Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Reproduction ; 141(3): 343-55, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21183657

ABSTRACT

Bioactivation of precursor proteins by members of the proprotein convertase (PC) family is essential for normal reproduction. The Pcsk6 gene is a member of the PC family that is expressed in numerous ovarian cell types including granulosa cells and oocytes. We hypothesized that loss of PCSK6 would produce adverse effects in the mouse ovary. Mice incapable of expressing PCSK6 (Pcsk6(tm1Rob)) were obtained, and reproductive parameters (serum hormones, whelping interval, estrus cyclicity, and fertility) were compared to Pcsk6(+/+) mice. While Pcsk6(tm1Rob) female mice are fertile, they manifest reduced reproductive capacity at an accelerated rate relative to Pcsk6(+/+) mice. Reproductive senescence is typically reached by 9 months of age and is correlated with loss of estrus cyclicity, elevated serum FSH levels, and gross alterations in ovarian morphology. A wide range of ovarian morphologies were identified encompassing mild, such as an apparent reduction in follicle number, to moderate--ovarian atrophy with a complete absence of follicles--to severe, manifesting as normal ovarian structures replaced by benign ovarian tumors, including tubulostromal adenomas. Targeted gene expression profiling highlighted changes in RNA expression of molecules involved in processes such as steroidogenesis, gonadotropin signaling, transcriptional regulation, autocrine/paracrine signaling, cholesterol handling, and proprotein bioactivation. These results show that PCSK6 activity plays a role in maintaining normal cellular and tissue homeostasis in the ovary.


Subject(s)
Ovarian Diseases/genetics , Ovary/physiology , Proprotein Convertases/genetics , Animals , Estrous Cycle/blood , Estrous Cycle/genetics , Female , Follicle Stimulating Hormone/blood , Gene Expression , Male , Mice , Mice, Transgenic , Mutant Proteins/genetics , Mutant Proteins/physiology , Ovarian Diseases/pathology , Ovarian Diseases/physiopathology , Ovary/abnormalities , Ovary/metabolism , Ovary/pathology , Ovulation/genetics , Ovulation/physiology , Proprotein Convertases/physiology , Reproduction/genetics , Reproduction/physiology , Time Factors
SELECTION OF CITATIONS
SEARCH DETAIL
...