Search

Recurrent spontaneous abortion (RSA) is defined as the loss of three or more consecutive pregnancies during the first trimester of embryonic intrauterine development. This kind of human infertility is frequent among the general population since it affects 1 to 5% of women. In half of the cases the etiology remains unelucidated. In the present study, we used interspecific recombinant congenic mouse strains (IRCS) in the aim to identify genes responsible for embryonic lethality. Applying a cartographic approach using a genotype/phenotype association, we identified a minimal QTL region, of about 6 Mb on chromosome 1, responsible for a high rate of embryonic death (∼30%). Genetic analysis suggests that the observed phenotype is linked to uterine dysfunction. Transcriptomic analysis of the uterine tissue revealed a preferential deregulation of genes of this region compared to the rest of the genome. Some genes from the QTL region are associated with VEGF signaling, mTOR signaling and ubiquitine/proteasome-protein degradation pathways. This work may contribute to elucidate the molecular basis of a multifactorial and complex human disorder as RSA.

In mammals, fertility is governed by a considerable number of genes, as materialized by the decreased or impaired fertility of ~20% of knock-out mice. We wished to study fertility parameters as quantitative genetic characters (QTL), using a very original model of interspecific recombinant congenic mice developed at the Pasteur Institute

MAMMIFERTMAMMIFERT; absent

Most repository concepts for high-Ievel wastes and spent fuel in both crystalline and clay host rocks call for the use of significant amounts of bentonite barriers as a buffer between the waste packages and the host rock. The behaviour of bentonite barriers in the repository environment is influenced by mechanical, hydrological, thermal, chemical and radiological conditions, which are variable in both time and space. Integrated performance assessment needs ta identify and assess all relevant aspects for the performance of this component of the repository system. Benipa (Bentonite barriers in integrated performance assessment) was a research project, within the fifth framework programme of the European Union, which started in September 2000 and was planned for 36 months. Participants in the project were: two national agencies, which are responsible for national HLW management (Enresa as project coordinator, Spain; NAGRA, Switzerland) and six research centres (GRS, Germany; IRSN, France; NRG, the Nederlands; SCK-CEN, Belgium; VTT, Filand; ZAG, Slovenia). The overall objective of Benipa was to assess the state of the art in the treatment of bentonite barriers in integrated performance assessment, evaluating the capacity and consistency of methods and data available to convincingly justify the capacity of bentonite to perform their assigned safety functions. The project analysed and integrated the numerous developments achieved in the study of the bentonite barriers. Current repository concepts were reviewed and referent cases were selected for modelling. The necessity of using predictive models to evaluate '- potential consequences in performance assessment is well recognised. To this aim, available information on FEPs was compiled and processed in order to evaluate the bases for decisions in integrated performance assessment. The evaluation of the influences of many significant FEPs requires the development and application of conceptual models, comparing results between models of different degrees of abstraction and simplification. Assessment codes at process and integrated level must be analysed and upgrated where necessary. New, more advanced calculations at process and integrated level need to be carried out, in order to verify model performance and to evaluate the sufficiency of available assessment methods. Also, sensitivity and optimisation analyses must be perfomed.

Sperm motility is a key function in the process of fertilization. Significant gaps in the knowledge of the mechanisms of control and modulation of sperm motility still remain. It is well known that the percentage of motile sperm is correlated with fertility in vivo but the recent development of assisted reproductive technologies and the extensive use of objective methods to assess sperm movement in vitro indicate that the quality of sperm movement is important too for fertilization. However, the exact pattern of motility characteristics to fulfill fertilization in vitro and in vivo are not clearly established essentially because of the lack of multiparametric and controlled studies in vitro and prospective studies in vivo. There is also presently no evidence for an improvement of fertility when using different pharmacological approaches to increase sperm motility in vitro. Therefore, further efforts are required to improve our basic knowledge of the relations between sperm motility and fertility with the aim to adapt and apply it to the problem of male infertility.