Acetylation: Describes the reaction that introduces an acetyl group onto a protein, such as a histone.
Allele: Human genes occur in pairs, one on each chromosome of a chromosome pair. Each gene of the pair is called an “allele.” Although each allele specifies the same gene, alleles can differ slightly from each other and give rise to proteins that may differ in form and significance. For instance, in the case of some flowers, the allele on one chromosome may produce a red petal color and the other a white petal color.
Amino acid: A set of 20 different molecules used to build proteins. Proteins consist of one or more chains of amino acids called polypeptides. The sequence of the amino acid chain causes the polypeptide to fold into a shape that is biologically active. The amino acid sequences of proteins are encoded in the genes.
Apoptosis: Series of biochemical reactions occurring in a cell whereby cells undergo a process of self-destruction; also known as programmed cell death or cell suicide.
Bases: The basic building blocks of DNA and RNA. The bases used to make DNA are adenine (A), cytosine (C), guanine (G), and thymine (T). In RNA, the base uracil (U) takes the place of thymine. Bases are attached to a phosphate group and a sugar molecule (either ribose in RNA or deoxyribose in DNA) to build DNA or RNA.
Blastocyst: A distinct stage of embryo development when the undifferentiated cells of the zygote implant in the uterine lining and differentiate into two cell types: the inner cell mass that will develop into the fetus, and the trophectoderm that will develop into the placenta.
Carrier: An individual who carries and is capable of passing on a genetic mutation associated with a disease and may or may not display disease symptoms. In some cases, carriers are associated with diseases inherited as recessive traits, whereby an individual having one normal allele and one mutated
allele does not have the disease. For such recessive traits, in order to have the disease, an individual must inherit mutated alleles from both parents. Because carriers of recessive alleles may not display the disease, two “normal” appearing carriers may produce children with the disease.
Cell: A fundamental unit of life comprised of a membrane-encapsulating cytoplasm and genetic material (DNA or RNA) contained in a nucleus. First discovered by Robert Hooke in 1665 in cork, then in living plant tissue using an early microscope rebuilt after Anton van Leeuwenhoek’s microscopes.
Cell cycle: The orderly sequence of events in which a cell duplicates its contents, including its genetic material, and divides into two cells.
Cell fate: The final cell type that an undifferentiated cell is destined to become. Usually refers to the outcome of cell differentiation during the process of development.
Cell nucleus: Membrane-bounded organelle common to all eukaryotic cells that contains and separates the genetic material (DNA and associated proteins organized into chromosomes) from the remainder of the cell (the cytoplasm).
Chromatin: In the nucleus of each cell, DNA is packaged into chromatin made up of DNA tightly coiled many times around proteins called histones that support its structure.
Chromosome: A structure visualized during cell division containing condensed chromatin and its associated genes as the unit of inheritance. Humans have 46 chromosomes, 22 pairs of autosomes (the non-sex chromosomes), and the sex chromosomes either XX (females) or XY (males).
CpG: Cytosine-adjacent-to-guanine amino acid sites in the human genome.
Developmental origins of health and disease (DOHaD): The theory that environmental exposures early in life can have lasting effects on health and susceptibility to disease into adulthood. Sometimes referred to as Fetal Origins of Disease Hypothesis or Barker Hypothesis.
Developmental toxicity: The ability of a toxicant to cause an adverse effect in a developing organism. Examples of developmental toxicants include chemicals such as diethylstilbestrol, lifestyle factors such as alcohol, and drugs such as retinoic acid.
Differentiation: Process whereby cells/tissues become more specialized during embryonic development.
DNA: Deoxyribonucleic acid, the genetic material of most organisms. It is made of a double-helically coiled sugar-phosphate backbone, held together by organic base pairs (adenine with thymine; guanine with cytosine). This generates two complementary strands of base-pairs. The entire sequence of the human genome contains billions of base-pairs.
DNA adduct: A chemical covalently bound to a DNA base, such as benzo[a]pyrene, which can cause a DNA mutation, and which is frequently used as biomarkers to reflect exposure, as the presence of such an adduct reflects prior exposure to that chemical.
DNA damage: Any damage to DNA, which if unrepaired can cause defects such as mutation, chromosome breakage, or loss of portions of chromosomes.
DNA methylation: The reversible addition of a methyl (CH¬3) group to the DNA. It usually occurs at DNA cytosine nucleotides followed by guanosine (C-phosphate-G; CpG) and generally (but not always) functions to represses gene expression.
DNA methyltransferases (DNMT): Enzymes that catalyze the transfer of a methyl group to DNA from S-adenosylmethionine.
DNA sequence: The sequence of bases in 5'→3' direction (printed left to right) along a strand of DNA. There are four organic bases: adenine (A), thymine (T), guanine (G), and cytosine (C), which define the sequence in a single strand DNA. The DNA sequence of a gene will determine the amino-acid composition of a protein.
DNA structure: The physical shape of DNA molecules, such as coiling into tight loops or other shapes, can determine how, where, and when genes are expressed.
Embryo: A term used to describe the early life stage of a developing organism after fertilization. In humans, the embryo begins after fertilization of an oocyte by a sperm cell and persists up until week 14 of pregnancy.
Embryogenesis: The formation and development of an embryo, referring to early pregnancy beginning with fertilization of an oocyte by sperm.
Embryonic stem (ES) cells: ES cells are self-renewing cells isolated from the vertebrate inner cell mass of a developing embryo. As ES cells are totipotent they are capable of differentiating into any somatic cell or tissue, but they also preserve their capability to remain within the developmental pathway of germ cells. Thus, they are part of the germ line.
Embryotoxicity: The toxic effect of a substance on an embryo in the first period of pregnancy, between conception and the fetal stage. Effects may include malformations and variations, malfunctions, altered growth, prenatal death, and altered postnatal function.
Environmental deflection: The cumulative effect of environment mediated change away from baseline epigenetic drift.
Enzyme: A protein that facilitates (catalyzes) a specific biochemical reaction. Many enzymes work together to build up and break down biomolecules within the cell. Enzymes drive key processes such as DNA replication, the addition of epigenetic marks on chromatin, and transcription of DNA into RNA and translation of RNA into proteins.
Epigenetic code: In addition to the genetic code of DNA that specifies how genes are made into proteins, the epigenetic code specifies, via DNA methylation and histone modifications, which genes are turned on (transcribed) and which genes are turned off.
Epigenetic drift: The stochastic accumulation of changes in the epigenome associated with age.
Epigenetic inheritance: The transmission of epigenetic information from a dividing cell to its daughter cells. In the case of epigenetic alterations, such alterations may occur in one cell and be inherited by daughter cells after cell division—this is referred to as mitotic inheritance; when the alterations occur in the germ line of a parent, the changes may be passed down to offspring (and possibly subsequent generations)—this is referred to as meiotic (or generational) inheritance.
Epigenetic marks: Chromatin features that govern gene expression and are not part of the genetic code. These include methylation of DNA and covalent modification of histone proteins. The primary histone modification that is considered an epigenetic mark is methylation, although other modifications, such as acetyl, ubiquitin, phosphate, and poly(ADP)ribose, are sometimes also grouped in this category. Importantly, alterations induced by environmental exposures, both DNA and histone methylation, can be passed down from mother to daughter calls after cell division, or if they occur in the germ line, from parent to offspring (and possibly subsequent generations).
Epigenetic reprogramming: In biology, epigenetic reprogramming refers to changes in patterns of epigenetic marks, such as DNA or histone methylation. This can refer to the normal process of erasure and reestablishment of epigenetic marks that occurs after fertilization, or the response to environmental exposures that perturb normal epigenetic programming, resulting in establishment of an abnormal epigenetic program.
Epigenetics: This term is most commonly taken to refer to processes responsible for heritable changes in gene expression that do not result from change in actual gene sequences.
Epigenome: The epigenome refers to the entirety of the epigenetic marks of chromatin, analogous to the “genome” which refers to all the genes of an organism. Within a single organism, while virtually all cells have the same genome, different cell types have distinct epigenomes that specify which genes are turned on or off to determine each cell type.
Epigenome environment interaction (ExE): When the response to an environmental exposure is a combination of both the exposure and the epigenome of the exposed cell/individual. This ExE interaction can occur, for example, if the epigenome itself is the target of the exposure and/or if the pattern of gene expression determined by the epigenome modifies the response to the environmental agent.
Epimutations: A heritable change in gene activity that is not associated with a DNA mutation but rather with gain or loss of DNA methylation or other heritable modifications of chromatin.
Estrogen: A female steroid hormone produced by the ovaries and, in lesser amounts, by the adrenal cortex, placenta, and male testes. Estrogen helps control sexual development, including the physical changes; influences ovulation in the monthly menstrual cycle; lactation after pregnancy; aspects of mood; and the aging process.
Fertilization (conception): The process of sexual reproduction when the fusion of gametes (sperm and oocyte) initiate the development of a new individual organism.
Fetotoxicity: Toxic effects on the fetus in the later period of pregnancy after organogenesis.
Folate: Vitamin B9; is needed by the body to synthesize, repair, and methylate DNA and histones; alcohol consumption can lead to folate deficiency.
Gamete: A reproductive germ cell—an egg cell in the female or sperm in the male. Reproductive germ cells are haploid (that is, they carry only 23 chromosomes (only one chromosome from each of the 22 pairs plus one sex chromosome, X or Y).
Gametogenesis: The process by which diploid (46 chromosomes) precursor cells undergo meiotic division to become haploid (23 chromosomes) gametes.
Gene: The smallest unit of heredity, usually that portion of DNA that encodes a protein.
Gene expression: The transcription of genes to form RNA. This process represents one of the critical processes to translate genetic information into functional components of the cell, such as via production of messenger RNA (mRNA) and ribosomal (rRNA) and ultimately proteins.
Gene silencing: Refers to the outcome of epigenetic modification(s) that turns a gene off so that it is not transcribed into RNA.
Gene transcription: A cell uses a gene as a template to make a transcript (also called an mRNA molecule); this transcript will be further processed and then be translated to make a protein.
Generational health effect: Describing health effects of an exposure to a past (parental) generation that manifests in subsequent generations, such as children or grandchildren.
Generational inheritance: Refers to effects inherited by subsequent generations; may be intergenerational or transgenerational.
Genetic code: Three bases in a DNA or RNA sequence called a codon, each of which specifies for 1 of the 20 amino acids (e.g., the bases ATG specify the amino acid methionine) in a protein. Genes are frequently tens of thousands of base-pairs long, with every three bases of the DNA sequence coding for the amino acids that are used to make the protein.
Genome: All the DNA in an organism or cell, especially with reference to the total sequence of nucleotide bases, or “letters” of the genetic code.
Genome environment interaction (GxE): When the response to an environmental exposure is a combination of both the exposure and the genome of the exposed cell/individual. This often occurs when a particular genotype changes the way an environmental chemical is metabolized (making it more or less potent), or how DNA damage by an environmental exposure is repaired (increasing or decreasing mutation frequency). GxE interactions explain how human populations with the same environmental exposure will respond differently to that exposure due to genetic heterogeneity in the population.
Genotype: The complete genetic makeup of an individual organism that is determined by the specific variants (i.e., alleles) of each gene carried by the individual. Differences in alleles among individuals can account for the differences in phenotype, and response to environmental exposures, observed among those individuals.
Germ cell: Oocyte (egg) of females or spermatocyte (sperm) of males. A kind of cell that is part of the germ line and is involved in the reproduction of organisms.
Germ line: The series of germ cells each descended from earlier cells in the lineage of germ cells, containing the genetic material to be passed to successive generations.
Heterogeneity: A quality describing diverse, dissimilar, and not uniform components.
Heterozygous: Carrying two different variants (i.e., alleles) of a given gene.
Histone modification: The addition or subtraction of any one of several chemical groups to an individual amino acid of a histone. These modifications can include acetylation, methylation, phosphorylation, and ubiquitination (among others).
Histones: Proteins upon which chromatin is tightly wound and that function to package and organize DNA in the nucleus, termed a nucleosome. Epigenetic modifications occur on both the DNA strand and the histone proteins that make up a nucleosome.
Implantation: The stage of pregnancy at which the embryo adheres to the wall of the uterus in order to receive oxygen and nutrients from the mother, usually between 6 and 12 days after ovulation. At this stage of prenatal development, the embryo is called a blastocyst.
Imprinting: A phenomenon by which certain genes are epigenetically marked to identify the parent of origin of each allele (i.e., from the mother or the father). In general, imprinting serves to direct the expression of only one allele, either from the mother or father, and silence the other allele, so that the gene is expressed in a parent-of-origin fashion. For example, for certain genes only the copy inherited from the father will be expressed while the gene from the mother is silent.
Induced pluripotent stem cells (iPSCs): Pluripotent stem cells derived from adult cells, such as embryonic cells or skin cells, that can be “reprogrammed” to give rise to many cell types. This technology is important to the fields of personalized and regenerative medicine, and to understanding the patient-specific underpinnings of disease.
Inner cell mass (ICM): Cells of the blastocyst, surrounded by the trophectoderm, which will develop into a fetus.
Intergenerational inheritance: Generally used to describe the effects of events affecting parents (e.g., in response to an environmental exposure) that manifest in subsequent generations (children, grandchildren, etc.). Such inheritance is thought to occur via events affecting the germ line or on the developing embryo and its germ line (which will eventually produce grandchildren).
Meiosis: The formation of egg and sperm cells by which diploid (46 chromosomes) cells undergo DNA replication, followed by two rounds of cell division, producing four haploid (23 chromosome) gametes.
Meiotic inheritance: The transmission of genetic and epigenetic information through the germ line.
Messenger RNA (mRNA): Key intermediary molecule generated when a gene is expressed (i.e., when the information encoded in the gene is converted into a protein product by the cell); mRNA levels for a gene are used as an indicator of how “active” the gene is (i.e., how much of the protein is produced).
MicroRNA (miRNA): Single-stranded, non-protein-coding RNAs about 21–24 nucleotides in length expressed in plants and animals. They bind to their target gene’s 3’ untranslated region and generally block transcription or promote mRNA degradation.
Mitochondria: Structures within cells that generate most of the cells’ energy through the production of adenosine triphosphate (ATP), a molecule that provides the energy needed for many key metabolic reactions.
Mitochondrial genome: A circular molecule of double-stranded DNA in the mitochondria that is 16,569 base-pairs long and contains 37 genes coding for 2 rRNAs, 22 tRNAs, and 13 polypeptides.
Mitosis: The cellular process that replicates chromosomes and produces two identical nuclei in preparation for cell division, followed by the equal division of the cell nuclei and other cell contents into two daughter cells.
Mitotic inheritance: The transmission of genetic and epigenetic information daughter cells during cell division (mitosis).
Mutagenicity: Ability of a physical, chemical, or biological agent to induce (or generate) heritable changes (mutations) in DNA. Often mutations change, or result in loss of, function of a gene, and if inherited, can change phenotype and/or cause disease.
Mutation: A change in the DNA base pair sequence at a particular locus in an organism. The term is used specifically to indicate point mutations (change in a single base), but is often loosely used to include other alterations such as chromosomal changes, including translocations, deletions, and inversion of larger DNA segments. Many physical (i.e., radiation) and chemical (i.e., benzo-[a]-pyrene) agents, as well as normal biological processes (i.e., reactive oxygen species formed during cellular metabolism) and transposable DNA elements can cause mutations.
Noncoding RNA (ncRNA): RNA molecules that are not used as a template to produce proteins, for example, microRNA.
Nucleosome: A nucleosome is a section of DNA that is wrapped around a core of proteins (histones); it is a fundamental subunit of chromatin. Each nucleosome is composed of a little less than two turns of DNA wrapped around a set of eight histones (a histone octamer).
Nucleus: The organelle-compartment of a eukaryotic cell that contains DNA organized into chromosomes; separated from the cytoplasm by double membrane perforated by nuclear pores.
Omics: The fields of study in biology ending in -omics, including genomics, proteomics, and metabolomics. Omics aims to collectively characterization the biological molecules that translate into structure, function, and dynamics of an organism.
Oocyte (ovocyte or egg): A female gametocyte or germ cell that divides twice by mitosis and meiosis into two other oocytes or into two ootids. It is involved in reproduction.
Organogenesis: The phase of embryonic development when cellular differentiation occurs and the internal organs are formed.
Oxidative stress: An imbalance between oxidants (e.g., reactive oxygen species [ROS]) and antioxidants that can lead to excessive oxidation and cell damage.
Pathophysiology: The processes and mechanisms operating in an organism that lead to or accompany a disease state.
Phenotype: The observable structural or functional characteristics of an individual organism that result from the interaction of its genetic makeup (i.e., genotype) with environmental factors.
Piwi-interacting RNA (piRNA): A class of small noncoding RNA molecules that form complexes and interact with piwi proteins (regulatory proteins involved in stem cell differentiation). piRNA complexes have been linked to gene silencing of retrotransposons and other genetic elements in germ line cells.
Placenta: Temporary membranous vascular organ that develops in mammals when young are developing in the womb. It attaches to the fetus via the umbilical cord and is expelled after birth.
Polymorphism: The presence of two or more variants (i.e., alleles) of a gene or other DNA sequence in a population.
Primordial germ cell: Precursor cells to gametes. These cells are designated in early embryo development and migrate to the developing ovaries or testes to develop into oocytes or sperm.
Progesterone: Progesterone is a female steroid hormone that is secreted by the corpus luteum, a temporary endocrine gland that the female body produces to prepare the endometrium for the potential of pregnancy after ovulation.
Protamine: A small protein found in the nucleus that replaces histones during spermatogenesis and play a role in the condensation and stabilization of DNA in the formation of sperm.
Protamine compaction: The process by which protamines compact DNA during spermatogenesis.
Protein: A polypeptide chain or complex of polypeptide chains, each consisting of a long string of amino acids. Amino acid sequences are specified by the underlying DNA sequence of the gene that encodes that protein.
Reactive oxygen species (ROS): Highly reactive oxygen–containing free radicals that are generated during oxidative metabolism. ROS can react with and damage lipids, proteins, and DNA in cells, causing oxidative stress. Common ROS include hydrogen peroxide, superoxide radicals, and hydroxyl radicals.
Repetitive elements: Patterns of bases in DNA or RNA that are repeated throughout the genome that can have structural and regulatory impact on DNA. More than two-thirds of the human genome consists of repetitive elements.
Reproductive toxicity: The ability of a toxicant to interfere with normal reproduction function, resulting in adverse effects on sexual function and fertility in adult males and females.
Retrotransposon: DNA segment that can duplicate itself and thus multiply in the genome; during this process, the original DNA sequence first copies itself into RNA and then back into DNA, which is then incorporated back into the genome; retrotransposons make up a substantial portion of the genome.
Ribonucleic acid (RNA): A nucleic acid that is generally single stranded and plays a role in transferring information from DNA to the protein-forming system of the cell.
Somatic cell: Any cell of the body, except germ cells.
Sperm: A male reproductive (germ) cell.
Spermatocytes: A male gametocyte derived from a spermatogonium, and gives rise to haploid spermatids through meiosis, which in turn give rise to mature sperm cells. Spermatocytes are found in the male gonads of sexually reproducing organisms. In humans, they are found in the seminiferous tubules of the testis.
Spermatogenesis: The process occurring in the male gonad of sexually reproducing organisms wherein the undifferentiated male germ cells develop into spermatocytes, which then transform into spermatozoa. It occurs in the male testes and epididymis in a stepwise fashion. The entire process can take approximately 64 days.
Stem cell: Primal undifferentiated cells that retain the ability to differentiate into other cell types.
Targeted chemical screening: Analyses for sets of preselected compounds determined to be important. Methods used to identify these substances are based on known chemical properties, such as their fragmentation profile and retention time. Quantification is achieved by comparing molecular characteristics with internal standards of known concentration. They are the gold standard exposure biomarker when measuring exposure to chemicals that are biologically relevant.
Teratogenicity: The ability of a substance to produce a permanent abnormality in structure or function, restriction of growth, or death of the embryo or fetus. Teratogens can produce a congenital malformation (a birth defect). Teratogens include radiation, maternal infections, chemicals, and drugs.
Testosterone: Male sex hormones produced in a testis that help to develop and maintain secondary sexual characteristics and are required for spermatogenesis.
Toxicant: Any substance that can have a toxic effect, including synthetic, biologic, or naturally occurring substances. Toxicants can be poisonous.
Transcription: Biochemical process in which an intermediary molecule called messenger RNA is generated based on the genetic information of the DNA.
Transfer RNA (tRNA): A kind of RNA molecule, about 76 to 90 nucleotides long, that translates the code carried by mRNA to into an amino acid to be synthesized into a protein.
Transgenerational inheritance: Parent-to-child inheritance of an environmentally induced genetic or epigenetic change, without direct exposure of the child. The term “transgenerational” is often used broadly to describe all environmental effects that can be transmitted from one generation to the next, However, it is important to distinguish parental (or intergenerational) effects, such as the impact of in utero exposure to particular nutritional, hormonal, or stress/toxin environments on the developing embryo and its germ line (which will eventually produce grandchildren), from truly transgenerational effects that are found in generations that were not exposed to the initial signal or environment that triggered the change.
Translation: The process of making proteins based on genetic information encoded in messenger RNA.
Transposable element (transposon): Sequences of DNA that move around to different positions within the genome of a single cell. The process is called transposition. DNA transposons move by a cut-and-paste mechanism, while replicative transposons usually move via RNA intermediates.
Trophectoderm (trophoblast): The cells forming the outer layer of a blastocyst, which provide nutrients to the embryo and develop into the placenta.
Untargeted chemical screening: Analyses used to screen for hundreds to thousands of compounds using high-resolution mass spectrometry methods coupled to gas chromatography or liquid chromatography. The overall chromatogram contains reproducible features that represent thousands of chemical constituents of the sample, but the identity of the vast majority of the compounds represented by the chromatogram are unknown. Statistical methods allow researchers to use features of the chromatogram in analyses without knowing the compound’s identity to narrow research efforts. While less quantitative, untargeted assays capture a greater breadth of compounds than targeted assays and allow for the discovery of new chemicals that are biologically relevant. Once a compound is identified in an untargeted assay as biologically relevant, targeted assays for that chemical are developed.
Zygote: A cell formed by the fusion of two gametes, that is, fertilization. Its genome is a combination of the DNA in each gamete.