Increased female fertility in aquaporin 8‐deficient mice

Abstract

SummaryAquaporin-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 2/2 mothers compared with wild-type mothers in crossmating experiments. Comparison of ovulation in the two genotypes demonstrated that AQP8 2/2 ovaries released more oocytes (9.5 6 1.9 vs. 7.1 6 2.1 in normal ovulation and 37.8 6 6.7 vs. 27.9 6 5.7 in superovulation). Histological analysis showed increased number of corpus luteums in mature AQP8 2/2 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 AQP82/2 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 AQP82/2 mice. The results indicated significantly lower apoptosis rate in AQP8 2/2 granulosa cells (21.3 6 3.6% vs. 32.6 6 4.3% in AQP81/1 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. IUBMBIUBMB Life, 62(11): 852-857, 2010

Pregnant phenotype in aquaporin 8-deficient mice

“…In the reproductive system, AQP8 is strongly expressed in the testis and sperm in the male and in the ovary, oviduct, uterus, placenta, amnion, chorion and cervix in the female [16][17][18][19][20][21][22][23][24][25] . While an earlier study [26] of AQP8 null mice reported no significant differences in comparison to wild type controls with the exceptions of an increase in testicular volume and a reduction in water permeability within the testes, we observed that AQP8 deficiency increased the number of mature follicles and the resulting fertility of female mice [27] . The present study aims to survey the role of AQP8 during pregnancy in AQP8-KO mice.…”

“…Furthermore, while embryo number progressively decreased with advancing gestational age in both groups, embryo number was greater in the AQP8-KO group compared to wild type, with a comparable incidence of atrophic embryos. These results may be associated with an increase in follicular maturation and ovulation, as an increase in corpus luteum number has previously been reported in mature AQP8-KO ovaries [27] .…”

“…The reproductive impact of AQP8 deficiency has been addressed previously. Yang et al [26] reported that the weight and size of the testes in AQP8-KO mice were remarkably elevated, and a recent study [27] from our laboratory has shown elevated fertility in female AQP8-KO mice. Consistent with these studies, data presented here suggested an AQP8-mediated effect on female fertility.…”

“…Our previous study [27] suggested that AQP8-KO mice displayed a greater number of mature follicles via reduced granulosa cell apoptosis, thus increasing the fertility of female mice. However, it remains unclear whether the findings reported here, namely, elevation in fetal/neonatal weight, amount of amniotic fluid and placental weight, are related to reduced apoptosis of placental cells.…”

“…Regarding our research, the number of embryos per female was elevated in AQP8-KO mice, as were fetal/neonatal weights, without post-term delivery. The rise in number of embryos per female may be associated with an increase in follicular maturation and ovulation in AQP8-KO mice [27] , and the increase in amniotic fluid and larger placentas may provide a superior environment in utero as well as more nutrients to the fetuses to allow higher fetal/neonatal weights.…”