Lytic cytomegalovirus replication and the hormones of human pregnancy

The frequency of human cytomegalovirus (CMV) excretion during pregnancy denoting active infection has been demonstrated to increase as gestation advances and at term involves a significant percentage of women. This increase enhances the risk of congenital infection of the fetus. Thus it appears that some factor(s) unique to the condition of pregnancy favors susceptibility to maternal CMV infection. We designed our studies to investigate the possible association of the continuously rising levels of selected hormones and this increased susceptibility. Progesterone, 17 beta-estradiol, and cortisol were added to tissue culture media in final concentrations to match those occurring in term pregnancy serum. Two strains of human foreskin cells, one neonatal and the other fetal, were treated with either single or paired combinations of hormone-containing media. Lytic CMV replication in neonatal foreskin cells was enhanced by a maximum of 5.7-fold when these cells were treated with cortisol. Such enhancement did not occur in the fetal cells. No synergistic effects were seen when cortisol was used in combination with other hormones nor when neonatal foreskin cells were replicated for at least three generations in either single or paired combinations of hormones prior to use. Differential hormonal enhancement of CMV replication in vitro suggests a possible mechanism for the increased incidence of CMV infection observed during human pregnancy.