Transplacental carcinogenesis is a series of genotypic and/or

phenotypic In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...

changes in the cells of a

fetus A fetus or foetus (; : fetuses, foetuses, rarely feti or foeti) is the unborn offspring of a viviparous animal that develops from an embryo. Following the embryonic development, embryonic stage, the fetal stage of development takes place. Pren ...

due to ''

in utero The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic and fetal development of one or more fertilized eggs until bir ...

'' exposure to

carcinogens A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruse ...

. Specifically, these changes are identified as malignant by virtue of their

metastatic Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

potential.

Transplacental transfer

The link between a pregnant mother and the fetus is such that "at all sites of direct cell-to-cell contact, maternal tissues (

decidua The decidua is the modified mucosal lining of the uterus (that is, modified endometrium) that forms every month, in preparation for pregnancy. It is shed off each month when there is no fertilized egg to support. The decidua is under the influe ...

and

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...

) are juxtaposed to extraembryonic cells (

trophoblast The trophoblast (from Greek language, Greek : to feed; and : germinator) is the outer layer of cells of the blastocyst. Trophoblasts are present four days after Human fertilization, fertilization in humans. They provide nutrients to the embryo an ...

).” According to Cunningham, "after conception, a biomolecular communication system is established between the fetus and mother that is operative from before the time of nidation and continues through and beyond the time of

parturition Birth is the act or process of bearing or bringing forth offspring, also referred to in technical contexts as parturition. In mammals, the process is initiated by hormones which cause the muscular walls of the uterus to contract, expelling the f ...

." This communication system is essential to all facets of the

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

. "

Physiological Physiology (; ) is the science, scientific study of function (biology), functions and mechanism (biology), mechanisms in a life, living system. As a branches of science, subdiscipline of biology, physiology focuses on how organisms, organ syst ...

processes such as fetal nutrition and

fetal development Prenatal development () involves the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal deve ...

progress directly from

embryo An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sp ...

nic/fetal tissue-directed modifications of maternal responses." Notably, the

placenta The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...

is the principal site of transfer between mother and fetus. A fetus is exposed via the placenta to all substances which are present in the peripheral circulation of the mother. Overall, the abundance of

toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...

s contained within cigarette smoke that is inhaled by the mother exerts a direct impact by altering the placental and fetal

cell proliferation Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation ...

and differentiation. The vital balance of cellular activity is disrupted. "The association of in utero exposure to such

carcinogen A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruse ...

s and the subsequent development of

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

has been reported for all

childhood cancer Childhood cancer is cancer in a child. About 80% of childhood cancer cases in high-income countries are being able to treat with modern treatments and good medical care. Yet, only 10% of children with cancer live in high-income countries where pro ...

s combined and particularly for childhood

acute lymphoblastic leukemia Acute lymphoblastic leukemia (ALL) is a cancer of the Lymphocyte, lymphoid line of blood cells characterized by the development of large numbers of lymphoblast, immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, ...

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...

, and brain tumors."

Fetal cell sensitivity

Fetal cells are most sensitive to carcinogens during the early stages of

gestation Gestation is the period of development during the carrying of an embryo, and later fetus, inside viviparous animals (the embryo develops within the parent). It is typical for mammals, but also occurs for some non-mammals. Mammals during pregn ...

. Notably, early in the gestational period, there is a high rate of

cell division Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...

. Additionally, the cells exhibit undifferentiated characteristics. These compounding factors illustrate the basis for this heightened cellular sensitivity to

genotoxic Genotoxicity is the property of chemical agents that damage the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, but some genotoxic s ...

agents. For example, it has been proven that during exposure

nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...

binds to receptors of the fetal cells through which developmentally important signaling occurs in many developing

organs In a multicellular organism, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to a ...

and tissues. Because the binding of these receptors is unanticipated by the regulated activity of the fetal cells it can be inferred that this is a disruption in the cellular process which can lead to detrimental effects such as the deregulation of vital signaling, expression, or repair. As indicated above, should this exposure occur during the early stages of gestation, the fetus will be more susceptible to such damage. In addition to receptor binding, it has also been proven that fetal tissues are suspected as "privileged targets of

neoplastic A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

changes" in light of the vast amount of

and differentiation taking place. Notably, tumors are arrived at via proliferating cells. In the event that proliferating cells become uncontrolled, by any measure, this

mutated In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA replication, DNA or viral rep ...

activity would certainly be characteristic of an increased risk in one's chances of developing

Transplacental transfer

Fetal cell sensitivity

References

Further reading