General anatomy : 1st week of development

 

General embryology 

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The main events of 1^st week

1.     Fertilization

2.     Zygote formation

3.     Initiation of cleavage division

4.     Formation of morula

5.     Morula converts into blastocyst

6.     Implantation

Developmental anatomy or  Embryology (from Greek  embryon, "the unborn, embryo"; and  logia mean a branch of learning; a study of a particular subject) is the study of the formation and development of embryo from conception to birth .

 Additionally, embryology encompasses the study of congenital disorders that occur before birth, known as teratology.

Prenatal /Gestational period: The prenatal period is defined as the gestational period, from conception to birth. 

Embryologically, the whole gestation period is subdivided into three period:

a)    Germinal period/ pre-embryonic period: it extends from 1^st to 2^ndweek of development. This period includes fertilization, cleavage division, morula and blastocyst  formation, implantation and formation of bi-laminar germ disc.

b)    Embryonic period / period of organogenesis: it extends from the 3^rd to 8^th week. During this period , the three germ layers  formed from gastrulation (the ectoderm, endoderm, and mesoderm) form the internal organs of the organism. Both the germinal period and embryonic period arethe most sensitive period to teratogenesis when exposure to a teratogenic agent has the greatest likelihood of producing a malformation.

c)     Fetal period: it extends from the 9 week  to birth.

Post - natal development

1. Infancy (from birth to 1^st year)

2. Childhood (from 2^nd to 12^th year)

3. Puberty (from 13^th to 16^th year)

4. Adolescence (from 17^th to 18^th year)

5. Adult (from 19^th to 25^th year)

 

Ontogeny ,  it is the complete life cycle and the process of   development of organism from a single cell, an egg cell or a zygote, to an adult organism.  

It includes  prenatal, postnatal development, maturity, senility  and death of an organism. It is a gradual process of expression of the blue print of life which store within the genome of zygote.

Phylogeny is the history of the evolution of a species or group.

It is the study of relationships among different groups of organisms and their evolutionary development.

Ontogeny repeats phylogeny

Ontogeny repeats phylogeny was expressed by Ernst Haeckel which explains that the development of embryo of an organism from fertilization to gestation goes through various stages of growth and development that resembles successive adult stages in the evolution of the organism's remote ancestors.

The various stages from fertilization of an organism is known as ontogeny and resemblance with remote ancestors is known as phylogeny. This theory is also known as theory of recapitulates or biogenetic law.

In the development of human kidney, three stages of development observed pronephros, mesonephrose and metanaphrose

·         Pronephric kidney appears first in the early weeks of development in the neck and upper thoracic regions. This kidney persists in adult forms of some fishes and cyclostomes but in man it completely disappears.

·         mesonephric kidney appear  replacing pronephric kidney,  which is appears in the lower thoracic and lumbar regions and these kidney persists as permanent kidney in most of the fishes and amphibian. In human mesonephric kidney soon degenerates.

·         metanephric kidney appear  replacing mesonephric kidney which appears first in the lumbo-sacral region and these kidneys persists as permanent kidney in reptiles, birds and mammals.

So the development of human kidney shows the chronology of development that man kidney first cross the fish and then replies stage and ascend and reach the mammalian stage, the final stage of development.

This events explain the famous quote “ontogeny repeats phylogeny” or  "Ontogeny recapitulates phylogeny".

 

Gestational age / Length of the pregnancy: it is calculate in two ways

1. From 1^st day of last menstrual period: 280 days or 40 weeks

2. After fertilization: 266 days or 38 weeks

Common embryological terms:

Conceptus:the embryo and its adnexa or associated membranes

Embryo:the developing human during its early stages of development. It extends to the end of the eighth week

Fetus:after the embryonic period the developing human is called a fetus.

Abortion:it is defined as the spontaneous or induced termination of pregnancy before fetal viability. 

Menopause: the permanent cessation of the menses

Menarche:establishment or beginning of the menstrual function.

Embryonic period /period of organogenesis: 3^rd to 8^th weeks of intrauterine life is known as embryonic period, most major organ and organs systems are formed during this period.

Organizer: a region of the embryo that is capable of determining the differentiation of other regions.

•      Primary organizer: primitive streak (it induces the development of notochord)

•      Secondary organizer: notochord (it induces the development of neural tube)

•      Tertiary organizer: neural tube (it induces the development of somites of paraxial mesoderm)

Induction: it is the process of influence of an inductor (chemical substance) on the differentiation of adjacent cells or the development of an embryonic structure.

Inductor: A tissue elaborating a chemical substance that acts to determine the growth and differentiation of embryonic parts.

Evocator: a substance or tissue that induces differentiation of embryonic parts.

Basic process in development

1. Growth

2. Differentiation

3. Induction

4. Migration

5. Apoptosis or program cell death

Growth: means increase in the bulk of tissue which takes place by

1. cells division,
2. increasing cell size or
3. increased accumulation of intercellular substance

types of growth or Growth is occurred in three ways

•      Multiplicative growth: (cell number is increase by cell division) EX: epidermis of skin, intestinal epi

•      Auxetic growth: (cell size is increase) EX: oocytes, some neurons 

•      Accretionary growth: (increase accumulation of intercellular substance ) EX: bones, cartilage

Differentiation: is a complicated process in which groups of cells assume special characteristics and functions

Totipotent cells: are able to produce a separate embryo under favorable conditions

Pluripotent cells: are groups of cells which produce specific type of tissue

Cells of human body

1. Somatic cells
2. Germ cells

Somatic cells of body are three types:

•      Permanent cells: they do not divide in post natal life (after birth) . Ex: neuron

•       Labile cells are cells that multiply constantly throughout life. ex: epidermis of skin(replace within one month) , intestinal epithelium(replace daily) ,

•      Stable cells are cells that multiply only when needed. Ex : liver, skeletal muscle

Germ cells:are two types male and female germ cells

Female germ cell:Oocyte:the female germ or sex cell produced in the ovaries

•      Immature female germ cells:Oogonia/ Diploid /Chromosome number: 46 ( 44 autosomes+ XX)/At intrauterine life, they increase their number by mitosis  

•      Mature female germ cells:Ovum ( mature oocyte ) / Haploid/Chromosome number: 23 (22 autosomes + X) / After puberty uptomenopouse, only one ovum is produced by meiosis in each month

Male germ cell: Sperm:the male germ cell produced in the testes.

•      Immature male germ cells :Spermatogonia/Diploid /Chromosome number: 46 ( 44 autosomes+ XY)/ At  puberty they start to increase their number by mitosis  and continued until death

•      Mature male germ cells :Spermatozoa / Haploid / Chromosome number: 23 (22 autosomes + X Or 22 autosomes + Y) / At  puberty they start to increase their number by meiosis &  continued until death

Difference between male & female germ cell

•      Female germ cells :	•      Male germ  cells
•      Only one type: 22X •      22 autosomes •      1  Sex chromosome X	•      two types : 22X  & 22Y •      22 autosomes and one sex chromosome  either X or Y  •      SN: a single male germ cell never contain both X & Y

 

 

Gametogenesis

It is the process of formation and development of male and female gametes.

·         Gametes are derived from primordial germ cells.

·          It is formed in the epiblast during the 2^nd  week

·         Then  move to the wall of the yolk sac  during the 4^th week ,

·         these cells begin to migrate from the yolk sac to the developing gonad, where they arrive by the end of the 5^th week

Oogenesis:it is the sequence of events by which oogonia are transformed into mature

oocytes.

This maturation begins before birth and completed after puberty and continues to the menopause (the permanent cessation of the menses)

Maturation of oocytes:

Before birth

Primordial germ cells (arrived in the gonad by the end of the 5^th week)

Differentiate into oogonia ( at5^th month its number reaches maximum about 7 million)

Primary oocytes : oogonia enlarge to form primary oocytes.

Primordial follicle – a primary oocyte with its surrounding flattened follicular epithelium.

Near the birth, the primary oocyte remainarrested in prophase of meiosis I(diplotene stage) and do not finished meiosis I before puberty

At puberty

Primary follicle: follicular cell became cuboidal and zona pellucida begin to form

Growing follicle: follicular cells forming the stratified layer of granulose cells and well-defined zona pellucida

Secondary follicle: fluid filled spaces developed within the granulosacells

.

Graafian follicle

It is the mature form of ovarian follicle containsingle cavity within the granulosa cells

Shortly before ovulationthe primary oocyte completes thefirst meiotic division and became secondary oocyte.

The division is unequal, the secondary oocyte receives almost all the cytoplasm but the 1^st polar body receives very little.

The secondary oocyte begins 2^nd meiotic division but arrest at metaphase.

Meiosis II is completed only if the oocyte is fertilized.

 

Ovarian cycle

It is a regular monthly cyclic change in the ovaries (which start at puberty) comprising the development of ovarian follicles, ovulation and formation of corpus luteum constitute the ovarian cycle.

It has three phases are

i) Follicular phase: follicular development

ii) LH surge (ovulation)

iii) Luteal phase

•       Correlation between ovarian and menstrual cycle

Ovarian cycle	Development / event occurred	Hormone	Duration(Normal duration 28 days )	Menstrual cycle (Normal duration 28 days)
Follicular phase	Growth of ovarian follicles by FSH Follicle stimulating hormone secreted from anterior pituitary	Growing ovarian follicle secreted estrogen	14-21 days before ovulation	Menstrual phase 1-4 days (Without fertilization degeneration of corpus luteum is occurred so less progesterone is produce which  causebreak down of endometrium.) Proliferative phase (5-14 days )proliferation of endometrium by estrogen secreted from growing ovarian follicles
LH surge	Ovulation occurred due to sudden increase secretion of LH (luteinizing hormone) from anterior pituitary		24 hrs
Luteal phase	Development of corpus luteum by LH	Luteinizing hormone, develop corpus luteum which secrete estrogen and progesterone.	14 days after ovulation (14-28 days)	Secretory phase (From 14-28 days) progesterone promotes growth of endometrium by increasing proliferation, cellular hypertrophy, and deposition of extracellular matrix and uterus ready for implantation. Corpus luteum produce progesterone, inhibitin and estradiol .

SN:  An LH surge is a rapid increase of the luteinizing hormone (LH) in a woman's bloodstream that occurs 24-48 hours prior to ovulation which is responsible for  release of a mature egg around the second week of each menstrual cycle

•       At luteal phase of ovarian cycle, estrogen level in the body become high. This is known as a "secondary estrogen surge.

Menstrual cycle :

•       The endometrium of uterus undergoes monthly cyclic changes for implantation of zygote during reproductive life of a woman called menstrual cycle.

The phases of menstrual cycle

 

1. Menstrual phase
2. Proliferative(follicular)  phase
3. Secretory (progestational) phase

 

How the menstrual cycle is controlled?

 

Both ovarian and menstrual cycle is controlled by the Hypothalamic-Pituitary-Gonadal (HPG) Axis.

Gonadotropin releasing hormone (GnRH) from the hypothalamus stimulates luteinizing hormone (LH) and follicular stimulating hormone (FSH) release from the anterior pituitary gland.

LH and FSH are gonadotropins that act primarily on the ovaries in the female reproductive tract:

·         FSH binds to granulosa cells to stimulate follicle growth, permit the conversion of androgens (from theca cells) to oestrogens and stimulate inhibin secretion

·         LH acts on theca cells, cause ovulation, growth of corpus luteum which produce progesterone, inhibin A and estradiol.

The menstrual cycle is controlled by both positive and negative feedback systems:

·         High oestrogen levels (in the absence of progesterone) positively feedback on the HPG axis.

·         Moderate oestrogen levels exert negative feedback on the HPG axis

·         Oestrogen in the presence of progesterone exerts negative feedback on the HPG axis

·         Inhibin selectively inhibits FSH at the anterior pituitary

1. Hypothalamus secrete GnRH > act on anterior pituitary > anterior pituitary secrete FSH > FSH act on ovary > FSH developed ovarian follicles > ovarian follicle secrete estrogen > estrogen cause proliferation of  endometrium of uterus, this phase known as  proliferative phase of menstrual cycle.

2. After ovulation corpus luteum start to grow and secrete inhibitin which selectively inhibit anterior pituitary to secrete FSH > so no further development of ovarian follicles

3. Well developedcorpus luteum also secrete progesterone promotes growth of endometrium by increasing proliferation, cellular hypertrophy, and deposition of extracellular matrix and uterus ready for implantation, this phase known as secretory phase of menstrual cycle.

Spermatogenesis

Definition: It is the sequence of events by which spermatogonia are transformed into mature sperms or spermatozoa.

This maturation process begins at puberty and continues into old age

In male the primordial germ cells remain dormant until puberty.

At puberty, after several mitotic divisions of the spermatogonia, primary spermatocytes (diploid)  are formed. They are the largest cells of seminiferous tubules and enters a prolonged prophase (22 days)

Each primary spermatocyte is completed meiosis Ito form two haploid secondary spermatocytes

Subsequently, two secondary spermatocytes complete the meiosis II to form four spermatids

Spermiogenesis

The spermatids are gradually transforms into mature sperm or spermatozoa by a process known as spermiogenesis.

These changes include:

1. Loss of cytoplasm.
2. Formation of acrosomes which covers half the nuclear surface, derived from the golgi region of spermatid contain enzymes that assist penetration of corona radiata and zona pellucida during fertilization
3. Condensation of nucleus
4. Formation of neck, middle piece, and tail
5. The mitochondria arranged in the middle piece as mitochordial sheath

The time required for a spermatogonium to become a mature spermatozoon is approximately74 days

 

Difference between oogenesis and spermatogenesis

Location	Testes	Ovary
Number of gamete produce	Life long production (millions)	Fixed amount ( only mature 400)
Per day gemate produce	Millions sperm produce per day	One ovum  per 28 days cycle
Gamete per germ cells	Four	One ovum and 2-3 polar body
Beginning of the process	At puberty	At fetal life
Time of gamete formation	Continuous	Once in a month
End of process	Life long but reduces in later part of life	End at menopause
Time of gamete release	Anytime	Once in a month
Meiotic division	Uninterrupted	Arrested
Name of immature cell	Oogonia	Spermatogonia
Name of mature cell	Ovum	Spermatozoa
Release of germ cell	During ejaculation	During ovulation
Motility of mature germ cell	Motile	Not motile

 

Fertilization

Definition: The process by which male and female gametes fuse to form zygote

Site of fertilization: the ampullary region of the uterine tube

Spermatozoa are not able to fertilize the oocyte immediately uponarrival in the female genital tract but must undergo a) capacitation  b) acrosome reaction to acquire this capability.

Capacitation :is a period of conditioning in the female reproductive tract that in the human lasts approximately 7 hours

The acrosome reaction:which occurs after binding to the zona pellucida, is induced by zona proteins.

The phases of fertilization include

Phase 1: penetration of the corona radiata

Phase 2: penetration of the zona pellucida.

Phase 3: fusion of the oocyte and sperm cell membranes.

The main results of fertilization are as follows

• restoration of the diploid number of chromosomes
• determination of sex
• initiation of cleavage

Egg responses in three ways when the spermatozoon has entered the oocyte

1.      Cortical and zona reactions:

a) The oocyte membrane becomes impenetrable to other spermatozoa.

b) Zona pellucida alters its structure and composition to prevent sperm binding and penetration.

2.      Resumption of the second meiotic division.

3.      Metabolic activation of the egg.

Zygote

This cell formed by the union of an oocyte and a sperm during fertilization

·         Cleavage:itis a series of mitotic divisions that results in an increase in cells, blastomeres, which become smaller with each division.

·        Morula: the 12-16 cell stage of the early embryo at 3 days post conception

• Blastocyst:after the morula enters the uterus from the uterine tube, a fluid filled cavity –  the blastocyst cavity –develops inside it . This change converts the morula into a blastocytes

Q: In which phase of menstrual cycle implantation is occurred?

Ans:implantation is occurred at the secretory phase of menstrual cycle, during this time endometrium is rich in nutrition, secretion present within the glands, stroma cells, also known as decidual cells  are  rich in glycogen and lipid ,

 

Implantation

The process during which the blastocyst attaches to the endometrium and subsequently embeds in it.

Time of implantation

It occurs at 6 days after fertilization and by the 11 th to 12^th days of development the blastocyst is completely embedded in the endometrial stroma.

Implantation bleeding

Bleeding may occur at the implantation site as a result of increase blood flow into the lacanarspaces.

Implantation bleeding occur near the 28^th day of menstrual cycle, it may confused with normal menstrual bleeding.

Mechanism of implantation:

 it has three stages:

(a) the blastocyst contacts the implantation site of the endometrium (apposition);

(b) trophoblast cells of the blastocyst attach to the receptive endometrial epithelium (adhesion); and

(c) invasive trophoblast cells cross the endometrial epithelial basement membrane and invade the endometrial stroma (invasion) 

Normal sites of implantation: The blastocyst implants in the endometrium along the anterior or posterior wall of uterus near the fundus.

(Trophoblast cells of blastocyst invade the epithelium and underlying endometrial stroma with the help of proteolytic enzymes)

Abnormal implantation:

1.        Implantation in abdominal cavity

2.        Implantation in the pouch  of Douglas

3.        Implantation in the ampullary region of f. tube (most common)

4.        Implantation in the internal os

5.        Ovarian implantation

6.        Interstitial implantation

7.        Tubal implantation

Decidua

Decidua means gravid endometrium.

Decidualization / Decidua reaction

·         Stromal cells of the endometrium become polyhedral and loaded with glycogenand lipids

·         Stromal cells begin to secrete cytokines, growth factors, and proteins like IGFBP1 and prolactin along with extracellular matrix (ECM) proteins such as fibronectin and laminin. The increased production of these ECM proteins turns the endometrium into the dense structure known as the decidua,

·         Presence of decidual white blood cells (leukocytes),

·         intercellular spaces are filled with extravasate

·         the tissues is edematous

At first it occur at the site of implantation but soon spread throughout the endometrium.

Parts of deciduas:it is divided into three parts

1.       Decidua basalis :parts of decidua deep to the developing embryo which contributes to the development of placenta

2.       Decidua capsularis :part of decidua which surround the embryo and it is separated from the uterine cavity

3.       Decidua parietalis :rest of the decidua excluding decidua basalis and decidua capsularis

 

 

Chorion

It is a highly specialized extra-embryonic membrane that participates in the formation of the placenta.

Formation :it is formed by

1.     Somatopleuric layer of extraembryonic mesoderm

2.     Cytotrophoblast

3.     Syncytotrophoblast

Parts of chorion:

It has two parts

·        Chorion frondosum:the part of chorion where chorionic villi are well developed and it form the fetal parts of placenta.

·        Chorion leave:the part of chorion where chorionic villi are less developed.

Chorionic villi

Numerous small finger-like projections arise from the surface of the chorion is known as  chorionic villi.

Types of chorionic villi:

Primary, Secondary, Tertiary