Increased Sperm Production Research Articles

AXDND1 is required to balance spermatogonial commitment and for sperm tail formation in mice and humans

Dynein complexes are large, multi-unit assemblies involved in many biological processes via their critical roles in protein transport and axoneme motility. Using next-generation sequencing of infertile men presenting with low or no sperm in their ejaculates, we identified damaging variants in the dynein-related gene AXDND1. We thus hypothesised that AXDND1 is a critical regulator of male fertility. To test this hypothesis, we produced a knockout mouse model. Axdnd1−/− males were sterile at all ages but presented with an evolving testis phenotype wherein they could undergo one round of histologically replete spermatogenesis followed by a rapid depletion of the seminiferous epithelium. Marker experiments identified a role for AXDND1 in maintaining the balance between differentiation-committed and self-renewing spermatogonial populations, resulting in disproportionate production of differentiating cells in the absence of AXDND1 and increased sperm production during initial spermatogenic waves. Moreover, long-term spermatogonial maintenance in the Axdnd1 knockout was compromised, ultimately leading to catastrophic germ cell loss, destruction of blood–testis barrier integrity and immune cell infiltration. In addition, sperm produced during the first wave of spermatogenesis were immotile due to abnormal axoneme structure, including the presence of ectopic vesicles and abnormalities in outer dense fibres and microtubule doublet structures. Sperm output was additionally compromised by a severe spermiation defect and abnormal sperm individualisation. Collectively these data identify AXDND1 as an atypical dynein complex-related protein with a role in protein/vesicle transport of relevance to spermatogonial function and sperm tail formation in mice and humans. This study underscores the importance of studying the consequences of gene loss-of-function on both the establishment and maintenance of male fertility.

Effect of Edible Bird Nest Supplementation Against Busulfan-Induced Oligospermia in Adult Rats

WHO estimates that between 48 million couples and 186 million individuals are facing infertility globally. Male infertility contributes to one-third of the problem with oligospermia as a primary underlying cause. Edible bird nest (EBN), a nutritional natural product, has the potential to improve male fertility status. However, the scientific evidence on oligospermia is sparse. Therefore, this study aimed to evaluate the effectiveness of EBN supplementation in busulfan-induced oligospermia of adult rats. Thirty-six eight-week-old Sprague Dawley male rats (N=36) were randomly and equally divided into six groups (n=6): Control, Sham, Busulfan, EBN 250, 500, and 1000 mg/kg/daily. A single dose of 10 mg/kg busulfan was injected intraperitoneally to induce oligospermia. Daily EBN supplementation was administered for 28 consecutive days, started one day following the busulfan injection. Findings showed that sperm concentration, spermatogenesis index scoring, seminiferous tubule diameter, and germ cell height were reduced in busulfan-induced oligospermia. Meanwhile, the apoptosis status was significantly increased. EBN supplementation had significantly increased sperm concentration, spermatogenesis index scoring, germ cell height, and gene expression of p38 and MAPK14. EBN supplementation also reduced apoptosis in the oligospermia group in a dose-dependent manner. In conclusion, daily EBN supplementation has a protective effect in busulfan-induced oligospermia by increasing sperm production, preserving histological features of the testes, reducing apoptosis, and improving gene expression of p38 and MAPK14.

285 Impact of feeding strategies on semen concentration, motility, and morphology of the mature AI boar

Abstract The objective of this experiment was to determine if varying feeding strategies of maintenance requirements of boars impacts semen concentration, motility, morphology, and cortisol of the working boar. This experiment was conducted at Purdue University over two 9-wk periods with 1-wk before each 9-wk period serving as baseline for analysis. Boars (n = 28; Acuity and Topig Norvsin) from two age groups (9 and 15 mo) and two genetics (maternal and terminal) were used. Boars were blocked by breed and age and randomly allocated to receive one of three feed intake levels of a corn-soybean meal-based diet formulated to meet NRC (2012) maintenance requirements: HIGH (150% maintenance, n = 9); MAIN (100% maintenance, n = 10); and LOW (80% maintenance, n = 9) during the first 9-wk period. During the second 9-wk period remaining HIGH and LOW boars were crossed-over to opposite treatments (HIGH-LOW, n = 9; LOW-HIGH, n = 7), and maintenance boars were unchanged (MAIN-MAIN, n = 8). Semen was collected once/wk using the gloved hand method and 3 mL of ejaculate was diluted in 27 mL of extender (Androhep Plus, Minitube). Semen concentration (Nucleocounter SP-100), motility (Computer Assisted Sperm Analysis, CASA, CEROS II), and sperm cell morphology (phase-contrast, bright-field microscopy) were analyzed. Data were analyzed using PROC MIXED in SAS 9.4 with boar as experimental unit with main effects of feed intake and age with phase (3-wk period) as repeated measure. Significance was determined at P < 0.05 and a trend 0.05 < P ≤ 0.10. Three-way interactions for the first 9-wk period of feed intake*age*phase was observed for total sperm (P < 0.10) and total normal sperm (P < 0.05) with old boars fed HIGH treatment increasing sperm production, but old boars fed MAIN and LOW decreasing sperm production while young boars had minimal changes in sperm production regardless of feeding levels in the first 9-wk period. No other interactions or main effects were observed for the first period. During the second 9-wk period two-way interactions were observed for total sperm (FI*Age; P < 0.05) and total normal sperm (FI*Age; P < 0.01) with old LOW-HIGH boars having the highest total sperm and total normal sperm concentrations and young LOW-HIGH boars having the least total sperm and total normal sperm concentrations. HIGH-LOW fed boars had the greatest decrease in semen volume compared with the other treatments (FI*Phase; P < 0.01). Boars fed MAIN had minimal impacts on semen parameters compared with HIGH and LOW feed intake treatments. HIGH and LOW feed intake was observed to impact semen parameters in old boars faster than young boars with neither age being able to return to their baseline semen parameters observed at the start of the trial. Future research is needed with varying ages and feed intakes to better understand how nutritional strategies impact semen quantity and quality in the boar stud.

An Overview of Potential Applications for Nanotechnology, Probiotics, and Medicinal Plants in Infertility Problems

Abstract:Various assisted reproductive technologies (ART) are applied in the infertility treatment. However, considerable attention is addressed to use alternative approaches, such as non-biotechnology, probiotics, and traditional medicinal plants to treat cancerous and non-cancerous cases of infertility. Nanotechnology was remarkably aided in treatment, diagnosis, and drug delivery. The existing data of this technology might demonstrate the enormous potential of nanomaterials and their viability in clinical trials for the study of reproductive issues. In order to understand the function of the microbiome in infertility and the many good effects of probiotics in illnesses such as colon cancer, obesity, diabetes, and inflammatory bowel disease, research on infertility must be conducted. Healthy reproductive systems are important for successful fertility in males and females, and using probiotics can help reduce the associated complications. Besides, in vivo models are required to determine the probiotics proper administration, identify the functional species, effective doses, administration forms, and the effects of their combination with conventional antibiotics. In addition, medicinal herbs should be explored, notably in the treatment of male infertility and the improvement of sperm abnormalities. The antioxidant capacity, anti-inflammatory reactions, increased sperm production, and increased testosterone levels in the blood are all examples of medicinal plant benefits. More study is needed to establish specific findings on which substances are involved and have effective and safe fertility potential. This review presents an overview of potential applications for nanotechnology, probiotics, and medicinal plants in infertility, discussing the advantages, their feasibility, and associated concerns, which demand more investigations to set of clinical applications.

PSIV-9 Salmate Dha+ Fish Oil Supplement Fed to Boars and Impact on Sperm Production and Spermatogenesis

Abstract Previous studies have found omega-3 fatty acid supplementation increased sperm production in boars, but the mechanism has not been demonstrated. The current study was undertaken to determine if the increase in sperm production was due to a reduction in germ cell apoptosis during spermatogenesis. Mature Duroc boars (438 to 686 days of age) were fed either a control diet of corn, soybean meal, 5% fiber, plus vitamins and minerals per NRC requirements or the control diet plus a proprietary blend of fish oil, Salmate DHA+ supplemented diet with 1.83 gm DHA (Docosahexaenoic Acid, c22:6 omega3) from 26 gm Salmate DHA+ (The Ballard Group, Inc. and Feedworks USA, LTD.) ∙animal-1∙day-1 added to the control diet. The control diet was fed to all boars (n = 10) for 62 days and then Salmate DHA+ was added to the diet of 5 of the boars while the other 5 continued the control diet for another 62 days. At the end of the experiment all boars were slaughtered, the testes collected, slices removed, fixed with Karnovsky’s fixative, post-fixed with 70% ethanol, embedded with acrylic resin, 2-micron sections taken, and sections stained with Toluidine Blue. During the control and Salmate DHA+ feeding, boars were on routine semen collection. The boar stud provided the date of collection, total sperm collected, and age of individual boars. To confirm the impact on sperm production, semen data was evaluated for all boars on the first 62 days of the control diet (before period) and then for control and Salmate DHA+ boars from day 22 to 62 after Salmate DHA+ feeding started (after period). A total of 107 ejaculates were evaluated in the study. Total sperm per ejaculate (X 109) of the control boars was 105.7 ± 7.3 vs. 110.9 ± 10.4 in the before vs. after period (P >0.05). The total sperm per ejaculate (X 109) in the Salmate DHA+ boarswas 103.4 ± 5 vs. 122.8 ± 7 in the before vs. after period (P < 0.05). To examine apoptosis via histology, the number of round spermatids (RS) and Sertoli cells (SC) were counted in 10 stage 1 seminiferous tubules for each boar with adjustments made for cell nucleoli or nuclei size and thickness of the histology section. The ratio of RS/SC or Sertoli Cell Index was then determined to estimate how many RS survived apoptosis in spermatogenesis. The Sertoli Cell index was 9.46 ± 0.84 vs. 15.03 ± 0.97, respectively, for Control and Salmate DHA+ boars (P < 0.01). The number of RS/SC increased 1.59-fold due to Salmate DHA+ treatment and may explain the increased sperm per ejaculate after Salmate DHA+treatment. The exact mechanism of how apoptosis was reduced however awaits further research. Work was supported by The Ballard Group, Inc and Feedworks USA, LTD.

The Effect of Thyme Honey on the Histopathological Changes of the Testis in Relation to the Side Effects of Valproic Acid in Adult Male Wistar Rats

Introduction. Valproic acid (VPA) is a widely used drug in the treatment of emotional and nervous depression, mental imbalances, epilepsy, and control of bipolar disorders. Despite its therapeutic effects, VPA has toxic effects on male reproduction. The testis is an organ sensitive to oxidative stress. On the other hand, thyme honey contains antioxidant compounds. The aim of this study was to investigate the effect of thyme honey on the histopathological changes of the testis in relation to the side effects of VPA in adult male Wistar rats. Methods. In this study, 48 Wistar rats were used, which were randomly divided into equal eight groups and received their desired substances. Including the control group, Th1, Th2, and Th3 groups receiving 1, 2, and 3 g/kg of thyme honey, respectively, VPA (500 mg/kg), VPA + Th1 (500 mg/kg of VPA + 1 g/kg of thyme honey), VPA + Th2 (500 mg/kg of VPA + 2 g/kg of thyme honey), and VPA + Th3 (500 mg/kg of VPA + 3 g/kg of thyme honey). After 60 days, evaluation of malondialdehyde (MDA), total antioxidant capacity (TAC), and histological studies of hematoxylin-eosin and Masson’s trichrome staining were performed. Results. The use of thyme honey significantly improved some parameters related to spermatogenesis, and in addition, it increased sperm production in the honey groups. In addition, the changes in MDA levels in the groups have shown a decrease in the amount of lipid peroxidation in the VPA + Th2 group. The amount of TAC also increased after increasing the dose of thyme honey. Conclusion. Based on the results of this study, it seems that thyme honey has been able to reduce the side effects of VPA to some extent due to its high percentage of antioxidants.

Origin, domestication, taxonomy, botanical description, genetics and cytogenetics, genetc diversity and breeding of chickpea (Cicer arietinum L.)

The chickpea or chick pea (Cicer arietinum) is an annual legume of the family Fabaceae, subfamily Faboideae. Its different types are variously known as gram or Bengal gram, chhana, chana, or channa, garbanzo or garbanzo bean, or Egyptian pea. Also known as ceci beans, Indian peas, kadale kaalu, sanaga pappu, and shimbra. The Sanskrit name for chickpea is chennuka, and hence, the name chana in the Sanskrit-derived languages such as Hindi. Chickpea is a cool season legume crop grown world- wide as a food crop. The seed is the main edible part of the plant. Chickpea is a cheap and important source of protein for those people who cannot afford animal protein or who are largely vegetarian. Furthermore, chickpea is also a good source of minerals (calcium, phosphorus, magnesium, zinc and iron), unsaturated fatty acids, fibre and β-carotene). Chickpea also plays an important role in maintaining soil fertility by fixing nitrogen at rates of up to 140 kg/ha/year. Therefore, this crop requires relatively low inputs of nitrogen as it derives 70% of its N through symbiotic N2 fixation and benefits other cereal crops as well. On the basis of seed colour and geographical distribution, chickpea is grouped into two types: desi (Indian origin) and kabuli (Mediterranean and Middle Eastern origin). Desi seeds are brown, black or green in colour and are cultivated as a legume crop. Kabuli seeds are white to cream coloured and are used for cooking purposes for humans. The seed weight generally ranges from 0.1 to 0.3 g for desi and 0.2 to 0.6 g for kabuli/. The desi type accounts for about 80–85% of total chickpea production, and is grown mostly in Asia and Africa, while the kabuli types are largely grown in West Asia, North Africa, North America and Europe. Chickpeas appear in early recordings in Turkey about 3500 BCE and in France 6790 BCE. India produces the most chickpeas worldwide but they are grown in more than 50 countries. An excellent source of carbohydrate, protein, fiber, B vitamins, and some minerals, they are a nutritious staple of many diets. Chickpea is widely grown for its nutritious seeds. Chickpeas are an important food plant in India, Africa, and Central and South America. The seeds are high in fibre and protein and are a good source of iron, phosphorus, and folic acid. As with other legumes, chickpeas have a symbiotic association with nitrogen-fixing bacteria and can be rotated with nitrogen-intensive crops such as cereals to improve soil conditions. Till 17th century, roasted and grounded chickpeas and were brewed as a substitute for a coffee in Europe. Around 800 AD, chickpeas were associated with Venus, the Roman Goddess for beauty and love as it improves fertility by increasing sperm production, stimulating menstruation and lactation. In this review article on Origin, Domestication, Taxonomy, Botanical Description, Genetics and Cytogenetics, Genetic Diversity, Breeding, Uses, Nutritional Value and Health Benefits of Chickpea are discussed.

Increasing sperm production and improving cryosurvival of semen in aged roosters after diet-supplemented with selenium in Thai native chickens.

Aging roosters typically exhibit subfertility with decreasing semen quality, whereas Thai native roosters reared in rural areas were raised for a longer duration than their usual lifespan. The present study therefore aimed to assess the effect of selenium supplementation as an antioxidative substance in diets to improve the semen cryopreservation of aged roosters. Semen samples were collected from young (n=20) and aged (n=20) Thai native roosters (Pradu Hang Dum) at 36 and 105 weeks of age when starting the experiment, respectively. They were fed diets in non-supplemented or supplemented selenium (0.75 ppm). Fresh semen quality and lipid peroxidation of fresh semen was evaluated before cryopreservation using the traditional liquid nitrogen vapor method. Post-thaw sperm quality and fertility potential were determined. Advancing age is unrelated to decreasing fresh semen quality (p > 0.05). However, lipid peroxidation in rooster semen depended on age, and the malondialdehyde (MDA) concentration increased in aged roosters (p < 0.05). Selenium supplementation in diets significantly decreased the MDA concentration and increased the sperm concentration (p < 0.05). In contrast, cryopreserved semen was affected by advancing rooster age, and selenium influenced sperm quality (p < 0.05). Younger roosters had higher post-thaw sperm quality and fertility potential than aged roosters (p < 0.05). Likewise, diet selenium supplements improved post-thaw sperm quality and fertility compared with the non-supplement group. Rooster's age does not influence the rooster sperm quality of fresh semen, while sperm cryotolerance and fertility were greater in young roosters than in aged roosters. However, those of aged roosters could be improved by dietary selenium supplementation.

P-102 Inhibition of RANKL increases the number of motile sperm in a subgroup of infertile men

Abstract Study question Does inhibition of RANKL increase semen quality in infertile men? Summary answer Overall, inhibition of RANKL (Denosumab) did not affect semen quality. However, in a subgroup of men with high serum AMH sperm production was significantly increased. What is known already Currently, there is no treatment available for male infertility, but studies in animal and preclinical human data have suggested a role for RANKL in male reproduction. Study design, size, duration A single-center, double-blinded, randomized clinical trial in 100 infertile men randomly assigned (1:1) to s.c. injection with 60 mg/mL Denosumab or s.c. saline injection 1 mL (0.9%) (placebo). The primary endpoint was changes in semen production, though the study was designed as an explorative study, with the aim of investigating the profile of which infertile men who would have a beneficial treatment outcome of Denosumab. Participants/materials, setting, methods All participants were infertile men referred to our andrological clinic due to impaired semen quality. Blood and semen samples were collected at baseline and after one and two cycles of spermatogenesis on day 80 and day 160, respectively. Main results and the role of chance There were no differences in semen quality or reproductive hormones at day 80 or day 160 between men treated with Denosumab or placebo. However, men with a serum AMH ≥ 40 pmol/L had a significant increase in total motile sperm (143% (SD 116%); p = 0.011), progressive motile sperm (133% (SD 100%); p = 0.039) and a borderline increase in sperm concentration (64% (SD 95%); p = 0.056) at day 80 compared to baseline. Further stratifying men according to both serum AMH (≥ 40 pmol/L) and serum RANKL (highest 50%), showed a significantly higher increase in sperm concentration (107% (SD 111%) vs. -8% (SD 68%); p = 0.009), total motile sperm (256% (SD 270%) vs. 31% (SD 125%); p = 0.039) and progressive motile sperm (191% (SD 194%) vs. 18% (SD 134%) p = 0.013) at day 80 in men treated with Denosumab compared to placebo treated men. Furthermore, serum FSH (-28% (SD 33%) vs. 0%, (SD 22%); p = 0.041) and serum LH (-29% (SD 28%) vs. 20% (SD 51%), p = 0.048) were significantly lower and testosterone/LH ratio (50% (SD 51%) vs. -7% (SD 43%); p = 0.024) significantly higher at day 80 in men treated with Denosumab compared to placebo treatment. Limitations, reasons for caution This is a report from a randomized clinical trial, with an explorative design. Randomized clinical trials in a predefined group of infertile men with high serum AMH, are needed to explore if inhibition of RANKL improves semen quality and pregnancy rate in infertile couples with male factor infertility. Wider implications of the findings The increase in sperm production after Denosumab treatment in infertile men with preserved Sertoli cell function needs to be validated, in a trial selecting men based on serum AMH. Ultimately, Denosumab may be a potential breakthrough in treating male infertility at least in some infertile men with high serum AMH. Trial registration number NCT03030196

The possible protective effect of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate on tramadol-induced testicular damage in rats

BackgroundTramadol provokes oxidative stress that gives rise to apoptosis with alterations in the cellular structure and adversely influences male fertility. A specific inhibitor of nuclear factor kappa B (NF-κB), pyrrolidine dithiocarbamate (PDTC), has observable antioxidant and anti-inflammatory characteristics and enhances the improvement of organs damage caused by various agents. The impact of PDTC on testicular damage caused by tramadol has not been previously examined.ObjectiveThis study was designed to investigate the potential impact of pyrrolidine dithiocarbamate on testicular damage provoked by chronic tramadol usage.Materials and methodsForty healthy adult male albino rats were included in this study. Rats were randomly and equally divided into 4 groups: group (I), control group; group (II), pyrrolidine dithiocarbamate (PDTC) group; group (III), tramadol (Tr) group; and group (IV), Tr + PDTC group. This study measured serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and free testosterone levels. Testicular malondialdehyde (MDA), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) levels, and superoxide dismutase (SOD), glutathione peroxidase (GPX), and caspase-8 and caspase-3 activities were also detected. Immuno-histochemical evaluation of inducible NOS (iNOS) expression in testicular tissue along with histopathological examination of testicular tissue has been studied.ResultsTramadol caused a significant reduction in serum FSH, LH and testosterone levels, epididymal sperm count, and motility, as well as testicular GPX and SOD activities. On the other hand, a significant elevation of testicular MDA, IL-1β, IL-6, and TNF-α levels and caspase-8 and caspase-3 activities were found. However, PDTC administration with tramadol showed significantly increased sperm production and motility and alleviated tramadol-induced disturbance in other measured parameters in the Tr + PDTC group compared to the Tr group. Moreover, co-administration of PDTC with tramadol significantly alleviated the histopathological structure of testicular tissue and the increased iNOS expressions noticed in the tramadol-treated group.ConclusionConsidering the protective effects of PDTC against the reproductive toxicity induced by tramadol, this compound can be used as a possible protective and treating target for tramadol-induced reproductive toxicity.

Preliminary analysis of hormonal and seminal sperm parameters of subfertile and fertile stallions treated with the GnRH agonist lecirelin

Subfertility is relatively common in stallions and few treatments are available to improve the semen characteristics of affected animals. The GnRH therapy, however, has been reported to improve sperm quality in individual clinical cases. The aim of this study was to evaluate therapeutical effects of daily GnRH analogue lecirelin treatment on sperm characteristics of fertile and subfertile stallions and to assess differences in the endocrine response among groups. Stallions were divided into untreated (n=3), fertile control (n=4) and subfertile (n=4) groups. Fertile and sub-fertile stallions received saline or 0.05 mg lecirelin, respectively, daily for 60 days and were evaluated for >90 days post-treatment. Ejaculates were collected biweekly, but semen and serum samples were evaluated weekly. Fertile stallions were characterized as having normal seminal parameters and a 75% conception rate. Subfertile stallions had low total and progressive motility (< 50% and 20%, respectively), sperm count, abnormal morphology (>30% of major defects), and ≈20% conception rate in the previous breeding season. Testicular response was assessed by determination of the concentrations of testosterone and estrone sulphate (interstitial compartment), anti-Müllerian hormone (AMH) and inhibin-B (tubular compartment) and correlated with sperm kinetics and production. Sperm kinetics were evaluated by CASA (IVOS Version 12 Hamilton Thorne Research, MA, USA), sperm concentration by Neubauer hemocytometer (Optik Labor®, Lancing, England), serum concentrations of inhibin- B, AMH and estrone sulfate weredetermined by ELISA and testosterone by RIA. Data were analyzed by ANOVA for repeated measures. In the subfertile group, testosterone concentrations decreased from week 0 to 6 (667 vs 302 pg/ml, respectively P<0.05), but tended to recover 1 month after treatment ceased (469 to 977pg/ml, respectively, P<0.08). Concentrations of all hormones were positively correlated with one another and with total sperm number (P<0.01), the highest between inhibin-B and estrone sulphate (R2=0.72) (P<0.01). No statistically significant effects on other hormones or semen characteristics were detected irrespective of group. Despite non statistical difference between groups, it is important to note that total sperm number increased by 60% 30 days after the beginning of the treatment and remained elevated by the end of the evaluation period in the fertile group. These data suggest that the treatment increased sperm production, but further investigations are underway. In conclusion, lecirelin treatment did not affect hormonal and seminal parameters in treated stallions, and did not affect testicular function. The correlation between hormones and sperm output indicates that these hormones are potentially valuable biomarkers for testicular function. Acknowledgements: São Paulo Research Foundation (FAPESP, grant #2019/01119-8 and #2022/03405-0), John P. Hughes Endowment and Clinical Endocrinology Laboratory, UC-Davis.

Sperm competition increases sperm production and quality in Cataglyphis desert ants.

Sperm competition is a pervasive evolutionary force that shapes sperm traits to maximize fertilization success. Indeed, it has been shown to increase sperm production in both vertebrates and invertebrates. However, sperm production is energetically costly, which may result in trade-offs among sperm traits. In eusocial hymenopterans, such as ants, mating dynamics impose unique selective pressures on ejaculate. Males are sperm limited: they enter adulthood with a fixed amount of sperm that will not be renewed. We explored whether sperm competition intensity was associated with sperm quantity and quality (i.e. sperm viability and DNA fragmentation) in nine Cataglyphis desert ants. Our results provide phylogenetically robust evidence that sperm competition is positively correlated with sperm production and sperm viability. However, it was unrelated to sperm DNA integrity, indicating the absence of a trade-off involving this trait. These findings underscore that sperm competition may strongly mould sperm traits and drive reproductive performance in eusocial Hymenoptera.

Male infertility and gonadotropin treatment: What can we learn from real-world data?

Gonadotropin therapy to treat specific male infertility disorders associated with hypogonadotropic hypogonadism is evidence-based and effective in restoring spermatogenesis and fertility. In contrast, its use to improve fertility in men with idiopathic oligozoospermia or nonobstructive azoospermia remains controversial, despite being widely practiced. The existence of two major inter-related pathways for spermatogenesis, including FSH and intratesticular testosterone, provides a rationale for empiric hormone stimulation therapy in both eugonadal and hypogonadal males with idiopathic oligozoospermia or nonobstructive azoospermia. Real-world data (RWD) on gonadotropin stimulating for these patient subsets, mainly using human chorionic gonadotropin and follicle-stimulating hormone, accumulated gradually, showing a positive therapeutic effect in some patients, translated by increased sperm production, sperm quality, and sperm retrieval rates. Although more evidence is needed, current insights from RWD research indicate that selected male infertility patients might be managed more effectively using gonadotropin therapy, with potential gains for all parties involved.

Differential responsiveness of spermatogonia to retinoic acid dictates precocious differentiation but not meiotic entry during steady-state spermatogenesis†.

The foundation of mammalian spermatogenesis is provided by undifferentiated spermatogonia, which comprise of spermatogonial stem cells (SSCs) and transit-amplifying progenitors that differentiate in response to retinoic acid (RA) and are committed to enter meiosis. Our laboratory recently reported that the foundational populations of SSCs, undifferentiated progenitors, and differentiating spermatogonia are formed in the neonatal testis in part based on their differential responsiveness to RA. Here, we expand on those findings to define the extent to which RA responsiveness during steady-state spermatogenesis in the adult testis regulates the spermatogonial fate. Our results reveal that both progenitor and differentiating spermatogonia throughout the testis are capable of responding to exogenous RA, but their resulting fates were quite distinct-undifferentiated progenitors precociously differentiated and proceeded into meiosis on a normal timeline, while differentiating spermatogonia were unable to hasten their entry into meiosis. This reveals that the spermatogonia responding to RA must still complete the 8.6day differentiation program prior to their entry into meiosis. Addition of exogenous RA enriched testes with preleptotene and pachytene spermatocytes one and two seminiferous cycles later, respectively, supporting recent clinical studies reporting increased sperm production and enhanced fertility in subfertile men on long-term RA analog treatment. Collectively, our results reveal that a well-buffered system exists within mammalian testes to regulate spermatogonial RA exposure, that exposed undifferentiated progenitors can precociously differentiate, but must complete a normal-length differentiation program prior to entering meiosis, and that daily RA treatments increased the numbers of advanced germ cells by directing undifferentiated progenitors to continuously differentiate.

Sexual selection drives the coevolution of male and female reproductive traits in Peromyscus mice.

When females mate with multiple partners within a single reproductive cycle, sperm from rival males may compete for fertilization of a limited number of ova, and females may bias the fertilization of their ova by particular sperm. Over evolutionary timescales, these two forms of selection shape both male and female reproductive physiology when females mate multiply, yet in monogamous systems, post-copulatory sexual selection is weak or absent. Here, we examine how divergent mating strategies within a genus of closely related mice, Peromyscus, have shaped the evolution of reproductive traits. We show that in promiscuous species, males exhibit traits associated with increased sperm production and sperm swimming performance, and females exhibit traits that are predicted to limit sperm access to their ova including increased oviduct length and a larger cumulus cell mass surrounding the ova, compared to monogamous species. Importantly, we found that across species, oviduct length and cumulus cell density are significantly correlated with sperm velocity, but not sperm count or relative testes size, suggesting that these female traits may have coevolved with increased sperm quality rather than quantity. Taken together, our results highlight how male and female traits evolve in concert and respond to changes in the level of post-copulatory sexual selection.

Comparison of short and long-acting testosterone replacement therapy for better sperm production and testosterone levels in male late-onset hypogonadism

Introduction: Testosterone Replacement Therapy (TRT) is the standard treatment for male late-onset hypogonadism. Short-acting and long-acting testosterone are currently available treatments and have been approved by the Food and Drug Administration (FDA). The administration of exogenous testosterone is known to increase sperm production and T levels in men suffering from late-onset hypogonadism. However, limited research compares the efficacy of these two types of TRT. Objective: This study aims to compare the efficacy of short-acting and long-acting testosterone replacement therapy on sperm production and T levels in men suffering from late-onset hypogonadism. Methods: We searched for electronic databases including PubMed, Cochrane Library, EMBASE, Scopus, Web of Science, Allied and Complementary Medicine Database (AMED), and Google using keywords. All studies were evaluated by three independent reviewers who resolved differences by consensus. Results: We identified 21 studies that met our inclusion criteria. After applying the inclusion criteria, only 21 database sources remain for further analysis. Conclusion: Long-acting formulas affect blood more. RCTs show TU boosts libido and testosterone. Male infertility may result from long-acting TU blocking LH and FSH. TRP improves erections by increasing motile sperm and libido. Peanut allergy-related short-acting TRT causes nausea, itching, and injection-site pain.

Effect Of Suvarna Bhasma (Gold Calx) On Reproductive System Of Male Albino Rats

“Suvarna Bhasma” (gold calx) (SB) prepared as per Ayurveda, a practicing medical system, is prescribed as a medicine in several ailments including conditions like oligozoospermia and asthenoszoospermia in male infertility. SB is prepared from pure metal gold by one of the processing methods detailed in Ayurveda classics. Gold along with other elements was reported in normal human seminal plasma. . In human pathological semen samples, the level of gold was less than normal. Gold may have a role in physiological activity of sperm as shown in case of other elements. The present study supports the hypothesis that the presence of gold is essential for sperm motility. Here we studied the effect of SB on male reproductive organs and semen from epididymis of rat. Present study was performed using Charles foster strain albino rats. Rats were divided into two groups of ten each namely, Group 1 (control) and Group 2 (study). Animals in study group were orally given a fixed amount of SB for 15 days. At the end of the study treated animals showed increase in body weight (&lt;0.05) and testicular weight. In treated animals total sperm count (&lt;0.05) and percentage of sperm motility were increased in epididymal fluid. Histological study showed increase in interstitial area of testes (&lt;0.001), proliferation and branching of the epithelial layer of seminal vesicle. In the Study (gold treated) Group, the increased gold level in genital system may be responsible for the increase in sperm production and motility.

254 Effects of Nutrition on Bull Fertility

Abstract The greatest effects of nutrition on bull fertility occur by providing a relatively high plane of nutrition during calfhood when the seminiferous epithelium of the testes is developing. A high plane of nutrition from 5 to 25 weeks of age results in greater circulating gonadotropin concentrations, greater testicular volume, and greater sperm production at maturity. At this age, diet can be manipulated by creep feeding bull calves with both protein and energy supplements which could accelerate puberty and increase sperm production. Increased rate of gain in bull calves post-weaning can accelerate puberty a few weeks, but excess post-weaning gain and fat buildup in the neck of the scrotum can have detrimental effects on fertility. Considerable emphasis has been placed on specific micronutrient (especially minerals) effects on peripubertal bull fertility. Trace mineral supplementation is believed to be critical for optimal fertility and both copper (Cu) and zinc (Zn) supplementation have influenced male fertility in other species. However, there are no guidelines for recommended levels of these minerals to ensure fertility. Providing organic or complexed compared to inorganic mineral to peripubertal bulls have increased liver concentrations of mineral and in some cases, have accelerated puberty, but enhanced fertility-associated measures have not been realized. Because both Cu and Zn are present in the ejaculate, mineral needs during the breeding season may differ from the off-season. During the breeding season, bulls can lose 10 to 20% of their weight and need to re-gain this weight before the next breeding season. Divergent planes of nutrition provided to mature bulls during the off-season revealed enhanced sperm energy and stress-fighting potential with decreasing plane of nutrition. Specific mineral supplementation during the off-season in mature bulls provides no beneficial effect on fertility-associated measures. In summary, significant effects of nutrition post-weaning on bull fertility-associated measures have not been realized.

Pupal Cues Increase Sperm Production but Not Testis Size in an Insect.

Simple SummaryAnimals adjust their resource allocation strategies to maximize their reproductive benefit under dynamic socio-sexual environments. For example, male insect adults increase their testicular investment with the perceived increase of rivals to gain a competitive advantage in fathering offspring. To date, it is not clear whether insect pupae, which do not feed and crawl, can fine-tune their investment in sperm and testis size according to their social-sexual settings. This knowledge is vital to understanding how male insects respond to their surroundings experienced at different life stages. Using a moth which produces both fertile and unfertile sperm, we demonstrated for the first time that after detecting cues from conspecific pupae regardless of sex, male pupae increased production of both types of sperm at the same rate but kept testis size unchanged. Because most morphological traits are formed during the larval stage in insects, testis size may be fixed after pupation, allowing little room for the pupae to adjust testis size with social changes. Like adults, male pupae with fully grown testes have sufficient resources to produce more sperm of both types according to the perceived increase of sperm competition risk. Theoretic and empirical studies show that social surroundings experienced by male insects during their larval or adult stage can influence their testicular investment in diverse ways. Although insect pupae do not feed and crawl, they can communicate using sex-specific and/or non-sex specific cues. Yet, it is unknown, in any insect, whether and how male pupae can fine-tune their resource allocation to sperm production and testis size in response to socio-sexual environments. We investigated this question using a moth, Ephestia kuehniella, which produces fertile eupyrene sperm and unfertile apyrene sperm. We held male pupae individually or in groups with different sex ratios, and dissected adults upon eclosion, measured their testis size, and counted both types of sperm. We demonstrated that after exposure to conspecific pupal cues regardless of sex, male pupae increased production of eupyrenes and apyrenes at the same rate but kept testis size unchanged. We suggest that testis size is fixed after pupation because most morphological traits are formed during the larval stage, allowing little room for pupae to adjust testis size. Like adults, male pupae with fully grown testes have sufficient resources to produce more sperm of both types according to the perceived increase in sperm competition risk.

Maca Root (Lepidium meyenii) Extract Increases the Expression of MMP-1 and Stimulates Migration of Triple-Negative Breast Cancer Cells

Maca root (Lepidium meyenii) extract is a worldwide consumed food supplement for sexual dysfunctions, increasing sperm production and its motility, and alleviating menopausal symptoms. Once maca root has a role in cell proliferation and motility, and its consumption may increase along with age, mainly in menopausal women, we aimed to investigate the plant effects on triple-negative breast cancer (TNBC) cell lines. Standardized maca root powdered extract showed significant cytotoxic activity in both MDA-MB-231 and Hs578T cells, and the IC50s were 2000 μg/ml and 3000 μg/ml, respectively. Both cell lines showed an increase in migratory capacity. Using bioinformatics tools, we established genes involved in the metastatic process, CAV1, LAMA4, and MMP-1, and the mRNAs expression was assessed by qPCR. Comparing the treated cells to the negative control, CAV1 presented a decreased expression by 2-fold in MDA-MB-231. LAMA4 presented a decrease by 4-fold in Hs578T cells. MMP-1 showed substantially increase mRNA expression in MDA-MB-231 by 86-fold and in Hs578T by 5-fold. To the best of our knowledge, this is the first study indicating that the human consumption of maca may be dangerous due to the upregulation in MMP-1 expression and the increase in TNBC migrated cells.