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The risk factors of spermatogenesis. Various endogenous and exogenous factors affect control mechanisms of spermatogenesis
Source publication
The male reproductive system consists of testes, a series of ducts connecting the testes to the external urethral orifice, accessory sex glands, and the penis. Spermatogonial stem cells differentiate and mature in testes and epididymides, and spermatozoa are ejaculated with exocrine fluids secreted by accessory sex glands. Many studies have clarifi...
Citations
... In recent years, the incidence of male reproductive system diseases has increased, attracting substantial attention from researchers worldwide. Male reproductive system diseases primarily affect the penis, testis, prostate, vas deferens, and epididymis (1). Various microorganisms, environmental factors, and long-term smoking or alcohol abuse may affect male reproductive function (2)(3)(4)(5), leading to diseases such as erectile dysfunction (ED) (6), prostate cancer (PCa) (7), varicocele (8), and infertility (9). ...
As an important gas signaling molecule, hydrogen sulfide (H2S) affects multiple organ systems, including the nervous, cardiovascular, digestive, and genitourinary, reproductive systems. In particular, H2S not only regulates female reproductive function but also holds great promise in the treatment of male reproductive diseases and disorders, such as erectile dysfunction, prostate cancer, varicocele, and infertility. In this review, we summarize the relationship between H2S and male reproductive organs, including the penis, testis, prostate, vas deferens, and epididymis. As lower urinary tract symptoms have a significant impact on penile erection disorders, we also address the potential ameliorative effects of H2S in erectile dysfunction resulting from bladder disease. Additionally, we discuss the regulatory role of H2S in cavernous smooth muscle relaxation, which involves the NO/cGMP pathway, the RhoA/Rho-kinase pathway, and K⁺ channel activation. Recently, various compounds that can alleviate erectile dysfunction have been reported to be at least partly dependent on H2S. Therefore, understanding the role of H2S in the male reproductive system may help develop novel strategies for the clinical treatment of male reproductive system diseases.
... In clinical and scientific work, semen parameters, including semen volume, sperm concentration, sperm count, sperm progressive motility, and total motility, are often used as indicators to assess male fertility [4]. Spermatogenesis is a dynamically changing physiological process [5], which is easily influenced by lifestyle and diet. A review by Ostojic pointed out that creatine is a potential supplement for couples preparing for pregnancy, while another review indicated that the intake of myo-inositol is an effective supplement for sperm quality [6]. ...
Background
Semen quality significantly influences conception, and its preservation is crucial for couples seeking pregnancy. We investigated dietary and lifestyle risk factors impacting semen quality.
Methods
A total of 466 males from the Guangzhou Women and Children’s Medical Center’s pre-pregnancy consultation clinic were recruited between January 2021 and March 2023 for inclusion. Semen analysis was performed, and diet and lifestyle data were gathered via questionnaire. Logistic regression was utilized to examine the link between diet, lifestyle variables, and semen quality.
Results
Smoking worsened progressive sperm motility (38.0% vs. 36.0%, t = 2.262; P = 0.049). Alcohol consumption impaired progressive motility (40.5 ± 17.8% vs. 34.7 ± 16.1%, t = 3.396; P < 0.001) and total motility (56.0% vs. 64.0%; P = 0.001). Using plastic beverage bottles for oil or seasonings lowered sperm concentrations (40.4% vs. 59.0% vs. 65.5%; P = 0.032). A sweet diet correlated with higher total sperm motility (55.0% vs. 60.0%, 62.0% vs. 63.2%; P = 0.017). Higher milk product intake improved sperm concentration (41.610⁶vs. 63.710⁶ vs. 66.1*10⁶; P = 0.021) and motility (54.5% vs. 56.0% vs. 63.0%; P = 0.033). More frequent egg consumption increased semen volume (3.1 mL vs. 3.8 mL vs. 4.0 mL; P = 0.038). Roughage intake enhanced sperm concentration (160.810⁶ vs. 224.610⁶; P = 0.027), and adequate sleep improved progressive sperm motility rate (35.4% ± 18.2% vs. 40.2 ± 16.3%, F = 3.747; P = 0.024) and total motility (52.7% vs. 61.5%; P = 0.013). The regression model showed that using plastic containers for condiments was a protective factor for semen volume (OR: 0.12; CI 0.03–0.55; P = 0.006), sperm concentration (OR: 0.001, CI 0.00–0.30; P = 0.012), and count (OR: 0.12, CI 0.03–0.48; P = 0.003). Milk and egg consumption were also protective for semen volume (OR: 0.18, CI 0.06–0.51; P = 0.001 and OR: 0.11, CI 0.03–0.55; P = 0.006, respectively), while sufficient sleep benefitted total sperm motility (OR: 0.47, CI 0.24–0.95; P = 0.034).
Conclusions
Smoking and drinking, type of condiment container, diet preference, sleep duration, and milk, roughage, and egg consumption may reduce semen quality.
... Spermatogenesis is a complex process of producing sperm, while the testicular microenvironment is crucial to the normal development of spermatogenesis (Horvath-Pereira et al., 2023). It regulates the proliferation, differentiation, and maturation of germ cell (Miyaso et al., 2022). The testicular microenvironment is composed of testicular cells and intercellular substance. ...
... The testicular microenvironment is composed of testicular cells and intercellular substance. Changes in immune homeostasis (Miyaso et al., 2022;Wang et al., 2018), somatic cells in testis (Zhao et al., 2020), blood-testis barrier, temperature, and the paracrine factors may all contribute to changes in the testicular microenvironment. ...
An increasing number of men require long-term drug therapy for various diseases. However, the effects of long-term drug therapy on male fertility are often not well evaluated in clinical practice. Meanwhile, the development of stem cell therapy and exosomes treatment methods may provide a new sight on treating male infertility. This article reviews the influence and mechanism of small molecule medications on male fertility, as well as progress of stem cell and exosomes therapy for male infertility with the purpose on providing suggestions (recommendations) for evaluating the effect of drugs on male fertility (both positive and negative effect on male fertility) in clinical application and providing strategies for diagnosis and treatment of male infertility.
... The epididymis is a highly convoluted tubular structure adjacent to the testis and is divided into three main regions: the caput, corpus, and cauda (Sullivan et al. 2019). Sperm produced in the testes travel through the epididymis, where they acquire motility and the ability to fertilize eggs through sperm maturation (Ahn et al. 2022;Miyaso et al. 2022). The epididymis plays a vital role in this process by providing an optimal environment, including essential nutrients and various molecules secreted by epithelial cells in the epididymis (Sullivan and Mieusset 2016). ...
Nesfatin-1, a polypeptide hormone derived from the nucleobindin 2 (NUCB2) precursor protein, is known to regulate appetite and energy metabolism. Recent studies have also shown that NUCB2/nesfatin-1 is expressed in the reproductive organs of mice. However, the expression and potential role of NUCB2/nesfatin-1 in the mouse epididymis remain unclear. Therefore, we investigated the expression of NUCB2/nesfatin-1 in the mouse epididymis and its potential function. NUCB2/nesfatin-1 was detected in the epididymis by qRT-PCR and western blotting, and high expression levels were observed in epididymal epithelial cells by immunohistochemical staining. Pregnant mare’s serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) injections significantly increased NUCB2/nesfatin-1 expression in the epididymis. After castration, NUCB2/nesfatin-1 expression in the epididymis decreased, but was significantly increased by testosterone injection. Nesfatin-1-binding sites were found in the middle piece of testicular sperm, but were scarcely detected in the sperm head. By contrast, nesfatin-1 binding sites were identified on the sperm head within the epididymis. Furthermore, nesfatin-1 treatment inhibited the acrosome reaction in epididymal sperm. These results suggest that the nesfatin-1 protein produced in the epididymis binds to nesfatin-1 binding sites on the sperm head and plays a role in suppressing the acrosome reaction before ejaculation.
... Male gamete differentiation occurs during spermatogenesis, a genetic and molecular program during which immature GC undergo several stages of cell division (mitotic and meiotic) and then, by intimate biochemical and morphological modification, to produce mature SPZ (Dunleavy et al., 2019). The entire progression is regulated not only by a sophisticated network of autocrine/paracrine/endocrine factors, but also by modulating the expression of several exclusive testicular genes (Venditti et al., 2020a;Miyaso et al., 2022). ...
This paper confirms the damaging effects produced by MP and Cd on testicular activity in the rat. Oral treatment with both chemicals resulted in testicular damage, documented by biomolecular and histological alterations, particularly by impaired morphometric parameters, increased apoptosis, reduced testosterone synthesis, and downregulation of the steroidogenic enzyme 3β-HSD. We also demonstrated, for the first time, that both MP and Cd can affect the protein level of PTMA, a small peptide that regulates germ cell proliferation and differentiation. Interestingly, the cytoarchitecture of testicular cells was also altered by the treatments, as evidenced by the impaired expression and localization of DAAM1 and PREP, two proteins involved in actin- and microtubule-associated processes, respectively, during germ cells differentiation into spermatozoa, impairing normal spermatogenesis. Finally, we showed that the effect of simultaneous treatment with MP and Cd were more severe than those produced by MP alone and less harmful than those of Cd alone. This could be due to the different ways of exposure of the two substances to rats (in drinking water for Cd and in oral gavage for MP), since being the first contact in the animals’ gastrointestinal tract, MP can adsorb Cd, reducing its bioavailability through the Trojan-horse effect.
... Therefore, the combined defects of activation failure and polyspermy may explain the reduction in fertility. Typically, sperm abnormalities are mainly related to alterations in the spermatogenic process, which is closely associated with the physiological state of the reproductive organs [29,30]. In this study, pathological changes were found in the testes and epididymis of Plcz1 m3 male mice according to histological analysis combined with declined sperm quality, which indicated that Plcz1 can be involved in physiological homeostasis of these organs and spermatogenic process. ...
Phospholipase C zeta1 (Plcz1) was known to be a physiological factor in sperm that activates oocytes to complete meiosis by triggering Ca2+ oscillations after fertilisation. However, the role of male Plcz1 in spermatogenesis and early embryo development in progeny has been controversial. Plcz1 knockout (Plcz1−/−) mouse model (Plcz1m3 and Plcz1m5) was generated by using the CRISPR-Cas9 system. The fertility of Plcz1−/− mice was evaluated by analysing the number of offsprings, sperm quality, pathological changes in the testis and epididymis. RNA-seq and RT-PCR were performed to screen differentially expressed genes and signalling pathways related to fertility in Plcz1−/− mice. Further mechanism was explored by using Plcz1−/− cells. Plcz1 knockout led to hypofertility in male mice. In particular, a significant time delay in development and polyspermy was found in eggs fertilized by both Plcz1m3 and Plcz1m5 sperm. Interestingly, a decline in sperm quality combined with pathological changes in epididymis was found in Plcz1m3 mice but not in Plcz1m5 mice. Notably, abnormal cytoskeleton appears in epididymis of Plcz1m3 mice and Plcz1−/− cells. Cytoskeleton damage of epididymis is involved in fertility decline of males upon Plcz1 deficiency in this model.
... During spermatogenesis, spermatids undergo various epigenetic modi cations including DNA methylation, histone modi cations, and small non-coding RNA loading [15]. Although most sperm histones are replaced by protamine at the end of spermatogenesis, various histone modi cations are established during spermatogenesis and may be involved in the regulation of gene expression and other epigenetic modi cations [16,17]. ...
Various reports have described epigenetic transgenerational inheritance through sperm. However, the detailed mechanism remains unclear. In this study, we focused on DNA methylation and analyzed the effects on the next generation of sperm from mice treated with valproic acid (VPA) as an inducer of epigenomic changes. Administration of 200 mg/kg/day VPA to mice for 4 weeks caused transient histone hyperacetylation in the testes and DNA methylation changes in sperm, including promoter CpGs of genes related to brain function. Oocytes fertilized by VPA-treated mouse sperm showed some methylation fluctuations at the morula stage. Pups fathered by these mice also showed behavioral changes in the light/dark transition test after maturation. Brain RNA-seq of these mice showed decreased expression of many genes related to brain and neural function. Comparison of the sperm DNA methylation status of the next generation of mice with that of the parental generation revealed the disappearance of the methylation changes observed in the sperm of the parental generation. These findings suggest that VPA-treated mice may be a useful simple epigenetic transgenerational inheritance model for histone hyperacetylation.
... Sertoli cells act as the mediator between germ cells and endocrine signaling, from controlling spermatogenesis by hormones (follicle stimulating hormone [FSH] and testosterone [T]), originating from outside of the seminiferous tubule (6)(7)(8). Sertoli cells also have direct impacts on germ cell development through paracrine signaling (9)(10)(11). These roles are all key elements required to orchestrate the symphonic cyclicity of steady-state spermatogenesis within the adult testis. ...
Since their initial description by Enrico Sertoli in 1865, Sertoli cells have continued to enchant testis biologists. Testis size and germ cell carrying capacity are intimately tied to Sertoli cell number and function. One critical Sertoli cell function is signaling from Sertoli cells to germ cells as part of regulation of the spermatogenic cycle. Sertoli cell signals can be endocrine or paracrine in nature. Here we review recent advances in understanding the interplay of Sertoli cell endocrine and paracrine signals that regulate germ cell state. Although these findings have long-term implications for treating male infertility, recent breakthroughs in Sertoli cell transplantation have more immediate implications. We summarize the surge of advances in Sertoli cell ablation and transplantation, both of which are wedded to a growing understanding of the unique Sertoli cell niche in the transitional zone of the testis.
... The accumulation of basic knowledge regarding the microenvironment of spermatogenesis and maturation will be helpful to solve these problems. In this special issue, Miyaso et al. (2022) review the microenvironment of the male reproductive tissues and its control, such as genetic and epigenetic control of spermatogenesis, the blood-testis barrier, and neuroendocrine-immune control. Wakayama et al. (2022) introduce a simplified flowchart to determine the stages of mouse spermatogenesis. ...
