Human Physiology, 14th edition (2016)

(Tina Sui) #1

740 Chapter 20


by the host’s immune system. Similarly, iPS cells derived from
a patient’s fibroblasts may produce differentiated tissues that
won’t be immunologically rejected. However, there are differ-
ences between iPS cells and embryonic stem cells, including a
large number of sites where the four transducing factor genes
are inserted by the virus into the host DNA. These might cause
genetic disruptions that may induce tumor formation and cancer.
To address these concerns, scientists produced iPS cells
from patients with Parkinson’s disease, removed the four trans-
ducing genes from the iPS cells, and then induced the cells to
develop into dopaminergic neurons.
Such neurons could be used to learn about the sporadic form
of Parkinson’s disease (the most common form), and hopefully
be the basis for future treatments. Other techniques for generat-
ing iPS cells without leaving the transforming genes in the host
chromatin are also being developed. Together with the recent
demonstration that iPS cells derived from the fibroblasts of a
person with ALS (chapter 12) can differentiate into motor neu-
rons, these reports and others encourage hope for the potential
therapeutic benefits of iPS cells in regenerative medicine.
In summary, there are two ways that stem cells genetically
identical to a patient can be produced. One is by somatic cell
nuclear transfer—taking the nucleus from a differentiated cell
(such as a fibroblast) of the patient and transferring it to the cyto-
plasm of an enucleated egg. The newly formed diploid egg cell
is then stimulated to develop into a blastocyst, from which plu-
ripotent ES cells are derived. The other technique involves using a
cocktail of transcription factors to transform a patient’s differenti-
ated cell into an iPS cell. However, scientists have found subtle
differences in the degree of DNA methylation (and thus epigenetic
regulation) between these two different types of patient-derived
pluripotent stem cells, and between each of those and the pluripo-
tent blastocyst cells formed following normal fertilization. This
calls into question the safety of such stem cell therapies, and indi-
cates that more research is required before the promise of regen-
erative medicine using these technologies can be realized.
In an effort to circumvent problems with pluripotent stem
cells, scientists have tried to convert one differentiated adult
cell directly into another, a technique called transdifferentia-
tion. Different groups have reported varying degrees of success
at converting fibroblasts into dopaminergic neurons, glutamine-
releasing neurons, myocardial cells, and others. However, as
with the two methods of producing patient-specific pluripotent
stem cells, more research is required before transdifferentiation
can be safely used in regenerative medicine.


Implantation of the Blastocyst and


Formation of the Placenta


If fertilization does not take place, the corpus luteum begins
to decrease its secretion of steroids about 10 days after ovula-
tion. This withdrawal of ovarian steroids with the death of the
corpus luteum causes the sloughing of the endometrium (men-
struation) following day 28 of the typical cycle. If fertilization
and implantation have occurred, these events must obviously
be prevented to maintain the pregnancy.


Chorionic Gonadotropin
The blastocyst saves itself from being eliminated with the
endometrium by secreting a hormone that indirectly prevents
menstruation. Even before the sixth day, when implantation
occurs, the trophoblast cells of the chorion secrete chorionic
gonadotropin, or hCG (the h stands for “human”). This hor-
mone is identical to LH in its effects and therefore is able to
maintain the corpus luteum past the time when it would oth-
erwise regress. The secretion of estradiol and progesterone is
thus maintained and menstruation is normally prevented.
The secretion of hCG declines by the 10th week of preg-
nancy ( fig.  20.44 ). Actually, this hormone is required for only

CLINICAL APPLICATION
Pregnancy tests use monoclonal antibodies against the
beta subunit of hCG to assay for the presence of hCG in
blood or urine. Because hCG is produced not by the mother
but by the trophoblast embryonic cells, the test should
normally be negative if the woman is not pregnant, unless
she took exogenous hCG to treat infertility. False negative
results occur when the test is performed too early, because
hCG does not reach detectable levels until implantation,
which may not occur until as late as day 12. Considering
that sperm may survive in a woman’s reproductive tract for
up to 5 days, a pregnancy test may be falsely negative for
more than two weeks following intercourse. However, the
standard home pregnancy test is very reliable when per-
formed a week after a missed menstrual period.

Figure 20.44 The secretion of human chorionic
gonadotropin (hCG). This hormone is secreted by trophoblast
cells during the first trimester of pregnancy, and it maintains the
mother’s corpus luteum for the first 5½ weeks. After that time,
the placenta becomes the major sex-hormone-producing gland,
secreting increasing amounts of estrogen and progesterone
throughout pregnancy.

Months of pregnancy

Increasing hormone concentration

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Human chorionic
gonadotropin

Progesterone

Estrogen
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