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1.
Mol Endocrinol ; 27(5): 814-27, 2013 May.
Article in English | MEDLINE | ID: mdl-23518924

ABSTRACT

Testis size and sperm production are directly correlated to the total number of adult Sertoli cells (SCs). Although the establishment of an adequate number of SCs is crucial for future male fertility, the identification and characterization of the factors regulating SC survival, proliferation, and maturation remain incomplete. To investigate whether the IGF system is required for germ cell (GC) and SC development and function, we inactivated the insulin receptor (Insr), the IGF1 receptor (Igf1r), or both receptors specifically in the GC lineage or in SCs. Whereas ablation of insulin/IGF signaling appears dispensable for GCs and spermatogenesis, adult testes of mice lacking both Insr and Igf1r in SCs (SC-Insr;Igf1r) displayed a 75% reduction in testis size and daily sperm production as a result of a reduced proliferation rate of immature SCs during the late fetal and early neonatal testicular period. In addition, in vivo analyses revealed that FSH requires the insulin/IGF signaling pathway to mediate its proliferative effects on immature SCs. Collectively, these results emphasize the essential role played by growth factors of the insulin family in regulating the final number of SCs, testis size, and daily sperm output. They also indicate that the insulin/IGF signaling pathway is required for FSH-mediated SC proliferation.


Subject(s)
Follicle Stimulating Hormone/metabolism , Receptor, Insulin/metabolism , Sertoli Cells/cytology , Sertoli Cells/metabolism , Animals , Cell Count , Cell Differentiation/drug effects , Cell Differentiation/genetics , Cell Proliferation , Cell Shape/drug effects , Female , Fetus/cytology , Fetus/embryology , Gene Expression Profiling , Germ Cells/cytology , Germ Cells/drug effects , Germ Cells/metabolism , Humans , Leydig Cells/cytology , Leydig Cells/drug effects , Leydig Cells/metabolism , Male , Mice , Mice, Inbred C57BL , Mutation/genetics , Organ Size/drug effects , Organ Size/genetics , Proto-Oncogene Proteins c-akt/metabolism , Receptor, IGF Type 1/genetics , Receptor, IGF Type 1/metabolism , Receptor, Insulin/genetics , Seminiferous Tubules/cytology , Seminiferous Tubules/drug effects , Seminiferous Tubules/metabolism , Signal Transduction/drug effects , Signal Transduction/genetics , Spermatogenesis/drug effects , Spermatogenesis/genetics , Spermatozoa/cytology , Spermatozoa/drug effects , Spermatozoa/metabolism , Thyroid Hormones/pharmacology
2.
Fertil Steril ; 95(2): 835-6, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20971464

ABSTRACT

Three commercial, nonspermicidal gels used in fertility practice were found to be toxic to sperm in a 24-hr sperm survival assay; these included Felis, Replens, and Aquasonic Gel, which is used for transvaginal ultrasound during ovulation monitoring. In contrast, Pre-Seed did not cause any sperm toxicity, suggesting its appropriate use by patients who are trying to conceive, as well as clinicians during fertility procedures.


Subject(s)
Gels/pharmacology , Lubricants/adverse effects , Reproductive Medicine/methods , Spermatozoa/drug effects , Ultrasonography/methods , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Humans , Male , Organic Chemicals/pharmacology , Semen Analysis , Spermatocidal Agents/pharmacology , Spermatozoa/physiology , Time Factors
3.
Restor Neurol Neurosci ; 21(3-4): 141-50, 2003.
Article in English | MEDLINE | ID: mdl-14530576

ABSTRACT

OBJECTIVE: Brain injury and altered psychomotor development in infants, children and adults after cardiac surgery using cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) is still a matter of concern. Early diagnosis and identification of brain injury that has occurred or is ongoing by measurement of biochemical markers in serum may have diagnostic and prognostic value. The aim of the experimental studies in an animal model was therefore to investigate the release patterns of astroglial and neuronal markers in serum and to determine the morphological and immunohistochemical changes in the brain of animals undergoing similar perfusion conditions of CPB and a period of DHCA. METHODS: Fourteen New Zealand rabbits, (weight, 3.1 +/- 0.25 kg) were anesthetized, intubated and mechanically ventilated. Four animals were sham operated and served as controls. After median sternotomy the animals were connected to CPB by cannulation of the aorta and right atrium. Full flow CPB (200-250 ml/kg/min) was initiated to achieve homogeneous systemic cooling. Circulatory arrest of 60 minutes was induced when rectal and nasopharyngeal temperature of 14 degrees C was achieved. After rewarmed reperfusion and establishment of stable cardiac ejection the animals were weaned from CPB and monitored for 6 hours. Then the animals were killed, the brain was immediately removed and cut in standardized sections. These were fixated, embedded in paraffin and stained for further quantitative histological studies. In the brain astrocyte reactivity for S-100B was assessed immunocytochemically (DPC Immustain Los Angeles, USA). Monoclonal mouse anti-human neurospecific enolase (NSE) antibody was used for the localization of NSE in the fixed and paraffin embedded brain (NSE-DAKO, H14). The concentrations of S-100B protein and neurospecific enolase (NSE) in the serum were analyzed using a commercially available immunoluminometric assay (LIA-mat, Sangtec 100, Byk-Sangtec). Immunospecific monoclonal anti-parvalbumin antibody was used for the detection of parvalbumin in the brain. Serum concentrations of parvalbumin were analyzed using a newly developed ELISA method. RESULTS: In all experimental animals a significant increase of the serum concentration of the astroglial protein S-100B was found immediately after reperfusion and the termination of CPB. In contrast the serum levels of the neuronal proteins parvalbumin and NSE were not increased, but rather decreased. Light microscopy and electron microscopy revealed perivascular astrocytic swelling and minor neuronal cell injury. In comparison to the sham operated animals, increased immunohistochemical staining of S-100B was found. This increased reactivity of S100B antibody was found in the astrocytic processes with immediate connection to the perivascular space and around the perivascular oedema. The immunocytochemical stainings for NSE and parvalbumin in the neuronal cells was not different from that of sham-operated animals and indicated well preserved neurons.


Subject(s)
Astrocytes/metabolism , Biomarkers/blood , Cardiopulmonary Bypass , Neurons/metabolism , Reperfusion Injury/blood , Animals , Astrocytes/pathology , Cardiopulmonary Bypass/adverse effects , Nerve Growth Factors , Neurons/pathology , Rabbits , Reperfusion Injury/pathology , S100 Calcium Binding Protein beta Subunit , S100 Proteins/blood
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