A THOUGHTFUL CONCEPTION
Sex
The pleasure of sexual intercourse is a biological enticement to get adults to bring
together their germ cells, to create a baby, to ensure that there will be future adults to repeat this
cycle forever. While readers of A Thoughtful Conception certainly are interested in sexual
intercourse, we are equally interested in how babies become who they are, an interest that
stimulates us to learn about genetics!
UNION OF EGG AND SPERM CHROMOSOMES. Sexual intercourse leading to the
fertilization of an egg by a sperm is fundamentally a genetic process. Fertilization enables the
genetic information of two people – a woman and a man – to be united in one person. Of even
greater importance for the survival of the species is genetic mixing that occurs throughout the
process of getting egg and sperm together. Let us look at how this mixing takes place.
Human babies must have cells that contain two complete sets of chromosomes, a
maternal set and a paternal set. Of course, the mother and father of the baby also have cells with
two complete sets of chromosomes. A simple merger of the man’s chromosomes with a
woman’s chromosomes would give twice the normal number. Nature has created a way to
reduce the number of chromosomes given to a baby by its parents. This process is a special type
of cell division called meiosis, which occurs in the gonads, the testes and ovaries of men and
women (see Fig.3).
Meiosis is illustrated by a cartoon of a generalized
gamete, whether egg or sperm. Only two
chromosomes are shown for simplicity. At the
beginning of meiosis (A), the chromosomes are
dispersed throughout the nucleus. At an early stage
into meiosis (B), the chromosomes become distinct
and the nuclear membranes begin to dissolve. The
DNA in each chromosome duplicates itself (see Fig. 2)
in a manner so that both copies (chromatids) are
fastened together at the centromere (see Fig. 3),
giving the appearance of two “arms” and two “legs.”
Meiosis
Chromosomal material is exchanged between the two
Figure 3
members in a process called recombination. At an
advanced stage (C), the chromosomes pair off with each other in the middle of the cell. Also
at this stage, the nuclear membrane is completely dissolved and spindle fibers of protein
connect the chromosomes in the middle of the cell to the sides. One member of each pair
of recombined chromosomes moves to opposite sides of the cell. In the next stage (D), a
nuclear membrane reforms around each of the two sets of chromosomes, creating two cells
with half the normal number of chromosomes, one from each pair. In the next division of
meiosis, each of the two cells divides so that meiosis finally produces four cells: two cells
with one set of recombined chromosomes and two cells with the second set of
chromosomes.
Human male and female germ cells each start out with 46 chromosomes consisting of 23
pairs. These immature germ cells undergo meiosis so that one chromosome from each pair of
chromosomes goes into each mature germ cell, whether egg or sperm. Mature germ cells have
23 chromosomes, not 23 pairs, each of which is representative of one of the original 23 pairs.
Therefore, mature germ cells have only one set of chromosomes. Some of these chromosomes
have come from the person’s mother whereas others have come from the person’s father. Thus,
many different sets are possible.
Meiosis, however, is more than a reduction in the number of chromosomes carried by
germ cells. Something else of great importance to genetics also occurs in the ovary and in the
testis; parts of chromosomes are exchanged between the chromosome pairs. During meiosis the
two members of each chromosome pair get very close so that a portion of the maternal member
may be exchanged for a similar portion of the paternal member. This excha nge is normal; it is
supposed to result in an equal swap between two members of a pair. The outcome, of course, is
an exchange or recombination of genes between maternal and paternal chromosomes. Genes on
swapped segments of chromosomes will be different, just as we know that mothers and fathers
are different people in many, many ways. After the exchange takes place, the two members of
each chromosomal pair are no longer identical to maternal and paternal chromosomes found in
other cells of the body. It is these pairs of changed chromosomes that are separated and go into
germ cells. Thus, with different maternal and paternal chromosomes inherited and
recombination further increasing variability, every baby resembles its parents but is unique.
In men, sperm production begins at puberty and continues for life. For a woman, oocyte
production begins when she is still a fetus and her ovaries are being formed. Weeks before birth,
the fetal ovaries normally develop the maximum number of eggs she will ever ha ve – a total of
6 to 7 million. Further development of these eggs, each one being very immature with 23
chromosomal pairs, is put on hold for many years. Gradually, a few eggs at a time will be
reabsorbed by their ovary. At her first menstrual period, she has 300,000 to 400,000 immature
eggs remaining, half in each ovary. By menopause, few eggs remain.
In a different process beginning at puberty, a few immature eggs (maybe 10) resume
meiosis each month. Only one normally goes to completion with the fo rmation of a fully mature
egg having 23 individual chromosomes, a process requiring two to three months. Throughout a
woman’s fertile years, only about 500 eggs become fully mature. There is no storage of mature
eggs. Each month, one mature egg is usually ovulated and released from an ovary. It must then
be fertilized or wasted, discharged from the body.
The natural place for fertilization is a Fallopian tube of a woman (See Fig. 4). A woman
normally has two Fallopian tubes, one for each ovary, that channel eggs into her uterus. Each
month, one mature egg, under control of hormones, is released from an ovary into its Fallopian
tube. During each sexual intercourse, sperm are released into the vagina. Sperm must travel
from the vagina through the uterus and into each Fallopian tube where an egg may be waiting for
fertilization (See Fig. 4). Fertilization occurs when one sperm fuses with an ovulated egg,
combining two sets of 23 chromosomes each, to form a zygote with one complete set of 46
chromosomes or 23 pairs. A zygote divides to form a two-cell embryo, each cell with 23 pairs of
chromosomes.
The formation of a normal embryo obviously depends on perfect completion of male and
female meiosis followed by perfect completion of fertilization. These are complex processes
with many opportunities for error. We will soon discuss what happens when there are errors.
Immature eggs in the ovary develop through a
process called meiosis. Each developing egg
becomes surrounded by a blister of fluid that
ruptures, releasing the egg in a process called
ovulation. The released egg enters the Fallopian
tube which then moves the egg into the uterus.
Fertilization of the egg by sperm occurs in the
Fallopian tube. The journey of the egg to the uterus,
whether fertilized or not, takes 7 to 10 days. The
fertilized egg will develop into a cluster of cells, an
embryo, during the trip to the uterus. The fertilized
egg becomes embedded in the uterine wall. An
unfertilized egg will be shed from the uterus during
menstruation.
Egg Fertilization
Figure 4
A cell that breaks away from an early embryo can form a separate embryo, a twin. In this
case, the twin has the same chromosomes as the original embryo, so the twins will be “identical.”
This means that they come from the same zygote. Identical twins occur in three to four out of
every 1,000 births. If, by chance, more than one egg is released and fertilized, each of these
zygotes can form a twin, but they will not be identical because their chromosomes will each have
a different set of genes. Fraternal twins occur in 4 to 16 out of every 1,000 births.
Even though each cell in the developing fetus and even in the adult person typically has a
full set of genetic instructions originating from the zygote, these cells do not perform all possible
genetic instructions. Cells have specialized functions. Only a few cells make melanin; a few
others make hemoglobin, and so on. Any cell has the instructions for all of these activities, but
only genes appropriate for a cell’s specialized work are switched on.
CHROMOSOMES DETERMINE SEX. Of the 23 pairs of human chromosomes,
members of 22 pairs are structurally similar to each other; DNA of both members carry genes for
the same proteins. These are called autosomes to distinguish them from the 23rd pair. Human
autosomal pairs are designated with Arabic numerals 1 through 22. The two chromosomes of the
23rd pair are quite different from each other. One is much larger than the other and is called the X
chromosome. The smaller chromosome is referred to as the Y chromosome. Some of the genes
on the Y chromosome match with those on the X chromosome; these allow Y to pair with X. X
and Y chromosomes are called sex chromosomes and are responsible for determining a person’s
sex. Cells in women typically have two X chromosomes; cells in men, one X and one Y (See
Fig. 5).
When a woman’s immature eggs with two X chromosomes undergo meiosis, all of the
mature eggs end up with one X chromosome. When immature sperm with both X and Y
chromosomes undergo meiosis, half of the mature sperm have an X chromosome, the others have
a Y chromosome. When a sperm with an X chromosome fertilizes an egg, the XX zygote
becomes female. When a sperm with a Y chromosome fertilizes an egg, the XY zygote becomes
male. Fathers alone give Y chromosomes to sons. Thus, it is the sperm that determines the sex
of the child.
Pictured are the 23 pairs of chromosomes from a
single human cell. The cell was stained to reveal the
bands in the chromosomes and then photographed.
Note the X and Y chromosomes. A female would have
two X’s and no Y.
A fetus whose cells lack a Y chromosome will
become a girl, a woman. The X chromosome does
Normal Karyotype for Human Male
NOT cause an embryo to become female – that would
Figure 5
happen with or without the X just as long as the Y
chromosome is not present. A fetus whose cells have a
Y chromosome will become a boy, a man. Genes located on the Y chromosome help determine
male sex. All genes on the Y are responsible for maleness or sperm production. One of the most
important of these genes is called SRY (sex-determining region Y). SRY causes cells to produce
a substance called TDF (testis-determining factor). TDF causes embryonic gonads to develop
into testes; without TDF the gonads become ovaries. Testes produce the male hormone
testosterone, which is essential to the development of male characteristics.
There are important genes on the X chromosome for the development of male-gender
characteristics as well. For example, the X chromosome has a gene that produces the receptor for
testosterone. Testosterone is useless in the absence of testosterone receptors. A baby with the
XY chromosomes and testes that are producing testosterone would have female genitalia if it
lacks testosterone receptors.
Just as meiosis reduces the number of chromosomes carried by germ cells so that the
zygote and subsequent embryo does not receive a double dose of genes, it is important that
human females do not receive a double dose of X chromosome genes. One X chromosome
works quite well, as demonstrated by all men with XY chromosomes. (Well, maybe!) In order
to prevent both X chromosomes in women from overwhelming her cells, each female cell
randomly inactivates one X chromosome. In some cells, the X she received from her mother is
inactivated while in other cells the X she received from her father is the one inactivated.
Because of X- inactivation in women, a variant in one X chromosome will affect only
some of her cells if the other X is free from the variant. For example, the gene for red/green
color vision is on the X chromosome. When a person is unable to see one of these colors, the
gene for that color located on the X chromosome must be altered or missing. In a woman, if one
X chromosome has the gene for color vision and one X chromosome has a gene with an altered
or absent gene for color vision; this woman will still be able to see color. A man whose only X
chromosome has an altered or absent gene for color vision will be unable to see the color. Thus,
men are much more likely than women to be color blind. The genetics of muscular dystrophy
and of the blood-clotting disorder hemophilia make them also X- linked traits, and therefore they
affect men more frequently than women.
CHROMOSOME ABNORMALITIES. Chromosome abnormalities at conception are
extremely common in humans, occurring in an estimated 30 to 50 percent of embryos. No other
animal has such an extraordinarily high frequency of abnormalities. Most of these errors are so
severe that normal embryologic development cannot occur and they are lost as miscarriages.
About half of embryos and fetuses lost to miscarriage in the first trimester of pregnancy have a
chromosomal disorder. This number of chromosomal abnormalities is reduced to slightly less
than 1 percent in newborns.
Down syndrome occurs when there is an extra chromosome 21 in the embryo (see Fig.
6). This leads to moderate mental retardation, a typical facial appearance and may be associated
with other abnormalities such as heart defect and susceptibility to leukemia. Turner syndrome
occurs when there is a missing X chromosome, so the female only has one X chromosome. This
leads to infertility and may be associated with other abnormalities such as a heart defect (See
Fig. 7). An embryo with an XXY karyotype would develop into a male with Klinefelter
syndrome, which is also associated with infertility and other potential problems (See Fig. 8).
Figure 6
Figure 7
Down syndrome Karyotype
Note an extra chromosome 21.
Figure 8
Turner syndrome Karyotype
Klinefelter syndrome Karyotype
Note one X and no Y chromosomes. Note two X and one Y chromosomes.
The frequency of trisomy (conditions with an extra chromosome) increases dramatically
with the mother’s age. For example, the frequency of Down syndrome is approximately 1/1500
at age 20, but increases to 1/30 by 45 years of age (see Fig. 9). Thus, it is important to try to plan
pregnancies at an earlier maternal age if possible.
Risk of a Down Syndrome Baby
with Advancing Maternal Age
Figure 9
Structural chromosomal abnormalities also occur when a chromosome break leads to a
loss, an addition or a rearrangement of chromosomes. These can be lethal early during
development, or they may cause the birth of a child with mental and physical abnormalities.
Balanced rearrangements (e.g., translocation) occur when the genetic material is present in the
correct amount but parts of chromosomes have been switched. In these cases, the individual
carrying the chromosomal rearrangement is normal, but difficulties generally occur when the
chromosomes try to pair in meiosis and chromosomally unbalanced sex cells lead to
miscarriages, infertility and sometimes chromosomally abnormal children. Structural
abnormalities of chromo somes are rare in the general population but are seen more commonly in
infertility clinics.
The majority of chromosomal abnormalities are numerical; that is, there are extra or
missing chromosomes (i.e., aneuploidy). This type of error generally occurs at meiosis
(discussed previously; see Fig. 3). For most chromosomes, especially the larger ones, this leads
to an early miscarriage. However, some abnormalities do survive to term. A baby that goes to
term with altered chromosomes will be worthy of love, but he or she will be different in ways
that may be obvious – physically, mentally, or both. Also, many people who have chromosome
abnormalities are infertile.