Retained fetal bone post abortion causing infertility

Fetal bone retention is a rare but under-diagnosed complication after abortion. If left untreated, it can cause menstrual dysfunction and secondary infertility. We present a case of a 39 year old woman who undergone abortion 20 years ago but suffered with secondary infertility due to retained fetal bone.

Molecular Modulation of Fetal Liver Hematopoietic Stem Cell Mobilization into Fetal Bone Marrow in Mice

Development of hematopoietic stem cells is a complex process, which has been extensively investigated. Hematopoietic stem cells (HSCs) in mouse fetal liver are highly expanded to prepare for mobilization of HSCs into the fetal bone marrow. It is not completely known how the fetal liver niche regulates HSC expansion without loss of self-renewal ability. We reviewed current progress about the effects of fetal liver niche, chemokine, cytokine, and signaling pathways on HSC self-renewal, proliferation, and expansion. We discussed the molecular regulations of fetal HSC expansion in mouse and zebrafish. It is also unknown how HSCs from the fetal liver mobilize, circulate, and reside into the fetal bone marrow niche. We reviewed how extrinsic and intrinsic factors regulate mobilization of fetal liver HSCs into the fetal bone marrow, which provides tools to improve HSC engraftment efficiency during HSC transplantation. Understanding the regulation of fetal liver HSC mobilization into the fetal bone marrow will help us to design proper clinical therapeutic protocol for disease treatment like leukemia during pregnancy. We prospect that fetal cells, including hepatocytes and endothelial and hematopoietic cells, might regulate fetal liver HSC expansion. Components from vascular endothelial cells and bones might also modulate the lodging of fetal liver HSCs into the bone marrow. The current review holds great potential to deeply understand the molecular regulations of HSCs in the fetal liver and bone marrow in mammals, which will be helpful to efficiently expand HSCs in vitro.

Ultrastructure of the Adult Hematopoietic Stem Cell Niche Defined Using Correlative Light and Electron Microscopy

Hematopoietic stem and progenitor cells (HSPCs) that originate from the hemogenic endothelium in the dorsal aorta finally home and engraft within the adult niche, the fetal bone marrow. Within the bone marrow, HSPCs are retained in a complex microenvironment surrounded by niche cells such as megakaryocytes, peripheral nerves, endothelial and mesenchymal stromal cells. While it is known that niche cells secrete hematopoietic factors that are essential for HSPCs to self-renew and repopulate the blood lineages, the ultrastructure of this niche is not well defined as current imaging technology does not allow direct visualization of the fetal bone marrow niche. Zebrafish share a similar hematopoietic ontogeny to mammals, and because the embryos are transparent, intrinsic HSPC interactions with the niche can be directly visualized. To precisely locate rare HSPCs within the large dense kidney marrow, the presumptive adult niche, we genetically tagged endogenous HSPCs to track them live using lightsheet microscopy, followed by high-resolution serial block-face scanning electron microscopy (SBEM) (XY = 10.8 nm/pixel, Z = 70 nm/pixel). Using this technique, we could visually track single mCherry+ HSPCs, then confirm their exact location in the SBEM dataset with high contrast APEX2 peroxidase label. We found HSPC clusters within vessel lumens, as well as single HSPC in a novel perivascular niche. In this perivascular site, a single HSPC simultaneously contacted one mesenchymal stromal cell, multiple endothelial cells, a glial-like cell, and other hematopoietic cells. After extensive tracing of the glial-like cells within the 3D SBEM data, we identified that these cells extended as a long chain and formed contact with HSPCs. Our search for candidate structures in the kidney marrow region suggested that the glial-like cells could be dopamine beta-hydroxylase positive (dbh+) cells. Through fluorescence imaging, we observed cytoplasmic projections extending from dbh+ cells into Runx+ HSPC clusters. To confirm the identity of these glial-like cells, we performed fluorescence imaging of dbh+ transgenic larvae followed by SBEM. By correlating the two datasets, we identified dbh+ glial-like cell in contact with a single HSPC in the niche. Furthermore, treatment with a neurotoxin, 6-hydroxydopamine, led to a significant reduction in HSPC numbers within the niche highlighting the biological significance of dbh+ cells. In summary, through this approach, we could identify a previously unknown cell type within the zebrafish adult hematopoietic niche that is pivotal in maintaining the HSPC pool. Our finding validates the importance of having multiple niche cells that concurrently regulate HSPCs within their niche. Importantly, our approach can be applied to characterize the ultrastructure of rare cells, such as other stem cells, and their niche by using multiple imaging modalities and can also lead to the identification of previously uncharacterized cell types. Further, we can now identify novel intercellular structures that form between an unperturbed HSPC in its endogenous perivascular niche. Disclosures No relevant conflicts of interest to declare.

Nanoparticles from Equine Fetal Bone Marrow-Derived Cells Enhance the Survival of Injured Chondrocytes

Recent studies have shown that mesenchymal stem cells (MSCs) can play a restorative role against degenerative joint diseases in horses. The purpose of this study was to investigate whether fetal bone marrow-derived cells (BMC)-derived nanoparticles (BMC-NPs) can stimulate the survival of equine chondrocytes. Equine fetal BMCs were isolated and characterized, and the role of BMC-NPs s in equine chondrocytes undergoing inflammatory cell death was examined. BMCs have several characteristics, such as the potential to differentiate into chondrocytes and osteocytes. Additionally, BMCs expressed immunoregulatory genes in response to treatment with tumor necrosis factor-alpha (TNF-α) and Interleukin 1 beta (IL-1β). We found that BMC-NPs were taken up by equine chondrocytes. Functionally, BMC-NPs promoted the growth of chondrocytes, and reduced apoptosis induced by inflammatory cytokines. Furthermore, we observed that BMC-NPs upregulated the phosphorylation of protein kinase B (Akt) in the presence of IL-1β, and reduced the phosphorylation of TNF-α-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the chondrocytes. Cumulatively, our study demonstrated that equine fetal BMC-NPs have the potential to stimulate the survival of chondrocytes damaged by inflammatory cytokines. Thus, BMC-NPs may become an alternative cell-free allogenic therapeutic for degenerative joint diseases in horses.

Periconception maternal low-protein diet adversely affects male mouse fetal bone growth and mineral density quality in late gestation

Adverse programming of adult non-communicable disease can be induced by poor maternal nutrition during pregnancy and the periconception period has been identified as a vulnerable period. In the current study, we used a mouse maternal low-protein diet fed either for the duration of pregnancy (LPD) or exclusively during the preimplantation period (Emb-LPD) with control nutrition provided thereafter and postnatally to investigate effects on fetal bone development and quality. This model has been shown previously to induce cardiometabolic and neurological disease phenotypes in offspring. Micro 3D computed tomography examination at fetal stages Embryonic day E14.5 and E17.4, reflecting early and late stages of bone formation, demonstrated LPD treatment caused increased bone formation of relative high mineral density quality in males, but not females, at E14.5, disproportionate to fetal growth, with bone quality maintained at E17.5. In contrast, Emb-LPD caused a late increase in male fetal bone growth, proportionate to fetal growth, at E17.5, affecting central and peripheral skeleton and of reduced mineral density quality relative to controls. These altered dynamics in bone growth coincide with increased placental efficiency indicating compensatory responses to dietary treatments. Overall, our data show fetal bone formation and mineral quality is dependent upon maternal nutritional protein content and is sex-specific. In particular, we find the duration and timing of poor maternal diet to be critical in the outcomes with periconceptional protein restriction leading to male offspring with increased bone growth but of poor mineral density, thereby susceptible to later disease risk.