Aquaporins and (in)fertility: More than just water transport.

Aquaporins (AQPs) are a family of channel proteins that facilitate the transport of water and small solutes across biological membranes. They are widely distributed throughout the organism, having a number of key functions, some of them unexpected, both in health and disease. Among the various diseases in which AQPs are involved, infertility has been overlooked. According to the World Health Organization (WHO) infertility is a global public health problem with one third of the couples suffering from subfertility or even infertility due to male or female factors alone or combined. Thus, there is an urgent need to unveil the molecular mechanisms that control gametes production, maturation and fertilization-related events, to more specifically determine infertility causes. In addition, as more couples seek for fertility treatment through assisted reproductive technologies (ART), it is pivotal to understand how these techniques can be improved. AQPs are heterogeneously expressed throughout the male and female reproductive tracts, highlighting a possible regulatory role for these proteins in conception. In fact, their function, far beyond water transport, highlights potential intervention points to enhance ART. In this review we discuss AQPs distribution and structural organization, functions, and modulation throughout the male and female reproductive tracts and their relevance to the reproductive success. We also highlight the most recent advances and research trends regarding how the different AQPs are involved and regulated in specific mechanisms underlying (in)fertility. Finally, we discuss the involvement of AQPs in ART-related processes and how their handling can lead to improvement of infertility treatment.

Exogenous Supplementation of Silicon Improved the Recovery of Hyperhydric Shoots in Dianthus caryophyllus L. by Stabilizing the Physiology and Protein Expression.

Hyperhydricity is one of the major problems hindering in vitro propagation of Dianthus caryophyllus L. Silicon (Si) is a well-known beneficial element renowned for its stress amelioration properties in plants. This study has demonstrated the physiological and molecular mechanism behind the Si-mediated recovery from hyperhydricity in D. caryophyllus L. 'Green Beauty'. Four weeks old hyperhydric shoots obtained from temporary immersion system were cultured on the Murashige and Skoog medium supplemented with 0 (control), 1.8 mM, or 3.6 mM of potassium silicate (K2SiO3). After 2 weeks of culture, we observed only 20% of hyperhydric shoots were recovered in control. On the other hand hyperhydricity, shoot recovery percentage in 1.8 mM and 3.6 mM of Si were 44% and 36%, respectively. Shoots in control possessed higher lipid peroxidation rate compared to the Si treatments. Similarly, damaged stomata were detected in the control, while Si treatments restored the normal stomatal development. Expressions of superoxide dismutase, guaiacol peroxidase, and catalase varied between the control and Si treatments. Furthermore, a proteomic analysis showed that as compared with the control Si up-regulated 17 and 10 protein spots in abundance at 1.8 and 3.6 mM of Si, respectively. In comparison to the 3.6 mM, 1.8 mM of Si treatment up-regulated 19 proteins and down-regulated 7 proteins. Identified proteins were categorized into six groups according to their biological roles such as ribosomal binding, oxido-reduction, hormone/cell signaling, metal/ion binding, defense, and photosynthesis. The proteomic results revealed that Si actively involved in the various metabolisms to accelerate the recovery of the shoots from hyperhydricity. Thus, the outcomes of this study can be utilized for addressing the molecular insight of hyperhydricity and its recovery mechanism by the supplementation of Si. Therefore, we conclude that active involvement of Si in the regulation and signaling process of proteins at 1.8 mM concentration could be efficient to trigger the reclamation process of hyperhydric carnation shoots.

Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India.

We performed a genome-wide association study (GWAS) and a multistage meta-analysis of type 2 diabetes (T2D) in Punjabi Sikhs from India. Our discovery GWAS in 1,616 individuals (842 case subjects) was followed by in silico replication of the top 513 independent single nucleotide polymorphisms (SNPs) (P < 10⁻³) in Punjabi Sikhs (n = 2,819; 801 case subjects). We further replicated 66 SNPs (P < 10⁻4) through genotyping in a Punjabi Sikh sample (n = 2,894; 1,711 case subjects). On combined meta-analysis in Sikh populations (n = 7,329; 3,354 case subjects), we identified a novel locus in association with T2D at 13q12 represented by a directly genotyped intronic SNP (rs9552911, P = 1.82 × 10⁻8) in the SGCG gene. Next, we undertook in silico replication (stage 2b) of the top 513 signals (P < 10⁻³) in 29,157 non-Sikh South Asians (10,971 case subjects) and de novo genotyping of up to 31 top signals (P < 10⁻4) in 10,817 South Asians (5,157 case subjects) (stage 3b). In combined South Asian meta-analysis, we observed six suggestive associations (P < 10⁻5 to < 10⁻7), including SNPs at HMG1L1/CTCFL, PLXNA4, SCAP, and chr5p11. Further evaluation of 31 top SNPs in 33,707 East Asians (16,746 case subjects) (stage 3c) and 47,117 Europeans (8,130 case subjects) (stage 3d), and joint meta-analysis of 128,127 individuals (44,358 case subjects) from 27 multiethnic studies, did not reveal any additional loci nor was there any evidence of replication for the new variant. Our findings provide new evidence on the presence of a population-specific signal in relation to T2D, which may provide additional insights into T2D pathogenesis.

Effects of leptin on in vitro maturation, fertilization and embryonic cleavage after ICSI and early developmental expression of leptin (Ob) and leptin receptor (ObR) proteins in the horse.

BACKGROUND: The identification of the adipocyte-derived obesity gene product, leptin (Ob), and subsequently its association with reproduction in rodents and humans led to speculations that leptin may be involved in the regulation of oocyte and preimplantation embryo development. In mice and pigs, in vitro leptin addition significantly increased meiotic resumption and promoted preimplantation embryo development in a dose-dependent manner. This study was conducted to determine whether leptin supplementation during in vitro maturation (IVM) to horse oocytes could have effects on their developmental capacity after fertilization by IntraCytoplasmic Sperm Injection (ICSI). METHODS: Compact and expanded-cumulus horse oocytes were matured in medium containing different concentrations (1, 10, 100, 1000 ng/ml) of recombinant human leptin and the effects on maturation, fertilization and embryo cleavage were evaluated. Furthermore, early developmental expression of Ob and leptin receptor (Ob-R) was investigated by immunocytochemical staining. RESULTS: In expanded-cumulus oocytes, the addition of leptin in IVM medium improved maturation (74% vs 44%, for 100 ng/ml leptin-treated and control groups, respectively; P < 0.05) and fertilization after ICSI (56% vs 23% for 10 ng/ml leptin-treated and control groups, respectively; P < 0.05). However, the developmental rate and quality of 8-cell stage embryos derived from leptin-treated oocytes (100 ng/ml) was significantly reduced, in contrast to previous data in other species where leptin increased embryo cleavage. Ob and Ob-R proteins were detected up to the 8-cell stage with cortical and cytoplasmic granule-like distribution pattern in each blastomere. CONCLUSION: Leptin plays a cumulus cell-mediated role in the regulation of oocyte maturation in the mare. Species-specific differences may exist in oocyte sensitivity to leptin.