A5107341815- Phosphodiesterase function and regulation
- Reproductive Biology and Fertility
- Receptor Mechanisms and Signaling
- Cholinesterase and Neurodegenerative Diseases
- Ovarian function and disorders
- Sperm and Testicular Function
- RNA Research and Splicing
- Reproductive System and Pregnancy
- Epigenetics and DNA Methylation
- Neuroendocrine regulation and behavior
- Synthesis and Catalytic Reactions
- Asthma and respiratory diseases
- Microtubule and mitosis dynamics
- Pluripotent Stem Cells Research
- Renin-Angiotensin System Studies
- Mast cells and histamine
- Genetics, Aging, and Longevity in Model Organisms
- RNA modifications and cancer
- Chemical synthesis and alkaloids
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Neuropeptides and Animal Physiology
- Renal and related cancers
- Endometriosis Research and Treatment
- Nitric Oxide and Endothelin Effects
- Animal Genetics and Reproduction
Broad Center
2013-2024
University of California, San Francisco
2015-2024
Reproductive Science Center
2015-2024
University Medical Center Hamburg-Eppendorf
2018
Universität Hamburg
2018
The University of Texas Health Science Center at Houston
2017
Medizinische Hochschule Hannover
2017
University of Regensburg
2017
Chapman University
2017
Purdue University West Lafayette
2017
Before ovulation in mammals, a cascade of events resembling an inflammatory and/or tissue remodeling process is triggered by luteinizing hormone (LH) the ovarian follicle. Many LH effects, however, are thought to be indirect because restricted expression its receptor. Here, we demonstrate that stimulation induces transient and sequential epidermal growth factor (EGF) family members amphiregulin, epiregulin, beta-cellulin. Incubation follicles with these factors recapitulates morphological...
Catecholamines signal through the beta2-adrenergic receptor by promoting production of second messenger adenosine 3',5'-monophosphate (cAMP). The magnitude this is restricted desensitization receptors their binding to beta-arrestins and cAMP degradation phosphodiesterase (PDE) enzymes. We show that coordinate both processes recruiting PDEs activated in plasma membrane mammalian cells. In doing so, limit activation membrane-associated cAMP-activated protein kinase simultaneously slowing rate...
To acquire the ability to fertilize, spermatozoa undergo complex, but at present poorly understood, activation processes. The intracellular rise of cAMP produced by bicarbonate-dependent soluble adenylyl cyclase (sAC) has been suggested play a central role in initiating cascade events that culminates maturation. Here, we show targeted disruption sAC gene does not affect spermatogenesis dramatically impairs sperm motility, leading male sterility. mutant are characterized total loss forward...
In the preovulatory ovarian follicle, mammalian oocytes are maintained in prophase meiotic arrest until luteinizing hormone (LH) surge induces reentry into first division.Dramatic changes somatic cells surrounding and follicular wall also induced by LH necessary for ovulation.Here, we provide genetic evidence that LH-dependent transactivation of epidermal growth factor receptor (EGFR) is indispensable oocyte cell cycle, synthesis extracellular matrix causes cumulus expansion, follicle...
It is well established that cAMP signaling an important regulator of the oocyte meiotic cell cycle. Conversely, function cGMP during maturation less clear. Herein, we evaluated expression cGMP-hydrolyzing phosphodiesterases (PDEs) in somatic and germ compartments mouse ovarian follicle demonstrate PDE5 preferentially expressed cells. Cyclic GMP a potent inhibitor hydrolysis from extracts, with 50% inhibitory concentration 97 nM. Luteinizing hormone (LH) stimulation cultured preovulatory...
Oocyte maturation, fertilization, and early embryonic development occur in the absence of gene transcription. Therefore, it is critical to understand at a global level post-transcriptional events that are driving these transitions. Here we used systems approach by combining polysome mRNA profiling bioinformatics identify RNA-binding motifs mRNAs either enter or exit pool during mouse oocyte maturation. Association with polysomes correlates active translation. Using this strategy, identified...
Lipopolysaccharide (LPS) stimulation of the innate immune response requires activation signaling cascades that culminate in synthesis and secretion proinflammatory cytokines. Given inhibitory effects phosphodiesterase (PDE) inhibitors on LPS-induced cytokine production, we have investigated LPS responses mice deficient PDE4 (type 4 cAMP-specific PDE)-B PDE4D. mouse peripheral leukocytes induced PDE4B mRNA accumulation increased activity. This was completely absent but not induction tumor...
The second messenger cAMP has been implicated in the regulation of mammalian and amphibian oocyte maturation. Although a decrease intraoocyte levels precedes germinal vesicle breakdown (GVBD), gonadotropin induction ovulation maturation is associated with major increases ovarian follicles. In system, isolated oocytes undergo spontaneous maturationin vitrobut this process blocked by treatment phosphodiesterase (PDE) inhibitor, IBMX, which levels. contrast, same when added to cultured...
Previous studies showed that epidermal growth factor (EGF) and TGFalpha mimic the action of LH on resumption oocyte maturation. We tested whether EGF-like agents, such as amphiregulin (AR), epiregulin (ER), betacellulin (BTC), also mediate stimulation ovulatory response in rat. induced transient follicular expression AR, ER, BTC mRNA, reaching a maximum after 3-h incubation. Furthermore, addition to culture medium could some actions. AR ER fully simulated LH-induced meiosis vitro, whereas...
A combination of pharmacological and genetic approaches was used to determine the role type 4 cAMP-specific cyclic nucleotide phosphodiesterase (PDE4) in reversing α2-adrenoceptor–mediated anesthesia, a behavioral correlate emesis non-vomiting species. Among family-specific PDE inhibitors, PDE4 inhibitors reduced duration xylazine/ketamine–induced anesthesia mice, with no effect on pentobarbital-induced anesthesia. The rank order tested 6-(4-pyridylmethyl)-8-(3-nitrophenyl)quinoline (PMNPQ)...
The mediation of cAMP effects by specific pools protein kinase A (PKA) targeted to distinct subcellular domains raises the question how inactivation signal is achieved locally and whether similar targeting phosphodiesterases (PDEs) sites cAMP/PKA action could be observed. Here, we demonstrate that Sertoli cells testis contain an insoluble PDE4D3 isoform, which shown immunofluorescence target centrosomes. Staining PDE4D PKA shows co-localization with PKA-RIIalpha RIIbeta in centrosomal...