Morphologic manifestations of testicular and epididymal toxicity

Vidal, Justin D.; Whitney, Katharine M.

doi:10.4161/21565562.2014.979099

Cited by 83 publications

(56 citation statements)

References 59 publications

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“…Testosterone is delivered to the epididymis through the seminiferous tubular fluid produced by Sertoli cells. Any compound causing decreased testicular testosterone results in decreased seminiferous tubular diameter, atrophy of the luminal epithelium, or vacuolization in Sertoli cells [30]. Hence, it could be that administration of BA induced these effects rather than alleviating diabetic alteration via reduced testosterone levels.…”

Section: Discussionmentioning

confidence: 99%

Effects of Betulinic Acid on the Male Reproductive System of a Streptozotocin-Nicotinamide-Induced Diabetic Mouse Model

Ahangarpour

Oroojan

Khorsandi

et al. 2016

World J Mens Health

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PurposeThe present study was conducted to evaluate the favorable or harmful effects of betulinic acid (BA) on a diabetic reproductive system.Materials and MethodsIn this experimental study, 60 male Naval Medical Research Institute mice (20∼25 g) were randomly divided into 6 groups: control, diabetes, diabetes+BA (10, 20, and 40 mg/kg), and diabetes+ metformin (200 mg/kg). A diabetic model was induced by a single dose of streptozotocin (STZ) (65 mg/kg) injection intraperitoneally 15 minutes after an intraperitoneal administration of nicotinamide (NA) (120 mg/kg). BA and metformin were gavaged for 2 weeks after confirmed diabetes induction in the treatment groups. One day after the last treatment, plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were evaluated. The cauda epididymis and testis were removed to analyze the sperm count and testis histopathology.ResultsLH levels increased in diabetic (p<0.001) and diabetic BA-treated mice (p=0.009). Plasma levels of testosterone (p< 0.001) and sperm count (p=0.04) decreased in these groups when compared to the control group. Furthermore, administration of 10 mg/kg (p=0.001), 20 mg/kg (p=0.004), or 40 mg/kg (p<0.001) of BA led to a greater reduction in plasma testosterone levels compared to the diabetes group. Seminiferous tubule vacuole numbers increased in diabetic and diabetic BA-treated mice, but testis morphology and FSH level assessment revealed no significant differences between the groups.ConclusionsSTZ-NA can induce diabetic alterations in the male reproductive system and the administration of BA in diabetic treated mice resulted in a worse outcome.

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Section: Discussionmentioning

confidence: 99%

Effects of Betulinic Acid on the Male Reproductive System of a Streptozotocin-Nicotinamide-Induced Diabetic Mouse Model

Ahangarpour

Oroojan

Khorsandi

et al. 2016

World J Mens Health

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“…Additionally, studies using Sertoli cells isolated from adult rats following chronic exposed to 2,5-hexanedione that identified MT-based cytoskeleton to be one of the primary targets of toxicants are also consistent with findings in vivo as summarized above, illustrating the significance of this in vitro model. In fact, accumulating evidence has suggested that the Sertoli cell cytoskeleton is a common target of multiple toxicants (for reviews, see [29-31, 44-46]). Furthermore, other in vivo studies using cadmium chloride (CdCl2, Mr 183.31) also supported the notion that the Sertoli cell, such as the blood-testis barrier (BTB), is more susceptible to environmental toxicants.…”

Section: Dosing Issues Of Toxicants Used For Studiesmentioning

confidence: 99%

Is toxicant-induced Sertoli cell injury in vitro a useful model to study molecular mechanisms in spermatogenesis?

Mruk

Lee

et al. 2016

Seminars in Cell & Developmental Biology

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Sertoli cells isolated from rodents or humans and cultured in vitro are known to establish a functional tight junction (TJ)-permeability barrier that mimics the blood-testis barrier (BTB) in vivo. This model has been widely used by investigators to study the biology of the TJ and the BTB. Studies have shown that environmental toxicants (e.g., perfluorooctanesulfonate (PFOS), bisphenol A (BPA) and cadmium) that exert their disruptive effects to induce Sertoli cell injury using this in vitro model are reproducible in studies in vivo. Thus, this in vitro system provides a convenient approach to probe the molecular mechanism(s) underlying toxicant-induced testis injury but also to provide new insights in understanding spermatogenesis, such as the biology of cell adhesion, spermatid transport, and others. Herein, we provide a brief and critical review based on studies using this in vitro model of Sertoli cell cultures using primary cells isolated from rodent testes versus humans to monitor environmental toxicant-mediated Sertoli cell injury, and this information is relevant to the molecular mechanisms that regulate spermatogenesis. In short, recent findings have shown that environmental toxicants exert their effects on Sertoli cells to induce testis injury through their action on Sertoli cell actin- and/or microtubule-based cytoskeleton. These effects are mediated via their disruptive effects on actin- and/or microtubule-binding proteins. Sertoli cells also utilize differential spatiotemporal expression of these actin binding proteins to confer plasticity to the BTB to regulate germ cell transport across the BTB.

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“…In addition, Leydig cells also express MHC‐II when participating in antigen‐presenting activity, which also supports our findings concerning an immune response in the testicle due to the exposure to E171 (Tokuda, Kasahara, & Levy, ). Germ cell injury is a primary morphologic indicator of cytotoxic compounds, including some NPs and the mechanism of injury is related to the unbalance of pro‐apoptotic and anti‐apoptotic signaling (e.g., p53, Fas and Bcl systems) but also growth factors (Vidal & Whitney, ).…”

Section: Discussionmentioning

confidence: 99%

Food‐grade titanium dioxide (E171) by solid or liquid matrix administration induces inflammation, germ cells sloughing in seminiferous tubules and blood‐testis barrier disruption in mice

Rodríguez-Escamilla

Medina‐Reyes

Rodríguez‐Ibarra

et al. 2019

J of Applied Toxicology

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Food‐grade titanium dioxide labeled as E171 has been approved for human consumption by the Food and Drug Administration (USA) and by the European Union for five decades. However, titanium dioxide has been classified as a possible carcinogen for humans by the International Agency of Research in Cancer raising concerns of its oral intake and the translocation to bloodstream, which could disturb barriers such as the blood‐testis barrier. There is evidence that titanium dioxide by intragastric/intraperitoneal/intravenous administration induced alterations on testosterone levels, testicular function and architecture, but studies of the E171 effects on the testicle structure and blood‐testis barrier are limited. E171 is contained not only in foods in liquid matrix but also in solid ones, which can exert different biological effects. We aimed to compare the effects of E171 consumption in a solid matrix (0.1%, 0.5% and 1% in pellets) and liquid suspension (5 mg/kg body weight) on testis structure, inflammation infiltrate and blood‐testis barrier disruption of male BALB/c mice. Results showed that none of the administration routes had influence on body weight but an increase in germ cell sloughing and the infiltrate of inflammatory cells in seminiferous tubules, together with disruption of the blood‐testis barrier were similar in testis of both groups even if the dose received in mice in liquid matrix was 136 or 260 times lower than the dose reached by oral intake in solid E171 pellets in 0.5% E171 and 1% E171, respectively. This study highlights the attention on matrix food containing E171 and possible adverse effects on testis when E171 is consumed in a liquid matrix.

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Morphologic manifestations of testicular and epididymal toxicity

Cited by 83 publications

References 59 publications

Effects of Betulinic Acid on the Male Reproductive System of a Streptozotocin-Nicotinamide-Induced Diabetic Mouse Model

Effects of Betulinic Acid on the Male Reproductive System of a Streptozotocin-Nicotinamide-Induced Diabetic Mouse Model

Is toxicant-induced Sertoli cell injury in vitro a useful model to study molecular mechanisms in spermatogenesis?

Food‐grade titanium dioxide (E171) by solid or liquid matrix administration induces inflammation, germ cells sloughing in seminiferous tubules and blood‐testis barrier disruption in mice

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