scholarly journals Wuzi-Yanzong prescription alleviates spermatogenesis disorder induced by heat stress dependent on Akt, NF-κB signaling pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Su-Qin Hu ◽  
Dian-Long Liu ◽  
Chun-Rui Li ◽  
Ya-Hui Xu ◽  
Ke Hu ◽  
...  
Keyword(s):  
Heat Stress ◽  
Germ Cells ◽  
Serum Testosterone ◽  
Akt Pathway ◽  
Seminiferous Tubules ◽  
Tam Receptors ◽  
Phosphorylated Akt ◽  
Medicine Prescription ◽  
Apoptosis And Inflammation ◽  
Stress Dependent

AbstractAkt and nuclear factor kappa B (NF-κB) signaling pathways are involved in germ cell apoptosis and inflammation after testicular heat stress (THS). We observed that after THS induced by the exposure of rat testes to 43 °C for 20 min, their weight decreased, the fraction of apoptotic testicular germ cells significantly increased, and the proliferation of germ cells was inhibited. In addition, THS lowered serum testosterone (T) level, whereas the levels of follicle stimulating hormone and luteinizing hormone were not significantly changed. The ultrastructure of the seminiferous tubules became abnormal after THS, the structure of the blood-testis barrier (BTB) became loose, and the Sertoli cells showed a trend of differentiation. The level of phosphorylated Akt was reduced, whereas the amount of phosphorylated NF-κB p65 was augmented by THS. Wuzi-Yanzong (WZYZ), a classic Chinese medicine prescription for the treatment of male reproductive dysfunctions, alleviated the changes induced by THS. In order to determine the mechanism of action of WZYZ, we investigated how this preparation modulated the levels of T, androgen receptor (AR), erythropoietin (EPO), EPO receptor, and Tyro-3, Axl, and Mer (TAM) family of tyrosine kinase receptors. We found that WZYZ activated the Akt pathway, inhibited the Toll-like receptor/MyD88/NF-κB pathway, and repaired the structure of BTB by regulating the levels of T, AR, TAM receptors, and EPO. In conclusion, these results suggest that WZYZ activates the Akt pathway and inhibits the NF-κB pathway by acting on the upstream regulators, thereby improving spermatogenesis deficit induced by THS.

scholarly journals Regeneration of Leydig cells in ectopically autografted adult mouse testes

Reproduction ◽  
2015 ◽  
Vol 149 (3) ◽  
pp. 259-268 ◽  
Author(s):  
Himesh Makala ◽  
Lavanya Pothana ◽  
Surabhi Sonam ◽  
Ashwini Malla ◽  
Sandeep Goel
Keyword(s):  
Germ Cells ◽  
Leydig Cell ◽  
Adult Mouse ◽  
De Novo ◽  
Serum Testosterone ◽  
Serum Testosterone Level ◽  
Seminiferous Tubules ◽  
Testicular Development ◽  
Intrinsic Factors ◽  
Specific Proteins

Ectopic autografting of testis tissue is a promising approach for studying testicular development, male germline preservation and restoration of male fertility. In this study, we examined the fate of various testicular cells in adult mouse testes following ectopic autografting at 1, 2, 4 and 8 weeks post grafting. Histological examination showed no evidence of re-establishment of spermatogenesis in autografts, and progressive degeneration of seminiferous tubules was detected. Expression of germ cell-specific proteins such as POU5F1, DAZL, TNP1, TNP2, PRM1 and PRM2 revealed that, although proliferating and differentiating spermatogenic germ cells such as spermatogonia, spermatocytes and spermatids could survive in autografts until 4 weeks, only terminally differentiated germ cells such as sperm persisted in autografts until 8 weeks. The presence of Sertoli and peritubular myoid cells, as indicated by expression of WT1 and ACTA2 proteins, respectively, was evident in the autografts until 8 weeks. Interestingly, seminal vesicle weight and serum testosterone level were restored in autografted mice by 8 weeks post grafting. The expression of Leydig cell-specific proteins such as CYP11A1, HSD3B2 and LHCGR showed revival of Leydig cell (LC) populations in autografts over time since grafting. Elevated expression of PDGFRA, LIF, DHH and NEFH in autografts indicated de novo regeneration of LC populations. Autografted adult testis can be used as a model for investigating Leydig cell regeneration, steroidogenesis and regulation of the intrinsic factors involved in Leydig cell development. The success of this rodent model can have therapeutic applications for adult human males undergoing sterilizing cancer therapy.

437. Whole body heat stress induces selective germ cell apoptosis in mice

2008 ◽  
Vol 20 (9) ◽  
pp. 117 ◽  
Author(s):  
H. Wechalekar ◽  
B. P. Setchell ◽  
W. G. Breed ◽  
M. Ricci ◽  
C. Leigh ◽  
...  
Keyword(s):  
Heat Stress ◽  
Germ Cell ◽  
Germ Cells ◽  
Wilcoxon Test ◽  
Whole Body ◽  
Seminiferous Tubules ◽  
Heat Treated ◽  
Significant Difference ◽  
Whole Body Heat Stress ◽  
Body Heat

Introduction: In scrotal mammals, heat stress (43°C/ 20 min) to the scrotum results in germ cell death in the testes1, abnormal spermatozoa, and infertility2 whereas two days of whole body heating (36°C, 12 h/ day) reduces testes weight, sperm numbers and fertility3. The aim of the present study was to determine the intratesticular effects of whole body heating on germ cell maturation and apoptosis. Methods: C57BL/6 mice (n = 16) were housed at 37–38°C for 8 h/ day for 3 days while controls (n = 4) were kept at 23–24°C. Animals from heat treated (n = 4), and control groups (n = 1) were sacrificed at 16 h, 7, 14 and 21 days post exposure to heat. Testes were weighed and analysed by t-test. In testes from each animal, two sections 70µm apart were end labelled for TdT-mediated-dUTP nick (TUNEL). Apoptosis was determined in 200 seminiferous tubules by a colour threshold set in the particle analysis program (Olympus).The tubules were staged as I-VI (early), VII-VIII, IX-X and XI-XII (late) and results analysed using Wilcoxon test. Results: The weights of testes were significantly reduced in heat-treated animals (P < 0.05) at 16 h, 7 and 14 days with no significant difference at 21 days. Apoptosis was significantly higher in the heat-treated group in stages I-VI and XI-XII at 16 h, 7 and 14 days (P < 0.05). In addition, in stages VII-VIII and IX-X apoptosis was significantly higher at 16 h (P < 0.05) with no statistical difference between other time intervals. By day 21, the levels of apoptosis did not differ significantly from the controls in any of the stages (P > 0.05).Conclusion: Whole body heat stress can induce stage and cell specific degeneration of the germ cells in the seminiferous epithelium. The germ cells undergoing apoptosis are spermatogonia, primary spermatocytes and early spermatids. In addition, heat stress produces significant apoptosis of germ cells in the hormone dependent stages VII-VIII immediately after heat stress. (1) Rockett, J.C. et al. (2001) Biol. Reprod. 65:229–239. (2) Banks, S. et al. (2005) Reproduction 129:505–514. (3) Yaeram, J. et al. (2006) Reprod. Fert. Dev. 18:647–653.

Thermally induced stress revealed behavioral, hormonaland histological disturbances in mice model

2016 ◽  
Author(s):  
Wang Genlin ◽  
Shahar Bano Memon ◽  
Li Lian ◽  
Javaid Ali Gadahi
Keyword(s):  
Heat Stress ◽  
Leydig Cells ◽  
Hormone Level ◽  
Serum Testosterone ◽  
Seminiferous Tubules ◽  
Mice Model ◽  
Histological Changes ◽  
Thermally Induced ◽  
Significant Difference ◽  
Low Levels

Behavioral, hormonal and histological changes caused by heat stress at 30 and 40oC were studied in mice model. As a result, obnoxious activities like restlessness and hyperactivity were observed. Rectal temperature was significantly increased at 40oC as well as the increase in water intake, whereas, the feed intake remained consistent. Body weight significantly decreased at 40oC. Serum testosterone has shown a decrease in both groups. At day 7 of the treatment, low levels of growth hormone were recorded whereas no significant difference was recorded at day 15. Adrenocorticotropic hormone level was significantly decreased in both groups at day 7. Shrinking of the seminiferous tubules with irregular appearance containing less spermatozoa was also observed at 40oC. Testicular degeneration and atrophy of leydig cells were also observed. Finally, we concluded that heat stress adversely affects the male reproductive functions along with hormonal imbalances and decline in the spermatogenesis.

Heat Stress and Pulsed Unfocused Ultrasound: The Viability of these Physical Approaches for Drug Delivery into Testicular Seminiferous Tubules

2020 ◽  
Vol 17 (5) ◽  
pp. 438-446 ◽  
Author(s):  
Yuanyuan Li ◽  
Mohammad Ishraq Zafar ◽  
Xiaotong Wang ◽  
Xiaofang Ding ◽  
Honggang Li
Keyword(s):  
Drug Delivery ◽  
Heat Stress ◽  
Targeted Drug Delivery ◽  
Therapeutic Agents ◽  
Seminiferous Tubules ◽  
Adult Mice ◽  
Targeted Drug ◽  
To Receive ◽  
Unfocused Ultrasound ◽  
Blood Testis Barrier

Aim: To investigate the application of Scrotal Heat Stress (SHS) and Pulsed Unfocused Ultrasound (PuFUS) to explore Blood-Testis Barrier (BTB) permeability in adult mice. Background: The BTB provides a stable microenvironment and a unique immune barrier for spermatogenesis. Meanwhile, it blocks macromolecular substances access, including therapeutic agents and antibodies, thereby it decreases the therapeutic or immunocontraception effects. Objectives: To determine the viability of these physical approaches in delivering macromolecular substances into seminiferous tubules. Material & Methods: Mice were subjected to receive single SHS intervention at 39°C, 41°C, or 43°C for 30 min. Whereas, mice received the PuFUS intervention at 1.75w/cm2, 1.25w/cm2, and 2.5w/cm2 for 2 min, 5 min, and 10 min, respectively. The Biotin and macromolecular substances (IgG, IgM, and exosomes) were separately injected into the testicular interstitium at different times following SHS or PuFUS interventions, to observe their penetration through BTB into seminiferous tubules. Results: As detected by Biotin tracer, the BTB opening started from day-2 following the SHS and lasted for more than three days, whereas the BTB opening started from 1.5h following PuFUS and lasted up to 24h. Apparent penetration of IgG, IgM, and exosomes into seminiferous tubules was observed after five days of the SHS at 43°C, but none at 39°C, or any conditions tested with PuFUS. Conclusion: The current results indicate that SHS at 43°C comparatively has the potential for delivering macromolecular substances into seminiferous tubules, whereas the PuFUS could be a novel, quick, and mild approach to open the BTB. These strategies might be useful for targeted drug delivery into testicular seminiferous tubules. However, further studies are warranted to validate our findings.

scholarly journals Oxidative stress increases megalin expression in the renal proximal tubules during the normoalbuminuric stage of diabetes mellitus

2018 ◽  
Vol 314 (3) ◽  
pp. F462-F470 ◽  
Author(s):  
Yoshifumi Kurosaki ◽  
Akemi Imoto ◽  
Fumitaka Kawakami ◽  
Masanori Yokoba ◽  
Tsuneo Takenaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Hydrogen Peroxide ◽  
High Glucose ◽  
Renal Cortex ◽  
Dependent Manner ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphorylated Akt ◽  
Stress Dependent ◽  
Phosphatidylinositol 3

Megalin, an endocytic receptor expressed in proximal tubule cells, plays a critical role in renal tubular protein reabsorption and is associated with the albuminuria observed in diabetic nephropathy. We have previously reported increased oxidant production in the renal cortex during the normoalbuminuric stage of diabetes mellitus (DM); however, the relationship between oxidative stress and renal megalin expression during the normoalbuminuric stage of DM remains unclear. In the present study, we evaluated whether oxidative stress affects megalin expression in the normoalbuminuric stage of DM in a streptozotocin-induced diabetic rat model and in immortalized human proximal tubular cells (HK-2). We demonstrated that increased expression of renal megalin accompanies oxidative stress during the early stage of DM, before albuminuria development. Telmisartan treatment prevented the diabetes-induced elevation in megalin level, possibly through an oxidative stress-dependent mechanism. In HK-2 cells, hydrogen peroxide significantly increased megalin levels in a dose- and time-dependent manner; however, the elevation in megalin expression was decreased following prolonged exposure to severe oxidative stress induced by 0.4 mmol/l hydrogen peroxide. High-glucose treatment also significantly increased megalin expression in HK-2 cells. Concurrent administration of the antioxidant N-acetyl-cysteine blocked the effects of high glucose on megalin expression. Furthermore, the hydrogen peroxide-induced increase in megalin expression was blocked by treatment with phosphatidylinositol 3-kinase and Akt inhibitors. Increase of phosphorylated Akt expression was also seen in the renal cortex of diabetic rats. Taken together, our results indicate that mild oxidative stress increases renal megalin expression through the phosphatidylinositol 3-kinase-Akt pathway in the normoalbuminuric stage of DM.

Inhibitory Effect of Tributyltin on Expression of Steroidogenic Enzymes in Mouse Testis

2008 ◽  
Vol 27 (2) ◽  
pp. 175-182 ◽  
Author(s):  
Suel-Kee Kim ◽  
Jong-Hoon Kim ◽  
Jung Ho Han ◽  
Yong-Dal Yoon
Keyword(s):  
Germ Cells ◽  
Leydig Cells ◽  
Serum Testosterone ◽  
Hydroxysteroid Dehydrogenase ◽  
Reproductive Organs ◽  
Inhibitory Effect ◽  
Testicular Development ◽  
Steroidogenic Enzymes ◽  
Hormone Production ◽  
Induced Apoptosis

Tributyltin (TBT) is known to disrupt the development of reproductive organs, thereby reducing fertility. The aim of this study was to evaluate the acute toxicity of TBT on the testicular development and steroid hormone production. Immature (3-week-old) male mice were given a single administration of 25, 50, or 100 mg/kg of TBT by oral gavage. Lumen formation in seminiferous tubule was remarkably delayed, and the number of apoptotic germ cells found inside the tubules was increased in the TBT-exposed animals, whereas no apoptotic signal was observed in interstitial Leydig cells. Reduced serum testosterone concentration and down-regulated expressions of the mRNAs for cholesterol side-chain cleavage enzyme (P450scc), 17α-hydroxylase/C17–20 lyase (P45017α), 3β-hydroxysteroid-dehydrogenase (3β-HSD), and 17β-hydroxysteroid-dehydrogenase (17β-HSD) were also observed after TBT exposure. Altogether, these findings demonstrate that exposure to TBT is associated with induced apoptosis of testicular germ cells and inhibition of steroidogenesis by reduction in the expression of steroidogenic enzymes in interstitial Leydig cells. These adverse effects of TBT would cause serious defects in testicular development and function.

scholarly journals Germ cell-induced immune suppression in mice. Effect of inoculation of syngeneic spermatozoa on cell-mediated immune responses.

1982 ◽  
Vol 155 (6) ◽  
pp. 1719-1729 ◽  
Author(s):  
U Hurtenbach ◽  
G M Shearer
Keyword(s):  
Germ Cells ◽  
Immune Suppression ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Seminiferous Tubules ◽  
Immune Functions ◽  
Cytotoxic Lymphocyte ◽  
Testicular Cells ◽  
Killer Cell Activity

Spleen cells from mice injected intravenously with syngeneic male germ cells exhibited reduced immune functions as determined by natural killer cell activity, mixed lymphocyte reactivity and cytotoxic lymphocyte (CTL) function. The decrease in CTL responses to trinitrophenyl-modified self (TNP-self) was detected as early as 4 d after sperm injection and was observed to H-2 alloantigens 3 wk after injection. Radiosensitive suppressor T cells were found to suppress the CTL response to TNP-self. Suppression lasted for a period of at least 7 wk after a single inoculation of the germ cells. Some variability in immune suppression capability was observed using different preparations of germ cells which are not yet completely understood. Sperm were more effective in inducing suppression than testicular cells derived from the seminiferous tubules. Furthermore, sperm from older animals were more effective than those from younger mice. These findings are discussed with respect to possible regulatory influences of germ cells on the immune system when the blood-testes barrier is broken.

scholarly journals Aphrodisiac Activity of Eulophia macrobulbon Extract on Erectile Dysfunction in Male Aged Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Watcharaporn Preedapirom ◽  
Kanokwan Changwichit ◽  
Piyarat Srisawang ◽  
Kornkanok Ingkaninan ◽  
Pornnarin Taepavarapruk
Keyword(s):  
Erectile Dysfunction ◽  
Serum Testosterone ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Sildenafil Citrate ◽  
Male Rats ◽  
Cgmp Level ◽  
Seminiferous Tubules ◽  
Aged Rats ◽  
Sexual Performance

This study investigated the effect of Eulophia macrobulbon (EM) extract on sexual performance in aged-related erectile dysfunction (ED) rats. The ethanol EM extract at the doses of 15, 150, and 450 and sildenafil citrate at the dose of 5 mg/kg body weight (BW) were administered orally to the aged male rats once daily for 21 days. Mating parameters and intracavernosal pressure (ICP) were measured to evaluate their sexual and erection functions. Numbers of sperm and sperm motility as well as the diameter of seminiferous tubules were observed. The serum testosterone and 3’,5’-cyclic guanosine monophosphate (cGMP) concentration in the rat penile tissue were analyzed. The results showed the significant increased sexual motivation, copulatory performance, and ICP of aged rats treated with sildenafil citrate and all doses of EM extract as compared to control aged rats. Moreover, their serum testosterone levels were slightly increased and significant increase in penile cGMP concentration was observed in these aged rats treated with sildenafil citrate and EM extract. The results suggest that treatment with EM could inhibit activity of PDE5 in penile tissue resulting in the increased cGMP level and bring to the improvement of erectile function and sexual performance.

scholarly journals Minireview: Transcriptional Regulation of Gonadal Development and Differentiation

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1035-1042 ◽  
Author(s):  
Susan Y. Park ◽  
J. Larry Jameson
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Cell Types ◽  
Gonadal Development ◽  
Targeted Mutagenesis ◽  
Seminiferous Tubules ◽  
Molecular Pathways ◽  
Theca Cells ◽  
Main Cell

The embryonic gonad is undifferentiated in males and females until a critical stage when the sex chromosomes dictate its development as a testis or ovary. This binary developmental process provides a unique opportunity to delineate the molecular pathways that lead to distinctly different tissues. The testis comprises three main cell types: Sertoli cells, Leydig cells, and germ cells. The Sertoli cells and germ cells reside in seminiferous tubules where spermatogenesis occurs. The Leydig cells populate the interstitial compartment and produce testosterone. The ovary also comprises three main cell types: granulosa cells, theca cells, and oocytes. The oocytes are surrounded by granulosa and theca cells in follicles that grow and differentiate during characteristic reproductive cycles. In this review, we summarize the molecular pathways that regulate the distinct differentiation of these cell types in the developing testis and ovary. In particular, we focus on the transcription factors that initiate these cascades. Although most of the early insights into the sex determination pathway were based on human mutations, targeted mutagenesis in mouse models has revealed key roles for genes not anticipated to regulate gonadal development. Defining these molecular pathways provides the foundation for understanding this critical developmental event and provides new insight into the causes of gonadal dysgenesis.

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