Browsing by Author "Shio Kumar Singh"

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A comprehensive review on the decabromodiphenyl ether (BDE-209)-induced male reproductive toxicity: Evidences from rodent studies
(Elsevier B.V., 2023) Debarshi Sarkar; Parul Midha; Shashanka Sekhar Shanti; Shio Kumar Singh
Polybrominated diphenyl ethers (PBDEs), a class of brominated flame retardants (BFRs), are employed in various manufactured products to prevent fires, slow down their spread and reduce the resulting damages. Decabromodiphenyl ether (BDE-209), an example of PBDEs, accounts for approximately 82 % of the total production of PBDEs. BDE-209 is a thyroid hormone (TH)-disrupting chemical owing to its structural similarity with TH. Currently, increase in the level of BDE-209 in biological samples has become a major issue because of its widespread use. BDE-209 causes male reproductive toxicity mainly via impairment of steroidogenesis, generation of oxidative stress (OS) and interference with germ cell dynamics. Further, exposure to this chemical can affect metabolic status, sperm concentration, epigenetic regulation of various developmental genes and integrity of blood-testis barrier in murine testis. However, the possible adverse effects of BDE-209 and its mechanism of action on the male reproductive health have not yet been critically evaluated. Hence, the present review article, with the help of available literature, aims to elucidate the reproductive toxicity of BDE-209 in relation to thyroid dysfunction in rodents. Further, several crucial pathways have been also highlighted in order to strengthen our knowledge on BDE-209-induced male reproductive toxicity. Data were extracted from scientific articles available in PubMed, Web of Science, and other databases. A thorough understanding of the risk assessment of BDE-209 exposure and mechanisms of its action is crucial for greater awareness of the potential threat of this BFR to preserve male fertility. © 2023 Elsevier B.V.
Acute exposure to perfluorononanoic acid in prepubertal mice: Effect on germ cell dynamics and an insight into the possible mechanisms of its inhibitory action on testicular functions
(Academic Press, 2019) Shilpi Singh; Shio Kumar Singh
Perfluoroalkyl acids (PFAAs) are anthropogenic compounds used globally in a variety of commercial products. Perfluorononanoic acid (PFNA), a member of PFAAs, is detected in human blood and this has been reported to cause hepatotoxic, immunotoxic, and developmental and testicular toxic effects in laboratory animals. We have recently shown that the acute exposure to PFNA in prepubertal Parkes (P) mice impairs spermatogenesis by inducing oxidative stress and inhibiting testosterone biosynthesis in the testis. The present study was aimed to examine the effect of acute exposure to PFNA in prepubertal P mice on germ cell dynamics and to understand the possible mechanisms of action of this compound on testicular functions. PFNA (2 and 5 mg/kg body weight) was orally administered to male mice for 14 days from postnatal day 25–38. The treatment caused a decrease in overall germ cell transformation. The results also reveal that impairment in testicular functions in treated mice is associated with alterations in cholesterol and glucose homeostasis; further, an inhibition in expressions of growth hormone receptor (GHR), insulin-like growth factor-1 (IGF-1), insulin-like growth factor-1 receptor (IGF-1R), androgen receptor (AR), phosphorylated mammalian target of rapamycin (p-mTOR) and peroxisome proliferator activated receptor α (PPAR α) in the testis is also implicated in this action. The findings thus suggest involvement of multiple factors which altogether contribute to the alterations in spermatogenic process and testosterone production following acute exposure to PFNA in prepubertal mice. © 2019 Elsevier Inc.
Anti-androgenic and anti-proliferative properties of methanolic leaf extract of Allamanda cathartica Linn. in adult mouse testis: Evidences from in vivo and in silico studies
(Elsevier Ltd, 2025) Rakesh Raman; Rimple Kaur; Swanand Kulkarni; Deepanshu Joshi; Jyoti Parkash; Suresh Thareja; Debarshi Sarkar; Shio Kumar Singh
Dysregulation in androgen production causes a variety of clinical disorders like male pattern baldness, hirsutism, acne vulgaris, benign prostatic hyperplasia, prostate cancer and polycystic ovarian syndrome. Although the common synthetic drugs used to treat these diseases have many side effects, there is growing demand for alternative and herbal therapies. Allamanda cathartica Linn. (family, Apocynaceae) is traditionally used to treat variety of diseases because of its hepatoprotective, antidiabetic, anti-inflammatory, antitumor and antimicrobial properties. However, the effects of Allamanda leaves on testosterone production still remain elusive. The present study aims to elucidate the effect and possible mode(s) of action of the methanolic leaf extract of A. cathartica (MLEAC) on androgen biosynthesis and germ cell proliferation in adult mouse testis. Adult male C57BL/6J mice were orally administered MLEAC (150 and 300 mg/kg body weight/day) or distilled water (controls) for 42 days. MLEAC treatment caused non-uniform degenerative changes in the histoarchitecture of testis. The treatment also had negative impact on serum testosterone level with downregulation of the expressions of major steroidogenic proteins (StAR, CYP11A1, 3β-and 17β-HSD3). Flow cytometry and immunohistochemical analyses showed impaired gem cell proliferation in MLEAC-treated mice testes. The GC-MS method identified 20 phytocompounds in MLEAC. The in silico study further revealed that GC-MS-derived phytochemicals have the potential to bind with major steroidogenic proteins in testis. MLEAC treatment thus causes suppression of germ cell proliferation via downregulation of testosterone production. Keeping in view the traditional use of Allamanda, the present findings may prove helpful in the search of a plant-based anti-androgenic compound. © 2025 Elsevier Ltd
Antifertility efficacy of Coccinia indica in male mice and its possible mechanisms of action on spermatogenesis
(Academic Press Inc., 2017) Hari Prakash Verma; Shio Kumar Singh
The purpose of the present study was to investigate the antifertility efficacy of Coccinia indica and its possible mechanisms of action on testicular functions in Parkes male mice. Mice were orally administered 50% ethanolic leaf extract of Coccinia indica (200 and 500 mg kg−1 body weight day−1) or distilled water (controls) for 35 days. To assess reversibility, additional mice were treated with 500 mg kg−1 body weight of Coccinia or distilled water for 35 days and sacrificed 56 days later. Several male reproductive parameters such as motility, viability, morphology and number of spermatozoa in the cauda epididymidis, histopathology, serum level of testosterone, and fertility indices were evaluated; further, activities of 3β- and 17β-hydroxysteroid dehydrogenases, western blot analyses of StAR protein, cytochrome P450scc enzyme and of caspase-3, germ cell apoptosis by TUNEL, and lipid peroxidation and antioxidant enzymes activities in the testis were assessed. Toxicological parameters were also examined. Histologically, testes in Coccinia-treated mice showed nonuniform diverse degenerative changes in the seminiferous tubules. Treatment had adverse effect on serum level of testosterone, steroidogenic markers in the testis and on sperm parameters in the cauda epididymidis. The treatment also affected oxidative status of the testis and induced germ cell apoptosis. Serum levels of alanine aminotransferase, aspartate aminotransferase and creatinine, and haematological parameters were, however, not affected in treated mice. Fertility of the extract-treated males was also suppressed, but their libido remained unaffected. By 56 days of treatment withdrawal, the above parameters recovered to control levels, suggesting that the Coccinia treatment causes reversible suppression of spermatogenesis and fertility in P mice, without producing detectable signs of toxicity. Further, suppression of spermatogenesis may be caused by germ cell apoptosis resulting from deficiency of testosterone, which, in turn, may result from the adverse effect of C. indica treatment on steroidogenesis and oxidative status in the testis. © 2016 Elsevier Inc.
Antispermatogenic and antifertility effects of fruits of Piper nigrum L. in mice
(2009) Raghav Kumar Mishra; Shio Kumar Singh
Effect of oral administration (25 and 100 mg/kg body wt/day, for 20 and 90 days) of fruit powder of Piper nigrum L. on the male reproductive organs of mice, Parkes strain, was investigated. Various reproductive end points such as organs weight, histopathology, sperm parameters, sialic acid and fructose contents, and fertility indices were assessed. Histologically, testes in treated mice, except in those treated with 100 mg of dose for 90 days, showed non-uniform degenerative changes in the seminiferous tubules, as both affected and normal tubules were observed in the same section. In mice treated with 100 mg dose for 90 days, degenerative changes were observed in all the tubules. Affected seminiferous tubules showed intraepithelial vacuolation, loosening of germinal epithelium, occurrence of giant cells, and mixing of spermatids of different stages of spermatogenesis; in severe cases, the tubules were lined by mainly a layer of Sertoli cells. Percentage of affected tubules in testes of Piper-treated mice was dose-and duration-related. Further, Piper nigrum treatment for 20 days did not cause appreciable alterations in histological appearance of the epididymis, while the treatment for 90 days caused detectable alterations in the duct. The treatment also had adverse effects on sperm parameters, levels of sialic acid and fructose, and on litter size. Fifty six days after cessation of treatment, the alterations induced in the reproductive organs recovered to control levels, though the litter size in females impregnated by Piper-treated males remained significantly decreased compared to controls.
Chronic exposure to perfluorononanoic acid impairs spermatogenesis, steroidogenesis and fertility in male mice
(John Wiley and Sons Ltd, 2019) Shilpi Singh; Shio Kumar Singh
Perfluoroalkyl acids (PFAAs) are widely used in commercial applications and that they are ubiquitous and persistent in the environment. Perfluorononanoic acid (PFNA), a member of PFAAs, has been detected in human and wildlife. Previous acute exposure studies have shown the adverse effect of PFNA on the testis. The present study was aimed to examine the effect of chronic PFNA exposure, from prepuberty to adulthood, on testicular functions and fertility in Parkes (P) male mice and to investigate the possible mechanism(s) of its action. PFNA (0.2 and 0.5 mg/kg) was orally administered to P male mice for 90 days from prepuberty (postnatal day [PND] 25) to adulthood (PND 114). Histologically, testes in PFNA-treated mice showed non-uniform degenerative changes in the seminiferous tubules. The treatment also had adverse effects on testicular expression of steroidogenic markers, serum levels of cholesterol and testosterone, sperm parameters and on litter size. A marked increase in the level of lipid peroxidation and decrease in the activities of antioxidant enzymes were observed in the testis of PFNA-treated mice compared to controls. Further, a significant decrease in expression of proliferating cell nuclear antigen (PCNA) and in the number of PCNA-positive cells, and an increase in expression of caspase-3 were also noted in PFNA-treated mice testis. In conclusion, the results suggest that chronic exposure to PFNA in male mice interferes with testosterone biosynthesis and causes oxidative stress in the testis, leading to alterations in spermatogenesis, sperm quality and fertility potential. © 2018 John Wiley & Sons, Ltd.
Citrus limon extract: Possible inhibitory mechanisms affecting testicular functions and fertility in male mice
(Taylor and Francis Ltd, 2016) Nidhi Singh; Shio Kumar Singh
The effect of oral administration of 50% ethanolic leaf extract of Citrus limon (500 and 1,000 mg/kg body weight/day) for 35 days on fertility and various male reproductive endpoints was evaluated in Parkes strain of mice. Testicular indices such as histology, 3β- and 17β-HSD enzymes activity, immunoblot expression of StAR and P450scc, and germ cell apoptosis by TUNEL and CASP- 3 expression were assessed. Motility, viability, and number of spermatozoa in the cauda epididymidis, level of serum testosterone, fertility indices, and toxicological parameters were also evaluated. Histologically, testes in extract-treated mice showed nonuniform degenerative changes in the seminiferous tubules. Treatment had adverse effects on steroidogenic markers in the testis and induced germ cell apoptosis. Significant reductions were noted in epididymal sperm parameters and serum level of testosterone in Citrus-treated mice compared to controls. Fertility of the extract-treated males was also suppressed, but libido remained unaffected. By 56 days of treatment withdrawal, alterations induced in the above parameters returned to control levels suggesting that Citrus treatment causes reversible suppression of spermatogenesis and fertility in Parkes mice. Suppression of spermatogenesis may result from germ cell apoptosis because of decreased production of testosterone. The present work indicated that Citrus leaves can affect male reproduction. © 2016 Taylor & Francis.
Decabromodiphenyl ether (BDE-209) exposure to lactating mice perturbs steroidogenesis and spermatogenesis in adult male offspring
(Academic Press, 2021) Debarshi Sarkar; Shio Kumar Singh
Decabromodiphenyl ether (BDE-209) is widely used as a flame retardant in many products like electronic equipments, plastics, furniture and textiles. BDE-209, a thyroid hormones (THs)-disrupting chemical, affects male reproductive health through altered THs status in mouse model. The present study was designed in continuation to our earlier work to elucidate whether early life exposure to BDE-209 has a long term potential risk to male reproductive health. This study, therefore, aimed to evaluate the effect of maternal BDE-209 exposure during lactation and to elucidate possible mechanism(s) of its action on male reproduction in adult Parkes mice offspring. Lactating female Parkes mice were orally gavaged with 500, and 700 mg/kg body weight of BDE-209 in corn oil from postnatal day (PND) 1 to PND 28 along with 6-propyl-2-thiouracil (PTU)-treated positive controls and vehicle-treated controls. Male pups of lactating dams were euthanized at PND 75. Maternal BDE-209 exposure during lactation markedly affected histoarchitecture of testis and testosterone production with concomitant down-regulation in the expression of various steroidogenic markers in adult offspring. Maternal exposure to BDE-209 during lactation also interfered with germ cell dynamics and oxidative status in testes of adult mice offspring. A decreased expression of connexin 43 and androgen receptor was also evident in testes of these mice offspring; further, number, motility and viability of spermatozoa were also adversely affected in these mice. The results thus provide evidences that maternal exposure to BDE-209 during lactation causes reproductive toxicity in adult mice offspring. © 2020 The Authors
Decreased expression of orexin 1 receptor in adult mice testes during alloxan-induced diabetes mellitus perturbs testicular steroidogenesis and glucose homeostasis
(Elsevier B.V., 2017) Deepanshu Joshi; Debarshi Sarkar; Shio Kumar Singh
Diabetes mellitus (DM) affects male reproductive system and causes infertility. The male reproductive health is largely dependent upon uptake and proper utilization of glucose by testicular cells. Results show involvement of orexin A (OXA) and its receptor (OX1R) in regulation of steroidogenesis and glucose homeostasis in adult mice testis. However, the role of OX1R in regulation of testicular functions during hyperglycemia has not been investigated so far. The present study, therefore, examined the role of OX1R in regulation of steroidogenesis and glucose homeostasis in testis of adult mice during alloxan-induced type 1 DM. A significant decrease was noted in body weight and testis weight in alloxan-treated mice compared to controls. The blood glucose level, however, was markedly increased in treated animals than in controls. Further, serum and intratesticular level of testosterone, activities of testicular steroidogenic enzymes, and expressions of various steroidogenic markers, OX1R, glucose transporter 3 (GLUT3) and Wilms' tumor gene (WT1) were downregulated in treated mice. The level of glucose, activity of lactate dehydrogenase (LDH) and lactate concentration in the testes of diabetic mice were also decreased; a significant increase in the number of testicular apoptotic cells with concomitant increase in the expression of caspase-3 was noted in these mice. Furthermore, DM affected germ cell proliferation with decreased expression of proliferating cell nuclear antigen (PCNA). Results thus suggest that type 1 DM impairs testicular steroidogenesis and glucose homeostasis through inhibition of OXA/OX1R signaling cascade due to decreased OX1R expression in adult mice, thereby affecting germ cell survival and their proliferation in the testis. © 2017 Elsevier Inc.
Effect of 17 α-cyanomethyl-17 β-hydroxy-estra-4,9-dien-3-one on reproductive organs of the male laboratory mouse
(1998) Sumana Chakravarty; Shio Kumar Singh
The effect of subcutaneous administration (10, 15 and 20 mg/kg body weight/day, for 21days; and 20 mg/kg body weight/day, for 28 days) of 17α -cyanomethyl-17β-hydroxy- estra-4, 9-dien-3-one (STS 557) on the male reproductive organs of the Parkes strain mouse was investigated.The effect of the treatment on the testis was not uniform; both regressed and normal seminiferous tubules were observed in the same section of the organ. Furthermore, the histological changes observed in the seminiferous tubules in testes of STS 557 - treated mice were not different in different dosage groups. In general, in moderately affected seminiferous tubules, the germinal epithelium was thin and consisted of Sertoli cells, spermatogonia, spermatocytes and spermatids; such tubules showed presence of many vacuoles in the epithelium. In severe cases, the tubules had collapsed and were lined by mainly Sertoli cells, spermatogonia and spermatocytes. The treatment also caused marked depression in motility and concentration of spermatozoa in cauda epididymidis, weight of accessory sex glands and in the levels of sialic acid and fructose in the epididymis and seminal vesicle ,respectively. By 56 days of drug withdrawal, the alterations induced in the reproductive organs returned to control levels, suggesting that STS 557 treatment induces reversible alterations in the male reproductive organs of Parkes strain mouse.
Effect of aqueous leaf extract of Azadirachta indica on the reproductive organs in male mice
(2005) Raghav Kumar Mishra; Shio Kumar Singh
Effect of oral administration (50, 100, and 200 mg/kg body weight/day, for 28 days) of aqueous leaf extract of neem (Azadirachta indica) on the male reproductive organs of the Parkes (P) strain mice was investigated. The treatment had no effect on body weight and the reproductive organs weight. In treated mice, testes showed both normal and affected seminiferous tubules in the same sections; the affected seminiferous tubules showed intraepithelial vacuolation, loosening of germinal epithelium, marginal condensation of chromatin in round spermatids, occurrence of giant cells, mixing of germ cell types in stages of spermatogenesis and degenerated appearance of germ cells. In severe cases, the tubules were lined with Sertoli cells only, Sertoli cells and rare germ cells, or with Sertoli cells and several germ cells but without cellular association patterns. Also, the frequency of affected seminiferous tubules in testes of the extract-treated mice was significantly higher than the controls, though this remained unaffected in mice treated at 50 mg/kg body weight of the extract. Doses at 50 or 100 mg/kg body weight of neem leaf extract did not cause appreciable alterations in histological appearance of the epididymis, while a dose of 200 mg/kg body weight caused marked alterations both in histological appearance and the level of sialic acid in the duct. The treatment also had adverse effects on motility, morphology, and number of spermatozoa in the cauda epididymidis, level of fructose in the seminal vesicle, and on litter size. After 42 days of withdrawal of the treatment, the alterations induced in the reproductive organs recovered to control levels. Our results suggested that treatment with neem leaf extract caused reversible alterations in the male reproductive organs of P mice.
Effect of aqueous leaf extract of Dalbergia sissoo Roxb. on spermatogenesis and fertility in male mice
(Informa Healthcare, 2014) Hari Prakash Verma; Shio Kumar Singh
Objectives: Antifertility effects of Dalbergia sissoo in male mice were investigated. Methods: Adult Parkes strain male mice were orally administered aqueous leaf extract of Dalbergia sissoo (50 and 100 mg/kg body weight/day) or distilled water or no treatment (controls) for 35 days (n = 5/group). Motility, viability and number of spermatozoa in the cauda epididymidis; testis histology; serum level of testosterone; and toxicological parameters were evaluated. To assess reversibility, more mice were treated with 100 mg/kg body weight of Dalbergia sissoo or distilled water (n = 5/group) for 35 days and sacrificed 56 days later. Fertility was also assessed separately. Results: Histologically, testes of Dalbergia-treated mice showed dissimilar degenerative changes in the seminiferous tubules. Significant reductions were noted (i) in epididymal sperm motility, viability and number, and (ii) in serum level of testosterone in Dalbergia-treated mice compared to controls. However, serum levels of alanine aminotransferase, aspartate aminotransferase and creatinine, and haematological parameters were not affected. Also libido of Dalbergia-treated males showed no change, but their fertility was markedly suppressed. By 56 days of treatment withdrawal, alterations induced in the above parameters returned to control levels. Conclusions: Dalbergia sissoo treatment caused reversible suppression of spermatogenesis and fertility in P mice, without eliciting detectable toxic effects. © 2014 The European Society of Contraception and Reproductive Health.
Effect of gestational exposure to perfluorononanoic acid on neonatal mice testes
(John Wiley and Sons Ltd, 2019) Shilpi Singh; Shio Kumar Singh
Perfluoroalkyl acids (PFAAs) are widely used in commercial products and are found in many goods of daily use. Perfluorononanoic acid (PFNA) is one of the PFAAs that possesses endocrine disrupting properties and we have recently shown that PFNA affects testicular functions in Parkes mice. Exposure to environmental endocrine disruptors during fetal life is believed to affect gonadal development and they might produce reproductive abnormalities in males. Therefore, the present study examined the effect of gestational exposure to PFNA on the testes of neonatal mice offspring. Pregnant Parkes mice were orally administered PFNA (2 and 5 mg/kg body weight) or distilled water from gestational day 12 until parturition. Male pups were killed on postnatal day 3. PFNA treatment decreased testosterone biosynthesis by inhibiting expression of steroidogenic acute regulatory protein, cytochrome P450scc, and 3β- and 17β-hydroxysteroid dehydrogenase; proliferation of testicular cells was also affected in treated mice. Furthermore, a marked decrease in expression of Wilms tumor 1, steroidogenic factor 1 and insulin-like factor 3 was noted in neonatal mice testes, indicating that the PFNA treatment may affect the development of the testis. Moreover, observation of the dose-related expression of anti-müllerian hormone and c-Kit in neonatal mice testes is also suggestive of an interference with gonadal development by PFNA exposure. In conclusion, the results suggest that the gestational exposure to PFNA decreased testosterone biosynthesis and altered the expression of critical factors involved in the development of the testis, thereby advocating a potential risk of PFNA to male reproductive health. © 2019 John Wiley & Sons, Ltd.
Effect of neonatal hypothyroidism on prepubertal mouse testis in relation to thyroid hormone receptor alpha 1 (THRα1)
(Academic Press Inc., 2017) Debarshi Sarkar; Shio Kumar Singh
Thyroid hormones (THs) are important for growth and development of many tissues, and altered thyroid status affects various organs and systems. Testis also is considered as a thyroid hormone responsive organ. Though THs play an important role in regulation of testicular steroidogenesis and spermatogenesis, the exact mechanism of this regulation remains poorly understood. The present study, therefore, is designed to examine the effect of neonatal hypothyroidism on prepubertal Parkes (P) strain mice testis in relation to thyroid hormone receptor alpha 1 (THRα1). Hypothyroidism was induced by administration of 6-propyl-2-thiouracil (PTU) in mother's drinking water from birth to day 28; on postnatal day (PND) 21 only pups, and on PND 28, both pups and lactating dams were euthanized. Serum T3 and T4 were markedly reduced in pups at PND 28 and in lactating mothers, while serum and intra-testicular testosterone levels were considerably decreased in pups of both age groups. Further, serum and intra-testicular levels of estrogen were significantly increased in hypothyroid mice at PND 28 with concomitant increase in CYP19 expression. Histologically, marked changes were noticed in testes of PTU-treated mice; immunohistochemical and western blot analyses of testes in treated mice also revealed marked decrease in the expression of THRα1 at both age groups. Semiquantitative RT-PCR and western blot analyses also showed reductions in both testicular mRNA and protein levels of SF-1, StAR, CYP11A1 and 3β-HSD in these mice. In conclusion, our results suggest that neonatal hypothyroidism alters localization and expression of THRα1 and impairs testicular steroidogenesis by down-regulating the expression SF-1, thereby affecting spermatogenesis in prepubertal mice. © 2016 Elsevier Inc.
Effect of polybrominated diphenyl ether (BDE-209) on testicular steroidogenesis and spermatogenesis through altered thyroid status in adult mice
(Academic Press Inc., 2016) Debarshi Sarkar; Jayita Pal Chowdhury; Shio Kumar Singh
Polybrominated diphenyl ethers (PBDEs), a class of brominated flame retardants (BFRs), have been widely used in many products to minimize the risk of fire, mainly by mixing in polymer products. BDE-209, a congener of PBDEs having structural similarity with thyroid hormones, acts as an endocrine disruptor by interfering with thyroid homeostasis. However, little is known about the effect of BDE-209 exposure on testicular steroidogenesis and spermatogenesis. This study was therefore conducted in adult mice to examine the effect of BDE-209 on testicular steroidogenesis and spermatogenesis in relation to thyroid status, and to explore possible mechanism(s) of its action. Adult Parkes strain male mice were orally gavaged with 750 and 950 mg/kg BW of BDE-209 in corn oil for 35 days. Significant reductions were noted in the levels of serum total T3, T4 and testosterone in mice treated with 950 mg/kg BW of BDE-209 compared to controls; histologically, testes showed nonuniform degenerative changes in the seminiferous tubules as both affected and normal tubules were observed in the same section; further, number and viability of spermatozoa were also adversely affected in cauda epididymidis of these mice. Semiquantitative RT-PCR and western blot analyses also showed significant reductions in both testicular mRNA and protein levels of steroidogenic factor 1 (SF-1), steroidogenic acute regulatory (StAR) protein, cytochrome P450scc (CYP11A1), 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD) in 950 mg dose treated-mice compared to controls. Immunohistochemical and immunoblot analyses further revealed a marked decrease in proliferating cell nuclear antigen (PCNA) positive cells in testes of 950 mg dose of BDE-209-treated mice. However, 750 mg dose of BDE-209 had no effect on the above parameters. In conclusion, our results suggest that exposure of BDE-209 to adult mice causes reduction in serum levels of thyroid hormones and altered thyroid status may partly result into impairment of testicular steroidogenesis because of down-regulated expression of SF-1, thereby causing suppression of spermatogenesis. © 2015 Elsevier Inc.
Effect of standardized extract of Bacopa monnieri (CDRI-08) on testicular functions in adult male mice
(Elsevier Ireland Ltd, 2017) Shishir Kumar Patel; Shilpi Singh; Hemant Kumar Singh; Shio Kumar Singh
Ethnopharmacological relevance Bacopa monnieri (BM) has been used in India since the time of Rig-Veda for augmentation of learning, memory, brain health etc. Aim of the study The memory augmenting effect of BM is well documented. CDRI-08 is a standardized extract of Bacopa monnieri, but its effect on the male reproductive health has not been investigated. Therefore, the aim of the present study was to examine the effect of CDRI-08 administration on the male reproductive organs with special emphasis on testis in adult mice. Materials and methods CDRI-08, containing at least 55% bacosides (the major constituent of BM), was investigated for its effect on testicular functions in adult Parkes (P) mice. A suspension of CDRI-08 was orally administered in doses of 40 and 80 mg kg−1 body weight day−1 for 28 days and various male reproductive end points were evaluated. Results Compared to control, CDRI-08 treatment caused a significant increase (p<0.05) in spermatogenic cell density (germinal epithelial height: control, 55.03±4.22 vs 40 mg, 67.15±2.65 and 80 mg, 69.93±3.76; and tubular diameter: control, 206.55±2.62 vs 80 mg, 253.23±12.19), PCNA index (control, 59.85±2.09 vs 40 mg, 82.17±1.56 and 80 mg, 84.05±3.51) and in steroidogenic indices in the testis, and in sperm viability (control, 0.67±0.010 vs 80 mg, 0.80±0.04) in cauda epididymidis of the treated mice. On the other hand, however, the same treatment caused a significant decrease (p<0.05) in abnormal sperm morphology (control, 21.72±1.06 vs 40 mg, 10.63±1.50 and 80 mg, 15.86±0.87) in cauda epididymidis, and in lipid peroxidation level in testis of the treated mice compared to controls. Conclusion The results suggest that treatment with CDRI-08 extract improves sperm quality, and spermatogenic cell density and steroidogenic indices in the testis of P mice. © 2016 Elsevier Ireland Ltd
Effect of Trigonella foenum-graecum L. seed extract on the reproductive system of male mice and possible mechanism of its action on spermatogenesis
(John Wiley and Sons Inc, 2022) Akanksha Singh; Debarshi Sarkar; Shio Kumar Singh
Fenugreek seed exhibits antidiabetic, antineoplastic, hepatoprotective, antidepressant and immunomodulatory properties. Fenugreek also causes antifertility effects in rodents. However, the impact of fenugreek seed on male reproduction and the possible mode of its action are not properly evaluated. Herein, we examined the effect of aqueous seed extract of fenugreek (FSE) and the possible mechanism of its action on male reproductive health in mice. Parkes mice were orally administered FSE (600 mg/kg body weight/day) or distilled water for 28 and 56 days, respectively. Various sperm parameters, histopathology, serum testosterone level and fertility indices were assessed. Furthermore, steroidogenic enzymes activities, oxidative status and germ cell dynamics in the testis were evaluated. Toxicological endpoints were also assessed. Treatment with FSE caused degenerative changes in the testis histoarchitecture. The treatment also affected various sperm parameters and concentrations of sialic acid and fructose in the epididymis and seminal vesicle, respectively. Fenugreek treatment also had negative impact on oxidative status and germ cell dynamics in the testis; fertility indices were also affected in female mice impregnated by the extract-treated male mice, though libido of the treated male mice remained unaffected. Results show that treatment with FSE caused adverse effects on the male reproductive health and pregnancy outcome in Parkes mice. © 2022 Wiley-VCH GmbH.
Evaluation of antifertility potential of Brahmi in male mouse
(2009) Akanksha Singh; Shio Kumar Singh
Background: The purpose of the present study was to evaluate the effect of Bacopa monnieri (Brahmi) on fertility of male laboratory mouse. Study Design: Mice of the Parkes (P) strain were orally administered Brahmi (250 mg/kg body weight/day, for 28 and 56 days), and effect of the treatment on reproductive organs and fertility was investigated. Recovery and toxicological studies were also carried out. Results: The treatment caused reduction in motility, viability, morphology, and number of spermatozoa in cauda epididymidis. Histologically, testes in mice treated with the plant extract showed alterations in the seminiferous tubules, and the alterations included intraepithelial vacuolation, loosening of germinal epithelium, exfoliation of germ cells and occurrence of giant cells. In severe cases, the tubules were lined by only Sertoli cells or Sertoli cells, spermatogonia and spermatocytes. Significant reductions were also noted in height of the germinal epithelium and diameter of the seminiferous tubules in Brahmi-treated mice compared to controls. Epididymis in treated males showed slight alterations in histological appearance. The treatment had no effect on levels of testosterone, alanine aminotransferase, aspartate aminotransferase and creatinine in blood serum, hematological parameters and on liver and kidney histoarchitecture. In Brahmi-treated males, libido remained unaffected, but fertility was notably suppressed. The alterations caused in the above reproductive endpoints by the plant extract were reversible, and by 56 days of treatment withdrawal, the parameters recovered to control levels. Conclusions: The results in P mice thus suggest that Brahmi treatment causes reversible suppression of spermatogenesis and fertility, without producing apparent toxic effects. © 2009 Elsevier Inc. All rights reserved.
From the Guest Editor's desk...
(2005) Shio Kumar Singh
[No abstract available]
Histologic changes in the mouse testis after bilateral vasectomy
(2000) Shio Kumar Singh; Sumana Chakravarty
Aim: To study the effect of vasectomy on histological appearance of the testis. Methods: Parkes strain mice were used as the animal model; they were bilaterally vasectomized (Vx) or sham-operated (So) and killed at intervals of 4, 6, 9, and 12 months after the operation. Testes were excised from 5 Vx and 5 So mice at each interval and processed for histological examination. Results: Testes of So mice showed normal histological features. By contrast, marked alterations were observed in the seminiferous tubules in testes of Vx mice, except in those killed 4 months after the operation. The seminiferous epithelium in the tubules was only 2-3 layers thick and showed much depletion of germ cells; in severe cases, the epithelium consisted of only a thin layer of Sertoli cells, spermatogonia and a few spermatocytes. Exfoliation of germ cells, occurrence of multinucleated giant cells and vacuolated appearance of the epithelium were of common features in the tubules. Furthermore, lumen of the rete testis in Vx mice was greatly dilated and showed accumulation of spermatozoa with immature germ cells; in mice vasectomized for 6-12 months, several macrophages ingesting spermatozoa were often observed in the lumen of the rete testis. Spermatic granuloma was also sometimes noticed in corpus or in cauda regions of the epididymis in mice vasectomized for 6-12 months. Conclusion: We suggest that consequences of vasectomy should be thoroughly understood in order to make this method rather more popular as a reversible method of male contraception. © 2000, Asian Journal of Andrology.