Epithelial cell protein milk fat globule?epidermal growth factor 8 and human chorionic gonadotropin regulate stromal cell apoptosis in the human endometrium

RIGGS RM; BOCCA SM; ANDERSON S; FRANCHI A; RHAVI BS; OEHNINGER S.

FERTILITY AND STERILITY

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2012 vol. 98 p. 1549 - 1556

0015-0282

Objective: To study the regulation of apoptosis in human endometrial cells. The specific aims were to determine whether milk fat globule? epidermal growth factor 8 (MFG-E8), a novel endometrial epithelial protein, modulates caspase activation and DNA fragmentation; and to examine whether hCG, an early embryonic product, regulates Bax and Bcl-2 equilibrium, as well as MFG-E8 expression. Design: Primary cultures of human endometrial epithelial cells (EECs) and endometrial stromal cells (ESCs). Setting: Academic center. Patient(s): Ovulatory women aged 21?30 years. Intervention(s): Treatment with MFG-E8 and hCG. Main Outcome Measure(s): Apoptotic activity was quantified using a luciferase assay. Deoxyribonucleic acid fragmentation was detected by TUNEL assay. Bax, Bcl-2, and MFG-E8 messenger RNA expression levels were determined by quantitative reverse transcription-polymerase chain reaction. Immunocytochemistry was used to establish cell purity and presence of MFG-E8 and hCGR (receptor) proteins. Result(s): Endometrial epithelial cells were cytokeratin(+), vimentin(-), MFG-E8(+), and hCG-R(+), whereas ESC were vimentin(+), cytokeratin(-), MFG-E8(-), and hCG-R(+). Treatment of ESC with MFG-E8 resulted in a 13-fold increase in caspase activity and a 30-fold increase in TUNEL. On the other hand, hCG decreased messenger RNA expression of Bax in ESC. Conclusion(s): Milk fat globule?epidermal growth factor 8 has proapoptotic activity, suggesting participation in endometrial remodeling via an epithelial?stromal cell paracrine effect. Conversely, pregnancy levels of hCG has opposite effects on stromal cells.