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- Al-Alem, Linah, et al.
(författare)
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Chemokine Ligand 20: A Signal for Leukocyte Recruitment During Human Ovulation?
- 2015
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 156:9, s. 3358-69
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Tidskriftsartikel (refereegranskat)abstract
- Ovulation is one of the cornerstones of female fertility. Disruption of the ovulatory process results in infertility, which affects approximately 10% of couples. Using a unique model in which the dominant follicle is collected across the periovulatory period in women, we have identified a leukocyte chemoattractant, chemokine ligand 20 (CCL20), in the human ovary. CCL20 mRNA is massively induced after an in vivo human chorionic gonadotropin (hCG) stimulus in granulosa (>10 000-fold) and theca (>4000-fold) cells collected during the early ovulatory (12-18 h) and late ovulatory (18-34 h) periods after hCG administration. Because the LH surge sets in motion an inflammatory reaction characterized by an influx of leukocytes and CCL20 is known to recruit leukocytes in other systems, the composition of ovarian leukocytes (CD45+) containing the CCL20 receptor CCR6 was determined immediately prior to ovulation. CD45+/CCR6+ cells were primarily natural killer cells (41%) along with B cells (12%), T cells (11%), neutrophils (10%), and monocytes (9%). Importantly, exogenous CCL20 stimulated ovarian leukocyte migration 59% within 90 minutes. Due to the difficulties in obtaining human follicles, an in vitro model was developed using granulosa-lutein cells to explore CCL20 regulation. CCL20 expression increased 40-fold within 6 hours after hCG, was regulated partially by the epithelial growth factor pathway, and was positively correlated with progesterone production. These results demonstrate that hCG dramatically increases CCL20 expression in the human ovary, that ovarian leukocytes contain the CCL20 receptor, and that CCL20 stimulates leukocyte migration. Our findings raise the prospect that CCL20 may aid in the final ovulatory events and contribute to fertility in women.
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| 2. |
- Puttabyatappa, Muraly, et al.
(författare)
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Induction of Tissue Factor Pathway Inhibitor 2 by hCG regulates Periovulatory Gene Expression and Plasmin Activity.
- 2017
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 158:1, s. 109-120
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Tidskriftsartikel (refereegranskat)abstract
- A key event during the process of ovulation is an increased proteolytic activity that aids in breakdown of the follicular wall to permit oocyte release. How the activity of these proteases is regulated is still not known. We hypothesize that Tissue Factor Pathway Inhibitor 2 (TFPI2), a matrix-associated Kunitz-type serine protease inhibitor, plays a role in regulating proteolytic activity during the periovulatory period as in other tissues. TFPI2 is secreted into the extracellular matrix (ECM) where it is postulated to regulate physiological ECM remodeling. The expression profile of TFPI2 during the periovulatory period was assessed utilizing a well-characterized human menstrual cycle model and a gonadotropin-primed rat model. Administration of an ovulatory dose of hCG increased TFPI2 expression dramatically in human and rat granulosa and theca cells. This increase in Tfpi2 expression in rat granulosa cells required hCG-mediated EGFR, PKA, ERK1/2, p38 MAPK and thrombin receptor PAR1-dependent cell signaling. A siRNA-mediated knockdown of TFPI2 in rat granulosa cells resulted in increased plasmin activity in the granulosa cell conditioned media. Knockdown of TFPI2 also reduced expression of multiple genes including Il6 and Areg. Overexpression of TFPI2 using an adenoviral vector partially restored the expression of Il6 and Areg in TFPI2 siRNA treated rat granulosa cells. These data support the hypothesis that TFPI2 is important for moderating plasmin activity and regulating granulosa cell gene expression during the periovulatory period. We therefore propose that through these actions, TFPI2 aids in the tissue remodeling taking place during follicular rupture and corpus luteum formation.
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