From the epididymis to the egg: participation of CRISP proteins in mammalian fertilization
ASIAN JOURNAL OF ANDROLOGY
Authors: Da Ros, Vanina G.; Weigel Munoz, Mariana; Battistone, Maria A.; Brukman, Nicolas G.; Carvajal, Guillermo; Curci, Ludmila; Gomez-Elias, Matias D.; Cohen, Debora J.; Cuasnicu, Patricia S.
Abstract
Mammalian fertilization is a complex process that involves different steps of interaction between the male and female gametes. In spite of its relevance, the molecular mechanisms underlying this process still remain to be elucidated. The present review describes the contribution of our laboratory to the understanding of mammalian fertilization using Cysteine-RIch Secretory Proteins (CRISP) as model molecules. Substantial evidence obtained from in vitro assays and knockout models shows that epididymal CRISP1 associates with the sperm surface with two different affinities during maturation, and participates in the regulation of signaling pathways during capacitation as well as in both sperm-zona pellucida interaction and gamete fusion. These observations can be extended to humans as judged by our findings showing that the human homolog of the rodent protein (hCRISP1) is also involved in both stages of fertilization. Evidence supports that other members of the CRISP family secreted in the testis (CRISP2), epididymis (CRISP3-4) or during ejaculation (CRISP3) are also involved in sperm-egg interaction, supporting the existence of a functional redundancy and cooperation between homolog proteins ensuring the success of fertilization. Together, our observations indicate that CRISP proteins accompany spermatozoa along their transit through both the male and female reproductive tracts. We believe these results not only contribute to a better mechanistic understanding of fertilization but also support CRISP proteins as excellent candidates for future research on infertility and contraception.
Genes involved in hemorrhagic transformations that follow recombinant t-PA treatment in stroke patients
PHARMACOGENOMICS
Authors: Fernandez-Cadenas, Israel; Del Rio-Espinola, Alberto; Domingues-Montanari, Sophie; Mendioroz, Maite; Fernandez-Morales, Jessica; Penalba, Anna; Rubiera, Marta; Hernandez-Guillamon, Mar; Rosell, Anna; Delgado, Pilar; Chacon, Pilar; Ribo, Marc; Alvarez-Sabin, Jose; Molina, Carlos A.; Garcia-Arumi, Elena; Montaner, Joan
Abstract
Aim: Despite the benefits of recombinant t-PA (rt-PA) for stroke patients some of them suffer from adverse hemorrhagic transformations (HTs) following treatment. Our objective is to study the transcriptomics of HTs patients. Methods: We studied by microarrays 11 blood samples from patients with stroke that had received rt-PA of whom six of them had suffered a HT. For replication step RNA was collected from 14 new subjects (seven with HT, seven without) and then analyzed by real-time PCR. Four proteins were measured by ELISA in 72 new subjects to analyze their role as potential protein biomarkers. Results: The microarray ana-lysis revealed that 14 genes were altered among the HT patients. The replication study confirmed these results for six genes. Two of them (BCL2 and OLFM4) are associated with apoptosis, whereas the other four (LTF, LCN2 [also known as NGAL], CEACAM8 and CRISP3) are involved in the regulation of neutrophil processes. Conclusion: Our data revealed that genes related to apoptosis and neutrophil regulation pathways could be associated with HTs after rt-PA.