Neogeneses

The development and health of a fetus can be severely impaired by prenatal exposure to myriad circumstances, processes, and substances. The sheer number of factors that are potentially harmful to a fetus is staggering. “An agent that induces developmental abnormalities in a fetus. The process that results in these abnormalities is called teratogenesis; a teratomorph is a fetus or offspring with these abnormalities,” is The American Psychological Association’s definition of a teratogen (APA Dictionary of Psychology, n.d.). When suspected teratogens are included with known teratogens, concentrations or lengths of exposures required to cause impactful harm being ignored, estimates can quickly rise into the hundreds of thousands. A list of harmful synthetic chemicals alone could easily populate such a list.

Some teratogens can be mild, others can be commonplace, and others still are profoundly toxic even in small amounts. While any toxin may be poisonous to an adult, it is important to remember that it’s only during pregnancy that a toxin is said to be a teratogen. Similarly, a person battling smallpox would be considered to have a viral infection, but for a developing fetus, their mother’s smallpox infection could be viewed as a teratogenic concern. In terms of human development, while teratogens denote in utero concerns, it can be useful to extend the reach of harmful developmental factors to the overall health of men and women of child-bearing age. Parental health has the potential to affect a fetus long before conception has even occurred, with prior exposures to problematic factors longitudinally acting as de facto teratogens. Similarly, epigenetics, mutagenesis and other reproductive system concerns are worth additional considerations.

Teratogens can be classed over several broad and varying categories. Deviations of classification and recognition usually depend on which nation, professional body, or health system is involved, yet true discrepancies as to the identification and inclusion of teratogens are relatively rare. If using five primary categories, teratogens include: infectious agents (active infections while a woman is pregnant, e.g., bacterial, viral, parasitic), physical agents (hyperthermia, injury), maternal health (pre-existing conditions known to impact a pregnancy, e.g., diabetes), environmental toxins (heavy metals, herbicides, industrial products/byproducts), and drugs (prescription, recreational, homeopathic, or supplemental). These final two of these categories, “environmental toxins” and “drugs,” are of present interest. Environmental toxins and drugs are either exposed or created by the machinations of humanity, byproducts of anthropogenic processes, and relatively new to the Earth – much like humankind.

Autism is but one developmental condition thought to have many contributing causes. Despite the scientific progress that exists in the Anthropocene era (named for the ‘responsible’ species), definitive etiologies for most disorders remain largely in the realm of speculation. The rapid increase of autism’s prevalence follows the industrial revolution, an interesting correlation, yet the vast complexity of any individual case prevents any definite links from being scientifically established as a root cause. While the professional community strategizes to uncover various causes, contact with heavy metals and other environmental toxins are a historical and contemporary under close etiologic consideration for autism as well as other disorders (Landrigan et al., 2012). Regardless of teratogenic components, answers remain elusive.

As a historical primer for any discussion of teratogens, the thalidomide scandal of the late 1950s and early 1960s is a valuable bit of history. Thalidomide has a side effect that reduces hyperemesis gravidarum (morning sickness), so it was prescribed to pregnant women who suffered this symptom while pregnant. The teratogenic effects of the drug were previously unknown. A single dose of thalidomide can cause severe birth defects, severe congenital disorders which often take the form of physical abnormalities. The microbiologic mechanisms of thalidomide’s actions are complex. Most noticeably, it acts to prevent a developing fetus’ tissues from forming in the correct shapes (Vargesson, 2015). Thalidomide is so teratogenically potent that both men and women are recommended to discontinue use for at least a full month before potentially conceiving. Blood donors are banned from donating blood for a month after discontinuing thalidomide, which helps to ensure fetal health if a pregnant woman needs a transfusion of blood.

Thalidomide still has recognized uses in treating several seemingly unrelated disorders and remains on the World Health Organization’s Model List of Essential Medications (DailyMed – Thalidomide Capsule, 2021). The National Library of Medicine, a department within the National Institutes of Health, effectively contrasts the “’black’ Boxed Warning” of Embryo-Fetal Toxicity with thalidomide’s current and valid cases of in the same document. Thalidomide is just one teratogen. The scandal served to bring teratogens into popular awareness, installing the drug as a permanent fixture of discussions within the professional community and the public alike.

Teratogens are usually most impactful in the earliest stages of fetal development, when young cells are rapidly dividing and beginning to differentiate. The first few days and weeks after conception (and during the first trimester in general) is the window of time in which when an embryo is most prone to developing major structural defects from teratogenic exposures (Critical Periods of Development, 2021). Some teratogens cause more trouble in the second and third trimesters of pregnancy, linked to minor fetal structural defects, yet still capable of causing major functional defects. In these cases, since the major structures (like organs or limbs) are already mostly formed, teratogens instead interfere with or damage the viability of these tissues, organs, and organ systems, and the qualities of a normal development. The resulting structural or functional defects, like any congenital defect, can impact the health and quality of life throughout a lifetime. Remembering that such exposures are preventable, yet also sometimes impossible to prevent, clearly casts a light on the ubiquity of the ‘environmental toxin’ and ‘drug’ categories of teratogens.

Not all teratogens require maternal exposure during a pregnancy; some exposures can occur years or generations before conception. Persisting environmental toxins, often called persisting organic pollutants (POPs), can linger in an environment. POPs do not readily break down and continue to pollute the organic and inorganic aspects of an ecosystem perpetually. POPs are often found in soil, permeate the hydrologic cycle, are absorbed by plants, and penetrate humanity’s food supply as much as they do nature herself. A famous example can currently be seen in the health of people who live in modern-day Vietnam.

During the Vietnam war, various herbicides were used in attempts to clear the flora of the Vietnamese jungles to visually expose enemy positions. “Agent Orange,” named for the orange stripe on containing barrels, was more useful than the other color-coded barrels – like Agent Pink or Agent Red. In industrial synthesis, dozens or hundreds of other compounds can be useful to create any given product. Some scientists contest that Agent Orange itself isn’t particularly teratogenic, but compounds used in its synthesis certainly are. Agent Orange is known to contain an incredibly potent variety of POP called TCDD (King & Chou, 2017). One of many chemicals broadly classed as Dioxins, TCDD (2,3,7,8-Tetrachlorodibenzodioxin) is perhaps the most harmful of the hundreds of permutations within the dioxin chemical class. Even after soldiers left Vietnam, Agent Orange remains, causing birth defects of many varieties.

Major structural defects caused by teratogens, like the dioxin(s) found in Agent Orange, will impair any chance of a good quality of life. Spina Bifida is most common and one of the more tragic, as it primarily effects the formation of the human spine and nervous system – the miraculous organ system that sets humanity apart from any other known form of life. Exposure to TCDD and other highly toxic POPs can also cascade through generations; TCDD is thought to have an epigenetic action. Such compounds have harmful effects that qualify as transgenerational and epimutagenic (affecting the structure and chemical composition of the DNA in germ cells, but not affecting the base pairs), as these traits can become heritable in genotype and thus expressed in phenotype (Manikkam et al., 2012). Mutagenesis, caused by similarly powerful teratogens, could be permanent within the lineages of those exposed. More generations must first and unfortunately pass to reach a scientific conclusion, even if the hypothesis breaks down into simplest of logic. There are many compounds which pose such threats to the genetic code and the developing fetus. Agent Orange simply had widespread publication.

To understand the scope of environmental toxins, Chemsec, an organization hoping to regulate hazardous chemicals, disseminates a bold statement on their website: “Chemical researchers are convinced that hazardous chemicals are a global threat comparable to climate change,” (Chemsec, n.d.). Their website notes a shocking statistic: seventy-three percent of the chemical compounds produced or used in Europe, totaling 220 million tons per year, are hazardous to human health. These are only the officially reported numbers in Europe. The phrase ‘harmful to human health’ applies to embryos and fetuses; it’s safe to say these compounds can act as teratogens.

Endocrine-disrupting chemicals continue to garner the attention of professionals and researchers. These are not one class of chemicals, but rather any chemical that can offset the natural patterns of the human endocrine system (Konieczna et al., 2015). Many (if not all) such compounds are also teratogenic and may even be connected to epigenetic shifts in human populations (Diamanti-Kandarakis et al., 2009). Phthalates and BPA are popular examples of endocrine-disrupting chemicals, as are dioxins. Phthalates and BPA (Bisphenol A) can be found in some kinds of plastics, common household products, and are used extensively in industrial and commercial settings. Regulations have reduced their presence, but they are not eliminated worldwide and remain as pollutants.

Exposure to a compound like BPA is usually subtle yet constant. A single can of soup is unhealthy (many have a BPA lining) but is relatively manageable for a healthy human body to process and remove. Daily prepackaged foods, leftover, stored, and reheated in plastic containers, these become constant vectors for such chemicals to infiltrate the body. Small amounts of daily exposures amount to incessant micro doses. Since BPA mirrors estrogen molecularly, it has an affinity for locations in the human body that would regularly respond to the presence of estrogen, regardless of gender or pregnancy status (Konieczna et al., 2015).

Endocrine disrupters perform feats of hormonal trickery well enough to earn their name.  Considering that the male and female reproductive systems are a part of the endocrine system, the seats of androgens and estrogens and their respective germ cells, all of which sometimes come together to produce an embryo, the teratogenic connection becomes clear.  There is a very low chance to not have any exposure to endocrine-disrupting chemicals, as they are seemingly omnipresent within modern civilization, like many other teratogens.

Endocrine disruptors in general are implicated in causing or contributing to many reproductive issues. Reduced semen quality, male and female urogenital malformations, polycystic ovarian syndrome (PCOS), and precocious puberty are some of the more commonly known disorders linked to these chemicals (Diamanti-Kandarakis et al., 2009). If epigenetic concerns of potentially activating disorders like PCOS or male/female infertility were not frightening enough, the studies referenced in the work of Diamanti-Kandarakis also point out that some of these concerns may even become heritable.

Far more recently than the teratogenic benchmark set by thalidomide, some commonly prescribed drugs are proving to be teratogenic. Valproic acid, an anti-convulsant often dispensed as a mood stabilizer for sufferers of various mood disorders, can cause of a recently identified condition dubbed “fetal valproate syndrome” (FVS). The syndrome may be dose dependent in women who are or may become pregnant. FVS is marked by major structural abnormalities like neural tube defects and cleft palates in the children of valproic acid patients (Koren et al., 2006).

Metformin made international medical news in the last year for reports of male children being born with reproductive defects. Fathers who were taking this blood-sugar stabilizing drug at the time of conception suffered reproductive abnormalities which altered the viability and overall quality of their sperm. These abnormalities were severe enough to affect the reproductive systems of their children assigned male at birth (Tseng, 2022). Metformin is now less favored in treating adults who wish to reproduce.

Not all teratogens and causes of birth defects result from chemicals, infections, or modern medical treatments – some can be unexpected and are generally ignored as being innocuous. Even though most people know about the dangers of sun exposure, x-rays, and nuclear fallout, few consider sources of radiation surrounding “modern” life. While it is safe to assume a healthy adult would not want to stand in an x-ray booth for scores of hours each week, an extreme analogy, this occurs to a milder degree with current wireless communications technologies. Cell and Wi-Fi services for the web-connected and Internet of Things (IoT) devices are simply different wavelengths and intensities of the same thing – the spectrum of light. The spectrums used vary between intended application and various international standards, yet many of these wavelengths can sufficiently penetrate human flesh. The medical journal, Andrology, reports some complex data about cell phones and male infertility. They recommend, as a failsafe, that men not store their phones in their trouser pockets, far easier said than done (Liu et al., 2014).

It’s clear that reproductive toxins and teratogens are a ubiquitous part of modern human life. Even if the world was to unite to solve terminal problems like climate change, war, disease, famine, malaise, or unrest, even the common cold, purging environmental toxins from the environment is a tall order. To cleanse ecosystems of a single class of POPs would involve extracting countless culprit molecules from the Earth, water, plants, animals, microorganisms, and the air. Microplastics have been repeatedly detected in rain and air samples, so common and widespread that they can readily be found in samples of human blood (Leslie et al., 2022). This is the same for many environmental teratogens, depending on their physical properties and how easily they travel. Limiting the concentration and severity of teratogenic exposure is the best order of business for anyone alive – especially women and men who hope to have children. In Europe, the so-called “Great Detox” would be a step in the right direction, a legislative move towards the ban of thousands of toxic compounds, including the “forever chemicals” like the POP “star” known as TCDD of Agent Orange. (European Environmental Bureau, 2022).

The Anthropocene age may be marked by humans terraforming and processing Earth into unnatural forms, leaving an indelible fingerprint. How these pollutions will affect the future generations, morally tasked with attempting to clean the fallout of humanity itself, this weight foisted on their existence is beyond all ethical conception. Short of technologies yet to be conceived by these future generations, limiting the damage to our home, to our own kind, to children unborn and alive is the staging ground and work for any hopes of a solution. It may become that utopia is the result of the lessons of dystopia, should the development of the children of humankind be able to be so stalwart and prevail.

References

  APA Dictionary of Psychology. (n.d.). Retrieved July 29, 2022, from https://dictionary.apa.org/teratogen/

  Chemsec. (n.d.). This is why you should care about hazardous chemicals – ChemSec. Retrieved July 29, 2022, from https://chemsec.org/about-us/why-care-about-hazardous-chemicals/

  Critical Periods of Development. (2021, March 1). MotherToBaby. https://mothertobaby.org/fact-sheets/critical-periods-development/

  DailyMed – Thalidomide Capsule. (2021, March 11). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2eda833b-1357-4ed4-a093-194524fcb061

  Diamanti-Kandarakis, E., Bourguignon, J.-P., Giudice, L. C., Hauser, R., Prins, G. S., Soto, A. M., Zoeller, R. T., & Gore, A. C. (2009). Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement. Endocrine Reviews, 30(4), 293–342. https://doi.org/10.1210/er.2009-0002

  European Environmental Bureau. (2022, May 25). The great detox – largest ever ban of toxic chemicals announced by EU. The Great Detox. https://eeb.org/the-great-detox-largest-ever-ban-of-toxic-chemicals-announced-by-eu/

  King, J., & Chou, C. (2017, March 7). Agent Orange Birth Defects | The Embryo Project Encyclopedia. https://embryo.asu.edu/pages/agent-orange-birth-defects

  Konieczna, A., Rutkowska, A., & Rachoń, D. (2015). Health risk of exposure to Bisphenol A (BPA). Roczniki Panstwowego Zakladu Higieny, 66(1), 5–11. https://pubmed.ncbi.nlm.nih.gov/25813067/#:~:text=Therefore%2C%20BPA%20has%20been%20shown,polycystic%20ovary%20syndrome%20(PCOS).

  Koren, G., Nava-Ocampo, A. A., Moretti, M. E., Sussman, R., & Nulman, I. (2006). Major malformations with valproic acid. Canadian Family Physician, 52(4), 441–447. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1481679/

  Landrigan, P. J., Lambertini, L., & Birnbaum, L. S. (2012). A Research Strategy to Discover the Environmental Causes of Autism and Neurodevelopmental Disabilities. Environmental Health Perspectives, 120(7), a258–a260. https://doi.org/10.1289/ehp.1104285

  Leslie, H. A., van Velzen, M. J. M., Brandsma, S. H., Vethaak, A. D., Garcia-Vallejo, J. J., & Lamoree, M. H. (2022). Discovery and quantification of plastic particle pollution in human blood. Environment International, 163, 107199. https://doi.org/10.1016/j.envint.2022.107199

  Liu, K., Li, Y., Zhang, G., Liu, J., Cao, J., Ao, L., & Zhang, S. (2014). Association between mobile phone use and semen quality: a systemic review and meta-analysis. Andrology, 2(4), 491–501. https://doi.org/10.1111/j.2047-2927.2014.00205.x

  Manikkam, M., Tracey, R., Guerrero-Bosagna, C., & Skinner, M. K. (2012). Dioxin (TCDD) Induces Epigenetic Transgenerational Inheritance of Adult Onset Disease and Sperm Epimutations. PLoS ONE, 7(9), e46249. https://doi.org/10.1371/journal.pone.0046249

  Tseng, C.-H. (2022). The Effect of Metformin on Male Reproductive Function and Prostate: An Updated Review. The World Journal of Men’s Health, 40(1), 11–29. https://doi.org/10.5534/wjmh.210001

  Vargesson, N. (2015). Thalidomide‐induced teratogenesis: History and mechanisms. Birth Defects Research, 105(2), 140–156. https://doi.org/10.1002/bdrc.21096