Reproductive Sciences最新文献

Retinoic acid (RA) regulates all four major events in spermatogenesis; spermatogonial differentiation, meiotic entry, spermiogenesis, and spermiation. For the pre-meiotic phase, Sertoli cells are the source of RA and for the post-meiotic phase, pachytene spermatocytes are the source of RA. While the entire spermatogenic process is regulated by RA, how each of these phases is regulated by RA remains completely unknown. Homeobox B1 (Hoxb1) has two retinoic acid response elements (RARE) upstream and downstream of the gene. In this study, we investigated if RA facilitates spermatogenesis by its action on Hoxb1. The expressions of the Hoxb1 and Sonic hedgehog (Shh) genes were analyzed in the post-natal mouse testes and the testicular localizations of Hoxb1, Shh and Gli1 were analyzed by immunohistochemistry in the adult rat testis. To delineate the signaling mechanisms, Hoxb1 expression was altered in vitro and in vivo using retinoic acid and miR-361-3p. Finally, the levels of miR-361-3p and HOXB1 were analyzed in infertile human sperm samples. Hoxb1 and Shh gene expressions were found to be low in the testis of post-natal Swiss mice of 7, 14, 28, 35, and 60 days, after which the expressions of both spiked. Immunohistochemistry in the adult mouse testis showed the expressions of Hoxb1, Shh, and Gli1 in the elongating spermatids. Exposure of GC2 cells to RA and in vivo IP RA injection upregulated Hoxb1 and Shh signaling in the testis with increased expressions of Shh, Gli1, and Hdac1. Retinoic acid administration in Swiss mice compromised sperm production and reduced epididymal sperm count. The analysis of infertile human semen samples revealed an increased level of HOXB1 and a decreased level of miR-361-3p as compared to fertile controls. We conclude that retinoic acid regulates late stage of spermatogenesis (spermiogenesis) by affecting Hoxb1 and Shh signaling.

Endometriosis (EMT) -related infertility has been a challenge for clinical research. Many studies have confirmed that abnormal alterations in the immune microenvironment and glycolysis are instrumental in causing EMT-related infertility. Recently, our research team identified several key glycolysis-immune-related genes in the endometrial cells of EMT patients. This study aimed to further investigate the expression patterns of pyruvate dehydrogenase kinase 3 (PDK3), glypican-3 (GPC3), and alcohol dehydrogenase 6 (ADH6), which are related to glycolysis and immunity, in the follicular microenvironment of infertile patients with EMT using enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR) assays. According to the results, compared to the patients with tubal factor infertility, the concentrations of PDK3 and GPC3 were considerably increased in the follicular environment of EMT patients, while ADH6 expression was significantly reduced. The number of oocytes retrieved, the transferable embryo rate, and the cumulative clinical pregnancy rate of EMT patients were significantly reduced, and there was a correlation with the level of PDK3, GPC3, and ADH6 in Follicular Fluid (FF). The area under the receiver operating characteristic (ROC) curve for predicting clinical pregnancy in infertile patients with EMT for PDK3, GPC3, ADH6, and their combination was 0.732, 0.705, 0.855, and 0.879, respectively (P < 0.05). In conclusion, our research indicates that glycolysis-immune-related genes may contribute to infertility in EMT patients through immune infiltration, and disruption of mitochondrial and oocyte functions. The combined detection of PDK3, GPC3, and ADH6 in FF helps to predict clinical pregnancy outcomes in infertile patients with EMT.

To investigate the impact of Sitagliptin against obesity and the underlying mechanism. Obese immature mice were treated with 10, 30, and 90 mg/kg Sitagliptin, respectively. The body weights were recorded and the level of serum biochemical indexes were detected. The visceral fat ratio of each mouse was determined. The pathological change in adipose tissues was determined by HE staining, while F4/80 and CD206 levels in adipose tissues were determined by the immunohistochemical analysis. Lipid formation was evaluated by Oil red O staining assay. RAW264.7 cells were stimulated using oxLDL, followed by being incubated with different concentrations of Sitagliptin. The release of ADPN, IL-6, IL-1β, TNF-α, and the activity of SOD, was measured by ELISA assay. Western blotting was applied to determine adipsin, Nrf2, Keap1, and HO-1 protein levels. ROS level was checked using the DCFH-DA assay. RT-PCR assay was utilized to detect the mRNA levels of IL-6, IL-1β, TNF-α, Nrf2, Keap1, and HO-1. The body weight gain, infiltration of multinucleated cells, enlarged size of adipocytes, increased lipid accumulation, elevated visceral fat ratio, declined ADPN level, upregulated adipsin, and disordered serum biochemical indexes in obese immature mice were statistically significantly reversed by Sitagliptin. Excessive release of inflammatory factors and upregulated F4/80 and CD206 were observed in obese immature mice, which were statistically significantly repressed by Sitagliptin. Furthermore, the elevated MDA level, increased SOD activity, and inhibited Nrf2 pathway in obese immature mice were significantly reversed by Sitagliptin. In oxLDL stimulated RAW264.7 cells, increased release of inflammatory factors, ROS, and MDA, elevated SOD activity, and inactivated Nrf2 pathway were observed, which were statistically significantly abolished by the treatment of Sitagliptin. Sitagliptin alleviated obesity in immature mice by inhibiting inflammation and oxidative stress.

There is a chronic inflammation in PCOS patients, which is correlated with the pathogenesis of PCOS. IL-18 and IL-18BP are related with some inflammatory diseases, while less explored in PCOS. Whether IL-18BP could be a potential drug of PCOS remains unknown.IL-18 and testosterone levels were evaluated in serum of 10 non-PCOS control patients and 20 PCOS patients. Female C57/BL6 mice were gavaged with letrozole to induce PCOS mouse model and IL-18 level was evaluated in the serum of PCOS mouse model, and IL-18 is intraperitoneally injected in female mice, IL-18BP is intraperitoneally injected in the PCOS mice models. Then the body weights, estrous cycles, reproductive hormones and morphology of ovaries were analyzed. The level of ovarian chronic inflammation, fibrosis and endoplasmic reticulum (ER) stress are evaluated.IL-18 levels are increased in the serum of PCOS patients and PCOS mice models respectively. The serum DHEAS, iWAT weight and adipocyte size were increased in IL-18 group compared to the control group (P < 0.05). In the PCOS mouse model treated with IL-18BP, the body weight and serum LH/FSH ratio was decreased compared to the PCOS group (P < 0.05). The expression levels of inflammatory factors and fibrosis-related genes, the expression level of endoplasmic reticulum stress-related genes, and the ROS positive area of ovarian tissue was decreased (P < 0.05).IL-18 is involved in inducing PCOS phenotypes, while IL-18BP relieves PCOS phenotypes by alleviating ovarian chronic inflammation, fibrosis and ER stress in PCOS mice.

Women with endometriosis were deemed more prone to COVID-19 infection in some reports. Considering that endometriosis-related aberrant immune response, understanding how COVID-19 vaccination influences its clinical status is crucial. The aim of this meta-analysis was the evaluate the susceptibility to COVID-19 infection and modifications of symptoms following COVID-19 vaccination in women with endometriosis. Electronic searches on EMBASE, MEDLINE, Scopus, Cochrane at CENTRAL, Scielo.br, LILACS and other databases were searched from inception to March 2024. Studies were eligible if they analyzed the incidence of infection in endometriosis women or the changes in symptoms after two doses of COVID-19 vaccine and had a control group. Four studies (2249 women) were included. No increased susceptibility to COVID-19 infection due to presence or absence of endometriosis was retrievable (risk ratio (RR) 1.42 [95% CI 0.88 to 2.27]; I² = 33%). Patients with endometriosis did not experience an overall worsening of symptomatology relative to controls (RR 1.58 [95% CI 0.67 to 3.75]; I² = 94%). An increase in the risk of dysmenorrhea worsening was noted (RR 1.88 [95% CI 1.11 to 3.17]; I² = 63%). No other differences regarding menstrual flow (RR 1.25 [95% CI 0.70 to 2.23]; I² = 78%), intermenstrual bleeding (RR 1.14 [95% CI 0.83 to 1.56]; I² = 39%) and pelvic pain (RR 2.55 [95% CI 0.65 to 10.05]; I² = 80%) compared to controls was retrievable. Therefore, mRNA vaccines do not seem to lead to worsening of symptomatology in endometriotic women. However, a slight temporary increase in dysmenorrhea may be present. Moreover, endometriosis does not seem to increase the risk of contracting COVID-19.

To analyze whether combinations of polymorphisms within FSHR gene influence ovarian response (OR) to stimulation. A multicenter prospective cohort study was conducted from 11/2016-06/2019 in Europe and Asia including predicted normo-responders under 38y. Patients underwent ovarian stimulation using fixed-dose 150 IU rFSH in a GnRH antagonist protocol. FSHR variants rs6165, rs6166 and rs1394205 were genotyped and combined in diplotypes. OR was compared following multivariable regression. rs6165/rs6166 genotype AG/AG exhibited more hypo-response (33.1% vs. 24%,adjOR 1.77 [95%CI 1.08-2.90]) and lower Follicle to Oocyte Index (FOI) compared with other diplotypes (EMD -11.72 [95%CI -20.89;-2.55]). Genotype GG/AA showed less hypo-response (19.1% vs. 31%, adjOR 0.48 [95%CI 0.24-0.96]), while AA/AA had higher FOI (EMD 20.04 [95%CI 4.51;35.56]). Concerning rs6165/rs1394205, less oocytes (EMD -1.99 [95%CI -3.57;-0.42]) and lower FOI (EMD -12.07 [95%CI -23.09;-1.05]) were retrieved with genotype AG/AG and higher FORT with genotype AA/AG (EMD 17.88 [95%CI 3.77;31.98]). Regarding rs6166/rs1394205, less hypo-response (16.3% vs. 29.5%,adjOR 0.42 [95%CI 0.19-0.97]), more oocytes (EMD 3.45 [95%CI 1.57;5.34]) and higher FOI (EMD 17.57 [95%CI 4.41;30.73) were found with genotype AA/GG. Genotype AA/AG presented higher FORT (EMD 13.47 [95%CI 2.51,24.42]), while more hypo-response (56.3% vs. 26.4%,adjOR 6.30 [95%CI 1.88;21.08]) and lower FOI (EMD -23.51 [95%CI -45.04;-1.97]) was reported with AG/AA. In accordance with our previous studies, FSHR polymorphisms have a statistically significant impact on OR, both individually and in association. However, only rs6166/rs1394205 genotype AA/GG seems to have a clinically significant effect, with a decrease in the prevalence of hypo-response, higher oocyte yield and increase in FOI.

Present investigations were undertaken to record the vulnerability of testis to nickel oxide nano and microparticles in Wistar rat with special reference to their preferred bioaccumulation, consequent generation of reactive species, reciprocal influence on testosterone synthesis, DNA damage in spermatids and histopathological changes. Suitable numbers of rats were gavaged NiONPs or NiOMPs (5 mg/kg b.w.each) for 15 and 30 days. Testes en bloc were removed and processed for the estimation of selected parameters. Results showed that rat testes could accumulate nickel in an exposure time dependent manner. Generation of malondialdehyde, a denominator of ROS, increased significantly in the testes of NiONPs treated rats. Moreover, serum testosterone values also increased in NiONPs treated rats. Higher DNA damage in sperms was also recorded. Nano and microparticles of nickel, both could induce specific dose and time dependent lesions in the testis of rat. Histopathological results revealed degeneration of germinal epithelium and spermatocytes; hypertrophy of seminiferous tubules and necrosis. SEM results also indicated specific morphological changes in cellular components of tubules. This study suggests that testis is also vulnerable to the adverse effects of NiONPs alike liver and kidney. Both micro and nanoparticles of nickel elicited differential effects in a dose and exposure time dependent manner. However, NiONPs induced greater overall toxicity than NiOMPs. The results are expected to be helpful in determining the human reproductive health risks, associated with environmental/ occupational exposure to nanoparticles of nickel.

Endometrial cancer is a malignant tumor that commonly occurs in the female reproductive system and its incidence is still increasing. The mechanism of the development of endometrial cancer has not yet been fully clarified, so we need to continuously study the relevant mechanisms of endometrial cancer and continue to explore its biomarkers in order to discover more precise and effective treatment methods for endometrial cancer. RT-qPCR (Real-Time quantitative Polymerase Chain Reaction) experiments were used to detect the expression level of MMP23B (Matrix Metalloproteinase 23B) in endometrial cancer cells; the clinical data of the TCGA (The Cancer Genome Atlas) database were downloaded, and gene expression profiles were analyzed to investigate the correlation between MMP23B (Matrix Metalloproteinase 23B) and the survival prognosis of endometrial cancer, and functional enrichment analysis was performed on MMP23B (Matrix Metalloproteinase 23B) related genes. After silencing MMP23B (Matrix Metalloproteinase 23B), CCK8 (Cell Counting Kit-8), RT-qPCR (Real-Time quantitative Polymerase Chain Reaction), scratch assay, and transwell assay were used to detect cell viability, levels of apoptotic factors, migration rate, and invasion number of endometrial cancer, respectively. MMP23B (Matrix Metalloproteinase 23B) was highly expressed in endometrial cancer, which is closely related to a poor survival prognosis for endometrial cancer, and may act on endometrial cancer through apoptosis-related functions. The downregulation of MMP23B (Matrix Metalloproteinase 23B) reduced the cell viability of endometrial cancer cells, upregulated the expression levels of CASP3 (Caspase-3), CASP8 (Caspase-8) and CASP9 (Caspase-9) in cells, and inhibited cell migration and invasion.

Around 7% of the male population in the world are entangle with considerable situation which is known as male infertility. Photobiomodulation therapy (PBMT) is the application of low-level laser radiation, that recently used to increase or promote the various cell functions including, proliferation, differentiation, ATP production, gene expressions, regulation of reactive oxygen spices (ROS), and also boost the tissue healing and reduction of inflammation. This systematic review's main idea is a comprehensive appraisal of the literatures on subjects of PBMT consequences in four light ranges wavelength (blue, green, red, near-infrared (NIR)) on sperm cell characteristics, in vitro and in vivo. In this study, PubMed, Google Scholar, and Scopus databases were used for abstracts and full-text scientific papers published from 2003-2023 that reported the application of PBM on sperm cells. Criteria's for inclusion and exclusion to review were applied. Finally, the studies that matched with our goals were included, classified, and reported in detail. Also, searched studies were subdivided into the effects of four ranges of light irradiation, including the blue light range (400-500 nm), green light range (500-600 nm), red light range (600-780 nm), and NIR light range (780-3000 nm) of laser irradiation on human or animal sperm cells, in situations of in vitro or in vivo. Searches with our keywords results in 137 papers. After primary analysis, some articles were excluded because they were review articles or incomplete and unrelated studies. Finally, we use the 63 articles for this systematic review. Our category tables were based on the light range of irradiation, source of sperm cells (human or animal cells) and being in vitro or in vivo. Six% of publications reported the effects of blue, 10% green, 53% red and 31% NIR, light on sperm cell. In general, most of these studies showed that PBMT exerted a positive effect on the sperm cell motility. The various effects of PBMT in different wavelength ranges, as mentioned in this review, provide more insights for its potential applications in improving sperm characteristics. PBMT as a treatment method has significant effectiveness for treatment of different medical problems. Due to the lack of reporting data in this field, there is a need for future studies to assessment the biochemical and molecular effects of PBMT on sperm cells for the possible application of this treatment to the human sperm cells before the ART process.