Carbonic Anhydrase Regulate Endometrial Gland Development in the Neonatal Uterus1

Carbonic anhydrases (CAs) are zinc metalloenyzmes that catalyze the reversible conversion of carbon dioxide to carbonic acid and are involved in respiration, calcification, acid-base balance, and formation of fluids. Transcriptional profiling of the developing neonatal mouse uterus detected expression of Car1, Car2, Car11, and Car13 between Postnatal Days (PNDs) 3 and 18. In the neonatal mouse uterus, Car2 and Car11 mRNAs were predominantly localized in endometrial epithelial and stromal cells, respectively, whereas Car13 mRNA was detected in both epithelia and stroma. CAR2 protein was detected primarily in the endometrial epithelia and from PND 3 to PND 18 in the uteri of neonatal mice. To determine whether CA regulated uterine development, neonatal mice were treated s.c. with acetazolamide, a CA inhibitor, from PND 3 to PND 18. Treatment with acetazolamide decreased CA activity in the uterus and the number of endometrial glands without apparent effects on differentiation of the stroma or myometrium. In the neonatal sheep uterus, CA2 mRNA was initially expressed at birth (PND 0) in the endometrial luminal epithelium and was predominantly expressed in the developing glandular epithelium from PND 7 to PND 56. These results support the hypothesis that CA has a functional role in endometrial gland development during postnatal uterine morphogenesis.