Reproductive Toxicology - Research Groups

Group in Basel

Reproductive toxicology I (Christian De Geyter, co-applicant)
To overcome the problem of infertility after chemotherapy, we have performed a prospective feasibility study for the cryostorage of uninseminated oocytes and have achieved the first successful pregnancy with this method in Switzerland (17). However, with conventional freezing methods the pregnancy rates are low. An alternative strategy for preserving ovarian function could consist of cryostorage of oocytes and granulosa cells prior to chemotherapy and to reconstitute ovarian function after recovery from the malignant disease. Until recently, it was impossible to maintain ovarian granulosa cells in culture over prolonged time periods without loss of their main characteristics. Using granulosa cells taken from a granulosa cell tumor, our research unit was the first to produce an immortalized granulosa cell line (18). Further experiments have demonstrated that the antrum of a Graafian ovarian follicle contains a subset of undifferentiated stem cells, which retain all the characteristics of multipotent stem cells of the mesodermal lineage. We achieved to create a culture environment, in which a subpopulation of granulosa cells retained their characteristics, such as receptivity to FSH and their steroidogenic potential. This was achieved by culturing granulosa cells in a three dimensional scaffold on collagen I. With the support of the laboratory animal facilities at the University Hospital of Zürich three-dimensional collagen-granulosa scaffolds are now being transplanted into the ovaries of immuno-incompetent mice (nude mice). This experiment will demonstrate whether these granulosa cells, cultured over prolonged time periods in the presence of LIF, can reassume their function in their physiological niche. We have also studied to toxicity of chemo- and radiotherapy on spermatogenesis in humans (19).

Group in Lausanne

Reproductive Toxicology II (Alice Panchaud, Laura Rothuizen, co-applicants)
The Swiss Teratogen Information Service (STIS) is the centre of reference for evaluating the risk related to exposures to therapeutic and non-therapeutic agents during reproduction, pregnancy or breastfeeding. Its activity touches a specific field in toxicology: applied reproductive human toxicology. Since 1992, the STIS prospectively gathers all exposures and their outcomes that are reported by healthcare professionals seeking evaluation of the risk of exposures to therapeutic and non-therapeutic agents on reproduction, pregnancy or breastfeeding (58). The critical amount of data necessary for toxicoepidemiological studies are created through sharing of these cases with the European (ENTIS) and the North American (OTIS) teratovigilance networks.

Group in Geneva

Reproductive Toxicology III (Stylianos Antonarakis, Ariane Giacobino, co-applicants)
A number of studies have demonstrated that embryonic, fetal or postnatal exposures to various agents can induce adult onset phenotypes or diseases. The mechanism for this early-in-development basis of adult-onset disease, however, is largely unknown, but may involve epigenetic alterations in the genome including DNA methylation. Environmental factors such as irradiation, chemicals and toxins have shown a potential for inducing epigenetic defects. Among them the endocrine disruptors have recently been described as potentially very detrimental. These are exogenous substances that alter function(s) of the endocrine system and consequently can lead to endocrine disruption and cause adverse health effects in an intact organism or in its progeny. Example of endocrine disruptors are bisphenol A, phtalates, dioxine or DDT which can be found in substances like cleaning products, paints, glues, cosmetics and pesticides. It is therefore of high interest and strong relevance for human health to further explore, possible specific methylation changes subsequent to an exposure to endocrine disruptors on spermatogenesis (72-75).

Last Updated on Thursday, 25 March 2010 15:39 Created: Thursday, 02 April 2009 15:54