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1.  Land Banking: A Mechanism for Urban Sustainable Development in China 
Ambio  2012;41(8):904-906.
PMCID: PMC3492562  PMID: 22627873
2.  Ovarian FAM110C (Family with Sequence Similarity 110C): Induction During the Periovulatory Period and Regulation of Granulosa Cell Cycle Kinetics in Rats1  
Biology of Reproduction  2012;86(6):185.
FAM110C belongs to a family of proteins that regulates cell proliferation. In the present study, the spatiotemporal expression pattern of FAM110C and its potential role were examined during the periovulatory period. Immature female rats were injected with equine chorionic gonadotropin (eCG) followed by human chorionic gonadotropin (hCG) and ovaries or granulosa cells were collected at various times after hCG administration (n = 3/time point). Expression levels of Fam110c mRNA and protein were highly induced both in intact ovaries and granulosa cells at 8 to 12 h after hCG treatment. In situ hybridization analysis demonstrated Fam110c mRNA expression was induced in theca and granulosa cells at 4 h after hCG, primarily localized to granulosa cells at 8 h and 12 h, and decreased at 24 h after hCG. There was negligible Fam110c mRNA detected in newly forming corpora lutea. In rat granulosa cell cultures, hCG induced expression of Fam110c mRNA was inhibited by RU486, whereas NS398 and AG1478 had no effect, suggesting that Fam110c expression is regulated in part by the progesterone receptor pathway. Promoter activity analysis revealed that an Sp1 site was important for the induction of Fam110c expression by hCG. Overexpression of FAM110C promoted granulosa cells to arrest at the G1 phase of the cell cycle but did not change progesterone levels. In summary, hCG induces Fam110c mRNA expression in granulosa cells by activation of an Sp1-binding site and the actions of progesterone. Our findings suggest that FAM110C may control granulosa cell differentiation into luteal cells by arresting cell cycle progression.
Human chorionic gonadotropin induces Fam110c mRNA expression in granulosa cells, which promotes their arrest at the G1 phase of the cell cycle; this suggests that FAM110C may control granulosa cell differentiation into luteal cells.
PMCID: PMC3386148  PMID: 22460667
differentiation; granulosa cell; ovary; ovulation; progesterone; SP1
3.  Ovarian Expression and Regulation of the Stromelysins During the Periovulatory Period in the Human and the Rat1 
Biology of Reproduction  2011;86(3):78.
The matrix metalloproteinases (MMPs) are postulated to facilitate follicular rupture. In the present study, expression of the stromelysins (MMP3, MMP10, MMP11) was analyzed in the periovulatory human and rat ovary. Human granulosa and theca cells were collected from the dominant follicle at various times after human chorionic gonadotropin (hCG). Intact rat ovaries, granulosa cells, and residual tissue (tissue remaining after granulosa cell collection) were isolated from equine CG (eCG)-hCG-primed animals. Mmp10 mRNA was highly induced in human granulosa and theca cells and intact rat ovaries, granulosa cells, and residual tissue. Localization of MMP10 to granulosa and theca cells in both human and rat ovarian follicles was confirmed by immunohistochemistry. Mmp3 mRNA was unchanged in human cells and rat granulosa cells, but increased in intact rat ovaries and residual tissue. Mmp11 mRNA decreased following hCG treatment in human granulosa and theca cells as well as rat granulosa cells. Regulation of Mmp10 in cultured rat granulosa cells revealed that the EGF inhibitor AG1478 and the progesterone receptor antagonist RU486 suppressed the induction of Mmp10 mRNA, whereas the prostaglandin inhibitor NS398 had no effect. Studies on the Mmp10 promoter demonstrated that forskolin plus PMA stimulated promoter activity, which was dependent upon a proximal AP1 site. In conclusion, there are divergent patterns of stromelysin expression associated with ovulation, with a marked induction of Mmp10 mRNA and a decrease in Mmp11 mRNA, yet a species-dependent pattern on Mmp3 mRNA expression. The induction of Mmp10 expression suggests an important role for this MMP in the follicular changes associated with ovulation and subsequent luteinization.
Expression of the metalloproteinase Mmp10 mRNA is stimulated by hCG prior to follicular rupture in both the human and the rat ovary, indicating involvement in ovulation and subsequent luteinization.
PMCID: PMC3316269  PMID: 22116802
extracellular matrix; granulosa cells; matrix metalloproteinase; ovulation; ovulatory cycle; proteinases; theca cells
4.  Identification of Hepsin and Protein Disulfide Isomerase A3 as Targets of Gelatinolytic Action in Rat Ovarian Granulosa Cells During the Periovulatory Period1  
Biology of Reproduction  2011;85(4):858-866.
The matrix metalloproteinase (MMP) family is believed to play a role in the ovulatory process because MMP inhibitors block oocyte release. However, little is known about the mechanisms by which the MMPs affect ovulation. The present study investigated the degradomic actions of the gelatinases, MMP2 and MMP9, by identifying gelatinolytic targets in periovulatory granulosa cells. Granulosa cells were collected from immature rats 48 h after equine chorionic gonadotropin treatment and were cultured with human chorionic gonadotropin (hCG) in the absence or presence of a specific MMP2/9 inhibitor ((2R)-2-[(4-biphenylylsulfonyl)amino]-3-phenylpropionic acid) for an additional 24 h. The conditioned media was analyzed for gelatinolytic activity, progesterone, and peptide profiles. Gelatinolytic activity and progesterone were induced in response to hCG; however, there was no difference in progesterone between cells treated with or without the inhibitor. Peptide fragments of proteins altered in the presence of the gelatinase inhibitor were identified by two-dimensional gel electrophoresis and mass spectrometry. Protein disulfide isomerase A3 (PDIA3), which plays a role in protein folding, was identified as a peptide that decreased in the presence of inhibitor while the serine protease hepsin, was found to increase with inhibitor treatment. Subsequent experiments established that PDIA3 and hepsin were targets of MMP2/9 action by cleavage with MMP2 and Western blot analysis, respectively. Additionally, hepsin was identified as a gelatinolytic target in ovarian cancer cells. In the present study, proteomics has identified proteins that may be involved in novel ways in the complex cascades that are mediated by gelatinolytic MMPs during the periovulatory period.
Gelatinases from rat granulosa cells degrade hepsin and protein disulfide isomerase A3.
PMCID: PMC3184295  PMID: 21734266
corpus luteum; hepsin; matrix metalloproteinase; ovulation; protein disulfide isomerase A3
5.  Correction: Hormonal Induction of Polo-Like Kinases (Plks) and Impact of Plk2 on Cell Cycle Progression in the Rat Ovary 
PLoS ONE  2012;7(9):10.1371/annotation/0e8ec400-2a84-45fe-81d4-bbf20d8124c9.
PMCID: PMC3462132
6.  Correction: Hormonal Induction of Polo-Like Kinases (Plks) and Impact of Plk2 on Cell Cycle Progression in the Rat Ovary 
PLoS ONE  2012;7(8):10.1371/annotation/1a9779fe-f0ab-4937-a3ce-1bc7fb0268df.
PMCID: PMC3414586
7.  Hormonal Induction of Polo-Like Kinases (Plks) and Impact of Plk2 on Cell Cycle Progression in the Rat Ovary 
PLoS ONE  2012;7(8):e41844.
The highly conserved polo-like kinases (Plks) are potent regulators of multiple functions in the cell cycle before and during mitotic cell division. We investigated the expression pattern of Plk genes and their potential role(s) in the rat ovary during the periovulatory period. Plk2 and Plk3 were highly induced both in intact ovaries and granulosa cells in vivo after treatment with the luteinizing hormone (LH) agonist, human chorionic gonadotropin (hCG). In vitro, hCG stimulated the expression of Plk2 in granulosa cells, but not Plk3. This induction of Plk2 expression was mimicked by both forskolin and phorbol 12 myristate 13-acetate (PMA). Moreover, Plk2 expression was reduced by inhibitors of prostaglandin synthesis or the EGF pathway, but not by progesterone receptor antagonist (RU486) treatment. At the promoter level, mutation of the Sp1 binding sequence abolished the transcriptional activity of the Plk2 gene. ChIP assays also revealed the interaction of endogenous Sp1 protein in the Plk2 promoter region. Functionally, the over-expression of Plk2 and Plk3 arrested granulosa cells at the G0/G1 phase of the cell cycle. In contrast, the knockdown of Plk2 expression in granulosa cells decreased the number of cells in the G0/G1 stage of the cell cycle, but increased granulosa cell viability. In summary, hCG induced Plk2 and Plk3 expression in the rat ovary. Prostaglandins and the EGF signaling pathway are involved in regulating Plk2 expression. The transcription factor Sp1 is important for Plk2 transcriptional up-regulation. Our findings suggest that the increase in Plk2 and Plk3 expression contributes to the cell cycle arrest of granulosa cells which is important for the luteinization of granulosa cells during the periovulatory period.
PMCID: PMC3411565  PMID: 22870256
8.  Land Consolidation: An Approach for Sustainable Development in Rural China 
Ambio  2010;40(1):93-95.
PMCID: PMC3357731  PMID: 21404828

Results 1-8 (8)