Search Results (41)

Male infertility is an under-recognized global health burden. Accumulating evidence position the intestinal microbiota as a pivotal regulator of testicular function, underpinning the emerging gut microbiota–testis axis. This narrative review introduces the conceptual term “androbactome”, referring to gut microorganisms and microbial genes that are hypothesized to influence androgen biosynthesis, spermatogenesis, and broader reproductive endocrinology. The documented worldwide decline in sperm concentration heightens the urgency of clarifying microbe-mediated influences on male reproductive capacity. The synthesis of preclinical and clinical findings reveals four principal pathways by which dysbiosis compromises fertility: systemic inflammation, oxidative stress, endocrine disruption, and epigenetic alteration. Lipopolysaccharide-driven cytokinaemia, reactive oxygen species generation, hypothalamic–pituitary–gonadal axis suppression, and aberrant germ cell methylation collectively impair sperm quality and hormonal balance. Short-chain fatty acids, secondary bile acids, and indole derivatives emerge as pivotal messengers within this crosstalk. Therapeutic approaches targeting the androbactome, namely dietary optimization, probiotic or prebiotic supplementation, and fecal microbiota transplantation, have demonstrated encouraging improvements in sperm parameters and testosterone levels, yet the causal inference is constrained by predominantly cross-sectional designs and limited long-term safety data. Recognizing the androbactome as a modifiable determinant of male fertility may open new avenues for personalized diagnosis, risk stratification, and adjunctive therapy in regard to idiopathic infertility. The integration of multi-omics platforms to characterize microbial and metabolomic signatures promises to enrich diagnostic algorithms and guide precision interventions, but rigorously controlled longitudinal and interventional studies are required to secure a translational impact. Full article

Mpox (MPX), caused by the Monkeypox virus (MPXV), is a zoonotic orthopoxvirus infection with increasing global relevance due to sustained human-to-human transmission. While primarily known for cutaneous and systemic involvement, emerging evidence suggests that MPX may also disrupt endocrine function. This narrative review aims to synthesize current clinical, experimental, and epidemiological findings on MPX-related endocrine complications. We explore the potential impact of MPXV on the thyroid, adrenal glands, and gonads, and discuss the underlying mechanisms, clinical manifestations, and implications for patient management. MPX has been implicated in viral-induced subacute thyroiditis, with cases exhibiting thyrotoxicosis followed by hypothyroidism, likely mediated by direct viral infiltration or immune dysregulation. Additionally, MPX may contribute to adrenal insufficiency through viral invasion, immune-mediated destruction, or hypothalamic–pituitary–adrenal (HPA) axis dysfunction, exacerbating metabolic and inflammatory complications. MPXV’s persistence in testicular tissue raises concerns about reproductive health, with potential implications for fertility, hormone production, and viral transmission. The virus may also modulate host steroid pathways through interactions with glucocorticoid, androgen, and estrogen receptors, influencing immune responses and disease severity. Given these findings, clinicians should maintain vigilance for endocrine dysfunction in MPX patients, particularly in immunocompromised individuals. The role of steroid therapy in MPX remains complex, requiring careful balancing of its anti-inflammatory benefits against potential risks of viral persistence and immune suppression. Further research is essential to clarify MPX’s endocrine impact and optimize management strategies. Full article

The growing demand for plastic products has led to an increase in human exposure to microplastics (MPs). MPs have been shown to have detrimental effects on reproductive function, while probiotics have demonstrated promise in enhancing fertility. This study aimed to determine the protective effects of Lactobacillus brevis GKJOY against reproductive damage induced by polystyrene microplastics (PS-MPs) in male rats. In the cell study, LC540 cells were treated with L. brevis GKJOY postbiotic (PGK), gamma-aminobutyric acid (GABA), and PS-MPs to evaluate their effects on cell viability and reactive oxygen species (ROS) production. In the animal experiment, rats were treated with a low dose of L. brevis GKJOY (GK1X, 50 mg/kg), a medium dose (GK2X, 100 mg/kg), or a high dose (GK4X, 200 mg/kg). The results showed that PGK and GABA reduced the levels of ROS and protected against oxidative stress. In contrast, PS-MPs increased ROS levels and had harmful effects on cell viability. In the animal study, testicular injuries caused by PS-MPs led to disruption of the hypothalamic–pituitary–gonadal (HPG) axis and a decrease in reproductive hormone levels. However, treatment with L. brevis GKJOY reduced oxidative stress and pro-inflammatory cytokine levels, restored hormonal imbalances, and led to significant improvements. L. brevis GKJOY effectively mitigated reproductive damage in male rats due to its dual function as a probiotic and neurotransmitter modulator. In conclusion, L. brevis GKJOY, which functions as both a probiotic and a GABA producer, may offer superior protection against male reproductive damage. Full article

Over the years, caloric intake has remained a subject of profound scrutiny. Within the scientific community, there has been rigorous debate to ascertain which path is most ideal for enhancing quality of life and extending the human lifespan. Caloric restriction has been shown to be a promising contributor towards longevity and delaying the onset of age-related diseases. This diet consists of a reduction in caloric intake while maintaining essential energy and nutritional requirements to achieve optimal health while avoiding malnutrition. However, the effects of this nutritional regimen on male reproductive health have not yet been comprehensively studied. Nevertheless, such a complex process will certainly be regulated by a variety of metabolic sensors, likely sirtuins. Evidence has been gathered regarding this group of enzymes, and their ability to regulate processes such as chromatin condensation, the cell cycle, insulin signaling, and glucose and lipid metabolism, among many others. Concerning testicular function and male fertility, sirtuins can modulate certain metabolic processes through their interaction with the hypothalamic–pituitary–gonadal axis and mitochondrial dynamics, among many others, which remain largely unexplored. This review explores the impact of caloric restriction on male fertility, highlighting the emerging role of sirtuins as key regulators of male reproductive health through their influence on cellular metabolism. Full article

Inhibin (INH) plays a key role in the regulation of the reproductive performance of geese. It inhibits follicle-stimulating hormone (FSH) secretion from the anterior pituitary gland to regulate spermatogenesis. Immunization against INH in male geese leads to the production of antibodies to neutralize the INH activity that enhances testicular function and gonadotropin production. The objectives of the present research were to elaborate on the effects of inhibin (INH) immunization on testicular histology, plasma LH, pituitary PRL mRNA, and hypothalamic VIP mRNA expressions in Yangzhou ganders. A total of 60 birds were selected and divided into control (CON) and INH-immunized (INH-immunized) groups, having 30 in each group. In this experiment, the ganders were immunized with INH three times, and birds in the CON group were inoculated with bovine serum albumin (BSA). The analyzed data revealed that immunization against inhibin had no significant effects on improving the plasma concentration of LH hormone; however, significant effects were observed on the germ cell line, hypothalamic VIP mRNA, and pituitary PRL mRNA expressions. It is concluded that INH (INH) immunization is an effective tool to improve reproductive efficiency in Yangzhou ganders; however, INH immunization may harm pituitary PRL mRNA and hypothalamic mRNA expressions and LH plasma concentration. Seasonality played a vital impact on the hypothalamus–pituitary–gonadal (HPG) axis. Full article

Background/Objectives: The hormonal aspect of undescended testes (UDTs) in prepubertal boys, i.e., after mini-puberty, is poorly understood. The aim of this study was to evaluate the hormonal function of UDTs before orchidopexy in prepubertal boys and its correlation with testicular parameters. Methods: The study included 90 prepubertal boys (0.9–8.8 years) with UDTs and 57 age-matched boys with testes in the scrotum (control). The testicular volume (TV), testicular atrophy index (TAI), and testicular growth potential (TGP) of the UDTs were assessed before orchidopexy and 18–24 months after. The analysis included FSH, LH, T, DHT, E2, Inh B, INSL3, and AMH levels. Results: The UDT group demonstrated a significantly higher FSH level and lower Inh B/FSH ratio than controls. Boys with UDTs aged under six years exhibited significantly higher FSH and LH levels and lower Inh B/FSH and T/LH ratios. The TV level of descended and undescended testes, both before and after surgery, was significantly positively related to T and DHT levels, but negatively with Inh B, INSL3 levels, Inh B/AMH, and Inh B/FSH. Conclusions: Hormonal evaluation of the hypothalamus–pituitary–testicular axis and Sertoli and Leydig cell function in prepubertal boys (after mini-puberty) may predict the further development and function of UDTs and may serve as a diagnostic tool in testicular descent disorder. Full article

Background/Objectives: Minipuberty is thought to play an important role in the sexual maturation of infants. Maternal disorders during pregnancy were found to have an impact on the activity of the reproductive axis in the first year of life. This prospective, matched, cohort study was aimed at investigating whether the course of minipuberty in boys is affected by maternal gestational diabetes mellitus (GDM). Methods: The study population consisted of three matched groups of boys: infants born to women with poorly controlled GDM, sons of women with adequately controlled GDM, and infants of healthy women with normal carbohydrate tolerance during pregnancy (control group). Salivary levels of testosterone, androstenedione, DHEA-S and estradiol, and urinary concentrations of FSH and LH were repeatedly measured over the first 12 months of life. Hormone levels were correlated with the size of genital organs (testicular volume and penile length), which were measured at each visit. Results: Compared with the remaining groups, the male offspring of women with poorly controlled GDM were characterized by higher concentrations of both gonadotropins, higher salivary testosterone levels, lower salivary DHEA-S concentrations, and longer periods of detection for LH and testosterone. Levels of gonadotropin, testosterone and DHEA-S in sons of mothers with poorly controlled GDM correlated with mean levels of glycated hemoglobin during pregnancy. Moreover, the infant boys assigned to this group were characterized by larger sizes of the testes and penis. Over the entire study period, there were no differences in hormone levels, testicular volume and penile length between sons of adequately treated women with GDM and sons of healthy women. Conclusions: The obtained results indicate that GDM, if poorly controlled, may affect the activity of the reproductive axis and postnatal growth of male genital organs in the offspring. Full article

Background: Male patients with congenital hypogonadotropic hypogonadism (CHH) have impaired postnatal activation of the hypothalamic–pituitary–gonadal axis that occurs during mini-puberty. The aim of this study was to report our experience using gonadotropin replacement therapy for mini-puberty in male infants with CHH and to establish treatment recommendations. Methods: The patients included in this retrospective case series (n = 9) were diagnosed in the postnatal period due to micropenis, with two being accompanied by cryptorchidism and four with other associated hormonal deficits. All patients started treatment with gonadotropins early after diagnosis, between 2 weeks and 5 months of age, with a schedule of discontinuous injections with subcutaneous human chorionic gonadotropin (62.5–500 IU) two times per week and recombinant follicle-stimulating hormone-alpha (37.5–75 IU) three times per week. Results: The data from our study show an early response, ranging from almost undetectable levels of testosterone at diagnosis to elevated levels after starting treatment, as well as a positive clinical response with increases in testicular volume and penis size in all cases without requiring complementary treatment with testosterone esters and without adverse effects. Conclusions: Our results show that gonadotropin replacement therapy is a well-tolerated and effective treatment for testicular and penile problems in male patients with CHH. Full article

Precocious puberty (PP) requires appropriate management to prevent short adult height, psychosocial issues, and other adverse outcomes. Genetic diagnosis potentially improves the management of PP. Pathogenic NR0B1 variants, which typically cause X-linked adrenal hypoplasia congenita, can also affect gonadal function. While boys with NR0B1 variants usually exhibit hypogonadotropic hypogonadism during adolescence, previous reports have suggested that minipuberty, a physiological transient activation of the hypothalamic–pituitary–gonadal axis during infancy, occurs in these patients and can persist beyond a typical duration. In rare cases, NR0B1 variants cause PP. PP associated with NR0B1 variants has unique features such as early onset and high serum testosterone levels that are often disproportionate to testicular size. Three underlying mechanisms have been proposed for the association between PP and NR0B1 variants: (1) adrenocorticotropic hormone (ACTH)-dependent, (2) gonadotropin-dependent, and (3) ACTH- and gonadotropin-independent mechanisms. The factors contributing to PP vary among cases. Determining the underlying mechanisms is crucial for adopting appropriate therapeutic strategies to control PP. However, as the detailed molecular networks mediating these mechanisms are largely unclear, further research is needed to pave the way for a more effective and personalized management of patients with PP associated with NR0B1 variants. Full article

Heat stress due to climate warming can significantly affect the synthesis of sex hormones in male adolescents, which can impair the ability of the hypothalamus to secrete gonadotropin-releasing hormone on the hypothalamic–pituitary–gonadal axis, which leads to a decrease in luteinizing hormone and follicle-stimulating hormone, which ultimately negatively affects spermatogenesis and testosterone synthesis. For optimal spermatogenesis, the testicular temperature should be 2–6 °C lower than body temperature. Heat stress directly affects the testes, damaging them and reducing testosterone synthesis. Additionally, chronic heat stress abnormally increases the level of aromatase in Leydig cells, which increases estradiol synthesis while decreasing testosterone, leading to an imbalance of sex hormones and spermatogenesis failure. Low levels of testosterone in male adolescents lead to delayed puberty and incomplete sexual maturation, negatively affect height growth and bone mineral density, and can lead to a decrease in lean body mass and an increase in fat mass. In order for male adolescents to acquire healthy reproductive capacity, it is recommended to provide sufficient nutrition and energy, avoid exposure to heat stress, and provide foods and supplements to prevent or repair testosterone reduction, germ cell damage, and sperm count reduction caused by heat stress so that they can enter a healthy adulthood. Full article

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, usually diagnosed during the reproductive period. Both MS and its commonly used animal model, experimental autoimmune encephalomyelitis (EAE), exhibit sex-specific features regarding disease progression and disturbances in the neuroendocrine and endocrine systems. This study investigates the hypothalamic–pituitary–adrenal (HPA) axis response of male and female Dark Agouti rats during EAE. At the onset of EAE, Crh expression in the hypothalamus of both sexes is decreased, while males show reduced plasma adrenocorticotropic hormone levels. Adrenal gland activity is increased during EAE in both males and females, as evidenced by enlarged adrenal glands and increased StAR gene and protein expression. However, only male rats show increased serum and adrenal corticosterone levels, and an increased volume of the adrenal cortex. Adrenal 3β-HSD protein and progesterone levels are elevated in males only. Serum progesterone levels of male rats are also increased, although testicular progesterone levels are decreased during the disease, implying that the adrenal gland is the source of elevated serum progesterone levels in males. Our results demonstrate a sex difference in the response of the HPA axis at the adrenal level, with male rats showing a more pronounced induction during EAE. Full article

The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and paracrine pathways. Male fertility hinges on the availability of testosterone, a cornerstone of spermatogenesis, while follicle-stimulating hormone (FSH) signaling is indispensable for the proliferation, differentiation, and proper functioning of Sertoli and germ cells. This review covers the research on how androgens, FSH, and other hormones support processes crucial for male fertility in the testis and reproductive tract. These hormones are regulated by the hypothalamic–pituitary–gonad (HPG) axis, which is either quiescent or activated at different stages of the life course, and the regulation of the axis is crucial for the development and normal function of the male reproductive system. Hormonal imbalances, whether due to genetic predispositions or environmental influences, leading to hypogonadism or hypergonadism, can precipitate reproductive disorders. Investigating the regulatory network and molecular mechanisms involved in testicular development and spermatogenesis is instrumental in developing new therapeutic methods, drugs, and male hormonal contraceptives. Full article

In recent years, immune checkpoint inhibitors (ICIs) have become a viable option for many cancer patients, including specific subgroups of pediatric patients. Despite their efficiency in treating different types of cancer, ICIs are responsible for a number of immune-related adverse events, including inflammatory toxicities, that can affect several organs. However, our knowledge of the impact of ICIs on the testis and male fertility is limited. It is possible that ICI treatment affects testicular function and spermatogenesis either directly or indirectly (or both). Treatment with ICIs may cause increased inflammation and immune cell infiltration within the seminiferous tubules of the testis, disturbing spermatogenesis or testosterone deficiency (primary hypogonadism). Additionally, the interference of ICIs with the hypothalamic–pituitary–gonadal axis may alter testosterone production, affecting testicular function (secondary hypogonadism) and spermatogenesis. This review provides an overview of the available evidence on the potential association between ICIs and the disruption of spermatogenesis, with special focus on ICIs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1). Moreover, it highlights the need for further investigations and encourages the discussion of associated risks and fertility-preservation considerations between clinicians and patients. Full article

Approximately 16% of North American couples are affected by infertility, with 30% of cases being attributable to male factor infertility. The regulation of reproductive hormones via the hypothalamic–pituitary–gonadal axis is important for spermatogenesis and subsequently male fertility. Maintaining iron homeostasis is critical to normal reproductive physiological function. This cross-sectional study’s objective was to determine the association between serum biomarkers of iron and reproductive hormones. Men experiencing infertility (n = 303) were recruited from Mount Sinai Hospital, Toronto. Serum was analyzed for iron and ferritin as biomarkers of iron status and reproductive hormones (follicle-stimulating hormone, luteinizing hormone, testosterone, estradiol, and prolactin), which were the primary outcome. Associations were determined using non-parametric Spearman’s rank correlation coefficient, linear regressions, and logistic regressions. A significant independent monotonic inverse relationship between serum iron and prolactin (p = 0.0002) was found. In linear regression analyses, iron was inversely associated with luteinizing hormone (unadjusted p = 0.03, adjusted p = 0.03) and prolactin (unadjusted p = 0.001 and adjusted p = 0.003). Serum ferritin was inversely associated with both gonadotropins, follicle-stimulating hormone (adjusted p = 0.03), and luteinizing hormone (adjusted p = 0.02). These findings suggest that biomarkers of iron are associated with pituitary-produced reproductive hormones, which play a role in the hypothalamic–pituitary–gonadal signaling pathway involved in spermatogenesis, testicular testosterone production, and male fertility. Full article

Background and objective—Obesity is a prevalent health concern that notably impairs male fertility through hormonal disruptions and other pathophysiological alterations. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can significantly reduce weight. This narrative review synthesizes the existing literature discussing the impact of glucagon-like peptide-GLP-1 RAs on the male reproductive system, particularly on the hypothalamic–pituitary–gonadal axis and spermatogenesis, highlighting their potential impact on male fertility. Material and methods—PubMed database was used for the retrieval of English-language articles published up to November 2023. This non-systematic literature review predominantly concentrates on both pre-clinical and clinical studies pertaining to GLP-1 RAs, specifically exploring their impact on male reproductive hormones and sperm parameters. Results—GLP-1 receptors have been identified within the male reproductive system according to the existing literature. While the exact mechanisms are not well understood, they appear to be involved in glucose homeostasis and energy metabolism, both vital processes in spermatogenesis. Multiple clinical trials have demonstrated the efficacy of GLP-1 RAs for promoting weight loss. Recent studies show that the use of GLP-1 RAs in obese males may enhance sperm metabolism, motility, and insulin secretion in vitro, along with positive effects on the human Sertoli cells. Recent clinical trials discussed in this review demonstrate weight loss associated with GLP-1 RAs is correlated with improvements in sperm count, concentration, and motility. However, the direct impact of GLP-1 RAs on male reproductive hormones remains unclear, necessitating further research to confirm their potential role in treating male infertility. Conclusions—This narrative review summarizes the existing literature discussing the potential impact of GLP-1 RA on the male reproductive system, emphasizing their potential therapeutic role in addressing idiopathic infertility in obese men. Despite numerous studies exploring the influence of GLP-1 and GLP-1 RAs on reproductive hormones, testicular function, and spermatogenesis, further clinical trials are crucial to validate initial evidence. Longer follow-up periods are essential to address uncertainties regarding the long-term repercussions and outcomes of GLP-1 RA use. While this holds true, the current literature suggests that GLP-1RAs show promise as a potential therapeutic approach for improving sperm parameters in obese men. Full article