Active immunization against gonadotropin-releasing hormone (GnRH) affects the immune system by inhibiting testosterone production. Our previous study investigated the effects of GnRH immunization on thymic T-cell generation, migration, and colonization in peripheral immune organs. However, the mechanisms by which GnRH immunization influences B cell generation and the characteristics of B cell colonization in peripheral immune organs remain unclear. Herein, GnRH immunization enhanced B cell generation by reducing apoptosis. GnRH immunization did not markedly affect the cell cycle of bone marrow cells, B cell development-related signaling molecules, or the percentage of B cells in the blood, spleen, or inguinal lymph nodes. After testosterone supplementation in GnRH-immunocastrated rats, the generation of B cells in the bone marrow was significantly reduced, and the apoptosis of B cells was remarkably increased. Testosterone did not significantly affect the cell cycle of bone marrow cells or the proportion of B cells in the blood, spleen, or inguinal lymph nodes of the GnRH-immunocastrated rats. Overall, these results clarify the mechanisms related to B cell expansion in the bone marrow and the settlement characteristics of B cells in peripheral immune organs after GnRH immunization.
Recent research has shed light on the intricate connection between efferocytosis and infertility, revealing its dysregulation as a contributing factor in various reproductive diseases. Despite the multifaceted nature of infertility etiology, the impact of insufficient clearance of apoptotic cells on fertility has emerged as a focal point. Notably, the removal of apoptotic cells through phagocytosis in the female reproductive system has been a subject of extensive investigation in the field of infertility. Additionally, special functions performed by immune system cell types, such as macrophages and Sertoli cells, in the male reproductive system underscore their significance in spermatogenesis and the efferocytosis of apoptotic germ cells. Dysregulation of efferocytosis emerges as a critical factor contributing to reproductive challenges, such as low pregnancy rates, miscarriages, and implantation failures. Moreover, defective efferocytosis can lead to compromised implantation, recurrent miscarriages, and unsuccessful assisted reproductive procedures. This review article aims to provide a comprehensive overview of efferocytosis in the context of infertility. Molecular mechanisms underlying efferocytosis, its relevance in both female and male infertility, and its implications in various reproductive diseases are elucidated. The elucidation of the intricate relationship between efferocytosis and infertility not only facilitates diagnosis but also paves the way for targeted therapeutic interventions.
The reproductive tract, as a lumen connected to the outside world, its microbial community is influenced by various factors. The changes in its microbiome are closely related to women's health. The destruction of the micro ecological environment will lead to various infections, such as Bacterial vaginosis, sexually transmitted infections, adverse pregnancy outcomes, infertility and tumors. In recent years, with the continuous development and progress of molecular biology, research on reproductive tract microbiota has become a clinical hotspot. The reproductive tract microbiota is closely related to the occurrence and development of female reproductive tract diseases such as vaginitis, pelvic inflammation, PCOS, cervical lesions, and malignant tumors. This article reviews the research on the relationship between vaginal microbiota and female reproductive tract diseases, in order to provide theoretical basis for the prevention and treatment of female reproductive tract diseases.
Released from trophoblast and other fetal cells, placental extracellular vesicles (EVs) reach the maternal peripheral blood and modulate immune responses. Increased EVs in plasma of preeclampsia (PE) patients indicate their involvement in the etiology of this condition. This study addresses the uptake of plasma EVs by peripheral blood mononuclear cells (PBMCs) and explores the underlying internalization mechanisms. Plasma EVs were isolated from women with normotensive pregnancy (EVNP) and those with PE (EVPE), and characterized by cryo-transmission electron microscopy, nanoparticle tracking analysis, Western blotting, flow cytometry, and micro bicinchoninic acid assay (micro-BCA). To investigate whether the origin of PBMCs affects uptake, samples from males, pregnant women, and non-pregnant women were included. Primary PBMCs and macrophages derived from the human leukemia monocytic cell line THP-1 were incubated with PKH-stained EVs, and uptake was assessed by flow cytometry and confocal microscopy. Key molecules involved in monocyte differentiation and macrophage function were evaluated in EV-treated cells using LEGENDplex™ assay and real-time polymerase chain reaction (RT-PCR). Independent of the PBMC source, EVs were mostly captured by monocytes and in a lower proportion by T lymphocytes. Capture of EVPE was higher than of EVNP in primary T lymphocytes, monocytes, and THP-1-derived macrophages. After inhibition by Wortmannin and Cytochalasin D, EV internalization by THP-1-derived macrophages was significantly inhibited but not completely abolished. No defined polarization profile of treated THP-1-derived macrophages could be identified. These findings provide evidence of EV modifications in PE, which enhance their uptake by monocytes and other immune cells, mainly through phagocytosis and endocytosis.
In the eukaryotic system, exosomes are categorized as unique extracellular vesicles with dimensions ranging from 30 to 150 nm. These vesicles contain a variety of endogenous molecules, such as proteins, DNA, mRNA, microRNA, and circular RNA. They are essential for a wide range of metabolic events and have the potential to be used as therapeutic or diagnostic targets for a number of diseases, including ovarian diseases. By inducing changes in the surrounding environment, the donor exosomes transfer their contents to the receiving cells, so demonstrating the biological implications of major interactions between cells. Mesenchymal stem cells (MSCs) have produced exosomes have shown promise as a treatment for premature organ failure (POF or POI). Furthermore, exosomal transport has many complexities, and contributes to the pathophysiology of ovarian cancer by affecting cell growth, migration, metastastsis and etc. Owing to these facts, in this paper, we present the progress developed in the understanding of exosomes as a viable therapeutic avenue and indisputable prognostic targets in ovarian disorders.
Background: Epidermal growth factor (EGF) protein family is essential for implantation and maintenance of normal pregnancy. Results of our previous study on the high incidence of autoantibodies to EGF in patients with pregnancy loss indicated a strong association between EGF autoantibodies and antiphosphatidylserine/prothrombin antibodies (aPS/PT), which are observed in the plasma of patients with thrombosis and adverse pregnancy outcomes.
Objectives: To investigate the association between EGF autoantibodies and aPS/PT in patients with pregnancy loss.
Patients and methods: Plasma specimens were analyzed from patients who experienced pregnancy loss. Direct binding studies using recombinant proteins of the fragments were conducted to determine the antigenic binding sites of aPS/PT, before examining the cross-reactivity of EGF and aPS/PT binding sites.
Results: Of the 219 patients with pregnancy loss, 26 (11.9 %) were positive for aPS/PT. Moreover, incidence of antihuman EGF autoantibodies (anti-hEGF) was significantly higher in aPS/PT-positive patients than in aPS/PT-negative patients (18/26, 69.2 % and 58/193, 30.1 %, respectively; p = 0.0003). Of the aPS/PT-positive patients, 42.3 % recognized fragment 1 + 2 (F1 + 2), and 61.5 % recognized α-thrombin. Presence of anti-hEGF was correlated with recognition of α-thrombin but not of F1 + 2. Moreover, polyclonal antibodies against EGF recognized α-thrombin, and those against α- thrombin recognized hEGF.
Conclusions: In patients with pregnancy loss, aPS/PT recognize F1 + 2 and α-thrombin. Furthermore, α-thrombin and hEGF are immunologically cross-reactive. Therefore, autoantibody-associated disruption of the EGF system may be a cause of pregnancy loss.
Backgrounds: Recent studies have found Several lncRNAs were proved differential expression in diminished ovarian reserve (DOR) patients, however, the mechanism of DOR caused by lncRNAs is still largely unclear.
Methods: High throughput sequencing was performed in ovarian GCs extracted from women with normal ovarian function and women with DOR. Bioinformation analysis was used to analyze the sequencing data and identify the differential expression of lncRNAs. Quantitative RT-PCR (qRT-PCR) was used to verify the sequencing results. Situ fluorescence hybridization (FISH) followed by confocal microscopy and qRT-PCR were used to explore the location and expression of LncRNA-THBS4 in GCs. The significantly enriched signaling pathways of LncRNA-THBS4 were identified by KEGG. The study used RNA interference technology to decipher LncRNA-THBS4 function by silencing LncRNA-THBS4 in GCs. Western blot and qRT-PCR were used to explore the mRNA and protein expressions of key factors of PI3Ks pathway. The pro-apoptotic protein and anti-apoptotic protein were detected by western blot. The proliferation and apoptosis of GCs were detected by MTT assay and Flow cytometry.
Results: 197 lncRNAs with significant differences in expression levels were detected between control and DOR group by high throughput sequencing. The study found the expression of LncRNA-THBS4 in GCs was positively correlated with Anti-Mullerian hormone (AMH) (p = 0.0020, r = 0.4742)、antral follicle count (AFC) (p = 0.0007, r = 0.5130)、good embryo rate (p = 0.0006, r = 0.5210), negatively correlated with basal FSH level (p = 0.0007, r = －0.5152). LncRNA-THBS4 was mainly localized in the cytoplasm of GCs. LncRNA-THBS4 silencing could inhibit the PI3Ks pathway; decrease the levels of anti-apoptotic protein, inhibit the proliferation of GCs; increase the levels of apoptosis protein, enhance the apoptosis of GCs.
Conclusions: The expression level of lncRNA-THBS4 is correlated with ovarian function indicators and pregnancy outcomes in women. LncRNA-THBS4 may participate in the pathogenesis of DOR by affecting the proliferation and apoptosis of GCs via regulating PI3K/AKT/mTOR signaling pathway.
We wished to ascertain if there is an association between neutrophil extracellular traps and endometriosis (EMS). We collected the lesional tissues and normal endometrium of 30 patients suffering from endometriosis. Samples were also taken from healthy controls. Blood from the peripheral circulation was collected to isolate serum and neutrophils. A mouse model of endometriosis was also created. Expression of citrullinated histone and the myeloperoxidase level in tissue were measured by immunofluorescence staining and western blotting. The myeloperoxidase level in peripheral blood serum was measured by enzyme-linked immunosorbent assay. Staining (Trypan Blue) and flow cytometry were used to measure the apoptosis of neutrophils in peripheral blood. BALB/C mice were modeled by allotransplantation, and the experimental parameters noted above quantified. The myeloperoxidase content in the peripheral blood of patients with endometriosis was increased compared with that in healthy controls. Flow cytometry showed that the percent apoptosis of neutrophils in patients with endometriosis was lower than that in healthy controls. Expression of citrullinated histone was higher in the endometriosis group in humans and mice compared with respective controls according to immunofluorescence staining and western blotting. Our data suggest that a high concentration of neutrophil extracellular traps was observed in humans and mice suffering from endometriosis.
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