrium – thick layer of smooth muscle iii. Perimetrium – peritoneal covering lining the outside wall b. From puberty to menopause, the endometrium undergoes a cycle of 28 days under hormonal control by the ovary c. During this menstrual cycle, endometrium passes through 3 stages i. Proliferative phase – growth under influence of estrogen ii. Secretory phase (2-3 days after ovulation) – in response to progesterone from the corpus luteum 1. If fertilization occurs then endometrium assists in implantation and contributes to formation of placenta a. Three distinct layers are seen in endometrium i. Compact layer (superficial) ii. Spongy layer (intermediate) iii. Basal Layer (thin) b. Normally the human blastocyst implants in the endometrium along the anterior or posterior walls of the uterus c. Implantation occurs with the help of enzymes secreted by the syncytiotrophoblast, which allows the blastocyst to embed into the uterine wall. 2. If fertilization does not occur during this phase, then shedding of parts of endometrium marks beginning of the menstrual phase. iii. Menstrual phase 1. Blood from superficial arteries and parts of endometrium are shedded 2. 3-4 days during menstrual phase, compact and spongy layer are expelled from the uterus and only basal layer remains Changes in the surface of the blastocyst. a. Trophoblastic (Syncytiotrophoblastic) cells over the embryoblast pole begin to penetrate between the epithelial cells of the uterine mucosa. b. Molcules involved in the attachment and invasion of the trophoblast are integrins and extracellular matrix molecules, Fibronectin and laminin. Page |6 c. These molecules takes part in a signaling pathway that regulate trophoblast differentiation so that implantation is the result of mutual trophoblastic and endometrial action. 7. Development of the blastocyst during the second week a. 8th day: blastocyst partially embedded into endometrial stroma i. Trophoblast becomes 1. Cytotrophoblast: inner layer of mononucleated cells 2. Syncytiotrophoblast: outer multinucleated zone ii. Embryoblast differentiates into 1. Hypoblast: cuboidal cells 2. Epiblast: columnar cells iii. Small cavity appears within the epiblast which enlarges amniotic cavity 1. Amnioblasts form the roof of the cavity from epiblast th b. 9 day: blastocyst more deeply embedded into endometrium i. Lacunae form in the syncytiotrophoblast ii. Exocoelomic cavity (Primitive yolk sac) appears from 1. Exocoelomic (Heuser’s) membrane (single layer of flat cell) - develops from Hypoblast. 2. Hypoblast th th c. 11 and 12 day: blastocyst is completely embedded into endometrium, so that the epithelium cell almost entirely cover the hole in the uterine wall (+Fibrin Coagulum) i. Exocoelomic membrane: From hypoblast. Proliferate and lines the exocoelomic cavity (Primitive yolk sac). ii. Extraembryonic Coelom: forms from spaces in the extraembryonic mesoderm 1. Extraembryonic somatopleuric mesoderm – lines the cytotrophoblast and amnion 2. Extraembryonic splanchnopleuric mesoderm – lines the yolk sac d. 13th day: endometrium surface has fully healed i. Hypoblast produce cells that proliferate and form a new cavity in the yolk sac. 1. Secondary yolk sac: as it forms, portions of the exocoelomic cavity pinch off and become the exocoelomic cyst 2. Extraembryonic coelom chorionic cavity Page |7 8. Developmental map of the blastocyst (the epiblast fate map) Somites: Paired blocks of mesoderm cells along the vertebrate body axis that form during early vertebrate development and differentiate into dermal skin, bone and muscle. 9. Homeobox genes, determination of body axes a. HOX genes codes for transcription factors which regulates the morphogenesis i. There are 38 HOX genes in 4 parallel series ii. 4 copies on 4 different chromosomes The establishment of the body axes takes place before and during gastrulation. b. 3 axis i. Anteroposterior (Craniocaudal) axis 1. Signaled by cells at the anterior cranial margin of embryonic disc. 2. Expresses genes essential for the head formation. 3. Once the head end is established, the primitive streak forms caudally, which is maintained and expressed by nodal gene family. 4. Cells at posterior margin of embryonic disc secretes an activin-like molecule that induce primitive streak formation Page |8 ii. Dorsoventral axis 1. Once the streak is formed a number of genes regulate formation of dorsal and ventral mesoderm, and head and tail structures. 2. Bone morphogenetic protein-4 (BMP-4) and fibroblast growth factor (FGF) is secreted throughout the embryonic disc, thus ventralizing the mesoderm into the intermediate and lateral plate mesoderm iii. Transverse axis 1. Left right asymmetry is regulated by a cascade of genes, which initiates when the streak is formed. 2. FGF-8, secreted by cells in the node and streak, induces Nodal and Lefty-2 expression on the left side. These genes upregulate transcription factors responsible for left sidedness. 10.Gastrulation The process whereby the cells of the blastocyst are translocated to establish three germ layers, ecto-, endo- and mesoderm. a. Occurs during 3rd week of gestation with the formation of the primitive streak on the surface of the epiblast i. The bulge of the cephalic end of the primitive streak is the primitive node ii. Epiblast cells migrate towards primitive streak and detach from epiblast and slip into the streak iii. The Epiblast cells invaginate (inward movement), and some cell displace hypoblast and become endoderm and others form the mesoderm between the epiblast and newly formed endoderm iv. The cells remaining in the epiblast ectoderm “Thus, the epiblast is the source of all three germ layers”. v. As more cells migrate through primitive node, they fuse the contact with extraembryonic mesoderm and become the prechordal mesoderm at the cephalic end vi. The cells after become the notochordal plate b. As hypoblast cells are replaced by migrating endoderm cells moving in the streak, the notochord proliferates and detaches from endoderm and becomes the definitive notochord c. The prechordal plate forms the mouth since it is cephalic while the cloacal membrane forms at the caudal end which forms the anus i. 16th day: The cloacal membrane appears and the posterior wall of the yolk sac forms the allantois d. Migration of cells ceases at 4th week Page |9 11.Neurulation, derivatives of the ectoderm Neurulation is a part of organogenesis in vertebrate embryos. Steps of neurulation: The process begins when the ectoderm germ layer form the neural plate. The neural plate folds in upon itself to form the neural tube. a. Surface ectoderm in midline dorsal to the notochord differentiates into microdermal cells = neural plate b. Elongated, slippershaped neural plate expands towards the primitive streak. c. End of 3rd week: i. lateral edges of neural plate becomes elevated = neural folds ii. Depressed midregion forms the neural groove d. Neural folds approach each other at midline and fuse = neural tube e. Cephalic and caudal ends of neural tube communicate with amniotic cavity by way of cranial and caudal neuropores f. Day 25 closure of cranial neuropore g. Day 27 closure of caudal neuropore h. Neurolation completed and CNS is represented by a closed tubular structure with : i. A narrow caudal portion = spinal cord ii. Broader cephalic portion characterized by dilations = brain vesicles i. As the neural folds elevate and fuse, cells at the crest of the neuroectoderm begin to dissociate from their neighbors = neural crest j. Crest cells leave the neural folds after closure of the neural tube and migrate along one of two pathways : i. A dorsal pathway through the dermis, where they will enter the ectoderm and form melanocytes in the skin and hair follicles ii. A ventral pathway through the anterior half of each somite to become sensory ganglia, sympathetic and enteric neurons, Schwann cells and cells of the adrenal medulla. k. By the time the neural tube is closed, two ectodermal thickenings become visible in the cephalic region. i. The otic placodes 1. Forms otic vesicles for hearing. ii. The lens placodes 1. 5th week, form the lenses of the eye P a g e | 10 l. Derivatives of the Ectodermal Germ Layer i. CNS and PNS ii. Placodes : lens, otic, and olfactory iii. The epidermis : hair and nail 12.Differentiation and derivatives of the mesodermal germ layer a. Intraembryonic Body Cavity divides the intraembryonic mesoderm in 3 parts i. Paraxial mesoderm 1. Beginning of 3rd week paraxial mesoderm is organized into segments known as somitomeres (in head) 2. Formation proceeds cephalocaudally 3. Somitomeres are further organized into somites which first arise in the occipital region (20th day) 4. Divides by transverse grooves into 42-44 pairs of somites (not head) a. 4 occipital b. 8 cervical c. 12 thoracic d. 5 lumbar e. 5 sacral f. 8-10 coccygeal 5. The first occipital and 5-6 coccygeal disappear 6. Remaining somites divide into 3 parts a. Sclerotome – ventromedial part i. Bones, cartilage, and ligaments b. Myotome – middle part i. Skeletal muscle of chest, abdomen, and limbs c. Dermatome – dorsal part i. Dermis ii. Subcutaneous tissue ii. Intermediate mesoderm 1. Connects paraxial mesoderm with lateral plate 2. Differentiates into urogenital structures iii. Lateral plate mesoderm 1. 2 parts a. Visceral mesoderm – surrounds wall of gut b. Parietal mesoderm – surrounds intraembryonic cavity of body wall P a g e | 11 Derivatives of mesoderm iv. Paraxial 1. Part of skull, muscles, and vertebrae v. Intermediate 1. Urogenital system vi. Lateral 1. Visceral – serous membranes around the organs 2. Parietal – serous membranes, body wall, and limbs vii. C.t. + Supportive tissue, heart, blood, lymphvessels. 13.Cephalo-caudal and lateral folding. Early differentiation of the endoderm a. Lateral folding: somites start to rapidly grow laterally which divides and splits the yolk sac into 3 parts before the gut is formed i. Intraembryonic part (which becomes gut) ii. Extraembyonic part (which stays as yolk sac) iii. Connecting duct (becomes vitelline duct) b. Cephalo-caudal folding: the curving of the embryo in a sagittal plane i. 3 parts 1. Foregut – separated from the amnion by buccopharyngeal membrane a. Created from endoderm 2. Midgut – connected with yolk sac by the vitelline duct 3. Hindgut – separated from the amnion by the cloacal membrane ii. The buccopharyngeal eventually ruptures (4th week) creating an open connection between amniotic cavity and primitive gut iii. The cloacal membrane ruptures (7th week) creates an opening for the anus c. Both types of folding partially incorporate the allantois into the body, where it forms the cloaca. The distal part of allantois remains in the connecting stalk. i. By the 5th week, the yolk sac duct, allantois and umbilical vessels are restricted to the region of the umbilical ring. d. Derivatives of endoderm i. The gastrointestinal tract is the main organ system derived from endoderm. ii. Epithelial lining of respiratory tract iii. Epithelial lining of urinary bladder and urethra iv. Epithelial lining of tympanic cavity and auditory tube v. Reticular stroma of tonsils and thymus vi. Parenchyma of thyroid, parathyroid, liver, and pancreas P a g e | 12 14.Development of the muscular system a. Skeletal muscle i. Cells from myotome (middle part of somites from paraxial mesoderm) migrate to their definite locations and differentiate to myoblast and fuse to form long multi nucleated fibers. ii. 5th week: myotome cells are divided into 2 parts. 1. Epimere a. Dorsal portion b. Forms extensor muscles c. Innervated by dorsal primary ramus 2. Hypomere a. Ventral portion b. Forms muscles of limbs and body wall c. Innervated by ventral primary ramus iii. Myofibrils soon appear in the cytoplasm, and by the end of 3rd month, cross striations appear. iv. Head musculature – All voluntary muscles of the head region are derived from paraxial mesoderm. v. Limb musculature – Mesenchyme derived from the dorsolateral cells of the somites that migrate to the limb buds to form muscles. b. Smooth muscle i. Cells of visceral mesoderm (lower part of lateral plate mesoderm) surround the gastrointestinal tract (GI tract) and vascular system ii. Differentiate into smooth muscle cells c. Cardiac muscle i. Cell of visceral mesoderm surround the endothelial heart tube ii. Differentiate to myoblasts and adhere to one another by intercalated dics iii. Myoblasts develop as in skeletal but don’t fuse, but form special bundles called Purkinje fibers 15.Growth of the bones: Increase in length and diameter a. … b. … c. … P a g e | 13 16.External appearance of the embryo, development of the fetus, full-term baby a. 2nd week i. Bilaminar germ discs ii. Amniotic cavity iii. Yolk sac iv. Extraembryonic mesoderm v. Extraembryonic coelom rd b. 3 week i. Gastrulation ii. Parachordal plate iii. Primitive streak and node iv. Notochord v. Trilaminar germ disc (intraembryonic mesoderm, endoderm, and ectoderm) vi. 2 mm embryo length rd c. 3 and 4th week i. Neurulation 1. Neural tube 2. Neural crest ii. Cephalo-caudal and lateral folding 1. Gut a. Foregut b. Midgut c. Hindgut 2. Viteline duct 3. Definitive yolk sac rd th d. 3 to 8 week i. Organogenesis 1. All major organs develop 2. Limbs develop 3. Knee and elbow joints develop 4. Fingers separate 5. Tail disappears 6. 25 mm length of embryo e. 9th week – delivery = fetal period i. Maturation of tissues and organs ii. Fast growth of body iii. 3rd month 1. Head constitutes half of the length 2. Eyes found ventrally 3. Ears found laterally P a g e | 14 iv. v. vi. vii. viii. ix. x. 4. Limbs are proportional 5. External genitalia can be seen th 4 month 1. Head a third of length 2. Eyelids 5th month 1. Muscular activity initiates (movements can be felt by mother) 2. Fetus is covered with fine hair (lanugo hair) on eyebrows and head th 6 month 1. Reddish skin 2. Wrinkled appearance because of lack of underlying connective tissue 3. Some organs function but the respiratory and CNS have not differentiated sufficiently and there is little coordination between them th 7 month 1. 90% survival rate if born at this time 2. Subcutaneous fat pads deposit 3. Maturation of nervous system 4. 25 cm th 40 week 1. Head is a quarter of body length 2. 35-50 cm length of body 3. 3 – 3.5 kg Premature < 37 weeks Postmature > 40 weeks 17.Fetal membranes, umbilical vessels and cord at full term. Formation of the placenta Fetal membranes: 1. Amnion, inner fetal membrane 2. Chorion, outer fetal membrane The placenta is a temporary organ present only in female placental mammals during gestation. The placenta is composed of two parts, one of which is genetically and biologically part of the fetus (from chorion frondosum), the other part of the mother (Decidua basalis). It is implanted in the wall of the uterus, where it receives nutrients and oxygen from the mother's blood and passes out waste. This interface forms a barrier, the placental barrier. P a g e | 15 Placentation – “Formation of the placenta” In the early weeks of development, villi cover the entire surface of chorion. Villi on embryonic pole continues to grow and becomes the chorion Frondosum (fetal placenta). The Decidua over the chorion frondosum , the decidua basalis (maternal placenta), consists of: 1. Basal layer 2. Spongy layer 3. Compact layer The compact layer, is tightly connected to the chorion frondosum. Chorion frondosum + Decidua Basalis = Placenta Other parts of chorion and decidua either degenerate or fuse with one another resulting in either the obliteration of uterine lumen or chorionic cavity. Umbilical vessels and cord The placenta is connected to the fetus via the umbilical cord, which is composed of blood vessels surrounded by connective tissue (Wharton’s Jelly). The Jelly Wharton is rich of proteoglycans and function as a protective layer for the umbilical vessels. The walls of the arteries are muscular and contain many elastic fibers. Umbilical blood vessels work in an opposite manner; Arteries carry used oxygen from the fetus and the veins carry fresh oxygen to the fetus. 18.Twinnings a. Dizygotic twins (70% of twins) i. Simultaneous fertilization of 2 oocytes and 2 different spermatozoa ii. The zygotes implant separately in the uterus and grow individually therefore having their own placentas, amniotic cavity, and chorionic cavity iii. Placentas might fuse -> Unequal growth. b. Monozygotic twins i. 1 oocyte is fertilized by 1 spermatozoa ii. Zygote splits at two cell stage and two separate zygotes develop iii. Each embryo has own placenta and amniotic cavity, and different chorionic cavity iv. If late separation occurs at bilaminar germ disc stage (before formation of primitive streak), then both embryos will have their placentas, amniotic cavities, and chorionic cavities together v. If separation fails to complete = conjoined twins a. Siamese b. Thoracopagus P a g e | 16 c. Craniopagus d. Parasitic e. Etc. 19.The factors causing malformations a. Environmental Factors i. Infections 1. Rubella 2. Toxoplasma ii. Ionizing radiation iii. Chemical agents 1. Drugs 2. Vitamins 3. Alcohol 4. Pollution iv. Hyperthermia b. Genetic mutations i. Dominant, recessive 1. Hemophilia 2. Phenylketonuria c. Chromosomal factors i. Numerical Abnormalities Trisomy 13,18, 21 Turner XO Multiple X syndromes Klinefelter XXY ii. Structural abnormalities Breaks resulted from: Deletions – Le jeune disease – “Cri du chat” Inversions Translocations d. Disruptions i. Vascular accidents 1. Bowel atresis ii. Amniotic bands 1. Amputation e. Deformations i. Mechanical forces 1. Compression 2. Clubfeet (due to compression in amniotic cavity) P a g e | 17 f. Maternal Diseases i. Diabetes P a g e | 18