Water transport in highly water-permeable membranes is conducted by
water-selective pores--namely, water channels. The cloning of water channels
revealed the water-selective characteristics of these proteins when expressed in
Xenopus oocytes or reconstituted in liposomes. In adition to the function as water
channels, cloning of a member of the water channel that also transports nonionic
small molecules such as urea and glycerol .
NCBI Summary:
The aquaporins are a family of water-selective membrane channels. This gene encodes a member of a subset of aquaporins called the aquaglyceroporins. This protein allows passage of a broad range of noncharged solutes and also stimulates urea transport and osmotic water permeability. This protein may also facilitate the uptake of glycerol in hepatic tissue . The encoded protein may also play a role in specialized leukocyte functions such as immunological response and bactericidal activity. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
General function
Channel/transport protein
Comment
Expression of aquaporin 9 in granulosa cells of patients with polycystic ovary syndrome in IVF-cycles]. [Lu XE et al. (2007) To investigate aquaporin 9 (AQP9) mRNA and protein expression in antrum follicle and luteinizing granulosa cells of polycystic ovarian syndrome (PCOS) ovary, and its relation to follicular fluid steroids hormone levels during IVF cycles. AQP9 mRNA expression on luteinizing granulosa cells in IVF cycles was detected by RT-PCR. AQP9 protein expression in antrum follicles of PCOS ovary and luteinizing granulosa cells was measured by immunohistochemistry. The concentrations of estradiol (E2), progesterone (P) and testerone (T) in follicular fluid were measured by radioimmunoassay (RIA). The expression of AQP9 mRNA in luteinizing granulosa cells during IVF cycles was positive by RT-PCR. No significant differences in AQP9 mRNA levels in granulosa cells between PCOS and control group were found during IVF cycles. The expression level of AQP9 mRNA in large follicles was higher than that in small follicles, but not significantly. The immunoreactivity for AQP9 was localized in membrane and cytoplast of granulosa cells in antrum follicles from PCOS ovary and luteinizing granulosa cells during IVF cycles. Multiple regression analysis showed that AQP9 mRNA levels on granulosa cells were not correlated with E2, P and T levels in follicular fluid during IVF cycles. AQP9 may play an important role in the follicle development and antrum formation through water transport and AQP9 may be involved in the mechanism of follicle development in PCOS.//////////////////
Cellular localization
Plasma membrane
Comment
candidate123
Ovarian function
Antrum/Follicular fluid formation, Oogenesis
Comment
Spatiotemporal expression of aquaporin 9 is critical for the antral growth of mouse ovarian follicles††. Lee SE et al. (2020) Although a few aquaporins (AQPs) expressed in granulosa cells have been postulated to mediate fluid passage into the antrum, the specific expression of AQPs in different follicle cell types and stages and their roles have not been evaluated extensively. The spatiotemporal expression of aquaporin (Aqp) 7, 8, and 9 and the functional roles of Aqp9 in antral growth and ovulation were examined using a superovulation model and 3-dimensional follicle culture. Aqp9 was expressed at a high level in the rapid growth phase (24-48 h post equine chorionic gonadotropin (eCG) for superovulation induction) compared to Aqp7 (after human chorionic gonadotropin (hCG)) and Aqp8 (8-24 h post eCG and 24 h post hCG). A dramatic increase in the expression and localization of Aqp9 mRNA in theca cells was observed, as evaluated using quantitative reverse transcription-polymerase (RT-PCR) coupled with laser capture microdissection and immunohistochemistry. AQP9 was located primarily on the theca cells of the tertiary and preovulatory follicles but not on the ovulated follicles. In phloretin-treated mice, the diameter of the preovulatory follicles and the number of ovulated oocytes decreased. Consistent with these findings, knocking down Aqp9 expression with an Aqp9 siRNA inhibited follicle growth (0.28:1 = siRNA:control) and decreased the number of ovulated follicles (0.36:1 = siRNA:control) during in vitro growth and ovulation induction. Based on these results, the expression of AQPs is under the control of the physiological status, and AQP9 expression in theca during folliculogenesis is required for antral growth and ovulation in a tissue-specific and stage-dependent manner.//////////////////
Expression regulated by
Steroids
Comment
Altered aquaporin expression in women with polycystic ovary syndrome: hyperandrogenism in follicular fluid inhibits aquaporin-9 in granulosa cells through the phosphatidylinositol 3-kinase pathway. Qu F et al. BACKGROUND The present study was designed to evaluate whether the alteration of aquaporin-9 (AQP-9) expression in granulosa cells (GCs) of patients with polycystic ovary syndrome (PCOS) was associated with the hyperandrogenism in follicular fluid (FF). METHODS We recruited infertile women with PCOS (n = 14) and infertile women with tubal blockage (controls, n = 31) for this study. We examined total testosterone (TT), free androgen index (FAI), sex hormone-binding globulin (SHBG), FSH, LH and estradiol in FF. Real-time PCR and western blotting were performed to assess AQP-9 expression in GCs, including effects of dihydrotestosterone (DHT) in vitro. RESULTS AQP-9 protein was localized in the nucleus, cytoplasm and cell membrane of the human GCs. The TT, FAI and LH levels were all higher, and SHBG levels lower, in the FF of women with PCOS versus controls (P = 0.0145, 0.0001, 0.0191, 0.0001, respectively). AQP-9 mRNA level in GCs of patients with PCOS was tightly correlated with the TT, SHBG levels and FAI in FF (P = 0.0020, 0.0001, 0.0020, respectively). In vitro, DHT (10(-9) mol/l) decreased AQP-9 mRNA (lowest at 12 h) and protein levels in control GCs (P = 0.0005, 0.0247, respectively). The inhibitory effect of DHT on AQP-9 mRNA was attenuated by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor (P = 0.0013). Fifty micromolar 4-(hydroxymercuri) benzoic acid sodium salt (PMB) and 10(-9) mol/l DHT blunted the swelling of GCs in hypotonic medium, respectively (P = 0.0350, 0.0027). CONCLUSION Hyperandrogenism in FF of women with PCOS inhibited AQP-9 in GCs through the PI3K pathway.
Ovarian localization
Oocyte, Granulosa
Comment
Expression of aquaporin 1, 5 and 9 in the ovarian follicles of cycling and early pregnant pigs. Skowronska A et al. (2014) Aquaporins (AQPs) are water channel proteins responsible for water homeostasis and important for proper functioning of all body systems, including reproductive structures. This study was designed to determine their localization and quantitative changes in the pig ovary during different stages of the estrous cycle and early pregnancy. The expression of AQP 1, 5 and 9 proteins was determined by immunocytochemistry and Western blot analyses. AQP1 was found in the plasma membranes of capillary endothelium, AQP5 - in the plasma membranes of granulosa cells of developing follicles and flattened follicle cells of the primordial follicles, and AQP9 - in granulosa cells of the developing follicles. In the cyclic pigs, the expression of AQP1 and 5 proteins was the highest on Days 18-20, but did not change significantly between Days 2-4, 10-12 and 14-16 of the cycle. In pregnant pigs (Days 14-16 and 30-32), the expression of AQP1 and 5 did not change and was similar to that observed during Days 10-12 and 14-16. In turn, AQP9 expression did not change between all studied periods. In conclusion, studied AQP are localized in different cells populations, the endothelial and granulosa cells, and AQP1 and 5 seem to be crucial for follicular development in pigs.//////////////////
J.L. Stanton et al 2001 reported a set of 840 mouse oocyte genes with well-matched
human homologues. The aquaporin 9 gene was found in the mouse oocyte EST.
GenBank contains 14 477 expressed sequence tags (EST) derived from mouse oocyte cDNA libraries: 3499 of these
are from two unfertilized oocyte libraries and 10 978 are from two fertilized oocyte libraries. Gene expression profiles
were obtained for these libraries by matching library EST to UniGene clusters. The 14 477 EST identified 4226
UniGenes. These were screened using HomoloGene to identify 1386 homologous UniGene clusters in two other species
with one of the matches being human. Within these human matches, 840 encoded named proteins, 223 encoded
hypothetical proteins, and 323 encoded clustered EST. The set of named genes provides the first step in establishing a
database of genes expressed in mouse oocytes and, by extension, human oocytes.
Follicle stages
Primary, Secondary, Antral, Preovulatory
Comment
Nisha A McConnell,et al 2002 reported that Growth and differentiation of the ovarian follicle occurs in two distinct phases. In the first phase, a primordial follicle develops into a pre-antral follicle through the proliferation of the granulosa cells. The second phase of development occurs as the fluid-filled antrum forms and expands in size. Formation and expansion of the antrum requires an influx of water which, hypothetically, may occur by movement through the interior of the cells (transcellular transport) or by movement around the follicular cells (pericellular transport). To assess the contribution of these mechanisms to follicular water permeability, antral follicles were incubated with 3H2O and 14 C-inulin (a complex sugar restricted to the extracellular compartment) and the resulting radioactivity entering the follicle assessed. Kinetic analysis indicated a time-dependent increase in both molecules, although by 10 minutes a significantly greater fraction of water had entered the follicle than inulin. Calculation of the rate of movement (fractional influx/minute, a measure of follicular permeability) indicated the follicle was 3.5-fold more permeable to water than inulin. These results suggest that water movement into an antral follicle occurs primarily by transcellular transport. To determine if transcellular processes are mediated by proteinaceous water channels, termed aquaporins, follicles were pre-incubated for 25 minutes with 50 mM HgCl2 (a nonspecific aquaporin inhibitor) and the resulting permeability to H2O and inulin determined by our assay. In this experiment, HgCl2 had very little effect on inulin movement, but decreased H2O transport levels to that of inulin. These results suggest that H2 O enters a developing antrum primarily by passing through aquaporins in the plasma membrane of the follicular cells. To assess the functional presence of aquaporins in granulosa cells, we demonstrate that swelling of individual cells in response to a hypotonic insult is attenuated by preincubation with 50 mM HgCl2. Flow cytometry indicated the presence of aquaporins-7, -8, and -9 in granulosa cells, thus identifying candidate aquaporins to translocate water movement into an antral follicle. Together, these results suggest that the water permeability of an antral follicle occurs primarily through a transcellular mechanism, which may be mediated by the functional presence of aquaporins-7, -8, and -9 in rat granulosa cells.
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
1 mutations
Species: human
Mutation name: type: naturally occurring fertility: subfertile Comment: The role of aquaporins in polycystic ovary syndrome - A way towards a novel drug target in PCOS. Wawrzkiewicz-Jałowiecka A et al. (2017) Aquaporins (AQPs) are transmembrane proteins, able to transport water (and in some cases also small solutes, e. g. glycerol) through the cell membrane. There are twelve types of aquaporins (AQP1-AQP12) expressed in mammalian reproductive systems. According to literature, many diseases of the reproductive organs are correlated with changes of AQPs expression and their malfunction. That is the case in the polycystic ovary syndrome (PCOS), where dysfunctions of AQPs 7-9 and alterations in its levels occur. In this work, we postulate how AQPs are involved in PCOS-related disorders, in order to emphasize their potential therapeutic meaning as a drug target. Our research allows for a surprising inference, that genetic mutation causing malfunction and/or decreased expression of aquaporins, may be incorporated in the popular insulin-dependent hypothesis of PCOS pathogenesis. What is more, changes in AQP's expression may affect the folliculogenesis and follicular atresia in PCOS.//////////////////