CHAPTER 29  DEVELOPMENT & INHERITANCE

 

Fertilization occurs when genetic material from ovum and sperm merge into a single nucleus. Only about 1% of the 300-500 million sperm ejaculated reach the secondary oocyte. Fertilization usually occurs in the Fallopian tube 12-24 hours after ovulation. Sperm can travel up the Fallopian tube and reach the oocyte within minutes, but they are not capable of fertilization at that point.  The oocyte is surrounded by several layers of follicular cells, the corona radiata, and a glycoprotein layer, the zona pellucida. After several hours in the female reproductive tract sperm, have undergone capacitation and are capable of fertilization. Release of enzymes of the acrosomes of a number of sperm enable one sperm to penetrate the protective layers of the oocyte--syngamy. Syngamy causes the secondary oocyte to complete Meiosis II and form the ovum. The fertilized ovum contains a nucleus that is a combination of chromosomal material from both ovum and sperm and is diploid.

 

Dizygotic (fraternal) twins are produced when 2 ova are released and both are fertilized by separate sperm. They may or may not be the same sex and are no more closely related than other siblings.

 

Monozygotic (identical) twins develop from a single fertilized ovum that splits at an early stage of development. They are always the same sex and contain identical genetic material.

 

After fertilization, rapid mitotic cell division called cleavage takes place. A solid mass of cells called the morula is produced (still in the uterine tube). Although there are greater numbers of cells, the morula is still about the same size as the zygote. The progressively smaller cells it contains are called blastomeres.

 

By the fifth day the morula has changed into a hollow ball of cells, the blastocyst, and reached the uterine cavity. The blastocyst has these parts:

   1. Trophoblast---outer covering that comes in contact with the uterine wall and enables the blastocyst to burrow into the endometrium

 

   2. Inner cell mass

 

   3. Blastocele---fluid-filled cavity

 

The blastocyst remains free in the uterus for 1 - 2 days. About 6 - 7 days after fertilization the blastocyst attaches to the endometrium--implantation. The blastocyst then proceeds to burrow into the endometrium.

 

At this stage, the trophoblast has 3 functions:

   1. Secretes enzymes that allow the blastocyst to burrow into the uterine wall

   2. Develops into the chorion (one of the fetal membranes)

   3. Secretes hCG, which causes the corpus luteum, to continue to secrete estrogens and progesterones to maintain the pregnancy.

 

                      

        Secondary oocyte

        Mature ovum (already fertilized)

        Zygote

        Morula

        Blastocyst---this stage implants (burrows in to the wall of the uterus)

 

Following implantation, the endometrium is known as the decidua and consists of:

    1. Decidua basalis—portion between embryo and stratum basalis of the uterus—will form the maternal part of the placenta

   2. Decidua capsularis—portion between embryo and uterine cavity

   3. Decidua parietalis—remaining endometrium 

 

 

EMBRYONIC DEVELOPMENT

 

The first 2 months of development are the period of the embryo--study is embryology. After implantation the inner cell mass of the blastocyst differentiates into the 3 primary germ layers: ectoderm, endoderm and mesoderm. Cell migrations that establish the 3 germ layers are called gastrulation. All tissues and organs of the body will develop from these.

 

Endoderm forms the epithelial lining of most internal body structures, such as the GI tract, the respiratory tract, etc. and the epithelium of many glands

 

Mesoderm forms muscle, bone and other connective tissue, the peritoneum and the endothelium of blood vessels

 

Ectoderm forms skin and nervous system

 

Embryonic membranes, which protect and nourish the embryo and later the fetus also form during this time:

   1. Yolk sac--early site of blood cell formation, contains cells that migrate to ovaries or testes and differentiate into oogonia or spermatogonia

   2. Amnion--entirely surrounds embryo and creates a cavity filled with amniotic fluid in which the embryo floats. It acts as a shock absorber and helps regulate fetal body temperature. Embryonic cells are sloughed off into this fluid and can be removed and examined by amniocentesis.

   3. Chorion--forms the embryonic part of the placenta, also surrounds the fetus outside the amnion

   4. Allantois--its blood vessels help form the connection between mother and baby

 

 

 

PLACENTA

The placenta is developed by the 3rd month of pregnancy. It is formed by the chorion of the embryo and the endometrium of the mother. It allows oxygen, carbon dioxide, nutrients and wastes to diffuse back and forth between the blood of mother and baby. Equally important, the placenta produces several hormones that maintain pregnancy. At first, these hormones come from the corpus luteum, but it could not sustain an entire pregnancy.

 

One thing that the placenta does NOT do is screen out nearly all harmful substances from reaching the baby. Not too long ago, medicine gave the placenta way too much credit for this. Pregnant women were not warned much about smoking, alcohol, medications, etc. Now we have learned that while the placenta does give some protection, most things in the mother’s blood do cross over to the baby. Fortunately, most microorganisms do not cross the placenta, although some viruses pass through.

 

Fingerlike projections of the chorion, chorionic villi, grow into the endometrium and contain blood vessels of the allantois which will come in close contact with the blood of the mother in intervillous spaces. Following exchange, blood travels from the placenta to the baby by way of the umbilical vein. Blood flows through 2 umbilical arteries from the baby's circulation to the placenta. The umbilical arteries and vein are located in the umbilical cord.

 

At delivery the placenta detaches from the uterus and is called the afterbirth.

 

 

 

 

 

PRENATAL DIAGNOSTIC TESTS

 

 

1. Fetal ultrasonography--the big advantage is no known risk to mother or baby. Sound waves are reflected back from the fetus and converted to an image (sonogram) on a screen. It is used to determine fetal age, viability and growth, to determine fetal position, multiple pregnancies and some abnormalities.

 

2. Amniocentesis--some of the amniotic fluid is withdrawn and fetal cells and dissolved substances are studied. It can detect certain genetic disorders as well as determining fetal maturity and well-being. It can be used at 14-16 weeks of gestation and can detect almost 350 genetic defects. Guided by ultrasound, a needle is inserted into the amniotic fluid and about 10 ml of fluid is withdrawn. There is a small risk of spontaneous abortion (.5%).

 

3. Chorionic villus sampling--this test can give the same results as amniocentesis and can be performed at about 8 weeks. Guided by ultrasound, either a catheter is inserted vaginally or a needle through the abdominal wall is used to remove some chorionic villus tissue. The risk of spontaneous abortion is slightly higher (1-2%).

 

FETAL GROWTH

The period of the fetus is months 3-9 of development. By the end of the period of the embryo all organs are present. They will continue to grow and develop for the next 7 months.

                    

 

HORMONES OF PREGNANCY

 

The corpus luteum secretes estrogens and progesterone for the first 3-4 months. These hormones maintain the lining of the uterus and prepare the mammary glands for lactation. In the 3rd month the placenta begins to secrete higher levels of these hormones and the corpus luteum degenerates. The chorion secretes hCG to maintain the corpus luteum so long as it is needed.

 

The placenta also secretes:

   Human chorionic somatomammotropin, which encourages development of breast tissue and regulates metabolism.

   Relaxin (also produced by ovaries), which relaxes symphysis pubis and pelvic ligaments and helps dilate the cervix

    Corticotropin-releasing hormone (CRH)---may help establish timing for birth. Cortisol is produced in response and encourages maturation of the fetal lungs.

 

 

Gestation is the period during which zygote, embryo or fetus is carried in the female reproductive tract. In humans this is 266 days. Obstetrics is the branch of medicine.

 

PARTURITION AND LABOR

 

Labor--process by which the fetus is expelled

 

At the end of gestation secretion of progesterone, which inhibits uterine contractions, drops as the level of estrogens rises. This plays a role in causing labor to begin. The placenta produces corticotrophin releasing hormone, which causes the baby's pituitary to secrete ACTH. In response, the fetal adrenal glands secrete cortisol and DHEA. The cortisol encourages maturation of the baby's lungs, and some of the DHEA is converted to estrogens. The estrogens cause smooth muscle fibers of the uterus to develop oxytocin receptors. Prostaglandins also play a role.

 

In a positive feedback cycle, oxytocin from the posterior pituitary stimulates uterine contractions. These begin at the top of the uterus and move downward, pushing the baby against the cervix and, when cervical dilation is complete, out through the vagina. 3 stages of labor:

   1. Dilation--regular contractions lead to complete dilation of the cervix (10cm). The amniotic sac usually ruptures during this stage.

   2. Expulsion--time from complete cervical dilation to delivery

   3. Placental--time from delivery to expulsion of the placenta by continued uterine contractions. These contractions also constrict blood vessels in the uterine wall, controlling bleeding.

 

In response to the stress of birth, the adrenal medulla of the baby secretes high levels of epinephrine and norepinephrine, which helps clear the lungs, mobilize nutrients and promote a rich blood supply to the brain and heart.

 

During the 6 weeks following delivery the uterus is reduced in size by the process of involution. The cervix returns to pre-pregnancy condition.

 

 

 

ADJUSTMENTS OF THE FETUS AT BIRTH

 

Respiratory system--this system is fairly well developed by the 7th month of gestation, but the lungs remain collapsed or filled with amniotic fluid. Immediately after delivery carbon dioxide begins to build up and the baby begins to breathe. The fluid is either suctioned out or drains out with breathing.

 

Cardiovascular system--with the first breath, the foramen ovale (between atria) closes as two flaps of heart tissue fold together and fuse. Muscle in the walls of the ductus arteriosus contract and begin to close the vessel off, but closure is usually not complete until about 3 months after birth.

 

Both pulse and respiration are rapid in newborns (resp. 45/minute, pulse 120-160/minute). These gradually decline.

 

The infant's liver may not immediately function adequately, causing a temporary jaundice to develop in up to 50% of normal newborns.

 

 

 

 

INHERITANCE

This is the passage of hereditary traits from one generation to another. Genetics is the branch of biology. Genetic counseling offers advice on genetic problems.

 

Genome--complete genetic makeup of an organism (about 100,000 genes in a human)

 

Genotype--all genes present, both those expressed and those not expressed

 

Nuclei of all human cells except gametes contain 23 pairs of chromosomes (diploid number). Homologous chromosomes contain genes that control the same traits. Genes at the same location on homologous chromosomes that control the same traits are called alleles.

 

Dominance---a dominant gene is one that dominates other genes present for a trait--if one fully dominant gene for a trait is present the trait will be expressed regardless of the presence of other genes.

 

A recessive gene is one that may be present but will not be expressed unless no dominant allele is present.

 

A person with the same gene for a trait present on both homologous chromosomes (identical alleles) is said to be homozygous. A person with 2 different alleles is heterozygous.

 

For example, the gene that causes a person to have freckles is dominant (no freckles is recessive). Dominant genes are represented by capital letters, recessive by lower case:

    F = freckled

    f = no freckles

Everyone has 2 of these genes, so the possibilities are:

    FF (homozygous)                     These possibilities are described as the

    ff (homozygous)                       possible genotypes.

    Ff (heterozygous)

 

 

Phenotype is the way the genetic makeup is expressed. Although the genotype differs, FF and Ff would have the same phenotype (both freckled).  The phenotype of ff would be no freckles.

 

Charts called Punnett squares are used to determine the possible ways gametes can combine to produce diploid offspring.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Normal traits are most often dominant, abnormal traits are most often recessive, particularly if the defect is serious. This is because few individuals with the problem may live to reproduce--in some cases they will even die in utero, so dominant abnormalities tend to die out.

 

A cell having missing or added chromosomes is said to be aneuploid. This is usually the result of nondisjunction---homologous chromosomes do not separate during meiosis I.

   Monosomic cell--missing a chromosome

   Trisomic cell--extra chromosome (trisomy 21 is Down syndrome)

 

Although it is easiest to understand, simple dominant-recessive inheritance is not the only possibility. Many traits are influenced by more than 1 pair of genes and other factors such as environment can also play a role in gene expression.

 

Incomplete dominance--neither allele is completely dominant over the other and heterozygous individuals have a phenotype intermediate between the 2. In flowers (snapdragons):

   PP=red

   pp=white

   Pp=pink

In humans, sickle cell anemia is an example:

   HbA = normal hemoglobin                                 HbA  HbA  =normal

   HbS = abnormal hemoglobin                             HbA  HbS  =minor symptoms

                                                                           HbS HbS=severe disease

Hair texture is another:

   H = curly hair                                      HH = curly hair

   H1 = straight hair                                 H1 H1 = straight hair

                                                               H H1 = wavy hair

 

Multiple allele inheritance--although a single individual can have only 2 alleles for a gene, some genes may have more than 2 alternate forms.

   Human ABO blood groups: 3 alleles, A, B, and O. Also these alleles are codominant. This means that if more than one is present, both can be expressed.

 

  GENOTYPE

PHENOTYPE

       A A

      A

       A O

      A

       B B

      B

       B O

      B

       A B

     A B

       O O

      O

 

 

Polygenic inheritance—there is not always one single gene that controls a trait. In fact, quite frequently the combined effects of many genes influence a particular trait. Examples in humans are skin color, eye color, hair color, height and body build. Polygenic inheritance is also influenced by environment.

 

 

 

INHERITANCE OF SEX

Chromosome pair #23 differs between males and females. Females have 2 full-size X chromosomes. The #23 chromosome pair is called the sex chromosomes--the other 22 pairs are called autosomes. Males have one X chromosome and a smaller Y chromosome in this pair. Females have 2  X chromosomes.

 

Male gametes (sperm) can carry either the X or the Y chromosome; female gametes only an X. Sex is determined at fertilization by the sperm. All embryos develop alike until the 7th week. At that point, if the Y chromosome is present, it will initiate male development.

 

 

SEX-LINKED INHERITANCE

 

The X chromosome carries genes for traits other than sex determination. Males, having only one X chromosome, will have only 1 gene present for those traits located on the "missing" part of the Y chromosome. Females will have 2 copies of these genes, since they have two X chromosomes. These are called sex-linked traits and they show up much more often in males. In females they usually appear only when both X chromosomes carry the abnormal trait.

 

Red-green Colorblindness--due to missing photopigments, red and green will look the same.

 

   C = normal color vision

   c  =  red-green colorblindness

 

   XC XC =normal female

   XC Xc =female carrying recessive gene (normal color vision)

   Xc Xc =colorblind female

 

   XC Y =normal male

   Xc Y =colorblind male

 

Other examples:

   Classic hemophilia

   Fragile X Syndrome

   Non-functional sweat glands

   Juvenile muscular dystrophy

 

 

 

 

TERATOGENS

Any agent or influence that causes developmental defects in the embryo a teratogen. Many of these do the most damage in the very earliest weeks of gestation, sometimes even before the mother is aware of the pregnancy.

   1. Chemicals & drugs--almost all of these cross the placenta and many can harm the embryo/fetus

         Pesticides

         Defoliants

         Some hormones

         Some antibiotics

         LSD

         Marijuana

         Cocaine

   2. Alcohol--number one teratogen. Excessive intake during pregnancy causes fetal alcohol syndrome, which includes characteristic physical deformities and learning and behavior problems.

   3. Smoking--low birth weight and higher fetal mortality. Associated with cardiac abnormalities, cleft lip & palate and sudden infant death syndrome

   4. Irradiation--X-rays or other radioactivity may cause small head size, mental retardation, and skeletal abnormalities