Expressions of aquaporin family in human luteinized granulosa cells and their correlations with IVF outcomes

Abstract

Objective: The purpose of this study was to investigate the association between mRNA for specific aquaporins (AQPs) expressed in human luteinized granulosa cells (GCs) and their expression levels, and in vitro fertilization (IVF) outcomes. Methods: Prospective observational study involving 111 women undergoing a stimulated IVF cycle was performed. Luteinized GCs were obtained at the time of oocyte retrieval. The mRNA expressions of AQP0-12 were explored by RT-PCR in GCs from another 27 women, and mRNAs for AQP0, 8 and 10 were not detected. Real-time quantitative RT-PCR (qRT-PCR) was performed to quantify mRNA level of AQP1-7, 9, 11, and 12. The mRNA for luteinizing hormone receptor (LHR) and steroidogenic acute regulatory protein (StAR) were also quantified by qRT-PCR. Results: In samples from 111 women, retrieved oocyte number was negatively associated with the mRNA levels of AQP1, 4, 6, and 11 and LHR (r = -0.311, r = -0.233, r = -0.203, r = -0.194, and r = -0.202, respectively, p<0.05 for each), however, after adjustment for womans age and serum anti-müllerian hormone (AMH) levels, only correlation with AQP1 was found (r = -0.299, p<0.05). Body mass index was negatively associated (after adjustment of age) with the mRNA level of AQP7 (r = -0.259, p<0.05). The fertilization rate was i positively associated with the mRNA level of AQP7 (r=0.269, p<0.05). The number or quality of embryos or clinical pregnancy was not associated with the mRNA levels of any of ten AQP subtypes. The mRNA levels for the ten AQP subtypes were correlated positively with LHR expression but negatively with StAR expression. Amongst high responders (oocyte number ≥14), the mRNA levels of AQP11 (1.4 ± 0.7 versus 1.7 ± 0.6) and LHR (1.3 ± 0.7 versus 1.7 ± 0.7) were significantly lower in the group with PCOS than in the non-PCOS group. Conclusions: The mRNA of AQP1-7, 9, 11, and 12 was expressed in human luteinized GCs and mRNA level of AQP1 was negatively associated with retrieved oocyte number and mRNA level of AQP7 was positively associated with fertilization rate. AQP1 may be one of the factors that modulate individual ovarian response to exogenous gonadotropin. The mRNA level of AQP7 was positively associated with fertilization rate, which is a surrogate marker of oocyte competence, thus expression of AQP7 could be a marker for adequate folliculogenesis and healthy oocytes.