Reproduction In Male Mice Research Articles

Long-term effect of exposure to triethylene glycol dimethacrylate (TEGDMA) on male mouse reproduction.

Our study investigated the impact on male mouse fertility and reproduction of long-term (14 weeks) exposure to triethylene glycol dimethacrylate (TEGDMA), a co-monomer of resin-based compounds, at doses of 0.01, 0.1, 1, and 10ppm. Test and control mice were then paired with sexually mature untreated female mice and their fertility evaluated. Females paired with males exposed to all TEGDMA doses exhibited a significant decline in pregnancy rates, and significant increases in the total embryonic resorption-to-implantation ratio, except for males exposed to 0.01ppm TEGDMA. Males in the highest dose group (10ppm) showed significant increases in seminal vesicle and preputial gland weights. They also had significantly higher serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) than the controls, and the 0.01ppm dosage group for FSH levels. TEGDMA exposure resulted in notable histopathological alterations in the testis, with detachment of germ cells and shedding of germinal epithelium into the tubule lumen. These results strongly indicate that TEGDMA exposure has detrimental consequences on the reproductive abilities and functions in male mice through disruption of the standard hormonal regulation of the reproductive system, leading to changes in spermatogenesis and ultimately leading to decreased fertility.

Effects of the adsorption behavior of polyamide microplastics on male reproductive health by reduction of testosterone bioavailability

Microplastics (MPs) are global environmental pollutants with potential toxicity concerns, and their effects on the reproductive system have attracted increasing attention. This study investigated the interaction between MPs and mammalian biomolecules, focusing on the relationship between the testosterone adsorption behavior of MPs and male reproductive health. The adsorption capacity of different types of MPs for testosterone was evaluated in vitro experiments. Polyamide (PA)-MPs exhibited stronger adsorption, while polymethyl methacrylate (PMMA)-MPs displayed the weakest adsorption. Sorption equilibrium between PA-MPs and testosterone was achieved within 6 h, fitting the Pseudo-2nd-order model and Langmuir isotherm. The effects of MPs on male reproduction in mice was determined in vivo experiments. Male mice were treated with 0.1 and 0.5 mg/d PA-MPs/PMMA-MPs by gavage once per day for 28 days. The results showed that only 0.5 mg/d PA-MP exposure induced decreased serum testosterone levels, increased testicular testosterone levels compared to the control, and more severe damage to seminiferous tubule structure, sperm motility and sperm morphology compared to the PMMA-MPs group. Meanwhile, PA-MPs could reduce intracellular nuclear translocation of androgen receptor (AR) mediated by testosterone, while PMMA-MPs had no impact. The study revealed that PA-MP adsorption reduced testosterone bioavailability and caused sperm quality to decline, offering new insights into the combined toxicity mechanism of MPs in male mammals.

LP-11: The transgenerational effects of the fine particulate matter on reproduction of male mice in early life stage and the role of methylation of inhibin

LP-11: The transgenerational effects of the fine particulate matter on reproduction of male mice in early life stage and the role of methylation of inhibin

Melatonin improves the ability of spermatozoa to bind with oocytes in the mouse.

Melatonin is a powerful antioxidant regulating various biological functions, including alleviating male reproductive damage under pathological conditions. Here, we aim to analyse the effect of melatonin on normal male reproduction in mice. Male mice received an intraperitoneal injection of melatonin (10mg/kg body weight) for 35 consecutive days. The testis and epididymis morphology, and epididymal sperm parameters were examined. PCNA, HSPA2, SYCP3, ZO-1 and CYP11A1 expressions in epididymis or testis were detected by immunohistochemistry or Western blotting. Male fertility was determined by in vivo and in vitro fertilisation (IVF) experiments. The differentially expressed sperm proteins were identified by proteomics. No visible structural changes and oxidative damage in the testis and epididymis, and no significant side effects on testis weight, testosterone levels, sperm motility, and sperm morphology were observed in the melatonin-treatment group compared with the control group. Spermatogenesis-related molecules of PCNA, SYCP3, ZO-1, and CYP11A1 showed no significant differences in melatonin-treated testis. However, PCNA and HSPA2 increased their expressions in the epididymal initial segments in the melatonin-treatment group. Normal sperm fertilisation, two-cell and blastocyst development were observed in the melatonin-treated group, but melatonin significantly enhanced the sperm binding ability characterised as more sperm binding to one oocyte (control 7.2±1.3 versus melatonin 11.8±1.5). Sperm proteomics demonstrated that melatonin treatment enhanced the biological process of cell adhesion in sperm. This study suggests that melatonin can promote sperm maturation and sperm function, providing important information for further research on the physiological function and protective effect of melatonin in male reproduction.

Identification of biallelic variations of CEP70 in patients with male infertility.

Male infertility is a severe health issue caused by complex and multifactorial pathological conditions. Genetic factors are a major cause of male infertility. CEP70, a centrosomal protein, has been reported to play an important role in male reproduction in mice. However, the role of CEP70 in human male infertility is limited. Whole exome sequencing and Sanger sequencing were used to identify the genetic cause of the infertile patients. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy were further conducted to explore morphological and ultrastructural defects in spermatozoa from the patient. Immunofluorescence staining was used to detect the pathogenicity of the identified variants and the particular expression of CEP70 in testis. In this study, we identified biallelic mutations of CEP70 in two unrelated infertile male individuals with oligoasthenoteratozoospermia that followed a recessive inheritance pattern. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy showed that morphological and ultrastructural defects in the acrosome and flagellum of sperm from the patient in a pattern strikingly similar to that in Cep70-/- male mice. The results of immunofluorescence staining suggested that CEP70 was normally expressed in the acrosome and flagellum of control sperm but was hardly detected in the sperm of patient carrying CEP70 variation. We also explored the particular expression pattern of CEP70 during spermatogenesis in humans and mice. Biallelic mutations of CEP70 might be a novel genetic cause of human male infertility, which could potentially serve as a basis for genetic counseling and diagnosis of male infertility.

ADAD2 functions in spermiogenesis and piRNA biogenesis in mice.

Adenosine deaminase domain containing 2 (ADAD2) is a testis-specific protein composed of a double-stranded RNA binding domain and a non-catalytic adenosine deaminase domain. A recent study showed that ADAD2 is indispensable for the male reproduction in mice. However, the detailed functions of ADAD2 remain elusive. This study aimed to investigate the cause of male sterility in Adad2 mutant mice and to understand the molecular functions of ADAD2. Adad2 homozygous mutant mouse lines, Adad2-/- and Adad2Δ/Δ , were generated by CRISPR/Cas9. Western blotting and immunohistochemistry were used to reveal the expression and subcellular localization of ADAD2. Co-immunoprecipitation tandem mass spectrometry was employed to determine the ADAD2-interacting proteins in mouse testes. RNA-sequencing analyses were carried out to analyze the transcriptome and PIWI-interacting RNA (piRNA) populations in wildtype and Adad2 mutant testes. Adad2-/- and Adad2Δ/Δ mice exhibit male-specific sterility because of abnormal spermiogenesis. ADAD2 interacts with multiple RNA-binding proteins involved in piRNA biogenesis, including MILI, MIWI, RNF17, and YTHDC2. ADAD2 co-localizes and forms novel granules with RNF17 in spermatocytes. Ablation of ADAD2 impairs the formation of RNF17 granules, decreases the number of cluster-derived pachytene piRNAs, and increases expression of ping-pong-derived piRNAs. In collaboration with RNF17 and other RNA-binding proteins in spermatocytes, ADAD2 directly or indirectly functions in piRNA biogenesis.

Deletion of GABAB receptors from Kiss1 cells affects glucose homeostasis without altering reproduction in male mice.

Kisspeptin and γ-amino butyric acid (GABA), synthesized in the central nervous system, are critical for reproduction. Both are also expressed in peripheral organs/tissues critical to metabolic control (liver/pancreas/adipose). Many kisspeptin neurons coexpress GABAB receptors (GABABR) and GABA controls kisspeptin expression and secretion. We developed a unique mouse lacking GABABR exclusively from kisspeptin cells/neurons (Kiss1-GABAB1KO) to evaluate the impact on metabolism/reproduction. We confirmed selective deletion of GABABR from Kiss1 cells in the anteroventral periventricular nucleus/periventricular nucleus continuum (AVPV/PeN; immunofluorescence and PCR) and arcuate nucleus (ARC), medial amygdala (MeA), pituitary, liver, and testes (PCR). Young Kiss1-GABAB1KO males were fertile, with normal LH and testosterone. Kiss1 expression was similar between genotypes in AVPV/PeN, ARC, MeA, bed nucleus of the stria terminalis (BNST), and peripheral organs (testis, liver, pituitary). Kiss1-GABAB1KO males presented higher fasted glycemia and insulin levels, an impaired response to a glucose overload, reduced insulin sensitivity, and marked insulin resistance. Interestingly, when Kiss1-GABAB1KO males got older (9 mo old) their body weight (BW) increased, in part due to an increase in white adipose tissue (WAT). Old Kiss1-GABAB1KO males showed higher fasted insulin, increased pancreatic insulin content, insulin resistance, and significantly decreased pancreatic kisspeptin levels. In sum, lack of GABABR specifically in Kiss1 cells severely impacts glucose homeostasis in male mice, reinforcing kisspeptin involvement in metabolic regulation. These alterations in glucose homeostasis worsened with aging. We highlight the impact of GABA through GABABR in the regulation of the pancreas kisspeptin system in contrast to liver kisspeptin that was not affected.NEW & NOTEWORTHY We developed a unique mouse lacking GABAB receptors specifically in Kiss1 cells to evaluate the impact on reproduction and metabolism. Knockout males showed a severe impact on glucose homeostasis, which worsened with aging. These results reinforce the proposed kisspeptin involvement in metabolic regulation and highlight the impact of GABA through GABABR in the regulation of the peripheral pancreas kisspeptin system.

Conditional deletion of Hspa5 leads to spermatogenesis failure and male infertility in mice

Heat shock proteins (HSPs) have important roles in different developmental stages of spermatogenesis. The heat shock 70 kDa protein 5 (HSPA5) is an important component of the unfolded protein response that promotes cell survival under endoplasmic reticulum (ER) stress conditions. In this study, we explored the function of HSPA5 in spermatogenesis, by generating a germ cell-specific deletion mutant of the Hspa5 gene (conditional knockout of the Hspa5 gene, Hspa5-cKO) using CRISPR/Cas9 technology and the Cre/Loxp system. Hspa5 knockout resulted in severe germ cell loss and vacuolar degeneration of seminiferous tubules, leading to complete arrest of spermatogenesis, testicular atrophy, and male infertility in adult mice. Furthermore, defects occurred in the spermatogenic epithelium of Hspa5-cKO mice as early as Cre recombinase expression. Germ cell ablation of Hspa5 impaired spermatogonia proliferation and differentiation from post-natal day 7 (P7) to P10, which led to a dramatic reduction of differentiated spermatogonia, compromised meiosis, and led to impairment of testis development and the disruption of the first wave of spermatogenesis. Consistent with these results, single-cell RNA sequencing (scRNA-seq) analysis showed that germ cells, especially differentiated spermatogonia, were dramatically reduced in Hspa5-cKO testes compared with controls at P10, further confirming that HSPA5 is crucial for germ cell development. These results suggest that HSPA5 is indispensable for normal spermatogenesis and male reproduction in mice.

Deletion of Aldh4a1 Leads to Impaired Sperm Maturation in Mice

ALDH4A1, a member of the aldehyde dehydrogenase superfamily, is a key enzyme in the mitochondrial proline metabolism pathway. Recent studies have shown that mutations in aldh4a1 lead to reduced fertility and reproductive premature aging of male nematodes. However, the effect of ALDH4A1 on fertility of male mice has not been studied. In this study, we used CRISPR-Cas9 technology to construct a knockout mouse model of Aldh4a1 for the first time to explore the effect of this gene on the reproduction of male mice. The results showed that compared with WT male mice, Aldh4a1^(-/-) male mice were fertile, had normal spermatogenesis but defect in sperm maturation in the epididymis documented by impaired motility, increased morphological abnormalities and increased spontaneous acrosome reaction. In addition, transmission electron microscopy showed vacuoles in the sperm mitochondria, and fracture in the neck of sperms and vacuoles in these mice. These results revealed that ALDH4A1 plays a vital role in the structure of sperm flagellum and the process of sperm maturation in mice.

Cyanidin-3-O-Glucoside Supplement Improves Sperm Quality and Spermatogenesis in a Mice Model of Ulcerative Colitis.

Impaired fertility and low sperm quality are the global health problem with high attention. It has been noted that inflammation may impact fertility by affecting testicular spermatogenesis. Cyanidin-3-O-glucoside is a natural functional pigment with various health benefits. Nevertheless, studies on the mechanism by which C3G protects male reproduction in mice with ulcerative colitis remain scarce. The purpose of this study is to illustrate the potential mechanism of C3G for improving impaired fertility caused by colitis. A DSS-induced colitis model was applied to assess the effects of sperm quality with colitis and the health benefit role of C3G. Results indicated that C3G-treated mice exhibited higher body weight, longer colon length, less crypt damage and focal inflammation infiltration. Being consistent with that, low sperm count, low testis weight, high inflammation levels and abnormal thickness of seminiferous epithelium also observed in the DSS group were significantly recovered upon C3G treatment. These findings suggested that colitis has a close link to impaired fertility. Further analysis found that C3G could significantly suppress the inflammatory mediators in serum. Results conjointly indicated that C3G might improve the impaired fertility of mice with colitis by inhibiting inflammatory cytokines through the blood–testis barrier. C3G could be a promising daily supplement for ameliorating impaired fertility caused by colitis.

Effects of the Ethanol Extracts of Ficus deltoidea leaves on the Reproductive Parameters in Male Mice

BACKGROUND: Indonesia, and in particular East Kalimantan, has a very high diversity of flora that has the potential to be used as traditional medicine. One type of flora is the leaves of Ficus deltoidea Jack. At present, there are no available data about the impact of F. deltoidea leaf ethanol extract on the male reproductive system. AIM: The present study aims to investigate the effect of F. deltoidea leaf ethanol extract on several parameters of reproductive function in male mice, including changes in testicular biochemistry, reproductive hormones profile, and histopathology of the testes after subchronic exposure. METHODS: In total, 25 male mice were divided into five groups: The control group and four treatment groups that received extract doses of 125, 250, 500, and 1000 mg/kgbw for 28 days, respectively. At the end of the treatment, surgery was performed, weight of body and reproductive organs (testis, epididymis, and seminal vesicles) were measured, and testicular biochemistry, reproductive hormone profile, antioxidant activity, and testes histopathology were analyzed. RESULTS: In the subchronic toxicity test, there were no significant changes in body weight or in weight and relative weight of reproductive organs. Levels of testosterone, luteinizing hormone and follicle-stimulating hormone, protein, cholesterol, and activity of enzymes in the testes (alkaline phosphatase, lactate dehydrogenase, and glutamyltransferase) and activity of the enzyme superoxide dismutase increased significantly in the treated mice when compared to control mice (p < 0.05). Glycogen levels were not significantly different, but lipid peroxide (MDA) decreased significantly, though it did not change the histological structure of the testes. CONCLUSION: Ethanolic extract of the leaves of F. deltoidea Jack does not cause toxic effects and even has a beneficial effect on the reproduction of male mice by increasing fertility, reproductive hormones, and antioxidant activity, and it does not change the histological structure of the testes.

Distinct effects of growth hormone deficiency and disruption of hypothalamic kisspeptin system on reproduction of male mice

Growth hormone (GH) deficiency is a common cause of late sexual maturation and fertility issues. To determine whether GH-induced effects on reproduction are associated with alterations in hypothalamic kisspeptin system, we studied the male reproduction in two distinct GH deficiency mouse models. In the first model, mice present GH deficiency secondary to arcuate nucleus of the hypothalamus (ARH) lesions induced by posnatal monosodium glutamate (MSG) injections. MSG-induced ARH lesions led to significant reductions in hypothalamic Ghrh mRNA expression and consequently growth. Hypothalamic Kiss1 mRNA expression and Kiss1-expressing cells in the ARH were disrupted in the MSG-treated mice. In contrast, kisspeptin immunoreactivity remained preserved in the anteroventral periventricular and rostral periventricular nuclei (AVPV/PeN) of MSG-treated mice. Importantly, ARH lesions caused late sexual maturation and infertility in male mice. In our second mouse model, we studied animals profound GH deficiency due to a loss-of-function mutation in the Ghrhr gene (Ghrhrlit/lit mice). Interestingly, although Ghrhrlit/lit mice exhibited late puberty onset, hypothalamic Kiss1 mRNA expression and hypothalamic kisspeptin fiber density were normal in Ghrhrlit/lit mice. Despite presenting dwarfism, the majority of Ghrhrlit/lit male mice were fertile. These findings suggest that spontaneous GH deficiency during development does not compromise the kisspeptin system. Furthermore, ARH Kiss1-expressing neurons are required for fertility, while AVPV/PeN kisspeptin expression is sufficient to allow maturation of the hypothalamic-pituitary-gonadal axis in male mice.

Leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balance

BackgroundEnergy balance is closely related to reproductive function, wherein hypothalamic kisspeptin mediates regulation of the energy balance. However, the central mechanism of kisspeptin in the regulation of male reproductive function under different energy balance states is unclear. Here, high-fat diet (HFD) and exercise were used to change the energy balance to explore the role of leptin and inflammation in the regulation of kisspeptin and the hypothalamic-pituitary-testis (HPT) axis.MethodsFour-week-old male C57BL/6 J mice were randomly assigned to a normal control group (n = 16) or an HFD (n = 49) group. After 10 weeks of HFD feeding, obese mice were randomly divided into obesity control (n = 16), obesity moderate-load exercise (n = 16), or obesity high-load exercise (n = 17) groups. The obesity moderate-load exercise and obesity high-load exercise groups performed exercise (swimming) for 120 min/day and 120 min × 2 times/day (6 h interval), 5 days/week for 8 weeks, respectively.ResultsCompared to the mice in the normal group, in obese mice, the mRNA and protein expression of the leptin receptor, kiss, interleukin-10 (IL-10), and gonadotropin-releasing hormone (GnRH) decreased in the hypothalamus; serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels and sperm quality decreased; and serum leptin, estradiol, and tumor necrosis factor-α (TNF-α) levels and sperm apoptosis increased. Moderate- and high-load exercise effectively reduced body fat and serum leptin levels but had the opposite effects on the hypothalamus and serum IL-10 and TNF-α levels. Moderate-load exercise had anti-inflammatory effects accompanied by increased mRNA and protein expression of kiss and GnRH in the hypothalamus and increased serum FSH, LH, and testosterone levels and improved sperm quality. High-load exercise also promoted inflammation, with no significant effect on the mRNA and protein expression of kiss and GnRH in the hypothalamus, serum sex hormone level, or sperm quality. Moderate-load exercise improved leptin resistance and inflammation and reduced the inhibition of kisspeptin and the HPT axis in obese mice. The inflammatory response induced by high-load exercise may counteract the positive effect of improving leptin resistance on kisspeptin and HPT.ConclusionDuring changes in energy balance, leptin and inflammation jointly regulate kisspeptin expression on the HPT axis.

The Effect of Exposure to Bisphenol A on Spermatozoon and the Expression of Tight Junction Protein Occludin in Male Mice

Although bisphenol A (BPA) has been associated with impaired spermatogenesis, the mechanisms remain unclear. Tight junction occludin plays important roles in spermatogenesis. The objective of the present study was to explore the effects of BPA exposure in adolescent mice. Male mice were orally treated with low-dose (0.05 mg/kg/d), middle-dose (5.0 mg/kg/d), or high-dose (50 mg/kg/d) BPA in corn oil from postnatal day (PND) 35 to 65. Animals were killed on PND 65 and PND 125. On PND 65, the sperm count, sperm motility, and the expression of occludin showed a dose-related decline. On PND 125, the sperm count, sperm motility, and the expression of occludin were in recovery. However, there remained significant decreases in these parameters in the 50 mg/kg/d group on PND 125 compared with the control. The dose-related effects on the measured parameters and occludin expression suggest an early suppressive or damaging effect on the blood–testis barrier followed by recovery after dosing ceased. At a BPA dose of 50 mg/kg/d, recovery did not occur, suggesting that higher doses of BPA may cause irreversible damage to reproduction in male mice.

Prenatal exposure to an environmentally relevant phthalate mixture disrupts testicular steroidogenesis in adult male mice

Endocrine disrupting chemicals (EDCs) in the environment are considered to be a contributing factor to the decline in the sperm quality. With growing evidence of the harmful effects of EDCs on the male reproductive system, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects reproductive outcomes and androgen synthesis. In this study, an environmentally relevant composition of phthalates (15% DiNP, 21% DEHP, 36% DEP, 15% DBP, 8% DiBP, and 5% BBzP) that were detected in urine samples of pregnant women in Illinois, United States, was used. Pregnant CD-1 mice (F0) were orally dosed with a vehicle or the phthalate mixtures (20 µg/kg/day, 200 µg/kg/day, 200 mg/kg/day, or 500 mg/kg/day) from gestational day 10.5 to the day of birth. Then, the indices of the reproductive function of the F1 males born to these dams were assessed. Those male mice prenatally exposed to the phthalate mixture had smaller gonads, prostates and seminal vesicles, especially in the 20 µg/kg/day and 500 mg/kg/day phthalate mixture groups, compared to the controls. Importantly, at the age of 12 months, those prenatally exposed mice had significantly lower serum testosterone concentrations accompanied by the decreased mRNA expression of testicular steroidogenic genes (StAR, Cyp11, and Cyp17) and impaired spermatogenesis. Taken together, this study found that prenatal exposure to environmentally relevant doses of a phthalate mixture caused a life-long impact on the reproduction in male mice.

Effects of Fetal Exposure to Asian Sand Dust on Development and Reproduction in Male Offspring.

In recent experimental studies, we reported the aggravating effects of Asian sand dust (ASD) on male reproduction in mice. However, the effects of fetal ASD exposure on male reproduction have not been investigated. The present study investigated the effects of fetal ASD exposure on reproduction in male offspring. Using pregnant CD-1 mice, ASD was administered intratracheally on days 7 and 14 of gestation, and the reproduction of male offspring was determined at 5, 10, and 15 weeks after birth. The secondary sex ratio was significantly lower in the fetal ASD-exposed mice than in the controls. Histologic examination showed partial vacuolation of seminiferous tubules in immature mice. Moreover, daily sperm production (DSP) was significantly less in the fetal ASD-exposed mice than in the controls. DSP in the fetal ASD-exposed mice was approximately 10% less than the controls at both 5 and 10 weeks. However, both the histologic changes and the DSP decrease were reversed as the mice matured. These findings suggest that ASD exposure affects both the fetal development and the reproduction of male offspring. In the future, it will be necessary to clarify the onset mechanisms of ASD-induced male fetus death and male reproductive disorders.

The Protective Effects of Melatonin Against Oxidative Stress and Inflammation Induced by Acute Cadmium Exposure in Mice Testis.

Cadmium (Cd) is widely used in daily life and was recently recognized as a possible source of human toxicity due to its ability to accumulate in organs. Previous studies have shown that Cd exposure may cause testicular toxicity through oxidative stress and an inflammatory effect. Melatonin has been demonstrated to be an effective anti-oxidant and has an anti-inflammatory effect. The aim of the present study was to investigate the toxicological effects of Cd on reproduction in male mice and the potential protective action of melatonin against these adverse effects. Adult male mice were injected intraperitoneally with Cd at a dose of 2mg/kg body weight per day for seven consecutive days with or without melatonin pretreatment. Sex organ weight, sperm parameters including sperm quality, apoptosis, acrosome integrity, mitochondrial membrane potential, testicular morphology, serum sex hormone, inflammatory status, and oxidative stress were evaluated. The results showed that significant adverse effects were observed in the male reproductive system after Cd exposure, including alterations in sperm parameters, increased DNA damage, and sex hormone disturbance. Acute Cd exposure also significantly increased malondialdehyde (MDA) contents, decreased glutathione (GSH) and superoxide dismutase (SOD) activities, and upregulated levels of the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1β), in the testis. In contrast, melatonin pretreatment significantly alleviated these toxic effects, and its mechanism may involve inhibiting MDA level, restoring GSH and SOD activities, and reducing the upregulation of TNF-α and IL-1β. Our data suggest that oxidative stress and inflammation are involved in Cd-induced toxicity in the male reproductive system and that co-administration of melatonin exerts a protective effect against Cd-induced male reproductive toxicity.

Differential proteome and gene expression reveal response to carbon ion irradiation in pubertal mice testes

Heavy ion radiation, a high linear energy transfer (LET) radiation, has been shown to have adverse effects on reproduction in male mice. The aim of this study was to profile and investigate the differentially expressed proteins in pubertal male mice testes following carbon ion radiation (CIR). Male mice underwent whole-body irradiation with CIR (1 and 4Gy), and MALDI-TOF/TOF analysis was used to investigate the alteration in protein expression in 2-DE (two-dimensional gel electrophoresis) gels of testes caused by irradiation after 14 days. 8 differentially expressed proteins were identified and these proteins were mainly involved in energy supply, the endoplasmic reticulum, cell proliferation, cell cycle, antioxidant capacity and mitochondrial respiration, which play important roles in the inhibition of testicular function in response to CIR. Furthermore, we confirmed the relationship between transcription of mRNA and the abundance of proteins. Our results indicated that these proteins may lead to new insights into the molecular mechanism of CIR toxicity, and suggested that the gene expression response to CIR involves diverse regulatory mechanisms from transcription of mRNA to the formation of functional proteins.

The effect of mahogunin gene mutant on reproduction in male mice: a new sight for infertility?

Mahogunin is an important mediator of chromogenesis and neurodegeneration. Mahoganoid is a mutation of the mahogunin gene, which causes a pleiotropic phenotype that includes suppression of obesity, spongiform neurodegeneration and improvement of insulin sensitivity. Our previous research found that mahoganoid widely expressed in the male rat reproductive system, and mahoganoid-deficient mice have reduced embryonic viability. But the reproductive change in mahogunin knockout (md(nc) ) male mice has not been reported previously. Here, we report that the mahogunin mRNA also widely exists in reproductive system of male mice, and its mRNA expression in the testis was in accordance with the first spermatogenesis wave cycle. Moreover, we find that md(nc) male mice were able to mate with females but no pups are delivered. Besides, the sperms' active progressive motility and hormone secretion (E2, FSH, LH, PRL) were obviously decreased while abnormal sperm rate showed no significant difference in md(nc) compared to wild-type (WT) male mice. This study indicates the mahogunin deficiency results in the infertility of male mice, disruption of hormones secretion and impaired active progressive motility, which may additionally illuminate the aetiology of male infertility in human.

Protective effects of N-acetylcysteine against arsenic-induced oxidative stress and reprotoxicity in male mice

Arsenic is a well-known environmental toxic metalloid element and carcinogen that affects multiple organ systems including tissue lipid peroxidation and reproduction. The present study was aimed to investigate the protective role of N-acetylcysteine (NAC) on arsenic-induced testicular oxidative damage and antioxidant and steroidogeneic enzymes and sperm parameters in mice. Arsenic was administered through drinking water to mice at a concentration of 4.0 ppm sodium arsenite (actual concentration 2.3 ppm arsenic) for 35 days. The body weight of treated mice did not show significant change as compared with the control mice. In arsenic exposed mice there was a significant decrease in the weight of the testis, epididymis and prostate gland as compared with the control animals. Significant reduction was observed in epididymal sperm count, motile sperms and viable sperms in mice exposed to arsenic indicate decreased spermatogenesis and poor sperm quality. The activity levels of testicular 3β- and 17β-hydroxysteroid dehydrogenases and circulatory levels of testosterone were also decreased in arsenic treated mice indicating reduced steroidogenesis. A significant increase in the activities of lipid peroxidation and a significant decrease in the activities of antioxidant enzymes were observed in the testis of mice exposed to arsenic. In addition, significant increase in the testicular arsenic levels was observed during arsenic intoxication. No significant changes in the oxidation status and selected reproductive variables were observed in the N-acetylcysteine alone treated mice. Whereas, intra-peritoneal injection of NAC to arsenic exposed mice showed a significant increase in the weights of reproductive organs, reduction in arsenic-induced oxidative stress in the tissues and improvement in steroidogenesis over arsenic-exposed mice indicating the beneficial role of N-acetylcysteine to counteract arsenic-induced oxidative stress and to restore the suppressed reproduction in male mice.