Introduction to embryology - Medicine and Dentistry

Medical Embryology introduction

1. RS MAALMAN COURSE: INTRODUCTION TO HUMAN BODY PA/MEDICINE LEVEL 100

2. 16/08/2023 R. S. MAALMAN 2 TOPIC: Introduction to Embryology By Maalman August, 2023

3. Purpose Objectives Introduction Definitions Division Relevance of embryology Divisions 3 Overview

4. To introduce students to embryology and its relevance in their field of study. To enable students have an overall pictorial view of sequential processes that takes place beginning from gametes formation and fertilization to a fully developed functional adult species. 4 Purpose

5. To define embryology and discuss the role of embryology in medicine and research. To list and briefly explain the various periods of mammalian prenatal development 5 Objectives

6. 6 Introduction

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8. 8 What is embryology??

9. It is the science that deals with development and growth of an individual within the uterus. Embryology is the study of the origin and development of an organism. Embryology is the study of the development of the embryo into a fully developed functional newborn. Embryology is the study of changes that occur from the formation of the zygote until fully developed into a functional newborn . 9 Some Definitions!

10. Embryology is the study of events, sequential processes of growth and differentiation arising as a result of a fertilized ovum progressing to a fully formed functional individual mammal. Branches Ontogeny: origin and the development of an organism from the fertilized egg to its mature form Teratology: study of malformations 10 Definitions..

11. Embryologic events/process: General embryology Pre-zygotic period Immediate post-zygotic period Embryonic period Foetal period Systemic embryology Development of all the organ systems 11 Major divisions

12. 12 Why teach/study embryology?

13. Provides understanding of how the male and female gametes arise, mature, their transport to bring about fertilization and fusion of their genetic materials. Bridges the gap between prenatal development and obstetrics, perinatal medicine, pediatrics, and clinical anatomy Firms up ones understanding of the anatomy of the body better, explaining the structural sequence of development of the body and its different organ systems. Helps to explain anatomical relationships and positions of structures. 13 Justification

14. Understanding the basic principles of teratology. To recognize the timing of developmental events which is of crucial importance in the analysis of birth defects or in a variety of medicolegal contexts. Prenatal diagnosis and possible management or cure of some congenital anomalies. Enhances the study and understanding of pathology and clinical medicine. Interpret structural and functional abnormalities in clinical practice. 14 Cont’d..

15. 9. Understanding embryo-technology Artificial insemination in vivo and in vitro fertilization Embryo imaging Cloning 10. Treatment of sub-fertility/fertility issues. 11. Valuable tool for the study and practice of obstetrics and pediatrics. 12. Settling of disputes 13. ……Add to the list! 15 Cont’d..

16. Stages of embryology Four stages: prezygotic processes – gametogenesis etc. Pre-embryonic period – (1 -2 weeks) embryonic period (3-8)- Gastrulation to organogenesis foetal period (9-40 wks )

17. Note the following stages: Zygote Embryo Foetus 17 Terminologies

18. Next lecture; Pre-zygotic period ( Read before you come to class!! ) Thank you

19. The pre-zygotic processes (Gametogenesis) The process of formation and development of specialized generative cells, gametes ALWAYS by Meiosis Two types: Oogenesis Spermatogenesis 16/08/2023 R. S. MAALMAN 20

20. Gametogenesis : OOGENESIS Process begins before birth and is completed after puberty Continues to menopause By the 4 th month, some oogonia begin to differentiate to form primary oocytes, By the 5 th month there are about 7,000,000 oogonia and primary oocytes 16/08/2023 R. S. MAALMAN 21

21. Steps in Oogenesis The primary oocyte to primordial follicle The p.o. surrounded by zona pellucida P. o. begin the first meiotic division. However, oocyte maturation inhibitor ( by follicular cells ) diplotene stage of the 1 st meiotic division; phase called DICTYOTENE 16/08/2023 R. S. MAALMAN 22

22. Steps in Oogenesis, cont. At birth only about 700,000 primary oocytes as most degenerated Oogenesis RESUMES at puberty Ovum is in dictyotene for about 12 - 50 years old High frequency of meiotic errors, such as nondisjunction 16/08/2023 R. S. MAALMAN 23

23. Steps in Oogenesis, cont. (ovarian cycle) At puberty, under the influence of a FSH , 5-15 follicles begin developing at a time PRIMARY Follicle stage - follicular cells become cuboidal SECONDARY follicle - Soon small lakes of fluid appear TERTIARY Graafian - when these small lakes coalesce into ONE lake 16/08/2023 R. S. MAALMAN 24

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26. SPERMATOGENESIS The sequence of events by which spermatogonia are transformed into mature sperms . Three phases: Spermatogonial phase Spermatocyte phases (meiosis) Spermatids phase (spermiogenesis) 16/08/2023 R. S. MAALMAN 27

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28. Spermatid Phase ( Spermiogenesis ) Spermatids undergo extensive cell remodeling as they differentiate into mature sperm. Transforms itself into a small agile sperm by a process called SPERMIOGENESIS 16/08/2023 R. S. MAALMAN 29

29. COMPARISON OF SPERMATOGENESIS AND OOGENESIS SPERMATOGENESIS OOGENESIS Time of starting At puberty Before birth Process Continuous Temporary stoppage In DICTYOTENE Between ovulation and fertilization Time of ending Old age Permanent stoppage at MENOPAUSE Method In overlapping waves Non-overlapping cycles Nos. starting maturation Millions of primary spermatocytes 5-15 primary oocytes Nos. of mature gametes produced from one meiotic division Four One Total nos. of gametes produced 100 million/dl 1 Types of gametes produced Y-bearing AND X bearing sperms X-bearing ova only Approximate duration to form a gamete 3 months 14 days Morphology Small head and a tail Large and round Vascular barrier Zona occludens of Sertoli cells Zona pellucida and follicular cells Onerous responsibility Determinant of sex of baby Feeding famished sperm at fertilization 30 16/08/2023 R. S. MAALMAN

30. Maturation of gametes (Ovum) The development of the ovarian follicle is characterized by growth and differentiation of primary oocyte Proliferation of the follicular cells Formation of zona pellucida The development of the connective tissue capsules – theca folliculi from the ovarian stroma

31. Maturation of gametes (spermatozoon)

32. Morphology of a mature sperm and a mature oocyte

33. Specimen question Compare and contrast: a spermatozoon and an ovum Spermatogenesis and oogenesis

34. Transport of Gametes The great event of fertilisation occurs in the outer one-third of the uterine tube - ampulla. Sperm transport in the Female Genital Tract occurs by a combination of two mechanisms : –  Motility of spermatozoa – they move at the speed of 2-3 mm/hour –  Contractions in the female genital tract 16/08/2023 R. S. MAALMAN 35

35. Transport of Gametes cont. List the barriers to sperm transport from the vagina to the ampulla of the uterine tube How do oocyte and sperm transported to the site of fertilization 16/08/2023 R. S. MAALMAN 36

36. Fertilization The process by which sperm and egg unite. Three phases exist: Phase 1: Passage of a sperm through the corona radiata. Dispersal of the follicular cells of the corona radiata The action of the enzyme hyaluronidase released from the acrosome of the sperm. Tubal mucosal enzymes and Movements of the tail of the sperm also appear to assist the dispersal. 16/08/2023 R. S. MAALMAN 37

37. Fertilization: Phase 2 I. Sperm binding and penetration of the zona pellucida Sperm binding occurs through the interaction of sperm glycosyltransferases and ZP3 receptors located on the zona pellucida . Sperm binding triggers the acrosome reaction , Release of acrosomal enzymes, e.g. esterases , acrosin , and neuraminidase which cause lysis of the zona pellucid. 16/08/2023 R. S. MAALMAN 38

38. Fertilization: Phase 2 II. Penetration of the zona pellucida requires acrosomal enzymes, specifically acrosin , a proteolytic enzyme. Sperm contact with the cell membrane of a secondary oocyte triggers cortical reaction , Entails the release of cortical granules (lysosomes) from the oocyte cytoplasm. Polyspermy block , which renders the secondary oocyte cell membrane impermeable to other sperm . 16/08/2023 R. S. MAALMAN 39

39. Phase 3: FERTILIZATION Fusion of sperm and oocyte cell membranes The entire sperm (except the cell membrane) enters the cytoplasm. The sperm nuclear contents and the centriole pair persist, but the sperm mitochondria and tail degenerate. The sperm nucleus becomes the male pronucleus . All mitochondrial DNA is of maternal origin ). 16/08/2023 R. S. MAALMAN 40

40. FERTILIZATION CONT. The secondary oocyte completes meiosis II, forming a mature ovum and a second polar body. The nucleus of the mature ovum is now called the female pronucleus . M/f pronuclei fuse, forming a zygote ( its existence terminates when the first cleavage division occurs. Syngamy is successful completion of fertilization 16/08/2023 R. S. MAALMAN 41

41. THANKS ZYGOTE IS FORMED!! WHAT NEXT?

42. FROM ZYGOTE TO BLASTOCYST & IMPLANTATION 16/08/2023 R. S. MAALMAN 43

43. Learning Performance Objectives Define/describe cleavage division of zygote Explain implantation Indicate sources of nourishment from zygote to implantation Explain how twins are formed (???) 16/08/2023 R. S. MAALMAN 44

44. Cleavage Division Succession of rapid divisions resulting in large number of smaller cells ( blastomeres ). No synthesis of new cytoplasm; thus, fractionation of oversize single cell (zygote). 16/08/2023 R. S. MAALMAN 45

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48. Cleavage Division - consequence From 8-cell stage onwards, number of blastomeres not necessarily even. Why? 12-16-cell stage, morula arrives in uterine cavity, approx. 5-8 days post fertilization At approx. 32-cell stage, morula changes shape and acquires a new name. 16/08/2023 R. S. MAALMAN 49

49. 16/08/2023 R. S. MAALMAN 50 Blastocyst

50. Implantation blastocyst arrives the endometrium in the secretory phase Blastocyst hatching out of ZP exposes trophoblast to secretory endometrium Blastocyst attached to endometrium with ICM closest to uterine wall. 16/08/2023 R. S. MAALMAN 51

51. Implantation Adherence, attachment, and erosion of endometrium resulting in “burrowing” of blastocyst into uterine wall = implantation.

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53. 16/08/2023 R. S. MAALMAN 54 Implanted Blastocyst

54. Decidual Formation Under influence of progesterone and hCG Culminates in decidualization 16/08/2023 R. S. MAALMAN 55

55. Site of Implantation Usually – body of uterus, upper part of posterior wall near the midline. Implantation anywhere outside the body of the uterus, known as ectopic pregnancy. Common ectopic site is within oviduct – tubal pregnancy. Subject to rupture. Abdominal among small intestines, even in liver can be carried till Caesarean delivery at 28 wks. 16/08/2023 R. S. MAALMAN 56

56. 16/08/2023 R. S. MAALMAN 57 Ectopic sites

57. 16/08/2023 R. S. MAALMAN 58 Relative Occurrence of Ectopic implantation at various sites

58. Twin Formation Total separation of conceptus at 2-cell stage results in identical twins. Identical twins develop from same zygote, hence monozygotic twins. Sex of embryos. Fertilization of two separate ova by two different sperms results in two zygotes, hence dizygotic or fraternal twins. Sex of embryos. 16/08/2023 R. S. MAALMAN 59

59. Pictures

60. SECOND WEEK OF DEVELOPMENT R. S. MAALMAN

61. BLASTOCYST FORMATION On the 4 th  day the  morula  is  transformed into a  blastocyst . Cells of the inner cell mass( embryoblast ) outer cell mass, or trophoblast

62. BLASTOCYST FORMATION

63. BLASTOCYST FORMATION  The blastocyst attaches to the endometrial epithelium with it's embryonic pole on the 6 th day Trophoblast differentiate into inner cytotrophoblast outer syncytiotrophoblast The blastocyst usually implants on the posterior uterine wall . The implantation begins at the end of the first week and is completed by the end of the second week During the 6th day, the blastocyst attaches to the endometrial epithelium.

64. BLASTOCYST FORMATION The  syncitiotrophoblast  has two important secretory functions: 1.       Secretion of hydrolytic enzymes;    essential for erosion and penetration of the endometrium 2.      Secretion of Human Chorionic Gonadotrophin  (HCG), maintained the corpus luteum It is essential for maintenance of pregnancy. 

65. SECOND WEEK OF DEVELOPMENT

66. SECOND WEEK OF DEVELOPMENT the embryoblast also differentiate into two layers: hypoblast layer- a layer of small cuboidal cells epiblast layer - a layer of high columnar cells adjacent to the amniotic cavity, the

67. SECOND WEEK OF DEVELOPMENT Together, the layers form a flat disc. a small cavity appears within the epiblast . This cavity enlarges to become the amniotic cavity. Epiblast cells adjacent to the cytotrophoblast are called amnioblasts Together with the rest of the epiblast , they line the amniotic cavity. The endometrial stroma adjacent to the implantation site is edematous and highly vascular.

68. SECOND WEEK OF DEVELOPMENT

69. SECOND WEEK OF DEVELOPMENT

70. SECOND WEEK OF DEVELOPMENT Flattened cells probably originating from the hypoblast, form a exocoelomic membrane (Hauser's membrane) This membrane and the hypoblast form the lining of the exocoelomic cavity ( primitive yolk sac ).

71. SECOND WEEK OF DEVELOPMENT Cells derived from the yolk sac form the extraembryonic mesoderm and fill the space between the trophoblast externally and the amnion and the exocoelomic membrane internally . Large cavities within the extraembryonic mesoderm become confluent and form the extraembryonic coelom .

72. SECOND WEEK OF DEVELOPMENT The extraembryonic coelom splits the extraembryonic mesoderm into two layers: extraembryonic somatic mesoderm , extraembryonic splanchnic mesoderm The extraembryonic somatic mesoderm and the two layers of trophoblast constitute the chorion .

73. SECOND WEEK OF DEVELOPMENT The extraembryonic somatic mesoderm and the extraembryonic part of the ectoderm constitute the amnion The endodermal germ layer produces additional cells which form a new cavity, known as the secondary or definitive yolk sac . The extraembryonic coelom expands to form a large chorionic cavity , within which the embryo and the attached amniotic and yolk sac are suspended by the connecting stalk.

74. IMPLANTATION VIDEO

75. Applied embryology Family planning methods : hormonal, barrier, safe period (abstinence) and intrauterine devices. Fertility management : copulation profile, semen analysis, integrity of the ovarian/menstrual cycle and implantation problem (intrauterine space occupying lesion) Control of sex of the embryo : timing of intercourse, in vitro technique of separating the X and Y bearing sperms using their differential swimming ability, microscopic differences between X and Y sperms Artificial insemination

76. Applied embryology (cont.) In vitro fertilization and embryo transfer; Stimulation of ovarian follicles Laproscopic aspiration mature follicle Oocytes placed in culture medium Sperm added immediately Fertilized oocytes (zygotes) are monitored Between 8-16 cells stage, the zygotes are transfer the uterine cavity What is a surrogate mother

77. Specimen question How will you investigate a couple who has an infertility problem http://fertility.treatmentabroad.com/treatments/in-vitro-fertilisation-ivf-types what are the meaning of the following terms in this context? 1. IVF , 2. GIFT . 3. ZIFT  4. ICSI Explain how twins are form. What is mosaicism ? Amenorrhea, Dysmenorrhea, Menorrhagia Premenstrual dysphoria ( PMD ) Menopausal

78. Gastrulation Commencement of Embryonic Period of Development

79. Definition Gastrulation is the process by which the early embryo is transformed into a body consisting of multiple cell and tissue types Marks commencement of embryonic period that extends from wk 3-8 Involves several types of (morphogenetic) movements and shape changes Results in transformation of bilaminar embryonic disc to a trilaminar one: ectoderm, mesoderm and endoderm

80. Gastrulation  Three important structures form primitive streak notochord   neural tube

81. Gastrulation – the Process Begins with appearance of Primitive Streak that appears early in 3rd wk PS is first recognized as a midline thickening of ectodermal cells at the posterior (or tail) of the embryo Embryo at this stage is pear-shaped, having a broader anterior (head) end and tapering to a narrow posterior end.

82. Gastrulation – the Process

83. Gastrulation – the Process In the region of the primitive streak and its cephalic end (the  primitive node ), the epiblast cells move inward ( invaginate ) to form a new cell layer ( intraembryonic mesoderm ) between the epiblast and hypoblast. Some of the epiblast cells displace hypoblast, there by creating the embryonic  endoderm .

84. Gastrulation – the Process The cells remaining in the epiblast form the  ectoderm . Cells migrating cranially through the primitive node form the notochordal process (prospective notochord), which defines the primitive axis of the embryo

85. Gastrulation – The Process PS cells form a rod-like structure that extends approx. three-fifths the length of the embryo. Cells that move internally later will migrate over the endoderm and form (intra) embryonic mesoderm. Cells that remain on the surface will form ectoderm. Migrating PS cells move laterally, cephalically, and caudally b/n ectoderm and endoderm of embryonic disc.

86. Gastrulation – the Process Note that mesoderm does not extend b/n ecto - and endo-derm of the buccopharyngeal and cloacal membranes. At caudal end of embryo, mesoderm passes round cloacal membrane to become continuous with extraembryonic mesoderm of the body stalk.

87. Formation of Notochord While PS is giving rise to (intra)embryonic mesoderm, a soild cord of cells grows cephalically from primitive knot b/n ecto - and endoderm. The cord of cells known as notochord become attached just caudal to the region of the buccopharyngeal membrane. Notochord undergoes complicated dev’t to give rise to a solid rod of cells that forms a central axis of the embryo.

88. Notochord • After notochord forms, embryo now has Anterior-posterior, dorsal –ventral, as well as Lt. and Rt. Sides Axial symmetry is established. Notochord induces formation of neural tube from ectoderm, that gives rise to brain and spinal cord. Spinal cord and caudal part of base of skull develop around notochord.

89. Fate of Notochord In later dev’t it degenerates in region of vertebral body, but in intervetebral region it enlarges to form the nucleus pulposus of intervetebral disc. After giving rise to (intra)embryonic mesoderm, PS usually degenerates. When cells of PS fail to degenerate they give rise to tumours in midline known as teratomas . Teratomas vary from simple cysts to mass of material composed of different types of well differentiated tissues.

90. Left-Right asymmetry is established at gastrulation Leftward beating of cilia at node moves secreted molecules sonic hedgehog (Shh) & FGF-8 to the left side of embryo. Causes left side genes Nodal and Pitx2 to be expressed which then pattern developing organs. If cilia are defective, Shh and Fgf8 can randomly end up on right side, resulting in reversal of symmetry, aka situs inversus (liver on the left, spleen on the right, etc.) Situs can be complete (everything reversed) or partial (only some organs reversed).

91. Situs Inversus

92. What happens if there is “not enough” gastrulation? Caudal agenesis ( sirenomelia ) Premature regression of the primitive streak leads to widespread loss of trunk and lower limb mesoderm. VATeR association: V ertebral defects A nal atresia T racheo -esophageal fistula R enal defects VACTeRL association: those above plus… C ardiovascular defects L imb (upper) defects

93. Teratogenesis Associated With Gastrulation Holoprosencephaly – due high doses of alc. Caudal dysgenesis ( sirenomelia ), genetic abnormalities and toxic insults.

94. If the primitive streak fails to regress, multipotent primitive streak cells can develop into multi-lineage tumors (containing ecto-, meso-, and endodermal tissues). What happens if there is “too much” gastrulation? Sacrococcygeal teratoma

95. Sacrococcygeal Teratoma (SCT)

96. Neuralation Development of Central Nervous System Organogenesis By Maalman

97. NEURULATION Neurulation is concurrent with gastrulation (formation of intraembryonic mesoderm) in the 3 rd wk. It is the process whereby the neural plate forms the neural tube. Development of the neural tube into the brain and spinal cord proceeds throughout intrauterine life.

98. Neurulation : Introduction Accomplishes three major things , it creates: the neural tube , which gives rise to the central nervous system. the neural crest , which migrates away from the dorsal surface of the neural tube, and gives rise to a diverse set of cell types. the epidermis, which covers over the neural tube once it is created, and forms superficial layer of skin.

99. Neurulation Neural plate – 3rd wk Site – b/n primitive knot and oro -pharyngeal memb . Induction – hedgehog (notochord); & noggin. Neural groove/folds. Neural tube

100. Neurulation

101. Head- and Tail-fold Developing CNS associated with rolling of embryo in head and tail regions. Thus, formation of Head fold and Tail fold resp.ly Embryo assumes a curved shape by 4th wk.

102. Signalling Molecules Involved -1 Neurulation occurs in response to soluble growth factors secreted by the notochord. Ectodermal cells are induced to form neuroectoderm from a variety of signals. Ectoderm sends and receives signals of BMP4 (bone morphogenic protein) and cells which receive BMP4 signal develop into epidermis. The inhibitory signals chordin , noggin and follistatin are needed to form neural plate. These inhibitory signals are created and emitted by the notochord.

103. Signalling Molecules Involved -2 Cells which do not receive BMP4 signaling due to the effects of the inhibitory signals will develop into the anterior neuroectoderm cells of the neural plate. Cells which receive FGF (fibroblast growth factor) in addition to the inhibitory signals form posterior neural plate cells.

104. Anterior & Posterior Neuropores Fusion of neural groove commences in midline – 4 th somite . Region of initial closure = future jxn b/n brain & SC Extends cranially & caudally. Ant. ( rostral ) neuropore closes first – day 26 Post. (caudal) neuropore closes 2 days later.

105. Once completely formed, the neural tube detaches from the remainder of the surface ectoderm, and sinks below it into the underlying mesenchyme . During fusion of the neural folds, cells on the lateral margins do not become incorporated in the neural tube, but form a strip of ectodermal cells ( known as Neural Crest ) that lie between the neural tube and surface ectoderm.

106. Cells of the neural crest migrate to form various structures, including: a. Cranial sensory ganglia b. Posterior root ganglia c. Parasympathetic ganglia of the GIT. d. Sympathetic ganglia. e. Cells of the suprarenal (adrenal) medulla. f. Schwann cells. g. Melanocytes h. Parafollicular cells of thyroid gland. i . Odontoblasts of teeth

107. The cephalic end of the neural tube dilates to form three primary vesicles, namely; Forebrain ( Prosencephalon ), Midbrain ( Mesencephalon ), and hindbrain ( Rhombencephalon ). The caudal end of the neural tube elongates, remains narrow and forms the spinal cord.

108. Anomalies of NT closure. Failure of the neural tube to close through out the length of the body results in a condition called craniorachischisis . Failure of the cranial and caudal neuropore closure results in conditions called anencephaly and spina bifida resp.ly

109. Spina Bifida variations A. Occulta B. SB with meningocoele C. SB with meningomyocoele D. SB with myeloschisis

110. Anomalies of brain A. Meroanencephaly B. Meningoencephalocoele C. Microcephaly D. Hydrocephalus

111. Differentiation of the wall of the Neural Tube. Wall of neural tube becomes pseudostratified ( neuroepithelium ) known as Matrix layer. Proliferation of neuroepithelial cells produces a layer of cells on the lateral side of the Matrix layer, known as Mantle layer. Cells of the Mantle layer are known as primitive neurocytes , and give rise to processes that become nerve fibres or axons.

112. The nerve fibres grow peripherally (laterally) from cell bodies (nuclei) of the primitive neurocytes . The mantle layer containing nerve fibres and cell bodies will become the grey matter of the nervous system. The peripheral nerve fibres of the neurocytes become myelinated and form the Marginal Layer, which will form the white matter of the nervous system. In addition to primitive neurocytes the neuroepithelial cells also give rise to two types of cells, namely; Oligodendrocytes and Astrocytes ( neuroglial cells).

113. A third type of neuroglial cell, Microglia develops from surrounding mesenchymal cells which migrate into the developing spinal cord along with blood vessels. Finally the neuroepithelial cells differentiate into the 4th type of neuroglial cell known as Ependyma , which form the lining (epithelium) of the cavities in the brain and spinal cord.

114. Formation of SC from NT In narrow caudal part of the neural tube below the three (primary) brain vesicles, accumulation of neurocytes during formation of the mantle and marginal layers proceeds in such a way that the lateral walls are thicker with thinner roof and floor plates. A larger ventral (anterior) thickening becomes apparent first, followed by a dorsal (posterior) thickening. The thickened ventral portion of each lateral wall is known as Basal lamina or plate; and the thickening of the dorsal walls that appear later is known as Alar lamina or plate.

115. Cells of the basal plate, which will become the anterior horn cells of the spinal cord are more numerous and larger than those of the alar plate.

116. ?? THANKS