Characterization of the concentration gradient of prostaglandin H synthase 2 mRNA throughout the pregnant baboon uterus.

The present study was designed to determine the effect of the spatial gradient from the cervix to the uterine fundus on the control of local prostaglandin H synthase (PGHS) 2 mRNA expression. We performed total cesarean hysterectomies during the last trimester in 12 pregnant baboons, 7 not in labor and 5 in labor, and examined PGHS2 mRNA expression throughout the uterus. PGHS2 mRNA abundance was quantified by in situ hybridization and northern blot analysis in the uterine fundus, lower uterine segment and the different segments of the cervix. Quantitative northern blot and in situ analysis demonstrated a gradient of PGHS2 mRNA expression, with the highest levels at the level of the lower portion of the cervix and decreased expression through the mid- and upper portion of the cervix and lower uterine segment; the lowest levels of expression were seen in the uterine fundus. Moreover, cellular localization of PGHS2 mRNA and protein demonstrated high levels of expression in the cervical glandular epithelial cells with only occasional staining of smooth muscle cells in pregnant baboons. Decreased PGHS2 mRNA concentration gradient from the cervical external os to the fundus suggests that prostaglandin (PG) production in the uterus and cervix strongly depends on anatomical relations. This increased local PG production activity may be critical to pregnancy-associated lower uterine segment elongation, cervical softening and effacement in primate labor. These data provide a compelling biological basis for the use of PGHS2 inhibitors in the prophylaxis of preterm birth and cervical incompetence.