The role of meis1 in primitive and definitive hematopoiesis during zebrafish development

Background

The Meis1 protein represents an important cofactor for Hox and Pbx1 and is implicated in human and murine leukemias. Though much is known about the role of meis1 in leukemogenesis, its function in normal hematopoiesis remains largely unclear. Here we characterized the role of the proto-oncogene, meis1, during zebrafish primitive and definitive hematopoiesis.

Design and Methods

Zebrafish embryos were stained with o-dianisidine to detect hemoglobin-containing cells and Sudan black to quantify neutrophils. The numbers of other cells (scl-, gata1- and alas2-positive cells) were also quantified by measuring the corresponding stained areas of the embryos. We used anti-Meis1 antibody and whole mount immunohistochemistry to determine the pattern of expression of Meis1 during zebrafish development and then analyzed the functional role of Meis1 by knocking-down the meis1 gene.

Results

Using antisense morpholino oligomers to interrupt meis1 expression we found that, although primitive macrophage development could occur unhampered, posterior erythroid differentiation required meis1, and its absence resulted in a severe decrease in the number of mature erythrocytes. Furthermore a picture emerged that meis1 exerts important effects on later stages of erythrocyte maturation and that these effects are independent of gata1, but under the control of scl. In addition, meis1 morpholino knock-down led to dramatic single arteriovenous tube formation. We also found that knock-down of pbx1 resulted in a phenotype that was strikingly similar to that of meis1 knock-down zebrafish.

Conclusions

These results imply that meis1, jointly with pbx1, regulates primitive hematopoiesis as well as vascular development.     

Cyst aspiration or GnRH antagonist administration for ovarian cysts detected at the start of fresh in vitro fertilization cycles*

The primary objective of this study is to investigate the effect of transvaginal ultrasonogram (TVUS)-guided cyst aspiration or gonadotropin releasing hormone antagonist (GnRH-ant) administration for the management of solitary ovarian cysts detected at the start of in vitro fertilization (IVF) cycles on the outcomes of the same cycles. This is a single-center, retrospective, cohort study of patients who had TVUS-guided cyst aspiration or GnRH-ant treatment for ovarian cysts detected at the start of IVF during a 5-year period. Four hundred and three patients met inclusion criteria: 41 (10.2%) underwent cyst aspiration and 362 (89.2%) were treated with GnRH-ant. There was no difference in the demographics or baseline IVF cycle characteristics of the two groups. Patients treated with GnRH-ant had a longer duration of ovarian stimulation (10.8?±?3.45 days versus 9.05?±?4.06 days, p?=?0.003) and required higher gonadotropin doses (3887.7?±?1097.8?IU versus 3293.7?±?990.5?IU; p?=?0.01) compared with the cyst aspiration group. There was no difference in the clinical pregnancy (43.9% versus 41.4%), spontaneous miscarriage (9.76% versus 8.01%) and live birth (34.1% versus 33.4%) rates between the groups. Our findings suggest that cyst aspiration is comparable to GnRH-ant administration for the management of solitary ovarian cysts detected at the start of IVF cycles.