Studies have reported the adverse effects of hyperuricemia on male reproduction, but the mechanism is still unclear. The purpose of this study is to explore the mechanism of hyperuricemia on reproductive system damage in male rats. The rats were divided into a control group and a model group. Rats were given hypoxanthine and potassium oxonate dissolved in 0.5% (w/v) sodium carboxymethyl cellulose solution to induce the hyperuricemia (HUA) model. After 6 weeks, the blood, testis, and epididymis tissues of the anesthetized rats were collected for further experiments and analysis. Compared with the control rats, the serum uric acid of HUA rats was significantly increased, and the serum testosterone, sperm count, and motility were significantly decreased. The protein expression of testosterone-related molecules CYP11A1, 3β-HSD, and StAR was downregulated in the testis of HUA rats. The protein expression of blood–testis barrier (BTB) related molecules ZO-1 and Connexin43 was downregulated in the testis of HUA rats. Compared with the control group, the zinc content and zinc-containing enzymes (ALP and LDH) were decreased, and the mRNA and protein expression of zinc transporters (ZnT4 and ZIP7) were downregulated in the testis of HUA rats. Furthermore, the level of MDA increased and the activities of CAT, GSH-PX, and SOD decreased in the testicular tissue of HUA rats. The PI3K/AKT/mTOR pathway in the testis of HUA rats was activated. However, there was no significant change in the protein expression of autophagy associated molecules LC3, Beclin1, and ATG5 in the testis of HUA rats. Thus, the conclusion is that hyperuricemia can lead to the destruction of BTB, impaired testosterone synthesis, and decreased sperm count and motility in male rats, mainly by inducing zinc homeostasis imbalance and oxidative stress, rather than autophagy.

Bisphenol A (BPA) is a contaminant widely found in food packaging that can reduce sperm quality and impair male fertility. Zinc (Zn) is an important antioxidant involved in many important biological functions. The aim of this study was to explore the protective effect and mechanism of Zn on reproductive toxicity induced by BPA. Male ICR mice were divided into a control group, a BPA group and a BPA + Zn group. The results showed that the body weight, sperm count and sperm motility of the animals in the BPA group were significantly reduced, and testicular structure was damaged. BPA decreased the levels of serum total Zn, testis-free zinc, ADH and ALP, upregulated the expression of ZnT4 protein, and down-regulated the expression levels of ZIP8, ZIP14, ZnT1, MT and MTF1 protein, resulting in the imbalance of testicular Zn homeostasis. BPA down-regulates the antioxidant enzymes SOD and GSH-Px, and increases MDA, leading to oxidative stress. BPA up-regulates TF, TFR and STEAP3 and down-regulates SLC7A11, GPX4, FPN1 and FTH protein levels, resulting in abnormal iron metabolism and ferroptosis. BPA down-regulated anti-apoptotic protein Bcl-2, up-regulated pro-apoptotic markers Bax, caspase-9, caspase-8 and caspase-3, and induced apoptosis. BPA also increased the phosphorylation of JNK and ERK1/2, but did not increase the phosphorylation of P38. Zn significantly increased body weight and sperm quality, improved testicular morphology, down-regulated p-JNK/JNK and p-ERK/ERK levels, improved oxidative stress, and reduced ferroptosis and apoptosis. In conclusion, Zn regulates Zn homeostasis and down-regulates the MAPK signaling pathway, thereby inhibiting ferroptosis and apoptosis, alleviating BPA-induced oxidative stress and ultimately improving male reproductive damage.

The long-term use of tripterygium glycosides (TG) can lead to male reproductive damage. Research indicates that zinc and selenium exhibit a synergistic effect in the male reproductive system, with the combined preparation demonstrating superior therapeutic effects compared to individual preparations. The purpose of this study was to explore the specific mechanism by which zinc and selenium mitigate reproductive toxicity induced by TG in male rats. Rats were randomly assigned to three groups: control group (C group), model group (M group, receiving TG at 30 mg/kg/day), and model + zinc + selenium group (ZS group). The ZS group was also given TG gavage for the first 4 weeks. Starting from the fifth week until the conclusion of the eighth week, the ZS group received an additional protective treatment of 10 mg/kg/day Zn and 0.1 mg/kg/day Se 4 h after TG administration. Following euthanasia, blood samples, rat testis, and epididymis tissues were collected for further experiments. Combined zinc-selenium treatment corrects the imbalance of zinc-selenium homeostasis in testicular tissue induced by TG. This is achieved by upregulating the expression of metal transcription factor (MTF1) and zinc transporters ZIP8 and ZIP14 and downregulating the expression of ZnT10. Improvement of zinc and selenium homeostasis enhanced the expression of zinc-containing enzymes (ADH, LDH, and ALP) and selenoproteins (GPx1 and SELENOP) in the testis. At the same time, zinc and selenium mitigate TG-induced reproductive damage by promoting the activity of antioxidant enzymes and upregulating the expression of proteins associated with the oxidative stress pathway, including Nrf2, Keap1, HO-1, PI3K, and p-AKT.

OBJECTIVE:To explore the expressions of zinc homeostasis-related proteins, G protein-coupled receptor 39 (GPR39) and ANO1 mRNA in the sperm of patients with asthenozoospermia (AS), and analyze their correlation with sperm motility. METHODS:We collected semen samples from 82 male subjects with PR+NP < 40%, PR < 32% and sperm concentration > 15×10⁶/ml (the AS group, n = 40) or PR+NP ≥ 40%, PR ≥ 32% and sperm concentration > 15×10⁶/ml (the normal control group, n = 42). We analyzed the routine semen parameters and measured the zinc content in the seminal plasma using the computer-assisted sperm analysis system, detected the expressions of zinc transporters (ZIP13, ZIP8 and ZNT10), metallothioneins (MT1G, MT1 and MTF), GPR39, and calcium-dependent chloride channel protein (ANO1) in the sperm by real-time quantitative PCR (RT qPCR), examined free zinc distribution in the sperm by laser confocal microscopy, and determined the expressions of GPR39 and MT1 proteins in the sperm by immunofluorescence staining, followed by Spearman rank correlation analysis of their correlation with semen parameters. RESULTS:There was no statistically significant difference in the zinc concentration in the seminal plasma between the AS and normal control groups (P>0.05). Compared with the controls, the AS patients showed a significantly reduced free zinc level (P<0.05), relative expressions of MT1G, MTF, ZIP13, GPR39 and ANO1 mRNA (P<0.05), and that of the GPR39 protein in the AS group (P<0.05). No statistically significant differences were observed in the relative expression levels of ZIP8, ZNT10 and MT1 mRNA between the two groups (P>0.05). The relative expression levels of GPR39, ANO1, MT1G and MTF mRNA were positively correlated with sperm motility and the percentage of progressively motile sperm (P<0.05). CONCLUSION:The expressions of zinc homeostasis proteins (MT1G, MTF and ZIP13), GPR39 and ANO1 mRNA are downregulated in the sperm of asthenozoospermia patients, and positively correlated with sperm motility.

Background: Zinc (Zn)is an essential trace element for spermatogenesis and its deficiency causes abnormal spermatogenesis. Objective: The present study was conducted to examine the mechanisms by which Zn-deficient diet impairs sperm morphology and its reversibility. Methods: 30 SPF grade male Kunming (KM) mice were randomly divided into three groups, 10 mice per group. Zn-normal diet group (ZN group) was given Zn-normal diet(Zn content= 30 mg/kg)for 8 weeks. Zn-deficienct diet group (ZD group) was given Zn-deficienct diet(Zn content< 1 mg/kg)for 8 weeks. Zn-deficient and Znnormal diet group(ZDN group)was given 4 weeks Zn-deficienct diet followed by 4 weeks Zn-normal diet. After 8 weeks, the overnight fasted mice were sacrificed, and blood and organs were collected for further analysis. Results: The experimental results showed that Zn-deficienct diet leads to increased abnormal morphology sperm and testicular oxidative stress.The rate of abnormal morphology sperm, chromomycin A3(CMA3), DNA fragmentation index (DFI), malondialdehyde (MDA) were significantly increased, and a-kinase anchor protein 4 (AKAP4), dynein axonemal heavy chain 1(DNAH1), sperm associated antigen 6(SPAG6), cilia and flagella associated protein 44(CFAP44), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), nuclear factor erythroid 2-related factor (NRF2), NAD(P)H:quinone oxidoreductase 1(NQO1) and heme oxygenase 1(HO1) were significantly decreased in the ZD group mice. While the changes in above indicators caused by Zn-deficient diet were significantly alleviated in the ZDN group. Conclusion: It was concluded that Zn-deficient diet causes abnormal morphology sperm and testicular oxidative stress in male mice. Abnormal morphology sperm caused by Zn-deficient diet are reversible, and Zn-normal diet can alleviate them.

Zinc is a vital trace element for normal function of the living system. In male, zinc is involved in various biological processes, an important function of which is as a balancer of hormones such as testosterone. For this purpose, studies related to the influence of zinc on serum testosterone were selected and summarized, including the effect of dietary zinc deficiency and zinc supplementation on testosterone concentrations. After preliminary searching of papers on databases, 38 papers including 8 clinical and 30 animal studies were included in this review. We concluded that zinc deficiency reduces testosterone levels and zinc supplementation improves testosterone levels. Furthermore, the effect degree of zinc on serum testosterone may vary depending on basal zinc and testosterone levels, zinc dosage form, elementary zinc dose, and duration. In conclusion, serum zinc was positively correlated with total testosterone, and moderate supplementation plays an important role in improving androgen.

微量元素硒通过多种途径调控炎症与氧化反应的过程,维持机体内环境的稳态.硒参与了精子发生、成熟、运动等生理活动过程,与男性生殖密切相关.精液硒含量与精液质量存在明显的相关性,适量补硒可以改善不育男性精液质量.本文从硒的生物学作用、硒对男性生殖内分泌的影响以及硒和硒蛋白与精液质量间的关系进行综述,并总结了补充硒及其他微量元素在降低生殖毒性、提高精液质量等方面的研究进展.

目的 分析甘油三酯异常对男性血清生殖激素、精液参数和微量元素的影响,探讨甘油三酯异常导致男性不育的病因.方法 选取2016年9月至2017年6月在6家医院不育门诊就诊的1126例男性作为研究对象.采用全自动生化分析仪检测血脂水平,计算机辅助分析系统分析精液参数,电化学发光法测定血清生殖激素浓度;采用电感耦合等离子原子发射光谱仪检测精浆铬、铜、铁、铅、硒和锌水平.结果 高甘油三酯血症组精液量异常率高于正常组,差异具有统计学意义(P<0.05);与正常组相比,甘油三酯异常组精液量和精子总数降低,血清睾酮浓度降低,精浆硒水平降低,差异具有统计学意义(P<0.05).结论 甘油三酯水平异常男性生殖内分泌紊乱、精液量和精子总数下降、精浆硒水平降低,甘油三酯水平异常可能是导致男性不育的原因.

目的 探讨高脂饮食诱导肥胖大鼠睾丸组织差异表达的环状RNAs(circRNA)及微小 RNA(miRNA).方法 通过高脂饲料构建肥胖大鼠模型,HE染色观察睾丸组织病理学变化,检测精子浓度、活力、DFI 和 CMA3+,高通量测序筛选肥胖大鼠睾丸组织差异表达的circRNAs及miRNAs,通过GO和KEGG分析其参与的主要生物学过程,最后构建 circRNA-miRNA-mRNA网络.结果 与正常组相比,肥胖组大鼠睾丸组织结构改变,精子浓度、活力显著降低(P<0.05),DFI、CMA3+显著升高(P<0.05).芯片筛选出肥胖组大鼠睾丸组织有 32 个差异表达的circRNAs和4 个差异表达的miRNAs.生物信息学分析显示这些基因可能通过Wnt信号通路、TNF信号通路和胰岛素分泌等通路调控肥胖引起的雄性生殖障碍.筛选差异显著且具有靶向关系的circRNA和miRNA:novel_circ_0003226/rno-miR-3544、novel_circ_0015575/rno-miR-9a-5p,并构建circRNA-miRNA-mRNA网络.结论 肥胖大鼠睾丸组织存在差异表达的circRNAs和miRNAs,这些差异基因可能通过circRNA-miRNA-mRNA网络调控肥胖引起的雄性大鼠生殖障碍.

Zinc deficiency has a huge impact on male reproduction. The zinc transporter (ZnT) family is involved in the maintenance of zinc homeostasis and testosterone synthesis. However, the underlying mechanisms remain to be investigated. Therefore, in this study, we aimed to determine the effect of zinc transporter 4 (ZnT4) on testosterone synthesis in male Kunming mice and mouse Leydig cells. The results of this study showed that compared with the zinc normal diet group (Con group), the zinc-deficient diet group (ZnD group) had decreased zinc content and increased ZnT4 expression in testicular tissues, and decreased serum testosterone levels, suggesting that ZnT4 may be involved in Leydig cell injury resulting from a zinc-deficient diet. Subsequently, mouse Leydig cell line TM3 cells were used to analyze the effect of ZnT4 downregulation on TM3 cell proliferation and apoptosis, on testosterone synthesis, and its underlying mechanisms. Here, we show that knockdown of ZnT4 can induce the accumulation of zinc, inhibit the viability, and induce apoptosis in TM3 cells. In addition, knockdown of ZnT4 downregulated testosterone concentration and expression of testosterone synthesis–related proteins steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase/D5-D4 isomerase (3β-HSD) in TM3 cells, while hCG could rescue their levels. We show that it is ZnT4 that plays a role in testosterone production through a mediated PI3K/Akt/mTOR autophagy pathway, whereas mTORC1 complex inhibitor (Rapa) blocks the decrease in testosterone levels caused by ZnT4 downregulation. In conclusion, the above results indicate that ZnT4 plays an important role in regulating testosterone synthesis.

精子发生于生精小管,离开生精小管的精子不具有受精能力,精子依次在液体微环境中经历了一系列的修饰过程(形态和生化),最终成为有受精能力的精子.体液环境中含有大量的细胞外囊泡,其中直径在100 nm左右的囊泡称为外泌体[1].

Zinc (Zn) is an essential trace element for human growth and its deficiency causes huge health impacts. The present study was conducted to examine the mechanisms by which Zn-deficient diet impairs reproductive function and its reversibility. Hence, SPF grade male Kunming (KM) mice were divided into three groups. Zn-normal diet group (ZN group) was provided with Zn-normal diet (Zn content = 30 mg/kg, DY19410Y) for 8 weeks. Zn-deficient diet group (ZD group) was provided with Zn-deficient diet (Zn content < 1 mg/kg, DY19401) for 8 weeks. Zn-deficient and Zn-normal diet group (ZDN group) was provided with 4 weeks Zn-deficient diet followed by 4 weeks Zn-normal diet. After 8 weeks, the overnight-fasted mice were sacrificed, and blood and organs were collected for further analysis. The results showed that Zn-deficient diet caused testicular structural disorders, decreased semen quality, imbalance in zinc homeostasis, and impaired autophagy. Semen quality, testosterone, serum Zn, testicular tissue Zn, testicular free Zn ions, alkaline phosphatase (ALP), zinc transporter 7(ZnT7), Beclin1, autophagy-related 5(ATG5), and the ratio of light chain 3(LC3) II/LC3I were significantly decreased, and ZnT4, Zrt-, Irt-like protein7 (ZIP7), and ZIP13 expression were significantly increased in ZD group mice, while the changes in above indicators caused by Zn-deficient diet were significantly alleviated in the ZDN group. It was concluded that Zn-deficient diet causes testicular structural disorders and decreased semen quality by causing imbalances in Zn homeostasis and impaired autophagy in male mice. Reproductive damages caused by Zn-deficient diet are reversible, and Zn-normal diet can alleviate them.