scholarly journals Dickkopf-Like1 Regulates Postpubertal Spermatocyte Apoptosis and Testosterone Production

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 404-412 ◽  
Author(s):  
Olga Dakhova ◽  
Diana O'Day ◽  
Noe Kinet ◽  
Nur Yucer ◽  
Mary Wiese ◽  
...  
Keyword(s):  
Leydig Cells ◽  
Fas Ligand ◽  
Sperm Count ◽  
Negative Regulator ◽  
Steroidogenic Factor 1 ◽  
Adult Testis ◽  
Adult Mice ◽  
Sperm Counts ◽  
Apoptotic Activity ◽  
The One

Dickkopf-like1 (Dkkl1) encodes a glycoprotein secreted by postmeiotic male germ cells. We report here that adult Dkkl1-deficient males have elevated sperm counts caused by a decrease in postpubertal spermatocyte apoptosis and display, upon aging, increased local production of testosterone. Molecular analyses identified the Fas death ligand (FasL) as a target for Dkkl1 pro-apoptotic activity in adult mice. Accordingly, adult FasL-deficient gld mice display an increased sperm count and decreased spermatocyte apoptosis phenotype similar to the one observed in Dkkl1-deficient mice. We also show that the elevated testosterone level observed in aging Dkkl1-deficient males is secondary to increased expression in Leydig cells of CYP11A and CYP17, two genes implicated in steroidogenesis. Furthermore, treatment of Leydig cells with Dkkl1 decreases DNA binding and transcriptional activity of steroidogenic factor 1, a pivotal regulator of gene expression in testis. Thus, this study establishes Dkkl1 as a negative regulator of adult testis homeostasis and identifies a novel, Dkkl1/FasL-dependent, regulation that specifically controls the number of postpubertal spermatocytes. Dickkopf-like 1 negatively regulates adult testis biology by promoting spermatocyte apoptosis via Fas ligand activation and by limiting testosterone synthesis in Leydig cells.

scholarly journals Impact of FasL Stimulation on Sclerostin Expression and Osteogenic Profile in IDG-SW3 Osteocytes

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 757
Author(s):  
Adela Kratochvilova ◽  
Alice Ramesova ◽  
Barbora Vesela ◽  
Eva Svandova ◽  
Herve Lesot ◽  
...  
Keyword(s):  
Cell Death ◽  
Fas Ligand ◽  
Bone Cells ◽  
Expression Profiles ◽  
Negative Regulator ◽  
Bone Homeostasis ◽  
Caspase Inhibitor ◽  
The One ◽  
The Impact ◽  
Mature Bone

The Fas ligand (FasL) is known from programmed cell death, the immune system, and recently also from bone homeostasis. As such, Fas signalling is a potential target of anti-osteoporotic treatment based on the induction of osteoclastic cell death. Less attention has been paid to osteocytes, although they represent the majority of cells within the mature bone and are the key regulators. To determine the impact of FasL stimulation on osteocytes, differentiated IDG-SW3 cells were challenged by FasL, and their osteogenic expression profiles were evaluated by a pre-designed PCR array. Notably, the most downregulated gene was the one for sclerostin, which is the major marker of osteocytes and a negative regulator of bone formation. FasL stimulation also led to significant changes (over 10-fold) in the expression of other osteogenic markers: Gdf10, Gli1, Ihh, Mmp10, and Phex. To determine whether these alterations involved caspase-dependent or caspase-independent mechanisms, the IDG-SW3 cells were stimulated by FasL with and without a caspase inhibitor: Q-VD-OPh. The alterations were also detected in the samples treated by FasL along with Q-VD-OPh, pointing to the caspase-independent impact of FasL stimulation. These results contribute to an understanding of the recently emerging pleiotropic effects of Fas/FasL signalling and specify its functions in bone cells.

scholarly journals Environmental and Nutritional Aspect in Male Infertility

1970 ◽  
Vol 10 (1) ◽  
pp. 16-19 ◽  
Author(s):  
Hamida Begum ◽  
ABM Moniruddin ◽  
Khairun Nahar
Keyword(s):  
Heavy Metals ◽  
Male Infertility ◽  
Sperm Count ◽  
Sperm Production ◽  
Male And Female ◽  
Exogenous Estrogen ◽  
Sperm Counts ◽  
And Function ◽  
Nutritional Aspect ◽  
Anatomical Defects

Male and female partner of a couple must be standard and fit to have the capacity to procreate. Studies confirm that male sperm counts are declining and environmental factors as pesticides, exogenous estrogen, heavy metals negatively impact spermatogenesis without any obvious anatomical defects. So, a number of nutritional therapies have been shown to improve sperm count and motility as carnitine, arginine, zinc, selenium and vitamin B12. Numerous anitioxidants have prove beneficial in treating male infertility as Vitamin C, Vitamin E, Glutathione and Coenzyme Q10. This article aims to highlight the correction of nutritional imbalances to encourage optimum sperm production and function, when there is idiopathic impaired spermatogenesis.   doi:10.3329/jom.v10i1.1997   J Medicine 2009; 10: 16-19   

Gonadal expression of c-kit encoded at the W locus of the mouse

Development ◽  
1990 ◽  
Vol 110 (4) ◽  
pp. 1057-1069 ◽  
Author(s):  
K. Manova ◽  
K. Nocka ◽  
P. Besmer ◽  
R.F. Bachvarova
Keyword(s):  
In Situ Hybridization ◽  
Germ Cells ◽  
Leydig Cells ◽  
Interstitial Tissue ◽  
Type B ◽  
Age Dependence ◽  
Oocyte Growth ◽  
Adult Mice

Recently, it has been shown that the c-kit proto-oncogene is encoded at the white spotting (W) locus in mice. Mutations of this gene cause depletion of germ cells, some hematopoietic cells and melanocytes. In order to define further the role of c-kit in gametogenesis, we have examined its expression in late fetal and postnatal ovaries and in postnatal testis. By RNA blot analysis, c-kit transcripts were not detected in late fetal ovaries but appeared at birth. The relative amount reached a maximum in ovaries of juvenile mice, and decreased in adult ovaries. c-kit transcripts were present in increasing amounts in isolated primordial, growing and full-grown oocytes, as well as in ovulated eggs. Little was detected in early 2-cell embryos and none in blastocysts. In situ hybridization revealed c-kit transcripts in a few oocytes of late fetal ovaries and in all oocytes (from primordial to full-grown) in ovaries from juvenile and adult mice. Expression was also observed in ovarian interstitial tissue from 14 days of age onward. Using indirect immunofluorescence, the c-kit protein was detected on the surface of primordial, growing and full-grown oocytes, as well as on embryos at the 1- and 2-cell stages; little remained in blastocysts. In situ hybridization analysis of testes from mice of different ages demonstrated expression in spermatogonia from 6 days of age onward. Using information provided by determining the stage of the cycle of the seminiferous epithelium for a given tubule and by following the age dependence of labeling, it was concluded that the period of expression of c-kit extends from at least as early as type A2 spermatogonia through type B spermatogonia and into preleptotene spermatocytes. Leydig cells were labelled at all ages examined. The expression pattern in oocytes correlates most strongly with oocyte growth and in male germ cells with gonial proliferation.

scholarly journals Neuregulin 1 Regulates Proliferation of Leydig Cells to Support Spermatogenesis and Sexual Behavior in Adult Mice

Endocrinology ◽  
2016 ◽  
Vol 157 (12) ◽  
pp. 4899-4913 ◽  
Author(s):  
Takashi Umehara ◽  
Ikko Kawashima ◽  
Tomoko Kawai ◽  
Yumi Hoshino ◽  
Ken-ichirou Morohashi ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
Leydig Cells ◽  
Neuregulin 1 ◽  
Adult Mice

Testicular toxicity of chlorpyrifos (an organophosphate pesticide) in albino rat

2007 ◽  
Vol 23 (7) ◽  
pp. 439-444 ◽  
Author(s):  
Suresh C Joshi ◽  
R. Mathur ◽  
N. Gulati
Keyword(s):  
Histopathological Examination ◽  
Sperm Count ◽  
The Body ◽  
Male Reproduction ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Albino Rat ◽  
Toxic Activity ◽  
Sperm Counts ◽  
Dose Levels

Organophosphates are among the most widely used synthetic insect pesticides. The widespread use of organophosphates has stimulated research into the possible existence of effects related with their reproductive toxic activity. Present study was therefore, undertaken to assess the effects of chlorpyrifos on testes, the main organ of male reproduction. Chlorpyrifos at the dose levels of 7.5, 12.5 and 17.5 mg/kg b. wt./day was administered orally to male rats of Wistar strain for 30 days to evaluate the toxic alterations in testicular histology, biochemistry, sperm dynamics and testosterone levels. The body weight of animals did not show any significant change, however, a significant reduction was observed in testes. Chlorpyrifos also brought about marked reduction in epididymal and testicular sperm counts in exposed males and a decrease in serum testosterone concentration. Histopathological examination of testes showed mild to severe degenerative changes in seminiferous tubules at various dose levels. Fertility test showed 85% negative results. A significant reduction in the sialic acid content of testes and testicular glycogen was noticed, whereas the protein and cholesterol content was raised at significant levels. All these toxic effects are moderate at low doses and become severe at higher dose levels. From the results of the present study it is concluded that chlorpyrifos induces severe testicular damage and results in reduction in sperm count and thus affect fertility. Small changes in sperm counts are known to have adverse affects on human fertility. Therefore, application of such insecticide should be limited to a designed programme. Toxicology and Industrial Health 2007; 23: 439—444.

Localization of EFA6 (exchange factor for ARF6) isoform D in steroidogenic testicular Leydig cells of adult mice

2018 ◽  
Vol 120 (3) ◽  
pp. 263-268
Author(s):  
Surang Chomphoo ◽  
Sawetree Pakkarato ◽  
Tarinee Sawatpanich ◽  
Hiroyuki Sakagami ◽  
Hisatake Kondo ◽  
...  
Keyword(s):  
Leydig Cells ◽  
Exchange Factor ◽  
Adult Mice

The effect of imatinib administered in the prenatal period on testis development in rats

2020 ◽  
pp. 096032712095845
Author(s):  
Z Topal Suzan ◽  
L Tumkaya ◽  
T Mercantepe ◽  
M Atak ◽  
HA Uydu
Keyword(s):  
Sperm Count ◽  
Group Analysis ◽  
Immunohistochemical Analysis ◽  
Study Groups ◽  
Control Group ◽  
Prenatal Period ◽  
Testis Development ◽  
Nuclear Maturation ◽  
Sperm Counts ◽  
Testis Tissue

Background: The purpose of this study was to examine the effects of exposure to imatinib in the prenatal period on testis development in rats. Methods: Although all the study groups received intraperitoneal imatinib on prenatal days 1–8, no pregnancy occurred in the Imatinib-80 group. Immunohistochemical analysis, TUNEL, c-kit and PDGF staining revealed no difference between the groups in terms of positivity scoring. Results: A significant decrease was detected in total sperm counts in the Imatinib-20 group compared to the control group, but the sperm count was higher in the Imatinib-60 group than in the Imatinib-20 group. At biochemical measurements, the drug increased oxidative stress in the testis and serum in the Imatinib-20 group, but caused a decrease in tissue in the Imatinib-60 group. Thiol measurements revealed a decrease in the testis and serum in the Imatinib-60 group, while an increase in serum measurements was observed in the Imatinib-40 group. Analysis revealed no difference between the groups in terms of protamine and histone gene expression levels in testis tissue exposed to imatinib. Conclusion: Our findings show that prenatal exposure to imatinib can lead to histopathological and biochemical changes in testis tissue, but that no adverse effect occurs in nuclear maturation of germ cells during spermiogenesis.

Rapid recovery of spermatogenesis after mitoxantrone, vincristine, vinblastine, and prednisone chemotherapy for Hodgkin's disease.

1997 ◽  
Vol 15 (12) ◽  
pp. 3488-3495 ◽  
Author(s):  
M L Meistrich ◽  
G Wilson ◽  
K Mathur ◽  
L M Fuller ◽  
M A Rodriguez ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Male Fertility ◽  
Sperm Count ◽  
Hodgkin’S Disease ◽  
Spermatogenic Cells ◽  
Sperm Production ◽  
Human Male ◽  
Sperm Counts ◽  
Abdominal Radiotherapy ◽  
Upper Abdominal

PURPOSE Because the effects of mitoxantrone on human male fertility were unknown, we determined prospectively the effects of three courses of mitoxantrone (Novantrone), vincristine (Oncovin), vinblastine, prednisone (NOVP) chemotherapy on the potential for fertility of men with Hodgkin's disease (HD). PATIENTS AND METHODS Semen analyses were performed on 58 patients with stages I-III HD before, during, and after chemotherapy and after the sperm count recovered from the effects of abdominal radiotherapy that was given after chemotherapy. RESULTS Before the initiation of treatment, 84% of the patients were normospermic. Sperm counts declined significantly within 1 month after the start of NOVP chemotherapy. In the month after chemotherapy, 38% of patients were azoospermic, 52% had counts < 1 million/ mL, and 10% had counts between 1 and 3 million/mL. Between 2.6 and 4.5 months after the completion of chemotherapy, sperm counts recovered rapidly to normospermic levels in 63% of patients. In the remaining patients who were followed up for at least 1 year after standard upper abdominal radiotherapy, counts also recovered to normospermic levels. CONCLUSION NOVP chemotherapy, like most other regimens, produced marked temporary effects or spermatogenesis. However, sperm production recovered very rapidly, within 3 to 4 months after the end of NOVP chemotherapy. This pattern was caused by killing differentiating spermatogenic cells, but there was little cytotoxicity or inhibition of stem cells from mitoxantrone or the other drugs. After the combination of NOVP plus abdominal radiotherapy, sperm counts and motility were restored in most patients to pretreatment levels, which were compatible with normal fertility.

α-Lipoic acid attenuates transplacental nicotine-induced germ cell and oxidative DNA damage in adult mice

2016 ◽  
Vol 27 (6) ◽  
Author(s):  
Santo K. Anto ◽  
Naresh Koyada ◽  
Sabbir Khan ◽  
Gopabandhu Jena
Keyword(s):  
Dna Damage ◽  
Germ Cell ◽  
Lipoic Acid ◽  
Oxidative Dna Damage ◽  
Sperm Count ◽  
Protective Role ◽  
Sperm Head ◽  
Smoking During Pregnancy ◽  
Adult Mice ◽  
Testicular Weight

AbstractBackground:Smoking during pregnancy is associated with numerous fetal and developmental complications and reproductive dysfunctions in the offspring. Nicotine is one of the key chemicals of tobacco responsible for addiction. The present study was aimed to investigate the protective role of α-lipoic acid (ALA) during the transplacental nicotine-induced germ cell and DNA damage in the offspring of Swiss mice.Methods:Pregnant mice were treated with nicotine (20 mg/kg/day) in drinking water from 10 to 20 days of gestation period, and ALA (120 mg/kg/day) was administered orally for the same period. Endpoint of evaluation includes general observations at delivery and throughout the study, litter weight and size, sperm count and sperm head morphology, while structural damages and protein expression were assessed by histology and immunohistochemistry, respectively.Results:Maternal nicotine exposure led to decreased growth rate, litter and testicular weight, testosterone level, 3β-HSD expression and sperm count as well as increased sperm head abnormalities, micronucleus frequency and 8-oxo-dG positive cells, and the effects have been restored by ALA supplementation.Conclusions:The present study clearly demonstrated that ALA ameliorates nicotine-associated oxidative stress, DNA damage and testicular toxicity in the offspring by improving steroidogenesis, spermatogenesis and sperm count.

Testicular oxytocin: effects of intratesticular oxytocin in the rat

1991 ◽  
Vol 130 (2) ◽  
pp. 231-NP ◽  
Author(s):  
H. D. Nicholson ◽  
S. E. F. Guldenaar ◽  
G. J. Boer ◽  
B. T. Pickering
Keyword(s):  
Leydig Cells ◽  
Light And Electron Microscopy ◽  
Male Rats ◽  
Plasma Testosterone ◽  
Epididymal Sperm ◽  
Long Term Effects ◽  
Sperm Counts ◽  
Term Administration

ABSTRACT The long-term effects of oxytocin administration on the testis were studied using intratesticular implants. Adult male rats had an Accurel device containing 20 μg oxytocin (releasing approximately 200 ng/day) implanted into the parenchyma of each testis; control animals received empty devices. The animals were killed at weekly intervals for 4 weeks. Some animals were perfused and the testes processed for light and electron microscopy. Blood was collected from the remaining animals for the measurement of testosterone, dihydrotestosterone, LH, FSH and oxytocin; epididymal sperm counts were measured and the testes were extracted and radioimmunoassayed for testosterone, dihydrotestosterone and oxytocin. Long-term administration of oxytocin resulted in a significant reduction in testicular and plasma testosterone levels throughout the 4-week period examined and, after 14 days of treatment, lipid droplets were seen in the Leydig cells of treated but not control animals. Concentrations of dihydrotestosterone in the plasma and testes of the oxytocin-treated animals, however, were significantly elevated after 7 and 14 days and at no time fell below control values. Plasma FSH levels were also lower in the oxytocin-treated animals. Intratesticular oxytocin treatment did not affect LH or oxytocin concentrations in the plasma, epididymal sperm counts or the number of Leydig cells in the testis. Empty Accurel devices had no effect on testicular morphology. This study provides the first evidence that oxytocin in vivo can modify steroidogenesis in the testis. Journal of Endocrinology (1991) 130, 231–238

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