Cell and Developmental Biology Commons^™

Evidence For Two Mechanisms Of Amino Acid Osmolyte Release From Hippocampal Slices, R. Franco, M. E. Torres-Marquez, H. Pasantes-Morales

School of Veterinary and Biomedical Sciences: Faculty Publications

A 30% decrease in osmolarity stimulated ³H-taurine, ³H-GABA and glutamate (followed as ³H-D-aspartate) efflux from rat hippocampal slices. ³H-taurine efflux was activated rapidly but inactivated slowly. It was decreased markedly by 100 μM 5-nitro-(3-phenylpropylamino) benzoic acid (NPPB) and 600 μM niflumic acid and inhibited strongly by tyrphostins AG18, AG879 and AG112 (25–100 μM), suggesting a tyrosine kinase-mediated mechanism. Hyposmolarity activated the mitogen-activated protein kinases (MAPK) extracellular-signal-related kinase-1/2 (ERK1/ERK2) and p38, but blockade of this reaction did not affect ³H-taurine efflux. Hyposmosis also activated phosphatidyl-inositide 3-kinase (PI3K) and its prevention by wortmannin (100 nM) essentially abolished …

Genomic Diversity Of Pseudomonas Aeruginosa In Cystic Fibrosis, Nathaniel Edwards Head

Theses, Dissertations and Capstones

Pseudomonas aeruginosa is a common environmental microorganism. However, it has the genetic capacity to cause diseases in patients with compromised host defense systems. Cystic fibrosis (CF) is one of the major hereditary diseases among Caucasian populations. CF patients are born with a defective chloride channel that is responsible for maintaining fluid and electrolyte balance across the lumen of the lung. This imbalance leads to the production of an abnormal dehydrated viscous mucous, prohibiting the patient from normally clearing the respiratory airway. Chronic pulmonary infections with P. aeruginosa are the major causes of high morbidity and mortality in CF. Two of …

Antioxidation Activity Of Dhea And Its Mechanisms, Sun Yang, Han Rui

Pharmacy Faculty Articles and Research

Objective: The aim of this study was to determine the anti-oxidative activity of a new chemopreventive agent--dehydroepiandrosterone (DHEA), and the mechanisms of action by which DHEA protect the thymocytes and DNA from oxidative damage. Methods: Agarose gel electrophoresis, flow cytometry, single cel! gel electrophoresis, chemiluminescence assay, triazolyl blue tetrazolumbromide (MTT) colorimetry, and three dimensional collagen gel assay were used. Results: In agarose gel electrophoresis, 10 nmol/L DHEA blocked the typical DNA degradation (DNA Ladder) induced by H₂O₂. DHEA 2. 5 nmol/L and 10 nmol/L both significantly decreased the percentage of characteristic apoptotic DNA …

Receptor Number And Caveolar Co-Localization Determine Receptor Coupling Efficiency To Adenylyl Cyclase, Rennolds S. Ostrom, Caroline Gregorian, Ryan M. Drenan, Yang Xiang, John W. Regan, Paul A. Insel

Pharmacy Faculty Articles and Research

Recent evidence suggests that many signaling molecules localize in microdomains of the plasma membrane, particularly caveolae. In this study, overexpression of adenylyl cyclase was used as a functional probe of G protein-coupled receptor (GPCR) compartmentation. We found that three endogenous receptors in neonatal rat cardiomyocytes couple with different levels of efficiency to the activation of adenylyl cyclase type 6 (AC6), which localizes to caveolin-rich membrane fractions. Overexpression of AC6 enhanced the maximal cAMP response to β1-adrenergic receptor (β1AR)-selective activation 3.7-fold, to β2AR-selective activation only 1.6-fold and to prostaglandin E2 (PGE2) not at all. Therefore, the rank order of efficacy in …

Amino Acid Osmolytes In Regulatory Volume Decrease And Isovolumetric Regulation In Brain Cells: Contribution And Mechanisms, Herminia Pasantes-Morales, Rodrigo Franco, M. Eugenia Torres-Marquez, Karla Hernandez-Fonseca, Arturo Ortega

School of Veterinary and Biomedical Sciences: Faculty Publications

Brain adaptation to hyposmolarity is accomplished by loss of both electrolytes and organic osmolytes, including amino acids, polyalcohols and methylamines. In brain in vivo, the organic osmolytes account for about 35% of the total solute loss. This review focus on the role of amino acids in cell volume regulation, in conditions of sudden hyposmosis, when cells respond by active regulatory volume decrease (RVD) or after gradual exposure to hyposmotic solutions, a condition where cell volume remains unchanged, named isovolumetric regulation (IVR). The amino acid efflux pathway during RVD is passive and is similar in many respects to the volume-activated anion …

Induction Of Apoptosis In Human Prostate Cancer Cells By Resveratrol, Gary Zulfikar Morris

Chemistry & Biochemistry Theses & Dissertations

Recently attention has been brought to trans-resveratrol's {TR) anticancer activity, as determined through a number of cultured cancer cell models. This activity was attributed to TR behaving as an estrogen, and the orientation of TR' s hydroxyl groups. Based on this work it was of interest to determine whether TR would also be toxic in prostate cancer cells; if toxic, did TR induce necrosis or apoptosis in the cells; was it toxic through hormone mediated pathways; and were TR's hydroxyl groups responsible for its biological activity. To this end, cellular viability was assessed in two different prostate cancer cell …

Interactions Of Igf-Ii And Cathepsin D In Mcf-7 Breast Cancer Cells, Jesika S. Faridi

Loma Linda University Electronic Theses, Dissertations & Projects

A primary role of the IGF-II/M6P receptor is to target lysosomal enzymes from the golgi to the lysosomes. This receptor has distinct binding sites for IGF-II and M6P, however, reciprocal interactions between these ligands have been observed (Kiess et al. 1989, 1990). Since IGF-II modulates the routing of cathepsin D in MCF-7 cells by blocking the intracellular binding of cathepsin D to the IGF-II/M6P receptor (De León et al. 1996), we hypothesized that expressing a mutant form of IGF-II that does not bind the IGF-II/M6P receptor will not interfere with lysosomal enzyme trafficking.

In our present study, we report the …

An Ultrastructural Survey Of The Nuchal Glands Of Rhabdophis Tigrinus (Serpentes: Colubridae), Kathleen A. Roberts

Biological Sciences Theses & Dissertations

Rhabdophis tigrinus, an Asian natricine snake, possesses a series of integumentary glands located in the nuchal skin. Previous studies indicated that the nuchal glands are of mesodermal origin, contain cardiac steroids analogous to bufotoxins found in the parotoid glands of toads, which are included in the snake's diet. The nuchal glands are defensive in function. Preliminary histological studies revealed differences in quality of the gland tissue compared to previous studies, and difference in fixation techniques were suspected. Seven specimens of R. tigrinus were fixed by perfusion using a conservative fixation process standard for electron microscopy. The nuchal gland series …

Efflux Of Osmolyte Amino Acids During Isovolumic Regulation In Hippocampal Slices, Rodrigo Franco, Octavio Quesada, Herminia Pasantes-Morales

School of Veterinary and Biomedical Sciences: Faculty Publications

The efflux of potassium (K⁺) and amino acids from hippocampal slices was measured after sudden exposure to 10% (270 mOsm), 25% (225 mOsm) or 50% (150 mOsm) hyposmotic solutions or after gradual decrease (22.5 mOsm/min) in external osmolarity. In slices suddenly exposed to 50% hyposmotic solutions, swelling was followed by partial (74%) cell volume recovery, suggesting regulatory volume decrease (RVD). With gradual hyposmotic changes, no increase in cell water content was observed even when the solution at the end of the experiment was 50% hyposmotic, showing the occurrence of isovolumic regulation (IVR). The gradual decrease in osmolarity elicited …

Whole Animal And Cellular Strategies In The Regulation Of Bone Mass In The Rat, Weidong Geng

Theses, Dissertations and Capstones

In order to determine the strategies in regulation of bone mass in the rat and better understand the pathophysiological mechanism of the postmenopausal osteoporosis, a series of studies were conducted at the whole animal and cellular level. At the whole animal level, female Sprague-Dawley rats were ovariectomized (Ovx) or sham-operated (control) at 18 weeks and the entire skeleton obtained at 24 weeks (baseline) or after an additional 31 day (28 week) interval on a normal (1.0%) or deficient (0.02%) calcium diet. Ovx rats on the normal calcium diet showed a 42% increase in whole body bone resorption and a 70% …

The Skn7 Response Regulator Of Saccharomyces Cerevisiae Interacts With Hsf1 In Vivo And Is Required For The Induction Of Heat Shock Genes By Oxidative Stress, Desmond C. Raitt, Anthony L. Johnson, Alexander M. Erkine, Kozo Makino, Brian Morgan, David S. Gross, Leland H. Johnston

Scholarship and Professional Work – COPHS

The Skn7 response regulator has previously been shown to play a role in the induction of stress-responsive genes in yeast, e.g., in the induction of the thioredoxin gene in response to hydrogen peroxide. The yeast Heat Shock Factor, Hsf1, is central to the induction of another set of stress-inducible genes, namely the heat shock genes. These two regulatory trans-activators, Hsf1 and Skn7, share certain structural homologies, particularly in their DNA-binding domains and the presence of adjacent regions of coiled-coil structure, which are known to mediate protein–protein interactions. Here, we provide evidence that Hsf1 and Skn7 interact in vitro and …

Cell Cycle-Dependent Binding Of Yeast Heat Shock Factor To Nucleosomes, Christina Bourgeois Venturi, Alexander M. Erkine, David S. Gross

Scholarship and Professional Work – COPHS

In the nucleus, transcription factors must contend with the presence of chromatin in order to gain access to their cognate regulatory sequences. As most nuclear DNA is assembled into nucleosomes, activators must either invade a stable, preassembled nucleosome or preempt the formation of nucleosomes on newly replicated DNA, which is transiently free of histones. We have investigated the mechanism by which heat shock factor (HSF) binds to target nucleosomal heat shock elements (HSEs), using as our model a dinucleosomal heat shock promoter (hsp82-ΔHSE1). We find that activated HSF cannot bind a stable, sequence-positioned nucleosome in G₁-arrested …

Identification Of The Transactivation Domain Of The Transcription Factor Sox-2 And An Associated Co-Activator, Tamara K. Nowling, Lance R. Johnson, Matthew S. Wiebe, Angie Rizzino

Nebraska Center for Virology: Faculty Publications

The importance of interactions between Sox and POU transcription factors in the regulation of gene expression is becoming increasingly apparent. Recently, many examples of the involvement of Sox-POU partnerships in transcription have been discovered, including a partnership between Sox-2 and Oct-3. Little is known about the mechanisms by which these factors modulate transcription. To better understand the molecular interactions involved, we mapped the location of the transactivation do-main of Sox-2. This was done in the context of its interaction with Oct-3, as well as its ability to transactivate as a fusion protein linked to the DNA-binding domain of Gal4. Both …

Cellular Release Of And Response To Atp As Key Determinants Of The Set-Point Of Signal Transduction Pathways, Rennolds S. Ostrom, Caroline Gregorian, Paul A. Insel

Pharmacy Faculty Articles and Research

The determinants of “basal” activity of signaling pathways regulating cellular responses are poorly defined. One possibility is that cells release factors to establish the set-point of such pathways. Here we show that treatment of Madin-Darby canine kidney cells with the nucleotidase apyrase decreases basal arachidonic acid release and cAMP production 30–40% and that inhibitors of P2Y receptor action also affect basal and forskolin-stimulated cAMP accumulation. Changing medium prominently increases extracellular levels of ATP in Madin-Darby canine kidney, COS-7, and HEK-293 cells. Mechanical stimulation of ATP release likely occurs in virtually every experimental protocol with cultured cells, implicating such release and …

Isovolumic Regulation In Nervous Tissue: A Novel Mechanism Of Cell Volume Regulation, O. Quesada, R. Franco, K. Hernandez-Fonseca, K. Tuz

School of Veterinary and Biomedical Sciences: Faculty Publications

Cell volume regulation is a property present in most animal cell lineages that allows them to recover their original volume after events of swelling or shrinkage. Such events can be caused by changes in external osmolarity or to osmotic gradients generated during normal cell functioning.4,6 The mechanism of cell volume regulation involves transmembrane fluxes of osmotically active solutes in the necessary direction to counteract the net gain or loss of intracellular water.9 The process through which cells recover their normal volume after swelling is named Regulatory Volume Decrease (RVD). This consists of the efflux of inorganic osmolytes, such as K …

Telomerase Activity In Human Preimplantation Embryos, Diane Lynne Wright

Theses and Dissertations in Biomedical Sciences

Telomerase, a ribonucleoprotein, has been described as an essential component of highly proliferative cells, which stabilizes the telomeres and avoids cellular senescence. Telomerase has been identified in various embryonic cell stages, hematopoietic cells, and in >85% of tumor tissue biopsies analyzed. The ability to measure the potential to proliferate successfully could provide an objective measure of an embryo's quality. The objectives of this study were to modify the telomeric repeat amplification protocol (TRAP) assay system for increased sensitivity to allow detection of telomerase activity in the single cell of an oocyte and embryo, obtain telomerase activity levels for the oocyte …

Natural Antibodies To Adrenal Hormones And Apolipoprotein E In Cardiovascular Physiology, Shabana Aafaqi

Student Works (2000-2009)

Natural autoantibodies (NAA} are autoantibodies that are present in the sera of healthy individuals. NAA can belong to the lgA, lgG and lgM isotypcs. They exhibit high degrees of polyreactivity and connectivity but low affinity to self antigens. The main function of NAA in healthy people is probably 10 clear the catabolic waste and ageing cells. In this study, an indirect Enzyme-linked lmmunosorbent Assay (ELISA) method was used to detect NAA against hormones, namely adreno-co11ical (hydrocortisone, aldostcrone, androstcncdionc), adrcno-medullary (adrenaline. noradrenaline) and other related steroid hormones (progesterone, testosterone, P-cstradiol). In eleven normal human serum (NHS), lgG anti-cortisol were delcctcd in …

Identification And Characterization Of Determinants Of Head And Neck Tumor Cell Invasion, Yangguan Wu

Theses and Dissertations in Biomedical Sciences

Head and neck squamous cell carcinoma (HNSCC) is a common malignant disease with poor prognosis. The majority of patients die from local invasion or lymphatic metastasis. The mechanism(s) underlining the invasiveness of HNSCC are poorly understood. Utilizing a panel of HNSCC cell lines previously established in our laboratory, we tested the application and relevance of the three-step hypothesis of tumor invasion to HNSCC and investigated the mechanism(s) pertaining to the regulation of each step in the invasive process. Data presented in this thesis demonstrated that tumor cell invasion in HNSCC is a complex process involving three repeated sequential steps: adhesion, …

Optimal Replication Activity Of Vesicular Stomatitis Virus Rna Polymerase Requires Phosphorylation Of A Residue(S) At Carboxy-Terminal Domain Ii Of Its Accessory Subunit, Phosphoprotein P, Leroy N. Hwang, Nathan Englund, Tapas Das, Amiya K. Florida, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

The phosphoprotein, P, of vesicular stomatitis virus (VSV) is a key subunit of the viral RNA-dependent RNA polymerase complex. The protein is phosphorylated at multiple sites in two different domains. We recently showed that specific serine and threonine residues within the amino-terminal acidic domain I of P protein must be phosphorylated for in vivo transcription activity, but not for replication activity, of the polymerase complex. To examine the role of phosphorylation of the carboxy-terminal domain II residues of the P protein in transcription and replication, we have used a panel of mutant P proteins in which the phosphate acceptor sites …

Immunohistochemical Evaluation Of Small Round Cell Tumors Of Childhood, Sajid H. Shah, Irshad N. Soomro, M. Shahid Siddiqui, Shahid Pervez, Sheema H. Hassan

Department of Pathology and Laboratory Medicine

Objective:

This study was done to evaluate the pediatric undifferentiated small round cell tumors with immunohistochemical staining.

Setting:

The present study included consecutive cases of small round cell tumors which were diagnosed in children (<15 years) in the section of Histopathology at the Aga Khan University Hospital, Karachi during the period of two years.

Methods:

The group of undifferentiated small round cell tumors were evaluated immunohistochemically by using a panel of antibodies on sections from routinely processed, formalin fixed, paraffin embedded tissue blocks.

Results:

The category of undifferentiated small round cell tumors included rhabdomyosarcoma (23.2%), primitive neuroectodermal tumor (17.9%), non-Hodgkin’s lymphoma (16.1%), neuroblastoma (14.2%), Ewing’s sarcoma (10.7%) in order of frequency. Osteosarcoma (Small cell variant), retinoblastoma and medulloblastoma comprised …

Insulinlike Growth Factor 1- And 2-Augmented Collagen Gel Repair Of Facial Osseous Defects, James S. Toung, Roy C. Ogle, Raymond F. Morgan, William H. Lindsey

School of Medical Diagnostics & Translational Sciences Publications

BACKGROUND: Defects of the facial bone structure are common problems for the facial plastic surgeon. Native type 1 collagen gels (T1CGs) have been shown to mediate repair of facial critical-size defects in rat models.

OBJECTIVE: To evaluate the efficacy of T1CG augmented with insulinlike growth factor (IGF) 1, IGF-2, and a combination of IGF-1 and IGF-2 on the repair of facial critical-size defects in a rodent model.

METHODS: Twenty-four retired male breeder Sprague-Dawley rats were divided into 4 groups of 6 animals. Facial critical-size defects were created by removing the nasalis bones with a bone-cutting drill. Defects were treated with …

Nucleotide Sequences For Detection Of Serpulina Hyodysenteriae, Gerald E. Duhamel, Robert Elder

School of Veterinary and Biomedical Sciences: Faculty Publications

The invention provides a method for detecting the presence of Serpulina hyodysenteriae in a biological Sample, an oligonucleotide primer and an S. hyodysenteriae-specific oligonucleotide probe useful in that method, and an article of manufacture that contains the primers and/or probe. Also provided are an about 2.3-kb DNA fragment derived from genomic DNA of S. hyodysenteriae and encoding for an about 56 kDa polypeptide, a recombinant expression vector containing the DNA fragment, the 56 kDa polypeptide and a monoclonal antibody reactive with the peptide, and a method of assaying for antibodies reactive with the 56 kDa peptide.

Interaction Of Laminin Beta2 With Eps8 And Desmin In Muscle Cells, Luke Xueliang Cui

Theses, Dissertations and Capstones

Laminin β2 is localized to the synaptic basal lamina (BL) in muscle and glomerular BL in kidney. To find interacting proteins, a mouse kidney cDNA library was screened with domain I of rat laminin β2 using the yeast two-hybrid system. Fifteen positive clones were found. The DNA sequence of three each of these clones corresponded to the phosphoprotein Eps8 (epidermal growth factor receptor pathway substrate clone 8, which is tyrosine phosphorylated after EGF stimulation) and the intermediate filament (IF) protein keratin. To determine if this interaction occurred in muscle cells, C2 cells transfected with the rat …

Cooperative Binding Of Heat Shock Factor To The Yeast Hsp82 Promoter In Vivo And In Vitro, Alexander M. Erkine, Serena F. Magrogan, Edward A. Sekinger, David S. Gross

Scholarship and Professional Work – COPHS

revious work has shown that heat shock factor (HSF) plays a central role in remodeling the chromatin structure of the yeastHSP82 promoter via constitutive interactions with its high-affinity binding site, heat shock element 1 (HSE1). The HSF-HSE1 interaction is also critical for stimulating both basal (noninduced) and induced transcription. By contrast, the function of the adjacent, inducibly occupied HSE2 and -3 is unknown. In this study, we examined the consequences of mutations in HSE1, HSE2, and HSE3 on HSF binding and transactivation. We provide evidence that in vivo, HSF binds to these three sites cooperatively. This cooperativity is seen …

Inhibition Of Cpla2-Mediated Arachidonic Acid Release By Cyclic Amp Defines A Negative Feedback Loop For P2y-Receptor Activation In Mdck-D1 Cells, Mingzhao Xing, Steven Post, Rennolds S. Ostrom, Michael Samardzija, Paul A. Insel

Pharmacy Faculty Articles and Research

In Madin-Darby canine kidney D1cells extracellular nucleotides activate P2Y receptors that couple to several signal transduction pathways, including stimulation of multiple phospholipases and adenylyl cyclase. For one class of P2Y receptors, P2Y2 receptors, this stimulation of adenylyl cyclase and increase in cAMP occurs via the conversion of phospholipase A2 (PLA2)-generated arachidonic acid (AA) to prostaglandins (e.g. PGE2). These prostaglandins then stimulate adenylyl cyclase activity, presumably via activation of prostanoid receptors. In the current study we show that agents that increase cellular cAMP levels (including PGE2, forskolin, and the β-adrenergic agonist isoproterenol) can inhibit P2Y receptor-promoted AA release. The protein kinase …

Plasmd Bearing A Cdna Copy Of The Genome Of Bovine Viral Diarrhea Virus, Chimeric Derivatives Thereof, And Method Of Producing An Infectious Bovine Wral Darrheavirus Using Sad Plasmid, Ruben O. Donis, Ventzislav B. Vassilev

School of Veterinary and Biomedical Sciences: Faculty Publications

A plasmid bearing a cDNA copy of the genome of bovine viral diarrhea virus (BVDV), chimeric derivatives of the plasmid and a method of producing an infectious bovine viral diarrhea virus using the plasmid are disclosed. The invention relates to a plasmid DNA molecule that replicates easily in E. coli and contains a sufficient portion of the genome of BVDV, cloned as cDNA, to be a suitable template to produce RNA in vitro which, upon transfection into bovine cells, gives rise to infectious BVDV. The BVDV created by the process of the invention can be engineered for use as a …

In Situ Hybridization For The Detection And Localization Of Swine Chlamydia Trachomatis, C. Chae, D.-S. Cheon, D. Kwon, O. Kim, B. Kim, J. Suh, D. G. Rogers, K. D. E. Everett, A. A. Anderson

School of Veterinary and Biomedical Sciences: Faculty Publications

Gnotobiotic piglets were inoculated intralaryngeally with swine Chlamydia trachomatis strain R33 or orally with swine C. trachmatis strain R27. Archived formalin-fixed, paraffin-embedded tissues from piglets euthanatized 4–7 days postinoculation were examined by in situ hybridization for C. trachomatis nucleic acid using a nonradioactive digoxigenin-labeled DNA probes that targeted specific ribosomal RNA or omp1 mRNA molecules of the swine C. trachomatis strains. Positive hybridization signals were detected in bronchial epithelial cells, bronchiolar epithelial cells, pneumocytes, alveolar and interstitial macrophages, and jejunal and ileal enterocytes. Chlamydia-infected cells had a strong signal that was confined to the intracytoplasmic inclusions. Positive hybridization signals were …

Increased Glutathione Metabolic Defense Capabilities In Cultured Alzheimer's Diseased Lymphoblast Cell Lines, Collin M. Shaw

Dissertations and Theses

The hypothesis to be tested states that the pathology of Alzheimer's disease (AD) involves elevated levels of oxidative stress, resulting in elevated levels of cellular oxidative defense mechanisms. If the premise is true, than AD pathologically afflicted cells should have a higher demand for glutathione (GSH) as an innate oxidative defense mechanism hence; greater GSH concentrations, increased GSH resynthesis capabilities, and increased levels of cystathionine gamma-lyase (CNase). Alzheimer diseased and age matched control lymphoblast cells, obtained from OHSU's Oregon Brain Aging Study, were cultured, and GSH biochemistry was subsequently evaluated. GSH was depleted by exposing cells to the GSH depleting …

Efficacy Of AllowashTm Solution In Solubilization Of Bone Marrow, Alyce Marie Linthurst

Biological Sciences Theses & Dissertations

LifeNet currently cleans allograft bone utilizing Allowash^TM Technology, which encompasses the use of a closed continuous circulation chamber to remove bone marrow by flushing it with Allowash^TM Solution for a prescribed time and temperature after which, it is rinsed with various solutions to remove residual detergent that could be toxic to the recipient. A portion of this process employs Allowash^TM Solution to improve the solubilization and removal of protein and cellular elements in the red bone marrow. This study examines the effectiveness of Allowash^TM Solution in comparison to its component detergents Nonidet P40, Nonoxynol 9 and …

Leukemia Inhibitory Factor (Lif): Murine Preimplantation Embryo Development, Implantation Rates, And Skeletal Development, Michael Hayes Mitchell

Theses and Dissertations in Biomedical Sciences

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine which demonstrates perplexing physiological effects. It has been demonstrated that LIF is essential for implantation in mice. Little is known relating to the manner by which LIF effects pre-implantation and post-implantation development. The objectives of this project were to determine the effects LIF on pre-implantation development, to determine the effects that it may have on implantation rates, successful pregnancy rates, and resorption rates, and to determine the effects that LIF has on the skeletal development of mice. For the embryo transfer experiments, embryos were exposed to test compounds in the transfer medium …