Bibliographic Details
| Title: |
Progesterone Inhibits Basal and TNF-α-Induced Apoptosis in Fetal Membranes: A Novel Mechanism to Explain Progesterone-Mediated Prevention of Preterm Birth. |
| Authors: |
Guoyang Luo1, Abrahams, Vikki M.1, Tadesse, Serkalem1, Funai, Edmund F.1, Hodgson, Eric J.1, Jinsong Gao2, Norwitz, Errol R.1 errol.norwitz@yale.edu |
| Source: |
Reproductive Sciences. Jun2010, Vol. 17 Issue 6, p532-539. 8p. |
| Subject Terms: |
*PROGESTERONE, *APOPTOSIS, *FETAL membranes, *PREMATURE labor, *PREGNANCY complications |
| Abstract: |
Objective: Progesterone supplementation prevents preterm birth (PTB) in some high-risk women, but its mechanism of action is not known. One third of PTB is associated with preterm premature rupture of membranes (PPROM).We hypothesize that progesterone may block proinflammatory cytokine-induced apoptosis of fetal membrane, thereby preventing PPROM and PTB. Methods: Fetal membranes were collected at elective repeat cesarean at term (no labor, no infection [n = 12]), washed, and cultured with/ without progesterone (125-500 ng/mL), 17a-hydroxyprogesterone caproate (125-500 ng/mL [17P]), or medroxyprogesterone acetate (10-7-10-6 mol/L [MPA]) for 24 hours. Membranes were then treated with/without lipopolysaccharide ([LPS] 100 ng/mL) or tumor necrosis factor alpha ([TNF-α] 50 ng/ mL) for 24 to 72 hours, harvested, and homogenized. Apoptosis was determined by evaluating caspase-3, -8, and -9 activities. Caspase activity in relative light units was measured on a luminometer and corrected for total protein. Results: Both TNF-α and LPS significantly increased caspase-3, -8, and -9 activity in term fetal membranes in a time-dependent fashion. Progesterone, 17P, and MPA significantly reduced TNF-α, but not LPS, induced caspase-3 activity. Interestingly, progesterone and MPA, but not 17P, also inhibited basal caspase-3 activity. Conclusion: Progesterone inhibits basal and TNF-α-induced apoptosis in term fetal membranes. This novel observation may explain in part the mechanism by which progesterone supplementation prevents PPROM and PTB in some high-risk women. The effect of progesterone on the basal levels of apoptosis suggests that this mechanism may also be important for normal labor at term. [ABSTRACT FROM AUTHOR] |
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