scholarly journals Influence of antifertility agents Dutasteride and Nifedipine on CatSper gene level in epididymis during sperm maturation in BALB/c mice

Reproduction ◽  
2018 ◽  
Vol 155 (4) ◽  
pp. 347-359 ◽  
Author(s):  
Archana Srivastav ◽  
Bendangla Changkija ◽  
Kunal Sharan ◽  
Geet Kumar Nagar ◽  
Falgun W Bansode

Calcium (Ca2+) signaling is critical for successful fertilization. In spermatozoa, capacitation, hyperactivation of motility and the acrosome reaction are all mediated by increases in intracellular Ca2+ through CatSper (sperm-specific cation channel). The CatSper channel complex contains four pore-forming α subunits (CatSper1–4) and five accessory subunits called β, δ, ε, γ and ζ. Genetic deletion of any of the four CatSper genes in mice results in loss of hyperactivated motility and male infertility. Despite their vital role in male fertility, almost very little is known about influence of antifertility agents on CatSper gene expression in epididymis and epididymal spermatozoa. Therefore, we performed quantitative real-time qPCR analysis for CatSper expression in the epididymis and epididymal sperm of BALB/c mice after treatment with Dutasteride (DS), a dual 5-α reductase inhibitor and Nifedipine (NF) a calcium channel blocker as positive control. We observed that treatment with antifertility agents Dutasteride and Nifedipine induced significant decreases in the caput and cauda epididymal sperm counts, motility and fertility which could partly be attributed to alteration in the normal morphology of the sperm associated with downregulation/upregulation of CatSper mRNAs in epididymis and epididymal spermatozoa of male BALB/c mice. These can be explained on the basis of interference with mechanisms affecting calcium ion signaling resulting in changes in intracellular calcium required for sperm activity, finally affecting sperm maturation and fertility of male BALB/c mice. These studies provide some novel avenues for developing new male contraceptives in future.

2021 ◽  
Vol 548 ◽  
pp. 7-13
Author(s):  
Zongzhuang Wen ◽  
Dongyue Liu ◽  
Haixia Zhu ◽  
Xiaoyang Sun ◽  
Yu Xiao ◽  
...  

Author(s):  
Surekha D. Shetty ◽  
Laxminarayana Bairy K. ◽  
AM Prasad ◽  
Satheesha Nayak B. ◽  
Ashwini Aithal P.

Background: Hormones play a vital role in initiating and maintenance of male reproductive or testicular function which includes the production of androgens and spermatozoa. Testosterone is essential for the initiation and maintenance of spermatogenesis. FSH is responsible for the stimulation of spermatogenesis. Semen analysis and hormone evaluation are essential parameters in the diagnosis of infertility in males. Objective: The aim of the present study is to evaluate the effect of sorafenib on FSH and intratesticular testosterone levels in male Swiss albino mice. Materials and Methods: The animals were segregated into control, positive control, and treatment groups (n=6). Treatment group received 25, 50 and 100 mg/kg body weight of sorafenib orally for seven consecutive days at intervals of 24 hours between two administrations. Positive control group received 100 mg/kg body weight of imatinib. The animals were sacrificed at the end of 1st, 2nd, 4th, 5th, 7th and 10th week after the last exposure to sorafenib. Results: The intratesticular testosterone level was significantly (P<0.05) reduced in treated groups and severe effect was observed on week 4th and 5th weeks. FSH level was increased significantly (P<0.05) in sorafenib treated groups of mice. Conclusion: The administration of sorafenib does affect testosterone and FSH level significantly, but this effect is reversible once the drug is withdrawn. This finding may help the clinicians to plan and address the fertility-related issues in young patients of reproductive age who are being treated with sorafenib for advanced renal cell carcinoma, hepatocellular carcinoma and differentiated thyroid carcinoma.


2018 ◽  
Vol 24 (3) ◽  
pp. 111-122 ◽  
Author(s):  
Jinghua Hu ◽  
D Jo Merriner ◽  
Anne E O’Connor ◽  
Brendan J Houston ◽  
Luc Furic ◽  
...  

1991 ◽  
Vol 130 (2) ◽  
pp. 231-NP ◽  
Author(s):  
H. D. Nicholson ◽  
S. E. F. Guldenaar ◽  
G. J. Boer ◽  
B. T. Pickering

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


Zygote ◽  
1999 ◽  
Vol 7 (3) ◽  
pp. 211-222 ◽  
Author(s):  
Gary N. Cherr ◽  
Ashley I. Yudin ◽  
Ming-Wen Li ◽  
Carol A. Vines ◽  
James W. Overstreet

The hyaluronic acid (HA)-rich extracellular matrix (ECM) of the cumulus oophorus is known to facilitate fertilisation. It has been suggested that HA may enhance fertilisation in a number of species, and in macaque sperm, HA has been shown to increase the number of acrosome reactions that follow sperm binding to the zona pellucida. In this study, we investigated the effects of HA on intracellular Ca2+ in capacitated cynomolgus macaque sperm. Fluorometry studies using the intracellular Ca2+ indicator Fluo-3 showed that addition of 100 μg/ml of HA induced a rapid increase in intracellular Ca2+. This Ca2+ increase (approximately 2–3 times above basal levels) was inhibited by preincubation of sperm with Fab fragments of anti-recombinant PH-20 IgG. The frequency of acrosome reactions in sperm exposed to HA was not above control levels. A synthetic gel was prepared with similar viscosity to the cumulus and with HA trapped in its matrix. Video imaging of individual sperm was used to demonstrate that capacitated sperm swimming into the HA gel had increased intracellular Ca2+ levels. Preincubation of sperm with Fab fragments of anti-PH-20 IgG inhibited the increased intracellular Ca2+ levels induced by the HA gel. Sperm in control gel (no HA) did not show increased intracellular Ca2+, while sperm in gel containing anti-PH-20 IgG showed increased Ca2+ (positive control). Sperm loaded with Fluo-3 were allowed to interact with cynomologus macaque cumulus masses, and sperm within the cumulus ECM clearly showed increased intracellular Ca2+ that was inhibited when sperm were preincubated in anti-PH-20 Fab. Fluorescein isothiocyanate (FITC)-HA was found to bind to sperm over the acrosomal region, corresponding to PH-20 localisation, and this binding could be inhibited by preincubation of sperm with anti-PH-20 fragments. The results of this study show that HA increases intracellular Ca2+ in macaque sperm through interaction with plasma membrane PH-20. We propose that HA binding to plasma membrane PH-20 induces an aggregation of receptors that in turn results in intracellular signalling. As a result, sperm have higher basal CA2+ levels and are more responsive to induction of the acrosome reaction after binding to the zona pellucida.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Elnaz Saki ◽  
Latifah Saiful Yazan ◽  
Razana Mohd Ali ◽  
Zalinah Ahmad

Chemoprevention has become an important area in cancer research due to low success rate of current therapeutic modalities. Diet plays a vital role in the etiology of cancer. This research was carried out to study the chemopreventive properties of germinated rough rice (GRR) crude extract in Sprague-Dawley rats induced with azoxymethane. Germination of rough rice causes significant changes in several chemical compositions of presently bioactive compounds. These compounds may prevent or postpone the inception of cancer. Fifty male Sprague-Dawley rats (6 weeks of age) were randomly divided into 5 groups which were (G1) induced with azoxymethane (AOM) and not given GRR (positive control), (G2) induced with AOM and given 2000 mg/kg GRR, (G3) induced with AOM and given 1000 mg/kg GRR, (G4) induced with AOM and given 500 mg/kg GRR, and (G5) not induced with AOM and not given GRR crude extract (negative control). To induce colon cancer, rats received two IP injections of AOM in saline (15 mg/kg) for two subsequent weeks. Organs were removed and weighed. Aberrant crypt foci (ACF) were evaluated histopathologically. β-Catenin expressions were determined by Western blot. Treatment with 2000 mg/kg GRR crude extract not only resulted in the greatest reduction in the size and number of ACF but also displayed the highest percentage of nondysplastic ACF. Treatment with 2000 mg/kg GRR also gave the lowest level of expression in β-catenin. Thus, GRR could be a promising dietary supplement for prevention of CRC.


2015 ◽  
Vol 113 ◽  
pp. 226-243 ◽  
Author(s):  
Valérie Labas ◽  
Lucie Spina ◽  
Clémence Belleannee ◽  
Ana-Paula Teixeira-Gomes ◽  
Audrey Gargaros ◽  
...  

1994 ◽  
Vol 17 (5) ◽  
pp. 256-261 ◽  
Author(s):  
R. WEISSENBERG ◽  
S. YOSSEFI ◽  
Y. OSCHRY ◽  
I. MADGAR ◽  
L. M. LEWIN

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