Male Reproductive Ability Research Articles

Metabolomics reveals that ferroptosis participates in bisphenol A-induced testicular injury

ObjectiveBisphenol A (BPA) is a common environmental endocrine disruptor that negatively impairs male reproductive ability. This study aimed to explore the alterations in serum metabolomics that occur following BPA exposure and the mechanism via which BPA induces the death of testicular cells in a male mouse model. MethodsThe mice were classified into two groups: BPA-exposed and control groups, and samples were collected for metabolomic determination, semen quality analysis, electron microscopy, enzyme-linked immunosorbent assay, quantitative real-time PCR, pathological staining, and Western blot analysis. ResultsBPA exposure caused testicular damage and significantly decreased sperm quality in mice. Combined with non-target metabolomic analysis, this was closely related to ferroptosis induced by abnormal metabolites of arachidonic acid and phosphatidylcholine, and the expression of its related genes, acyl CoA synthetase 4, glutathione peroxidase 4, lysophosphatidylcholine acyltransferase 3, and phosphatidylethanolamine-binding protein 1 were altered. ConclusionBPA induced ferroptosis, caused testicular damage, and reduced fertility by affecting lipid metabolism in male mice. Inhibiting ferroptosis may potentially function as a therapeutic strategy to mitigate the male reproductive toxicity induced by BPA.

Pathologies of the male reproductive system, having a different nature, and their impact on reproductive function

This work presents an overview of various pathologies that can affect the health of the male reproductive system and reproductive function. The authors consider such common conditions as varicocele, hypogonadism, epididymitis and prostatitis, and assess their impact on sperm quality, testosterone levels and the patency of the genitourinary tract. The article also discusses the methods of diagnosis and treatment of these pathologies, as well as their possible impact on the reproductive function of men. The study highlights the importance of timely diagnosis and treatment of these conditions in order to maintain the health of the male reproductive system and reproductive ability.

Integrated single cell transcriptome sequencing analysis reveals species-specific genes and molecular pathways for pig spermiogenesis.

Mammalian spermatogenesis is a highly complicated and intricately organized process involving spermatogonia propagation (mitosis) and meiotic differentiation into mature sperm cells (spermiogenesis). In pigs, spermatogonia development and the role of somatic cells in spermatogenesis were previously investigated in detail. However, the characterization of key molecules fundamental to pig spermiogenesis remains less explored. Here we compared spermatogenesis between humans and pigs, focusing on spermiogenesis, by integrative testicular single-cell RNA sequencing (scRNA-seq) analysis. Human and pig testicular cells were clustered into 26 different groups, with cell-type-specific markers and signalling pathways. For spermiogenesis, pseudo-time analysis classified the lineage differentiation routes for round, elongated spermatids and spermatozoa. Moreover, markers and molecular pathways specific to each type of spermatids were examined for humans and pigs, respectively. Furthermore, high-dimensional weighted gene co-expression network analysis (hdWGCNA) identified gene modules specific for each type of human and pig spermatids. Hub genes (pig: SNRPD2.1 related to alternative splicing; human: CATSPERZ, Ca[2+] ion channel) potentially involved in spermiogenesis were also revealed. Taken together, our integrative analysis found that human and pig spermiogeneses involve specific genes and molecular pathways and provided resources and insights for further functional investigation on spermatid maturation and male reproductive ability.

Association of living environmental and occupational factors with semen quality in chinese men: a cross-sectional study

Sperm quality can be easily influenced by living environmental and occupational factors. This study aimed to discover potential semen quality related living environmental and occupational factors, expand knowledge of risk factors for semen quality, strengthen men's awareness of protecting their own fertility and assist the clinicians to judge the patient’s fertility. 465 men without obese or underweight (18.5 < BMI < 28.5 kg/m2), long-term medical history and history of drug use, were recruited between June 2020 to July 2021, they are in reproductive age (25 < age < 45 years). We have collected their semen analysis results and clinical information. Logistic regression was applied to evaluate the association of semen quality with different factors. We found that living environment close to high voltage line (283.4 × 106/ml vs 219.8 × 106/ml, Cohen d = 0.116, P = 0.030) and substation (309.1 × 106/ml vs 222.4 × 106/ml, Cohen d = 0.085, P = 0.015) will influence sperm count. Experienced decoration in the past 6 months was a significant factor to sperm count (194.2 × 106/ml vs 261.0 × 106/ml, Cohen d = 0.120, P = 0.025). Living close to chemical plant will affect semen PH (7.5 vs 7.2, Cohen d = 0.181, P = 0.001). Domicile close to a power distribution room will affect progressive sperm motility (37.0% vs 34.0%, F = 4.773, Cohen d = 0.033, P = 0.030). Using computers will affect both progressive motility sperm (36.0% vs 28.1%, t = 2.762, Cohen d = 0.033, P = 0.006) and sperm total motility (57.0% vs 41.0%, Cohen d = 0.178, P = 0.009). After adjust for potential confounding factors (age and BMI), our regression model reveals that living close to high voltage line is a risk factor for sperm concentration (Adjusted OR 4.03, 95% CI 1.15–14.18, R2 = 0.048, P = 0.030), living close to Chemical plants is a protective factor for sperm concentration (Adjusted OR 0.15, 95% CI 0.05–0.46, R2 = 0.048, P = 0.001) and total sperm count (Adjusted OR 0.36, 95% CI 0.13–0.99, R2 = 0.026, P = 0.049). Time spends on computer will affect sperm total motility (Adjusted OR 2.29, 95% CI 1.11–4.73, R2 = 0.041, P = 0.025). Sum up, our results suggested that computer using, living and working surroundings (voltage line, substation and chemical plants, transformer room), and housing decoration may association with low semen quality. Suggesting that some easily ignored factors may affect male reproductive ability. Couples trying to become pregnant should try to avoid exposure to associated risk factors. The specific mechanism of risk factors affecting male reproductive ability remains to be elucidated.

Lumicrine signaling: Extracellular regulation of sperm maturation in the male reproductive tract lumen.

The behaviors of cells, tissues, and organs are controlled by the extracellular environment in addition to their autonomous regulatory system. Dysfunction of extracellular regulatory mechanisms affects not only the development and survival of organisms but also successful reproduction. In this review article, a novel extracellular regulatory mechanism regulating the mammalian male reproductive ability will be briefly summarized. In terrestrial vertebrates, spermatozoa generated in the testis are transported through the lumen of the male reproductive tract and become functionally mature during the transport. Recent studies with gene-modified animals are unveiling the luminal extracellular environment of the reproductive tract to function not only as the pathway of sperm transport and the site of sperm maturation but also as the channel for cellular communication to regulate sperm maturation. Of special interest is the molecular mechanism of lumicrine signaling, a transluminal secreted signal transduction in the male reproductive tract lumen as a master regulator of sperm maturation and male reproductive ability. The general significance of such transluminal signaling in the context of cell biology will also be discussed.

LncRNA5251 inhibits spermatogenesis via modification of cell-cell junctions

BackgroundMale factors-caused decline in total fertility has raised significant concern worldwide. LncRNAs have been identified to play various roles in biological systems, including spermatogenesis. This study aimed to explore the role of lncRNA5251 in mouse spermatogenesis.MethodsThe expression of lncRNA5251 was modulated in mouse testes in vivo or spermatogonial stem cells (C18-4 cells) in vitro by shRNA.ResultsThe sperm motility in two generations mice after modulation of lncRNA5251 (muF0 and muF1) was decreased significantly after overexpression of lncRNA5251. GO enrichment analysis found that knockdown lncRNA5251 increased the expression of genes related to cell junctions, and genes important for spermatogenesis in mouse testes. Meanwhile, overexpressing lncRNA5251 decreased the gene and/or protein expression of important genes for spermatogenesis and immune pathways in mouse testes. In vitro, knockdown lncRNA5251 increased the expression of genes for cell junction, and the protein levels of some cell junction proteins such as CX37, OCLN, JAM1, VCAM1 and CADM2 in C18-4 cells. LncRNA5251 is involved in spermatogenesis by modulation of cell junctions.ConclusionThis will provide a theoretical basis for improving male reproductive ability via lncRNA.

Developmental heat stress interrupts spermatogenesis inducing early male sterility in Drosophila melanogaster

Thermal stress leads to fertility reduction, can cause temporal sterility and thus results in fitness loss with severe ecological and evolutionary consequences, e.g., threatening species persistence already at sub-lethal temperatures. For males we here tested which developmental stage is particularly sensitive to heat stress in the model species Drosophila melanogaster. As developmental stages characterize the different steps of sperm development, we could narrow down which particular processes are heat sensitive. We studied early male reproductive ability and, by following recovery dynamics after a move to benign temperatures, we investigated general mechanisms behind a subsequent gain of fertility. We found strong support to suggest that the last steps of spermatogenesis are particularly sensitive to heat stress, as processes occurring during the pupal stage were mostly interrupted, delaying both sperm production and sperm maturation. Moreover, further measurements in the testes and for proxies of sperm availability indicating the onset of adult reproductive capacity matched the expected heat-induced delay in completing spermatogenesis. We discuss these results within the context of how heat stress affects reproductive organ function and the consequences for male reproductive potential.

Characterization, expression analysis and RNAi-mediated knockdown of two aquaporin genes in the cotton leafworm, Spodoptera littoralis (Lepidoptera: Noctuidae)

Aquaporins (AQPs) are integral membrane proteins that can transport water and small molecules across cell membranes in organisms. In a previous report, we identified an AQP (SlAQP1) gene of the cotton leafworm, Spodoptera littoralis. In the current study, we identify and characterize two more SlAQP genes and their developmental and tissues expression. Predicted amino acid sequence and phylogenetic analysis revealed that SlAQP2 is a glycerol channel belonging to the insect specific Eglp subfamily, whereas SlAQP3 is a water specific channel belonging to the Prip subfamily. SlAQP2 expression was detected mainly in the first four larval instars and adult males, whereas SlAQP3 was detected in all developmental stages. SlAQP2 gene expression was mainly detected in larval midgut and Malpighian tubules and adult male testes, whereas SlAQP3 was detected in all the tissues tested. RNAi mediated knockdown of each gene separately resulted in deleterious effects including larval and pupal mortality, deformed pupae and adults and prolonged development. Results were confirmed using qRT-PCR, which revealed downregulation of both genes after injection of larvae with gene specific dsRNA. Our results confirm the presence of Prip and Eglp AQPs in S. littoralis and suggest that Eglp has a role in male reproductive ability.

Bioinspired engineered nickel nanoparticles with multifunctional attributes for reproductive toxicity

Nickel nanoparticles (Ni-NPs) have potential applications in high-tech sectors such as battery manufacturing, catalysis, nanotube printing and textile. Apart from their increasing utilisation in daily life, there are concerns about their hazardous nature as they are highly penetrable in biological systems. The carcinogenic and mutagenic ability of Ni-NPs is evident but the research gaps are still there concerning the safety evaluation of Ni-NPs regarding male reproductive ability. This controlled randomized research was planned to assess the male reproductive toxicity of Ni-NPs in Sprague Dawley rats. Ni-NPs of spherical shape and mean particle size of 56 nm were used in the study, characterized by SEM, EDS and XRD. The twenty-five healthy rats (200–220 g) were used for toxicity investigation of Ni-NPs and divided into five groups; negative control (0 Ni-NPs), placebo group (0.9% saline) and three Ni-NPs treated groups (@ 15, 30 and 45 mg/kg BW). The results of 14 days of intraperitoneal exposure to Ni-NPs revealed that a higher dose (45 mg/kg BW) of Ni-NPs caused a significant reduction in body weight, serum testosterone, daily sperm production while the testis index and Ni accumulation and histological changes (necrosis in basement membrane and seminiferous tubules, vacuole formation) in testicular tissues increased with increasing dose of Ni-NPs. It can be concluded from the study that Ni-NPs have potential reproductive toxicity. This study provided the baseline data of Ni-NPs toxicity for the male reproductive system and can be applied for risk assessment in Ni-NPs based products.

Bisphenol A induces testicular oxidative stress in mice leading to ferroptosis.

Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.

Progress in the effect of human epididymis protein 4 on sperm maturation

Human epididymis protein 4(HE4) is a secretory glycoprotein found in human distal epididymis epithelial cells. It is often used in the early diagnosis, efficacy evaluation and monitoring of ovarian cancer, and also has been considered as an effective serum marker for many other types of cancer. However, its function in the process of sperm maturation is not fully unknown. The maturation of sperm in epididymis is characterized by the acquisition of motility and fertilization. As a member of the whey acid protein (WAP) family, several studies proposed the importance of HE4 in the maturity of sperm in epididymis. This article reviews the effect of HE4 on spermatozoa maturation in epididymis, which provides basis for the evaluation of male reproductive ability, early detection, early diagnosis and pathogenesis of male infertility.

Getah Virus Infection Rapidly Causes Testicular Damage and Decreases Sperm Quality in Male Mice.

Getah virus (GETV) is a zoonotic arbovirus that can cause infection in many animals. It can cause pyrexia and reproductive losses in animals. The objective of the study was to explore the effects of GETV on male reproductive ability. Male mice were injected with 100 × TCID50/0.1 ml in a volume of 100-μL GETV in their hindquarter muscle, resulting in decreased semen quality and testicular histopathological changes, and the virus was detected in the testes. At 0.5 dpi (day post-infection), male mice showed decreased sperm density, motility, and decreased serum testosterone concentration, an increased sperm malformation rate, vacuoles in spermatogonial cells/spermatocytes in spermatogenic tubules, and the highest virus copies in testis. At 2 dpi, the sperm density and motility reached the lowest value of 3.99 × 106/ml and 62.03%, and the malformation rate reached 43.67%. At 28 dpi, the sperm indexes of the experimental group gradually approached that of the control group, but there were still significant differences. Since then, histopathological changes have worsened, with the most severe histopathological changes at 7 dpi and gradual recovery. Up to 14 dpi, the virus was detected by qRT-PCR and immunohistochemistry, which showed that the virus was only present in the testicular interstitium. GETV infection can rapidly enter the testis of mice and reduce the semen quality of mice, which needs to be paid attention to in the prevention and control of GETV.

Rapamycin Ameliorates Radiation-Induced Testis Damage in Mice.

Male infertility is an important problem in human and animal reproduction. The testis is the core of male reproduction, which is very sensitive to radiation. The decline of male reproductive ability is a common trend in the world. Radiation is a physical factor leading to abnormal male reproductive function. To investigate the potential mechanisms of testicular damage induced by radiation and explore effective strategies to alleviate radiation-induced testis injury, C57BL/6 mice were irradiated with 8.0 Gy of X-ray irradiation. Testis and epididymis were collected at days 1, 3, and 7 after radiation exposure to analyze spermatogonia and sperm function. The results showed that radiation significantly destroyed testicular structure and reduced the numbers of spermatogonia. These were associated with mTORC1 signaling activation, decreased cellular proliferation and increased apoptotic cells in the irradiated testis. Rapamycin significantly blocked mTORC1 signaling pathway in the irradiated testis. Inhibition of mTORC1 signaling pathway by rapamycin treatment after radiation could significantly improve cell proliferation in testis and alleviate radiation-induced testicular injury after radiation exposure. Rapamycin treatment benefited cell survival in testis to maintain spermatogenesis cycle at 35 days after irradiation. These findings imply that rapamycin treatment can accelerate testis recovery under radiation condition through inhibiting mTORC1 signaling pathway.

Non-gonadal linear type traits can discriminate reproductive ability of breeding dairy bulls.

Linear type traits are easily measurable phenotypic characteristics that help breed characterization, selection of animals for breeding and found to be associated with animals' performance. Unlike cows, there have been limited studies linking body linear traits with male reproductive ability and semen cryo-preservability of breeding bulls. Present study reported the age-related changes in body linear type traits in Frieswal (N=378) dairy bulls and its relevance with reproductive potentials of breeding bulls. Our results indicated that body frame size traits were significantly and positively correlated with gonadal linear traits. Among the selected body mophometric parameters body length, chest girth and head circumference were the important body linear type traits having capability to discriminate between bulls of frozen semen doses (FSD) and non-FSD categories. Discriminant function has been developed based on body linear traits of crossbred dairy bulls to find out males of superior reproductive potentials. Our finding provided evidence that body length (humerous tuberosity to tuber ischii) was the most powerful linear body trait associated with breeding bulls' reproductive ability and semen quality.

Bull fertility and semen quality are not correlated with dairy and production traits in Brown Swiss cattle

Undisturbed reproduction is key for successful breeding of beef and dairy cattle. Improving reproductive ability can be difficult because of antagonistic relationships with other economically relevant traits. In cattle, thorough investigation of female fertility revealed unfavorable genetic correlations with various production phenotypes. However, the correlation between male reproductive ability and production traits remains poorly understood. Here, we investigated the genetic relationships among and between male fertility characteristics and economically relevant traits in a population of Brown Swiss cattle. We performed GWAS with imputed genotypes at nearly 12 million sequence variants for semen quality (sperm head and tail anomalies, motility, concentration, and volume), male fertility, and 57 production phenotypes. Allele substitution effects were then correlated on a trait-by-trait basis to estimate genetic correlations. Correlations between male reproductive characteristics and traits of economic value were small and ranged from −0.0681 to 0.0787. Among the semen quality parameters, sperm motility was negatively correlated with anomalies (head: r = −0.7083 ± 0.0002; tail: r = −0.7739 ± 0.0002) and volume (r = −0.1266 ± 0.0003), whereas volume was negatively correlated with concentration (r = −0.3503 ± 0.0002). Sire nonreturn rate was negatively correlated with sperm anomalies (head: r = −0.1640 ± 0.0002; tail: r = −0.1580 ± 0.0002) and positively correlated with motility (r = 0.1598 ± 0.0002). A meta-analysis of male reproductive traits identified 2 quantitative trait loci: a previously described region on chromosome 6 showed pleiotropic effects and a novel region on chromosome 11 was associated with sperm head anomalies. In conclusion, our results suggest that selection for economically important dairy and production phenotypes has little impact on semen quality and fertility of Brown Swiss bulls.

Protein kinases regulate hyperactivated motility of human sperm.

Protein kinases regulate hyperactivated motility of human sperm.

Sperm Quality and Environment: A Retrospective, Cohort Study among 21,715 Semen Samples in a Southern Province of China

To explore the differences of male semen parameters in different seasons of the year, so as to explore the potential climatic factors affecting spermatogenesis and male reproductive ability, we retrospectively analyzed 21,715 semen analysis data from January 2018 to February 2021, grouped by year and season, and finally the relationships among semen parameters and semen and meteorological parameters were compared. Environmental exposures prior to 3 months were analyzed and correlation analysis was performed.The semen concentration decreased year by year (p

The hypothesis that SARS-CoV-2 affects male reproductive ability by regulating autophagy

The outbreak of CoronaVirus Disease19 (COVID19) in December 2019 posed a serious threat to public safety, and its rapid spread caused a global health emergency. Clinical data show that in addition to respiratory system damage, some male patients with COVID-19 are also accompanied by abnormal renal function and even renal damage. As the main receptor of syndrome coronavirus 2 (SARS-CoV-2), angiotensin converting enzyme 2 (ACE2) is also found to be highly expressed not only in respiratory mucosa and alveolar epithelial cells, but also in renal tubule cells, testicular Leydig cells and seminiferous tubule cells. This suggests that SARS-CoV-2 has the possibility of infecting the male reproductive system, and the recent detection of SARS-CoV-2 in the patient's semen further confirms this theory. In previous studies, it has been found that ACE2 has the ability to regulate autophagy. Not only that, recent studies have also found that SARS-CoV-2 infection can also lead to a reduction in autophagy. All of these associate SARS-CoV-2 with autophagy. Furthermore, autophagy has been shown to have an effect on male reproduction in many studies. Based on these, we propose the hypothesis that SARS-CoV-2 affects male reproductive function by regulating autophagy. This hypothesis may provide a new idea for future treatment of COVID-19 male patients with reproductive function injury, and it can also prompt medical staff and patients to consciously check their reproductive function.

Male reproductive ageing: a tale of the whole ejaculate.

Ageing is nearly ubiquitous and encompasses all biological functions. We here focus on age-dependent changes in male reproductive capacity across a broad range of animal taxa. While there has been a long-standing focus on mating ability and overall reproductive success, we here highlight the underlying mechanisms that explain loss in fertilisation capacity in ageing males. Fertilisation is mediated by not only the presence of sperm, but also the cocktail of seminal fluid proteins that ensure sperm survival, capacitation and interaction with female physiology. Sperm ageing has received much attention in studies of male reproductive senescence; however, post-mating processes include a number of interlocked steps that together cumulate in successful fertilisation. As such we consider male ability to elicit female post mating responses such as uterine conformational changes, sperm storage and ovulation and the components within the ejaculate that mediate these post-mating processes. For the latter seminal fluid proteins are key and hence we reflect on age-dependent changes in quality of the entire ejaculate and its consequences for male reproductive capacity. While first studies accrue and highlight that changes in the non-sperm fraction can explain substantial variation in senescent male reproductive success and male ability to induce post-mating responses necessary for fertilisation many open questions still remain that warrant further investigations. One being what the potential age-dependent changes in composition are or whether there is a general decline and how this interacts with sperm to affect fertilisation success. Further, the impact females might have to ameliorate these changes will be an area of interest.

Pengaruh Pemberian Ekstrak Buah Pisang (Musa acuminate L) dan Buah Alpukat (Persea americana Mill) Terhadap Berat Hati Mencit (Mus musculus) Betina

Male reproductive ability ability has a linear correlation with libido and testosterone. Both are associated with various things main food consumption such as protein, vitamins and minerals. Aphrodisiac is an ingredient or drug that arouses sexual arousal or libido. Pumpkin is an example of food from plants with the highest content of zinc. This study was to determine whether there is a difference between the content of zinc on the peel, flesh and pumpkin seeds against sexual activity of mice. The experimental animals used were 24 male, group I mice as control group, Group II was grouped with pumpkin peel extract, Group III was grouped with extract of pumpkin flesh, Group IV was grouped with extract of pumpkin seeds. The dose used is 2gr / kg BB and volume of 0.2 ml is given for 35 days. Sexual Activity is observed every day by the position of male mice riding females. Based on Anova One Way test results showed there are differences in sexual activity mice males in each group (ρ 0.000). The difference of the result of the number of mounts indicated that the giving of yellow pumpkin extract had an effect on the increase of mating behavior of male mice. The group treated with the extract of pumpkin flesh showed the highest number of mice mounts (mean = 24,1667.Further research is needed to get a clearer picture of the composition of the pumpkin nutrients that indirectly affect fertility in men.