7.2 The trilaminar germ disk (3rd week)•Introduction

•Formation of the primitive streak •Genesis of the germ layers •Genesis of the notochord •Location of the epiblast cell target and the development of the primitive streak •The bilaminar membranes •Evolution of the mesoblast

•The paraxial mesoblast and the differentiation of the somites •The intermediate mesoblast •The lateral mesoblast

•The intraembryonic coelom •Induction of the neural plate - neurulation

Genesis of the notochordQuiz

Quiz 11

Quiz

Quiz 15

Around the 19th day cells that invade into the primitive node region and migrate along the median line cranially form the chordal process    7     (also known as the axial

process). One can compare this phenomenon with the sliding of a finger into a glove. Thanks to the transparency of the ectoblast this cell migration can be observed in the embryos of experimental animals.The chordal process grows longer through proliferation of the primitive node cells at its front end up to the prechordal plate    6    . At the same time the primitive streak recedes back into the caudal region    6    .

Fig. 5 - Primitive streak seen dorsally Legend

                                                                                                                                          

• The First Week

• Gametogenesis

• The ovum

• The formation of primary oocytes, from which ova are developed, is complete before birth. About 2,000,000 primary oocytes are present at birth, but by adolescence only about 40,000 remain. Over the reproductive period about 400 of these pass through maturation to ovulation.

• The maturation of ova occurs in follicles within the ovary, under hormonal control.

• All primary follicles are arrested in the prophase of the first meiotic division.

• The first meiotic division is completed just before ovulation but progress through the second meiotic division is halted in metaphase.

• If the ovum is fertilized the second meiotic division is completed.

• During the menstrual cycle, Follicle Stimulating Hormone (FSH) promotes growth of several primary follicles, with only one of these reaching ovulation. The final stages of maturation require Luteinizing Hormone (LH).

• Estrogen is produced by the growing follicle, contributing to the growth and development of the reproductive organs, and to the production of the LH surge causing ovulation.

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• At ovulation the secondary oocyte is expelled together with follicular fluid from the surface of the ovary. The fimbriated end of the fallopian tube becomes closely applied over the swelling follicle so that on rupture of the follicle the ovum normally passes into the fallopian tube.

• It is possible for the ovum to miss the fallopian tube and to be free in the peritoneal cavity.

• Oocytes are usually fertilized within 12 hours after ovulation, and may not survive for more than 24 hours before degenerating.

• The sperm

• Sperm are formed by the germinal epithelium of the seminiferous tubules of the testes.

• At puberty spermatogonia in the germinal epithelium divide, grow and transform into primary spermatocytes.

• Each spermatocyte then undergoes a meiotic division to form two haploid secondary spermatocytes.

• The secondary spermatocytes then undergo a second meiotic division to form spermatids which mature into sperm.

• Before sperm are functional and able to fertilize an ovum two events must take place.

• Capacitation is the process of sperm conditioning in which the glycoprotein coat and seminal proteins are removed from the surface of the sperm's acrosome.

• Sperm are capacitated in the uterus and fallopian tubes by uterine secretions.

• The Acrosome Reaction must be completed before sperm may fuse with the ovum.

• Contact with the corona radiata surrounding the ovum triggers the development of perforations in the acrosome, allowing the release of enzymes such as hyaluronidase which facilitate fertilization.

• Fertilization• Fertilization of the ovum involves

penetration of the sperm through the corona radiata, fusion of the oocyte and sperm cell membranes, completion of the second meiotic division of the secondary oocyte, and formation of the zygote.

• The fertilization process lasts about 24 hours. Fertilization usually occurs in the ampulla of the fallopian tube.

• A sperm contacts the zona pelucida and enters the ovum.

• This signals the completion of second meiosis and the second polar body is formed.

• The male and female pro-nuclei then fuse.

• The Zygote and the Blastocyst

• The zygote, formed by fusion of the two haploid gametes, is the first form of a new human being.

• The zygote undergoes a rapid series of mitotic divisions called cleavage.

• As division proceeds two cells are followed by four then eight etc.

• The zygote divides first into two cells then four, eight etc until it forms a ball of cells, the morula.

• The ball then develops a fluid filled core to form an early blastocyst.

• As the blastocyst matures the inner cell mass expands at one end.

• The blastocyst will attach itself to the endometrium at this pole.

• About three days after fertilization the zygote forms a ball of cells known as the morula.

• By four days the morula enters the uterus and develops a central cavity.

• At this stage the structure is termed a blastocyst.

• At six days the blastocyst attaches to the uterine wall to begin the process of implantation.

• Cell division continues rapidly until the blastocyst is formed into outer syncytiotrophoblast and inner cytotrophoblast layers.

• The cells of the syncytiotrophoblast invade the uterine epithelium.

• By seven days after fertilization the blastocyst is securely attached to the endometrium and the inner cell mass has divided to form the hypoblast.

• The inner cell mass and hypoblast will together form the embryonic disc which gives rise to the germ layers of the embryo.

• Clinical Application• Spontaneous abortion• Not all zygotes implant and survive. About

15% are aborted spontaneously, probably due to the presence of chromosomal abnormalities.

In-vitro fertilization• Secondary oocytes removed from mature

ovarian follicles may be fertilized outside of the body and the zygotes implanted in the uterus.  

 

• Formation of the embryonic disc

• The Second Week

• Implantation

• The process of development from a one-celled zygote to a late blastocyst takes about a week.

• During this time the zygote is travelling passively along the fallopian tube towards the uterus.

• However, the zygote may not enter the fallopian tube and may either attach to the ovary or float freely in the peritoneal cavity and attach to the mesentery or an organ such as the liver.

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• The progress of the zygote through the fallopian tube may also be impeded so that by the time the blastocyst is ready to implant, it is still in the fallopian tube.

• Ectopic pregnancies arise from implantation within the peritoneal cavity or in the fallopian tube.

• Ectopic pregnancies represent a significant risk for the mother, paricularly from tubal rupture and associated haemorrhage.

• Few ectopic pregnances progress further than eight weeks.

• Normally, implantation occurs in the endometrium in the upper body of the uterus.

• The late blastocyst attaches to the endometrium at its embryonic pole (inner cell mass).

• At the attachment site the blastocyst forms a syncytiotrophoblast - a syncitium formed by the fusion of several cells.

• The syncytiotrophoblast erodes and invades the endometrium.

• The syncytiotrophoblast expands and contacts the glands and blood vessels of the endometrium. From this stage onwards the developing embryo has access to a source of nutrition.

• The remaining cellular blastocyst is then termed the cytotrophoblast.

• The cells of the cytotrophoblast divide to form new cells which migrate into the syncytiotrophoblast and fuse with it.

• The syncytiotrophoblast begins to produce human chorionic gonadotrophin (hCG), detectable by the end of the second week.

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• If an ectopic pregnancy has occurred, the amount of hCG will be significantly less.

• The inner cell mass is then rearranged so that a cavity appears above it.

• The mass is then thinned out into the form of a two-layered disc.

• A layer of cells lines the cavity above the disc. These cells will become the amnion, and the cavity will become the amniotic cavity.

• The two layers of the disc begin to differentiate so that the upper layer is composed of larger cells forming the epiblast and the small cells of the lower layer forming the hypoblast.

• The cells of the hypoblast divide and migrate to form an inner lining for the cytotrophoblast.

• The chamber which is now enclosed is the primary yolk sac.

                           A - amniotic cavity C -cytotrophoblast ED - embryonic disc G - glands S-syncytiotrophoblast YS - primary yolk sac

• Development of the trophoblast

• As the syncytiotrophoblast expands, spaces appear within it, filled with secretions from the endometrial glands and blood from the eroded vessels.

• Expansion of the syncytiotrophoblast and continued erosion of vessels results in the development of a sponge-like syncytiotrophoblast.

• Since erosion of the vessels in the endometrium has occurred in both arterioles and vennules, a primitive circulation develops.

• There is now a large surface area of syncytiotrophoblast bathed in circulating maternal blood - a primitive placenta.

• Access to this source of nutrition allows for further growth of the embryo.

• As the trophoblast is growing, a separation occurs between the cytotrophoblast and the amnion and yolk sac.

• The cytotrophoblast grows rapidly and pushes out towards the blood spaces in the syncytiotrophoblast.

• The arrangement of syncytiotrophoblast and cytotrophoblast forms primary chorionic villi, present by the end of the second week.

• These villi will eventually be invaded by fetal blood vessels and will become the site of gas, nutrient and metabolite exchange between the embryo and mother.

                                                      

A - amniotic cavity C - Developing chorion

• The embryonic disc

• The embryonic disc is at first uniform, then later becomes polarised as a group of hypoblast cells enlarges as the prechordal plate.

• This indicates the head-end of the future embryo.

• At the end of the second week - beginning of the third week changes occur at the opposite (caudal) end of the epiblast.

• Cells from around the periphery of the disc migrate towards the midline forming a ridge caudally, the primitive streak.

• The primitive streak grows in a cranial direction, with an expanded cranial end, the primitive node.

• Cells produced in the primitive streak migrate to form a layer between the epiblast and the hypoblast, the mesenchyme, and to replace some of the hypoblast cells.

• This is the process of gastrulation in which the epiblast forms the ectoderm,

• the mesenchyme forms the mesoderm and

• the cells which migrate into the hypoblast form the endoderm.

• The ectoderm will form the skin and its glands and appendages, the nervous system, and parts of the mouth, nose, anus and external genitalia.

• The endoderm will form the epithelial lining of the digestive system and its glands, the lining of the respiratory tract down to the alveoli, the epithelium of the bladder and urethra.

• The mesoderm will form the rest of the tissue of the body including all of the connective tissues, muscle, blood and lymphatic vessels.

• Teratogenesis• During development the embryo and fetus are

susceptible to the effects of a wide range of agents such as drugs, chemicals and viruses.

• Each body system has a critical period during which it is vulnerable. In the period covered so far, environmental disturbances may affect cleavage of the zygote and implantation of the blastocyst.

• The end result is likely to be death and spontaneous abortion rather than congenital anomalies.