Sphingosine-1-phosphate (S1P) analog phytosphingosine-1-phosphate (P1P) improves the in vitro maturation efficiency of porcine oocytes via regulation of oxidative stress and apoptosis.

Phytosphingosine-1-phosphate (P1P) is a signaling sphingolipid that regulates various physiological activities. However, little is known about the effect of P1P in the context of reproduction. Thus, we aimed to investigate the influence of P1P on oocyte maturation during porcine in vitro maturation (IVM). Here, we report the expression of S1PR1-3 among P1P receptors (S1PR1-4) in cumulus cells and oocytes. When P1P was administered at concentrations of 10, 50, 100, and 1,000 nM during IVM, the metaphase II rate was significantly increased in the 1,000 nM (1 µM) P1P treatment group. Maturation rate improvement by P1P supplementation was observed only in the presence of epidermal growth factor (EGF). Oocytes under the influence of P1P showed decreased intracellular reactive oxygen species levels but no significant differences in glutathione levels. In our molecular studies, P1P treatment upregulated gene expression involved in cumulus expansion (Has2 and EGF), antioxidant enzymes (SOD3 and Cat), and developmental competence (Oct4) while activating extracellular signal-regulated kinase1/2 and Akt signaling. P1P treatment also influenced oocyte survival by shifting the ratio of Bcl-2 to Bax while inactivating JNK signaling. We further demonstrated that oocytes matured with P1P displayed significantly higher developmental competence (cleavage and blastocyst [BL] formation rate) and greater BL quality (total cell number and the ratio of apoptotic cells) when activated via parthenogenetic activation (PA) and in vitro fertilization. Despite the low levels of endogenous P1P found in animals, exogenous P1P influenced animal reproduction, as shown by increased porcine oocyte maturation as well as preimplantation embryo development. This study and its findings are potentially relevant for both human and animal-assisted reproduction.

Roles of Runx Genes in Nervous System Development.

Runt-related (Runx) transcription factors play essential roles during development and adult tissue homeostasis and are responsible for several human diseases. They regulate a variety of biological mechanisms in numerous cell lineages. Recent years have seen significant progress in our understanding of the functions performed by Runx proteins in the developing and postnatal mammalian nervous system. In both central and peripheral nervous systems, Runx1 and Runx3 display remarkably specific expression in mostly non-overlapping groups of postmitotic neurons. In the central nervous system, Runx1 is involved in the development of selected motor neurons controlling neural circuits mediating vital functions such as chewing, swallowing, breathing, and locomotion. In the peripheral nervous system, Runx1 and Runx3 play essential roles during the development of sensory neurons involved in circuits mediating pain, itch, thermal sensation and sense of relative position. Runx1 and Runx3 orchestrate complex gene expression programs controlling neuronal subtype specification and axonal connectivity. Runx1 is also important in the olfactory system, where it regulates the progenitor-to-neuron transition in undifferentiated neural progenitor cells in the olfactory epithelium as well as the proliferation and developmental maturation of specific glial cells termed olfactory ensheathing cells. Moreover, upregulated Runx expression is associated with brain injury and disease. Increasing knowledge of the functions of Runx proteins in the developing and postnatal nervous system is therefore expected to improve our understanding of nervous system development, homeostasis and disease.

Transcriptional regulation of mouse hypoglossal motor neuron somatotopic map formation.

Somatic motor neurons in the hypoglossal nucleus innervate tongue muscles controlling vital functions such as chewing, swallowing and respiration. Formation of functional hypoglossal nerve circuits depends on the establishment of precise hypoglossal motor neuron maps correlating with specific tongue muscle innervations. Little is known about the molecular mechanisms controlling mammalian hypoglossal motor neuron topographic map formation. Here we show that combinatorial expression of transcription factors Runx1, SCIP and FoxP1 defines separate mouse hypoglossal motor neuron groups with different topological, neurotransmitter and calcium-buffering phenotypes. Runx1 and SCIP are coexpressed in ventromedial hypoglossal motor neurons involved in control of tongue protrusion whereas FoxP1 is expressed in dorsomedial motor neurons associated with tongue retraction. Establishment of separate hypoglossal motor neuron maps depends in part on Runx1-mediated suppression of ventrolateral and dorsomedial motor neuron phenotypes and regulation of FoxP1 expression pattern. These findings suggest that combinatorial actions of Runx1, SCIP and FoxP1 are important for mouse hypoglossal nucleus somatotopic map formation.