BIOL 370 – Developmental Biology
Topic #20
Medical Aspects of Developmental Biology:
Birth Defects, Endocrine Disruptors, & Cancer
Lange
Fate of 20 hypothetical human eggs in the United States and western Europe
100%
84%
69%
42%
35%
31%
Down syndrome
Down’s Syndrome is a mixture of
various, albeit similar forms. The
most common form is more
specifically called Trisomy 21
Disorder. The CDC estimates that
about one of every ~700 babies born
in the United States each year is born
with Trisomy 21 Disorder.
Mosaic and relational pleiotropy
In this example, the gene’s
product is needed for both
tissues to develop
normally.
In this example, the gene’s
product is needed for one tissue,
but another product from the
initial tissue is requited to guide
normal development in a second
tissue.
Preimplantation genetics is performed on one or two blastomeres taken from an early blastocyst
Weeks of gestation and sensitivity of embryonic organs to teratogens
Fetal Alcohol Syndrome - a pattern of mental and physical defects that can
develop in a fetus in association with high levels of alcohol consumption during
pregnancy. Alcohol crosses the placental barrier and can stunt fetal growth or
weight, create distinctive facial stigmata, damage neurons and brain structures,
which can result in psychological or behavioral problems, and cause other
physical damage. The main effect of FAS is permanent central nervous system
damage, especially to the brain.
Comparison of a brain from an infant with fetal alcohol syndrome (FAS) with a brain from a normal
infant
Alcohol-induced craniofacial and brain abnormalities in mice
Genital anomalies can occur in women exposed to DES in utero
DES - Diethylstilbestrol is a synthetic
estrogen first synthesized in 1938.
• It is now classified as an endocrine
disruptor.
• From ~1940 to 1970, DES was
sometimes perscribed to pregnant
women to reduce the risk of
pregnancy complications and loss.
• Public awareness grew when in
1971, DES was shown to cause a
rare vaginal tumor in girls and
women who had been exposed to
this drug in utero.
Misregulation of Müllerian duct morphogenesis by DES
Bisphenol A (BPA) – chemical used in some plastics and epoxy resins. First
used in 1957, BPA-laden plastic is clear, tough, yet flexible. Plastic of this sort
is used to make a variety of common consumer goods (for example, baby and
water bottles, sports equipment, and CDs and DVDs) and lining water pipes.
Bisphenol A causes meiotic defects in maturing mouse oocytes
In these images, mouse oocytes are shown. (A) is showing normal meiosis
associated with normal maturation. (B) is showing abnormal meiosis caused by
BPA exposure. The result in the organism is decreased or absent fertility or
abnormal chromosomal numbers in the eggs (aneuploidy).
Bisphenol A induces mammary lesions in mice
In more and more studies, BPA is being tied to increased instances of breast cancer.
Developmental estrogen syndrome is manifest in climbing rates of breast cancer and testicular
dysgenesis
The unfortunately growing rate of exposures to environmental estrogens (endocrine
disrupting compounds) has been associated with a variety of reproductive and
associated systems abnormalities.
Seminiferous tubules from the testes of (A) a control rat and (B) a rat whose grandfather was born
from a mother injected with vinclozolin
Vinclozolin is a fungicide used to control a variety of plant diseases
including blights, rots and molds agriculturally. It is also used on
turf on golf courses. It has been implicated in reproductive system
issues as well as can be seen in (B) below.
Effects of estrogen implants on different strains of mice
Model of cancer stem cell production, using leukemia (a white blood cell tumor) as an example
Anatomical changes associated with hypertension
Activity of the liver gene for peroxisomal proliferator-activated receptor (PPARα) is susceptible to
dietary differences
New blood vessel growth to the site of a mammary tumor transplanted into the cornea of an albino
mouse
Embryonic stem cell therapeutics
End.