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There is a growing focus on understanding the role of the male microbiome in fertility issues. Although research on the bacterial communities within the male reproductive system is in its initial phases, recent discoveries highlight notable variations in the microbiome's composition and abundance across distinct anatomical regions like the skin, foreskin, urethra, and coronary sulcus. To assess the relationship between male genitourinary microbiome and reproduction, we queried various databases, including MEDLINE (available via PubMed), SCOPUS, and Web of Science to obtain evidence-based data. The literature search was conducted using the following terms "gut/intestines microbiome," "genitourinary system microbiome," "microbiome and female/male infertility," "external genital tract microbiome," "internal genital tract microbiome," and "semen microbiome." Fifty-one relevant papers were analyzed, and eleven were strictly semen quality or male fertility related. The male microbiome, especially in the accessory glands like the prostate, seminal vesicles, and bulbourethral glands, has garnered significant interest because of its potential link to male fertility and reproduction. Studies have also found differences in bacterial diversity present in the testicular tissue of normozoospermic men compared to azoospermic suggesting a possible role of bacterial dysbiosis and reproduction. Correlation between the bacterial taxa in the genital microbiota of sexual partners has also been found, and sexual activity can influence the composition of the urogenital microbiota. Exploring the microbial world within the male reproductive system and its influence on fertility opens doors to developing ways to prevent, diagnose, and treat infertility. The present work emphasizes the importance of using consistent methods, conducting long-term studies, and deepening our understanding of how the reproductive tract microbiome works. This helps make research comparable, pinpoint potential interventions, and smoothly apply microbiome insights to real-world clinical practices.

Background: Estrogens have pleiotropic mechanisms of action, and their cellular transduction pathways can modulate various proteins with differential tissue expression. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is one such protein whose role seems important, although little is known about this protein. However, very little is known about the expression of modulators involved in the estrogen-mediated pathways in the tissues of the male reproductive tract., Methods: In this study, we obtained autopsy specimens of testis and epididymis from 13 men of Caucasian descent. Expression levels were analyzed for both estrogen receptors (ESR1 and ESR2) and their co-regulators, including PELP1 and kinase c-Src (SRC)., Results: Protein expression was confirmed with western blot and immunocytochemistry techniques. The expression of both SRC and PELP1 was significantly higher in the testis compared to the epididymis (p=0.040 and p=0.002, respectively). Furthermore, a significant, positive correlation was observed between SRC and PELP1, regardless of tissue type p<0.0001, R=0.78). In the testis, PELP1 expression positively correlated with ESR1 expression (p=0.367, R=0.6)., Conclusions: Our study suggests a possible relationship between PELP1, SRC, and ESR1 in the human testis and epididymis. This study makes a valuable contribution to the field of estrogen-mediated pathways in the male reproductive tract and describes trends of analyzed genes' expression and presence. We think our results may open some new research directions of the estrogen signaling in the male reproductive system.

Sperm cells are target cells for both estrogens and xenoestrogens. Due to the specific structure of spermatozoa, these hormonal compounds may act on sperm in a non-genomic mechanism only. However, the ESR-mediated signaling pathways are still poorly understood. In this study, we obtained 119 samples from male participants of Caucasian descent who donated semen for standard analysis. We analyzed gene expression of estrogen receptors (ESR1 and ESR2) and their coregulators-proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), and cellular kinase c-Src (SRC). RNA level was established using reverse-transcribed RNA as a template, followed by a polymerase chain reaction. Proteins' presence was confirmed by western blot and immunocytochemistry techniques. "Normal" values of semen parameters were defined as follows: > 32% sperm with progressive motility, > 4% sperm cells with normal morphology, > 15 × 10 6 sperm per mL, > 58% live spermatozoa and leukocyte amount < 10 6 cells per mL, according to WHO 2010 reference. Semen parameters that deviated from these "normal" values were labeled as "abnormal". Gene expression ratios revealed significant, moderate, and negative correlations for ESR1/ESR2 and weak, negative ESR2/PELP1 correlations in the subgroup of patients with abnormal values of semen parameters. In addition, SRC/PELP1 was moderately and positively correlated in the subgroup with parameters within the reference values established by WHO 2010. Our study showed that both PELP1 scaffolding protein and SRC kinase might influence semen quality via ESRs. It seems that not the expression of a single gene may affect the sperm quality, but more gene-to-gene mutual ratio. Characterization of estrogen-signaling pathway-related genes' modulated expression in sperm cells could aid in better understanding sperm biology and quality., (© 2022. The Author(s).)

Introduction: The human body is constantly exposed to an extremely low electromagnetic field (ELF-EMF), in particular at 50 Hz, emitted by power lines, domestic distribution lines, electrical appliances, etc. It is assumed that the increase in electromagnetic exposure may cause adverse effects upon human health, as well as raising concerns regarding the impact on human fertility., Objective: The aim of this in vitro study was to investigate the influence of ELF-EMF with a frequency of 50 Hz on the motility of human sperm. At the same time, the effectiveness of the dielectric screen constructed by ADR Technology ® in absorbing the emitted radiation was examined., Material and Methods: Semen samples of 20 patients were exposed to the influence of an extremely low electromagnetic field. After 5, 15 and 30 min., spermatozoa motility was analysed using a computer-assisted spermatozoa motility analysis system. The following sperm motility parameters were examined: 1) velocity straight linear motility; 2) cross-beat frequency; 3) lateral head displacement; 4) homogeneity of progressive motility velocity., Results: It was found that the ELF-EMF presented a negative effect on the motility of human spermatozoa. A significant decrease in spermatozoa motility speed and a significant increase in lateral head deviation values were observed under the influence of the electromagnetic field. ELF-EMF did not show an effect on either lateral head displacement or homogeneity of progressive motility velocity., Conclusions: A positive effect of the dielectric screen ADR Technology® was found. This effect compensated spermatozoa motility changes induced with ELF-EMF.

Estrogens belong to a group of sex hormones, which have been shown to act in multidirectional way. Estrogenic effects are mediated by two types of intracellular receptors: estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2). There are two basic mechanisms of estrogen action: 1) classical-genomic, in which the ligand-receptor complex acts as a transcriptional factor and 2) a nongenomic one, which is still not fully understood, but has been seen to lead to distinct biological effects, depending on tissue and ligand type. It is postulated that nongenomic effects may be associated with membrane signaling and the presence of classical nuclear receptors within the cell membrane. Estrogens act in a multidirectional way also within cell organelles. It is assumed that there is a mechanism which manages the migration of ESR into the mitochondrial membrane, wherein the exogenous estrogen affect the morphology of mitochondria. Estrogen, through its receptor, can directly modulate mitochondrial gene expression. Moreover, by regulating the level of reactive oxygen species, estrogens affect the biology of mitochondria. The considerations presented in this paper indicate the pleiotropic effects of estrogens, which represent a multidirectional pathway of signal transduction.

Purpose: The survival rates for ovarian cancer patients remain very low, often as a result of late diagnosis due to the asymptomatic course of the early stage disease. Based on the important biological contribution of human chorionic gonadotropin to various key processes including; cell cycle control, DNA repair, cellular differentiation and developmental processes, we hypothesized that genetic polymorphisms in the genes promoter could be associated with ovarian cancer risk. Thus, the purpose of the study was to determine whether particular polymorphisms occur in the promoter region of the human chorionic gonadotropin polypeptide 5 encoding gene, and if so, are they associated with ovarian cancer outcome., Patients and Methods: We analyzed Central European females diagnosed with ovarian cancer (n=95) and controls (n=76) for the occurrence of at least one of three polymorphisms (rs7260002, rs7246045, rs540432391) and their impact on cancer risk. The fluorescence resonance energy transfer technique was used in order to conduct single nucleotide polymorphisms genotyping., Results: The occurrence of two studied polymorphisms, rs7260002 and rs540432391 present in the 5' upstream region of the chorionic gonadotropin (CG) gene were associated with an increased risk of ovarian cancer. The former polymorphism had a minor impact on cancer risk (P=0.049; OR=1.95; 95% CI=0.97-3.92), while the latter had a much larger impact and may be of great importance in the evaluation of cancer development in the analyzed population (p<0.001; OR 8.5; 95% CI 3.59-20.23)., Conclusions: The fluorescence resonance energy transfer application used in tracking the sequence promoter variations of genes expressed during tumorigenesis may be an important factor in early prediction of ovarian cancer. Taking under consideration the elevated CG expression associated with several different cancer types it seems reasonable to estimate if the analyzed polymorphisms could affect cancer outcome., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

INTRODUCTION    Pituitary adenomas are heterogenous lesions commonly observed in the central nervous system. Signal transduction of ghrelin, an endogenous ligand specific for growth hormone secretagogue receptor (GHSR), has been reported to be involved in the development of endocrine tumors. However, there are limited data concerning the role of ghrelin and its functional receptor in pituitary adenomas. OBJECTIVES    The aim of the study was to establish the expression pattern of GHRL and its functional receptor GHSR1a in human pituitary adenomas. PATIENTS AND METHODS    Tissue specimens, including somatotropinomas (n = 20), prolactinomas (n = 5), and nonfunctioning adenomas (n = 52) were obtained from 77 patients. Thirteen normal pituitaries served as controls. The expression pattern of GHRL and GHSR1a mRNAs was established using reverse transcription followed by quantitative polymerase chain reaction. RESULTS    Ghrelin mRNA was detected in 92.2% of the samples including controls, while GHSR1a transcripts were detected in 54.4% of the cases. Significant differences were found among subgroups in the GHSR1a expression (P <0.0001) but not in that of GHRL (P = 0.7). The relative GHSR1a expression level was significantly lower for nonfunctioning tumors than for the control group or somatotropinomas. Controls revealed a strong positive correlation between the expression of both genes (r = 0.8; P <0.0001), unlike adenomas, which showed a weak negative correlation (r = -0.3; P >0.05). The maximum tumor diameter for nonfunctioning adenomas was higher than that for somatotropinomas (mean [SD], 31.4 [76] mm vs 24.8 [10.9] mm; P = 0.01). Neither the GHRL nor GHSR1a expression showed a significant correlation with tumor size in the subgroups. CONCLUSIONS    The presence of GHRL and GHSR1a in the neural system indicates their effect on pituitary function regulation and suggests their possible role in adenoma pathogenesis.

Purpose: Physiological changes during menstrual cycle cause the endometrium and endometriosis to develop specific kind of tissues, especially in regard to the gene expression profiles, which may include also housekeeping genes, commonly used as reference genes (RGs) in quantitative studies. Reverse transcription, followed by quantitative polymerase chain reaction (RT-qPCR) is the most precise and commonly used method in gene expression studies. In order to reduce effects of technical approaches and biological variability of gene's expression level, the studies often employ RGs in experimental data normalization. However, the expression of RGs is not always stable and depends on several variables. Thus, the selection of appropriate RG is one of the most significant steps to obtain reliable results in RT-qPCR-based methods., Material and Methods: With the usage of RT-qPCR, we researched the expression of seven genes (ACTB, B2M, G6PD, GAPD, GUSB, HPRT and PPIA) as reliable reference genes in eutopic and ectopic endometrial tissue specimens obtained during standard surgery of women of reproductive age. Stability of expression level was analyzed by the most universal MS Excel plug-ins including: geNorm, NormFinder and BestKeeper. The descriptive statistics were evaluated using Statistica software., Results: The distribution of threshold (Ct) values was not equal. We identified genes with higher expression level (referring to Ct values) such as ACTB and B2M, medium e.g., GAPD and low expression level, e.g., G6PD and HPRT. We demonstrated that the stability of the analyzed reference genes was not homogenous, and different algorithms pointed to PPIA, GAPD and B2M as the most stable ones in eutopic and ectopic endometrium. On the contrary to these, GUSB and G6PD were the most unstable ones., Conclusions: In RT-qPCR-based analyses of gene expression level in eutopic and ectopic endometrium, we strongly recommend that a minimum of two reference genes are to be used and we determined that the most suitable seem to be PPIA and GAPD., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objectives: The aim of the study was to investigate the influence of 17β-estradiol (main endogenous estrogen) and selected xenoestrogens (genistein, bisphenol-A), individually and in combination, on the mitochondrial function of human sper-matozoa. In natural environment, human beings are exposed to multiple xenoestrogens, so their impact is combined with endogenous steroids., Material and Methods: The effects of ligands on human spermatozoa were assessed regarding the following phenomena: spermatozoa vitality (propidium iodide staining), phosphatidylserine membrane translocation (staining with annexin V marked with fluorescein), mitochondrial membrane potential (using JC-1 fluorochrome), and production of superoxide anion in mitochondria (using MitoSOX RED dye)., Results: Two-hour incubation of spermatozoa with 17β-estradiol, genistein, and bisphenol-A neither altered cell vitality nor stimulated phosphatidylserine membrane translocation. Incubation of spermatozoa with 17β-estradiol or bisphenol-A sepa-rately, as well as incubation with the three ligands simultaneously, resulted in altered mitochondrial membrane potential. Spermatozoa incubation with the three ligands significantly increased the mitochondrial superoxide anion level., Conclusions: It seems safe to conclude that human spermatozoa mitochondria are target cell structures for both, 17β-estradiol and xenoestrogens. The reaction to the 17β-estradiol and xenoestrogens mixture suggests a synergistic mechanism of action. Xenoestrogens may increase the sensitivity of spermatozoa to 17β-estradiol.

Erythromycin A cyclic 11,12-carbonate, a compound with high antibacterial activity, forms with L-aspartic acid a salt possessing valuable properties as a potential chemotherapeutic agent. The L-aspartate of erythromycin A cyclic 11,12-carbonate exhibits strong anti-bacterial activity, especially against Gram-positive bacteria and shows low toxicity. The serum and the lung tissue levels of the discussed salt after a single dose administration to a rat were measured in comparison with those of erythromycin, its L-aspartate, erythromycin cyclic 11,12-carbonate and its L-glutamate. The new erythromycin derivative showed definitely superior characteristics to those of the other substances tested. The activity of the L-aspartate of erythromycin A cyclic 11,12-carbonate in chemotherapy of experimental staphylococcal infection and experimental pneumococcal bronchopneumonia in mice is superior to that of the parent carbonate and erythromycin itself.