Gonadotropin-Releasing Hormone Regulates Human Trophoblastic Cell Invasion via TWIST-Induced N-cadherin Expression
Bibliographic record
Abstract
CONTEXT: GnRH and its receptor, GnRHR, were shown to promote trophoblastic cell invasion. Detection of elevated early development-related transcription factor TWIST and adhesion molecule N-cadherin in the invasive trophoblastic cells could suggest that GnRH promotes trophoblastic cell invasion through TWIST-regulated N-cadherin pathway. OBJECTIVE: This study sought to investigate the regulatory effect of GnRH on TWIST and N-cadherin expression as well as invasiveness in human trophoblastic cells. DESIGN: The expression of GnRHR, TWIST, and N-cadherin was first examined in human first-trimester chorionic villi by immunohistochemistry. Expression levels of GnRHR, TWIST, and N-cadherin were tested in primary extravillous trophoblastic (EVT) cells and an immortalized EVT cell line HTR-8/SVneo cells with incubation of GnRH and its antagonist, Antide. Small interfering RNA strategy was used to study the roles of TWIST and N-cadherin in basal- and GnRH-regulated trophoblast invasion. Matrigel-mediated transwell invasion assays were employed to assess cell invasion capacity. RESULTS: GnRHR, TWIST, and N-cadherin were detected at the invasive site of first-trimester human placenta. GnRH treatment significantly increased TWIST and N-cadherin expression in primary EVT as well as HTR-8/SVneo cells. Pretreatment with the GnRH receptor antagonist Antide attenuated the effects of GnRH on TWIST and N-cadherin expression. Invasive capacity of primary EVT and HTR-8/SVneo cell was reduced following siRNA-mediated knockdown of either TWIST or N-cadherin. Furthermore, by knocking down endogenous TWIST, the expression level of N-cadherin was reduced as well as GnRH-induced HTR-8/SVneo cell invasion. Treatment with GnRH induces AKT phosphorylation and Phosphoinositide3-kinase inhibitor LY294002 attenuates the effects of GnRH on TWIST and N-cadherin expression and trophoblastic cell invasion. CONCLUSION: Our results suggest that GnRH acts via its receptor to induce AKT phosphorylation, which contributes to elevated TWIST expression. Increased levels of TWIST subsequently induce N-cadherin expression, which promotes human trophoblastic cell invasion in vitro.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".