Search Results (295)

Soil-transmitted helminths (STHs) and Herpes Simplex Virus type 2 (HSV-2) are highly prevalent infections with overlapping distribution, particularly in resource-poor regions. STH/HSV-2 co-infections may impact female reproductive health. However, many aspects of STH/HSV-2 co-infections, including the role of microRNAs (miRNAs) in regulating female genital tract (FGT) immunity and their potential contribution to pathologies such as chronic inflammation, impaired mucosal defense, and reproductive tract cancers remain unclear. In this study we investigated the miRNA expression profiles in murine FGT tissues following single or co-infection with Nippostrongylus brasiliensis (Nb) and HSV-2 and explored predicted miRNA-mRNA targets and pathways. An analysis of miRNA sequencing data was conducted to determine differentially expressed (DE) miRNAs between infected FGT tissues and uninfected controls. Ingenuity Pathway Analysis was conducted to predict the immune-related target genes of the DE miRNAs and reveal enriched canonical pathways, top diseases, and biological functions. Selected representative DE miRNAs were validated using RT-qPCR. Our results showed a total of eight DE miRNAs (mmu-miR-218-5p, mmu-miR-449a-5p, mmu-miR-497a-3p, mmu-miR-144-3p, mmu-miR-33-5p, mmu-miR-451a, mmu-miR-194-5p, and mmu-miR-192-5p) in the comparison of Nb-infected versus uninfected controls; nine DE miRNAs (mmu-miR-451a, mmu-miR-449a-5p, mmu-miR-144-3p, mmu-miR-376a-3p, mmu-miR-192-5p, mmu-miR-218-5p, mmu-miR-205-3p, mmu-miR-103-3p, and mmu-miR-200b-3p) in the comparison of HSV-2-infected versus uninfected controls; and one DE miRNA (mmu-miR-199a-5p) in the comparison of Nb/HSV-2 co-infected versus uninfected controls (p-value < 0.05, |logFC| ≥ 1). Core expression analysis showed that, among other canonical pathways, the DE miRNAs and their predicted mRNA targets were involved in neutrophil degranulation, interleukin-4 and interleukin-13 signaling, natural killer cell signaling, interferon alpha/beta signaling, and ISGylation. Additionally, cancer was predicted as one of the significantly enriched diseases, particularly in the co-infected group. This is the first study to provide insights into the FGT miRNA profiles following Nb and HSV-2 single and co-infection, as well as the predicted genes and pathways they regulate, which may influence host immunity and pathology. This study highlights the role of miRNAs in regulating FGT immunity and pathology in the context of STH/HSV-2 co-infection. Full article

Background/Objectives: Endocrine disruptors (EDs) are xenobiotic chemicals that disrupt hormone signaling and homeostasis within the human body. Accumulative evidence proposes that EDs could affect systemic hormone balance and local microbial communities, including the female genital tract (FGT) microbiome. The FGT microbiome, and especially the vaginal microbiota, contributes significantly to reproductive health maintenance, defense against infection, and favorable pregnancy outcomes. Disruption of the delicate microbial environment is associated with conditions like bacterial vaginosis, infertility, and preterm birth. Methods: The present narrative review summarizes the existing literature on EDs’ potential for changing the FGT microbiome. We discuss EDs like bisphenol A (BPA), phthalates, and parabens and their potential for disrupting the FGT microbiome through ED-induced hormone perturbations, immune modulation, and epithelial barrier breach, which could lead to microbial dysbiosis. Results: Preliminary evidence suggests that ED exposure–microbial composition changes relationships; however, robust human evidence for EDs’ changes on the FGT microbiome remains scarce. Conclusions: Our review addresses major research gaps and suggests future directions for investigation, such as the necessity for longitudinal and mechanistic studies that combine microbiome, exposome, and endocrine parameters. The relationship between EDs and the FGT microbiome could be critical for enhancing women’s reproductive health and for steering regulatory policies on exposure to environmental chemicals. Full article

The female reproductive tract (FRT) serves as the core of human reproduction, and its health is directly related to population quantity and family happiness. The high incidence rate of female reproductive tract diseases globally poses a severe threat to women’s health. Nevertheless, the exploration of its physiological functions and pathological mechanisms still lacks satisfactory research models. Organoids, as an emerging technology, not only circumvent numerous ethical issues existing in in vivo experiments but also precisely replicate the morphological structure and characteristics of the simulated tissues. The purpose of this article is to summarize the basic paradigms of organoid establishment and their applications in female reproductive research. Specifically, this article summarizes the cell sources, extracellular scaffolds, and culture media used in the establishment of organoids. It also describes the applications and future development prospects of female reproductive tract organoids established in current research in physiological and pathological studies. The importance of organoid technology in the female reproductive tract research cannot be ignored. It has opened up new avenues for research in this field and greatly promoted the exploration of female reproductive health and disease mechanisms. Full article

Reproductive efficiency in cattle remains sub-optimal, with pregnancy rates often below 50%, despite fertilization rates approaching 100%, indicating that implantation failure and/or early embryonic loss are major limiting factors. This disparity highlights the need to understand the biological and physiological mechanisms underlying implantation failure. This review elucidates the cellular and molecular mechanisms underlying reduced pregnancy rates, with a particular focus on biological aging and fibrosis in the reproductive organs as emerging contributors to uterine dysfunction. Accumulated evidence suggests that metabolic demands associated with intensive breeding strategies aimed at maximizing meat and milk productivity may induce multiple forms of stress, including oxidative stress, metabolic stress, and inflammation, which accelerate biological aging and fibrosis in the female reproductive tract. However, the direct molecular mechanisms remain poorly characterized. We hypothesize that biological aging and fibrosis are interconnected mechanisms contributing to impaired uterine function, resulting in reduced implantation rates. By summarizing recent findings and adopting a comparative perspective, this review explores the extent to which insights from human and mouse models can be applied to cattle, considering species-specific reproductive physiology and metabolic adaptations. It explores their relevance to reproductive inefficiencies and discusses potential strategies to enhance fertility and extend bovine reproductive longevity. Full article

Unilateral renal agenesis (URA) is a urinary tract congenital anomaly characterized by a congenital absence or early developmental arrest of only one kidney. In the presence of a normal contralateral kidney, URA is typically considered a condition of minimal clinical significance as the solitary kidney often undergoes hypertrophy and can sufficiently perform the needed renal function after birth. However, postnatal studies suggest that URA has a significant association with other urinary and extra-urinary anomalies and may have implications for long-term health. This descriptive review focuses on the perinatal aspects of URA, emphasizing the main ultrasound findings to establish the prenatal diagnosis and to guide perinatal management. The pediatric implications of this diagnosis, particularly the high prevalence of long-term complications including hypertension, proteinuria, and a decreased glomerular filtration rate, are also briefly reviewed. URA is consistently associated with other ipsilateral urogenital anomalies. In females, there is a significant association with uterine anomalies that has significant implications for subsequent reproductive function. In males, the prevalence of both urinary and genital anomalies is also increased, which may also have implications for future fertility. Prenatal ultrasound offers the possibility of early diagnosis and parental counseling, which may result in timely intervention to reduce contralateral renal damage, prevent severe urogenital manifestations and co-morbidities, and improve fertility and the quality of life. Full article

Malignancies of the female upper reproductive tract, especially endometrial and ovarian cancers, generate a significant burden for women worldwide. The possible etiopathogenetic role of chronic human papillomavirus (HPV) infection in the carcinogenesis of the female upper genital tract is neither clearly established not completely understood. Therefore, we performed a literature review, using the PubMed and SCOPUS electronic databases, of the prevalence of HPV DNA in endometrial, primary fallopian tube, ovarian, and primary peritoneal cancers, as well as uterine sarcomas. The present investigation covered 35 studies from different countries on various continents. Overall, the prevalence of HPV was approximately 15% in all the above cancers. HPV DNA was isolated from 11%, 0%, 0%, and 14% of endometrial carcinomas, uterine sarcomas, primary fallopian tube cancers, and ovarian malignant neoplasms, respectively. No relevant studies on primary peritoneal cancers were retrieved. The predominant HPV strain from tumors of the upper female reproductive tract, regardless of the tumor site, was HPV-16, followed by HPV-18. The HPV DNA identified was exclusively from subtypes HPV-6, HPV-11, HPV-16, HPV-18, and HPV-33, which are responsible for the development of not only cervical cancer, but also condylomata acuminata. The findings of the present review indicate that HPV vaccination might prove to be a useful strategy in the prevention of HPV-related carcinomas of the upper genital tract in women. Full article

Seminal plasma, traditionally regarded as a passive transport medium for sperm, has emerged as a sophisticated biofluid orchestrating critical dialogues in reproductive physiology. Contemporary research reveals its multifunctional role in modulating endometrial receptivity through molecular priming of the female reproductive tract, a process essential for successful embryo implantation. Notably, seminal plasma contains numerous extracellular vesicles (EVs) that serve as critical mediators of intercellular communication via the regulation of biological processes in target cells. Through this sophisticated vesicular communication system, seminal plasma extracellular vesicles (SPEVs) coordinate critical reproductive events. Thus, it will be important to elucidate the molecular mechanisms by which SPEVs mediate reproductive processes, to provide knowledge that may improve fertility outcomes. Herein, we elucidated the emerging potential of SPEVs as non-invasive biomarkers for male fertility assessment and infertility diagnosis. Furthermore, this review systematically summarized current advances in SPEVs, highlighting their multifaceted roles in mediating sperm maturation, regulating sperm capacitation, and modulating embryo implantation through targeted delivery of bioactive signaling molecules. Full article

Dysbiosis, or an altered microbiota composition, has been implicated in chronic endometrial inflammation and recurrent implantation failure. Despite growing research on the relationship between the genital microbiome and reproductive health, few studies have examined its role in ectopic pregnancy. Therefore, our study focuses on the microbiota of the cervical canal in women diagnosed with an ectopic pregnancy. Material and methods: The study group consisted of nine women of a reproductive age who were hospitalized at the Department of Maternal and Child Health, Gynecology and Obstetrics, Clinical Hospital of the University of Poznań, between February and September 2023. In nine patients, an ectopic pregnancy was diagnosed based on a transvaginal ultrasound examination. The swabs were collected for quantitative microbiological culture (using Amies transport medium). The microbiological analyses involved quantitative culture on selected selective and differential media, following the Standard Operating Procedure developed by the Institute of Microecology. Results: A reduced Lactobacillus spp. count (≤5 × 10⁷ CFU/mL) was observed in 78% of the patients participating in the study, including those that produce H₂O₂, i.e., with strong protective properties for the environment of the female reproductive tract. The molecular analyses revealed Ureaplasma spp. (U. parvum and U. urealyticum) in 33% of the samples (three patients). However, Chlamydia trachomatis and Mycoplasma genitalium were not detected in any of the analyzed samples. Conclusions: The ease of obtaining material and the minimally invasive nature of lower reproductive tract examinations may allow for the evaluation of microbiota imbalances, helping to identify individuals at an increased risk of reproductive complications. Full article

Toll-like receptors (TLRs) play crucial roles in innate immunity, but their function in reproduction remains poorly understood. This study investigated the expression patterns and localization of TLR1-9 in the reproductive system of Hu sheep and their potential association with prolificacy. All TLRs were expressed in the oviduct, uterus, and ovary, with TLR6 showing significantly higher expression in the oviduct, while TLR3, TLR6, and TLR7 were predominantly expressed in the ovary. Following this initial screening, we focused on TLR2, TLR6, and TLR7 for detailed analysis. Immunohistochemical analysis revealed that TLR2, TLR6, and TLR7 were localized in the luminal epithelium and circular muscle of the oviduct, the luminal and superficial glandular epithelium of the uterus, and in ovarian follicles at all developmental stages. A comparative analysis between high-prolificacy (HP) and low-prolificacy (LP) Hu sheep demonstrated significantly lower TLR2 expression in the reproductive organs of HP sheep, while TLR6 expression was higher and TLR7 expression was lower in HP ovaries compared to LP ovaries. Notably, TLR7 was observed around apoptotic bodies of granulosa cells, suggesting a potential role in follicular development through the regulation of granulosa cell apoptosis. These findings establish a novel link between innate immunity and reproductive function in sheep, suggesting that TLRs, particularly TLR2, TLR6, and TLR7, may serve dual roles as immune sentinels and reproductive regulators influencing ovine fertility. Full article

The study of the microbiome has rapidly progressed over the past few decades, capturing the interest of both scientists and the general public. Nevertheless, there is still no widely agreed-upon definition for the term “microbiome” despite tremendous advances in our knowledge. The international scientific literature consistently underscores the difference between the human microbiome and human microbiota. Recent research has emphasized the importance of the female reproductive tract microbiome in fertility, impacting natural conception and assisted reproductive technologies (ARTs). This review explores the relationship between infertility and the microbiota of the female reproductive tract through a thorough evaluation of research papers and large-scale studies published up to 2024. The objective of this review is to critically assess current evidence on the role of the reproductive tract microbiome in female infertility and ART outcomes. Relevant papers were identified and analyzed through the electronic medical databases PubMed/MEDLINE and Scopus. A comprehensive synthesis of data from 36 original studies was performed, including observational, case–control, cohort, and randomized trials. By focusing on the vagina, cervix, and endometrium, this study offers a comprehensive overview of the microbiome throughout the female reproductive tract. RIF and poor reproductive outcomes are strongly linked to dysbiosis, which is characterized by a reduction in Lactobacillus species. Lactobacillus crispatus, in particular, plays a significant role in protecting against bacterial vaginosis and infertility. A thorough understanding of how the microbiome impacts fertility and the development of clinical strategies to improve reproductive outcomes requires standardized microbiome investigation techniques and larger, randomized trials that account for diverse patient characteristics. Full article

Mammalian fertilization depends on sperm successfully navigating a spatially and chemically complex microenvironment in the female reproductive tract. This process is often conceptualized as a competitive race, but is better understood as a collective random search. Sperm within an ejaculate exhibit a diverse distribution of motility patterns, with some moving in relatively straight lines and others following tightly turning trajectories. Here, we present a two-state random walk model in which sperm switch from high-persistence-length to low-persistence-length motility modes. In reproductive biology, such a switch is often recognized as “hyperactivation”. We study a circularly symmetric setup with sperm emerging at the center and searching a finite-area disk. We explore the implications of switching on search efficiency. The first proposed model describes an adaptive search strategy in which sperm achieve improved spatial coverage without cell-to-cell or environment-to-cell communication. The second model that we study adds a small amount of environment-to-cell communication. The models resemble macroscopic search-and-rescue tactics, but without organization or networked communication. Our findings provide a quantitative framework linking sperm motility patterns to efficient search strategies, offering insights into sperm physiology and the stochastic search dynamics of self-propelled particles. Full article

Sperm preparation is a critical step in assisted reproduction, aiming to isolate spermatozoa with optimal characteristics and high fertilizing potential. Traditional sperm selection methods involve centrifugation, which may cause sperm damage. Microfluidic sperm sorting (MSS) offers an alternative approach, mimicking the female reproductive tract environment, avoiding centrifugation, and reducing manipulation and processing time. This study aims to compare the performance of MSS and Swim-up (SU) in 26 normozoospermic, 31 hyperviscous normozoospermic, 15 oligozoospermic, and 9 asthenozoospermic subjects. Semen samples were collected from male subjects undergoing routine semen analysis at Careggi University Hospital, Florence. Sperm selection was carried out using both SU and MSS. The parameters assessed included sperm motility, viability, concentration, kinematics, DNA fragmentation (sDF), chromatin compaction, and oxidative status. Both SU and MSS improved sperm characteristics compared to unselected samples. MSS isolated high-quality spermatozoa with lower sDF and higher chromatin compaction than SU, not only in normozoospermic samples but also in samples with semen defects like hyperviscosity, low concentration and/or motility, and high sDF. In conclusion, the use of microfluidics may enhance the chances of successful fertilization and improve reproductive outcomes, especially for individuals with compromised semen quality where conventional methods may fail. Full article

Understanding reproductive biology and associated disorders is crucial for the clinical management of chelonians, particularly those maintained in captivity. This literature review presents an overview of the main pathological conditions affecting the female reproductive tract of these animals. For each condition, practical and effective diagnostic and therapeutic procedures are detailed. Commonly observed disorders include dystocia, ectopic eggs, follicular stasis, infertility, oophoritis, salpingitis, cloacitis, cloacal or oviductal prolapse, neoplasms, and ovarian torsion. The fundamental approach to these conditions always involves a thorough clinical examination, which requires extensive knowledge of the species, a clinical history, and management practices. Diagnostic procedures include physical exams, imaging techniques (ultrasound, radiography, CT, endoscopy), and surgical interventions. A shared feature of many pathologies is the influence of management errors and the presence of non-specific clinical signs. Full article

Immunocompetent cells of B lineage function in the humoral immunity system in the adaptive immune responses. B cells differentiate into plasmacytes upon antigen-induced activation and produce different subclasses of immunoglobulins/antibodies. Secreted immunoglobulins not only interact with pathogens to inactivate and neutralize them, but also involve the complement system to exert antibacterial activities and trigger opsonization. Endometrium is a mucosal tissue that lines the mammalian uterus and is indispensable for the establishment of a successful pregnancy. The lymphocytes of B cell lineage are a minority in the human cycling endometrium. Human endometrial B cells have therefore been understudied so far. However, the disorders of the female reproductive tract, including chronic endometritis and endometriosis, have highlighted the importance of further research on the endometrial B cell lineage. This review aims to revisit lymphopoiesis, maturation, commitment, and survival of B cells, shedding light on their physiological and pathological implications in the human endometrium. Full article

Diethylstilbestrol (DES) is a synthetic non-steroidal estrogen, which was widely used to prevent preterm birth and abortion from the 1940s to the 1970s. DES can increase the incidence of infertility, the abnormal reproductive tract, and autoimmune diseases. However, the mechanism underlying DES on early pregnancy in mice is unclear. This study evaluated the effects of DES on early pregnancy in mice, especially on uterine receptivity and decidualization. Newborn female mice were subcutaneously injected with 0.1 mg/kg DES, 1 mg/kg DES, or sesame oil as controls for 5 consecutive days. At 6 weeks old, these female mice were mated with 8–12-week-old fertile males to obtain pregnancy. The uteri of these mice were collected on days 4, 5, and 8 of pregnancy for further analysis. On days 5 and 8 of pregnancy, the number of implantation sites in 0.1 mg/kg DES group is similar to the control group, while almost no implantation sites are detected in the 1 mg/kg DES group. On day 4 of pregnancy, there was no significant difference in uterine receptive molecules between the control group and the 0.1 mg/kg DES group. However, the levels of uterine receptive molecules in the 1 mg/kg DES group are abnormal. In addition, 6 μM DES significantly inhibits mouse in vitro decidualization. The excessive activation of pyroptosis may lead to pregnancy failure. The pyroptosis-related molecules in the 1 mg/kg DES group were significantly up-regulated, suggesting that DES may contribute to pregnancy failure by over-activating pyroptosis. Full article