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Comment |
Water permeability of an ovarian antral follicle is predominantly transcellular and mediated by aquaporins. McConnell NA et al. Ovarian folliculogenesis is characterized, in part, by the formation and expansion of the fluid-filled antrum. Development of this cavity requires water influx, which may occur by transcellular or pericellular transport mechanisms. To assess the contribution of these mechanisms to the water permeability of an antral follicle, the rate of (3)H(2)O and (14)C-inulin (a complex sugar restricted to the extracellular compartment) uptake into isolated follicles was determined. The rate of H(2)O movement was 3.5-fold greater than that of inulin, suggesting that water enters a follicle primarily by transcellular pathways. Preincubation of the follicles with 50 microM HgCl(2) [a nonspecific aquaporin (Aqp) inhibitor] decreased H(2)O movement to levels seen with inulin, indicating that transcellular water movement is mediated through Aqp. To demonstrate the functional presence of Aqp in granulosa cells, we show that swelling in response to a hypotonic insult is attenuated by preincubation with 50 microM HgCl(2). Flow cytometry demonstrated the presence of Aqps-7, -8, and -9, thus identifying candidate Aqp potentially mediating water movement into antral follicles. These results suggest that water permeability of antral follicles occurs primarily through transcellular mechanisms, which may be mediated by Aqps -7, -8, and/or -9 in granulosa cells.
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Mutations |
2 mutations
Species: mouse
Mutation name: None
type: null mutation
fertility: fertile
Comment: Increased female fertility in aquaporin 8-deficient mice. Su W et al.
Occurrence of multi-oocyte follicles in aquaporin 8-deficient mice. Su W 2013 et al.
BACKGROUND
Granulosa cells play a key role in folliculogenesis and female reproduction. Our previous study demonstrated that water channel aquaporin-8 (AQP8) is expressed in mouse follicular granulosa cells and is an important determinant of granulosa cell apoptosis and follicular maturation. More roles of AQP8 in folliculogenesis remain to be determined.
FINDINGS
The present study reports the increased occurrence of multi-oocyte follicles (MOFs) in ovaries of AQP8 knockout mice. The MOFs in AQP8-deficient ovaries contained two or three oocytes, and distributed at various follicle stages including primary (12.5%), secondary (50%), antral (18.8%) and atretic (18.8%) follicles in 5-week ovaries. The MOF is occasionally seen in wild-type ovary only in primary and secondary follicles. The number of MOFs in AQP8-deficient ovary reduced with age (26.7 +/- 5.2 per ovary at 5 weeks old, 14 +/- 5.5 at 10 weeks old, and 3.3 +/- 5.1 at 20 weeks old). mRNA expression of AQP5, AQP7, AQP8, AQP11 and AQP12 was detected in neonatal mouse ovaries and in granulosa cells in 4 week old mouse ovaries. The expression of AQP7, AQP11 and AQP12 mRNAs are decreased significantly in neonatal AQP8-deficient ovaries, whereas AQP5 mRNA expression remains unchanged.
CONCLUSIONS
The emergence of MOFs is associated with AQP8 deficiency. The study suggested the involvement of AQP8 in the formation of follicles and provided new insight into the molecular mechanisms of folliculogenesis.
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Aquaporin-8 (AQP8) is a water channel expressed extensively in male and female reproductive systems. But its physiological functions are largely unknown. In the present study, we first found significantly increased number of offspring delivered by AQP8(-/-) mothers compared with wild-type mothers in cross-mating experiments. Comparison of ovulation in the two genotypes demonstrated that AQP8(-/-) ovaries released more oocytes (9.5 ? 1.9 vs. 7.1 ? 2.1 in normal ovulation and 37.8 ? 6.7 vs. 27.9 ? 5.7 in superovulation). Histological analysis showed increased number of corpus luteums in mature AQP8(-/-) ovaries, suggesting increased maturation and ovulation of follicles. By RT-PCR, western blot and immunohistochemistry analyses, we determined the expression of AQP8 in
mouse ovarian granulosa cells. Granulosa cells isolated from AQP8(-/-) mice showed 45% of decreased membrane water permeability than wild-type mice. As the atresia of ovarian follicles is primarily due to apoptosis of granulosa cells, we analyzed the apoptosis of isolated granulosa cells from wild-type and AQP8(-/-) mice. The results indicated significantly lower apoptosis rate in AQP8(-/-) granulosa cells (21.3 ? 3.6% vs. 32.6 ? 4.3% in AQP8(+/+) granulosa cells). Taken together, we conclude that AQP8 deficiency increases the number of mature follicles by reducing the apoptosis of granulosa cells, thus increasing the fertility of female mice. This discovery may offer new insight of improving female fertility by reducing granulosa cell apoptosis through AQP8 inhibition. ? IUBMB IUBMB Life, 62(11): 852-857, 2010.
Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Association of AQP8 in women with PCOS. Li Y 2013 et al.
Aquaporin 8 (AQP8) has been identified as a novel gene participating in female reproductive physiology. The present study was designed to determine whether an association exists between AQP8 and polycystic ovary syndrome (PCOS). This study recruited 192 women with PCOS and 191 controls. High-resolution melting and sequencing were employed to investigate the genotypes of six single-nucleotide polymorphisms within AQP8 (rs7198838, rs1076973, rs1076974, rs2287797, rs2287798 and rs2287796). A significant difference was found in rs2287798 between PCOS cases and controls (P=0.0007). Possible associations between AQP8 genotypes and three different phenotypes of this syndrome were investigated. The results support the earlier evidence for a possible role of AQP8 in the pathogenesis of PCOS. Further studies are still needed to elucidate its functional role. Aquaporin 8 (AQP8) has been identified as a novel gene participating in female reproductive physiology. The present study was designed to determine whether there is an association between AQP8 and polycystic ovary syndrome (PCOS). This study recruited 192 women with PCOS and 191 controls. High-resolution melting and sequencing were employed to investigate the genotypes of six single-nucleotide polymorphisms within AQP8 (rs7198838, rs1076973, rs1076974, rs2287797, rs2287798 and rs2287796). We observed a significant difference in allele frequency of rs2287798 between PCOS cases and controls (P=0.0007). The possible association between AQP8 genotypes and three different phenotypes of this syndrome in this locus were investigated. Our results support the earlier evidence for a possible role of AQP8 in the pathogenesis of PCOS. Further studies are still needed to elucidate its functional role.
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