General Embryology - Spermatogenesis and Oogenesis PDF
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DR. YOUSSEF SHOUKRY
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This document provides a comprehensive overview of spermatogenesis and oogenesis, covering definitions, stages, and key structures involved in each process. It also includes a discussion of possible anomalies.
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# General Embryology - Spermatogenesis and Oogenesis ## Spermatogenesis - **Definition**: A process by which complete motile spermatozoa are produced from primordial male germ cells called spermatogonia. Spermatogonia are transformed into sperms in the testis. - **Start**: It starts after puberty...
# General Embryology - Spermatogenesis and Oogenesis ## Spermatogenesis - **Definition**: A process by which complete motile spermatozoa are produced from primordial male germ cells called spermatogonia. Spermatogonia are transformed into sperms in the testis. - **Start**: It starts after puberty and continues into old age. - **Duration**: It takes about 60-64 days (including the process of spermio-genesis). - **Site**: In the seminiferous tubules of the testis. ### **Stages of Spermatogenesis** - **Stage of proliferation**: The spermatogonium divides by mitosis to form 2 daughter spermatogonia (each contains 23 pairs of chromosomes, 2n). - **Stage of growth**: Daughter spermatogonia enlarge to form primary spermatocytes (2n), the largest germ cells in the seminiferous tubules of the testis. - **Stage of maturation**: - **First meiotic division**: Primary spermatocyte divides by meiosis into 2 secondary spermatocytes (each contains 23 chromosomes). - **Second meiotic division**: Secondary spermatocyte divides into 2 spermatids (each contains 23 chromosomes). - **Stage of transformation**: Spermatids change into motile sperms: - **Nucleus condenses**: Into ovoid chromatin to form the head of the sperm. - **Aggregation of Golgi complex**: In the supranuclear area forming a big acrosomal vesicle (acrosomal cap) which covers the anterior half of the head. Acrosome secretes enzymes which facilitate penetration of the ovum. - **Centrioles**: The two centrioles (anterior and posterior), the axial filament starts from the posterior one. - **Mitochondria**: They collect in a helical sheath in the middle piece around the axial filament. - **Cytoplasm**: Most of it is shed. ## Structure of Sperm - **Head**: Acrosome + nucleus. - **Neck**: Follows the head and contains the centrioles. - **Body**: Middle piece containing the mitochondria. - **Tail**: End piece containing the axial filament. ## Seminal Fluid - **Spermatozoa**: Produced by the testis. - **Fluid secretions**: From the accessory sex glands: seminal vesicles, prostate and bulbo-urethral glands. - Seminal fluid is an alkaline fluid that contains fructose and Vitamin C. - The normal amount of one ejaculate is 3-5 cc. - Each cc. contains about 100 million sperm. - Men whose semen contains 20 million sperms per milliliter are probably fertile. - In ejaculation, spermatozoa pass through the duct of epididymis, vas deferens, ejaculatory duct and finally the urethra. - Sperms remain viable (able to fertilize ova) for only 48 hours after ejaculation. ## Anomalies of Spermatogenesis - **Abnormal forms of sperms**: Giant, dwarf, bicephalic... may be present in the semen, but should not exceed 20% of the total count. - **Necrospermia**: Dead sperms in the ejaculate. - **Oligospermia**: Sperm count is below normal. - **Azospermia**: Complete absence of sperm in the semen. ## Oogenesis - **Definition**: Changes that take place in the ovary during which the oogonia cells (primordial female germ cells) differentiate into secondary oocytes (ready for fertilization). - **Start**: From the 3rd month of intrauterine life till birth. Then continues after puberty (during each ovarian cycle), and after fertilization & ends at menopause. - **Site**: In the ovary. ### **Stages of Oogenesis** - **During Fetal Life (Pre-natal maturation):** - **Proliferation**: During early fetal life, oogonia proliferate by mitotic division giving daughter oogonia (each contains diploid (46=2n) number of chromosomes). - **Growth**: Each daughter oogonium increases in size to form primary oocytes, which contain (44 autosomes + 2X) chromosomes. - A primary oocyte, together with flat epithelial cells surrounding it, is known as a primordial follicle. - When the surrounding flat cells become cuboidal, the follicle is called a primary follicle. - All oogonia enlarge to form primary oocytes before birth. Primary oocytes begin the 1st meiotic division before birth, but completion of prophase does not occur until adolescence. - **Post-natal maturation:** - **At time of birth**: All primary oocytes have reached the 1st meiotic division and remain dormant until puberty under the effect of oocyte maturation inhibitor secreted by the follicular cells. - **At puberty**: - **First meiotic division**: The 1ry oocyte divides by meiosis giving: - 2ry oocyte (haploid (23=1n) number of chromosomes, 22+X). - 1st polar body (also haploid) receives a little amount of cytoplasm and is extruded to the perivitelline space where it degenerates. - **Second meiotic division**: Occurs after ovulation, only if fertilization occurs; the 2ry oocyte divides by mitosis into: - Mature ovum (haploid number of chromosomes, 22+X). - 2nd polar body (also haploid) extruded to the pervitelline space and degenerates. **N.B.:** - The number of 1ry oocytes for each ovary at birth is 700,000-2,000,000. - The number of 1ry oocytes for each ovary at puberty is 40,000; the rest undergo degeneration (atresia). - The long duration of the 1st meiotic division (up to 45 years) may account in part for the relatively high frequency of meiotic errors, such as non-disjunction (failure of paired chromatids to dissociate), that occur with increasing maternal age. - No primary oocytes form after birth in females, in contrast to the continuous production of primary spermatocytes in males. ## Differences Between Spermatogenesis and Oogenesis | Feature | Spermatogenesis | Oogenesis | |----------------|-----------------------------|-----------------------------| | Location | Testis | Ovary | | Start | After puberty | During intrauterine foetal life | | Duration | Continues till old age | Ends at menopause | | Daughter cells | 4 equal spermatids | 1 ovum and 3 polar bodies | | Transformation | Spermatid to motile sperm | No stage of transformation | ## Differences Between a Sperm and an Ovum (2ry Oocyte) | Feature | Sperm | Ovum | |----------------|----------------------------|----------------------------| | Size | Small (60 microns) total length | Large (120 microns) | | Number | Numerous (100 million/cc) | Rare (400) per cycles | | Motility | Highly motile | Immotile | | Coverage | Not covered by other cells | Covered by other cells | | Cytoplasm | Little cytoplasm | Abundant cytoplasm | | Types | 2 types: 22 + X or 22 + Y | Only 1 type: 22 + X | ## Female Reproductive Cycles Starting from puberty, females undergo reproductive cycles in the ovaries and uterus every 28 days. These cyclic changes are under the effect of hormones: FSH & LH (secreted by pituitary gland) and estrogen & progesterone (secreted by the ovary in response to pituitary hormones). ### **1) Ovarian Cycle** At puberty, under the influence of FSH, a number of 1ry oocytes begin to mature with each ovarian cycle, however, usually, only one primary follicle develops into a mature follicle & ruptures through the surface of the ovary to expel the oocyte. #### **Phases of the Ovarian Cycle:** - **Follicular phase (14 days)**: Controlled by FSH hormone & ends by ovulation. - **Follicular cells**: The follicular cells surrounding the primary oocyte proliferate to form several layers of granulosa cells (stratum granulosum) that become separated from the oocyte by a hyaline thick membrane termed zona pellucida. - **Stroma cells**: Stroma cells from the ovarian cortex condense around the stratum granulosum to form a sheath (theca) for the follicle. The theca divides into 2 layers: - **Theca interna**: Consists mainly of cells and blood capillaries. - **Theca externa**: Consists mainly of fibrous tissue and larger vessels. - **Fluid filled spaces**: Fluid filled spaces appear amidst the follicular cells and coalesce to form a single large cavity called the follicular antrum that separates the granulosa cells into 2 parts: - **Outer part**: Termed stratum granulosum. - **Inner part**: Termed corona radiata around the oocyte + cumulus ovalis (cumulus oophorus) attaching the oocyte to one side of the follicle. - **Growing follicle**: The oocyte & the surrounding follicular cells, in addition to the surrounding 2 theca sheathes, is now called the growing follicle or Graafian follicle. - **Theca interna**: Theca interna is the main source of estrogen hormone (the main ovarian hormone that regulates reproductive organs). - **Maturity**: With each Ovarian Cycle, a number of follicles begin to develop, but only one reaches full maturity while others degenerate and become atretic. - **Luteal phase (post ovulatory phase, 14 days)**: - **Corpus luteum**: It follows ovulation and leads to the formation of corpus luteum under the effect of luteinizing hormone (LH). - **Progesterone**: The corpus luteum will secrete progesterone hormone which is responsible for the secretory stage of the uterine cycle. ### **2) Uterine Cycle** Changes occur every 28 days in the endometrium of the uterus under the influence of ovarian hormones. During each ovarian cycle, the endometrium of the fundus and body of uterus undergoes changes that end bleeding (menstruation). The mucosa of cervix and uterine tubes are not involved in these cyclic changes. #### **Stages of the Uterine Cycle** - **Stage of menstruation (bleeding)** (duration: about 5 days): - **Blood lost**: About 50-60 cc. - **Contents**: Consists of blood and pieces of superficial layers of the endometrium. This blood does not clot. - **Stage of repair** (duration: about 3 days; from the 6th to the 9th day of menstrual cycle): - **Epithelial cells**: Epithelial cells from the bases of the uterine glands divide & spread to cover the raw endometrium by flat cells. - **Stage of proliferation** (duration: 7 days; from the 10th to the 16th day of menstrual cycle): - **Cells**: The cells become low columnar. - **Growth**: The endometrium grows to become 3 mm. thick. - **Uterine glands**: The uterine glands become longer & straight; later they become slightly convoluted. - **Stage of secretion** (duration: from the 17th day to the 28th day of menstrual cycle): - **Endometrium**: The endometrium becomes thicker (5-7 mm.) and is formed of 3 layers: superficial compact layer, middle spongy layer, and deep basal layer. - **Cells**: The cells become columnar. - **Uterine glands**: The uterine glands become more convoluted and full of secretion. - **Spiral arteries**: The spiral arteries become dilated and tortuous. - **Endometrium**: The endometrium becomes edematous and soft. **N.B.:** This stage is under the effect of the hormone progesterone secreted by the corpus luteum. **Possibilities on the 28th day of the menstrual cycle:** - **Fertilization had occured**: The endometrium becomes thicker & more vascular; no menstruation occurs. - **Fertilization did not occur**: Menstruation occurs on the 28th day and the cycle is repeated. ## Events of the First Week - **Definition.** It is the process of union between the male and female gametes to form the zygote. - **Site**. The lateral 1/3 of the uterine tube. ### **Steps of Fertilization** - **Preparatory steps:** - **Insemination**: After insemination, the sperms pass rapidly from the vagina into the uterus and the uterine tube (movement of sperm by its tail is helped by contraction of the uterus and uterine tubes). - **Fertilization**: Out of the 200-300 million ejected sperms in female genitalia, only 300-500 reach the site of fertilization. Only one of these succeeds to penetrate the secondary oocyte. - **Sperm viability**: The power of fertilization of the sperm is lost within 48 hours after ejaculation. - **Capacitation**: The sperms cannot fertilize an ovum before 2 processes happen: - **Capacitation (activation)**: Occurs in female genital organs for 7 hours during which the glycoprotein coat is removed from the plasma membrane overlying the acrosomal region. - **Acrosomal reaction**: Occurs after binding to the zona pellucida leading to the release of enzymes needed to penetrate the zona pellucida. - **Hyaluronidase**: Digests the corona radiata. - **Trypsin-like substance & zonalysin**: Penetrates the zona pellucida. - **Penetration of zona pellucida**: The release of acrosomal enzymes allows sperm to penetrate the zona, thereby coming in contact with the plasma membrane of the oocyte. - **Permeability**: Permeability of the zona pellucida changes when the head of the sperm comes in contact with the oocyte surface. - **Lysosomal enzymes**: This contact results in the release of lysosomal enzymes from cortical granules lining the plasma membrane of the oocyte. - **Zona reaction**: In turn, these enzymes alter properties of the zona pellucida (zona reaction) to prevent other sperm penetration. - **Union of 2ry oocyte + sperm cell membranes**: As soon as the sperm contact oocyte cell membrane, both cell membranes fuse. Then, the oocyte responds in 3 different ways: - **Vitelline membrane**: The oocyte membrane becomes impenetrable to other sperms. - **Zona pellucida**: The zona pellucida prevents entry of other sperms. - **Reduction division**: The oocyte finishes its 2nd step of reduction division to give 2nd polar bodies + the female pronucleus of the mature ovum. - **Pronuclei**: The head of the sperm becomes rounded (swollen) to form male pronucleus that unties with the female pronucleus to finish the process of fertilization. The activating factors are probably carried by the spermatozoon. - **Zygote**: The male and female pronuclei (each containing 23(n) chromosomes) unite together to form one nucleus (containing 46 chromosomes, 2n) and the fertilized ovum is now called the zygote. ## Results of Fertilization - **Meiotic division**: The oocyte completes its second meiotic division. - **Chromosomes**: The number of chromosomes become 46 again (restoration of normal chromosomal number, diploid). - **Sex determination**: a. Sperm of (22+Y) + ovum of (22+X) --> (44+XY) male offspring. b. Sperm of (22+X) + ovum of (22+X) --> (44+XX) female offspring. - **Determination of general characters**: Determination of the general characters by the autosomes. This allows variation in the human species through mingling of maternal and paternal chromosomes. - **Cleavage**: The zygote begins to divide to form the different organs. ## In Vitro Fertilization (IVF) - **Cases of sterility**: In cases of sterility, especially Fallopian tube occlusion, in vitro fertilization can be used as a treatment. - **Process**: Secondary oocytes are obtained from the wife by an endoscope and fertilized by sperms of the husband on a glass plate. - **Transfer**: Under special circumstances, a dividing zygote is obtained & transferred to the uterus of the wife. ## Cleavage Of The Zygote - **Definition**: Repeated division process (series of mitosis) by which a unicellular zygote is transformed into a multicellular mass of embryonic cells (blastomeres). These blastomeres become smaller with each successive cleavage division. - **Functions of zona pellucida**: - **Zonal block**: Prevents penetration of another sperm after fertilization. - **Blastomere cohesion**: Keeps blastomeres together during cleavage. - **Prevent adhesion**: Prevents adhesion of blastomeres to the uterine tube. - **Start**: Approximately 30 hours after fertilization. ### **Steps of Cleavage** - **Early stages**: After fertilization, the zygote shows 2 main features: - **Mitotic division**: It undergoes repeated mitotic divisions. - **Movement**: It moves towards the uterine cavity (by action of cilia of cells lining the uterine tube). - **Morula stage**: The zygote, by mitotic division, passes through stages: 2-cell stage, 4-cell stage, & so on till morula stage (12-16 cell stage) after 72 hours. - **Morula structure**: The morula will continue division, and the inner cells of the morula constitute the inner cell mass (embryo proper), and surrounding cells compose the outer cell mass (trophoblast). ### **Blastocyst Formation** - **4th day**: It reaches the uterine cavity on the 4th day after fertilization where it undergoes the following changes: - **Zona pellucida**: The zona pellucida disappears. - **Blastocele**: Fluid absorbed from the uterine cavity and/or secreted by trophoblast, accumulates in the morula leading to the formation of blastocyst. The cavity of the blastocyst is called blastocele. - **Cell masses**: The cells become arranged into 2 masses: - **Trophoblast**: Outer cell mass forms the trophoblast. - **Inner cell mass**: Inner cell mass (formative cell mass or embryoblast) will give rise to the embryo. - **Embryonic and abembryonic poles**: The pole of the blastocyst at which the inner cell mass is attached is termed the embryonic pole while the opposite one is the abembryonic pole. - **Results of cell cleavage**: Increase in number of cells & decrease in size of cells to reach normal size of the species. ## Embryonic stem cells (ES cells) - **Derivation**: Embryonic stem cells (ES cells) are derived from the inner cell mass of the embryo. - **Potential**: Because these cells are pluripotent and can form virtually any cell or tissue type, they have the potential for curing a variety of diseases, including diabetes, Alzheimer's and Parkinson's diseases, anemias, spinal cord injuries, and many others. ## Implantation - **Definition**: It is the process of embedding of blastocyst into the uterine wall. - **Site**: The normal site is the upper part of the body of the uterus, mainly the posterior wall, in the midline, near the fundus. ### **Steps of Implantation** - **6th day**: At the 6th day after fertilization, the trophoblastic cells over the embryonic pole adhere to the uterine wall then it erodes the endometrium and the whole blastocyst progressively penetrates it (start of implantation). - **2 layers**: The trophoblastic cells rapidly proliferate and become formed of 2 layers as soon as it touches the endometrium (Decidua): - **Outer Syncytial trophoblast**: Formed of a mass of protoplasm with randomly dispersed nuclei. - **Inner Cellular trophoblast (cytotrophoblast)**: Formed of cells with well-defined walls. - **9th day**: At about the 9th day, the blastocyst becomes more deeply embedded in the endometrium, and the penetration defect in the surface epithelium is closed by coagulation plug. - **11th and 12th days**: At the 11th and 12th days, the blastocyst becomes completely implanted, and the surface epithelium is restored. **N.B**: The blastocyst is superficially implanted in the compact layer of the endometrium and is deriving its nourishment from the eroded maternal tissues. ## Formation Of The Extra-Embryonic Mesoderm - **Origin**: Extra-embryonic (1ry) mesoderm arises from the hypoblast (1ry endoderm). - **Surrounding**: It surrounds the amnion and the yolk sac and separates them from the trophoblast. - **Extra-embryonic coelom**: Small cavities appear in this mesoderm, that coalesce together to form a single cavity called the extra-embryonic coelom, which splits the mesoderm into two layers: - **Outer layer**: Lining the trophoblast and covering the amnion, is called somatic or parietal layer of extraembryonic mesoderm. - **Inner layer**: Covering the yolk sac, is called visceral (splanchnic) layer of extraembryonic mesoderm. - **Chorionic plate and chorionic vesicle**: The trophoblast & the underlying somatic extra-embryonic mesoderm is called chorionic plate, and the blastocyst is now called chorionic vesicle. - **Connecting stalk**: The coelom incompletely surrounds the vesicle, as a part of the mesoderm persists without cavitation. This connects the caudal part of the embryonic disc to the wall of the chorionic vesicle. - **Blood vessels**: This area of extraembryonic mesoderm is termed the connecting (body) stalk through which foetal blood vessels pass between the embryo and placenta. - **Amniotic cavity**: Later, the amniotic cavity expands while the yolk sac shrinks, & the mesoderm covering the amnion comes in contact with that lining the chorion. - **Obliteration**: As a result, the extra-embryonic coelom becomes greatly obliterated. ## Development Of The Chorionic Villi The wall of the chorionic vesicle is termed the chorion. - **Layers**: It is composed of 3 layers (from outside to inside): - **Syncytiotrophoblast** - **Cytotrophoblast** - **Somatic layer of primary mesoderm** - **Chorionic villi**: The outer surface of the chorionic vesicle shows a large number of proliferations termed chorionic villi. - **Induction**: Thought to be induced by the underlying extra-embryonic somatic mesoderm, distributed as follows: - **Chorion frondosum**: The villi lying opposite the decidua basalis are well-developed. - **Chorion laeve**: The villi lying in contact with the decidua capsularis are less developed (atrophic). ## Types of Chorionic Villi - There are 3 types of villi according to the complexity of their structure: - **Primary villi**: Formed of the 2 layers of trophoblast, separated from each other by lacunae (spaces filled with maternal blood). - **Secondary villi**: 1ry villi invaded by cores of m mesoderm. - **Tertiary villi**: 2ry villi invaded by foetal blood vessels within the core of the 1ry mesoderm. ## Development of Placenta - **Definition**: The placenta is the primary site of nutrient and gas exchange between the mother and fetus. - **Components**: The placenta develops from two components: - **Fetal part**: Chorion frondosum. - **Maternal part**: Decidua basalis. - **4th month**: By the beginning of the 4th month, the placenta develops from two components. - **4th-5th month**: The decidual cells form a number of septa that project into the inter-villous space, but don't reach to the chorionic plate. These septa divide the placenta into a number of compartments called cotyledons. - **Full-term placenta**: - **Shape**: The full-term placenta is a flattened disc. - **Measurements**: - **Diameter**: 15-25 cm. - **Thickness**: 3 cm. - **Weight**: 500-600 gm. - **Coverage**: In general, it covers 25-30% of the internal surface of the uterus (its increase in thickness is due to branching of the existing villi). - **Surfaces**: - **Foetal surface**: The inner smooth surface which is covered by the amnion; the umbilical cord is attached near its centre. - **Maternal surface**: The outer rough surface that shows a number of elevated areas called cotyledons (15-20) separated from each other by grooves, representing the sites of the placental septa. ## Microscopic Structure of Placenta The placenta shows: - **Tertiary chorionic villi**: They will exhibit further changes to form foetal part of placenta: - **Stem or anchoring villi**: Extend from the chorion to get attachment to the decidua basalis. - **Free or absorbing villi**: Extend laterally to increase surface area, thus increase the change between fetal & maternal blood. - **Intervillous space**: Lined with syncytial trophoblast; it is filled with maternal blood from the maternal vessels which open into the spaces. - **Cytotrophoblastic shell**: The cytotrophoblast at the end of the anchoring villus penetrates the syncytiotrophoblast and extends in a lateral direction to fuse with similar cytotrophoblast from other villi thus forming a continuous shell surrounding the embryonic vesicle to prevent further penetration of decidua by syncytiotrophoblast. ## Placental Barrier - **Definition**: It is the membrane separating the maternal blood present in the intervillous space from the foetal blood present in the foetal vessels within the free villi. - **First half of pregnancy**: During the 1st half of pregnancy, it is thick and is composed of: - **Syncytiotrophoblast** - **Cytotrophoblast** - **1ry mesoderm** - **Endothelium of foetal blood vessels.** - **Second half of pregnancy**: By the 2nd half of pregnancy, the cytotrophoblast and primary mesoderm disappear; the other layers of the barrier become very thin and consequently more permeable allowing rapid exchange (syncytiotrophoblast + endothelium of fetal blood vessels). - **Mixing**: The maternal & foetal blood never mix together but remain always separated by a barrier except during birth, they could be mixed. ## Functions of The Placenta - - **Nutritive function**: By transporting: Water, glucose, amino acids, antibodies, antigens, free fatty acids, neutral fat, electrolytes and vitamins to the foetus. - **Respiratory function**: Exchange of oxygen & carbon dioxide takes place. - **Excretory function**: It gets rid of the few amounts of urine constituents secreted by the foetal kidney. - **Secretory function**: It secretes: Chorionic gonadotrophins, Estrogen, Progesterone & Placental lactogen. Chorionic gonadotrophins start to appear in mother's urine from the 9th day of pregnancy (detected by pregnancy tests). -**Barrier function**: It protects against the transmission of infection from mother to fetus. Antibodies also can pass from mother giving immunity to the fetus against some infections as diphtheria, measles, and small pox. But some viruses can pass as that of German measles, syphilis, poliomyelitis & AIDS. Rh factor antibodies & agglutinins can also pass. Also some drugs can pass. ## Placental Circulation - **Arterial circulation**: Fetal blood arrives to the placenta by 2 umbilical arteries which branch to form capillaries of the villi where gaseous exchange occurs with the maternal blood in the intervillous space around the villi. - **Venous circulation**: Finally, the oxygenated blood returns to the fetus by the left umbilical vein. ## Anomalies of The Placenta - **Abnormal attachment**: If the placenta is attached to the lower uterine segment (placenta previa) - **Placenta previa lateralis**: Just above internal os - **Placenta previa marginalis**: Covers internal os partially - **Placenta previa centralis**: Covers internal os completely - **Abnormal distribution of chorionic villi**: - **Diffuse placenta (placenta membranacea)**: The chorion frondosum occupies a more extensive area of the chorion - **Divided placenta**: Bipartite or tripartite; Separate accessory lobule (placenta succenturiata). - **Abnormal sites of umbilical cord attachment**: - **Battledore placenta**: The umbilical cord is attached to the margin of the placenta (normally, it is attached near its centre). - **Velamentous insertion of the cord**: The umbilical cord is attached to the adjacent foetal membranes just away from the margin of the placenta - **Chorion epithelioma**: Malignant tumour of placenta. ## Twins - **Uniovular (Monozygotic, One egg) twin**: - **Zygote**: 1 zygote - 2 embryos. - **Identical**: Identical except finger prints. Same sex. - **Placenta**: Usually single placenta & 1 or 2 amnion Sac. - **Incidence**: Incidence: 30%. - **Conjoined twins**: If the embryoblast or embryonic disc does not divide completely (incomplete separation), some identical twins become fused and various types of conjoined twins may form: - **Pygopagus**: At sacral region. - **Craniopagus**: At head region. - **Binovular (Dizygotic, Two eggs) twin**: - **Zygotes**: 2 ova + 2 sperms - 2 zygotes. - **Features**: Non identical i.e different features. - **Sex**: Same or opposite sex. - **Placenta**: Double placenta & amnion. - **Incidence**: Incidence 70% **N.B.:** The second week is known as the week of (2 s): - The trophoblast differentiates into two layers, the syncytiotrophoblast and cytotrophoblast. - The embryoblast differentiates into two layers, the epiblast and hypoblast. - The extraembryonic mesoderm splits into two layers, the splanchnic (visceral) and somatic (parietal) layers. - Two cavities, the amniotic and yolk sac cavities.