Liraglutide modulates adhesion molecules and enhances cell properties in three-dimensional cultures of olfactory ensheathing cells.

Cell transplantation using olfactory ensheathing cells (OECs) is a promising approach for nerve repair but there are numerous limitations with their delivery method. Three-dimensional (3D) cell culture systems potentially offer a powerful approach for cell production and delivery options. To further optimise the use of OECs, strategies to promote cell viability and maintain cell behaviours in 3D cultures become important. We previously demonstrated an anti-diabetic drug, liraglutide, could modulate OEC migration and re-model extracellular matrix in two-dimensional (2D) cultures. In the present study, we further investigated its beneficial effects in our 3D culture system using primary OECs. OECs treated with liraglutide at 100 nM showed improved cell viability and had modulated expression of N-cadherin and ß1-integrin (two important cell adhesion molecules). When formed into 3D spheroids, the pre-treated OECs generated spheroids with an increased volume and a decreased cell density compared to control spheroids. OECs that subsequently migrated out of the liraglutide pre-treated spheroids had higher capacity for migration with increased duration and length, which was attributed to a reduction in the pauses during the migration. Moreover, OECs that migrated out from liraglutide spheroids had a more bipolar morphology consistent with higher migratory capacity. In summary, liraglutide improved the viability of OECs, modulated cell adhesion molecules, and resulted in stable 3D cell constructs which conferred enhanced migratory capacity on the OECs. Overall, liraglutide may potentially improve the therapeutic use of OECs for neural repair by enhancing the generation of stable 3D constructs and increasing the migratory behaviour of OECs.

The role of Amh signaling in teleost fish--Multiple functions not restricted to the gonads.

This review summarizes the important role of Anti-Müllerian hormone (Amh) during gonad development in fishes. This Tgfß-domain bearing hormone was named after one of its known functions, the induction of the regression of Müllerian ducts in male mammalian embryos. Later in development it is involved in male and female gonad differentiation and extragonadal expression has been reported in mammals as well. Teleosts lack Müllerian ducts, but they have amh orthologous genes. amh expression is reported from 21 fish species and possible regulatory interactions with further factors like sex steroids and gonadotropic hormones are discussed. The gonadotropin Fsh inhibits amh expression in all fish species studied. Sex steroids show no consistent influence on amh expression. Amh is produced in male Sertoli cells and female granulosa cells and inhibits germ cell proliferation and differentiation as well as steroidogenesis in both sexes. Therefore, Amh might be a central player in gonad development and a target of gonadotropic Fsh. Furthermore, there is evidence that an Amh-type II receptor is involved in germ cell regulation. Amh and its corresponding type II receptor are also present in brain and pituitary, at least in some teleosts, indicating additional roles of Amh effects in the brain-pituitary-gonadal axis. Unraveling Amh signaling is important in stem cell research and for reproduction as well as for aquaculture and in environmental science.

The social status of the male Nile tilapia (Oreochromis niloticus) influences testis structure and gene expression.

Dominant and territorial behaviour are known social phenomena in cichlids and social stress influences reproduction and growth. The gonadotropic hormones trigger spermatogenesis and subordinate males have typically lower levels of gonadotropins than dominant males. In this study, we compared testis morphology and gene expression of dominant and subordinate Nile tilapia males (d- and s-males) in socially stable communities. The d-males had the highest gonadosomatic index but they were not the largest animals in the majority of studied cases. Long-term d-males showed large groups of Leydig cells and hyperplasia of the tunica albuginea due to numerous cytochrome-P450-11ß-hydroxylase (Cyp11b) expressing myoid cells. Increased Cyp11b expression in d-males was reflected by elevated 11-ketotestosterone plasma values. However, immunofluorescence microscopy and expression analysis of selected genes revealed that most s-males conserved their capability for spermatogenesis and are, therefore, ready for reproduction when the social environment changes. Moreover, in s-males gene expression analysis by quantitative RT-PCR showed increased transcript levels for germ line-specific genes (vasa, sox2 and dmc1) and Sertoli-specific genes (amh, amhrII and dmrt1) whereas gene expression of key factors for steroid production (sf1 and cyp11b) were reduced. The Nile tilapia is a promising model to study social cues and gonadotropic signals on testis development in vertebrates.