Developmental Biology and Stem Cells Introduction to Development 2024 PDF

Developmental Biology and Stem Cells Introduction to Development 2024 Diego Fraidenraich [email protected] Body of the uterus. Uterine tube. Fallopian tube. Ampulla. Fimbriae. Cervix. Vagina. Ovary. Oovum transport. Sperm transport. Follicle: They contain a single oocyte (immature ovum or eg...

Developmental Biology and Stem Cells Introduction to Development 2024 Diego Fraidenraich [email protected] Body of the uterus. Uterine tube. Fallopian tube. Ampulla. Fimbriae. Cervix. Vagina. Ovary. Oovum transport. Sperm transport. Follicle: They contain a single oocyte (immature ovum or egg). They are periodically initiated to grow and develop, resulting in ovulation of usually a single competent oocyte in humans. Hypothalamus 1 Gonadotropin-Releasing Hormone (GnRH) 1st level of hormonal control. 2nd level of hormonal control. 3rd level is Ovary, and during pregnancy Placenta (involves various hormones etc). FSH = Follicle Stimulating Hormone LH = Luteinizing Hormone 2 In female: ▪FSH and LH produce cyclic changes in the ovaries - ovarian cycle. ▪FSH Stimulates development of ovarian follicles, which in turn produces estrogen. ▪LH trigger ovulation, and corpus luteum stimulates production of progesterone. ▪Both FSH and LH induce growth of uterine endometrium. An ovarian follicle is a cellular structure found in the ovary where immature eggs mature, leading to ovulation. Corpus luteum: means yellow body in Latin, is what is left of the follicle after a woman ovulates. Ovarian follicle after releasing the ovum becomes the Corpus luteum and produces progesterone which is important for endometrial gland secretion. LH Hypothalamus Gonadotropin-Releasing Hormone (GnRH) 1. FSHOvarian follicle Estrogen. 2. LH surge leads to Ovulation. 3. After ovulation, the cells of corpus luteum produce progesterone. Both FSH and LH, induce growth of uterine endometrium1, and later Progesterone secreted by the corpus luteum2 play a role in preparing the uterus for implantation of the fertilized egg. 1 2 Ovarian cycle is a 28-day cycle. Four phases of endometrial (uterine wall) change. 1. Menstrual: Functional layer of uterine wall sloughed off-5days. 2. Proliferative: Lasts 9 days, coincides with ovarian follicles. Ovulation (day 14). 3. Secretary (luteal): Lasts 13 days. 4. Pregnancy or Gravid (if fertilization takes place). 4. Ischemic (if fertilization did not happen). Ovulation Ovulation: 1. Oocyte matures during menstrual cycle, and at mid-cycle (day 14) ovum is expelled (LH surge). 2. Freshly released ovum is surrounded by Zona Pellucida, Corona Radiata & some Sticky matrix cover. 3. Ovum transport: Takes 3-4 days to reach the uterus, and if not fertilized ovum degenerates. Sperm transport occurs both in male and in female reproductive systems. FERTILIZATION Is a complex sequence of coordinated molecular events. Begins with contact between sperm & ovum, and ends with the formation of zygote. It restores normal diploid number of chromosomes (zygote). Determines chromosomal sex-XY or XX of the embryo. Due to mingling of maternal & paternal chromosomes, the zygote is a genetically unique product (recombination). It causes metabolic activation of the egg, which is necessary for cleavage & subsequent development to occur. ▪Tubal transport of egg (to reach the uterus) takes 3-4 days. ▪Unfertilized egg degenerates. Freshly released ovum is surrounded by Zona Pellucida. Corona Radiata which are layers of follicular cells. Sticky matrix cover. MATURATION OF SPERM – Capacitation. In the uterus & uterine tube the sperm undergoes ‘Capacitation’. Glycoprotein coat & seminal protein are removed from the surface of the ‘Acrosome’ (fluid in the uterine tract helps this process). MATURATION OF SPERM - Acrosomal Reaction. Capacitation is completed before starting ‘Acrosomal Reaction’release of enzymes, which facilitate fertilization (penetration of sperm through corona radiata and attach to zona pellucida). How long it takes for the sperm to reach the uterine tube? 7-9 hours How long will it survive? 24-36 hours, but never more than 48 hours. Attachment to and Penetration of the Zona Pellucida. Zona Pellucida is made of Glycoproteins, consists of ZP1, ZP2, ZP3 and ZP4. Attachment of sperm to Zona Pellucida. ▪ZP2, & ZP3 Polymerize into long filaments, linked by ZP1 and ZP4. ▪ZP3 acts as a ‘sperm receptor’ and the binding of sperm to ZP3 triggers Zonal reaction. ZP4 ZP1 : 200 k and ZP4 ZP2 : 120 k ZP3 : 83 k Prevention of ‘Polyspermy’. Attachment of sperm to ZP3, and entry through ZP cause changes within the Oocyte (zonal reaction). Fast block: rapid electrical depolarization of plasma membrane within 2-3 seconds of fusion. Fast block is short lived (5 min.) Slow block: involves Ca++ from the site of fusion, release of polysaccharides etc. Zonal reaction: Cortical granules are present within the plasma membrane of the egg. The secretory products of cortical granules diffuse into Zona pellucida and hydrolyze the sperm receptor molecules, i.e. ZP3. This eliminate additional sperm binding to the Zona pellucida. Releases lysosomal enzymes PHASES OF FERTILIZATION Capacitation and Acrosomal reaction. Passage of sperm through Corona Radiata surrounding the Zona Pellucida. Penetration of Zona Pellucida surrounding the Oocyte. Fusion of plasma membrane of sperm and oocyte. Zonal reaction. Prevention of polyspermy. Formation of Pronucleus. Formation of Zygote. Female nucleus undergoes decondensation to form female pronucleus. Within the oocyte, the sperm nucleus undergoes decondensation to form male pronucleus. Fusion of male & female pronucleus, breakdown of membrane thus forming a Zygote – “unicellular embryo” with ‘diploid’ (46) chromosomes (with recombined chromosomes). The Zygote: Genetically unique – one half of its chromosomes comes from male and the other half from the female. Zygote contains a new combination of chromosome that is different from either parents. This is the basis of “biparental inheritance & variation” of the species. Cleavage. Consists of repeated mitotic divisions of zygote, resulting in increased cell number. In human, cleavage is a slow 6 days process as the zygote move through the uterine tube. Each cell of the divided zygote is called ‘Blastomere’. each of this is a ‘blastomere’. zygote ▪During cleavage the zygote is still enclosed within the ZP. ▪As the blastomeres divide, they progressively become smaller. ▪In the beginning (8 cell stage) blastomeres are ‘loosely’ organized. ▪Then ‘compaction’ occurs-mediated by cell surface adhesion molecules. Morula: This is a 32-cell stage ‘compacted’ embryo (day 4). Compaction also results in reorganization of the blastomeres. Compaction is a prerequisite to the next step-’Segregation’. As the morula migrates, uterine fluid moves into the morula creating a ‘cavity’. This is called a “blastocyst cavity”. Blastocyst embryo consist of two types of cells (“segregation”). Outer cell layer- “Trophoblasts”, surrounding the “Inner cell mass” or the “Embryoblast”. PROPERTIES OF CLEAVING EMBRYO (BLASTOMERES): Deletion experiment. Blastomeres up to 8-cell stage is ‘totipotent’ (omnipotent). Removing one Blastomere or killing one as shown in the figure still results in development of normal offspring. One blastomere transferred into different color mother; normal offspring of the original color mother is still produced. PROPERTIES OF CLEAVING EMBRYO (BLASTOMERES). Addition experiment. If a blastomere of a different strain is introduced into a blastocyst (transferred to a foster mother), a ‘mosaic’ offspring results with color markings characteristic of the strain of the introduced blastomere is produced. If the different cells emerged from the same zygote, it is called Mosaicism. Implantation. Lower animals (sea urchins, drosophila etc) lay eggs outside the body, the eggs must contain all the material required for the embryo to develop (small amount of yolk, but hatch fast). Birds & reptiles lay eggs outside the body (contain large amount of yolk to sustain longer gestation period). Mammals on the other hand - eggs contain small amount of yolk, longer gestation hence depends on placental development for intrauterine growth. Implantation - Prior to attachment zona pellucida is shed. FORMATION OF BILAMINAR EMBRYO- Hypoblast & Epiblast. Placentation. Summary of first and second weeks in development. Cleavage – a series of mitotic division, blastomeres, and morula. Reorganization of cells of morula into inner cell mass and outer Trophoblast. Formation of blastocyst. Implantation of blastocyst. Formation of bilaminar embryo. Placentation. GASTRULATION: FORMATION OF THREE GERMINAL LAYERS. Gastrulation: is the beginning of morphogenesis. occurs during the 3rd week. begins with the formation of Primitive Streak on the surface of the epiblast. is the process by which the bilaminar embryo is converted into a Trilaminar embryo. Gastrulation. Primitive streak formation.√ Formation of Trilaminar embryo. Formation of Notochord. Formation of Somites. Neurulation. Primitive streak results from the proliferation and migration of cells cells of epiblast to the median of the embryonic disc. The streak elongates by the addition of cells to its caudal end. The primitive streak establishes in the embryo: 1. Caudal-cranial direction. 2. Left-right symmetry. 3. Dorsal (back)-ventral (front) sides. Gastrulation. Primitive streak formation. Formation of Trilaminar embryo.√ Formation of Notochord. Formation of Somites. Neurulation. Formation of Trilaminar embryo Gastrulation. Primitive streak formation. Formation of Trilaminar embryo. Formation of Notochord.√ Formation of Somites. Neurulation. Formation of the notochord, neural ectoderm Hensen’s node Gastrulation. Primitive streak formation. Formation of Trilaminar embryo. Formation of Notochord. Formation of Somites.√ Neurulation. Trilaminar embryo ~ Formation of Somite Gastrulation. Primitive streak formation. Formation of Trilaminar embryo. Formation of Notochord. Formation of Somites. Neurulation.√