Medical Aspects of Developmental Biology: Birth Defects, Endocrine Disruptors, & Cancer Lange BIOL 370 – Developmental Biology Topic #20

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 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 (PPAR α ) 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

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