Reproduction and development.

Abstract

The currently developed and validated in vitro tests for female and male fertility and also for developmental toxicity are described and evaluated according to their potential use as screening or replacement alternatives to the established in vivo tests in reproductive and developmental toxicology. Alternative methods today can only be used to evaluate a few specific components of the integrated reproductive functions in both females and males. However, in the field of developmental toxicity testing there is a strong theoretical and empirical basis for the predictive power of in vitro screens using mammalian embryos as well as embryonic cells and tissues. Several of these assays have been validated or are currently undergoing validation in several laboratories and are > 80% concordant with in vivo results. Failure to achieve 100% accuracy reflects the inherent limitations of these systems, which are manageable, as the concordance rates are still good. The level of concordance suggests that these assays are adequate for screening purposes to complement traditional in vivo testing. The use of these assays as screens will save valuable in vivo testing resources for those compounds most likely to enter the market and to which people will be exposed.

Induced pluripotent stem cells: A new era for hepatology

“…A cell-based assay should be simple, fast, reproducible, and cost effective with a consistent supply. Traditionally, whole embryo cultures and cells for drug research and analysis have been derived from animal or human tissues; either as primary cultures in which batch-to-batch variability is a common problem or as immortalized lines which often harbor uncharacterized genetic abnormalities [124]. The mouse ES cell test [14,99] is also one of the most recently developed tests used to assess the embryotoxic potentials of test chemicals, however, it may not entirely mimic human pharmacological risk assessment due to differences in xenobiotic biotransformation pathways and capacities.…”

Whole Embryo Culture: An Important Tool in Developmental Toxicology Today

“…However, features such as the concentration and stability of the test substance in the culture medium, its possible metabolic transformation, its uptake and distribution in the different embryonic compartments (the yolk sac, the exocoelomic fluids and the embryo itself) may display "in vitro pharmacokinetics". This is especially important for interpreting mechanistic studies or extrapolating data from in vitro to in vivo or vice versa [90].…”

Use of an organotypic mammalian in vitro follicle growth assay to facilitate female reproductive toxicity screening

“…The guidelines for reproductive toxicity testing set forth by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use as well as the The Guidelines for Reproductive Toxicity Risk Assessment issued by the United States Environmental Protection Agency rely primarily on in vivo animal studies (European Medicines Agency, 1994; Environmental Protection Agency (EPA), 1996). There is a growing interest in developing alternatives to animal studies, which are costly, require extended periods of time to carry out, can only be used to screen a limited number of compounds, and only measure overt phenotypes such as infertility or teratogenicity (Spielmann, 1998; Zurlo, 2012). …”