Reproductive Sciences最新文献

Endometrial polyps are hyperplastic overgrowths of the endometrium that contain both glands and stroma. Myoma uteri is the most common benign tumor of the female pelvis and uterus. HOXA10, which is involved during the organogenesis of the uterus in the embryonic period. The aim of this study was to compare the expression levels of infertility-related genes in endometrial tissue obtained from patients with endometrial polyp and myoma uteri and from healthy controls. A total of 36 patients, including 15 women with endometrial polyp and 21 women with myoma uteri, and 23 healthy controls were enrolled in the study. All patients were evaluated using transvaginal ultrasonography. Endometrial tissue samples were collected from the patient and control groups between the 19th and 21st days of the menstrual cycle. Expression levels of the receptivity markers PROK1, PROKR1, PROK2, PROKR2 and HOXA10 genes were determined by RT- PCR. When the patients diagnosed with endometrial polyp and the healthy controls were compared, it was observed statistically significantly that the expression of PROKR1 increased in endometrium tissue of patients with endometrial polyp (p < 0.05). In patients diagnosed with myoma uteri, gene expression levels of endometrial PROKR1 was statistically significant increased and gene expression levels of PROK1, PROKR2, HOXA10 were found to be statistically significantly decreased compared to the controls (p < 0.05). Changes in the endometrial expression of the HOXA10 and prokineticin gene family in patients with myoma uteri and endometrial polyps may explain certain aspects of infertility in these patients.

Spermiogenesis is a unique process, in which round spermatids undergo morphological changes to form spermatozoa. Serine/Threonine Kinase 33 (STK33), a member of the serine/threonine protein kinase family, plays a pivotal role in spermiogenesis, manifested by the infertile phenotype of Stk33 knockout mice and patients carrying STK33 mutations. To date, the mechanism by which STK33 promotes spermiogenesis is not fully understood. Here we aimed to identify germ cell-specific proteins that interact with STK33. Using immunoprecipitation and mass spectrometry, 13 proteins were identified that potentially interact with STK33 in testicular germ cells. By comparing the expression patterns of the candidate genes in testicular germ cells, we selected Y-Box Binding Protein 2 (YBX2) and Testis Specific Serine Kinase Substrate (TSKS) for validation. When co-expressed in cultured cells, TSKS was immunoprecipitated by STK33, and vice versa. Furthermore, STK33 was recruited to the TSKS foci, likely through interaction with TSKS. Although proximity ligation assay demonstrated that STK33 and YBX2 form the complex in germ cells, their interaction was not recapitulated in cultured cells. Phosphorylation assays showed that STK33 was unable to phosphorylate both YBX2 and TSKS in vitro. Overall, these results suggest that STK33 regulates spermiogenesis through TSKS and YBX2, which warrants further investigation in vivo.

This research delves into the association of Kisspeptin and the KISS₁ gene (rs35431622) single nucleotide polymorphism with circulating sex hormones and semen parameters in males diagnosed with infertility. Eighty male participants were recruited from fertility clinic, were divided into two groups: Group A, characterized by normal sperm count and Group B, exhibiting low count. The analysis involved assessing hormone levels Kisspeptin, follicle stimulating hormone, luteinizing hormone, total testosterone and sex hormone binding globulin by utilizing ELISA, investigating the association of the KISS₁ gene SNP with these variables through Tetra amplification refractory mutation system-PCR and Gel Electrophoresis. The findings revealed that males a low sperm count displayed notably reduced levels of Kisspeptin and free testosterone, accompanied by increased luteinizing hormone and follicle stimulating hormone. The KISS₁ gene SNP rs35431622 (Q36R) demonstrated a 53.3% frequency of the heterozygous mutant TA genotype and OR 0.19 (CI 0.05-0.71) among infertile males, indicating its potential implications a risk factor for male infertility. This study emphasizes the significance of Kisspeptin in overseeing male reproductive health and highlights its potential as a marker for hormonal dysregulation in male infertility.

Exposure to toxic chemicals, such as plasticizers, alkylphenol compounds, and polychlorinated biphenyls (PCBs), has increased due to environmental contamination. PCBs, categorized as persistent organic pollutants (POPs), are lipophilic chemicals commonly used in lubricants, cutting oils, and electrical insulators. PCBs may have detrimental effects on hormone-producing glands, potentially contributing to male infertility. Thus, the objective of this study was to provide a comprehensive overview of the adverse effects of PCBs on the male reproductive system. Searches of three electronic databases were performed using MESH terms and 32 studies were included. Although the exact mechanism of action for PCBs remains unclear, several PCBs are regarded as potential endocrine disruptors due to their ability to interact with hormone signaling pathways. PCBs have been found to disrupt physiological functions by mimicking endogenous hormones as agonists or antagonists, altering patterns of hormone synthesis, hormone receptor affinities or numbers, and modulating enzymes involved in hormone secretion. These reports highlight the pleiotropic nature of PCB function and the susceptibility of the reproductive system. Endocrine-disrupting PCBs can mimic, alter, or block hormonal responses, inhibiting natural signaling to the testes and epididymis via various mechanisms such as binding to sex hormone-binding globulin and androgen-binding protein or blocking cell surface receptors. Furthermore, PCBs can alter the hormonal environment in the prostate or seminal vesicles by changing the affinity of androgens for their receptors. The testicles and genital organs may be susceptible to various estrogenic effects, leading to changes in the quality or quantity of their secretions and the volume of semen.

Endometriosis and ovarian endometrioma (OMA) cause dysmenorrhea and infertility. Current hormonal therapies for OMA treatment, may exhibit limited effectiveness. Hormonal treatments function by downregulate estrogen receptors (ERs) via progesterone receptor (PR) signaling; therefore, progestins are used for the treatment of endometriosis. Dienogest (DNG), an oral progestin, is highly selective for PRs. Previously we identified the association of azurocidin with DNG resistance. Herein, we aimed to examine the effect of azurocidin on OMAs and its clinical significance. We examined the effect of azurocidin on PR or ER and the action of DNG on the inflammatory cytokines IL-6 and IL-8 in OMAs used the human immortalized endometriotic epithelial Emosis-CC/TERT1 cell line, and measured azurocidin levels in human biological samples. DNG inhibited IL-6 and IL-8 production in vitro, which was suppressed in the presence of azurocidin. Additionally, the inflammatory cytokines IL-6 and IL-8 enhanced azurocidin production. Furthermore, azurocidin induced ER expression; the proliferation of EMosis-CC/TERT1 cells increased significantly upon incubation with 17β-estradiol and azurocidin. Overall, azurocidin inhibits the action of DNG by increasing estrogen sensitivity via promoting ER expression and endometriosis. Azurocidin concentrations in the blood and urine were higher in patients resistant to DNG therapy than in other patients. Thus, azurocidin may be associated with DNG resistance in OMAs.

Considering the similarity between the invasion processes of cancer cells and embryo implantation, three-dimensional culture models used to study cancer cell invasion can also be applied to embryo implantation studies. In our study, endometrial epithelial cell line (RL95-2) and spheroid-forming trophoblast-like choriocarcinoma cell line (JAR) were cultured on three different biocompatible tissue scaffolds: bacterial cellulose, collagen foam and collagen fibre. These scaffolds are frequently used in cancer cell metastasis and invasion studies, A three-dimensional endometrium-like culture system was established to quantitatively investigate the role of E-cadherin, N-cadherin, Vimentin, α-smooth muscle actin and Syndecan-1 proteins in the type 1 epithelial mesenchymal transition mechanism observed during the invasion step of the implantation process. Based on the findings from the three-dimensional cell culture, the bacterial cellulose scaffold promoted the proliferation of RL95-2 cells and delayed JAR spheroid formation. The collagen foam scaffold favored the proliferation of RL95-2 cells and accelerated JAR spheroid formation. The collagen fibre scaffold is important for supporting cell topography and, when combined with collagen foam, may offer a potential solution for investigating 3D endometrium-like culture systems. Immunocytochemical and immunofluorescence analyses showed that scaffolds modulate the invasion process by affecting the expression of epithelial mesenchymal transition proteins in cells. The findings suggest that different tissue scaffolds can produce varying effects in endometrium-like culture systems, and combinations of these materials may yield more effective results in future studies. This research represents a critical step in studying cell behavior in 3D culture systems and elucidates the mechanism of endometrial invasion.

Heat stress is considered as one of the most crucial environmental stressors affecting reproductive efficiency in mammals through modulation of the function of Corpus Luteum (CL) that plays a vital role in progesterone production and pregnancy maintenance. Therefore, this detailed systematic review seeks to bring forward the interdisciplinary perspectives on the impact of heat stress exposure on CL function regarding hormonal shift, luteal phase distortion and fertility receptivity. High temperatures are shown to impose oxidative stress, change blood perfusion within the CL, signal transduction which converts the signal from the signaling molecule into an intracellular reaction and impaired luteal activity. This review incorporates various scientific studies on these effects to different mammalian species concerning the associated physiological mechanisms. Besides this, it also considers the overall impact in warm stressed population in livestock breeding in the agricultural system as well as their conservation from a general perspective. Some of the prevention and control measures for heat related reproductive problems are also covered here, addressing the importance of finding the impact on the CL in order to put in place these interventions. This review may be used to inform future developments that may improve the CL function with regards to heat stress and possible solutions to help mammals reproduced under climate change tender environment and even rising temperatures globally.

Cervical cancer (CC) represents a major gynecologic health problem. Respecting the role of programmed cell death ligand-1 (PDL-1) in cancer prognosis, we investigated its relationship with cervical squamous cell carcinoma (CSCC) invasion, metastasis and prognosis. A total of 184 CSCC patients were retrospectively selected, with normal paracarcinoma tissues as the Control group. PDL-1 expression was assessed, and its relationship with CSCC prognosis and clinical value on predicting CSCC invasion/metastasis and poor prognosis were determined. PDL-1 was up-regulated in CSCC. CSCC patients at International Federation of Gynecology and Obstetrics stage II/III, and with lymph node metastasis (LNM), parauterine/vascular infiltration, and history of sexually transmitted diseases exhibited up-regulated PDL-1. The areas under the curve of PDL-1 on predicting the invasion and metastasis/poor prognosis of CSCC patients were 0.930 (95%Cl: 0.883-0.962)/0.935 (95%Cl: 0.886-0.967), with cut-off values of 23.27/24.86 (86.76%/80.95% sensitivity, 95.69%/92.68% specificity). The CSCC patients with highly-expressed PDL-1 showed increased cumulative incidence of poor prognosis. Additionally, occurence of vascular infiltration/LNM, and up-regulated PDL-1 were independent risk factors for poor prognosis in CSCC patients. Briefly, PDL-1 expression rised in CSCC. High PDL-1 expression might promote tumor infiltration and LNM, while close monitoring of its expression contributed to evaluating prognosis of CSCC patients.

The metabolomic approach has recently been used in the assessment of semen quality and male fertility. Additionally, the crucial roles of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) in metabolic syndrome (MetS) were reported. However, little information exists about the association between BCAAs and AAAs with semen parameters, particularly in men with and without MetS. Our objective was to explore the association between BCAAs and AAAs in blood and seminal plasma and sperm parameters in men with MetS (MetS +) and without MetS (MetS-). In a cross-sectional study between January-July 2022, we investigated 98 men (age: 25-42 years; MetS + : n = 28 and MetS-: n = 70) at Royan Institute, Tehran, Iran. All participants underwent anthropometric indices measurements using standard protocols. From each participant, a single fasting blood sample was collected on the same day that the semen sample was collected. The BCAAs and AAAs in blood and seminal plasma were measured using high-performance liquid chromatography (HPLC). The aromatase activity (total testosterone/ estradiol ratio) was significantly lower in MetS + (0.16) than MetS- (0.35) (p = 0.016). Semen parameters were similar between the MetS + and the MetS- groups. All BCAA and AAA family members, except tryptophan, were higher in the blood plasma of men with metabolic syndrome. Meanwhile, the seminal plasma of BCAA and AAAs were similar. Intriguingly, Valine in blood (r = -0.329; p < 0.001) and seminal (r = -0.237; p < 0.05) plasma were correlated with abnormal sperm morphology in patients without metabolic syndrome (MetS-). Further research is necessary to validate these findings and to explore the underlying mechanisms and interactions between the plasma BCAAs and AAAs and sperm parameters.