Article ; Online: Reduced fertility in vitro in mice lacking the cystatin CRES (cystatin-related epididymal spermatogenic): rescue by exposure of spermatozoa to dibutyryl cAMP and isobutylmethylxanthine.
2010 Volume 84, Issue 1, Page(s) 140–152
Abstract: The cystatin CRES (cystatin-related epididymal spermatogenic; Cst8) is the defining member of a reproductive subgroup of family 2 cystatins of cysteine protease inhibitors and is present in the epididymis and spermatozoa, suggesting roles in sperm ... ...
| Abstract | The cystatin CRES (cystatin-related epididymal spermatogenic; Cst8) is the defining member of a reproductive subgroup of family 2 cystatins of cysteine protease inhibitors and is present in the epididymis and spermatozoa, suggesting roles in sperm maturation and fertilization. To elucidate the role of CRES in reproduction, mice lacking the Cst8 gene were generated and their fertility examined. Although both male and female Cst8(-/-) mice generated offspring in vivo, spermatozoa from Cst8(-/-) mice exhibited a profound fertility defect in vitro. Compared to spermatozoa from Cst8(+/+) mice, spermatozoa from Cst8(-/-) mice were unable to undergo a progesterone-stimulated acrosome reaction and had decreased levels of protein tyrosine phosphorylation, suggesting a defect in the ability of Cst8(-/-) spermatozoa to capacitate. Incubation of Cst8(-/-) spermatozoa with dibutyryl cAMP and 3-isobutyl-1-methylxanthine rescued the fertility defect, including the capacity for sperm protein tyrosine phosphorylation. Both untreated Cst8(+/+) and Cst8(-/-) spermatozoa, however, exhibited similar increased total levels of cAMP and protein kinase A (PKA) activity throughout the capacitation time course compared to spermatozoa incubated under noncapacitating conditions. Taken together, these results suggest that mice lacking CRES may have altered local levels of cAMP/PKA activity, perhaps because of improper partitioning or tethering of these signaling molecules, or that the CRES defect does not directly involve cAMP/PKA but other signaling pathways that regulate protein tyrosine phosphorylation and capacitation. |
|---|---|
| MeSH term(s) | 1-Methyl-3-isobutylxanthine/pharmacology ; Aging ; Animals ; Bucladesine/pharmacology ; Cells, Cultured ; Cystatins/genetics ; Cystatins/metabolism ; Female ; Gene Expression Regulation ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mutation ; Sperm Motility/physiology ; Spermatozoa/drug effects ; Spermatozoa/physiology ; Time Factors ; Xanthines/pharmacology |
| Chemical Substances | Cystatins ; Xanthines ; Cst8 protein, mouse (149291-61-2) ; Bucladesine (63X7MBT2LQ) ; 1-Methyl-3-isobutylxanthine (TBT296U68M) |
| Language | English |
| Publishing date | 2010-09-01 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural |
| ZDB-ID | 1118-6 |
| ISSN | 1529-7268 ; 0006-3363 |
| ISSN (online) | 1529-7268 |
| ISSN | 0006-3363 |
| DOI | 10.1095/biolreprod.110.084855 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 551: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.