Editorial [Hot Topic: Advances in Developmental and Reproductive Toxicology (Executive Editor: Gian Mario Tiboni)]

The papers in this special issue of Current Pharmaceutical Design cover a wide spectrum of relevant and fascinating topics in the area of developmental and reproductive toxicology. There is increasing evidence that small gaseous molecules, such as dioxygen, carbon monoxide, nitric oxide and hydrogen sulphide, serve important roles in modulating a variety of physiological responses, including those involved in development. The article from Fukuto and Collins [1], besides providing an overview of the chemistry and biology of these soluble gases, summarizes the information regarding the teratogenicity of either excess or deficiency of gaseous signalling molecules. Drugs blocking the potassium current IKr, are potential human teratogens. The review from Karlsson et al. [2] supports the contention that the conventional methodology used for assessing drug teratogenicity, (based on repeated daily treatment during the gestational period covering organogenesis) is not optimal to characterize the teratogenic potential of agents having IKr blocking properties. In this context, the potential role of complementary teratology studies, including single gestation day dosing and studies using embryo culture, is discussed. The manuscript authored by Cecconi et al. [3], concentrates on the adverse effects of ethylenedithiocabamate, and with special reference to fungicide mancozeb, on mammalian ovary. The ability of mancozeb to induce spindle anomalies in meiotic cells and ultrastructural changes in ovarian somatic cells raises the possibility that mancozeb may also initiate cancerogenesis. The article presented by Younglay et al. [4] focuses on the potential negative impact of man-made environmental toxicants, including polychlorinated biphenyls and dioxins, organochlorines, phthalates, benzo-a-pyrene, synthetic polymers and the fungicide vinclozolin, on human developmental and reproductive function. Retinoic Acid Metabolic Blocking Agents (RAMBAs) represent a class of agent that have been designed to inhibit the CYP26 members of the cytochrome P450 family which regulates the local levels of all-trans retinoic acid. The article from McCaffery and Simons [5], besides describing the mechanism of action of the RAMBAs, also discusses the potential teratogenic potential of this class of agents. Kozyraki and Gofflot [6] summarize recent data on the biological function of the receptors cubilin, megalin and amnionless, and focus on their implication in embryonic nutrition and central nervous system malformations. The last article from Bremer and co-workers [7], besides providing a short overview on the current status of reproductive toxicity testing, introduce new concepts for assessing reproductive toxicity applicable to large scale toxicological programmes. I would like to express my sincere appreciation to the contributors. References [1] Fukuto JM, Collins MD. Interactive Endogenous Small Molecule (Gaseous) Signaling: Implications for Teratogenesis. Curr Pharm Des 2007; 13(29): 2952-2978. [2] Karlsson M, Danielsson BR, Nilsson M, Danielsson C, Webster WS. New proposals for testing drugs with-IKr blocking activity to determine their teratogenic potential. Curr Pharm Des 2007; 13(29): 2979-2988. [3] Cecconi S, Paro R, Rossi G, Macchiarelli G. The effects of the endocrine disruptors dithiocarbamates on the mammalian ovary with particular regard to mancozeb. Curr Pharm Des 2007; 13(29): 2989-3004. [4] Younglai EV, Wu YJ, Foster WG Reproductive Toxicology of Environmental Toxicants: Emerging Issues and Concerns. Curr Pharm Des 2007; 13(29): 3005-3019. [5] McCaffery P, Simons C. Prospective teratology of retinoid acid metabolic agents (RAMBAS) and loss of CYP26 activity. Curr Pharm Des 2007; 13(29): 3020-3037. [6] Kozyraki R, Gofflot F Multiligand endocytosis and congenital defects: roles of cubilin, megalin and amnionless. Curr Pharm Des 2007; 13(29): 3038-3046. [7] Bremer S, Pellizzer C, Hoffmann S, Seidle T, Hartung T. The development of new concepts for assessing reproductive toxicity applicable to large scale toxicological programmes. Curr Pharm Des 2007; 13(29): 3047-3058.