EMBRYO-LC1-Introduction to Embryology _ Gametogenesis.pdf

Embryogenesis: process of progression from a single cell to the period of establishing organ primordia...

Embryogenesis: process of progression from a single cell to the period of establishing organ primordia TOPIC OUTLINE Organogenesis: occurs during the 6th through the 8th week of the embryonic life, characterized by the growth and differentiation of I. INTRODUCTION TO EMBRYOLOGY tissues to organs II. THE REPRODUCTIVE SYSTEM III. WHAT IS GAMETOGENESIS? IV. FERTILIZATION A. Primordial Germ Cells Significance of Embryology: B. Clinical Correlation ○ explains the basics of gross anatomy V. THE CHROMOSOME THEORY OF INHERITANCE ○ explains the variations in human structure and birth VI. MITOSIS defects A. Stages of Mitosis Thalidomide drug: used by pregnant women in 1960s as to cure VII. MEIOSIS morning sickness A. Clinical Correlation ○ caused severe deformities including shortening of the VIII. GAMETOGENESIS limbs, and malformation of hands and digits A. Oogenesis B. Spermatogenesis I. INTRODUCTION TO EMBRYOLOGY Branch of science that deals with the formation, growth, and development of an embryo. It tackles different processes involved in the prenatal stage of development starting from the formation of gametes, fertilization, formation of zygote, development of embryo and fetus, and until the birth of a new individual. From a single cell to a baby in 9 months—a developmental process that represents an amazing integration of increasingly complex phenomena. The study of these phenomena is called embryology, and the field includes investigations of the molecular, cellular, and structural factors contributing to the formation of an organism. Hydrops fetalis: severe swelling in an unborn or newborn baby ○ hydramnios: excessive amount of amniotic fluid around a Figure 2. A “Thalidomide Baby” fetus during pregnancy ○ amniocentesis: extraction of amniotic fluid which will II. THE REPRODUCTIVE SYSTEM then be subjected to testing; for early detection of genetic and other chromosomal conditions Organogenesis of the Reproductive system ○ can be caused by severe anemia During the initial stages of gonadal development (during the 5th week), a thickened area of mesothelium develops on the medial side of the mesonephros (primitive kidney). Growing of this epithelium and the underlying mesenchyme produces a bulge on the medial side of the mesonephros termed as the gonadal ridge. Finger-like epithelial cords, or gonadal cords, will soon grow into the underlying mesenchyme. The indifferent (undifferentiated) gonad now consists of an external cortex and an internal medulla. Embryos with XX chromosomes will have the indifferent gonad to differentiate into an ovary, and the medulla regresses. On the other hand, embryos with XY chromosomes will have the indifferent gonad to differentiate into a testis, and the cortex regresses. Figure 1. Hydrops fetalis. Page 1 of 14 [EMBRYOLOGY] 1.01 INTRODUCTION TO EMBRYOLOGY: GAMETOGENESIS – Dr. Oandasan, MD Figure 5. The male and female gametes IV. FERTILIZATION It is the process by which male and female gametes fuse which Figure 3. A transverse section of the abdomen of a 40-day embryo showing its gonadal ridge. occurs in the ampullary region of the uterine tube (widest part of the tube and is close to the ovary) 1. The three phases of oocyte penetration: The Female Reproductive System ○ Phase 1: spermatozoa pass through the corona radiata eggs are from the ovaries; when a sperm fertilizes an egg, it barrier (penetration of the corona radiata) will be embedded to the uterine wall ○ Phase 2: one or more spermatozoa penetrate the zona ○ eggs are fertilized in the fallopian tube → uterus pellucida (penetration of the zona pellucida) ○ ectopic pregnancy: when a fertilized egg is embedded outside the uterus ○ Phase 3: one spermatozoon penetrates the oocyte membrane while losing its own plasma membrane (fusion of the oocyte and sperm cell membranes). 2. Formation of female and male pronucleus. 3. Formation of two cell-stage zygote with the normal diploid number of chromosomes (23 maternal and 23 paternal). 4. Zygote undergoes a series of mitotic divisions, increasing the numbers of cells, up to the formation of a blastocyst. Morula (mulberry): 16-cell Figure 4. The female reproductive system III. WHAT IS GAMETOGENESIS? Process by which the diploid germ cells undergo a number of chromosomal and morphological changes to form mature haploid Figure 6. Formation of Blastocyst gametes. Process involved in the maturation of the two highly specialized cells, Blastocyst inner cell mass: at one pole will form the embryo proper spermatozoa in males and ovum in females before they unite to Blastocyst outer cell mass: surrounds the inner cells and the form zygote. blastocyst cavity will form the trophoblast (later contributes to Spermatozoon + Ovum = Zygote placenta). Male gamete: sperm Female gamete: oocyte Page 2 of 14 [EMBRYOLOGY] 1.01 INTRODUCTION TO EMBRYOLOGY: GAMETOGENESIS – Dr. Oandasan, MD In preparation for fertilization, germ cells undergo gametogenesis, which includes meiosis, to reduce the number of chromosomes and cytodifferentiation to complete their maturation. Germ cells are directed toward the gonads by the mature cellular and non-cellular microenvironment that surround them or by tissue rearrangement that occur in the early embryos. If they fail to reach the ridges, the gonads will not develop. So, it has the inductive influence on the development of gonads into ovaries and testes. Determines sex of the embryo. Mitotic divisions increase their number during their migration and also when they arrive in the gonad. Figure 7. A human embryo OVIDUCT: fertilization occurs here. Figure10. Gastrulation and the germ layers CLINICAL CORRELATION TERATOMAS: tumors of disputed origin. It contains a variety of tissues, such as bone, hair, muscle, gut epithelia, thought that these tumors arise from pluripotent stem cells that can differentiate into any of the three germ layers or their Figure 8. Movement of the egg down the uterine wall derivatives PGCs that have strayed from their normal migratory paths after fertilization. Another source may be the epiblast cells that give rise to all three PRIMORDIAL GERM CELLS germ layers during gastrulation. Figure 11. Teratomas Figure 9. Movement of primordial germ cells during urogenital development V. THE CHROMOSOME THEORY OF INHERITANCE Gametes are derived from primordial germ cells (PGCs) that are formed in the epiblast during the second week, move through the primitive streak during gastrulation, and migrate to the wall of the 23,000 genes on 46 chromosomes yolk sac. Genes on the same chromosome tend to be inherited together and Appears in the wall of the endodermal layer of the yolk sac due to so are known as linked genes. their large size and high content of alkaline phosphatase, and migrate In somatic cells, chromosomes appear as 23 homologous pairs to by amoeboid movement toward the hind gut epithelium and then Form the diploid number of 46. through dorsal mesentery reach to the primordia of the gonads 22 pairs of matching chromosomes - DIPLOID (primitive sex glands). 22- autosomes, 1 pair of sex chromosomes This need for cellular migration causes the cells of the epiblasts to XX - the individual is genetically female move towards the hypoblasts and with which the third embryonic XY - the individual is genetically male layer (mesoderm) appears between the two previous layers. Page 3 of 14 [EMBRYOLOGY] 1.01 INTRODUCTION TO EMBRYOLOGY: GAMETOGENESIS – Dr. Oandasan, MD ○ The centrosomes are also duplicated at this stage which VI. MITOSIS will give rise to mitotic spindles. Mitosis: process whereby one cell divides, giving rise to two G2 Phase (Gap 2) daughter cells that are genetically identical to the parent cell. ○ The final preparation to be completed before the cell is ○ Used for almost all of your body’s cell division needs able to enter the first stage of mitosis. (somatic cells). It adds new cells during development and ○ The cell continues to grow and some cells are duplicated. replaces old and worn-out cells throughout your life. (khanacademy.org) STAGES OF MITOSIS Prophase - during this replication phase, chromosomes are extremely long, they are spread diffusely through the nucleus, and they cannot be recognized with the light microscope. ○ The chromosomes of the cell get ready to be moved around by coiling themselves up into tight little packages. As the chromosomes coil up, or condense, they become visible to the eye when viewed through a microscope. ○ During prophase: The chromosomes coil up and become visible. The nuclear membrane starts to break down. The nucleoli break down and become invisible. (Biology for Dummies, 2nd ed) Figure 12. The stages of mitosis INTERPHASE Technically not part of mitosis inter- means “between,” so interphase is literally the phase between cell divisions The cell is engaged in metabolic activity for the preparation of mitosis. Characteristics: ○ The nuclear membrane is intact throughout the interphase. ○ The DNA is so loosely intact that you can’t see chromosomes clearly with a light microscope. ○ Nucleolus may be visible. Figure 14. Chromosomes coiling in the Prophase stage Prometaphase - Each chromosome now consists of two parallel subunits, chromatids - joined at a narrow region common to both called the centromere. ○ Nuclear envelope begins to disappear. ○ Each sister chromatid develops a protein structure called a kinetochore in its centromeric region. ○ As the spindle microtubules extend from the centrosomes, some of these microtubules attracted and come into contact with and firmly bind to the kinetochores. ○ Once a mitotic fiber attaches to a chromosome, the chromosome will be oriented until the kinetochores of sister chromatids face the opposite poles. Eventually, all the sister chromatids will be attached via their Figure 13. Cell cycle of multicellular organisms having two phases: Interphase kinetochores to microtubules from opposing poles. and Mitotic phase Chromosomes continue to condense, shorten, and thicken, but only at prometaphase do the chromatids become distinguishable. Stages: G1 Phase (Gap 1) ○ Longest one of the entire cell cycle. ○ The cell grows and produces cell components.. The cell is accumulating the building blocks of chromosomal DNA and the associated proteins as well as accumulating sufficient energy reserves to complete the task of replicating each chromosome in the nucleus. ○ Note: some cells never leave this phase, they never divide. examples are the nerve cells. S Phase (Synthesis) ○ Period during which DNA is synthesized forming identical pairs of DNA molecules (sister chromatids). Page 4 of 14 [EMBRYOLOGY] 1.01 INTRODUCTION TO EMBRYOLOGY: GAMETOGENESIS – Dr. Oandasan, MD Figure 15. Chromatids become distinguishable in the Prometaphase stage Metaphase - the chromosomes line up in the equatorial plane, and their doubled structure is clearly visible. (Meta- means “middle,” so it’s officially metaphase when the chromosomes are lined up in the middle- Biology for dummies, 2nd ed) Each is attached by microtubules extending from the centromere to the centriole, forming the mitotic spindle. The chromosomes are tugged by the mitotic spindle until they’re all lined up in the middle of the cell. Figure 18. Nuclear envelope reforms in the Telophase stage (Notes: After telophase, what comes after is cytokinesis. It begins with an indentation, called a cleavage furrow, in the center of the cell. Cytoskeletal proteins act like a belt around the cell, contracting down and squeezing the cell in two. After cytokinesis is complete, the new cells move immediately into the G1 stage of interphase.) VII. MEIOSIS Type of cell division that takes place in the germ cells to generate male (sperm cell) and female (egg cell) gametes Meiosis requires two cell divisions, meiosis I and meiosis II, to reduce the number of chromosomes to the haploid number of 23. Figure 16. Alignment of chromosomes at the metaphase plate in the As in mitosis, male and female germ cells (spermatocytes and Anaphase stage primary oocytes) at the beginning of meiosis I replicate their DNA so that each of the 46 chromosomes is duplicated into sister chromatids. Anaphase - Centromere of each chromosome divides, marking the Meiosis I happens during pre-pubertal life and Meiosis II during puberty (specifically in males) beginning of anaphase, followed by migration of chromatids to opposite poles of the spindle. The chromosomes have separated and are moving toward the poles. Figure 17. Centromeres of the chromosomes divide in the Anaphase stage Telophase - chromosomes uncoil and lengthen, the nuclear envelope Figure 19. Stages of meiosis reforms, and the cytoplasm divides. Each daughter cell receives half of all doubled chromosome material and thus maintains the same number of chromosomes as the mother Homologous chromosomes then align themselves in pairs, a process cell. called synapsis. The reverse of prophase. ○ New nuclear membranes form around the two sets of chromosomes. ○ The chromosomes uncoil and spread throughout the nucleus. ○ The mitotic spindle breaks down. ○ The nucleoli reform and become visible again. (Biology for dummies, 2nd ed) Page 5 of 14 [EMBRYOLOGY] 1.01 INTRODUCTION TO EMBRYOLOGY: GAMETOGENESIS – Dr. Oandasan, MD Approximately 25% of conceptuses have a major chromosomal defect. 45,X [Turner syndrome], triploidy, and trisomy 16. Chromosomal abnormalities account for 10% of major birth defects, and gene mutations account for an additional 8%. Nondisjunction - one cell receives 24 chromosomes, and the other receives 22 instead of the normal 23. When, at fertilization, a gamete having 23 chromosomes fuses with a gamete having 24 or 22 chromosomes, the result is an individual with either 47 chromosomes (trisomy) or 45 chromosomes (monosomy). Women are advised to give birth before the age of 35 (30 from the latest studies) since environmental factors and stress can affect the quality of egg cells and cause meiotic nondisjunction Down syndrome / Trisomy 21 Extra copy of chromosome 21 In 95% of cases, the syndrome is caused by trisomy 21 resulting from Figure 20. Preparation of cell during Interphase and the crossing over meiotic nondisjunction during oocyte formation. of homologous chromosomes during Prophase I In 4% of cases of Down syndrome, there is an unbalanced translocation between chromosome 21 and chromosomes 13, 14, 15, Crossovers - critical events in meiosis I - interchange of chromatid or 21. segments between paired homologous chromosomes. 1% - mosaicism resulting from a trisomic conception followed by the Segments of chromatids break and are exchanged as homologous loss of the extra chromosome (inactive extra chromosome; not full chromosomes separate. blown Trisomy 21). As separation occurs, points of interchange are temporarily united ○ Characteristics: and form an X-like structure, CHIASMA. Growth retardation Genes that are far apart on a chromosome occur approximately 30 to Varying degrees of intellectual disability 40 crossovers with each meiotic I division. Craniofacial abnormalities - upward slanting eyes, epicanthal folds [extra skin folds at the Result of Meiotic Division medial corners of the eyes] Flat facies Small ears Cardiac defects Hypotonia Figure 21. Events occurring during the first and second maturation divisions Genetic variability is enhanced through Crossover, which redistributes genetic material. Random distribution of homologous chromosomes to the daughter cells. Each germ cell contains a haploid number of chromosomes so that at fertilization, the diploid number of 46 is restored. Disruption of processes such as meiosis may result in aneuploidy CLINICAL CORRELATION Birth Defects and Spontaneous Abortions: Chromosomal and Genetic Factors Aneuploid - any chromosome number that is not euploid; it is usually applied when an extra chromosome is present [trisomy] or when one is missing [monosomy]. Figure 22. Characteristics of Trisomy 21 Estimated that 50% of conceptions end in spontaneous abortion and Trisomy 18 (Edward’s Syndrome) that 50% of these abortuses have major chromosomal abnormalities. 1 in 5,000 85 % - lost between 10 weeks of gestation and term Page 6 of 14 [EMBRYOLOGY] 1.01 INTRODUCTION TO EMBRYOLOGY: GAMETOGENESIS – Dr. Oandasan, MD 2 months of age 5% live beyond 1 year Characteristics: ○ Intellectual disability ○ Congenital heart defects ○ Low-set ears ○ Flexion of fingers and hands ○ Syndactyly (extra set of fingers) ○ Micrognathia (small tongue) ○ Renal anomalies ○ Malformation of the skeletal system Figure 24. Characteristics of Trisomy 13 Klinefelter Syndrome The cells have 47 chromosomes with a sex chromosomal complement of the xxy type, and a sex chromatin [barr] body is found in 80% of cases. (Barr bodies are normally found only in females) Incidence is approximately 1 in 500 males Nondisjunction of the xx homologues - most common causative event. Characteristics: ○ Sterility ○ Testicular atrophy ○ Hyalinization of the seminiferous tubules ○ Gynecomastia Figure 23. Characteristics of Trisomy 18 Trisomy 13 (Patau’s Syndrome) The incidence of this abnormality is approximately 1 in 20,000 live births, and more than 90% of the infants die in the first month after birth. Figure 25. Characteristics of Klinefelter Syndrome Approximately 5% live beyond 1 year Characteristics: ○ Intellectual disability. Turner Syndrome ○ Holoprosencephaly - failure of the prosencephalon, or 45, X karyotype forebrain, to develop normally; causes a developing baby’s brain to not properly separate into the right and Only monosomy compatible with life left hemispheres (halves) 98% of all fetuses with the syndrome are spontaneously ○ Congenital heart defects aborted ○ Deafness 55% - monosomic for the X and chromatin body negative ○ Cleft lip and palate because of nondisjunction ○ Eye defects, such as microphthalmia (small eyes) 80% of these females - nondisjunction in the male gamete is anophthalmia (no eyes but with eye sockets) and the cause coloboma. (Webbed neck is the usual characteristic of patients with Turner’s syndrome) Page 7 of 14 [EMBRYOLOGY] 1.01 INTRODUCTION TO EMBRYOLOGY: GAMETOGENESIS – Dr. Oandasan, MD multiplying and will now form the first female gametes called oogonia. Figure 28. Development of a Graafian follicle from PGC migration Figure 26. Characteristics of Turner Syndrome Maturation of the oocytes begins before birth Triple X Syndrome ○ Once PGCs have arrived in the gonad of a genetic female, Patients with triple X syndrome [47, XXX] often go undiagnosed they differentiate into oogonia. because of their mild physical features. (Presents with ○ These cells undergo a number of mitotic divisions, and by intellectual instability) the end of the third month, they are arranged in clusters surrounded by a layer of flat epithelial cells. These flat epithelial cells are known as follicular cells. The oogonia are grouped in clusters in the cortical part of the ovary. Figure 27. Extra X-chromosome Figure 29. Clusters of oogonia surrounded by flat epithelial cells VIII. GAMETOGENESIS ○ The majority of oogonia continue to divide by mitosis, but OOGENESIS: some of them arrest their cell division in prophase of The process involved in the development of a mature ovum. (Note: meiosis I and form primary oocytes. the maturation of oocytes begins before birth and is completed after Not all oogonia will become Graafian follicles puberty. Oogenesis continues to menopause, which is the permanent as some of them will stay in the diplotene cessation of the menstrual cycle.) stage of meiosis I. From yolk sac: primitive germ cells at 3rd week ○ Oogonia will now increase rapidly in number; by the 5th ○ PGCs travel from the epiblast to the gonads à will form month of prenatal period, the total number of germ cells into female gamete or ovum. in the ovary will reach its maximum number. ○ Begins before birth- intrauterine Before birth, there are about 7 million primary ○ When PGCs undergo the process of gastrulation, it will oocytes + arrested oogonium form a multilayered cell; with 3 germ layers (ectoderm, ○ At this time, cell death begins, and many oogonia as well mesoderm, endoderm). as primary oocytes degenerate and become atretic. ○ As the PGCs reach the developing ovary, they will be ○ By the 7th month, the majority of oogonia have Page 8 of 14 [EMBRYOLOGY] 1.01 INTRODUCTION TO EMBRYOLOGY: GAMETOGENESIS – Dr. Oandasan, MD degenerated except for a few near the surface. All surviving primary oocytes have entered prophase of meiosis I, and are now surrounded individually by flat follicular epithelial cells. ○ A primary oocyte, together with its surrounding flat epithelial cells, is called a primordial follicle. Figure 31. Maturation of follicles Figure 30. Primordial follicles Maturation of oocytes continues at puberty 1. Near the time of birth, all primary oocytes have started prophase of meiosis I, but instead of proceeding into metaphase, they enter the diplotene stage, a resting stage during prophase that is characterized by a lacy network of chromatin. i. These will remain inactive until puberty or when a female child is born, some primary oocytes will be activated and are destined to Figure 32. An oocyte surrounded be zona pellucida ovulate 2. Primary oocytes remain arrested in prophase and do not a. As follicles continue to grow, cells of the theca folliculi organize into finish their first meiotic division before puberty is an inner layer of secretory cells - theca interna and outer fibrous reached; this arrested state is produced by oocyte capsule – theca externa. maturation inhibitor (OMI)- a small peptide secreted by b. Fluid-filled spaces appear between granulosa cells follicular cells. c. Coalescence of these spaces forms the ANTRUM, and the follicle is 3. The total number of primary oocytes at birth is estimated termed a VESICULAR or an ANTRAL follicle (note: Initially, the antrum to vary from 600,000 to 800,000. is crescent-shaped, but with time, it enlarges) 4. During childhood, most oocytes become atretic. d. Granulosa cells surrounding the oocyte remain intact and form the 5. Only approximately 40,000 are present by the beginning cumulus oophorus. of puberty, and fewer than 500 will be ovulated. i. Cumulus oophorus - consists of a cluster of granulosa cells 6. At puberty, a pool of growing follicles is established and that surround and support the oocyte. ii. The antral stage is the longest, whereas the mature continuously maintained from the supply of primordial vesicular stage encompasses approximately 37 hours prior follicles. to ovulation. 7. Each month, 15 to 20 follicles selected from this pool begin to mature. Some of these die, while others begin to accumulate fluid in a space called the antrum). Maturation of follicles ○ Antral or Vesicular stage (Note: the longest stage) ○ Mature Follicles or Graafian Follicles (Note: approximately 37 hours prior to ovulation.) Page 9 of 14 [EMBRYOLOGY] 1.01 INTRODUCTION TO EMBRYOLOGY: GAMETOGENESIS – Dr. Oandasan, MD g. With each ovarian cycle, a number of follicles begin to develop, but usually only one reaches full maturity. The others degenerate and become atretic. h. When the secondary follicle is mature, a surge in luteinizing hormone (LH) induces the preovulatory growth phase. i. Meiosis I is completed, resulting in formation of two daughter cells of unequal size, each with 23 double structured chromosomes. Figure 33. Antral follicle Figure 36. Formation of the secondary oocyte and the first polar body during Meiosis I Figure 34. Maturing stage j. Secondary oocyte - receives most of the cytoplasm; the other, the e. At maturity, the mature vesicular (graafian) follicle may be 25 mm or first polar body, receives practically none. more in diameter. k. The first polar body lies between the zona pellucida and the cell f. It is surrounded by the THECA INTERNA which is composed of cells membrane of the secondary oocyte in the perivitelline space. having characteristics of steroid secretion, rich in blood vessels, and theca externa. Which gradually merges with the ovarian connective tissue. Figure 37. Maturation of the oocyte Figure 35. A Graafian follicle Page 10 of 14 [EMBRYOLOGY] 1.01 INTRODUCTION TO EMBRYOLOGY: GAMETOGENESIS – Dr. Oandasan, MD Figure 38. A ruptured follicle l. The cell then enters meiosis II but arrests in metaphase Figure 40. Structure of the Testes approximately 3 hours before ovulation. m. Meiosis II is completed only if the oocyte is fertilized; otherwise, the cell degenerates approximately 24 hours after ovulation. The first polar body may undergo a second division. Figure 41. Cross-section of a seminiferous tubules where male gametes are formed SPERMATOCYTOGENESIS ○ begins at puberty ○ All of the events by which spermatogonia are transformed into spermatozoa (matured spermatogonia). ○ Spermatogonia: produced in the testis and will stay inside the seminiferous tubules (long coiled structures which are situated in the testicles/testis). Figure 39. Secondary oocyte in its arrested stage ○ At birth, germ cells in the male infant can be recognized in during Meiosis II the sex cords of the testis as large, pale cells surrounded by supporting cells. SPERMATOGENESIS ○ Supporting cells (Sertoli cells) Differs from oogenesis because the primordial follicles remain derived from the surface epithelium of the dormant (in the seminiferous tubules) until the time of puberty. testis in the same manner as follicular cell At puberty, the testes greatly increased the secretion of become sustentacular cells of Sertoli cells testosterone, a steroid hormone. The testerone will stimulate the growth of the secondary sex characteristics and it will also triggers the growth of the testes, maturation of semineferous tubules, and commencement of spermatogenesis. Phases: 1. Spermatocytogenesis 2. Spermiogenesis Page 11 of 14 [EMBRYOLOGY] 1.01 INTRODUCTION TO EMBRYOLOGY: GAMETOGENESIS – Dr. Oandasan, MD cell generations are joined by cytoplasmic bridges. ○ Thus, the progeny of a single type A spermatogonium form a clone of germ cells that maintain contact throughout differentiation. ○ Spermatogonia and spermatids remain embedded in deep recesses of Sertoli cells throughout their development. ○ In this manner, Sertoli cells support and protect the germ cells, participate in their nutrition, and assist in the release of mature spermatozoa. Figure 42. Sertoli Cells ○ Primordial germ cells (PGCs) give rise to spermatogonial stem cells. At regular intervals, cells emerge from this stem cell population to form type A spermatogonia, and their production marks the initiation of spermatogenesis. ○ Type A cells undergo a limited number of mitotic divisions to form clones of cells. ○ The last cell division produces type B spermatogonia, which then divides to form primary spermatocytes. ○ Primary spermatocytes then enter a prolonged prophase (22 days) followed by rapid completion of meiosis I and Figure 44. Immature spermatogenic cells formation of secondary spermatocytes. ○ During the second meiotic division, these cells immediately ○ Spermatogenesis is regulated by Luteinizing Hormone begin to form haploid spermatids. production by the pituitary gland. ○ LH binds to receptors on Leydig cells and stimulates Testosterone production, which in turn binds to Sertoli cells to promote spermatogenesis. ○ Follicle-stimulating hormone (FSH) is also essential because its binding to Sertoli cells stimulates testicular fluid production and synthesis of intracellular androgen receptor proteins. SPERMIOGENESIS ○ Starts when primary spermatocytes are already formed. ○ The series of changes resulting in the transformation of spermatids into spermatozoa: Formation of the acrosome, which covers half of the nuclear surface and contains enzymes (hydrolytic enzymes) to assist in penetration of the egg and its surrounding layers during fertilization. Condensation of the nucleus Formation of neck, middle piece (contains large helical mitochondria that generates energy for swimming), and tail (contains microtubule (9+2 structure) that form parts of the propulsion system of the spermatozoon) Figure 43. Type A spermatogonia Shedding of most of the cytoplasm as residual bodies that are phagocytized by Sertoli cells. ○ Throughout this series of events, from the time type A ○ Mature sperm present in the seminiferous tubules are not cells leave the stem cell population to formation of yet motile, therefore, unable to fertilize an egg. spermatids, cytokinesis is incomplete so that successive Page 12 of 14 [EMBRYOLOGY] 1.01 INTRODUCTION TO EMBRYOLOGY: GAMETOGENESIS – Dr. Oandasan, MD Figure 45. Parts of a mature sperm cell ○ In humans, the time required for a spermatogonium to develop into a mature spermatozoon is approximately 74 days, and approximately 300 million sperm cells are produced daily. Figure 47. Male gametes at different stages as observed from a seminiferous tubule SUMMARY: Figure 46. Spermiogenesis ○ When fully formed, spermatozoa enter the lumen of seminiferous tubules. ○ Pushed toward the epididymis by contractile elements in the wall of the seminiferous tubules. ○ Although initially only slightly motile, spermatozoa obtain full motility in the epididymis. ○ Motile spermatozoa in the epididymis are now capable of fertilization. Figure 48. Spermatogenesis and Oogenesis Page 13 of 14 [EMBRYOLOGY] 1.01 INTRODUCTION TO EMBRYOLOGY: GAMETOGENESIS – Dr. Oandasan, MD REFERENCES 1. Reference: Langman, J., & Sadler, T. W. (2012). Langman's medical embryology. 12 ed. Philadelphia: Wolters Kluwer Health. Pp. 23-24 2. Moore, K. L., N., P. T. V., & Torchia, M. G. (2020). The developing human: Clinically oriented embryology. Elsevier. Page 14 of 14