Environmental toxins and fetal development
Encyclopedia
It has long been known that the fetus can be sensitive to impacts from adverse environmental
exposures. Fetal development can be affected by exposures that occur to either parent prior to conception and to the mother post conception.
s or poison
s that were harmful to the pregnant woman often were as harmful, or more harmful, to the fetus. Infectious syndromes such as congenital rubella syndrome
and congenital syphilis
were examples. In the last century evidence emerged that certain environmental exposures that were not obviously harmful to the mother could cause serious harm to the fetus. Substances that caused birth defects and other adverse effects to the fetus, in the absence of recognized toxicity to mothers, were: genital abnormalities and vaginal cancer
occurring among girls born to mothers given the estrogenic hormone diethylstilbestrol
during pregnancy; phocomelia
(failure of growth of limb buds) to babies born to mothers who took thalidomide
to control nausea during pregnancy; and Minamata disease
, an epidemic of babies born with severe mental retardation and deformities due to mercury poisoning
caused by mothers eating methylmercury
contaminated fish from Minimata Bay in Japan
. More recently, maternal tobacco
smoking and even environmental tobacco smoke, modest consumption of ethanol
during pregnancy, and low levels of exposure to lead
and mercury
have been found to be have adverse impacts on fetal growth and development.
The healthy placenta
does form a barrier for most pathogens and for certain xenobiotic
substances. However, it is by design an imperfect barrier since it must transport substances required for growth and development, such as nutrients and immunoglobulins. Placental transport can be by passive diffusion
for smaller molecule
s that are lipid
soluble or by active transport
for substances that are larger and/or electrically charged
. Some toxic chemicals may be actively transported. For example, it is believed that lead
is transported using mechanisms designed for transport of iron
, calcium
and possibly other essential elements
such as zinc
. The dose
of a substance received by the fetus is determined by the amount of the substance transported across the placenta as well as the rate of metabolism
and elimination
of the substance. The fetus has immature metabolism
and is not able to detoxify substances very efficiently; the only routes of excretion
is via diffusion or active transport back to the maternal circulation or elimination into the amniotic fluid.
The timing and duration of exposure are critical. The level of response to a given dose may change dramatically depending on the stage of development at which a fetus is exposed.
To identify potential hazards for fetal development requires a basis of scientific information. In 2004, Brent proposed a set of criteria for identifying causes of congenital malformations that also are applicable to developmental toxicity generally. Those criteria are:
and persistence
are important aspects to consider since such substances are more likely to be present over several developmental stages than substances that are quickly eliminated. Such substances, known as persistent organic pollutant
s (POPs), include a number of chemicals that are known to have adverse effects on fetal development given the level and timing of exposure: polychlorinated biphenyl
s (PCBs), polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofuran
s and organochlorine insecticide
s such as DDT
are examples of such compounds that can be toxic to the fetus at high enough doses. Others, such as lead
and methylmercury
are persistent but not bioaccumulative. (Later, such chemicals continue to be passed from mother to baby via breast milk
.
A number of environmental toxins known to have adverse effects on fetal development are endocrine disruptor
s. Processes involved with differentiation and growth of embryonic and fetal cells are under the tight control of a myriad of messaging systems, some of which involve hormones. In particular, chemicals that mimic or otherwise disrupt the normal response to estrogen
, androgen
, or thyroid hormone
have been particularly of concern during fetal development.
Environmental carcinogens also are of concern during this time. Research has indicated that in utero exposure to carcinogens may confer much higher risks than later in life. This may be due to the rapid growth and differentiation of cells during this time, with, perhaps, less ability to repair the damage caused by carcinogens or to mount an effective immune response.
brain development of a fetus. In utero cocaine
exposure has been linked to the development of septo-optic dysplasia
.
Natural environment
The natural environment encompasses all living and non-living things occurring naturally on Earth or some region thereof. It is an environment that encompasses the interaction of all living species....
exposures. Fetal development can be affected by exposures that occur to either parent prior to conception and to the mother post conception.
Fetal development
Historically, it was recognized that certain infectionInfection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s or poison
Poison
In the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....
s that were harmful to the pregnant woman often were as harmful, or more harmful, to the fetus. Infectious syndromes such as congenital rubella syndrome
Congenital rubella syndrome
Congenital rubella syndrome can occur in a developing fetus of a pregnant woman who has contracted rubella during her first trimester. If infection occurs 0–28 days before conception, there is a 43% chance the infant will be affected. If the infection occurs 0–12 weeks after conception, there is a...
and congenital syphilis
Congenital syphilis
Congenital syphilis is syphilis present in utero and at birth, and occurs when a child is born to a mother with secondary syphilis. Untreated syphilis results in a high risk of a bad outcome of pregnancy, including mulberry molars in the fetus. Syphilis can cause miscarriages, premature births,...
were examples. In the last century evidence emerged that certain environmental exposures that were not obviously harmful to the mother could cause serious harm to the fetus. Substances that caused birth defects and other adverse effects to the fetus, in the absence of recognized toxicity to mothers, were: genital abnormalities and vaginal cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
occurring among girls born to mothers given the estrogenic hormone diethylstilbestrol
Diethylstilbestrol
Diethylstilbestrol is a synthetic nonsteroidal estrogen that was first synthesized in 1938. Human exposure to DES occurred through diverse sources, such as dietary ingestion from supplemented cattle feed and medical treatment for certain conditions, including breast and prostate cancers...
during pregnancy; phocomelia
Phocomelia
Phocomelia is an extremely rare congenital disorder involving the limbs . Étienne Geoffroy Saint-Hilaire coined the term in 1836....
(failure of growth of limb buds) to babies born to mothers who took thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
to control nausea during pregnancy; and Minamata disease
Minamata disease
', sometimes referred to as , is a neurological syndrome caused by severe mercury poisoning. Symptoms include ataxia, numbness in the hands and feet, general muscle weakness, narrowing of the field of vision and damage to hearing and speech. In extreme cases, insanity, paralysis, coma, and death...
, an epidemic of babies born with severe mental retardation and deformities due to mercury poisoning
Mercury poisoning
Mercury poisoning is a disease caused by exposure to mercury or its compounds. Mercury is a heavy metal occurring in several forms, all of which can produce toxic effects in high enough doses...
caused by mothers eating methylmercury
Methylmercury
Methylmercury is an organometallic cation with the formula . It is a bioaccumulative environmental toxicant.-Structure:...
contaminated fish from Minimata Bay in Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
. More recently, maternal tobacco
Tobacco
Tobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as a pesticide and, in the form of nicotine tartrate, used in some medicines...
smoking and even environmental tobacco smoke, modest consumption of ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
during pregnancy, and low levels of exposure to lead
Lead
Lead is a main-group element in the carbon group with the symbol Pb and atomic number 82. Lead is a soft, malleable poor metal. It is also counted as one of the heavy metals. Metallic lead has a bluish-white color after being freshly cut, but it soon tarnishes to a dull grayish color when exposed...
and mercury
Mercury (element)
Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...
have been found to be have adverse impacts on fetal growth and development.
The healthy placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
does form a barrier for most pathogens and for certain xenobiotic
Xenobiotic
A xenobiotic is a chemical which is found in an organism but which is not normally produced or expected to be present in it. It can also cover substances which are present in much higher concentrations than are usual...
substances. However, it is by design an imperfect barrier since it must transport substances required for growth and development, such as nutrients and immunoglobulins. Placental transport can be by passive diffusion
Diffusion
Molecular diffusion, often called simply diffusion, is the thermal motion of all particles at temperatures above absolute zero. The rate of this movement is a function of temperature, viscosity of the fluid and the size of the particles...
for smaller molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
s that are lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
soluble or by active transport
Active transport
Active transport is the movement of a substance against its concentration gradient . In all cells, this is usually concerned with accumulating high concentrations of molecules that the cell needs, such as ions, glucose, and amino acids. If the process uses chemical energy, such as from adenosine...
for substances that are larger and/or electrically charged
Electric charge
Electric charge is a physical property of matter that causes it to experience a force when near other electrically charged matter. Electric charge comes in two types, called positive and negative. Two positively charged substances, or objects, experience a mutual repulsive force, as do two...
. Some toxic chemicals may be actively transported. For example, it is believed that lead
Lead
Lead is a main-group element in the carbon group with the symbol Pb and atomic number 82. Lead is a soft, malleable poor metal. It is also counted as one of the heavy metals. Metallic lead has a bluish-white color after being freshly cut, but it soon tarnishes to a dull grayish color when exposed...
is transported using mechanisms designed for transport of iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
, calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
and possibly other essential elements
Chemical element
A chemical element is a pure chemical substance consisting of one type of atom distinguished by its atomic number, which is the number of protons in its nucleus. Familiar examples of elements include carbon, oxygen, aluminum, iron, copper, gold, mercury, and lead.As of November 2011, 118 elements...
such as zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
. The dose
Dose (biochemistry)
A dose is a quantity of something that may impact an organism biologically; the greater the quantity, the larger the dose. In nutrition, the term is usually applied to how much of a specific nutrient is in a person's diet or in a particular food, meal, or dietary supplement...
of a substance received by the fetus is determined by the amount of the substance transported across the placenta as well as the rate of metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
and elimination
Elimination
- Science and medicine :*Elimination reaction, an organic reaction in which two functional groups split to form an organic product*Elimination, clearance of a drug or other foreign agent from the body...
of the substance. The fetus has immature metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
and is not able to detoxify substances very efficiently; the only routes of excretion
Excretion
Excretion is the process by which waste products of metabolism and other non-useful materials are eliminated from an organism. This is primarily carried out by the lungs, kidneys and skin. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell...
is via diffusion or active transport back to the maternal circulation or elimination into the amniotic fluid.
The timing and duration of exposure are critical. The level of response to a given dose may change dramatically depending on the stage of development at which a fetus is exposed.
To identify potential hazards for fetal development requires a basis of scientific information. In 2004, Brent proposed a set of criteria for identifying causes of congenital malformations that also are applicable to developmental toxicity generally. Those criteria are:
- There are well conducted epidemiologyEpidemiologyEpidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...
studies consistently show a relationship between particular effects and exposure to the substance to humans. - Trends in data over time support a relationship between changing levels of exposure to a substance and the specific effect.
- Animal studies give evidence that the fetus is susceptible and provide biological information that is supportive of the human studies and specifically:
- evidence for a dose response;
- the embryonic stage of exposure is critical to whether the developmental effect will be produced;
- specificity between the substance and the effect to be produced; and
- lack of effects other than those produced by a specific substance (that are suggestive of a different mechanism).
Environmental toxins
BioaccumulationBioaccumulation
Bioaccumulation refers to the accumulation of substances, such as pesticides, or other organic chemicals in an organism. Bioaccumulation occurs when an organism absorbs a toxic substance at a rate greater than that at which the substance is lost...
and persistence
Persistence
Persistence may refer to:* Image persistence, in LCD monitors* Multidrug tolerance, a dormant, persistent state of a bacterial population* Persistence , the characteristic of data that outlives the execution of the program that created it...
are important aspects to consider since such substances are more likely to be present over several developmental stages than substances that are quickly eliminated. Such substances, known as persistent organic pollutant
Persistent organic pollutant
thumb|right|275px|State parties to the Stockholm Convention on Persistent Organic PollutantsPersistent organic pollutants are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes...
s (POPs), include a number of chemicals that are known to have adverse effects on fetal development given the level and timing of exposure: polychlorinated biphenyl
Polychlorinated biphenyl
Polychlorinated biphenyls are a class of organic compounds with 2 to 10 chlorine atoms attached to biphenyl, which is a molecule composed of two benzene rings. The chemical formula for PCBs is C12H10-xClx...
s (PCBs), polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofuran
Dibenzofuran
Dibenzofuran, is a heterocyclic organic compound with the chemical structure shown at right. It is an aromatic compound that has two benzene rings fused to one furan ring in the middle. All of the numbered carbon atoms have a hydrogen atom bonded to each of them...
s and organochlorine insecticide
Insecticide
An insecticide is a pesticide used against insects. They include ovicides and larvicides used against the eggs and larvae of insects respectively. Insecticides are used in agriculture, medicine, industry and the household. The use of insecticides is believed to be one of the major factors behind...
s such as DDT
DDT
DDT is one of the most well-known synthetic insecticides. It is a chemical with a long, unique, and controversial history....
are examples of such compounds that can be toxic to the fetus at high enough doses. Others, such as lead
Lead
Lead is a main-group element in the carbon group with the symbol Pb and atomic number 82. Lead is a soft, malleable poor metal. It is also counted as one of the heavy metals. Metallic lead has a bluish-white color after being freshly cut, but it soon tarnishes to a dull grayish color when exposed...
and methylmercury
Methylmercury
Methylmercury is an organometallic cation with the formula . It is a bioaccumulative environmental toxicant.-Structure:...
are persistent but not bioaccumulative. (Later, such chemicals continue to be passed from mother to baby via breast milk
Breast milk
Breast milk, more specifically human milk, is the milk produced by the breasts of a human female for her infant offspring...
.
A number of environmental toxins known to have adverse effects on fetal development are endocrine disruptor
Endocrine disruptor
Endocrine disruptors are chemicals that interfere with endocrine in animals, including humans. These disruptions can cause cancerous tumors, birth defects, and other developmental disorders...
s. Processes involved with differentiation and growth of embryonic and fetal cells are under the tight control of a myriad of messaging systems, some of which involve hormones. In particular, chemicals that mimic or otherwise disrupt the normal response to estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
, androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
, or thyroid hormone
Thyroid hormone
The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...
have been particularly of concern during fetal development.
Environmental carcinogens also are of concern during this time. Research has indicated that in utero exposure to carcinogens may confer much higher risks than later in life. This may be due to the rapid growth and differentiation of cells during this time, with, perhaps, less ability to repair the damage caused by carcinogens or to mount an effective immune response.
In utero cocaine exposure
Environmental factors such as the drug toxicity of recreational drugs can potentially interfere with the in uteroIn utero
In utero is a Latin term literally meaning "in the womb". In biology, the phrase describes the state of an embryo or fetus. In legal contexts, the phrase is used to refer to unborn children. Under common law, unborn children are still considered to exist for property transfer purposes.-See also:*...
brain development of a fetus. In utero cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
exposure has been linked to the development of septo-optic dysplasia
Septo-optic dysplasia
Septo-optic dysplasia , also known as de Morsier syndrome is a congenital malformation syndrome made manifest by hypoplasia of the optic nerve and absence of the septum pellucidum...
.