Prolactin Controls Infection-Associated Preterm Birth
Sandra E. Reznik, College of Pharmacy and Health Sciences, Department of Pharmaceutical Sciences
Abstract:
Background: In the United States, 12-13% of births are premature and preterm birth (PTB) accounts for the majority of perinatal morbidity and mortality. There is no FDA approved treatment for preterm labor.
Hypothesis: Our overlying hypothesis is that prolactin (PRL) can control infection-associated preterm birth.
Methods: Mice are injected intraperitoneally (ip) with an intermediate dose of lipopolysaccharide (LPS), causing approximately half of the mice to develop preterm birth (PTB) and the other half to carry their pups to term. Oligonucleotide microarray analysis is performed on gestational tissues collected from the two groups of mice in order to identify “protective” genes that prevent the mice from developing PTB. The validity of the microarray results is tested using real time rt pcr. In a second line of investigation, in vivo analysis of the effect of PRL on infection-associated PTB is performed. Finally, to identify the mechanism by which PRL acts to prevent PTB, Western blot analysis of Jak2 expression is carried out in gestational tissues collected from mice successfully protected from PTB with PRL vs. control mice delivering prematurely.
Results: Microarray analysis of placental tissues shows statistically significant up-regulation of several PRL family genes (p<0.05) in the mice protected from PTB. Real time rt pcr confirms microarray findings. Finally, Western blot analysis shows up-regulation of Jak2 proteins in placental tissue samples of mice protected from PTB by receiving PRL (p<0.05).
Conclusion: Taken together, the data indicate that PRL has a protective effect in controlling the development of infection-associated PTB. This action likely occurs via binding of PRL receptors present in the decidua, which leads to activation of the prototype Jak2/STAT5 signaling cascade. This finding may impact on a clinical disorder associated with a great deal of neonatal morbidy and mortality for which there is currently no satisfactory therapy.