Treatment Of Male Infertility Research Articles

Research progress on the role of lycopene in promoting mammalian spermatogenesis

A carotenoid called lycopene (LYC) is one of the most potent antioxidants. Superior physiological properties of LYC include cancer prevention, cholesterol reduction, antioxidant activity, scavenging of free radicals, immunity enhancement, prostate protection, and increased sperm viability. In recent times, male sperm quality has decreased. Following studies on LYC’s function in spermatogenesis, the therapy of male infertility diseases has made extensive use of it. Here, we give an accurate theoretical foundation for the use of LYC in large animal breeding and the treatment of male infertility in humans by summarising the variables influencing spermatogenesis and the enhancing effect of LYC on mammalian spermatogenesis.

The features of endometrial receptivity in women underwent in vitro fertilization procedure

The objective: to determine the endometrial receptivity markers in women who underwent the procedure of in vitro fertilization (IVF). Materials and methods. The study included 191 patients who applied to the reproductive department of Caspian International Hospital from 2020 to 2022 for an examination for infertility.The main group included 50 patients with infertility who underwent endometrial biopsy during the implantation window (7th–9th days after ovulation in the cycle preceding the IVF stage); the control group – 20 women who underwent treatment for male infertility with a positive program result.The patients underwent IVF according to the standard method. The following expression levels were determined: leukemia inhibiting factor (LIF); vascular endothelial growth factor (VEGF); transforming growth factor-β1 (TGF-β1). The percentage expression of area indices was estimated.Results. In the women of the main group absence of embryo transfer was in 5 (10%) cases, no pregnancy – 27 (54%) cases, presence of pregnancy – 23 (46%) cases, cycle disruption – 3 (6%) cases.According to the results of a histological examination in women of the control group, complete secretory transformation of the endometrium was determined in 85% of cases. In the main group complete secretory transformation of the endometrium was detected in 48%, defective secretory transformation – in 42%, morphological signs of endometrial changes corresponding to the average secretory phase of the cycle – in 10% of women.A significant decrease (p<0.001) in the expression of LIF in the histological structures (stroma) of the endometrium was revealed in the main study group compared to the control one. The most pronounced differences were observed in the expression level of TGF-β1 in the stroma (approximately 10-fold; p<0.001).Conclusions. Thus, infertile women who underwent IVF have multidirectional changes in endometrial receptivity markers: decrease in LIF expression in the stroma and epithelium, increase in VEGF expression in the stroma, and a significant increase in TGF-β1 expression in the stroma and epithelium. These changes indicate an abnormal functional state of the endometrium and affect the results of IVF in patients (absence of oocyte transfer and failure to conceive).

Exploring pathogenesis and biomarkers through establishment of a rat model of male infertility with liver depression and kidney deficiency.

To establish a rat model that accurately replicates the clinical characteristics of male infertility (MI) with Liver Depression and Kidney Deficiency (LD & KD) and investigate the pathogenesis. After subjecting the rats to chronic restraint stress (CRS) and adenine treatment, a series of tests were conducted, including ethological assessments, evaluations of reproductive characteristics, measurements of biochemical parameters, histopathological examinations, and analyses of urinary metabolites. Additionally, bioinformatics predictions were performed for comprehensive analysis. Compared to the control, the model exhibited significant manifestations of MI with LD & KD, including reduced responsiveness, diminished frequency of capturing estrous female rats, and absence of mounting behavior. Additionally, the kidney coefficient increased markedly, while the coefficients of the testis and epididymis decreased significantly. Sperm counts and viabilities decreased notably, accompanied by an increase in sperm abnormalities. Dysregulation of reproductive hormone levels in the serum was observed, accompanied by an upregulation of proinflammatory cytokines expressions in the liver and kidney, as well as exacerbated oxidative stress in the penile corpus cavernosum and testis. The seminiferous tubules in the testis exhibited a loose arrangement, loss of germ cells, and infiltration of inflammatory cells. Furthermore, utilizing urinary metabolomics and bioinformatics analysis, 5 key biomarkers and 2 crucial targets most closely linked to MI were revealed. The study successfully established a clinically relevant animal model of MI with LD & KD. It elucidates the pathogenesis of the condition, identifies key biomarkers and targets, and provides a robust scientific foundation for the prediction, diagnosis, and treatment of MI with LD & KD.

Harmine exhibits anti-apoptotic properties and reduces diabetes-induced testicular damage caused by streptozotocin in rats.

Diabetes mellitus induces fertility problems in men, mainly because of increased free radicals. Natural resources are effective for male infertility treatment. This study investigated the effects of harmine, an alkaloid available in Peganum harmala L., on the male reproductive system of diabetic rats. We divided 32 rats into four groups, and eight were randomly placed in each group. For diabetes induction, the animals received 50 mg/kg of streptozotocin intraperitoneally. After 1 week, animals received 15 mg/kg of harmine (28 days; intraperitoneal). Histopathological examinations, serum levels of male hormones, levels of nitric oxide (NO) and malondialdehyde (MDA) in the testes, total antioxidant capacity (TAC), insulin serum levels, fasting blood glucose levels, the apoptotic index, and semen analysis were assessed. The diabetes group exhibited morphological changes in testicular tissue, significant decreases in the diameter of the seminiferous tubule, the Johnsen score, testosterone, luteinizing hormone, follicle-stimulating hormone, insulin serum levels, and TAC in testicular tissue (p<0.01). Harmine treatment ameliorated the morphological changes in the testes and improved sperm parameters relative to the diabetes group (p<0.05). The NO and MDA levels in the testes, fasting blood glucose serum levels, and apoptotic index parameters were significantly elevated in the diabetes group, while in the diabetes+harmine group, these parameters were reduced (p<0.01). Harmine protects testicular tissue and sperm against diabetes-induced damage. This effect of harmine is associated with a rebalancing of the antioxidant capacity that subsequently decreases apoptosis in the testes.

Intracerebroventricular PROK2 infusion could increase the secretion of male reproductive hormones by stimulating the HPG axis.

Prokineticin 2 (PROK2), an important neuropeptide that plays a key role in the neuronal migration of gonadotropin-releasing hormone (GnRH) in the hypothalamus, is known to have regulatory effects on the gonads. In the present study, the impact of intracerebroventricular (icv) PROK2 infusion on hypothalamic-pituitary-gonadal axis (HPG) hormones, testicular tissues, and sperm concentration was investigated. Rats were randomly divided into four groups: control, sham, PROK2 1.5 and PROK2 4.5. Rats in the PROK2 1.5 and PROK2 4.5 groups were administered 1.5nmol and 4.5nmol PROK2 intracerebroventricularly for 7days via an osmotic mini pump (1µl/h), respectively. Rat blood serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone hormone levels were determined with the ELISA method in the blood samples after 7days of infusion. GnRH mRNA expression was determined with the RT-PCR in hypothalamus tissues. analyze Sperm concentration was determined, and testicular tissue was examined histologically with the hematoxylin-eosin staining method. It was observed that GnRH mRNA expression increased in both PROK2 infusion groups. Serum FSH, LH and testosterone hormone levels also increased in these groups. Although sperm concentration increased in PROK2 infusion groups when compared to the control and sham, the differences were not statistically significant. Testicular tissue seminiferous epithelial thickness was higher in the PROK2 groups when compared to the control and sham groups. The present study findings demonstrated that icv PROK2 infusion induced the HPG axis. It could be suggested that PROK2 could be a potential agent in the treatment of male infertility induced by endocrinological defects.

AMPK regulates immature boar Sertoli cell proliferation through affecting CDK4/Cyclin D3 pathway and mitochondrial function

Sertoli cell (SC) proliferation plays an important role in sperm production and quality; however, the regulatory mechanism of SC proliferation is not well understood. This study investigated the role of adenosine monophosphate-activated protein kinase (AMPK) in the regulation of immature boar SC activity. Cell counting kit-8, Seahorse XFe96, mitochondrial respiratory enzyme-related assay kits, and transmission electron microscopy were used to detect SC proliferative viability, oxygen consumption rate (OCR), mitochondrial respiratory enzyme activity, and the ultrastructure of primary cultured SCs in vitro from the testes of 21-day-old boars. A dual luciferase reporter assay was performed to determine the miRNA-mRNA target interaction. Western blotting was used to analyze cell proliferation-related protein expression of p38, p21, proliferating cell nuclear antigen (PCNA), Cyclin-dependent kinase 4 (CDK4), Cyclin D3, and phosphorylated retinoblastoma protein (Rb). Each experiment had a completely randomized design, with three replicates in each experiment. The results showed that the AMPK inhibitor (Compound C, 20 μM-24 h) increased cell proliferation viability, ATP production, and maximal respiration of SCs by 0.64-, 0.12-, and 0.08-fold (p < 0.05), respectively; increased the SC protein expression of PCNA, CDK4, Cyclin D3, and p-Rb by 0.13-, 0.09-, 0.88-, and 0.12-fold (p < 0.05), respectively; and decreased the SC protein expression of p38 and p21 by 0.36- and 0.27-fold (p < 0.05), respectively. The AMPK agonist AICAR (2 mM-6 h) significantly inhibited SC ultrastructure, OCR, mitochondrial respiratory enzyme activity, and cell proliferation-related protein levels. AMPK was validated to be a target gene of miR-1285 based on the result in which the miR-1285 mimic inhibited the luciferase activity of wild-type AMPK by 0.54-fold (p < 0.001). MiR-1285 mimic promoted the OCR of SCs, with 0.45-, 0.15-, 0.21-, and 0.30-fold (p < 0.01) increases in ATP production, basal and maximal respiration, and spare capacity, respectively. MiR-1285 mimic increased the mitochondrial respiratory enzyme activity of SCs, with 0.63-, 0.70-, and 0.97-fold (p < 0.01) increases in NADH-Q oxidoreductase, cytochrome c oxidase, and ATP synthase, respectively. Moreover, the miR-1285 mimic increased the protein expression of PCNA, CDK4, Cyclin D3, and p-Rb by 0.24-, 0.30-, 0.22-, and 0.13-fold (p < 0.05), respectively, and reduced the protein expression of p38 and p21 by 0.58- and 0.66-fold (p < 0.001). MiR-1285 inhibitor showed opposite effects on the above indicators and induced numerous autophagosomes and large lipid droplets in SCs. A high dose of estradiol (10 μM-6 h, showed a promotion of AMPK activation in a previous study) significantly inhibited SC ultrastructure, mitochondrial function, and proliferation-related pathways, while these adverse effects were weakened by Compound C treatment or miR-1285 mimic transfection. Our findings suggest that the activation and inhibition of AMPK induced by specific drugs or synthesized targeted miRNA fragments could regulate immature boar SC proliferative activity by influencing the CDK4/Cyclin D3 pathway and mitochondrial function; this helps to provide a basis for the prevention and treatment of male sterility in clinical practice.

Revitalizing classical Ayurveda practice in urban India—Contribution of Vaidya V. R. Padmanabha Rao

Abstract The renaissance of Ayurveda in contemporary times owes much to the remarkable contributions of exemplary practitioners. This paper explores the journey of Dr. V. R. Padmanabha Rao (1953–2020), an Ayurveda clinician who not only demonstrated excellence in clinical practice but also spearheaded the creation of “Agnivesha Ayurveda Anushthana,” an exclusive organization devoted to the education and training of Ayurveda doctors. Dr. Rao played a pivotal role in influencing and guiding numerous Ayurveda graduates to transition from allopathy to Ayurvedic clinical practice. His therapeutic knowledge was disseminated in a number of national and international forums, especially with regard to his successful treatment of male infertility. Central to his teachings was the concept of “How to be a successful Ayurveda clinician,” anchored in the three pillars of dual diagnosis (integrated Ayurveda and modern methods), the utilization of self-prepared classical medicines (single-herb therapy), and the cultivation of excellent clinical and administrative skills including documentation of clinical cases.

Phoenix dactylifera L. pollen versus pentoxifylline on improvement of sperm parameters in idiopathic male infertility: A randomized clinical trial

Ethnopharmacological relevancePhoenix dactylifera L. pollen is the male reproductive dust of palm flowers known as a natural product that is considered a strong stimulant of sexual potency and fertility in Iranian traditional medicine (ITM). In this regard, no evidence-based medications are empirically prescribed to treat IMI. However, applying traditional medicine for the treatment of male infertility has attracted more attention in recent years. Aim of the studyPhoenix dactylifera L. pollen was compared with pentoxifylline (PTX) to evaluate its efficacy on sperm parameters. Materials and methodsDuring this parallel randomized controlled trial, 80 adult men with asthenozoospermia, oligozoospermia, or teratozoospermia (age 20–35 years) were enrolled. In two separate groups of participants with a 1:1 ratio, participants received either 6 g of Phoenix dactylifera L. pollen powder daily or 400 mg of PTX tablets daily for 90 days. We measured the sperm parameters as well as the serum sex hormones in the sample. ANCOVA and t-tests were used to compare groups. ResultsThere was no significant difference between the study groups in terms of baseline characteristics or demographic characteristics. According to the results, participants who took Phoenix dactylifera L. pollen powder had significantly improved sperm concentration (p = 0.016), morphology (p = 0.029), sperm counts (p = 0.012), progressive motility (p = 0.016), total motility (p = 0.018), and reduced immotile sperms (p = 0.014) compared to those who took PTX. ConclusionsIn light of these results, Phoenix dactylifera L. pollen is recommended as a treatment factor for ameliorating IMI by enhancing sperm functional capacity and semen parameters.

Effectiveness of chromic catgut implantation in men with idiopathic infertility

Introduction: the treatment of idiopathic male infertility is empirical and controversial. Objective: to assess the effectiveness of chromic catgut implantation at selected acupuncture points according to traditional Chinese syndromic diagnosis in men with idiopathic infertility. Methods: quasi-experimental study with pre-test-post-test and control group, in 135 patients with idiopathic infertility divided into: study group (67 treated with catgut implantation) and control group (68 treated with medication). A traditional medical history was taken and descriptive and inferential statistics were used. Results: Mean age was similar in both groups (33.90 ± 6.28 years study group and 33.68 ± 5.6 years control group). Patients with Kidney yang vacuum predominated (55.2 % study group and 52.9 % control group). Both groups showed highly significant differences in sperm concentration, motility and morphology before and after treatments and between groups. Clinical improvement (64.2 % vs. 8.8 %), spermogram normalisation (53.7 % vs. 16.2 %) and pregnancy achievement (17.9 % vs. 4.4 %) were higher in patients treated with chromic catgut implantation compared to those using Clomiphene. Conclusions: chromic catgut implantation in selected acupuncture points according to traditional Chinese syndromic diagnosis in men with idiopathic infertility is effective because it improves sperm concentration, motility and morphology, normalises the spermogram and contributes to achieving pregnancies with increased fertility, to a greater extent than treatment with Clomiphene; together with the clinical improvement of the patients.

Androgenic Properties and Subchronic Toxicity of the Aqueous Extract of Pycnanthus angolensis (Welw.) Warb. Wood (Myristicaceae)

Aims: Pycnanthus angolensis (Welw.) Warb. also known as “Etengué” in the Baka language, is a medicinal plant used by the Baka Pygmies of Cameroon to treat erectile dysfunction. This study aimed to evaluate the androgenic activity and subchronic toxicity of the aqueous extract of Pycnanthus angolensis wood.&#x0D; Study Design: Experimental design.&#x0D; Place and Duration of Study: Laboratory of Biochemistry, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, between November 2022 and October 2023.&#x0D; Methodology: Twenty-five male Wistar strain rats were divided into 5 groups of 5 rats each including a positive control group that received testosterone enanthate (5 mg/kg) intramuscularly once a week; a normal control group that received distilled water (10 ml/kg) and three test groups which received 134 and 267 and 533 mg/kg of the aqueous extract of Pycnanthus angolensis daily per os. On the 29th day, the animals were killed, and several biochemical parameters were assessed for androgenic properties.&#x0D; Results: At a dose of 134 mg/kg, the extract significantly increased (p&lt;0.05) the levels of testicular cholesterol, testosterone and serum prostatic acid phosphatase activity compared to those of the normal control. A toxicity study showed that at doses of 134 and 267 mg/kg, the extract did not induce any significant variation (p&gt;0.05) in the creatinine level, but a significant reduction (p&lt;0.05) in of aspartate and alanine aminotransferase activities was recorded. Histopathology revealed destruction of testicular spermatozoa at a dose of 533 mg/kg compared to that of the controls.&#x0D; Conclusion: These results showed that at a dose of 134 mg/kg, the aqueous extract of Pycnanthus angolensis (Welw.) Warb. wood is capable of stimulating the production of androgens and is tolerated by the rat's body. Our results justified the traditional use of this plant for the treatment of male infertility and erectile dysfunction.

Resveratrol and male infertility: a systematic review of the literature.

The aim of this study is to provide an updated and comprehensive systematic review on the effects of resveratrol (RSV) in male infertility and sperm preservation. This systematic review followed the MOOSE guidelines for Meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Only original articles evaluating the effect of RSV on human spermatozoa in vivo or in vitro were included. Of the 1806 abstracts evaluated for eligibility, only 12 studies were included in the qualitative synthesis, of which three were prospective in-vivo studies and nine were in-vitro studies. Out of three human studies on RSV, only two studies administered RSV alone, one of them reported a positive impact and the other reported no significant impact on semen parameters. Overall, the in-vitro studies have reported the ability of RSV to protect spermatozoa against damage due to freeze-thaw cycles during cryopreservation. Other in-vitro studies have reported positive effects of RSV in fresh samples and protective effects in cell lines. Available in-vivo studies are controversial with regard to the effect of RSV in improving semen parameters. In-vitro studies support the use of RSV before sperm cryopreservation. Further well-designed prospective studies on large sample sizes are needed to fully understand the role of RSV in the treatment of male infertility in vivo.

A Systemic Review on Use of Medicinal Plant for Management of Male Infertility

A recent issue with current society is the fall in male infertility. In 50% of instances, couple infertility is caused by the failure in spermatogenesis of the male partner. The male reproductive system is impacted by a variety of factors that lead to infertility, including genitourinary tract infections, endocrine abnormalities, immunological factors, lifestyle, stress, and drug-related damage. There are medications and therapies for male infertility, but they are not very effective, have harmful side effects, and are contraindicated. Plants are among the greatest natural cures for illnesses since they have very few side effects and include a variety of phytoconstituents from different chemical classes. Depending on their concentration, plant bioactive such as flavonoids, polyphenols, glycosides, alkaloids, and terpenoids might have a variable effect on sperm quality - either positively or adversely. These compounds have been suggested as organic reactive oxygen species scavengers for the treatment of male infertility. This review makes an effort to compile the available information and offer perspectives for upcoming investigations on how plants affect male gonads. This review summarizes the most recent research on the use of phytoconstituents to increase testosterone production, support healthy spermatogenesis, and prevent age-related degenerative illnesses linked to low levels of testosterone. This review includes information on about 45 herbal plants that have been published in several papers. The articles have several headings, including plant taxonomy, bioactive components, impacts on fertility, and medical applications. This review provides information on the applications of natural sources for male fertility enhancement and their potential mechanisms of action.

The Role of Artificial Intelligence in Male Infertility: Evaluation and Treatment: A Narrative Review

Male infertility has affected an increasingly large population over the past few decades, affecting over 186 million people globally. The advent of assisted reproductive technologies (ARTs) and artificial intelligence (AI) has changed the landscape of diagnosis and treatment of male infertility. Through an extensive literature review encompassing the PubMed, Google Scholar, and Scopus databases, various AI techniques such as machine learning (ML), artificial neural networks (ANNs), deep learning (DL), and natural language processing (NLP) were examined in the context of evaluating seminal quality, predicting fertility potential, and improving semen analysis. Research indicates that AI models can accurately estimate the quality of semen, diagnose problems with sperm, and provide guidance on reproductive health decisions. In addition, developments in smartphone-based semen analyzers and computer-assisted semen analysis (CASA) are indicative of initiatives to improve the price, portability, and accuracy of results. Future directions point to possible uses for AI in ultrasonography assessment, microsurgical testicular sperm extraction (microTESE), and home-based semen analysis. Overall, AI holds significant promise in revolutionizing the diagnosis and treatment of male infertility, offering standardized, objective, and efficient approaches to addressing this global health challenge.

Mesenchymal Stem Cell Therapy for Azoospermia: Navigating Differentiation Challenges and Charting Future Frontiers in Male Fertility Treatment

This minireview explores the current landscape of stem cell therapy for azoospermia, focusing on the potential and challenges associated with Mesenchymal Stem Cells (MSCs). The discussion encompasses the precise regulation of MSC differentiation, safety considerations, and ethical implications. Recent advancements in optimizing differentiation protocols, improving engraftment efficiency, and ongoing clinical trials are highlighted. Despite the hurdles, MSCs emerge as a promising avenue for male infertility treatment. The conclusion emphasizes the necessity for continued research and clinical trials to unlock the full potential of MSC therapy in addressing the complexities of azoospermia.

"Acupuncture for the Treatment of Male Infertility: A Systematic Review and Meta-Analysis"

"Acupuncture for the Treatment of Male Infertility: A Systematic Review and Meta-Analysis"

Is Jackfruit Holding the Key Answer to Male Infertility? Outcomes of a Preliminary Pre-clinical Study

Purpose: The antioxidant activity of jackfruit can be a potential treatment for male infertility. The objectives of the study were to evaluate the effect of jackfruit (Artocarpus heterophyllus) extract on testicular dysfunction and cytogenetic changes induced by Chlorpyrifos in male Wistar albino rats by using sperm analysis, histopathologic analysis of testis, biochemical analyses, and cytogenetic studies; and to determine if these were dose-dependent. Methods: Ethanolic extract of jackfruit (JFE) (450mg/kg, 600mg/kg) and Chlorpyrifos (CPF) (17.5mg/kg) were used. Thirty male rats grouped into control, toxic (CPF), jackfruit, treatment-1 and -2 received distilled water+corn oil, chlorpyrifos, JFE, CPF 17.5mg+JFE 450mg/kg, and CPF 17.5mg+JFE 600mg/kg, respectively. Network pharmacology was used to track, and identify the active ingredients and target pathways. Results: Treatment groups particularly treatment 1 displayed greater weight gain. JFE was associated with an increased testicular weight (p&lt;0.05). Sperm motility significantly increased in the jackfruit, control, and treatment groups, particularly treatment 2. The increase in sperm count and motility were dose-dependent. There was a significant decrease in the DNA damage with JFE. There was an increase in the total protein in the treatment groups. Sperm motility, vitality, and total proteins are significantly reduced with CPF. There was a reduction in malondialdehyde (MDA) and an increase in catalase activity in the jackfruit treatment groups. Network analysis analysed 50 active compounds in JFE, and identified 12 potential targets. Conclusion: JFE has a positive impact on sperm count, motility, vitality, and chromatin integrity demonstrated by decreased DNA damage. Antioxidant assays, MDA, and catalase indicated strong antioxidant activity of JFE.

Challenges in differential diagnosis between obstructive and non‐obstructive azoospermia

AbstractBackgroundSome cases of non‐obstructive azoospermia (NOA) are characterized by normal clinical parameters, including testicular volume and levels of reproductive hormones, mimicking obstructive azoospermia (OA).MethodsWe performed a retrospective review of a consecutive series of 1417 patients undergoing primary surgical sperm retrieval between 2014 and 2023. Follicle‐stimulating hormone (FSH) level below 7.6 IU/l and normal testicular size with a long axis measurement &gt;4.6 cm were used as criteria to suspect OA.ResultsFour hundred and eighteen patients with normal testicular volume and FSH levels had an initial diagnosis of OA. Among them, 243 (58.1%) had histological signs of spermatogenic dysfunction, and 175 (41.9%) had true OA. One hundred eleven patients had long‐standing obstruction (median: 16.5 years) with a median Bergmann–Kliesch score (BKS) of 5 (interquartile range [IQR]: 4–6) and 100% sperm retrieval rate (SRR), though some required microdissection testicular sperm extraction (microTESE). Fifty‐eight patients with a history of epididymo‐orchitis had a median BKS of 4 (IQR: 2–6) and 100% SRR. Twenty patients with a history of unjustified medical treatment for male infertility had a median BKS of 3 (IQR: 1–4) and 80% SRR. Fifty‐four patients had uniform maturation arrest with a 5.5% SRR on microTESE.ConclusionMen with normal testicular volume and FSH level may have evidence of spermatogenic failure on pathology. Patients with complicated seminal tract obstruction commonly have hypospermatogenesis, but true NOA caused by uniform maturation arrest may also be observed. Patient counseling for suspected OA should not be overly optimistic, and couples should be warned about possibility of conversion to microTESE and risks of negative sperm retrieval.

Spem2, a novel testis-enriched gene, is required for spermiogenesis and fertilization in mice

Spermiogenesis is considered to be crucial for the production of haploid spermatozoa with normal morphology, structure and function, but the mechanisms underlying this process remain largely unclear. Here, we demonstrate that SPEM family member 2 (Spem2), as a novel testis-enriched gene, is essential for spermiogenesis and male fertility. Spem2 is predominantly expressed in the haploid male germ cells and is highly conserved across mammals. Mice deficient for Spem2 develop male infertility associated with spermiogenesis impairment. Specifically, the insufficient sperm individualization, failure of excess cytoplasm shedding, and defects in acrosome formation are evident in Spem2-null sperm. Sperm counts and motility are also significantly reduced compared to controls. In vivo fertilization assays have shown that Spem2-null sperm are unable to fertilize oocytes, possibly due to their impaired ability to migrate from the uterus into the oviduct. However, the infertility of Spem2−/− males cannot be rescued by in vitro fertilization, suggesting that defective sperm–egg interaction may also be a contributing factor. Furthermore, SPEM2 is detected to interact with ZPBP, PRSS21, PRSS54, PRSS55, ADAM2 and ADAM3 and is also required for their processing and maturation in epididymal sperm. Our findings establish SPEM2 as an essential regulator of spermiogenesis and fertilization in mice, possibly in mammals including humans. Understanding the molecular role of SPEM2 could provide new insights into future therapeutic treatment of human male infertility and development of non-hormonal male contraceptives.

MicroRNAs in Male Fertility.

Around 50% of all occurrences of infertility are attributable to the male factor, which is a significant global public health concern. There are numerous circumstances that might interfere with spermatogenesis and cause the body to produce abnormal sperm. While evaluating sperm, the count, the speed at which they migrate, and their appearance are the three primary characteristics that are analyzed. MicroRNAs, also known as miRNAs, are present in all physiological fluids and tissues. They participate in both physiological and pathological processes. Researches have demonstrated that the expression of microRNA genes differs in infertile men. These genes regulate spermatogenesis at various stages and in several male reproductive cells. Hence, microRNAs have the potential to act as useful indicators in the diagnosis and treatment of male infertility and other diseases affecting male reproduction. Despite this, additional research is necessary to determine the precise miRNA regulation mechanisms.

Sperm Toolbox-A selection of small molecules to study human spermatozoa.

Male contraceptive options and infertility treatments are limited, and almost all innovation has been limited to updates to medically assisted reproduction protocols and methods. To accelerate the development of drugs that can either improve or inhibit fertility, we established a small molecule library as a toolbox for assay development and screening campaigns using human spermatozoa. We have profiled all compounds in the Sperm Toolbox in several automated high-throughput assays that measure stimulation or inhibition of sperm motility or the acrosome reaction. We have assayed motility under non-capacitating and capacitating conditions to distinguish between pathways operating under these different physiological states. We also assayed cell viability to ensure any effects on sperm function are specific. A key advantage of our studies is that all compounds are assayed together in the same experimental conditions, which allows quantitative comparisons of their effects in complementary functional assays. We have combined the resulting datasets to generate fingerprints of the Sperm Toolbox compounds on sperm function. The data are included in an on-line R-based app for convenient querying.