Carbonic Anhydrase Regulate Endometrial Gland Development in the Neonatal Uterus1

Abstract

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.

Progesterone Inhibits Uterine Gland Development in the Neonatal Mouse Uterus1

“…Carbonic anhydrases (CAR) are hypothesized to have a key role in regulating neonatal mouse uterine adenogenesis by affecting GE cell migration and MMP activity [38]. Interestingly, inhibition of CAR2 activity in neonatal mice reduced endometrial gland development [38]. Collectively, available results support the idea that P4 deregulates MMP expression and activity in the endometrium, which impairs ECM remodeling required for GE cell proliferation, migration and/ or differentiation in the developing neonatal uterus.…”

“…Further, Car2 was reduced in P4-treated mice on PD 5 and 10. Carbonic anhydrases (CAR) are hypothesized to have a key role in regulating neonatal mouse uterine adenogenesis by affecting GE cell migration and MMP activity [38]. Interestingly, inhibition of CAR2 activity in neonatal mice reduced endometrial gland development [38].…”

“…As illustrated in Metalloproteinases are involved in extracellular matrix remodeling, and Mmp2, Mmp7, and the metalloproteinase regulators Car2 and Adamts1 are expressed in the developing and adult mouse uterus [37,38]. As illustrated in Figure 5, Adamts1 and Mmp2 expression were not affected (P .…”

Progesterone Downregulates Oestrogen-Induced Expression of CFTR and SLC26A6 Proteins and mRNA in Rats’ Uteri

“…Under the influence of oestrogen (E), there is an obvious fluid accumulation, while a reduction of fluid volume has been reported under progesterone (P) [3, 4]. While fluid accumulation is thought to be important for sperm and embryo transport, fluid loss has been proposed to assist closure of the uterine lumen, sandwiching the blastocyst between the two opposing walls of the uterus, prior to the attachment phase of implantation [5, 6]. …”

“…Secretion of HCO 3 − ,which plays an important role in sperm capacitation,embryo development, and reducing the uterocervical mucus elasticity for sperm penetration [6, 14], has been reported to involve the basolaterally located sodium-proton exchanger (NHE), sodium-bicarbonate cotransporter (NBC) [15, 16], and the apically located CFTR and Cl − /HCO 3 − exchanger (SLC26A6) [17]. In addition, carbonic anhydrase is also responsible for the intracellular HCO 3 − generation [14, 18].…”