Biomarkers of teratogenesis: Suggestions from animal studies

Abstract

a b s t r a c tBiomarkers of effect are measurable biochemical, physiological or other alterations within an organism that can be recognized as causing an established or potential impairment of embryo-fetal development. They may be identified studying the mechanisms of action of teratogens. Hyperacetylation of histones, oxidative stress, cholesterol and retinoic acid unbalance are some of the identified mechanisms of action of some known teratogens. Nevertheless, their use is not currently applicable in human pregnancy because of the difficulty of the choice of biological material, the time when the material must be obtained, and the invasivity of methods. Furthermore, before using them in human pregnancy studies, biomarkers should be validated in experimental animals and in epidemiologic studies. On the contrary, some biomarkers could be useful in the screening of developmental toxicity of chemicals and drugs, comparing molecules of the same chemical class or with the similar pharmacologic activity, and using adequate in vitro tests, in order to reduce the use of experimental animals.

Teratogens: a public health issue – a Brazilian overview

“…The most common mechanisms of action of teratogens are hyperacetylation, cholesterol imbalance, alteration of folate metabolism and folate antagonism, retinoic acid imbalance, endocrine disruption, vascular disruption and oxidative stress (Giavini and Menegola, 2012). …”

“…However, retinoic acid is also a signaling molecule in neural crest cells, which will originate various cell types and structures, such as intramembranous bone, cartilage, peripheral nerves and Schwann cells, and muscles, amongst others. Drugs such as isotretinoin can contribute to retinoic acid imbalance and lead to craniofacial and axial skeleton malformations (Giavini and Menegola, 2012). …”

“…Exogenous ROS sources include ultraviolet light (UV), UVA and UVB radiation, ionizing radiation, and chemical agents, while endogenous sources are related to cellular metabolism or oxidase enzymes (Hansen, 2006; van Gelder et al. , 2010; Giavini and Menegola 2012). Some of these agents (also called proteratogens) can be bioactivated by embryonic cytochrome P450 enzymes.…”

A perspective on molecular and cellular biology-based developmental toxicology biomarkers

“…adolescent's continued improvement and differentiation of their skeletal, nervous, and reproductive systems (Giavini and Menegola, 2012). Therefore, it appears unfair to limit the definition of developmental contaminants to substances that can harm an embryo or foetus when a mother is exposed to them during pregnancy.…”

“…In addition to birth problems, growth retardation, mortality (including the loss of embryos and foetuses), and functional impairments in the newborn are increasingly recognized as detrimental developmental impacts (Draskau et al, 2020). In laboratory animals, over 1,200 distinct substances have been found to have detrimental developmental consequences; however, the implications of exposure to many of these substances in humans are not well known (Giavini and Menegola, 2012;Luconi et al, 2022).…”