@article {88083,
	title = {In search of signaling pathways critical for ovarian graft reception: Akt1 is essential for long-term survival of ovarian grafts},
	journal = {Fertil Steril},
	volume = {101},
	year = {2014},
	month = {2014 Feb},
	pages = {536-44},
	abstract = {OBJECTIVE: To explore the role of Akt1, a principle modulator of angiogenesis, in ovarian graft reception and to investigate whether Akt1 deficiency can alter ovarian graft reception.

DESIGN: Experimental mouse model.

SETTING: Research institute.

ANIMAL(S): Donors: Akt1 knockout (Akt1(-/-)) and wild types (Akt1(+/+)) mice. Recipients: CD-1 nude immune deficient female mice.

INTERVENTION(S): Ovaries from Akt1(-/-) and Akt1(+/+) mice transplanted in the biceps femoris muscle of immunocompromised CD-1 mice, and ovarian graft viability, perfusion, and revascularization explored in vivo by magnetic resonance imaging (MRI).

MAIN OUTCOME MEASURE(S): Vascular density and permeability of newly formed graft blood vessels quantified by dynamic contrast-enhanced MRI 7, 14, 30, and 60 days after grafting as indicators for angiogenesis and reestablishment of blood perfusion.

RESULT(S): The Akt1(-/-) ovarian grafts showed a gradual decrease in angiogenic response with time after transplantation, ultimately leading to complete or near-complete graft destruction coinciding with massive follicular loss. Sixty days after transplantation, the mean blood volume fraction (fBV) and vessel permeability (PS) were statistically significantly lower in Akt1(-/-) transplants compared with Akt1(+/+).

CONCLUSION(S): Akt1 is essential for ovarian graft reception. However, surprisingly the impact of Akt1 deficiency was most profound not in the early stages of angiogenesis but rather in long-term survival of the graft.},
	keywords = {Animals, Female, Graft Survival, Mice, Mice, Knockout, Mice, Nude, Neovascularization, Physiologic, Ovary, Proto-Oncogene Proteins c-akt, Signal Transduction, Time Factors},
	issn = {1556-5653},
	doi = {10.1016/j.fertnstert.2013.10.007},
	author = {Cohen, Yoni and Dafni, Hagit and Avni, Reut and Raz, Tal and Biton, Inbal and Hemmings, Brian and Neeman, Michal}
}
@article {88081,
	title = {Major mouse placental compartments revealed by diffusion-weighted MRI, contrast-enhanced MRI, and fluorescence imaging},
	journal = {Proc Natl Acad Sci U S A},
	volume = {111},
	year = {2014},
	month = {2014 Jul 15},
	pages = {10353-8},
	abstract = {Mammalian models, and mouse studies in particular, play a central role in our understanding of placental development. Magnetic resonance imaging (MRI) could be a valuable tool to further these studies, providing both structural and functional information. As fluid dynamics throughout the placenta are driven by a variety of flow and diffusion processes, diffusion-weighted MRI could enhance our understanding of the exchange properties of maternal and fetal blood pools--and thereby of placental function. These studies, however, have so far been hindered by the small sizes, the unavoidable motions, and the challenging air/water/fat heterogeneities, associated with mouse placental environments. The present study demonstrates that emerging methods based on the spatiotemporal encoding (SPEN) of the MRI information can robustly overcome these obstacles. Using SPEN MRI in combination with albumin-based contrast agents, we analyzed the diffusion behavior of developing placentas in a cohort of mice. These studies successfully discriminated the maternal from the fetal blood flows; the two orders of magnitude differences measured in these fluids{\textquoteright} apparent diffusion coefficients suggest a nearly free diffusion behavior for the former and a strong flow-based component for the latter. An intermediate behavior was observed by these methods for a third compartment that, based on maternal albumin endocytosis, was associated with trophoblastic cells in the interphase labyrinth. Structural features associated with these dynamic measurements were consistent with independent intravital and ex vivo fluorescence microscopy studies and are discussed within the context of the anatomy of developing mouse placentas.},
	keywords = {Animals, Contrast Media, Female, Magnetic resonance imaging, Mice, Optical Imaging, Placental Circulation, Pregnancy, Trophoblasts},
	issn = {1091-6490},
	doi = {10.1073/pnas.1401695111},
	author = {Solomon, Eddy and Avni, Reut and Hadas, Ron and Raz, Tal and Garbow, Joel Richard and Bendel, Peter and Frydman, Lucio and Neeman, Michal}
}
@inbook {88212,
	title = {MRI, Intra-vital, and Ex-vivo Fluorescence Microscopy of the Mouse Uterine Vasculature and Placenta},
	booktitle = {The Guide to Investigation of Mouse Pregnancy},
	year = {2014},
	abstract = {<p>MRI and fluorescence microscopy provide complementary information on the structure and function of placental blood vessels. Due to the highly effective fetal-maternal barrier, dynamic contrast enhanced MRI using macromolecular contrast media probes exclusively the maternal blood flow in the placenta, providing information on the rate of flow into the placenta. Arterial spin labeling follows the motion of water across the fetal-maternal barrier, and thus this approach can provide information on perfusion. Arterial spin labeling achieved by tagging water passing through the uterine versus the ovarian arterial input, provide directional information for the two blood supplies, and can also help in non invasive positioning of the embryos along the uterine horns. Fluorescence intravital and ex vivo imaging provides for faster dynamic analysis and validation of maternal blood volume respectively.</p>},
	author = {Avni, Reut and Raz, Tal and Neeman, Michal}
}
@inbook {88211,
	title = {Multimodal Imaging of the Mouse Placenta},
	booktitle = {The Guide to Investigation of Mouse Pregnancy},
	year = {2014},
	abstract = {<p>Multimodal imaging is an important part of the study of placenta structure and function, as well as embryonic development, particularly in transgenic mice. The development of novel imaging techniques can contribute significantly to enhance our understanding of placental structure, exchange within the placenta, as well as the architecture and function of the maternal and fetal vasculature system, all of which are critical in the evaluation of the dynamic relationships between the mother, placenta, and fetus during pregnancy. Recent progress of a number of imaging approaches is described herein, including non-invasive MRI, ultrasound imaging, fluorescence microscopy, and photoacoustic imaging. Applications of these techniques are used to monitor the details of blood-flow patterns in the uterine arteries, to measure placental perfusion, and to characterize angiogenesis and vascular permeability, providing insight into placental and fetal pathologies. All of these findings eventually provide a better appreciation for the unique properties of mammalian development and reproduction.</p>},
	author = {Raz, Tal and Avni, Reut and Neeman, Michal}
}
@article {88082,
	title = {Ovarian dendritic cells act as a double-edged pro-ovulatory and anti-inflammatory sword},
	journal = {Mol Endocrinol},
	volume = {28},
	year = {2014},
	month = {2014 Jul},
	pages = {1039-54},
	abstract = {Ovulation and inflammation share common attributes, including immune cell invasion into the ovary. The present study aims at deciphering the role of dendritic cells (DCs) in ovulation and corpus luteum formation. Using a CD11c-EYFP transgenic mouse model, ovarian transplantation experiments, and fluorescence-activated cell sorting analyses, we demonstrate that CD11c-positive, F4/80-negative cells, representing DCs, are recruited to the ovary under gonadotropin regulation. By conditional ablation of these cells in CD11c-DTR transgenic mice, we revealed that they are essential for expansion of the cumulus-oocyte complex, release of the ovum from the ovarian follicle, formation of a functional corpus luteum, and enhanced lymphangiogenesis. These experiments were complemented by allogeneic DC transplantation after conditional ablation of CD11c-positive cells that rescued ovulation. The pro-ovulatory effects of these cells were mediated by up-regulation of ovulation-essential genes. Interestingly, we detected a remarkable anti-inflammatory capacity of ovarian DCs, which seemingly serves to restrict the ovulatory-associated inflammation. In addition to discovering the role of DCs in ovulation, this study implies the extended capabilities of these cells, beyond their classic immunologic role, which is relevant also to other biological systems. },
	keywords = {Animals, Anti-Inflammatory Agents, Antigens, Differentiation, CD11c Antigen, Chorionic Gonadotropin, Corpus Luteum, Cumulus Cells, Dendritic Cells, Diphtheria Toxin, Female, inflammation, Lymphangiogenesis, Mice, Mice, Inbred C57BL, Mice, Transgenic, Oocytes, Ovarian Follicle, Ovary, Ovulation, Ovum, Progesterone},
	issn = {1944-9917},
	doi = {10.1210/me.2013-1400},
	author = {Cohen-Fredarow, Adva and Tadmor, Ari and Raz, Tal and Meterani, Naama and Addadi, Yoseph and Nava Nevo and Solomonov, Inna and Sagi, Irit and Mor, Gil and Neeman, Michal and Dekel, Nava}
}
