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Glossary Acrosome A membrane-bound compartment at the tip of the sperm that releases lytic, egg-penetrating enzymes. Acrosome reaction Release of acrosomal enzymes. Allele Any one of the alternative forms of a gene that occupy the same locus (location on the chromosome). Amenorrhea The absence or suppression of menstruation. This state is normal before puberty, after menopause, and during pregnancy and lactation. Androgen Generic term for an agent, usually a hormone (e.g., testosterone), that stimulates activity of the accessory male sex organs, encouraging development of male sex characteristics. Androgens are produced chiefly by the testes but also by the adrenal cortex and the ovary. Antibody A protein produced by B lymphocytes in response to contact with an antigen from a foreign microorganism or molecular entity and triggered by T lymphocytes. Antibodies attach themselves to the foreign antigen, and to nothing else. This signals other elements of the immune system, including monocytes and macrophages, to destroy the invading organism. Antigen Any substance capable, under appropriate conditions, of induc- ing a specific immune response when coming into contact with a lymphocyte or antibody. Antiprogestins A substance that inhibits formation of progesterone, reduces its uptake by or effects on target organs, or interferes with its carriage or stability in the blood. 219

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220 NEW FRONTIERS IN CONTRACEPTIVE RESEARCH Antisense RNA A complementary strand of RNA that blocks the tran- scription of a naturally occurring (sense) messenger RNA molecule by binding to it. Autocrine signaling Secretion of a substance, such as a growth factor, that stimulates the secretory cell itself. Azoospermia Absence of living sperm in semen. Barrier method A contraceptive method that establishes a physical or chemical barrier between the sperm and ovum, e.g., condom, dia- phragm, foam, sponge, cervical cap. Some of the barrier contracep- tives are used in conjunction with a spermicidal agent. Bioavailability The degree to which a drug (or other substance) becomes available to the target tissue after administration. Biotechnology The collection of industrial processes that involve the use of biological systems. For some industries, the processes involve the use of genetically engineered organisms. Capacitation A process that takes place in the female reproductive tract by which sperm acquire the ability to fertilize an egg. cDNA see Complementary DNA cDNA subtraction hybridization methods A technique used to identify genes expressed differentially between two tissue samples. A large excess of mRNA from one sample is hybridized to cDNA from the other, and the double-stranded hybrids are removed by physical means. The remaining cDNAs are those that are not represented as RNA in the first sample and, thus, that are presumably expressed uniquely in the second sample. To improve specificity, the process is often repeated several times. Cervical cap Small latex or plastic cap that covers the cervix. Users of this barrier method of birth control must spread spermicidal cream or jelly inside the cap. Cervix Literally, "neck"; the constricted part of an organ; the cervix of the uterus is the lower and narrow end of the uterus that opens into the vagina. For pregnancy to occur, sperm must pass through the cervix into the uterus. Chemotaxis The attraction or repulsion of a cell by a chemical gradient. Chemotaxis affects the direction of motion only. Chorionic gonadotropin A glycoprotein produced by the primate placenta that plays a role in stimulating ovarian secretion of estrogen and progesterone during the first trimester of pregnancy. Clinical testing Trials to determine the safety and efficacy of a drug or device in humans. Complementary DNA (cDNA) DNA that is synthesized from a messen- ger RNA template by the enzyme reverse transcriptase. The single- stranded form of cDNA can be used as a probe to find a gene.

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GLOSSARY 221 Conception Generally the beginning of pregnancy. Conception is usually equated with the fertilization of the ovum by the sperm, but is some- times equated with the implantation of the fertilized ovum in the uter- . . . 1ne ~ .mmg. Condom A cylindrical sheath of latex, polyurethane, or sheep intestine worn over the penis during intercourse as a barrier method of contra- ception and as a prophylactic against sexually transmitted disease. Some condoms contain a spermicide to kill sperm to decrease the risk of pregnancy should a condom break or should semen leak over the outer rim of the condom. Contraception Anything that acts against conception, and therefore, any- thing that prevents the success of fertilization or implantation. Contraceptive immunogen Any molecular entity meant to directly elicit an immune reaction for birth control. Contraceptive prevalence rate The percentage of women currently using a contraceptive method. Contraceptive vaccines Vaccines which induce an immune response against proteins specific to the reproductive process and therefore block fertility. Cytokines Growth factors and immunoregulatory proteins such as inter- leukins that are secreted by cells and act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. Cytokines generally act locally in a paracrine or autocrine rather than endocrine manner. Developing country The World Bank defines a developing country as one a low- or middle-income country (less than $9,265 gross national income per capita in 1999) in which most people have a lower stan- dard of living with access to fewer goods and services than do most people in high-income countries. There are currently about 125 devel- oping countries with populations over 1 million; in 1997, their total population was more than 4.89 billion. Diaphragm A soft, rubber, dome-shaped device worn over the cervix and used with spermicidal jelly or cream for contraception. Diaphragms are circular, shallow, rubber domes with a firm but flexible outer rim that fit between the posterior vaginal wall (posterior fornix) and the recess behind the pubic arch. Dysmenorrhea Painful menstruation. Usually cramping lower abdomi- nal pain. May be associated with low back pain, nausea, diarrhea, or upper thigh pain. Efficacy The effectiveness of a form of contraception. Egg An ovum; a female gamete; an oocyte; a female reproductive cell at any stage before fertilization.

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222 NEW FRONTIERS IN CONTRACEPTIVE RESEARCH Embryo In humans, the developing organism from about 2 weeks after fertilization to the end of the seventh or eighth week. Endometrium The mucous inner lining of the uterus. Enzyme A protein molecule produced by a living cell that catalyzes chemical reactions of other substances without itself being changed or destroyed. Epididymis A coiled tubular structure where sperm cells mature and are nourished and which connects the testes to the vas deferens. Epithelium A membranous cellular tissue that lines a surface, a tube, or a cavity of a body, serving to enclose and protect other parts of the body and to produce secretions and excretions. Estrogen The primary female hormones; any natural or artificial substance that induces estrogenic activity, more specifically, the hormones estradiol and estrone produced by the ovary. Estrogens are produced chiefly by the ovary but also by the adrenal cortex, the testis, and the placenta. Expressed sequence tag A short cDNA sequence that has a single occur- rence in the human genome and whose location and base sequence are known. Failure rate The number of pregnancies occurring per 100 users of contra- ception per year. Family planning Programs or services to assist families to control the timing of reproduction through effective methods of birth control. Fetus A developing unborn offspring. In humans, the fetal period last from after the seventh or eighth week postfertilization (the end of the embryonic period) until birth. Follicle A small secretory sac or cavity. One type of follicle is an ovarian follicle which is a very small sac in the ovary in which an ovum matures and from which the egg is released. Follicle stimulating hormone (FSH) Anterior pituitary hormone which stimulates the ovary to ripen egg follicles. FSH stimulates sperm pro- duction in the testes in males. Forward genetic screens Also known as mutational screens, these screens identify a gene on the basis of a phenotype, for example, infertility, by inducing random mutations in an experimental cell or animal and then mapping and isolating the gene that causes the phenotype. Functional genomics The study of the structure and function of all the genes in a genome. Fusion proteins Proteins formed by the expression of a hybrid gene, which is formed by combining two separate gene sequences, through recombinant DNA technology. Gamete Male or female reproductive cell (sperm or ovum) containing a haploid set of chromosomes (produced by meiosis).

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GLOSSARY 223 Gene A complete chromosomal segment responsible for making a func- tional product, usually a protein. Gene expression profiling Analysis of the products (usually mRNA) of all the genes expressed in a given cell or tissue. Gene regulation The interactions between DNA and proteins that control the quantity and rate of the expression of a gene. Genetic network A model of how genes influence each other, represented as a diagram with nodes and directed edges. Genetic screens The process of testing individuals to determine whether they carry specific genes. See forward genetic screens, reverse genetic screens. Genotype The genetic constitution of an organism or cell, separate from its expressed features or phenotype. Germ cells The reproductive cells in the body; also called sex cells (in contrast to somatic cells). Glycan structures A structure made of polysaccharides (carbohydrates that are made up of chains of simple sugars, monosaccharides). Glycome A term designed to be parallel to the genome and the proteome, the whole set of glycans (polysaccharides) produced by an individual cell type or organism. Glycoprotein A protein with covalently attached polysaccharide or sugar units. Glycosylation The process of the addition of a polysaccharide to a polypeptide to make a glycoprotein. Glycosylphosphatidylinositol (GPI) A lipid that attaches to a protein and is inserted into the lipid bilayer of the plasma membrane to anchor the protein on the surface of the cell. Gonadotropin A substance having an affinity for, or stimulating effect on, the gonads, produced by the anterior pituitary or chorionic tissues of the early embryo. Good Clinical Practice An international ethical and scientific quality stan- dard for designing, conducting, recording, and reporting trials that involve human subjects. The International Conference on Harmoni- zation (ICH) guidance provides a unified standard for the European Union, Japan, and the United States, developed with consideration of the standards of the rest of the world and of the World Health Orga- nization. Ideally, compliance with GCP assures that the rights, safety, and well-being of trial subjects are protected and that the clinical trial data are credible. Good Laboratory Practice A framework developed by the Organisation for Economic Co-operation and Development that covers the organi- zation of test facilities and the conditions under which preclinical

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224 NEW FRONTIERS IN CONTRACEPTIVE RESEARCH safety studies are executed, with the goal of generating only high quality and reliable test data. Good Manufacturing Practice A set of principles and procedures which, when followed by manufacturers of therapeutic goods, helps ensure that the products manufactured will have the required quality. Various regulations and guides relating to GMP have been published by different countries and groups of countries. The United States has its standards monitored by the FDA. Heterozygous Having two different alleles of a specific gene. High-throughput methods Any approach using robotics, automated machines, and computers to process many samples at once. Homologous Similar in sequence and function. Homozygous Having two copies of the same allele of a specific gene. Hormone A messenger molecule of the body that helps coordinate the actions of various tissues. Hormones produce a specific effect on the activity of cells remote from their point of origin. Human chorionic gonadotropin (hCG) A glycoprotein hormone pro- duced by the human placenta that maintains the corpus luteum and causes it to secrete estrogen and progesterone. Measured in urine and blood to detect pregnancy. Human immunodeficiency virus (HIV) A virus that causes AIDS. It causes a defect in the body's immune system by invading and then multiplying within white blood cells. Hypothalamus A part of the brain below the thalamus that helps to regu- late basic functions such as sleep, appetite, body temperature, and fertility. It regulates the pituitary gland as well as other glands, in- cluding the ovaries and the thyroid. Immunocontraceptive method Any contraceptive method based on inter- ference of some step of the reproductive process by products of an immune reaction, be it antibodies or cells. Immunogen Any substance that is capable of eliciting an immune response. Implantation The process whereby an ovum burrows into the lining of the uterus 6 or 7 days after fertilization and attaches itself firmly. Suc- cessful implantation is essential to the development of the embryo. In vitro Literally, "in glass"; a biologic or biochemical process outside a . ~ wing organism. In viva Literally, "in life"; a biologic or biochemical process occurring within a living organism. Infertility Failure, voluntary or involuntary, to produce offspring. Injectable contraceptives Hormonal contraceptives given by injection. Two examples of injectable progestins are Depo-Provera (DMPA or depot medroxyprogesterone acetate), and norethindrone enanthate.

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GLOSSARY 225 Interaction domains Small portions of proteins that mediate and regulate protein complex formation. Intrauterine device (IUD) A flexible, usually plastic device inserted into the uterus to prevent pregnancy. May contain metal (generally copper) or hormones for added effectiveness. It produces a local sterile inflammatory response caused by the presence of a foreign body in the uterus which causes lysis of the blastocyst, and/or the prevention of implantation. IUDs may also prevent fertilization due to deleterious effects on spermatozoa as they pass through the uterus. Ion channel A transmembrane protein that allows the passage of ions through a lipid bilayer down an electrochemical gradient. Isoform Related but unique forms of a molecule. Kinase A phosphokinase, an enzyme that catalyzes the addition of a phos- phate group to another molecule. Knockdown models Animal models in which the level of expression of a particular gene is reduced. Knock-in models Animal models in which a specific gene has been added or overexpressed. Knockout models Animal models in which a specific gene is deleted or rendered nonfunctional. Lead compound A specific chemical that shows strong potential as a drug candidate to modulate a given target. Ligand A molecule that binds to another; usually refers to a soluble molecule such as a hormone that binds to a receptor. Lipidome A term is designed to be parallel to the genome or proteome, the collection of all the lipids produced by a cell or an organism. Luteinizing hormone (LH) An anterior pituitary hormone that causes a follicle to release a ripened ovum and become a corpus luteum. In the male it stimulates testosterone production and the production of sperm cells. Meiosis The specialized form of nuclear division in which the number of chromosomes is reduced to half by a second division in order to create sex cells. Membrane protein A protein embedded in the membrane of a cell. Menopause Cessation of menstruation; i.e., the last episode of physiologic uterine bleeding. After menopause, a woman is naturally infertile. Surgical menopause refers to the removal of a woman's ovaries before natural menopause occurs. Method failure rates This measures the effectiveness of a form of contra- ception based on only the method itself, assuming perfect use. See use effectiveness rates Microarrays A DNA microarray consists of a glass microscope slide or silicon chip onto whose surface thousands of specific DNA sequences

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226 NEW FRONTIERS IN CONTRACEPTIVE RESEARCH are spotted. Incubation with a labeled sample of nucleic acid such as mRNA can reveal which of the genes represented on the array are expressed in the sample and their relative levels. Microbicide An agent that kills or inactivates or prevents infection from various pathogens or microbes. Monoclonal antibodies Identical antibodies made from a single cell- that are generated in large quantities in the laboratory. Monthly methods Contraceptive methods that only are used once each month. Mutational screens Also known as forward genetic screens, these screens identify a gene on the basis of a phenotype, for example, infertility, by inducing random mutations in an experimental cell or animal and then mapping and isolating the gene that causes the phenotype. Nucleotide A compound consisting of a ribose or deoxyribose sugar joined to a phosphate group and a purine or pyrimidine base. These compounds, including adenosine monophosphate, are the basic struc- tural units of RNA and DNA. Oocyte The developing female gamete before completion and release, known as ovulation. Oral contraceptives (OC) Various progestin/estrogen or progestin com- pounds in tablet form taken by mouth; "the pill." Estrogenic and progestational agents have contraceptive effects by influencing normal patterns of ovulation, sperm or ovum transport, cervical mucus, implantation, or placental attachment. Osteoporosis An abnormal softening, porousness, or reduction in the quantity of bone, resulting in structural fragility. Causes appear to include estrogen deficiency, prolonged immobilization, and adrenal hyperfunction, which result in more bone resorption than formation. Ovaries The female gonads; glands where ova are formed; also the primary source of female hormones, estrogen and progesterone. Oviduct The tube through which eggs travel from the ovary to the uterus. Paracrine signaling Form of signaling in which the target cell is close to the cell that secretes a substance such as a growth factor. Pathogen A microbe capable of causing disease. Perfect use When the directions for use of a contraceptive method are followed and the method is used correctly for every act of intercourse. Perimenopause Traditionally defined as the few (3 to 5) years surround- ing a woman's last menstrual period; more recently it is being defined as beginning more than a decade before frank menopause, in the mid- thirties and early forties, coincident with the initiation of ovarian de- cline. Periodic abstinence methods Contraceptive methods that rely on timing of intercourse to avoid the ovulatory phase of a woman's menstrual

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GLOSSARY 227 cycle; also called fertility awareness or natural family planning. 1. The basal body temperature (RET) method uses daily temperature read- ings to identify the time of ovulation. 2. In the ovulation or Billings methods, women identify the relationships of changes in cervical mucus to fertile and infertile days. 3. The sympto-thermal method charts changes in temperature, cervical mucus, and other symptoms of ovulation (e.g., intermenstrual pain). Periovulatory period The time period immediately surrounding ovula- tion when the egg is ripening and is released. Pharmacokinetics The quantitative measure of drugs in the body, specifi- cally, absorption, distribution, localization in tissues, biotransforma- tion, and elimination. Phenotype The characteristics of an organism under a particular set of environmental or ecological conditions, regardless of the genetic makeup (the genotype) of the organism. Pituitary gland A small gland located at the base of the brain beneath the hypothalamus; serves as one of the chief regulators of body functions, including fertility. Most endocrine glands in the body are controlled by the pituitary. Also known as the hypophysis. Polymer A macromolecule made of repeating (monomer) units. Postmeiotic The stage after meiosis, when the number of chromosomes in the sexual cells has been reduced to create the mature form of the germ cells. Postpartum After childbirth. Pregnancy The interval from the completion of implantation of the blastocyst in the uterus until birth. Progesterone A steroid hormone produced by the corpus luteum, adrenals, or placenta. It is responsible for changes in the uterine endo- metrium in the second half of the menstrual cycle that are prepara- tory for implantation of the fertilized ovum, development of maternal placenta after implantation, and development of mammary glands. Prostaglandins A group of naturally occurring, chemically related long- chain fatty acids that have certain physiological effects, including stimulating contraction of uterine and other smooth muscles, lower- ing blood pressure, and affecting certain hormones. When pros- taglandins are produced as the endometrial lining degenerates, they may cause mild to severe menstrual cramps, diarrhea, nausea, and vomiting. Oral contraceptives diminish the prostaglandins released by the endometrial lining, decreasing menstrual cramps in users. Prostate A pale, firm, partly muscular, partly glandular body that sur- rounds the base of the male urethra in human and other mammals and discharges its secretion through ducts opening into the floor of the urethra.

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228 NEW FRONTIERS IN CONTRACEPTIVE RESEARCH Protein complex Structured ensembles of proteins and other molecules. Proteome The entire protein complement of a cell or an organism. Proteomics The science of defining and analyzing the entire protein complement (the proteome) involved in a particular biological process in a given cell, tissue, or organism. Receptor A molecular structure within or on the surface of a cell charac- terized by selective binding of a specific substance and a specific physiologic effect accompanies the binding. Recombinant DNA technology A series of procedures used to join together (recombine) DNA segments from different sources. Recombinant proteins Proteins created by recombinant DNA technology. Reverse genetic screens An experimental approach to find a gene's func- tion by reducing its expression (via knockout or knockdown ap- proaches) and then trying to identify the change in the phenotype. Ribazymes Also called RNA enzymes, ribozymes are enzymes made of nucleic acids (RNA), not proteins, that can catalyze reactions, often the breakdown of other RNAs, and thus can be used to inhibit gene expression. RNA interference (RNAi) An innate cellular process that is initiated when a double-stranded RNA molecule enters the cell, causing the activation of proteins that destroy both the invading RNA and the endogenous single-stranded RNAs with identical sequences inside the cell. Sertoli cells Cells in the testis to which spermatids attach. They provide support and nourishment as the spermatids develop into spermatozoa. Sexually transmitted infection (STI) Any infection that is communicated primarily or exclusively through intimate sexual contact. Sexually transmitted infections have been estimated to cause from 20 percent to 40 percent of infertility in the United States. STIs can adversely affect fertility by three primary mechanisms; pregnancy loss, prenatal deaths, and damage to male or female reproductive capacity. Side effect An effect of a drug other than the one it was administered to evoke. Somatic cells All the cells in the body besides germ cells; cells besides gametes and their precursors. Sperm antigens Substances on or in the sperm that in certain circum- stances elicit the production of antibodies. Spermatozoon Male reproductive cell (pi. spermatozoa). Spermatid Developing male germ cell that has not yet become a spermatozoan. Spermatogenesis The formation of spermatozoa. Spermicide A chemical substance that kills sperm, marketed in the form of foam, cream, jelly, film, and suppositories used for contraception. The spermicides used in almost all currently marketed spermicides

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GLOSSARY 229 are surfactants, which are surface-active compounds that destroy sperm cell membranes. Spermiogenesis The part of spermatogenesis when immature spermatids become spermatozoa. Sterilization A procedure that leaves the male or female incapable of reproduction. Sterilization is the most commonly employed method of birth control in the world. Steroid hormone A group of related hormones (biochemical substances produced in one place in the body and affecting cells elsewhere), based on the cholesterol molecule. They control sex and growth characteristics. Testosterone, progesterone, and estrogen are steroid hormones. Target A cellular structure or process that a drug or other therapeutic aims to modulate. Testosterone Male sex hormone produced in the testes. Transcriptome The complete pattern of gene transcription in a cell or tissue. Transporter protein A protein that spans the cell membrane and carries specific nutrients, ions, and other substances across the membrane. Transgenes Genes from another animal that are introduced into an organism by injecting them into newly fertilized eggs. The resulting animals are called "transgenic animals." Translational research Research that aims to develop clinical applications of basic sciences discoveries. Transposon A short sequence of DNA that can change location in the genome and normally contains genes that code for the proteins that enable it to change location. Unintended pregnancy A pregnancy that was not wanted by the woman at the time conception occurred, irrespective of whether contracep- tion was being used and whether or not a pregnancy was desired at some time in the future. Use effectiveness rate or use failure rates This measures the effective- ness of a form of contraception, taking into account typical rather than perfect use. See method failure rates. Uterus The hollow, pear-shaped, muscular, elastic reproductive organ where the embryo and then the fetus develops during pregnancy. Vagina The 3- to 5-inch-long muscular tube leading from the external genitals of the female to the uterus. Validation Verification that modulation of a target will produce, for con- traceptive targets, a contraceptive effect. Vas deferens The tube through which sperm pass from the epididymis to the ejaculatory duct and then into the urethra. It is this tube that is interrupted in the male sterilization procedure called vasectomy. Also called ductus deferens.

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230 NEW FRONTIERS IN CONTRACEPTIVE RESEARCH Vasectomy A surgical procedure in which segments of the vas deferens are removed and the ends tied to prevent passage of sperm. Vasec- tomy should be regarded as permanent, although reversal is possible in some cases. Withdrawal (coitus interruptus) Removing the penis from the vagina just prior to ejaculation. Zona pellucida The translucent, elastic, noncellular coating surrounding the ovum. Zygote The fertilized egg before it starts to divide.