GAMETOGENESIS AND DEVELOPMENT OF THE FERTILIZED OVUM 112007

GAMETOGENESIS AND DEVELOPMENT OF THE FERTILIZED OVUM : 

GAMETOGENESIS AND DEVELOPMENT OF THE FERTILIZED OVUM

Slide 2: 

22X or 22Y SPERM OVUM 44XX or 44XY

GAMETOGENESIS : 

GAMETOGENESIS

GAMETOGENESIS : 

GAMETOGENESIS Gametogenesis is the process of forming gametes (by definition haploid, n) from diploid cells (2n) of the germ line.

GAMETOGENESIS : 

GAMETOGENESIS Meiosis reduces the number of chromosomes by half (haploid, n). It contributes to genetic diversity. Mitosis maintains the number of chromosomes (diploid, 2n). It ensures that every cell carries the same set of chromosomes.

GAMETOGENESIS : 

GAMETOGENESIS MEIOSIS MITOSIS PROPHASE METAPHASE ANAPHASE TELOPHASE MEIOSIS I PROPHASE I METAPHASE I ANAPHASE I TELOPHASE I MEIOSIS II PROPHASE II METAPHASE II ANAPHASE II TELOPHASE II 44XY 44XY 22Y 22Y 22X 22X 44XY 44XY

GAMETOGENESIS : 

GAMETOGENESIS IN FEMALES Oogenesis is the process of forming an ovum by meiosis in specialized gonads known as ovaries. The female produces one egg per menstrual cycle (approximately 28 days).

GAMETOGENESIS : 

GAMETOGENESIS MEIOSIS MEIOSIS I MEIOSIS II 44XY 22Y 22Y 22X 22X OOGENESIS OVUM

GAMETOGENESIS : 

GAMETOGENESIS IN MALES Spermatogenesis is the process of forming spermatids by meiosis in specialized gonads known as testes. The male produces 200M sperm per day.

GAMETOGENESIS : 

GAMETOGENESIS MEIOSIS 44XY 22Y 22Y 22X 22X SPERMATOGENESIS MEIOSIS I MEIOSIS II

GAMETOGENESIS : 

GAMETOGENESIS SPERMATOGENESIS OOGENESIS OVUM

PRIMORDIAL GERM CELLS : 

PRIMORDIAL GERM CELLS Sperm and eggs arise from primordial germ cells (PGCs). These cells arise at about the 4th week of gestation in the yolk sac endoderm.

PRIMORDIAL GERM CELLS : 

PRIMORDIAL GERM CELLS The PGCs migrate by ameboid movement into the dorsal mesentery and then laterally into the gonadal ridges (near the site of the future kidneys). At the time of their arrival in the gonadal ridge, the female and male embryos are morphologically indistinguishable.

PRIMORDIAL GERM CELLS : 

PRIMORDIAL GERM CELLS Shortly after the PGCs take up residence in the gonadal ridge, at about 6th week of gestation, the differences in sexes become apparent. MALE gonad develops sex cords FEMALE MALE FEMALE gonadal ridge unchanged in morphology

ADULT GONADS : 

ADULT GONADS FEMALE MALE

PRIMORDIAL GERM CELLS : 

PRIMORDIAL GERM CELLS MALE PGCs are called spermatogonia FEMALE MALE FEMALE PGCs are called oogonia

MITOSIS : 

MITOSIS In females, the pattern of differentiation is markedly different from the males. Upon arrival in the gonadal ridge, the oogonia undergo MITOSIS, in which their numbers increase to 6-7 million. MITOSIS 6 - 7 M

OOGENESIS : 

Week 12: oogonia switch from mitosis to MEIOSIS. There is no further formation of oogonia. OOGENESIS Week 12: oogonia switch from mitosis to MEIOSIS. There is no further formation of oogonia. These cells that switch to meiosis are now called primary oocytes. Each cell begins oogenesis as a primary oocyte. 6 - 7 M

OOGENESIS : 

OOGENESIS MEIOSIS MEIOSIS I MEIOSIS II MEIOSIS I MEIOSIS II 6 - 7 M WEEK 12

PRIMARY OOCYTE : 

PRIMARY OOCYTE The cells replicate their DNA for the 1st meiotic division and then undergo crossing over during prophase I. Points of crossing over are called chiasmata.

PRIMARY OOCYTE : 

PRIMARY OOCYTE While still in prophase I & with the points of chromosome synapsis still visible, meiosis I is arrested.

PRIMARY OOCYTE : 

PRIMARY OOCYTE Primary oocytes arrested at prophase I have a visible nuclear membrane called the germinal vesicle. Soon after formation, each primary oocyte becomes surrounded by a single layer of flattened granulosa cells (primordial follicle). GERMINAL VESICLE PRIMORDIAL FOLLICLE

PRIMARY OOCYTE : 

PRIMARY OOCYTE The formation of the primordial follicle is a critical step designed for the preservation of the follicle. Germ cells destined to undergo atresia are incompletely surrounded by this mantle of primitive granulosa cells.

PRIMARY OOCYTE : 

PRIMARY OOCYTE Before menarche, majority of primary oocytes resume meiosis I at varying times (in utero, infancy, puberty), only to be lost short of ovulation in atresia and resolution. Hence, numbers rapidly fall: 7 million at 20th week of gestation 2 – 4 million at birth 400,000 at menarche PRIMORDIAL FOLLICLE

MENARCHE : 

MENARCHE Some primary oocytes remain arrested at prophase I until menarche. AT MENARCHE, a cohort of follicles are recruited, and develop during each cycle.

MENARCHE : 

MENARCHE With follicle ripening, meiosis resumes in a few follicles per cycle  primary oocytes proceed to metaphase I. However, only one dominant follicle (Graafian follicle) completes maturation and meiosis I and releases an egg  ovulation. SECONDARY OOCYTE

FOLLICULAR DEVELOPMENT : 

FOLLICULAR DEVELOPMENT

SUMMARY OF OOGENESIS : 

SUMMARY OF OOGENESIS WITH TWO POINTS OF ARREST

IMPORTANT EVENTS : 

IMPORTANT EVENTS PROPHASE I Member chromosomes of bivalents are held together only at certain points (chiasmata)  crossing-over of genetic materials take place at the chiasmata  contributes to genetic diversity. Crossing over between homologous chromosomes is likely to occur at several different points, resulting in chromosomes that are mixtures of the original two chromosomes. Meiosis is arrested. CHIASMATA

IMPORTANT EVENTS : 

IMPORTANT EVENTS METAPHASE I Highly contracted bivalents align themselves along the equatorial plate. Chromosomes derived from maternal and paternal sources line up at random to one another  contributes to genetic diversity. Example of possible arrangements of chromosomes during METAPHASE 1.

IMPORTANT EVENTS : 

IMPORTANT EVENTS TELOPHASE I Completion of meiosis I. Two daughter cells are formed. ASYMMETRICAL CYTOKINESIS One daughter cell receives majority of the cytoplasm (secondary oocyte). The 2nd daughter cell becomes the 1st polar body.

IMPORTANT EVENTS : 

IMPORTANT EVENTS METAPHASE II Ovulation  secondary oocyte proceeds to metaphase II. At the time it enters the fallopian tube, the egg is surrounded by a cumulus of granulosa cells (cumulus oophorus) and intimately surrounded by a clear zona pellucida  within the zona pellucida are the secondary oocyte and the 1st polar body. Meiosis is arrested.

OVUM & EMBRYO TRANSPORT : 

OVUM & EMBRYO TRANSPORT The ovum is surrounded by the cumulus oophorus, which allows the fimbria of fallopian tube to sweep up the egg; cilia beat unidirectionally inwards. Smooth muscle contractions also propel the ovum inwards.

OVUM & EMBRYO TRANSPORT : 

OVUM & EMBRYO TRANSPORT Under estrogen influence, the egg is “locked” in the tube at the fertilization site, near the junction of the isthmus & ampulla. Later, due to progesterone & prostaglandins, the tubal isthmus is relaxed  embryo is expelled into the uterus via smooth muscle contraction and ciliary motion. The egg is generally fertilized within 12 hours of ovulation; egg quality declines thereafter.

SPERMATOGENESIS : 

SPERMATOGENESIS

SPERMATOGENESIS : 

SPERMATOGENESIS Involves three major processes: Multiplication of spermatogenic cells Reductive meiotic division to achieve haploidy Formation of cellular structure to allow for protection and delivery of chromosomal package to egg

SPERMATOGENESIS : 

SPERMATOGENESIS

SPERMATOGENESIS : 

SPERMATOGENESIS In the male embryo, primordial germ cells (PGCs) remain in a resting state until puberty. Sex cords organize into seminiferous tubules, which collect into the rete testis.

SPERMATOGENESIS : 

SPERMATOGENESIS AT PUBERTY, lumen form in the seminiferous tubules; PGCs divide mitotically to form spermatogonia. After several mitotic divisions, some spermatogonia shift to meiosis (primary spermatocytes). The spermatogonia lie nearest the outer basement membrane.

SPERMATOGENESIS : 

SPERMATOGENESIS Each cell begins spermatogenesis as a primary spermatocyte. At the end of MEIOSIS II, four spermatids are produced.

SPERMIOGENESIS : 

SPERMIOGENESIS HEAD Contains the entire haploid genome Nucleus takes up 65% Acrosome at tip contains lytic enzymes which aid in penetration of the ovum MIDPIECE Helically arranged mitochondria which use glycolysis for energy production FLAGELLUM Typical cilium

SPERM MATURATION : 

SPERM MATURATION After leaving the testis, the sperm is an elongated, flagellated cell with numerous well-developed mitochondria that supply energy for movement & with a condensed nucleus covered by the acrosome. However, at this stage sperm are not motile & cannot fertilize eggs. They first pass through the epididymis where further modifications of the head and tail take place and where proteins synthesized by epididymal cells are applied to the sperm surface. Maturation events in the epididymis are androgen dependent.

SPERM MATURATION : 

SPERM MATURATION By the time the sperm reach the distal cauda epididymis, they are prepared for entry into the female reproductive tract where they undergo further modifications prior to fertilization. Upon ejaculation, sperm are still not capable of fertilization. They must first undergo CAPACITATION & ACROSOME REACTION.

SPERM TRANSPORT : 

SPERM TRANSPORT Sperm travel through the epididymis & vas deferens by fluid flow & smooth muscle peristaltic contractions of the vas. ORDER OF RELEASE INTO EJACULATE (average = 40-300 M sperm, 2 – 5 ml) Ampulla of the vas: major storage site of sperm  1st fraction of ejaculate is sperm-rich Prostatic secretions Emptying of seminal vesicles - most volume

SPERM TRANSPORT : 

SPERM TRANSPORT Semen coagulates immediately after ejaculation due to seminal vesicle proteins, but liquefies within 15 – 30 min through prostatic enzyme action. The alkaline pH (7.5 – 8.0) buffers the acid pH of the vagina.

CAPACITATION andACROSOME REACTION : 

CAPACITATION andACROSOME REACTION Occur as the sperm are transported through the cervical mucus, uterus & fallopian tubes. Activate enzyme systems within the sperm head and make it possible for the sperm to transgress the cumulus oophorus & zona pellucida.

CAPACITATION : 

CAPACITATION Capacitation is the physiologic change that sperm must undergo in the female reproductive tract before fertilization. It involves removal of proteins that coat the sperm. Sperm must be free of seminal plasma; uterine & oviductal fluids adsorb sperm surface proteins. It leads to a characteristic activated pattern of motility. Capacitated sperm show hyperactivate whiplash-type motion. In mammals, motility probably serves to aid the sperm in passing through the cumulus and zona. Capacitation time varies among species; but in general, it occurs within a few hours of ejaculation.

ACROSOME REACTION : 

ACROSOME REACTION After capacitation, the sperm undergoes acrosome reaction (AR). AR leads to (1) release of hydrolytic enzymes from the acrosome into the environment & (2) exposure of the inner acrosomal membrane of the sperm.

ACROSOME REACTION : 

ACROSOME REACTION The precise sequence of events leading to sperm-egg fusion varies among species and is not entirely known for humans. In some species, the AR is completed prior to zona binding. In many species, sperm apparently bind to the ZP before undergoing the AR. The zona pellucida protein (ZP3) then induces the AR & the sperm penetrates to reach the perivitelline space. In these species, sperm which undergoes the AR spontaneously prior to contact with the zona cannot bind to it or penetrate it.

ACROSOME REACTION : 

ACROSOME REACTION The AR serves two main purposes: Release of enzymes (hyaluronidase and protease) which dissolve investments surrounding the egg. After ovulation, the oocyte is surrounded by the cumulus oophorus, a cloud of cumulus cells held together by hyaluronic acid. Inside the cumulus is the zona pellucida (ZP), a glycoprotein shell around the egg. These must be traversed for fertilization to occur.

ACROSOME REACTION : 

ACROSOME REACTION The AR serves two main purposes: Release of enzymes (hyaluronidase and protease) which dissolve investments surrounding the egg. Hyaluronidase hydrolyzes the hyaluronic acid matrix of cumulus cells. Sperm bind to ZP via mannose receptor binding proteins. Acrosin (a membrane-bound acrosomal protease) dissolves the zona pellucida and enables sperm to penetrate it (20 min). After the AR, some of the acrosin remains associated with the inner acrosomal membrane. This remaining enzyme is brought into contact with the ZP at the time of sperm binding. Then, through the force of sperm motility and digestion by acrosin, the sperm penetrates the zona and gains access to the oocyte surface.

SPECIES SPECIFICITY : 

SPECIES SPECIFICITY Species specificity of fertilization is provided by the ZP and oocyte membrane. It is rare for sperm of heterologous species to pass through the zona.

DIFFERENCES : 

DIFFERENCES SPERMATOGENESIS: All 4 meiotic products develop into gametes. OOGENESIS: Most of the cytoplasm is placed into the large egg (asymmetrical cytokinesis). The other cells, the polar bodies, do not develop.

DIFFERENCES : 

DIFFERENCES In males, PGCs become diploid spermatogonia, which divide by mitosis at puberty. Then some of the spermatogonia become committed to meiosis. Spermatogonia committed to meiosis become primary spermatocytes. Males never run out of sperm. Diploid spermatogonia persist throughout life and serve as a continuous stem cell population. Meiosis I, Meiosis II, and the maturation process each take approximately 16 days (48 days total). SPERMATOGENESIS Meiosis I Mitosis Meiosis II

DIFFERENCES : 

DIFFERENCES In females, PGCs become diploid oogonia, which divide by mitosis until week 12, then all oogonia switch to meiosis. Oogonia committed to meiosis become primary oocytes. At birth, females have all the primary oocytes that they will ever have (2 M). There is no further production of oogonia. Ovulation occurs approximately once every 28 days. Females ovulate about 400 times during their lifetime. OOGENESIS Meiosis I Meiosis II

WHY … : 

WHY … … is there a finite number of oocytes at birth? It is not necessary for females to make millions of ova, since a female cannot carry millions of fetuses.  Thus, females do not need to have constant mitosis of their germ cells-- once a germ cell is used it does not need to be replenished.   … does the ovum receive all of the cytoplasm? No more than one ovum per month should be made.  The ovum needs to contain a lot of nutrients to get the embryo through its first set of divisions. The polar bodies do not need the nutrient-rich cytoplasm.

WHY … : 

WHY … … is meiosis is only completed when an egg is fertilized? Meiosis does not need to proceed if an embryo will not be formed. … are there so many spermatozoa, when only 1 is necessary to fertilize the ovum? It is common for humans to have high number of abnormal forms (30 – 40%). Heads can be large, amorphous, small, two, or pin. Can have two tails, or a bent midpiece. Sperm transport is fraught with “high mortality”. An average human ejaculate contains over one hundred million sperm, but only a few dozen complete the journey. And of these, only one will succeed in fertilizing the egg.

FERTILIZATION : 

FERTILIZATION

CHEMOTAXIS : 

CHEMOTAXIS Progesterone Helps increase sperm motility. Binds to a surface receptor on the sperm  allows an increase in intracellular Ca++  increases sperm motility (chemokinesis). Follicular fluid attracts sperm. Other chemical attractants may also be produced by the egg or the tissues surrounding it. Chemotaxis: process wherein sperm are attracted to the egg

FERTILIZATION : 

FERTILIZATION Fertilization usually occurs in distal 1/3 of oviduct

FERTILIZATION : 

FERTILIZATION Sperm passes the barrier of ZP. Attaches to cell membrane of egg and enters cytoplasm. Intracytoplasmic structures (coronal granules) arrange themselves around the outermost portion of the cytoplasm. Release of granule contents results in an alteration of the character of the ZP. Ca++ and proteolytic enzymes cause hardening of ZP (“ZONA REACTION”), which blocks further sperm binding.

FERTILIZATION : 

FERTILIZATION Sperm head swells  “male pronucleus” (formed within 16 hours). Egg becomes activated & completes meiosis II  2nd polar body is cast off. Female pronucleus swells Pronuclei do not fuse  nuclear membranes disappear (within 26 hours) Chromosomes arrange themselves on the developing spindle of the first mitotic division  diploid number of chromosomes is re-established  fertilized egg (ZYGOTE).

EARLY EMBRYONIC DEVELOPMENTANDIMPLANTATION : 

EARLY EMBRYONIC DEVELOPMENTANDIMPLANTATION

1ST TWO WEEKS : 

1ST TWO WEEKS BLASTOMERE MORULA BLASTOCYST IMPLANTATION

Slide 76: 

As cells continue to divide, they pass along the fallopian tube & enter the uterus. This takes 3-4 days after fertilization. It may arrive in the uterus in any form, from the 32-cell stage (morula) to the early blastula stage.

BLASTOMERE : 

BLASTOMERE CLEAVAGE Process of early mitotic cell divisions, which progressively reduces cell size. Total cell mass remains relatively constant.

MORULA : 

MORULA Day 4, 16-32 cells When there are about 16 cells, individual cells begin to adhere to one another. As the cells continue to divide, the morula passes along the fallopian tube and enters the uterus (3-4 days after fertilization).

BLASTOCYST : 

BLASTOCYST Day 5-6, 64+ cells As the morula enters the uterus, a fluid-filled cavity forms (blastocoele). Cavitation is an important transition from homogenous cells to differentiated cell functions: inner cell mass & outer trophoblastic layer. There is overt differentiation of inner & outer cell masses.

BLASTOCYST : 

BLASTOCYST The development of the blastocyst & separation of the embryonic disk cells from the trophoblastic cells make up the 1st stage of differentiation in the embryo.

BLASTOCYST : 

BLASTOCYST Cells of the early embryonic disk are multipotential. At this stage, teratogens are either completely destructive or have little / no effect.

BLASTOCYST : 

BLASTOCYST Before the blastocyst makes contact with the endometrium, the ZP will be shed  allows the embryo to fix to the endometrium (apposition). Shedding of the ZP Continued expansion of the blastocyst cavity eventually ruptures the ZP Trophoblastic cells digest the ZP ZP is broken down by endometrial enzymes

IMPLANTATION : 

IMPLANTATION Day 6-8, usually 3 days after the morula enters the uterus. Implantation depends on the development of early trophoblastic cells during the blastula stage. Digest away the ZP, Allow the embryo to attach to the endometrium, Allow the embryo to burrow within the endometrium.

IMPLANTATION : 

IMPLANTATION Trophoblast cells differentiate into syncytiotrophoblasts & cytotrophoblasts. Day 7 ½ - 9: Endometrial capillaries in contact with invading syncytiotrophoblasts are engulfed  form venous sinuses.

IMPLANTATION : 

IMPLANTATION The endoplasmic reticulum of the syncytiotrophoblast is probably responsible for the synthesis of hCG  well-developed by day 11. hCG is transferred via the sinuses before intact circulation to the developing embryo has been established. hCG is responsible for maintaining the corpus luteum, which in turn is necessary to maintain the pregnancy until the placenta takes over.

IMPLANTATION : 

IMPLANTATION

IMPLANTATION : 

IMPLANTATION

EMBRYONIC PERIOD : 

EMBRYONIC PERIOD EMBRYO: made up of embryo-forming cells grouped as the inner cell mass Differentiation of the embryonic disk proceeds rapidly.

EMBRYONIC PERIOD : 

EMBRYONIC PERIOD Week 3 (Day 14 – 21) Primitive streak forms in the caudal portion of the embryonic disk  embryonic disk grows and changes from a circular to a pear-shaped configuration. ECTODERM: epithelium facing superiorly (gives rise to CNS) ENDODERM: epithelium facing downward (towards the yolk sac) Neural plate develops with its notochordal process.

EMBRYONIC PERIOD : 

EMBRYONIC PERIOD Week 3 (Day 14 – 21) DAY 16: mesoderm begins to form Early mesoderm migrates cranially, passing on either side of the notochordal process, to meet in front  formation of the cardiogenic area (heart develops from this area). Later in the week, the extra-embryonic mesoderm joins with the yolk sac & developing amnion  contributes to developing membranes.

EMBRYONIC PERIOD : 

EMBRYONIC PERIOD Week 3 (Day 14 – 21) DAY 16: mesoderm begins to form Intra-embryonic mesoderm develops on each side of the notochord & neural tube to form longitudinal columns (PARAXIAL MESODERM). Each column thins laterally into the lateral plate mesoderm, which is continuous with the extra-embryonic mesoderm. The lateral plate mesoderm is separated from the paraxial mesoderm by a continuous tract of mesoderm (INTERMEDIATE MESODERM). DAY 20: paraxial mesoderm divide into paired SOMITES About 38 pairs of somites form in the next 10 days. Total of 40 – 44 pairs  give rise to body musculature.

EMBRYONIC PERIOD : 

EMBRYONIC PERIOD Week 3 (Day 14 – 21) DAY 15 – 16: angiogenesis Seen in the extra-embryonic mesoderm of the yolk sac. Embryonic vessels can be seen about 2 days later. Mesenchymal cells (ANGIOBLASTS) aggregate to form masses & cords (BLOOD ISLANDS). Spaces appear within the islands. Angioblasts arrange themselves around the spaces to form primitive endothelium. Isolated vessels form channels & then grow into adjacent areas by endothelial budding. Primitive blood cells develop from endothelial cells, but blood formation in the embryo does not begin until the 2nd month. Separate mesenchymal cells surrounding the primitive endothelial vessels differentiate into muscular and connective tissue elements.

EMBRYONIC PERIOD : 

EMBRYONIC PERIOD Week 3 (Day 14 – 21) Heart forms in a similar manner from mesenchymal cells in the cardiogenic area. Paired endothelial channels (HEART TUBES) develop by the end of week 3  fuse to form the primitive heart. DAY 21: heart linked up with blood vessels, forming a primitive cardiovascular system. Blood circulation starts, and this is becomes the 1st functioning organ system in the embryo.

EMBRYONIC PERIOD : 

EMBRYONIC PERIOD Week 4-7 All organ systems are formed.