Bisphenol A (BPA), a common environmental endocrine disruptor, has been shown to adversely affect male reproductive function. However, the mechanisms of reproductive impairment in both BPA-exposed males (F0) and their unexposed offspring (F1) remain unclear. Furthermore, there are currently no reports on that paternal Zinc (Zn) and/or Selenium (Se) supplementation ameliorate BPA-induced and transgenerational reproductive damage in F0 and F1, respectively. This study aimed to address these scientific issues by integrating transcriptomics and metabolomics. Our results revealed that BPA induced reproductive damage of F0 by altering the transport and homeostasis of Zn and Se, disrupting the synthesis and transformation balances of testosterone (T) and estradiol (E2), and increasing the oxidative stress and apoptosis levels. Furthermore, most of the changes of F0 was transmitted to F1 generation, causing reproductive damage to the male offspring. In contrast, supplementing with Zn and/or Se for F0 could alleviate these impacts of BPA on F0 and F1. Notably, the combination of Zn and Se was generally more effective compared to individual supplementation. The transcriptomics and metabolomics analyses revealed the overall mechanisms of Zn and/or Se alleviating BPA-induced testicular damage in F0 and F1 male mice. The reason why Zn and Se combined is superior to Zn or Se alone is related to their unique or additive regulatory roles on the oxidative phosphorylation pathway and antioxidant functions, which exhibits the characteristic of intergenerational transmission in male mice.

Background. Currently, there are few studies on the effects of hyperlipidemia on semen parameters and serum hormones in men. In this study, we divided the study subjects into two groups of normal and hyperlipidemia according to the criteria, and observed the differences between semen parameters and serum reproductive hormones in hyperlipidaemic men and normal men, to explore the potential associations between the indicators. Materials and Methods. Eight hundred eighty five men attending infertility clinics in six hospitals from September 2016 to June 2017 were selected. Their lipid levels, semen parameters, and serum reproductive hormone levels were tested, and a total of 480 men with normal lipids and 405 men with hyperlipidemia were selected according to the criteria, and the relationship between semen quality, serum reproductive hormones, lipids and semen parameters, and serum hormones was statistically analyzed. Results. There was no significant difference in semen parameters between hyperlipidaemic men and normal men (P > 0.05), serum testosterone levels were significantly lower in hyperlipidaemic men (P < 0.05), and there was a negative correlation between triglycerides (TG) and testosterone in the blood (P < 0.05).Conclusion. Hyperlipidemia does not affect male semen parameters, and changes in testosterone in hyperlipidaemic men may be related to triglycerides.

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.

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.

OBJECTIVE:To explore the potential impact of lipid metabolism-related single nucleotide polymorphisms (SNP) on semen quality in men. METHODS:We selected 284 semen samples from Xingtai Infertility Hospital and Hebei Human Sperm Bank collected between February and October 2023, 33 from oligozoospermia (OS), 97 from asthenozoospermia (AS) and 54 from oligoasthenozoospermia (OAS) patients and the other 100 from normal men. We performed computer-assisted semen analysis (CASA) of the samples, extracted blood DNA and, using the MassARRAY System, genotyped the target genes, determined the genotypes of 13 SNPs and compared their distribution, their correlation with BMI and semen quality in different groups. RESULTS:The mutant homozygous (TT) genotype of the FADS2 rs2727270 gene seemed to be a risk factor for AS (OR = 4.420, P= 0.047), while the APOA2 rs5082-A allele and MC4R rs17782313 heterozygous (TC) genotype important protective factors for OS (OR = 0.422 and 0.389; P= 0.045 and 0.043, respectively). A significantly higher sperm concentration was found associated with the MC4R rs17782313 heterozygous (TC) genotype than with the homozygous (CC) genotype. Stratification analysis showed that the protective effect of the TC genotype was decreased with increased BMI and remained with the interaction of the rs5082 and rs17782313 genotypes. CONCLUSION:FADS2 rs2727270, APOA2 rs5082 and MC4R rs17782313 were significantly correlated with the risk of abnormal semen parameters.

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.

This study aimed to identify differentially expressed LncRNAs in testis tissue of male rats induced by high-fat diet and their changes after zinc supplementation, by constructing a high-fat feeding rat model, and then supplemented with zinc, and observed the expression of LncRNA in three groups of normal, high-fat fed, and zinc-intervened rats. Experimental studies show that the semen parameters of male rats with high-fat diet were decreased but recovered after zinc supplementation, and the related LncRNA also changed. Zinc may improve the high-fat diet-induced reduction of semen parameters by changing the expression of related LncRNA.

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.

Tripterygium glycosides (TG) can seriously damage male reproductive function, and the reproductive system is difficult to restore after stopping the administration of TG in male rats. Zinc (Zn) is one of the most important trace elements in the human body and plays an important role in maintaining male fertility. The aim of this study was to investigate whether zinc supplementation could improve the testicular reproductive damage induced by TG toxicity in rats and to investigate its mechanism of action. The results showed that zinc sulfate (ZnSO4) could improve testicular tissue structure and semen parameters, promote testosterone synthesis, increase zinc-containing enzyme activity, increase zinc concentration in serum and testicular tissues, and maintain zinc homeostasis in male rats induced by TG toxicity. Zinc supplementation activated relevant signalling molecules in the KEAP1-NRF2/ARE pathway and alleviated TG-induced oxidative stress. Therefore, this study concluded that zinc supplementation could improve reproductive damage by regulating zinc homeostasis and the expression of genes related to oxidative stress.

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.