Midterms - DevBio PDF

History and Developmental Biology *Molecular and cell biology tell us about how individual genes and cells work. In development this means inducing factors, their DEFINITIONS:...

History and Developmental Biology *Molecular and cell biology tell us about how individual genes and cells work. In development this means inducing factors, their DEFINITIONS: receptors, signal transduction pathways, and transcription factors. *Embryology—descriptive study of development. *Developmental Biology—study of processes and mechanisms *Genetics tells us directly about the function of an individual gene behind development; mostly experimental and how it relates to the activities of other genes. Morphology is both *Phylogenetic development—gradual evolutionary history of a a consequence and a cause of the molecular events. species *Ontogenetic development—transformation of an organism within *The first processes of development create a certain simple its own lifetime morphology, which then serves as the basis on which further rounds of signaling and responses can occur, creating a progressively more Phases of Ontogenetic Development: complex morphology. *Gametogenesis *Fertilization Development DOES NOT happen by magic. *Cleavage *Information and mechanisms at the cellular and/or molecular levels *Gastrulation are needed to accomplish development. *Organogenesis *Growth and Histological Differentiation *Metamorphosis/ Regeneration Historical Background 1) Aristotle (340 BC) *Do all parts of a developing organism come into existence together and simply grow larger? *Is development a stepwise process characterized by progressive organization and an increase in complexity? *He observed that new structures arose progressively in embryos (e.g. blood, blood vessels, heart, blood vessels around organs). This supported epigenesis (17th century), i.e., the organism developed in a stepwise fashion from an unorganized state. *He believed that the embryo was formed from menstrual blood interacting with a male vital factor present in the semen. This creative force forms the maternal substance into embryonic body parts. 2) Bonnet & Swammerdam: (17th century) *Preformation Theory: embryonic parts are already present in the sperm or egg (animalculists or ovists) which simply grow in size in development. *Leeuwenhoek and other early microscopists claimed to have seen the homunculus. 3) Caspar Friedrich Wolff (1759) *Similar to epigenetic theory but postulated that a development force inherent in the matter of the embryo directs the laying down of body parts in sequence. *He laid the foundation for the Germ Layer Theory by showing that the material out of which the embryo is constructed is, in an early stage of development, arranged in the form of leaf-like layers. Descriptive and Comparative Embryology 4) Karl Ernst von Baer (1828) - most coherent Scope Of Developmental Biology embryological data *Baer’s law: More general features that are common to all members of groups of animals are developed in the embryo earlier than the more special features which distinguish the members of the group. *Ex: brain & spinal cord, notochord, segmented muscles, aortic arches (present in all vertebrates) develop earlier than hair, feathers, limbs (which are present in various classes) 5) Fritz Muller (1864), Ernst Haeckel (1868) *Biogenetic law: features that are inherited from the common ancestor of the group have an ancient origin, and develop earliest during ontogeny *Example: “Big 4” characteristics of all embryonic chordates (notochord, a dorsal hollow nerve cord, pharyngeal slits, and a post-anal tail) appear similar despite differences in adult appearance. *Divergent features are adaptations of the embryo to its surroundings (e.g. placenta) *However, an embryo does not “pass through” the adult stages Developmental biology unites the disciplines of molecular/cellular observed in lower animals. biology, genetics, and morphology. MIDTERMS-DevBio Notes by Learn Ontogeny recapitulates *The path of development could be experimentally altered by the Phylogeny introduction of new genes, or the selective removal of genes, or by an *RECAPITULATION THEORY - alteration of the regulatory relationships between genes. the development of individual organisms (ontogeny) follows (recapitulates) the same phases of Applications the evolution of larger ancestral *Understanding of the genetic or chromosomal basis of many human groups of related organisms birth defects which are due to mutations in genes that control (phylogeny); basis of the development. It is now possible to screen for some of these, using biogenetic law DNA of the embryo or chorionic villi, using molecular biology techniques. 6) August Weismann (1883) *Germ plasm theory - every germ cell during early development *Identification of several new growth regulatory substances, some of receives a complete set of units of heredity (“ids” or Mendel’s which have entered clinical practice. For example the hematopoietic “genes”) growth factors erythropoietin and granulocyteÐmacrophage *Development involves orderly unpacking of an embryo as dictated colony-stimulating factor (GM- CSF) have both been used for some by ids; interactions between parts make epigenetic development years to treat patients whose blood cells are depleted by cancer possible chemotherapy. Some other growth factors, such as the fibroblast *Each egg nucleus contain discrete localized determinants which growth factors (FGFs) have been used to assist the healing of result to unequal distribution of nuclear components during cleavage wounds. *Cells cannot change their fate if a blastomere is lost (mosaic model of development) *Discovered stem cell biology which has now become a huge science in its own right, with many potential medical applications. Experimental Embryology 7) Wilhelm Roux (1905) Future Impact *Heat-killed one of the 2 blastomeres of a frog’s egg. *Pharmaceutical industry can design potential new therapeutic drugs *Surviving cell developed half of a complete embryo effective against cancer or degenerative diseases such as diabetes, *Results either support both preformation and mosaic development, arthritis, and neurodegeneration. or reflect use of crude techniques which possibly caused defects in the other half. *Prenatal screening towards elimination of human congenital defects. *Production of human cells, tissues, or organs for transplantation, e.g., making pancreatic β-cells for treatment of diabetes, dopaminergic neurons for treatment of ParkinsonÕs disease, and cardiomyocytes for treatment of heart disease. *Methods maybe fused with tissue engineering which can potentially generate more complex tissues and organs starting with the constituent cell types. *Produce pharmaceuticals in the milk of sheep, or vaccines in eggs. 8) H. Driesch (1891), Endres (1895), Spemann (1901), *Human genetic manipulation may cause some serious ethical and Schmidt (1903) legal problems. *If cleavage cells of a sea urchin were completely separated, each develop into a whole embryo (regulative model of Summary Points development). *Development is epigenetic. *Massive cell rearrangements and *Although it is regulated by the nucleus, it takes place primarily in the migrations precede or accompany cytoplasm. specifications of development, allowing *It involves interactions between parts. cells to acquire different functions. *The parts arise within gradient patterns or fields. *Differentiation is in essence the development of the macromolecular pattern within the cell. Lingering thoughts Analytical (modern) Developmental Biology *Developmental Biology is not only a scientific discipline. It is also a 9) T.H. Morgan (1919), Watson & Crick (1953) —units of heredity social discourse that is deeply embedded in cultural concerns. composed of sequences of DNA base triplets are transformed into an array of proteins, which acting partly on their own or through other *Reproductive cloning, assisted reproductive technology (ART), chemical components, transforms the system that is an adult abortion, stem cell differentiation, genetic enhancement, gene organism. therapy, environmental estrogens, sex selection, and teratogenesis all converge on developmental biology. *Experimental and analytical embryology demonstrated the existence * It is crucial that we should be educated toward having more social of embryonic induction: chemical signals that controlled the pathways responsibility than we have ever wanted. of development of cells within the embryo. The 20th century experiments showed where and when these signals operated, but they could not identify the signals nor the molecular nature of the responses to them. *Molecular biology had started with the discovery of the 3-D structure of DNA in 1953, and became a practical science of gene manipulation in the 1970s. Once the toolkit had been assembled it could be applied to a whole range of biological problems. MIDTERMS-DevBio Notes by Learn The Female Reproductive System Bones of the pelvis ⊳ The acetabulum of the hip joint is formed by all 3 bones and articulates ith the head of the femur. ⊳ The hip joints are joined anteriorly by the midline pubic symphysis and posteriorly to the bones of the sacrum. MIDTERMS-DevBio Notes by Learn Internal Reproductive Organs MIDTERMS-DevBio Notes by Learn  Estrogen ⊳ There are three major forms of estrogen: ○ Estrone (E1) is the primary form of estrogen that your body makes after menopause. ○ Estradiol (E2) is the primary form of estrogen in your body during your reproductive years. It’s the most potent form of estrogen. ○ Estriol (E3) is the primary form of estrogen during pregnancy. ⊳ peaks in the days leading up to ovulation ⊳ thins your cervical mucus, so it would be easier for sperms to sim through ⊳ keeps your aginal alls thick, elastic and lubricated, reducing pain associated with penetratie sex ⊳regulates important processes in your skeletal, cardiovascular, and central nervous systems that impact your overall health Glands and hormones (non-reproductive functions) ⊳ Ovaries - theca cells make androgens, and the granulosa cells take the androgen and convert it into estrogen Progesterone ⊳ Skene's glands – “female prostate”; located in the anterior aginal ⊳ an endogenous steroid hormone that is commonly produced by the all near the urethra and help lubricate the agina during sex adrenal cortex as well as the gonads, which consist of the ovaries (infection 🡪 skenitis) and the testes. ⊳ Bartholin gland - located on each side of the aginal opening and Progesterone is also secreted by the ovarian corpus luteum during make a small amount of fluid to lubricate the agina and the ula the first ten weeks of pregnancy, followed by the placenta in the later (infection 🡪 bartholinitis phase of pregnancy. ⊳ maintenance of the uterus during pregnancy Phases of Menstrual Cycle ⊳Menstruation - 0-4 days ⊳Proliferative phase - 5-13 days ⊳Ovulation - day 14 due to surge of LH at day 13 ⊳Secretory phase - corpus luteum produces estrogen and progesterone; high levels of estrogen inhibits GNRH, so FSH level drops MIDTERMS-DevBio Notes by Learn  Inguinal Canal * - roughly 4 cm long - found about halfway along the inguinal ligament (superior to it) - conveys through the abdominal wall the spermatic cord (nerves, testicular artery and vein, lymphatic structures, ductus deferens) in males, and round ligament of the uterus in females - opening within pelvis is called deep (or internal) inguinal ring - prone to herniation Male Reproductive System Anterior Abdominal Wall and the Inguinal Canal Inguinal Ligament—Where femoral vessels and nerves run to * - roughly 4 cm long - found about halfway along the inguinal ligament (superior to it) - conveys through the abdominal wall nerves, blood vessels, lymphatic structures, ductus deferens in males, and round ligament of the uterus in females - opening within pelvis is called deep inguinal ring Rectus Abdominis—Contributes to pelvic stability and trunk flexion Anterolateral walls of the abdomen - surround the rectus abdominis - flexing and rotating the trunk Parts of the male reproductive system: - support contents of abdomen - increase intra-abdominal pressure during breathing or expelling air 1.Testes (gonads) – lie within the scrotum forcefully 2.Genital ducts a. Epididymis b. Vas deferens (ductus deferens) c. Ejaculatory duct d. Urethra 3.Accessory glands a. seminal vesicles b. prostate gland c. bulbourethral glands 4. Penis MIDTERMS-DevBio Notes by Learn Parts of Reproductive System Cremaster muscle – raise the testes and the scrotum upward for warmth and protection from injury (cremasteric reflex) Dartos muscle – responsible for wrinkling the overlying skin of the scrotum MIDTERMS-DevBio Notes by Learn Gametogenesis proliferation the process begins in the gonads. The PGCs move passively (without the need for energy) with underlying somatic cells, cross epithelial barriers, and respond to cues from their environment during active migration. Active migration takes place as PGCs move towards the developing somatic gonad. Effective migration requires cell elongation and polarity. (Cell polarity refers to spatial differences in shape, structure, and function within a cell.) Environmental guidance cues are required for the PGCs to initiate and sustain their mobility. Quality Control for PGCs PGCs could contain defects that could have a negative impact on later development - genetic mutations may be acquired because of proliferation in the Sexual Cycle in Mammals blastocyst. *Sexual periodicity is much less strongly developed in the male than PGCs that are unable to in the female. complete migration are removed *Among primates, the male is sexually potent throughout life. and those that are able to *Rutting season- a brief period of pronounced sexual activity among correctly respond to migration males; always coincides with estrus or heat period of females. cues are preferred. PGCs that are able to migrate ESTRUS CYCLE - repeated series of changes in the female the fastest and reach the gonad reproductive mechanisms. are more likely to colonize it and 1.Monestrous - breeds once a year give rise to future gametes. 2.Polyestrous - several breeding periods in a year: Those that go off route or don’t reach the gonad undergo * Pregnancy, starvation, extreme exposure or sickness suppress programmed cell death (apoptosis). estrus It is thought that every step after specification may function as a * Domestication may cause shift to polyestrous rhythm selective mechanism to ensure germ cells are of the highest quality * Critical initiating factors must be present (ex. light in rabbits) and may also be important for removing PGCs with abnormal epigenetic marks and in doing so preserving the germline. Gametogenesis 1.Origin of germ cells and their migration to the gonads Teratoma 2.Proliferation of germ cells by mitosis *A teratoma is a tumor made up of several types of tissue, such as 3.Meiosis hair, muscle, teeth, or bone. Teratomata typically form in the tailbone, 4.Final stages of maturation for gametes ovary, or testicle. *Cells deposited in extragonadal areas (mediastinum, sacrococcygeal Origin of germ cells and their migration to the gonads or oral regions) die, or develop into teratomas / fetus-in-fetu which *The precursors of the gametes are the primordial germ cells may contain mixtures of differentiated tissues. (PGCs). They form outside the gonads and migrate into the gonads during development. *Primordial germ cell migration is the process of distribution Post-mortem image of the host twin, of PGCs throughout the embryo during embryogenesis. demonstrating significant *For most organisms, PGC migration starts in the posterior of abdominal distension resulting from the embryo. the parasitic twin and 3 intra-peritoneal teratomas. A teratoma complete with teeth, eyes and veins; could have a malignant potential. PGC Migration One of the functions of PGC migration is to allow them to reach the gonad, where they will go on to form sperm or oocytes. In most mammals, specification (fate determination) occurs first, followed by migration, and then the MIDTERMS-DevBio Notes by Learn  4. Differentiate between the histological features and fates of type A and type B spermatogonia. 5. Differentiate among the meiotic products of spermatogenesis morphologically, chromosome number and location within the seminiferous tubule. 6. List the events that take place during spermiogenesis. 7. What is the route of the sperms in order to reach the egg, and what accounts for their decrease in numbers along the way? 8. What is the effect of capacitation on the sperm? *Leydig cells are active in the early differentiation of the male fetus and then undergo a period of inactivity at 5 months of fetal life. At puberty, they reactivate and remain so throughout life. *They secrete androgens and insulin-like protein 3 (INSL3) that stimulates descent of the testis during development and promotes meiotic divisions in the seminiferous tubules. *Leydig cell benign tumors are related to abnormal levels of hormone production. In prepubertal boys, this leads to sexual precociousness *In adults it leads to feminization and gynecomastia (development of breast in males). Spermatogenic germ cells are bound to the Sertoli cells. Their functions include: *Nourish and protect the developing sperm cells, and spermatogenesis occurs in their recesses *Synchronize and regulate the events of spermatogenesis *Secrete critical proteins (e.g., growth factors, ABP, inhibin) that are important for testes function and spermatogenesis *Secrete tubule fluid *Phagocytose residual bodies so cellular constituents can be recycled. *Control release of sperm cells. SPERMATOGENESIS. Guide questions: *Form the immunological blood-testis barrier (autoimmune infertility 1. Name the gametogenic and non-gametogenic cells of the testis. results if this barrier is broken down) through tight junctions 2. Describe the histological and physiological differences between connecting processes of adjacent Sertoli cells. Leydig and Sertoli cells. 3. Discuss the hormonal mechanisms that regulate formation and maturation of sperm cells in the human gonad. MIDTERMS-DevBio Notes by Learn  One type B cell commits to become 10 spermatocyte (1st division, several weeks); 20 spermatocyte (2nd division, 8 hrs.); spermatids. This spermatogenic epithelium maturation cycle is completed in humans in approximately 74 days. Cells are connected to each other by intercellular bridges of cytoplasm (bodies of Regnaud) which facilitates synchronous division and differentiation of sperm-producing cells. Protamine mRNAs are synthesized, but are translated only at the spermatid stage resulting to condensation of chromosomes; If this takes place earlier, sterility results. 3. Spermiogenesis (spermatid metamorphosis) a. Formation of the acrosome * Derived from Golgi bodies; acrosomal granule which contains enzymes to dissolve egg envelopes during fertilization enlarges and acrosomal cap forms from walls of vacuole * In other animals, acrosomal cones form rudiment of acrosomal SPERMATOGENESIS filament. In humans, this whole process is completed in approximately 74 * As acrosomal cap forms, nucleus rotates to face basal membrane of days. tubule. 1. Mitotic multiplication b.Condensation of the nucleus At birth, germ cells are recognized in sex cords of human * Loss of water and other nuclear structures except condensed testis as pale cells surrounded by Sertoli cells. chromatin Before puberty, sex cords acquire a lumen and become * Head may present varied shapes: ovoid and flattened from sides seminiferous tubules. (man), with pointed tip (rodents), corkscrew (birds), round (molluscs) The germ cells of the seminiferous tubules are diploid * About 10% of sperms are abnormal with defective heads or tails, spermatogonia. and variability in head size; greater than 20% may result in reduced Spermatogonia maintain their numbers throughout life fertility. by mitotic division. They become subdivided into type Ad (mitotic stem/reserve cells) c. Formation of neck, middle piece, and tail and type Ap spermatogonia which divide by mitosis for self- * A proximal centriole is located at the posterior surface of nucleus, renewal. and the distal centriole gives rise to axial filament of flagellum. Daughter cells of type Ap spermatogonia can give rise to type B * The distal centriole and axial filament in midpiece are surrounded by cells, which differentiate to become sperm-producing cells or fused mitochondria. preleptotene spermatocytes * A critical molecule for flagellar function is dynein, a protein attached to microtubules. Lack of this protein causes male sterility 2. Meiosis in Kartagener’s syndrome. One type B cell commits to become 10 spermatocyte (1st division, several weeks); 20 d. Shedding of most of the cytoplasm spermatocyte (2nd division, 8 hrs.); spermatids. * Sertoli cells degrade residual cytoplasm shed during 2. Meiosis spermatogenesis. MIDTERMS-DevBio Notes by Learn  OOGENESIS. Guide questions: 1. What are the gametogenic and non-gametogenic cells of the human ovary? 2. Describe the roles played by hormones in regulating the female menstrual cycle. 3. Describe the histological changes in the ovaries and the uterus during the proliferative, secretory and luteal phases. Correlate these changes vis-a-vis hormonal fluctuations. 4. Differentiate between: primordial follicle vs. primary follicle; secondary follicle vs. Graafian follicle; corona radiata vs. zona radiata; granulosa vs. thecal cells; corpus luteum vs. corpus albicans. 5. What activates the egg when it resumes its meiotic division after each arrest? MIDTERMS-DevBio Notes by Learn 1) Prenatal Maturation *PGCs arrive in female gonad at 3rd month, differentiate into oogonia, and divided by mitosis for a total of ~24 cell divisions. * By the 5th month, total # cells reach a maximum of 7 million. * Some oogonia mature to form 10 oocytes. * Continual decline until ovulation, menopause, death. a)primordial and primary follicle *Flat cells from surface epithelium of ovary (stromal cells) surround the 1° oocytes to form a primordial follicle. * Some oogonia and 1° oocytes degenerate (atresia) until the 7th month. * Remaining cells are estimated to be between 700,000 to 2 million. * Surviving oocytes enter meiosis I. Meiosis is arrested at diplotene. * By birth the complex of 1° oocyte and complete layers of follicle cells is called the primary follicle. 2) Postnatal Maturation *At puberty, approximately 40,000 cells survive; fewer than 500 will be ovulated; 5 to 15 primordial follicles mature with each ovarian cycle. *The LH surge of ovulation disrupts gap junction connections that * The oocyte undergoes a 500-fold increase in volume (10 μm in a releases meiotic inhibition, and allows the oocyte to resume meiosis II primordial follicle to 80 μm in a fully developed 10-12 hrs. before ovulation, with polar body I resting in its perivitelline follicle). space. * Concomitant with oocyte growth is an increase in the number of * Due to the LH surge, prostaglandins and oxytocin, the female may follicular granulosa cells, surrounded by stromal cells known as theca experience the mild to moderate Mittelschmerz pain of ovulation, and folliculi. a slight rise in basal body temperature (used in rhythm method of contraception). a) * At metaphase II, the ovum is ovulated surrounded by the zona *Granulosa cells and oocyte secrete glycoproteins on surface of pellucida and corona radiata. oocyte, the zona pellucida. * Fertilization may now take place. * Microvilli of follicular cells and oocyte interdigitate in zona pellucida which forms the zona radiata. * Superficial layer of follicle cells on zona pellucida is referred to as the corona radiata. * The 1° follicle enlarges and develops into a preantral follicle, which is the first stage of FSH receptivity, as now the follicle has acquired FSH receptors. * Proliferation of granulosa cells is mediated by a paracrine factor, GDF9 or activin, of the TGF-β family, and enhanced by the actions of FSH. * Granulosa cells secrete growth and differentiation factors that allow the oocyte to grow. * The oocyte maturation inhibitor (OMI), or meiotic inhibitory factor is secreted by follicular cells into the oocyte via gap junctions. * This arrest permits it to accumulate food reserves, mRNA, rRNA, cortical granules, morphogenetic factors, and protective chemicals (UV filters and DNA repair enzymes, distasteful chemicals, antibodies). b.Secondary follicle * Any follicular growth onward will require gonadotropin interaction with steroid hormones, and various peptides released by the dominant follicle. * Fluid-filled spaces appear between granulosa cells, coalesce & form the antrum, filled with a complex mixture of proteins, hormones, and other molecules synthesized or absorbed by the egg from other cells. * Nucleus (germinal vesicle) increases in size due to production of nuclear sap. * Amplification (oocyte lampbrush chromosomes) of gene copies for products needed in large quantities in the egg (mRNA, rRNA for chorion proteins) take place. c.Tertiary, vesicular, or Graffian follicle Antrum enlarges; granulosa cells around oocyte forms cumulus oophorus. Oocyte is surrounded by the theca externa, the connective tissue which merges with the ovarian stroma; and the theca interna, which synthesize the enzyme aromatase converting theca-derived androgens to estrogens. MIDTERMS-DevBio Notes by Learn Fertilization ▪ In mammals, only acrosome-intact sperms bind to ZP3 (as many as Generally consists of four major events: 1500 sperms bind to a mouse egg in vitro). 1. Contact and recognition between sperm and egg. In most cases, ▪ Binding to the egg would be accomplished by formation of this ensures that the sperm and egg are of the same species. enzyme-subtrate complex, with ZP3 as substrate. 2. Regulation of sperm entry into the egg. Only one sperm can ▪ Each sperm has galactosyl transferase (GalTase) enzyme on its ultimately fertilize the egg. This is usually accomplished by head, that transfers a galactosyl group from one molecule to another allowing only one sperm to enter the egg and inhibiting any (sperm of mutant mice that lack the GalTase gene/ GalTase- null mice others from entering. do not undergo the acrosome reaction and show extremely poor 3. Fusion of the genetic material of sperm and egg (amphimixis). penetration into the ZP). 4. Activation of egg metabolism to start development. ▪ At binding, the cortical granules are intact; acrosome is also intact Contact Recognition between Sperm & Egg 1. Chance encounters – swimming movements of enormous numbers of spermatozoa, with the egg being a relatively large target. 2. Chemotaxis- in many species, eggs secrete diffusible molecules that attract and activate the sperm. e.g., ▪ Fish sperms are observed to converge at the chorionic micropyle due to chemical attractants ▪ For instance, Resact isolated from the egg jelly of the sea urchin Arbacia punctulata cause sperms to aggregate near egg Mammalian Fertilization ▪ Fertilization occurs in the ampullary region of the human uterine tube. 200 to 300 million sperms are deposited in the female tract: 300 to 500 reach the site of fertilization. ▪ In mammals, sperm must undergo a period of conditioning, or capacitation, (about 7 hrs. in man) in the female tract before they are capable of fertilizing the egg. 3. ACROSOME REACTION: stimulation of the sperm by agents from the cumulus oophorus and corona radiata followed by binding to the ZP, leads to the acrosome reaction. ▪ The acrosome reaction is characterized by Na+ and Ca+2 influx and H+ efflux through sperm head plasma membrane. ▪ The latter involves an ATP-dependent H+ pump and leads to an increase in intracellular pH. ▪ Ca+2 is a known mediator of biomembrane fusion Gamete Binding & Recognition in Mammals 1. ATTACHMENT- a relatively loose, non-specific association between sperm and the egg’s thick extracellular coat, the zona pellucida. ▪ The ZP is a species-specific barrier to sperm binding and 4. SPERM PENETRATION penetration ▪ Mammalian penetration of the zona pellucida is accomplished by ▪ Some cross-species fertilization can occur (horse and donkey = sperm tail hyperactivated motility. mule; ▪ Sperm tail hyperactivation is responsible for the physical penetration some species of monkeys can cross fertilize) of the oocyte and caused by influx of Ca+2 via tail transmembrane ▪ Remove the ZP and other species sperm can channel fertilize the egg (in the Hamster Test for Male proteins called CatSpers (cation channels of sperm). Hence, Fertility, the human sperm can fertilize the activation of CatSpers is required for male fertility zona-less hamster egg. ▪ Three ZP glycoprotein sperm receptors are synthesized by a 5. SPERM-EGG FUSION growing oocyte: the species-specific ZP3, a polypeptide chain to ▪ Sperm motility ceases at the time of fusion. which asparagine (N-linked) and serine-threonine-linked ▪ The driving force for engulfment of the sperm comes from the (O-linked) oligosaccharides are covalently attached. contraction of actin and myosin in egg’s cortex. ▪ They assemble into long, interconnected filaments with ZP1 ▪ After fusion, the head, midpiece, and the tail of the human and ZP2. sperm enter the oocyte cytoplasm, but the plasma membrane ▪ ZP3 mediates sperm-specific egg binding; chemical removal of is left behind on oocyte surface. Later the tail is detached & O-linked oligosaccharides from ZP3 destroys its ability to serve as a degenerates. sperm receptor. ▪ A mammalian sperm interacts tangentially with the egg plasma ▪ ZP2 mediates subsequent sperm binding. membrane so that fusion occurs at the equator of the sperm ▪ ZP1 cross-links ZP2 and ZP3 as protein meshwork; not essential for head. fertilization but is important for structural integrity of zona pellucida; ▪ In mice, the ZP is about 6 mm thick, and a sperm crosses it at a mice that lack ZP1 produce embryos that hatch prematurely causing rate of 1 mm/min developmental problems 2. BINDING- attached sperms form relatively tenacious association with eggs. MIDTERMS-DevBio Notes by Learn  6. EGG ACTIVATION ▪ Alkalinization of the cytoplasm precedes an increase in oxidative metabolism, providing the stimulus for egg activation. ▪ Once a sperm has entered the egg, a sperm-soluble factor triggers the oocyte to complete its 2nd meiotic division, and the 2nd polar body is extruded 7. FUSION OF MALE AND FEMALE PRONUCLEI (AMPHIMIXIS): ▪ Glutathione of egg cytoplasm reduces disulfide bonds in protamines of sperm chromatin, causing the male pronucleus to uncoil and become vesicular. ▪ It moves towards the area of fusion together with the centrosome (spindle apparatus of 1st and subsequent cell divisions is provided by spermatozoon ▪ Each pronucleus replicates its DNA as it migrates. ▪ Their nuclear membranes break at point of contact and contents become surrounded by nuclear membrane of zygote nucleus MIDTERMS-DevBio Notes by Learn