Human chorionic gonadotropin exhibits potent inhibition of preterm delivery in a small animal model

OBJECTIVE: The purpose of this study was to test the capability of human ch orionic gonadotropin to inhibit prostaglandin-induced preterm delivery in a murine model. STUDY DESIGN: A preterm delivery model was developed by using intraperitone al injection of 20 mu g of prostaglandin F-2 alpha to induce preterm labor in C3H/HeN inbred mice. Mice were then pretreated with human chorionic gona dotropin 4 hours before administration of prostaglandin F-2 alpha, and time to delivery of the first pup was recorded. After initial promising results , mice were then given increasing intraperitoneal doses of human chorionic gonadotropin (100 IU, 250 IU, or 1000 IU or sodium chloride solution vehicl e) 4 hours after administration of prostaglandin F-2 alpha. The specificity of the human chorionic gonadotropin effect was assessed by treating mice w ith whole human chorionic gonadotropin, an equal mass dose of the beta-subu nit or the alpha-subunit of human chorionic gonadotropin, or an equal mass dose of luteinizing hormone 4 hours after administration of prostaglandin F -2 alpha. Delivery times between groups were compared by using the Mann-Whi tney U test and the log-rank test. Survival estimates were computed by usin g the Kaplan-Meier method. RESULTS: Pilot studies in 52 mice confirmed that a single intraperitoneal i njection of 20 mu g of prostaglandin F-2 alpha on day 16 (80% gestation) co nsistently induced preterm delivery compared with the effect of sodium chlo ride solution on control mice (prostaglandin F-2 alpha, 19.3 +/- 2.9 hours; sodium chloride solution, 53.5 +/- 13.6 hours; P < .0001). Mice pretreated with human chorionic gonadotropin (1000 IU) demonstrated significant delay s in delivery times compared with the prostaglandin-only group (prostagland in F-2 alpha only, 21.9 +/- 2.0 hours; human chorionic gonadotropin pretrea tment plus prostaglandin F-2 alpha, 48.5 +/- 20 hours; P < .0001; n = 17). Mice treated with human chorionic gonadotropin (100 IU, 250 IU, 1000 IU) 4 hours after administration of prostaglandin F-2 alpha demonstrated signific ant dose-dependent inhibition of preterm delivery compared with the prostag landin-only group (P < .00005; n = 34). Mice treated with the alpha-subunit or the beta-subunit of human chorionic gonadotropin after prostaglandin ad ministration did not demonstrate delays in delivery times (P = .46; n = 27) . Administration of luteinizing hormone delayed delivery compared with the effect of prostaglandin F-2 alpha on control animals (P < .05; n = 17); how ever, the effect was less pronounced than that seen with a mass equivalent of human chorionic gonadotropin. CONCLUSIONS: Human chorionic gonadotropin exhibits potent inhibition of pro staglandin-induced preterm delivery in mice. The effect is dose-dependent, and whole human chorionic gonadotropin is required to elicit inhibition. Fu rther studies are needed to determine the safety and efficacy of human chor ionic gonadotropin as a potential therapy for preterm labor inhibition in h uman pregnancy.