Connecting the Dots: Gender, Sexuality, and Societal Influences on Cognitive Aging and Alzheimer's Disease.

Alzheimer's disease (AD) has many etiologies and the impact of gender on AD changes throughout time. As a consequence of advancements in precision medical procedures and methodology, Alzheimer's disease is now better understood and treated. Several risk factors may be addressed to lower one's chances of developing Alzheimer's disease or associated dementia (ADRD). The presence of amyloid-α protein senile plaques, intracellular tau protein neurofibrillary tangles (NfTs), neurodegeneration, and neuropsychiatric symptoms (NPS) characterizes Alzheimer's disease. NPS is common in persons with Alzheimer's disease dementia, although its presentation varies widely. Gender differences might explain this clinical variability. The fundamental goal of this review research is to 1) emphasize the function of old age, sex, and gender in the development of Alzheimer's disease, dementia, and ADRD, and 2) explain the importance of sexual hormones, education, and APOE (Apolipoprotein E) status. This is a narrative summary of new ideas and concepts on the differences in the chance of developing dementia or Alzheimer's disease between men and women. A more thorough examination of risk and protective variables in both men and women might hasten research into the epidemiology of neurological illnesses such as dementia and Alzheimer's disease. Similarly, future preventive efforts should target men and women separately.

Tetrabromobisphenol A reduces male rats reproductive organ coefficients and disrupting sexual hormone by causing oxidative stress.

Tetrabromobisphenol A (TBBPA) has become a topic of public attention due to its pervasive detection in the environment and organisms in recent decades. However, limited information is available regarding the toxicity of TBBPA on reproductive ability of male mammals. Herein, the reproductive toxicity of TBBPA was investigated in male rats to fill the knowledge gap. In this study, male rats were exposed to TBBPA (0, 10, 100, and 1000 mg/kg) for 6 weeks. Subsequently, body and organ indexes, histopathological evaluation of testis and epididymis, ultrastructural observation of sperm, testosterone and progesterone levels, and oxidative stress indicators were conducted to reveal corresponding mechanisms. Results obtained showed that compare to the control group, the body weight, testes weight, epididymis weight, seminal vesicle and coagulation glands weight of rats in the 1000 mg/kg group lost 8.30%, 16.84%, 20.16%, 19.72% and 26.42%, respectively. Intriguingly, exposure to TBBPA (10, 100, 100 mg/kg) resulted in substantial pathological damage in testis, epididymis and sperm. TBBPA exposure also increased malondialdehyde (MDA) and hydrogen peroxide (H2O2) contents, as well as superoxide dismutase (T-SOD) and catalase (CAT) activities in testicular tissue. What's more, the testosterone and progesterone levels in male rat serum were significantly decreased after exposure to TBBPA for 6 weeks. Meanwhile, results of molecular docking showed that TBBPA has a strong affinity with estrogen receptors (ERs). These findings demonstrated that TBBPA exposure negatively impacts the reproductive ability of male rats, thus providing new insights for risk assessment for reproductive health under TBBPA exposure.

Role of Female Sex Hormones in ADPKD Progression and a Personalized Approach to Contraception and Hormonal Therapy.

This review navigates the intricate relationship between gender, hormonal influences, and the progression of autosomal dominant polycystic kidney disease (ADPKD), highlighting the limited literature on this crucial topic. The study explores the impact of female sex hormones on liver and renal manifestations, uncovering gender-specific differences in disease progression. Actually, hormonal therapy in women with ADPKD remains a challenging issue and is a source of concern regarding its potential impact on disease outcomes, particularly at the hepatic level. Notably, women with ADPKD exhibit a slower renal disease progression compared to men, attributed to hormonal dynamics. This review sheds light on the role of estrogen in regulating pathways of the renin-angiotensin-aldosterone system, revealing its complex interplay and implications for cardiovascular and renal health. Therapeutic considerations for fertile women with ADPKD, including contraception options, are discussed, emphasizing the necessity for personalized approaches. In the postmenopausal phase, the review evaluates the role of hormonal replacement therapy, considering its potential benefits and risks in the context of ADPKD. The review concludes by underscoring the imperative need for tailored treatment approaches for ADPKD patients, considering individual risks and benefits. The scarcity of literature underlines the call for further research to enhance our understanding of optimal hormonal therapies in the context of ADPKD, ultimately paving the way for innovative and personalized therapeutic interventions.

Understanding the Biological Relationship between Migraine and Depression.

Migraine is a highly prevalent neurological disorder. Among the risk factors identified, psychiatric comorbidities, such as depression, seem to play an important role in its onset and clinical course. Patients with migraine are 2.5 times more likely to develop a depressive disorder; this risk becomes even higher in patients suffering from chronic migraine or migraine with aura. This relationship is bidirectional, since depression also predicts an earlier/worse onset of migraine, increasing the risk of migraine chronicity and, consequently, requiring a higher healthcare expenditure compared to migraine alone. All these data suggest that migraine and depression may share overlapping biological mechanisms. Herein, this review explores this topic in further detail: firstly, by introducing the common epidemiological and risk factors for this comorbidity; secondly, by focusing on providing the cumulative evidence of common biological aspects, with a particular emphasis on the serotoninergic system, neuropeptides such as calcitonin-gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), substance P, neuropeptide Y and orexins, sexual hormones, and the immune system; lastly, by remarking on the future challenges required to elucidate the etiopathological mechanisms of migraine and depression and providing updated information regarding new key targets for the pharmacological treatment of these clinical entities.

Chlorothalonil as a potential endocrine disruptor in male zebrafish (Danio rerio): Impact on the hypothalamus-pituitary-gonad axis and sperm quality.

Chlorothalonil is a broad-spectrum organochlorine fungicide widely employed in agriculture to control fungal foliar diseases. This fungicide enters aquatic environments through the leaching process, leading to toxicity in non-target organisms. Organic contaminants can impact organism reproduction as they have the potential to interact with the neuroendocrine system. Although there are reports of toxic effects of chlorothalonil, information regarding its impact on reproduction is limited. The aim of the present study was to evaluate the influence of chlorothalonil on male reproductive physiology using the zebrafish (Danio rerio) as ecotoxicological model. Zebrafish were exposed for 7 days to two concentrations of chlorothalonil (0.1 and 10 µg/L) along with a control group (with DMSO - 0.001%). Gene expression of hypothalamus-pituitary-gonad axis components (gnrh2, gnrh3, lhr, fshr, star, hsd17b1, hsd17b3, and cyp19a1), as well as hepatic vitellogenin concentration were assessed. In sperm cells, reactive oxygen species (ROS) content, lipid peroxidation (LPO), mitochondrial functionality, and membrane integrity and fluidity were evaluated. Results indicate that exposure to the higher concentration of chlorothalonil led to a reduction in brain gnr2 expression. In gonads, mRNA levels of lhr, star, and hsd17b1 were decreased at both chlorothalonil concentrations tested. Similarly, hepatic vitellogenin concentration was reduced. Regarding sperm cells, a decreased ROS level was observed, without significant difference in LPO level. Additionally, a higher mitochondrial potential and lower membrane fluidity were observed in zebrafish exposed to chlorothalonil. These findings demonstrate that chlorothalonil acts as an endocrine disruptor, influencing reproductive control mechanisms, as evidenced by changes in expression of genes HPG axis, as well as hepatic vitellogenin concentration. Furthermore, our findings reveal that exposure to this contaminant may compromise the reproductive success of the species, as it affected sperm quality parameters.

How Food Choices Impact on Male Fertility.

PURPOSE OF REVIEW: Increasing evidence on the significance of nutrition in reproduction is emerging from both animal and human studies, suggesting an association between nutrition and male fertility. Here, we have highlighted the impact of the various food groups on reproductive hormones and on spermatogenesis, and the effects of classical and latest dietary patterns such as Mediterranean diet, Western diet, intermittent fasting, ketogenic diet, and vegan/vegetarian diet on male fertility. RECENT FINDINGS: Nutrients are the precursors of molecules involved in various body's reactions; therefore, their balance is essential to ensure the correct regulation of different systems including the endocrine system. Hormones are strongly influenced by the nutritional status of the individual, and their alteration can lead to dysfunctions or diseases like infertility. In addition, nutrients affect sperm production and spermatogenesis, controlling sexual development, and maintaining secondary sexual characteristics and behaviors. The consumption of fruit, vegetables, fish, processed meats, dairy products, sugars, alcohol, and caffeine importantly impact on male fertility. Among dietary patterns, the Mediterranean diet and the Western diet are most strongly associated with the quality of semen. Nutrients, dietary patterns, and hormonal levels have an impact on male infertility. Therefore, understanding how these factors interact with each other is important for strategies to improve male fertility.

Gonadal sex vs genetic sex in experimental atherosclerosis.

Epidemiological data and interventional studies with hormone replacement therapy suggest that women, at least until menopause, are at decreased cardiovascular risk compared to men. Still the molecular mechanisms beyond this difference are debated and the investigation in experimental models of atherosclerosis has been pivotal to prove that the activation of the estrogen receptor is atheroprotective, despite not enough to explain the differences reported in cardiovascular disease between male and female. This casts also for investigating the importance of the sex chromosome complement (genetic sex) beyond the contribution of sex hormones (gonadal sex) on atherosclerosis. Aim of this review is to present the dualism between gonadal sex and genetic sex with a focus on the data available from experimental models. The molecular mechanisms driving changes in lipid metabolism, immuno-inflammatory reactivity and vascular response in males and females that affect atherosclerosis progression will be discussed.

The male patient with obesity undergoing metabolic and bariatric surgery: changes in testosterone levels correlate with weight loss after one-anastomosis gastric bypass and Roux-en-Y gastric bypass.

BACKGROUND: Male obesity secondary hypogonadism (MOSH) is a common disease among men with obesity and can be associated with metabolic syndrome and a variety of metabolic problems ultimately leading to androgen deficiency. Metabolic and bariatric surgery is a well-established treatment option associated with significant weight loss and reduction in metabolic co-morbidities. OBJECTIVES: To evaluate the impact of surgery on plasma levels of sexual hormones and their effect on weight loss comparing 2 surgical methods (one-anastomosis gastric bypass [OAGB] and Roux-en-Y gastric bypass [RYGB]) in male patients with obesity. SETTING: University hospital, Austria. METHODS: Patients undergoing OAGB and RYGB between 2012 and 2017 were analyzed retrospectively. Follow-up in this study was up to 24 months. Systemic levels of sexual hormones (luteinizing hormone [LH]), follicle stimulating hormone [FSH], total testosterone [TT], sexual hormone binding globin [SHBG], 17 beta-estradiol [17bE], androstenedione [AS]) were retrieved at each visit. A linear mixed model was used to assess the correlation between changes in testosterone levels and percent excess weight loss (%EWL). RESULTS: In 30.8% of all patients, MOSH was present preoperatively. A significant increase of TT was observed postoperatively that led to a complete resolution of hypogonadism within the period observed. Bioavailable testosterone (bTT) and FSH levels significantly increased each month of follow-up after surgery (all P < .01). Levels of 17bE did not change significantly after surgery. The overall change of TT, comparing preoperative and 1-year postoperative TT levels (ΔTT), significantly correlated with %EWL. Changes in TT levels were not affected by the choice of surgical method. CONCLUSIONS: Serum plasma testosterone levels rise significantly after metabolic and bariatric surgery in male patients. The change of testosterone levels seems to play a role in continued weight loss after surgery. This is true irrespective of the surgical method used.

Effects of diabetes mellitus on sperm quality and fertility outcomes: Clinical evidence.

BACKGROUND: Diabetes mellitus is a global epidemic characterized by high morbidity and mortality. Diabetes mellitus can lead to acute and chronic systemic complications. Among them, a negative effect of diabetes mellitus on sperm quality and male/couple fertility has been suggested. However, available studies in diabetes mellitus men evaluated relatively small cohorts with discordant results. OBJECTIVES: To evaluate the clinical evidences of the effects of diabetes mellitus on sperm quality and fertility outcomes. METHODS: An extensive Medline search was performed identifying studies in the English language. RESULTS: The prevalence of diabetes mellitus in infertile men ranges from 0.7% to 1.4%, while the prevalence of infertility in diabetes mellitus men, evaluated in a few studies, ranges from 35% to 51%. Male diabetes mellitus seems to play a negative effect on couple fecundity, while being childless or subfertile men might increase the risk of diabetes mellitus. Available cross-sectional studies investigating semen parameters and male sexual hormones in men with diabetes mellitus are heterogeneous, assessed relatively small cohorts, show often discordant results and frequently are not directly comparable to derive robust conclusions. Two meta-analyses support a negative effect of diabetes mellitus on sperm normal morphology and no effect on sperm total count, with contradictory results regarding other semen parameters. Considering only studies on type 1 diabetes mellitus men, meta-analyses support a negative effect of diabetes mellitus on sperm motility and no effect on sperm total count, with contradictory results regarding other semen parameters. The rate of children observed among type 1 diabetes mellitus men was lower than controls, especially in subjects with a longer diabetes mellitus duration. Couples with a diabetes mellitus male partner undergoing assisted reproduction techniques showed lower pregnancy rates than controls. No study evaluated the impact of diabetes mellitus treatment on semen quality and male fertility. CONCLUSIONS: Overall, available data show that diabetes mellitus might impair male reproductive health and couple fertility. However, further larger and full of details studies are needed.

Body composition and sexual hormones for the glucose control of autoimmune diabetes in males: are they necessary to predict diabetes-related complications?

Background: Glucose control in diabetes is essential for avoiding diabetes-related complications. Aim: To determine the impact of body composition and sexual hormones in glucose control and diabetes-related complications, in males with autoimmune diabetes. Patients and methods: Thirty-nine patients with autoimmune diabetes and flash glucose monitoring were included. A morphofunctional nutritional evaluation with bioelectrical impedance vector analysis (BIVA), abdominal adipose tissue ultrasound, rectus femoris ultrasound and biochemical parameters, was performed. Results: Strong, positive correlations were observed between body composition parameters, biochemical variables and sexual hormones (p<0.05). Adipose tissue measured by BIVA and ultrasound was more significantly associated with glucose control (including time in range >70%, glucose variability <36% determined by flash glucose monitoring; p<0.05) and the presence of microvascular/macrovascular complications (p<0.05) than lean mass. After adjusting by the duration of diabetes, BMI, abdominal circumference, fat mass and phase angle increased the risk for microvascular complications (OR 1.32(1.00 - 1.73), OR 1.06(1.00 - 1.12), OR 1.14(1.01 - 1.20), 0R 0.3(0.10 - 0.91) respectively; for macrovascular complications: BMI OR 1.38(1.04 - 1.84) and fat mass OR 1.26(1.00 - 1.58)]. Sexual hormone levels did not influence on glucose control or the development of diabetes-related complications. Conclusion: Anthrpometric parameters, especially adipose tissue, were associated with glucose control and variability determined by flash glucose monitoring. Furthermore, changes in fat and lean mass were associated with the presence of microvascular and macrovascular complications. Thus, a comprehensive nutritional evaluation might be useful for the evaluation of males with autoimmune diabetes, in order to identify patients with increased risk of complications.

A comparison of the effects of cinnamon, ginger, and metformin consumption on metabolic health, anthropometric indices, and sexual hormone levels in women with poly cystic ovary syndrome: A randomized double-blinded placebo-controlled clinical trial.

Background/objectives: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women that can alter blood glucose, lipid profile and sexual hormonal level. Therefore, the evaluation of potential therapeutic agents in this population is important. The aim of the study was to determine the effects of cinnamon, ginger, and metformin intake on improvement of sex hormones level, metabolic health (lipid profiles, insulin level and fasting blood glucose) and anthropometric indices (weight, body mass index (BMI), etc.) in women with PCOS. Methods: A total of 100 women with PCOS were randomly assigned to one of the following four groups: cinnamon (500 mg of cinnamon, 3 × day), ginger (500 mg of ginger, 3 × day), metformin (500 mg of metformin 3 × day) or placebo. However, 17 participants were excluded for various reasons and consequently, 83 participants were considered for analysis. Sexual hormones, anthropometrics, glycemic and lipid markers were evaluated before and after the 8-week intervention. Results: Weight and BMI decreased significantly in all intervention groups. The consumption of metformin and cinnamon significantly decreased insulin resistance (HOMA-IR) in comparison to the placebo and ginger groups (P < 0.05). Moreover, a significant decrease in FSH (follicle-stimulating hormone) and LH (Luteinizing hormone) levels were observed in the ginger compared to the placebo group. While metformin and cinnamon significantly lowered testosterone levels (P < 0.05), none of the groups experienced a significant change in DHEA (dehydroepiandrosterone). Conclusion: Our findings suggest that in women with PCOS, cinnamon supplementation causes similar reductions in insulin resistance and testosterone level to that of metformin. Ginger supplementation decreased FSH and LH, hormonal effects not seen following metformin consumption. Overall, cinnamon and ginger supplementations may potentially be used as alternative treatment in women with PCOS. Clinical trial registration: [https://www.irct.ir/trial/28548], identifier [IRCT20171227038105N1].

La función sexual y su relación con los factores psicológicos en las mujeres con el síndrome de ovario poliquístico / Sexual function and its relationship to psychological factors in women with polycystic ovary syndrome

Introducción: El síndrome de ovario poliquístico tiene un notable impacto en la vida de las personas que lo padecen, siendo las áreas psicológica y sexual frecuentemente afectadas. Objetivos: Realizar una revisión bibliográfica sobre la función sexual y su relación con factores psicológicos en mujeres con síndrome de ovario poliquístico. Métodos: Se revisaron las bases de datos Google Scholar, Pubmed Central y SciELO Regional por intermedio del buscador web de Google. Algunos de los aspectos tratados en el artículo fueron los factores psicológicos, las hormonas sexuales y la función sexual, la imagen corporal y el síndrome de ovario poliquístico, y la función sexual y el síndrome de ovario poliquístico. Conclusiones: Los aspectos más estudiados del síndrome de ovario poliquístico han estado relacionados con la conceptualización y fisiopatología de la enfermedad, y las manifestaciones reproductivas y metabólicas. Otros aspectos igualmente importantes como los psicosociales y sexuales han sido muy escasamente abordados y los datos disponibles son contradictorios. Se requieren investigaciones de corte psicosocial para profundizar en las particularidades de la vida psicoemocional y sexual de esta población. Aún existe un campo novedoso poco explorado y permanecen vacíos de información en torno a la sexualidad que por su impacto influyen en el bienestar psicológico y la calidad de vida(AU)

Introduction: Polycystic ovary syndrome has a notable impact on the lives of those who suffer from it, with the psychological and sexual areas frequently affected. Objective: To carry out a literature review on sexual function and its relationship with psychological factors in women with polycystic ovary syndrome. Methods: Google Scholar, Pubmed Central and SciELO Regional databases were reviewed through the Google web search engine. Some of the aspects covered in the article were psychological factors, sex hormones and sexual function, body image and polycystic ovary syndrome, and sexual function and polycystic ovary syndrome. Conclusions: The reviewed literature allows affirming that in the Cuban and international context the most studied aspects of polycystic ovary syndrome have been related to the conceptualization and physiopathology of the disease, and its reproductive and metabolic manifestations. Other equally important aspects such as psychosocial and sexual aspects have been very scarcely broached and the available information is contradictory. Psychosocial research is needed to delve deeper into the particularities of the psychoemotional and sexual life of this population. There is still a novel field that has not been sufficiently explored and there are still gaps in the information on sexuality that, due to their impact, influence the psychological well-being and the patients' quality of life(AU)

Mast-Cell Response to Leishmania mexicana and Sand-Fly Salivary Proteins Is Modulated by Orchiectomy.

Mast cells (MCs) play a crucial role during Leishmania infections, which is transmitted through the bite of an infected sand fly that injects saliva together with the parasite. Sand fly saliva is a complex fluid that modulates the host immune response. In addition, hormonal factors modulate the host immune response and alter susceptibility to infections. Thus, to assess the impact of male sex hormones on the mast-cell (MC) response to Leishmania infections, we orchiectomized male mice, infected them with the parasite in the presence of sand fly salivary proteins, and analyzed the inflammatory response of MCs. Our results showed that the MC response to the parasite and vector salivary proteins differed between orchiectomized and sham-operated mice. In orchiectomized mice, MC showed a retarded activation pattern, associated with slower degranulation and weaker TNF-α, histamine, and tryptase staining in response to the infection with Leishmania mexicana combined with vector-salivary proteins, as compared to sham mice. Furthermore, neutrophil infiltration was slower in orchiectomized mice, and numbers of infected macrophages and lesion sizes were smaller. Our results show that, during Leishmania infection, male sex hormones modulate the mast-cell response against the parasite and salivary proteins of the sand fly vector, inducing an intense inflammatory response. Their absence in orchiectomized mice retards the inflammatory response, enabling better control of the infection and slower disease progression.

The effects of metformin and forskolin on sperm quality parameters and sexual hormones in type II diabetic male rats.

This study aimed to investigate the effects of metformin and forskolin independently and in combinations on the sperm quality parameters and sexual hormones of diabetic male rats. Fifty adult male rats were divided randomly into five identical groups, and diabetes mellitus was induced to the rats, except for the rats in the control group, using a high-fat diet and injection of Streptozotocin. Daily administration of metformin and forskolin independently and in combinations were performed for 8 weeks in different groups. Sperm quality parameters (including sperm count, morphology, sperm motility and Johnson score), testosterone, blood sugar level, Bax to Bcl-2 ratio mRNA expression level and oxidative stress levels were measured and compared between the investigated groups. Treating diabetic rats with metformin and forskolin resulted in significant improvement in sperm quality parameters, increased testosterone levels, reduced oxidative stress in blood and testicular tissue, and decreased blood sugar, and Bax to Bcl-2 ratio level. Although the combination of metformin with forskolin had a higher effect in some parameters such as testosterone levels compared to treatment with metformin or forskolin alone, this combination had not shown a synergistic effect in all the sperm quality parameters. Metformin and forskolin are effective anti-diabetic agents, which significantly improve the sperm quality and sexual hormone levels in diabetic rats. Combining metformin and gorskolin resulted in significantly better testosterone level and antioxidant activity in blood serum without significant effect on sperm quality of diabetic rats.

Sexual hormones in a coastal river adjacent to the Bohai Sea: Characteristic pollutants and dominantly influencing factors.

Characteristic sexual hormones (SHs) and the factors that dominantly influence their occurrence in coastal ecosystems are less understood. This study verified the relationships between SHs and environmental factors and further inferred the possible controlling mechanisms of SH distribution. A characteristic pollutant of SHs was first proposed by determining the contamination level and ecological risks of SHs (seven species) in a coastal river adjacent to the Bohai Sea. The results showed that the 17ß-oestradiol (17ß-E2), estriol (E3), and 17α-ethynylestradiol (EE2) had high mean concentrations of 11.20 (±1.31), 10.17 (±4.91), and 16.71 (±0.88) ng L-1, respectively, in the river water. The concentration of estrone (E1) was positively related to microbial substances of DOMs (p < 0.05). The humification index (HIX) had a negative relationship with E3 (p < 0.05). In water, the distribution of total SHs was regulated by the HIX and fluorescence index (FI), which might be related to photodegradation reactions. The 17α-oestradiol (17α-E2) and EE2 were related to humified organic matter, while E3 and androstenedione (ADD) were influenced by sewage input. The 17ß-E2, E1, and 17α-E2 may be derived from animal sources, while E3, ADD, EE2, and progesterone were from human activities. Oestrogens, including E1, 17α-E2, 17ß-E2, and EE2, displayed higher ecological risks than androgens and progesterone, with medium to high risk in most sites. The 17ß-E2 was regarded as a characteristic pollutant of SHs throughout the river system, which displayed the highest risk. This paper may provide a reference for SH risk management and control.

A systematic review and meta-analysis of the impacts of glyphosate on the reproductive hormones.

Worldwide use of glyphosate is constantly increasing and its residues are detected in drinking water, agriculture, and food products. There are controversial data regarding the potential reproductive adverse effects of glyphosate herbicide. Therefore, we conducted a systematic review and meta-analysis on the studies in which the alteration of at least one sexual hormone including testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol was reported as a measured outcome in rats. In November 2020, 284 articles were screened, of which eight were eligible for the meta-analysis. An overall considerable effect of glyphosate exposure was found on decreasing of testosterone (7 studies, WMD = - 1.48 ng/mL; 95% CI, - 2.34 to - 0.61; P = 0.001), LH (3 studies, WMD = - 2.03 mIu/mL; 95% CI, - 3.34 to - 0.71; P = 0.003), and FSH (3 studies, WMD = - 2.28 mIu/mL; 95% CI, - 5.12 to 0.55; P = 0.115). According to our results, glyphosate intake could have major effects on the health of reproductive system. Consequently, strict monitoring of the residual glyphosate content in the drinking water, agricultural crops, and food products is necessary.

Exploring the role of gut microbiome in male reproduction.

BACKGROUND: The impact of the gut microbiome on the organism has become a growing research focus with the development of 16S rRNA sequencing. However, the effect of the gut microbiome in male reproduction has yet to be investigated. OBJECTIVE: To overview on possible mechanisms by which the gut microbiome could affect male reproduction and therapeutic opportunities related to the gut microbiome METHODS: Authors searched PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane Library for medical subject headings terms and free text words referred to "male infertility" "testis" "gut microbiome" "insulin resistance" "erectile dysfunction" "therapy" "sex hormones" and "genital diseases" until December 2, 2021. RESULTS: Evidence suggests that immune system activation caused by the gut microbiome translocation not only leads to testicular and epididymal inflammation but can also induce insulin resistance together with gastrointestinal hormones such as leptin and ghrelin, which in turn affects the secretion of various sex hormones such as LH, FSH, and T to regulate spermatogenesis. In addition, the gut microbiome can influence spermatogenesis by controlling and metabolizing androgens as well as affecting the blood-testis barrier. It also promotes vascular inflammation by raising trimethylamine-N-oxide (TMAO) levels in the blood, which causes erectile dysfunction. The testicular microbiome and gut microbiome can interact to influence male reproductive function. This study discusses therapeutic options such as probiotics, prebiotics, and fecal microbiota transplantation, as well as the challenges and opportunities behind ongoing research, and emphasizes the need for additional research in the future to demonstrate the links and underlying mechanisms between the gut microbiome and male reproduction. Therapeutic options such as probiotics, prebiotics, and fecal microbiota transplantation are potential treatments for male infertility. DISCUSSION AND CONCLUSION: Gut microbiota may have a causal role in male reproduction health, therapeutic strategies such as supplementation with appropriate probiotics could be undertaken as a complementary treatment. In the future, additional research is needed to demonstrate the links and underlying mechanisms between the gut microbiome and male reproduction.

Effects of controlled ovarian stimulation on vascular barrier and endothelial glycocalyx: a pilot study.

PURPOSE: Controlled ovarian stimulation significantly amplifies the number of maturing and ovulated follicles as well as ovarian steroid production. The ovarian hyperstimulation syndrome (OHSS) increases capillary permeability and fluid extravasation. Vascular integrity intensely is regulated by an endothelial glycocalyx (EGX) and we have shown that ovulatory cycles are associated with shedding of EGX components. This study investigates if controlled ovarian stimulation impacts on the integrity of the endothelial glycocalyx as this might explain key pathomechanisms of the OHSS. METHODS: Serum levels of endothelial glycocalyx components of infertility patients (n=18) undergoing controlled ovarian stimulation were compared to a control group of healthy women with regular ovulatory cycles (n=17). RESULTS: Patients during luteal phases of controlled ovarian stimulation cycles as compared to normal ovulatory cycles showed significantly increased Syndecan-1 serum concentrations (12.6 ng/ml 6.1125th-19.1375th to 13.9 ng/ml 9.625th-28.975th; p=0.026), indicating shedding and degradation of the EGX. CONCLUSION: A shedding of EGX components during ovarian stimulation has not yet been described. Our study suggests that ovarian stimulation may affect the integrity of the endothelial surface layer and increasing vascular permeability. This could explain key features of the OHSS and provide new ways of prevention of this serious condition of assisted reproduction.

Microbiome and PCOS: State-of-Art and Future Aspects.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract microbiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid.