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 chorionic gonadotropin to inhibit prostaglandin-induced preterm delivery in a murine model.


METHODS
A preterm delivery model was developed by using intraperitoneal injection of 20 microgram of prostaglandin F(2)(alpha) to induce preterm labor in C3H/HeN inbred mice. Mice were then pretreated with human chorionic gonadotropin 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 vehicle) 4 hours after administration of prostaglandin F(2)(alpha). The specificity of the human chorionic gonadotropin effect was assessed by treating mice with whole human chorionic gonadotropin, an equal mass dose of the beta-subunit 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-Whitney U test and the log-rank test. Survival estimates were computed by using the Kaplan-Meier method.


RESULTS
Pilot studies in 52 mice confirmed that a single intraperitoneal injection of 20 microgram of prostaglandin F(2)(alpha) on day 16 (80% gestation) consistently induced preterm delivery compared with the effect of sodium chloride 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 delays in delivery times compared with the prostaglandin-only group (prostaglandin F(2)(alpha) only, 21.9 +/- 2. 0 hours; human chorionic gonadotropin pretreatment 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 significant dose-dependent inhibition of preterm delivery compared with the prostaglandin-only group (P <.00005; n = 34). Mice treated with the alpha-subunit or the beta-subunit of human chorionic gonadotropin after prostaglandin administration 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); however, the effect was less pronounced than that seen with a mass equivalent of human chorionic gonadotropin.


CONCLUSIONS
Human chorionic gonadotropin exhibits potent inhibition of prostaglandin-induced preterm delivery in mice. The effect is dose-dependent, and whole human chorionic gonadotropin is required to elicit inhibition. Further studies are needed to determine the safety and efficacy of human chorionic gonadotropin as a potential therapy for preterm labor inhibition in human pregnancy.
Kurtzman
J T
JT
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Louisville, KY, USA.
Spinnato
J A
JA
Goldsmith
L J
LJ
Zimmerman
M J
MJ
Klem
M
M
Lei
Z M
ZM
Rao
C V
CV
D000818:Animals; D006063:Chorionic Gonadotropin / Q000627:therapeutic use*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000627:therapeutic use; D015237:Dinoprost / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D005865:Gestational Age; D015292:Glycoprotein Hormones, alpha Subunit / Q000627:therapeutic use; D006801:Humans; D007274:Injections, Intraperitoneal; D007700:Kinetics; D007986:Luteinizing Hormone / Q000008:administration & dosage; D051379:Mice; D008809:Mice, Inbred C3H; D007752:Obstetric Labor, Premature / Q000139:chemically induced / Q000517:prevention & control*; D011247:Pregnancy
D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D015292:Glycoprotein Hormones, alpha Subunit; D007986:Luteinizing Hormone; D015237:Dinoprost