Longitudinal trends in testicular volume z scores from puberty to adulthood, sperm quality, and paternity outcomes after childhood cancer.

BACKGROUND: Childhood cancer therapy may cause subfertility. This study correlated cancer therapy exposures with testicular volumes from puberty to adulthood, spermatogenesis, and paternity outcomes in adulthood. METHODS: The study population comprised 255 male childhood cancer survivors (CCS) (survival ≥5 years, diagnosed in 1964-2000 at the Helsinki Children's Hospital) whose testicular volume was measured at ages 12 years (n = 38), 14 years (n = 57), 16 years (n = 63), 18 years (n = 105), and in adulthood (n = 43; median age, 27 years). Testicular volumes were converted to age-specific z scores. In addition, 92 CCS provided semen sample in adulthood (median age, 25.2 years); and paternity was evaluated through national register data (mean age at assessment, 37.6 years; n = 252). RESULTS: Compared with age-specific reference values, CCS generally exhibited low testicular volume z scores at ages 12-18 years. Testicular volume z scores in CCS treated exclusively with chemotherapy returned to the reference range in adulthood. In contrast, patients exposed to testicular radiation ≥1 gray (Gy) (median dose, 12 Gy) showed no late recovery in testicular size. Testicular radiation ≥1 Gy and a cyclophosphamide equivalent dose ≥12 g/m2 were identified as risk factors for azoospermia in adulthood. Patients exposed to testicular radiation ≥1 Gy and a cyclophosphamide equivalent dose ≥4 g/m2 had lower paternity rates. CONCLUSIONS: Testicular volume growth after prolonged follow-up suggests a potential late recovery of spermatogenesis in CCS treated exclusively with chemotherapy. However, alkylating agents increased the risk of having prolonged azoospermia and nonpaternity. High-dose testicular radiation causes long-term depletion of spermatogonia and was the strongest risk factor for azoospermia and nonpaternity.

The influence of male HBV infection on sperm quality, embryonic development, and assisted reproductive outcomes.

STUDY QUESTION: What is the impact of male hepatitis B virus (HBV) infection on sperm quality, embryonic development, and assisted reproductive outcomes? SUMMARY ANSWER: Male HBV infection did not affect assisted reproductive outcomes, but HBV is capable of impairing human sperm and embryo formation in the early stages following fertilization. WHAT IS KNOWN ALREADY: HBV is found in germ cells and early embryos of patients with HBV. HBV may impair human sperm function via increasing reactive oxygen species. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study of 1581 infertile couples, including 496 male patients clinically confirmed to have hepatitis B infection, and a laboratory study of effects of HBV proteins on early embryos, using human embryonic stem cells (hESCs), human sperm, and golden hamster oocytes. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 1581 infertile couples (24-40 years of age) who were admitted to a reproductive medicine center to undergo ART for the first time from January 2019 to November 2021 were selected as the study subjects. The case group was composed of 469 couples with hepatitis B surface antigen (HBsAg)-seropositive men and seronegative women (368 for IVF and 101 for ICSI treatment). The negative control group was composed of 1112 couples where both men and women were seronegative for hepatitis B antigen. We divided these couples into three comparison groups (IVF/ICSI, IVF, and ICSI). IVF of human sperm and hamster oocytes was used to evaluate the influence of the HBV HBs protein on formation of 2-cell embryos. Mitochondrial membrane potential (MMP) of hESCs was assayed via a fluorescence intensity system. Immunofluorescence staining of the phosphorylated histone H2A.X was applied to identify DNA damage to hESCs caused by the HBV X (HBx) protein. MAIN RESULTS AND THE ROLE OF CHANCE: Sperm concentration, total sperm number, and sperm with normal morphology were decreased in the couples with HBV-infected males in couples who were undergoing IVF/ICSI (male HBV(+) vs control: 469 vs 1112 individuals; sperm number, P < 0.01; normal sperm morphology, P < 0.01), IVF (368 vs 792; sperm number, P < 0.01; normal sperm morphology, P ≤ 0.05), and ICSI (101 vs 306; sperm number, P < 0.01; normal sperm morphology, P < 0.001). There was no significant difference in the number of embryo cleavages, blastocyst formation, biochemical pregnancy rate, clinical pregnancy rate, and live-birth rate between case and control groups. The 2PN fertilization rate in IVF/ICSI (P < 0.01) and ICSI (P < 0.05) couples, and the number of 2PN-fertilized oocytes in IVF (P < 0.001) couples were lower in couples with male HBV infection compared to control couples. HBV HBs protein reduced the MMP of human sperm and decreased 2-cell embryo formation in IVF of human sperm and zona-free-hamster oocyte. A reduction in fluorescence intensity and immunofluorescence staining of phosphorylated histone H2A.X indicated that HBx caused MMP impairment and DNA damage in human early embryonic cells, respectively. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: HBV can be examined in samples of sperm or discarded IVF early embryos from HBsAg-seropositive men and seronegative women. The hESC model in vitro may not fully mimic the natural embryos in vivo. WIDER IMPLICATIONS OF THE FINDINGS: This study furthers our understanding of the influence of male HBV infection on embryonic development. Our results suggest that a semen-washing process may be necessary for male patients with HBV undergoing ART to minimize the potential negative effects of HBV infection on the early embryo. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by grants from the National Natural Science Foundation of China, grant numbers 81870432 and 81570567 to X.Z., 81571994 to P.S., and 81950410640, the Natural Science Foundation of Guangdong Province, China (No. 2023A1515010660 to X.Z.), and the Li Ka Shing Shantou University Foundation (Grant No. L11112008). The authors have no conflicts of interest.

The prediction of semen quality based on lifestyle behaviours by the machine learning based models.

PURPOSE: To find the machine learning (ML) method that has the highest accuracy in predicting the semen quality of men based on basic questionnaire data about lifestyle behavior. METHODS: The medical records of men whose semen was analyzed for any reason were collected. Those who had data about their lifestyle behaviors were included in the study. All semen analyses of the men included were evaluated according to the WHO 2021 guideline. All semen analyses were categorized as normozoospermia, oligozoospermia, teratozoospermia, and asthenozoospermia. The Extra Trees Classifier, Average (AVG) Blender, Light Gradient Boosting Machine (LGBM) Classifier, eXtreme Gradient Boosting (XGB) Classifier, Logistic Regression, and Random Forest Classifier techniques were used as ML algorithms. RESULTS: Seven hundred thirty-four men who met the inclusion criteria and had data about lifestyle behavior were included in the study. 356 men (48.5%) had abnormal semen results, 204 (27.7%) showed the presence of oligozoospermia, 193 (26.2%) asthenozoospermia, and 265 (36.1%) teratozoospermia according to the WHO 2021. The AVG Blender model had the highest accuracy and AUC for predicting normozoospermia and teratozoospermia. The Extra Trees Classifier and Random Forest Classifier models achieved the best performance for predicting oligozoospermia and asthenozoospermia, respectively. CONCLUSION: The ML models have the potential to predict semen quality based on lifestyles.

Emerging trends in sperm selection: enhancing success rates in assisted reproduction.

This comprehensive review explores the evolving landscape of sperm selection techniques within the realm of Assisted Reproductive Technology (ART). Our analysis delves into a range of methods from traditional approaches like density gradient centrifugation to advanced techniques such as Magnetic-Activated Cell Sorting (MACS) and Intracytoplasmic Morphologically Selected Sperm Injection (IMSI). We critically assess the efficacy of these methods in terms of sperm motility, morphology, DNA integrity, and other functional attributes, providing a detailed comparison of their clinical outcomes. We highlight the transition from conventional sperm selection methods, which primarily focus on physical characteristics, to more sophisticated techniques that offer a comprehensive evaluation of sperm molecular properties. This shift not only promises enhanced prediction of fertilization success but also has significant implications for improving embryo quality and increasing the chances of live birth. By synthesizing various studies and research papers, we present an in-depth analysis of the predictability of different sperm selection procedures in ART. The review also discusses the clinical applicability of these methods, emphasizing their potential in shaping the future of assisted reproduction. Our findings suggest that the integration of advanced sperm selection strategies in ART could lead to more cost-effective treatments with reduced duration and higher success rates. This review aims to provide clinicians and researchers in reproductive medicine with comprehensive insights into the current state and future prospects of sperm selection technologies in ART.

Does COVID-19 affect sperm quality in males? the answer may be yes, but only temporarily.

BACKGROUND: The Corona Virus Disease 2019 (COVID-19) pandemic has raised concerns regarding its potential impact on male reproductive health. However, the impact of COVID-19 on sperm quality remains uncertain. This retrospective study aimed to investigate the short-term and relatively long-term effects of COVID-19 infection on sperm quality. METHODS: A total of 85 males with fertility requirements, who underwent semen evaluation at Guilin People's Hospital between June 2022 and July 2023, were included in the study. Changes in semen parameters were analyzed across three specific timeframes: within 6 months before COVID-19 infection, within 3 months after COVID-19 infection, and 3-6 months after COVID-19 recovery. RESULTS: The results revealed that the sperm concentration and total sperm number were significantly lower after infection compared to before, while in the recovery period, the sperm concentration, total sperm count, progressive motility, and normal morphology significantly increased. Comparing the three periods, the most significant difference was observed in sperm concentration, which exhibited a significant decrease after infection but returned to normal levels after recovery from COVID-19. CONCLUSIONS: These findings suggest that COVID-19 may exert some impact on sperm quality, particularly evidenced by decreased sperm concentration post-infection. Fortunately, these effects on semen parameters appear to be temporary, with gradual restoration of semen parameters within 3-6 months after recovery. However, further research is needed to explore the underlying mechanisms and long-term implications of these observed changes in semen parameters.

Male Fertility in Spondyloarthritis: from Clinical Issues to Cytokines Milieu. A Narrative Review.

PURPOSEOF REVIEW: Male fertility is an emergent issue that should be considered in clinical practice, when dealing with chronic inflammatory diseases in young men. As it is known, the chronic inflammation is the main pathophysiologic mechanism in some rheumatological conditions such as spondyloarthritis (SpA), Ankylosing Spondylitis (AS) and Psoriatic Arthritis (PsA). Therefore, it is paramount to be aware if these diseases could impair male fertility, both due to the inflammation or to the treatments needed: we reviewed the literature on the most relevant and recent evidence on male fertility in patients affected by SpA, AS and PsA. RECENT FINDINGS: Rheumatological inflammatory diseases (included SpA, AS and PsA) could impair the family planning in man life, especially when diagnosed at young age. Moreover, focusing on sperm quality, it seems that a link between sperm quality impairment and a higher disease activity exist. Focusing on therapies, Tumor Necrosis Factor inhibitors showed a safety profile on human male fertility in clinical studies. Recently, a prospective study and two double-blind placebo-controlled trials assessed the impact of methotrexate and Filgotinib on semen parameters, respectively, showing a safety profile of these drugs on human semen quality. However, there are no clinical data on the impact of Interleukin (IL)17 inhibitors(i), IL12-23i and IL23i. Concerning male fertility in SpA, AS and PsA, an unmet clinical need is still present and new studies are needed to understand the association between these diseases and male fertility, and the implication of the therapies used for these diseases. This narrative review provides an overview of the available data on male fertility in patients affected by SpA, AS and PsA.

Mechanistic Insights into 1,2-bis(2,4,6-tribromophenoxy)ethane-Induced Male Reproductive Toxicity in Zebrafish.

The novel brominated flame retardant, 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), has increasingly been detected in environmental and biota samples. However, limited information is available regarding its toxicity, especially at environmentally relevant concentrations. In the present study, adult male zebrafish were exposed to varying concentrations of BTBPE (0, 0.01, 0.1, 1, and 10 µg/L) for 28 days. The results demonstrated underperformance in mating behavior and reproductive success of male zebrafish when paired with unexposed females. Additionally, a decline in sperm quality was confirmed in BTBPE-exposed male zebrafish, characterized by decreased total motility, decreased progressive motility, and increased morphological malformations. To elucidate the underlying mechanism, an integrated proteomic and phosphoproteomic analysis was performed, revealing a predominant impact on mitochondrial functions at the protein level and a universal response across different cellular compartments at the phosphorylation level. Ultrastructural damage, increased expression of apoptosis-inducing factor, and disordered respiratory chain confirmed the involvement of mitochondrial impairment in zebrafish testes. These findings not only provide valuable insights for future evaluations of the potential risks posed by BTBPE and similar chemicals but also underscore the need for further research into the impact of mitochondrial dysfunction on reproductive health.

Effects of environmental temperature extremes exposure on sperm quality - Evidence from a prospective cohort study in Anhui Province, China.

Extreme weather is becoming more frequent due to drastic changes in the climate. Despite this, the body of research focused on the association between temperature extreme events and sperm quality remains sparse. In this study, we elucidate the impact of exposure to environmental temperature extremes on sperm quality. Data for this investigation were derived from the Anhui Prospective Assisted Reproduction Cohort, encompassing the period from 2015 to 2020. Parameters such as sperm concentration, total sperm count, total motility, progressive motility, total motile sperm count, and progressive motile sperm count were quantified from semen samples. We assessed the exposure of participants to temperature extremes during the 0-90 days prior to sampling. This investigation encompassed 15,112 participants, yielding 28,267 semen samples. Our research findings indicate that exposure to low temperature extreme for three consecutive days (at the first percentile threshold) has a detrimental correlation with sperm count parameters and concentration. Similar trends were observed with the second percentile threshold, where significant adverse effects typically manifested after a four-day exposure sequence. Analysis of high temperature extreme showed that exposure at the 98th percentile had adverse effects on all six sperm quality parameters, and the sperm count parameter was particularly sensitive to high temperature, showing significant results immediately after three days of exposure. When considering even more temperature extreme (99th percentile), the negative consequences were more pronounced on the sperm count parameter. Additionally, progressive motility showed a stronger negative response. In summary, parameters associated with sperm count are particularly vulnerable to temperature extremes exposure. Exposure to high temperature extremes environments may also be associated with a decrease in sperm concentration and vitality. The findings of this study suggest that male population should pay attention to avoid exposure to temperature extreme environment, which has important significance for improving the quality of human fertility.

Effects of different hormonal treatments on spermatogenesis advancement in hatchery-produced greater amberjack Seriola dumerili (Risso 1810).

In earlier studies, wild-caught greater amberjack Seriola dumerili (Risso, 1810) males reared in sea cages showed gametogenesis impairment and low sperm production and quality. Here, we (a) examined if F1 hatchery-produced males reared in sea cages also exhibit reproductive dysfunctions and (b) evaluated the effects of gonadotropin releasing hormone agonist (GnRHa) administration through injections (GnRHainj) or sustained-release implants (GnRHaimpl), and human chorionic gonadotropin (hGC) injections on spermatogenesis/spermiation enhancement. Fish were given a hormone treatment just prior to the spawning season, and were transferred to land-based tanks, according to an established spawning induction protocol. Blood samples (n = 6) were obtained on Days 0, 7 and 13 after treatment. Testis samples were obtained on Days 0 (n = 4) and 13 (n = 2 per treatment). The fish prior to their transfer from the sea cages to the land-based tanks, exhibited a low gonadosomatic index, altered sex steroid hormone profile and high density of testicular apoptotic cells. After transfer to tanks, there was a general depression of sex steroid plasma levels parallel to an increase in cortisol concentrations. Despite the negative effect on steroidogenesis by the transfer from the sea, the hormonal treatments increased the number of fish from where sperm could be obtained, as well as testis growth, and reduced testicular apoptosis. Treatment with hCG resulted in the most significant changes in spermatogenesis, while GnRHaimpl appeared to induce less intense, but likely longer-lasting effects. The study indicated that F1 hatchery-produced males also exhibited reproductive dysfunctions as wild-caught captive-reared greater amberjack, and that the observed positive effects of the hormone treatments on spermiation/spermatogenesis were likely mediated by factors other than sex steroid hormones.

Effect of natural astaxanthin on sperm quality and mitochondrial function of breeder rooster semen cryopreservation.

Cryopreservation causes higher reactive oxygen species (ROS) concentrations, leading to oxidative stress and lipid peroxidation damaging sperm, and using antioxidants can improve semen quality after freeze-thaw. Natural astaxanthin (ASTA) can be inserted into cell membranes and its antioxidant properties are stronger than other antioxidants. We aimed to investigate the effects of ASTA supplementation in the Beltsville Poultry Semen Extender (BPSE) on post-thaw rooster semen quality and to explore the potential mechanism of rooster semen quality change. The qualifying semen ejaculates collected from 30 adult male Jinghong No. 1 laying hen breeder roosters (65 wk old) were pooled, divided into four aliquots, and diluted with BPSE having different levels of ASTA (0, 0.5, 1, or 2 µg/mL). Treated semen was cryopreserved and kept in liquid nitrogen. The entire experiment was replicated three times independently. Sperm viability, motility, curvilinear velocity, amplitude of lateral head displacement, straightness, plasma membrane integrity, and acrosome integrity were observed to be highest (P < 0.05) with 1 µg/mL ASTA at freeze-thawing. Higher (P < 0.05) antioxidant enzyme (CAT-like, SOD) activities and free radical (·OH, O2.-) scavenging ability, less ROS and malondialdehyde (MDA) concentrations were recorded with the addition of appropriate concentrations of ASTA compared to control. In addition, the levels of mitochondrial membrane potential (MMP), adenosine triphosphate (ATP), and lactate dehydrogenase (LDH) in the 1 µg/mL ASTA group improved compared to the control group, and decreased the amount of AIF protein level but increased the Bcl-2 protein level (P < 0:05). Collectively, these results demonstrate that adding ASTA in the BPSE promoted rooster freeze-thaw sperm quality, which may be related to reducing ROS levels, protecting the antioxidant defense system, preventing lipid peroxidation, improving mitochondrial structural and functional integrity, and inhibiting sperm apoptosis.

Melatonin production improves Senegalese sole sperm motility at night, but fails as a supplement during cryopreservation.

Melatonin is a powerful antioxidant present in fish seminal plasma. This study aimed to understand melatonin's endogenous and exogenous effects on first-generation Senegalese sole sperm quality for sperm management applications. In the first experiment, samples were collected at mid-light (ML) and mid-dark (MD) daytimes, to evaluate the effects on sperm motility. In a second experiment, using confocal microscopy and melatonin-FITC, spermatozoa permeability to melatonin was evaluated and, after showing that it enters the nucleus and mitochondria by passive diffusion, exogenous melatonin toxicity and antioxidant potential during a cryopreservation assay were performed. The toxicity assay tested different melatonin concentrations (0.01, 0.1, 1, and 10 mM) and exposure times (3, 5, 15 and 30 min), and sperm motility parameters were measured (TM, PM, VCL, VSL, LIN) using CASA system. The best conditions (0.1 and 10 mM) were selected for the cryopreservation assay, and a set of post-thaw sperm quality analyses were performed (motility, viability, reactive oxygen species, lipid peroxidation, and DNA fragmentation). The motility analyzed at ML and MD showed significant differences in all parameters, mainly on velocities (VCL, VSL, VAP), that were significantly higher at MD. Supplemented melatonin did not influence spermatozoa motility, MDA content or DNA fragmentation, although a lower percentage of viable cells was obtained on the 10 mM treatment. Altogether, Senegalese sole spermatozoa motility was enhanced at night, putatively by endogenous melatonin through direct or indirect mechanisms, whereas supplemented melatonin did not confer extra protection during cryopreservation.

In vitro exposure of porcine spermatozoa to methylparaben, and propylparaben, alone or in combination adversely affects sperm quality.

Parabens (PBs) are widely used in the cosmetic, pharmaceutical, and food industries as preservatives of products. Because of its great use, humans and other organisms are highly exposed daily. However, little is known about the effect of PBs on male infertility. Therefore, the aim of the present study was to evaluate the effect of methylparaben (MePB) and propylparaben (PrPB), alone or in combination, on the physiological characteristics of pig in vitro exposed sperm to different concentrations (0, 200, 500, and 700 µM) for viability, motility, and acrosome integrity evaluation and (0, 200, 500, 700, 1000, and 2000 µM) for DNA fragmentation index evaluation, after 4 h of exposure. The results showed that sperm viability decreased after exposure to MePB from the concentration of 500 µM. In the PrPB and mixture groups, viability decreased at all concentrations except for the control. The decrease in viability of sperm exposed to PrPB was greater than that of the mixture and MePB groups. Sperm motility decreased in all the experimental groups exposed to PBs, at all concentrations, except for the control group. Acrosome integrity was not decreased in the MePB group; however, in the PrPB group, it decreased at a concentration of 200 µM and in the mixture at 500 µM. All groups exhibited DNA damage at different concentrations, except for the control group. Additionally, the effect of PBs on sperm quality was concentration-dependent. The results demonstrated that MePB and PrPB alone or in combination can have adverse effects on sperm quality parameters. MePB had lower toxicity than did both PrPB and the mixture. The mixture did not have an additive effect on any of the parameters evaluated. This could partially explain the link between PB exposure and infertility.

A systematic review focused on lubricant use and sperm quality: Improving human reproductive success by informing lubricants toxicity.

Lubricants play a pivotal role in human reproductive health, particularly concerning their impact on sperm parameters. In this systematic review, we assess the implications of both synthetic and natural or organic lubricants on sperm health and fertility, based on a compilation of 20 distinct studies. Synthetic lubricants, including K-Y Jelly, Replens, and Astroglide, predominantly containing ingredients like methylparaben and glycerin, have been linked to detrimental effects on sperm motility and chromatin integrity. Chemical characteristics, notably osmolality and pH, are central to understanding these effects. Despite the World Health Organization's osmolality recommendation of 380 mOsm/kg, many commercial products surpass this. Natural solutions offer varied results, while olive oil exhibits unfavorable effects on sperm health, egg white proves non-toxic, potentially benefitting sperm health. Conversely, Pre-Seed, widely endorsed in the research community, generally demonstrates minimal adverse impact on sperm. The review highlights the significance of lubricant selection in evidence-based reproductive strategies.

Exposure to ambient ozone and sperm quality among adult men in China.

BACKGROUND: Limited evidence exists regarding the association between ozone exposure and adverse sperm quality. We aimed to assess the association between ozone exposure and sperm quality, and identify susceptible exposure windows. METHODS: We recruited 32,541 men aged between 22 and 65 years old attending an infertility clinic in Wuhan, Hubei Province, China from 2014 to 2020. Ozone data were obtained from a satellite-based spatiotemporal model. Generalized linear models were used to estimate the association between ozone exposure and sperm quality parameters, including sperm concentration, sperm count, sperm total motility, and sperm progressive motility during the entire stage of sperm development (0-90 days before ejaculation) and three crucial stages (0-9 days, 10-14 days and 70-90 days before ejaculation). Stratified analyses were performed to evaluate whether associations varied by age, body mass index, and education levels. RESULTS: The final analysis included 27,854 adult men. A 10 µg/m3 increase in ozone concentrations during the entire stage of sperm development was associated with a -4.17 % (95 % CI: -4.78 %, -3.57 %) decrease in sperm concentration, -6.54 % (95 % CI: -8.03 %, -5.60 %) decrease in sperm count, -0.50 % (95 % CI: -0.66 %, -0.34 %) decrease in sperm total motility, and -0.07 % (95 % CI: -0.22 %, 0.09 %) decrease in sperm progressive motility. The associations were stronger during 70-90 days before ejaculation and among men with middle school and lower education for sperm concentration. CONCLUSIONS: Ozone exposure was associated with decreased sperm quality among Chinese adult men attending an infertility clinic. These results suggest that ozone may be a risk factor contributing to decreased sperm quality in Chinese men.

Fluorene-9-bisphenol impaired male fertility through disrupting the testicular function and local microenvironment.

Past studies have observed that BHPF induces multi-organ toxicity, however, whether it induces damage to male reproductive system and the specific mechanism remains unclear. In the present study, male mice were given 0, 2, 10 or 50 mg/kg/day of BHPF by gavage for 35 days to observe its effect on reproductive organ and sperm quality. The results indicated that BHPF decreased sperm count and sperm motility in a dose-dependent manner. Besides, our results demonstrated that BHPF triggered the proliferation inhibition and cell death of germ cells in vivo and in vitro. Also, BHPF reduced the expression of function markers for germ cells, Sertoli cells, and Leydig cells, indicating its damage to function of testis cells. Simultaneously, testicular microenvironment was found to be altered by BHPF, as presented with declined testosterone level and decreased expression of local microenvironment regulators. Overall, our findings indicated the detrimental effects of BHPF on male reproductive function in mice, suggesting testicular function and local microenvironment disturbance as mechanism underlying testicular damage.

Cresyl Diphenyl Phosphate exposure induces reproductive functional defects in men and male mice.

Cresyl Diphenyl Phosphate (CDP), as a novel organophosphate esters (OPEs), achieves widely used and exposed in multiple industries. However, its male reproductive toxicity and underlying mechanism remains unclear. In vivo, male mice were gavaged with CDP (0, 4, 20, or 100 mg/kg/d) for 8 weeks. And we treated TM3, TM4 and GC-2 cells with 0, 10, 25, and 50 µM CDP for 24 h to detect its reproductive toxicity effect in vitro. In our study, we revealed that CDP inhibited proliferation and induced apoptosis in mice testis and GC-2 cells, thereby leading to the decreased sperm quality. In mechanism, CDP trigger the oxidative stress and ROS production, thus partially causing DNA damage and cell apoptosis. Moreover, CDP exposure causes injury to Ledyig cells and Sertoli cells, thus disturbing the testicular microenvironment and inhibiting spermatogonia proliferation. In conclusion, this research reveals multiple adverse impacts of CDP on the male reproductive system and calls for further study of the toxicological effects of CDP on human health.

Physiological evaluation of seasonal sperm quality in a biannual spawner, Pacific abalone: Effects on in-vitro fertilization and cryotolerance.

Pacific abalone, Haliotis discus hannai, is a highly valuable gastropod mollusk commonly found in Southeast Asia. The present study aims to analyze the seminal plasma quality, sperm quality, and cryotolerance of the Pacific abalone sperm during its reproductive season. The seminal plasma quality was evaluated by analyzing biochemical and metabolite composition, enzymatic activity (superoxide dismutase, catalase, and glutathione), and lipid peroxidation (LPO) activity. The sperm quality was evaluated by analyzing motility, concentration, volume, ATP content, acrosome integrity (AI), plasma membrane integrity (PMI), mitochondrial membrane potential (MMP), DNA integrity, and fertilization potential. The cryotolerance capacity was evaluated by analyzing post-thaw motility, AI, PMI, MMP, and DNA integrity. Seminal plasma osmolarity was significantly higher (1123.3 ± 1.5 mOsmL-1) in May compared to other reproductive periods, with Cl- (516.8 ± 0.5 mM) and Na+ (460.2 ± 0.4 mM) as the dominant ions. The seminal plasma pH remained constant at 6.8 throughout the reproductive season. Improved enzymatic activity and lower LPO were detected in May or June. Sperm quality indicators were similar in May and June, except for sperm production. The fertilization potential (May: 93.0 ± 4.4%, June: 86.0 ± 7.2%) and hatching rate (May: 86.6 ± 5.78%, June: 82.3 ± 3.2%) of Pacific abalone were significantly higher in May or June than they were in other reproductive seasons. The motility (May: 50.19 ± 2.35%, June: 49.96 ± 1.60%), AI (May: 44.02 ± 3.46%, June: 42.16 ± 3.61%), PMI (May: 54.12 ± 3.29%, June: 52.82 ± 2.58%), and MMP (May: 44.02 ± 3.46%, June: 42.16 ± 3.61%) of the cryopreserved sperm were similar in May and June compared with those preserved in other reproductive seasons. The DNA integrity of the cryopreserved sperm was similar in May (80.3 ± 6.7%) or June (78.9 ± 7.4%) and had a higher cryotolerance than in other reproductive seasons. Hence, it can be suggested that May and/or June are suitable periods for sperm physiology experiments, artificial reproduction, and sperm cryopreservation of Pacific abalone.

Vigor King mitigates spermatogenic disorders caused by environmental estrogen zearalenone exposure.

Zearalenone (ZEN) has been shown to cause reproductive damage by inducing oxidative stress. Astaxanthin and L-carnitine are widely used to alleviate oxidative stress and promote sperm maturation. However, it remains uncertain whether they are effective in mitigating spermatogenesis disorders induced by ZEN. This study aimed to investigate the therapeutic efficacy and potential mechanisms of Vigor King (Vig), a compound preparation primarily consisting of astaxanthin and L-carnitine, in alleviating ZEN-induced spermatogenesis disorders. In the experiment, mice received continuous oral gavage of ZEN (80 µg/kg) for 35 days, accompanied by a rescue strategy with Vig (200 mg/kg). The results showed that Vig effectively reduced the negative impact on semen quality and improved the structural and functional abnormalities of the seminiferous epithelium caused by ZEN. Additionally, the accumulation of reactive oxygen species (ROS), DNA double-strand breaks, apoptosis, and autophagy abnormalities were all significantly ameliorated. Intriguingly, the GSK3ß-dependent BTRC-NRF2 signaling pathway was found to play an important role in this process. Furthermore, testing of offspring indicated that Vig could extend its protective effects to the next generation, effectively combating the transgenerational toxic effects of ZEN. In summary, our research suggests that Vig supplementation holds considerable promise in alleviating spermatogenesis disorders induced by zearalenone.

Association between semen parameters and recurrent pregnancy loss: An umbrella review of meta-analyses.

AIM: Recurrent pregnancy loss (RPL) is a common clinical reproductive problem. With research advancements, an increasing number of studies have suggested that male factors play an important role in RPL. However, the evaluation results of male sperm quality in published meta-analyses are inconsistent. We aimed to summarize the evidence of the association between semen factors and RPL and evaluate the level and validity of the evidence. METHODS: We searched PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus databases for systematic reviews or meta-analyses to evaluate the association between male semen parameters and RPL. The methodological quality of the included meta-analyses was assessed, and data and evidence were re-synthesized and stratified using a random-effects model. RESULTS: Seven meta-analyses and nine semen parameters were included in the final analysis. The methodological quality of all publications was considered low or very low. There was highly suggestive evidence for the association between sperm DNA fragmentation (SDF), sperm progressive motility rate, and RPL (class II). The evidence level for the association between sperm concentration, normal sperm morphology, sperm deformity rate, total motility, and RPL was suggestive evidence (class III). The evidence level for the association between sperm volume and sperm count and RPL was weak (class IV). There was no significant association between sperm pH and RPL (class NS). CONCLUSIONS: Our results suggest level II evidence for the association between male SDF and RPL, while the evidence level for the association between conventional semen routine parameters and RPL was low (classes III and IV).

Effect of silver nanoparticles on donkey sperm parameters and ultrastructure.

The aim of this study was to determine the effect of silver nanoparticles (AgNPs) on donkey sperm parameters and ultrastructure. AgNPs were synthesized, purified and resuspended in the extender. Nine frozen-thawed donkey sperm samples were exposed to different concentrations of AgNPs (0, 1.25, 2.5, 5, 12.5, 25 and 50 µg/mL). Sperm parameters: total (TMOT, %) and progressive (PMOT, %) sperm motility, plasma (LIVE, %) and acrosomal membrane integrity (AIS, %), and sperm morphology (MORF, %) were evaluated immediately after AgNPs exposure (T0) and after 2 h of incubation (T2). The interaction beween AgNPs and spermatozoa was visualized by transmission electron microscopy (TEM). At T0, sperm motility and AIS were reduced (p < .05) when using concentrations ≥50 and ≥25 µg/mL, respectively. At T2, sperm motility and LIVE were significantly decreased (p < .05) in concentrations ≥25 and ≥50 µg/mL, respectively. TEM analysis revealed nanoparticle adhesion to the acrosomal region of the plasma membrane. In conclusion, AgNPs at concentrations ≥25 µg/mL impair motility, acrosome and plasma membrane integrity of donkey sperm, which may be mediated by adhesion to the acrosomal region of the sperm surface membrane.