Pharmaceuticals and fertility

Rita Cortvrindt explains how reproductive functions can speed up the development of new drugs.

Why is it important that pharmaceutical companies screen compounds for their influence on fertility and embryonic development?
Rita Cortvrindt. Until now reproductive effects (female and male fertility, embryo toxicity and neonatal development) of a NCE are usually not taken into account during drug discovery or lead selection. However the reproductive system is susceptible to toxicities throughout almost the entire life span of an individual, with specific vulnerabilities during the different stages. A normal reproductive function is not only necessary to guarantee a successful procreation but also determines hormonal balance and influences the sense of an individual's well being. Early characterisation of potential reprotoxic effects is therefore of utmost importance. As there are now a number of in vitro bioassays available to screen the reproductive targets, requiring only minute amounts of product, reproductive toxicity screening can easily be incorporated in the early drug discovery process.

How can engaging the services of a contract laboratory specialising in the analysis of reproductive function help pharmaceutical companies to speed up the development of new drugs?
RC. Reproductive health is characterised by long-term processes determining hormone homeostasis, gamete quality and reproductive capabilities of the offspring and is very sensitive to all kinds of external factors, such as light, temperature, noise and handling. To assure solid and reproducible test outcomes a specialised facility is required. Only a dedicated staff and scientists with an in-depth knowledge of all the underlying physiological processes can warrant the correct assessment of the reproductive function. This holds true for in vivo studies but even more so for the performance of in vitro bioassays.

Standard reprotoxicity testing is based on a set of expensive long-lasting in vivo studies requiring vast amounts of compound, usually performed late in the drug-development process, risking a late discovery of devastating reproductive effects. Incorporation of a battery of innovative in vitro bioassays evaluating the main targets of the reproductive system during drug discovery and lead selection will reduce that risk and advance the drug-development process substantially.

What are the advantages of in vitro versus in vivo testing?
RC. In vitro test are usually characterised as being simple, quick, cheap and high throughput. However this type of simple cell culture systems are not very informative for most of the reproductive (t)issues. The target cells of the reproductive organs continuously differentiate and if used in a static state are prone to give false results. Relevant in vitro bioassays aiming to evaluate the reproductive function have to mimic the physiologic process of the target organ, implying long-term multi-parametric tissue cultures. They generate data sets covering several primary endpoints, allowing pinpointing the mechanism of action and NOAELs at the target (organ) level, necessary for the prediction of the in vivo harmful effect. The real advantage of these innovative bioassays, besides only requiring minute amounts of compound and being quicker than in vivo studies, is that the effect can be predicted and still fit into the drug-discovery process. EggCentris has developed already a battery of this type of multi-parametric bioassays, each representing a target organ.

How does EggCentris contribute to the achievement of reduction, refinement and replacement of animal experimentation (3R principle)?
RC. EggCentris was founded with the aim to offer the industry in vitro bioassays that can assess the reproductive function while applying the 3R principle. Long-term multi-parametric tissue cultures systems holding the key elements of the target organ were designed and shown to be highly predictive. Since they closely mimic the physiological processes, they reveal a physiological (in vitro) response to the tested compounds. A very dedicated and well-designed in vivo study will only be performed when no in vitro alternative is available to answer the question.

EggCentris R&D focuses on extending its battery of in vitro bioassays so that all the target organs of the reproductive system can be covered ultimately enabling us to entirely assess male and female fertility and embryo development in vitro.

Rita Cortvrindt is CEO and founder of EggCentris. She acquired expertise in the field of reproductive biology/medicine and toxicology over the last 20 years. Her main focus was on the development of innovative vitro methods that closely mimic the in vivo physiology. With EggCentris she aims to contribute to the 3R principle.