Int. J. Pharm. Sci. Rev. Res., ISSN: 0976 – 044X, 82(1), September – October 2023; Article No.

17, Pages: 105-111 DOI: 10.47583/ijpsrr.2023.v82i01.017

Review Article

A Review on Teratogenesis: Current Perspective

Renu Sharma, Disha Kesharwani*, Sandhya Mishra, Maneesha Kumari
Assistant Professor, Columbia Institute of Pharmacy, Raipur, Chhattisgarh, India.
*Corresponding author’s E-mail: disha@columbiaiop.ac.in

Received: 10-06-2023; Revised: 20-08-2023; Accepted: 26-08-2023; Published on: 15-09-2023.

ABSTRACT
Teratogenesis is derived from Greek word “Terato” which means monster. Teratogenesis results in the development of
morphologically abnormal individuals. These may include conditions like intellectual disabilities that don't have any visible structural
deformities. This defect is mainly produced by teratogens which is genesis of physical and functional defect in human’s embryo and
fetus. Teratogens have a variety of effects on embryos, including physical deformities, issues with the child's behavioral or emotional
development, and a decreased IQ in the child. Teratogens can also have an impact on pregnancies. Physical agents, metabolic
circumstances, infections, and finally, medications and chemicals, are the four groups into which teratogens are divided. A few
examples of teratogens are prescription medications like thalidomide, environmental poisons like cadmium, and environmental
pollutants like pesticides and endocrine disruptors. Viruses, such as the rubella and Zika viruses, physical constriction of the uterus,
and a poor diet are additional causes of teratogenesis. This review will examine the drug's history, the scope and kind of the harm it
caused, as well as the drug's mechanisms of action, including recent molecular developments and fresh research.
Keywords: Teratology, patents, Embryo deformity, Etiology.

INTRODUCTION • Hyperthermia

A prenatal toxic condition known as teratogenesis is

characterized by structural or functional flaws in
the growing embryo or fetus. In this phenomena,
birth abnormalities and malformations such intrauterine
growth retardation, fetal or embryonic mortality, and
• Maternal conditions like gestational diabetes 9-16.

transplacental carcinogenesis take place. The word

"teratology," which means "study of monsters," is Greek in
origin. Teratology is the study of mechanisms that cause
anomalies and birth disorders carried by environmental
causes other than genetics 1-5. Teratogens are any
substances capable of resulting in a birth abnormality or
malformation. Although in several cases, the causes of
abnormalities were not revealed clearly. The birth defects
might be genetic, chromosomal, or environmental (for
example, medications). However, some of the factors
promoting teratogenicity are depicted in figure-1 6-8. Figure 1: Factors promoting teratogenicity
Different types of the teratogens are- History of Teratology
• Chemical substances, such as prescription Experimental teratology was first described in 1928 in this
medications like thalidomide and retinoic acid; illicit study exposure to therapeutic radiation during pregnancy
substances such as alcohol and cocaine; it causes microcephaly baby in pregnant women. The
environmental toxins including heavy metals like 1930s saw the publishing of a series of studies using
cadmium; and pollutants like pesticides linked to pregnant pigs fed a diet lacking in vitamin A, which marked
reproductive and fertility problems, like the beginning of teratology as a contemporary science 17-
28
diethylstilbestrol during pregnancy. . The majority of the abnormalities encountered by these
piglets, which lacked eyes, were similar. OsefWarkany, a
• Infections including as rubella and Zika virus.
physician, is recognized as the founder of experimental
• Physical constraint or in-utero damage, such as teratology. He was the first to demonstrate, in the 1930s
clubfoot from oligohydramnios, where the amniotic and 1940s of the previous century, that foreign causes can
fluid is lost and the foetus is restricted, can occur. also cause CDDs in mammals 29-32. Various important
Amniotic band syndrome is one kind of physical harm events in the history relevant to teratogenesis is shown in
that occurs to a fetus while it is still inside the mother. table 1.
In severe situations, the condition can result in death.

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Table 1: Various important events in the history of two teratology information centers were established in
teratogenesis 1990 37-39.

Year Event 1. European Network of Teratology Information

Services (ENTIS)
1905 The first experimentally induced
developmental toxicity in mammals. Embryonic 2. Organization of Teratology Information
lethality induced by X-rays in cats. Specialists (OTIS)
1921 The first experimentally induced teratogenicity TERATOGENESIS ETIOLOGY
in mammals. Disorders in limbs in pigs induced
The branch of embryology specialized in studying the
by lipid diet.
etiology of abnormal development of embryo is known as
1928 The first experimentally induced teratogenicity “Teratology”. There are two etiological groups in which
in mammals. Disorders in limbs in pigs induced various teratogens participates for inducing congenital
by lipid diet. anomalies (1) primarily environmental (2) multifactorial
1929 The first description of malformations in origin. The sequence followed in the development of
humans caused by exogenous factors. teratogenesis is depicted in figure 243-48.
Microcephalia caused by X-ray irradiation of
the pelvis.
1933 Deficiency of vitamin and the first month
before pregnancy and during pregnancy.
1995 Recognition of food deficiency leading to
malformations in animals. Eye disorders in pigs
due to hypo-vitaminosi

The prevalence of abnormalities is higher in situations like

spontaneous abortions than in live-born newborns, which
may be a reflection of the fact that many of the most
severe issues are insurmountable barriers to survival. The
study of teratogenesis is critical for ensuring that
medications are secure and/or do not cause birth defects,
that is, that they are nonteratogenic. For this reason,
teratogenesis research is crucial for ensuring that
Figure 2: Etiology of teratogenesis
pharmaceuticals are safe 33-36.
ELEMENTS CAUSING TERATOGENESIS
Presently, the molecular mechanism of some of the
teratogens is known but for some of the reproductive Most foods or dietary ingredients have teratogenic effects,
toxicants and foetotoxicants it is still nameless. in addition to medications. Foods that include
Reproductive toxicants can cause disturbances in cell preservatives typically have a greater teratogenic effect.
division, enzyme system, water electrolyte balance, Therefore, packaged foods are prohibited during
membrane characteristics, energy transfer to foetal pregnancy. Direct or indirect exposure to various harmful
development and mutation. The factors causing birth chemicals during pregnancy can also leads to teratogenesis
defects can vary and their etiology is unknown. in the developing embryo. The major causative agents as
like foods, medications, chemical and infections are
Initially for understanding the situation and providing the
enlisted in the table no. - 2, 3, 4 and 5 30-41.
drafted information to health professionals and public, the

Table 2: Food products causing Teratogenicity

S.no Chemical Category Animal involved in Effect

constituents research
1 Sodium benzoate Preservative Long term consumption • Carnio facial deformation
(mice) • Mandibular hyperplasia
2 Potassium Preservative Long term consumption • Congenital eye abnormality
benzoate (mice) • Mal formed lenses
3 Asparatame Artificial sweetener Long term consumption • Retardation of brain
(chick) • Formation anencephaly
4 Vitamin A Fortifying agent - • Facial nerve paralysis

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• Under developed upper jaws

• Malformed ears
5 Taratzine Colouring agent - • Hepatorenal damage
• cardiomegaly
6 Carrageenan Stabilizers Chick embryo Prevention of cell activity and
morphogenesis as Carrageenan binds to cell
7 Alcohols Chemical Chicken and fish • Mortality eye defects
• facial defects

Table 3: Teratogenicity due to medications

S.no Drugs Maternal condition Adverse impact on embryo
1 ACE inhibitors • Hypertension • Neonatal renal failure
(Benzapril, Ramipril, • pulmonary
Qunaipril, Perindopril, • Hypoplasia
Trandopril)
• death
2 Methimazole • Hyperthyroidism • Skull Hypopalasia
• psychomotor delay
• growth retardation
• scalp defects
3 • Amiodarone • Thyroid • Neonatal thyroid dysfunction
• Radioiodine • Fetal Goitrhypothyroidsm
• Goitre
4 Trimethoprim • Bacterial infection • Neural tube defects
• Oral defects
• cardiovascular defect
5 Indomethacin • Fever • Oligohydramnios
• Inflammation • anuria
• Premature labour hydramnios • premature closure of ductus arterious
6 Quinine • Leg cramps • Deafness
• Malaria • Abortion
7 Misoprostol • Peptic ulcer disease • Congenital anomalies
• Cervical ripening
8 Penicillamine • Cystinuria • Connective tissue abnormalities
• Rheumatoid arthritis
9 Thalidomide • Insomnia • Limb reduction
• Oesophagus ulcers • Urogenital and gastro intestinal defect
• Oropharyngeal associated with AIDS • Carnival nerve anomalies
11 Retinoids • Dermatologic disease • Organogenesis
12 Cyclophosphamide • cancer,transplant rejection • Organogenesis
13 Methylene blue • Twin pregnancy • Jejunalartesia

IN VITRO DIAGNOSTIC METHODS The European Centre for the Validation of Alternative
Methods (ECVAM) on its 17th meeting endorsed three
There are several in-vitro diagnostic methods which help in
scientifically validated methods.
diagnosis of the condition. It can be classified into following
classes 1. Embryonic Stem Cell Test (EST) – Two permanent
murine cell lines i. e. D3 (Embryonic tissue) and 3T3
(a) Preliminary screen for developmental toxic agents
fibroblast cell (adult tissue) are used.
(b) Estimation of mechanism of normal and abnormal
2. Micromass Test
embryogenesis.
3. Whole Embryo Culture Test 41-42

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Table 4: Chemical causing teratogenesis approach to prevent teratogens. Planning for pregnancy
S.no Chemicals Malformation enables you to manage long-term medical concerns and
make modifications to their lifestyle, such as stop smoking
1 Mercury Brain development disorder and many more. The preventive measures that must be
2 Cadmium Limb anomalies taken during the pregnancy is shown in the figure 3 43-51.
3 Poly chlorinated Intra uterine growth
biphenyls retardation

Table 5: Infections causing teratogenesis

Infections Malformation
Cytomegalovirus • Brain and sensory anomalies
HIV • Growth failure
• microcephaly
• carnio facial defects
Rubella • Intrauterine growth retardation
• Cardiac defects
• Deafness and eye defects
Zika virus • Microcephaly
Figure 3: Preventive measures for teratogenesis
PREVENTION OF TERATOGENESIS
RECENT ADVANCEMENT IN TERATOGENESIS
Teratology has become a big problem today and it is
necessary to have new idea and new strategies to stop it. As research is a continuous process, various patents have
Teratogenesis starts from the womb of the mother and been published and granted in the field of efficient and fast
there is no cure for it after the birth of a child, it can be diagnosis and treatment of teratogenesis. Some of the work
prevented by avoiding teratogen at the different stages of published in recent years is cumulated in the below given
pregnancy. Counselling for pregnancy is the greatest table 6.

Table 6: Patents related to teratogenesis

S.No. Title Patent No. Published Work Inventor Date of Reference

Publication
1 Evaluation of CN107228925A This strategy effectively YaoMeicun, 2017-10-03 52
teratogenis cause examined the possible ChenJiefeng,
by Chinese teratogenesis of ChenZuanguang,
patent drug by Chinese patent drugs, Liao Min,
using zebra fish frequently carried out LiuTong, Liu
embryo toxicity analyses by Mengping, Huang
using zebra fish embryo Danping
2 The procedure for CN1069706772A The present invention Chen Zepeng 2017-05-24 53
finding extracts teratogen in Wan Shuqing
Teratogenesis- tobacco compound Lin Xianfeng
causing fertilizer using the
compounds in method of science.
tobacco chemical
fertilizer and their
use
3 Molecular genetic CN110714085A They summarized a Li Zhili 2020-01-21 54
marker related to report regarding swine Yuan Sheng
pig sperm sperm teratocarcinoma Zhang Nan
teratogenesis related molecular
Chi Shihong
rate and genetic marker.
application Yu Weiwei
thereof Kwong Wai Kin
Wang Meihong

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4 Blocking the EP0616534A1 They described about William F. Geber 1994-09-28 55

effect of the agents which can
teratogens on a block the effects of
fetus teratogens on fetus as
well as host.
5 Method of WO2013131841A1 They described about Eric Chiao, Sei 2015-05-18 56
determining the method for KAMEOKA, Kyle
teratogenic risk determining the risk of L. Kolaja
drug induced
teratogenesis.
They utilized
pluripotent stem cells.

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