Search Results (278)

The aim of this study was to evaluate the effects of a gonadotropin-releasing hormone analogue (GnRHa), administered through injections or with sustained-release implants, on spermiation and sperm quality in thicklip grey mullet, Chelon labrosus. Male broodstock transferred from extensive lagoons were randomly allocated to three treatment groups: (a) weekly saline injections (Saline-INJ), (b) weekly GnRHa injections (10 μg kg⁻¹ bw; GnRHa-INJ), and (c) a single GnRHa EVAc implant (50 μg kg⁻¹ bw; GnRHa-IMP). Males were maintained with females under the same treatment protocols and allowed to spawn. Sperm condition, density, motility, duration of motility, and androgen levels were evaluated weekly at five sampling points (Days 0, 7, 14, 21, and 28). All males exhibited complete spermiation during the first two weeks (Days 0 and 7), followed by a gradual decline throughout the rest of the study (Days 14 and 21). This pattern of decline was not as evident in the groups treated with GnRHa, especially in the GnRHa-INJ group. Sperm density, motility, and motility duration varied strongly over time; however, no significant differences were observed among treatments. GnRHa treatment prolonged the spermiation period and delayed its seasonal decline without significantly altering sperm quality. These results may enable more frequent sperm collection and greater sperm availability, as inferred from the spermiation condition (SCI) and qualitative observations. Full article

The perception that hormonal contraception causes weight gain is a general belief that frequently hinders the initiation and continuation of effective family planning. This narrative review analyses data from Cochrane systematic reviews and recent pharmacogenomic studies to separate patient perception from metabolic reality. Analysis of high-quality data, including Cochrane systematic reviews, indicates that the association between Combined Hormonal Contraceptives (CHCs)—including oral pills, the transdermal patch, and the vaginal ring—and weight gain is not supported by consistent high-quality evidence. Placebo-controlled trials demonstrate that these methods are weight-neutral on average. Perceived weight increases in CHC users are likely mediated in part by fluid retention linked to the estrogenic stimulation of the Renin–Angiotensin–Aldosterone System (RAAS), rather than adipose tissue accumulation. Conversely, Depot Medroxyprogesterone Acetate (DMPA) represents a verified clinical risk for weight gain, showing a demonstrated clinical association with significant fat mass accumulation. Hypothesized biological mechanisms for this increase include hypothalamic appetite stimulation and glucocorticoid-like activity. The etonogestrel implant occupies a complex middle ground. While population-level data suggests weight neutrality, recent exploratory pharmacogenomic research has identified a specific variant in the Estrogen Receptor 1 (ESR1) gene. For the minority of women carrying this variant, the implant may trigger clinically significant weight gain, suggesting a biological basis for their subjective experience despite statistical evidence. Ultimately, the persistence of the weight gain concern is fueled by the nocebo effect and the misattribution of natural age-related weight trajectories to contraceptive use. Full article

Endometriosis is a chronic hormone-responsive disorder linked to infertility, usually characterized by the presence of ectopic endometrium in the pelvis that disrupts local homeostasis. Advances in single-cell “omic” methods have revealed the remarkable cellular diversity within the eutopic endometrium and endometriosis lesions, uncovering distinct populations with unique transcriptional and functional profiles. These studies have highlighted alterations in immune cell subsets, stromal and epithelial cell signaling, and intercellular communication networks that collectively impair oocyte quality, embryo development, and endometrial receptivity in women with endometriosis. By dissecting the molecular signatures of individual cells, single-cell approaches provide insights into the mechanisms driving persistent inflammation, impaired angiogenesis, hormonal dysregulation, and immune dysfunction in endometriosis. Importantly, emerging evidence indicates that infertility and reduced assisted reproductive technology (ART) success in endometriosis reflect coordinated cellular and molecular dysfunction rather than solely anatomical abnormalities. Single-cell analyses of oocytes, granulosa cells, and endometrial cell populations demonstrate transcriptomic and epigenetic alterations affecting mitochondrial function, steroid metabolism, immune regulation, and implantation-related signaling pathways, offering a biological explanation for impaired implantation and variable ART outcomes. Integration of these findings with clinical observations supports the concept that endometriosis-associated reproductive failure arises from combined ovarian and endometrial defects detectable at the cellular level. Current single-cell studies highlight candidate biomarker signatures with the potential to improve patient stratification, predict ART outcomes, and guide individualized therapeutic strategies. As these discoveries are refined into clinically applicable biomarker panels, single-cell technologies are poised to bridge mechanistic understanding and precision reproductive medicine, enabling more personalized management approaches aimed at restoring reproductive competence in patients with endometriosis. Full article

The peri-implantation window is a tightly regulated temporal phase during which the human endometrium undergoes coordinated molecular remodeling to establish receptivity. MicroRNAs (miRNAs) contribute to implantation-related processes; however, whether dynamic endometrial regulatory signals are functionally reflected in circulation within a defined temporal framework remains unclear. We hypothesized that although individual miRNA identities differ between endometrial tissue and plasma, temporally regulated miRNAs in both compartments may exhibit overlap at the level of enriched biological pathways during the peri-implantation window. To test this hypothesis, we performed time-resolved small RNA sequencing on paired endometrial and plasma samples collected from 62 participants across progesterone exposure days P+3 to P+7 in hormonally controlled cycles. Temporal modeling identified 27 dynamic miRNAs in endometrial tissue and 17 in plasma (FDR < 0.05). Despite limited overlap at the individual miRNA level, functional enrichment analysis revealed recurrent overlap in apoptosis-, cell cycle-, aging-, inflammatory-, and metabolic-related pathways across compartments. Four miRNAs exhibited concordant directional temporal trends between tissue and plasma with moderate correlation coefficients. These findings suggest that dynamic miRNA-associated enrichment patterns during the peri-implantation window may exhibit pathway-level overlap despite divergence in specific molecular identities. This temporally aligned integrative framework provides a pathway-centric perspective for interpreting cross-compartment miRNA-associated temporal patterns and supports a hypothesis-generating systems-level view of human implantation biology. Full article

Three-dimensional (3D) organoid and co-culture models have emerged as transformative tools for studying human endometrial function, implantation, and placental development, overcoming key limitations of animal and two-dimensional in vitro systems. This review synthesises available information of recent advances in endometrial epithelial organoids (EEOs), trophoblast organoids (TBOs), and increasingly complex co-culture platforms incorporating stromal, vascular, and trophoblast compartments to model epithelial–stromal crosstalk, decidualisation, angiogenesis, and embryo implantation. Emerging developments include assembloid systems, synthetic and semi-synthetic extracellular matrices, and microfluidic organ-on-a-chip technologies that enable long-term culture, hormonal responsiveness, and patient-specific modelling. These approaches have recapitulated key features of the mid-secretory endometrium, placental villous architecture, trophoblast differentiation, and early implantation events while revealing disease-associated dysfunctions in conditions such as endometriosis, adenomyosis, polycystic ovarian syndrome, and endometrial cancer. Despite significant progress, current models remain limited by incomplete cellular diversity, polarity constraints, and challenges in fully modelling immune and vascular interactions. Collectively, emerging 3D organoid and co-culture systems provide physiologically relevant platforms to interrogate human reproductive biology, elucidate mechanisms underlying implantation failure and placental disease, and support the development of personalised therapeutic strategies to improve reproductive outcomes. Full article

Infertility affects a substantial proportion of women of reproductive age and is frequently associated with impaired endometrial receptivity. Successful implantation depends on tightly regulated hormonal, immune, apoptotic, and stress-response pathways within the endometrium. This pilot study aimed to evaluate the expression and distribution of granulocyte colony-stimulating factor (G-CSF), bone morphogenetic proteins 2/4 (BMP-2/4), heat shock protein 70 (HSP-70), apoptosis, progesterone, estrogen, and pentraxin-3 (PTX-3) in the endometrium of infertile women across different menstrual cycle days. A descriptive cross-sectional analysis was performed on endometrial tissue samples obtained from six infertile women aged 21–49 years at various menstrual cycle days. Routine histology, immunohistochemistry, TUNEL assay, and chromogenic in situ hybridization were used to assess tissue morphology, protein expression, apoptotic activity, and PTX-3 gene expression. Quantitative evaluation was applied to immunohistochemical markers and apoptosis, while PTX-3 expression was assessed semi-quantitatively. G-CSF expression showed low-to-moderate levels with a relative mid-cycle increase. BMP-2/4 demonstrated the highest overall positivity across most cycle days, with marked inter-sample variability. HSP-70 exhibited pronounced cycle-dependent variability. Apoptotic activity increased toward mid-to-late cycle days. Progesterone and estrogen positivity was heterogeneous and limited to selected cycle days. PTX-3 gene expression was highest during mid-cycle days and decreased toward later phases. No clear association with patient age was observed. Conclusions: The findings indicate distinct and cycle-dependent patterns of immune, morphogenetic, apoptotic, hormonal, and inflammatory markers in the endometrium of infertile women. These results highlight the dynamic nature of endometrial regulation and suggest that altered temporal coordination of these pathways may contribute to impaired endometrial receptivity. Full article

Primary Failure of Eruption (PFE) is a disorder characterized by aberrant tooth eruption, in which one or more teeth fail to follow the physiological eruptive pathway and remain partially or completely embedded within the bone or soft tissues. Although the etiopathogenesis of PFE is not yet fully elucidated, several contributing factors have been identified, including genetic alterations, hormonal disturbances, and systemic conditions. An expanding body of evidence points to the centrality of genetic determinants in the etiopathogenesis of PFE, supporting its occurrence in both syndromic contexts and non-syndromic presentations. Non-syndromic forms are closely related to heterozygous variants in the Parathyroid Hormone 1 Receptor (PTH1R) gene, located on chromosome 3p21, which encodes a receptor essential for the regulation of bone and dental growth and development. In most cases, pathogenic variants result in a non-functional receptor. To date, a substantial number 50 PTH1R variants have been documented in individuals exhibiting a phenotype consistent with PFE, underscoring the central involvement of this gene in the disorder’s molecular basis. Advances in understanding the genetic contribution to PFE emphasize the need for early diagnosis, as timely identification of the condition can prevent secondary dental complications and reduce reliance in adulthood on invasive orthodontic or surgical interventions, including extractions, orthognathic surgery, and implant-supported rehabilitation. This review aims to provide a comprehensive analysis of the spectrum of PTH1R variants implicated in PFE, examining genotype–phenotype correlations and their implications for diagnostic strategies and clinical management. Full article

Background and Objectives: Hypocalcemia due to hypoparathyroidism (HypoPTH) is the most common complication following thyroid surgery, typically resulting from iatrogenic removal, tissue damage, or compromised vascularization of the parathyroid glands. Patients with persistent HypoPTH are at risk for long-term complications such as osteoporosis, cardiac dysfunction, and renal impairment. Lifelong regulation of calcium levels is therefore essential to prevent morbidity and mortality associated with these complications. In this study, we aimed to evaluate the functional engraftment efficacy of 3D bioprinted human parathyroid tissue constructs in a xenograft model in vivo. Materials and Methods: Primary cells obtained from freshly excised human parathyroid tissue specimens were isolated and 3D bioprinted using alginate-based bioink. The bioprinted tissue constructs were implanted into CD1 athymic mice. Histopathological evaluation of the grafted constructs was performed at different time points. In addition, surface calcium-sensing receptor (CaSR) expression was assessed by immunofluorescence as an indicator of functional parathyroid tissue engraftment. Results: The presence of CaSR on parathyroid cells within the 3D-printed scaffolds confirmed the persistence of functional parathyroid cells following implantation. In tissue samples obtained during the first, second, and third weeks after implantation, CaSR positivity was consistently observed in the parathyroid cells. However, at the three-month follow-up, the pores within the scaffolds were found to be filled with calcified material and replaced by fibrotic tissue. At this stage, the absence of parathyroid hormone (PTH) expression indicated a loss of functional activity in the grafted biomaterial. Conclusions: Human primary parathyroid cells were successfully isolated, and a functional, hormone-active parathyroid tissue substitute was developed ex vivo using 3D-bioprinted hydrogel scaffolds combined with autologous cells. Although short-term functional engraftment was achieved, long-term graft viability and hormonal activity were limited due to scaffold degradation and fibrosis. These findings indicate the necessity for further improvement in scaffold biocompatibility to enhance the therapeutic potential of 3D-bioprinted parathyroid tissue constructs for in vivo applications. Full article

Objectives: The peritoneal cavity is a cavity outside the bloodstream, with a specific hormonal, immunological and microbiological micro-environment distinct from plasma. The mesothelial cells lining the peritoneal cavity react within seconds to minor trauma, such as blood, with retraction, acute inflammation and later inflammation. This mesothelial cell retraction exposes the basal membrane, facilitating the implantation of tumour cells. Acute inflammation enhances adhesion formation after surgery and causes pain. The aim of the review was to check the hypothesis that retrograde menstruation, occurring in most women, is sufficient to cause some peritoneal irritation. Design: A systematic review of menstrual C-reactive protein (CRP) concentrations, a non-specific marker of peritoneal inflammation (PROSPERO ID 536306). Results: All articles (n = 8) showed a variable increase in CRP concentrations during the menstrual and early follicular phase of 80 ± 36%. Conclusions: CRP concentrations are slightly increased during menstruation and the early follicular phase. This increase is likely due to retrograde menstruation, causing mesothelial cell retraction and acute pelvic inflammation. It seems logical that mesothelial cell retraction facilitates endometrial cell implantation and accounts for the anatomical distribution of endometriosis lesions. Acute pelvic inflammation may enhance postoperative adhesion formation. Full article

Background/Objectives: Sufficient preconception vitamin D may promote robust implantation and higher human chorionic gonadotropin (hCG) levels, potentially increasing nausea and vomiting in pregnancy. We assessed associations between maternal serum 25-hydroxyvitamin D (25(OH)D) at both preconception and 8 weeks’ gestation with nausea and vomiting during early pregnancy. We hypothesized that women with sufficient vitamin D status or those who improved their levels in early gestation, would have higher odds of nausea and vomiting compared to women who were deficient or insufficient. Methods: This secondary analysis of the randomized EAGeR Trial included women with 1–2 prior pregnancy losses and 25(OH)D measured at preconception (n = 774) and 8 weeks’ gestation (N = 641). Nausea and vomiting were captured via medical records and daily symptom diaries. 25(OH)D was categorized as deficient (≤20 ng/mL), insufficient (21–29 ng/mL), or sufficient (≥30 ng/mL). Logistic regression and generalized estimating equations (GEE) estimated associations. Results: Women who improved from deficient/insufficient preconception to sufficient by 8 weeks had higher odds of nausea and vomiting in early pregnancy compared to those remaining sufficient (aOR: 1.71; 95% CI: 1.12, 2.61). Conversely, those remaining deficient/insufficient (aOR: 0.34; 95% CI: 0.20, 0.60) or declining to deficiency (aOR: 0.44; 95% CI: 0.22, 0.87) had lower odds. In longitudinal models, deficiency was associated with lower odds of daily vomiting (aOR: 0.54; 95% CI: 0.28, 1.04), though estimates were imprecise. Conclusion: Dynamic changes in vitamin D status from preconception to early pregnancy appear to be associated with nausea and vomiting in early pregnancy. Improvement of sufficiency increased emesis odds, while persistent deficiency correlated with fewer symptoms. These findings suggest vitamin D may be associated with nausea and vomiting through hormonal or placental signaling mechanisms in early gestation. Full article

Three-dimensional (3D) cell culture models provide physiologically relevant systems that mimic the native endometrial environment better than 2D models and offer reliable platforms to study embryo implantation and maternal–embryo interactions. One widely used 3D culture model is the generation of spheroids. However, standardized and reproducible methods for generating uniform spheroids from trophoblast and endometrial stromal cells are limited. In this study, we established and validated a robust protocol for spheroid formation using human trophoblast (HTR8/SVneo, JEG3) and endometrial stromal (St-T1b, tHESC) cell lines. The protocol was further extended to generate spheroids from decidualized tHESC, representing a novel approach that closely reflects the receptive endometrial environment. Key parameters, including cell concentration and methyl cellulose supplementation, were optimized to produce compact and homogeneous spheroids. Spheroid formation was monitored at defined intervals (0, 8, 24, 32, and 48 h), and decidualized spheroids were assessed up to 72 h. Long-term cryopreservation over 11 months demonstrated high post-thaw viability across all spheroid types, as confirmed by Calcein-AM staining. This standardized workflow provides a reliable 3D model incorporating hormonally primed stromal cells and offers a practical platform to investigate the mechanisms underlying normal and trophoblast invasion in vitro. Full article

A significant and persistent issue in assisted reproduction is recurrent implantation failure (RIF), which is often observed even after the transfer of embryos of high morphological and/or genetic quality. Accumulating data suggest that exposure to chemicals with endocrine-disrupting effects (EDCs) may be associated with adverse implantation outcomes. Many environmentally widespread substances have the potential to interfere with the regulation of the endocrine system, affecting critical mechanisms involved in implantation, such as endometrial receptivity, steroid hormone receptor signaling, immune tolerance at the maternal–fetal interface, and the epigenetic regulation of genes that are essential for successful implantation. Experimental studies have shown that exposure to EDCs can alter gene expression in the endometrium, inflammatory pathways, and the dynamics of early embryonic development, while clinical and epidemiological data have associated increased levels of EDCs in the body with lower implantation rates in assisted reproductive technology (ART) cycles. This narrative review examines the implications of these findings in reproductive medicine, summarizes recent experimental and clinical data, and highlights the molecular mechanisms linking exposure to endocrine disruptors with recurrent implantation failure. Recognizing environmental chemical exposure as a potentially modifiable risk factor may offer new perspectives for the prevention of RIF and the development of more personalized therapeutic strategies. Full article

Considering the present environmental concerns, nanomaterial-based methods should be applied to achieve the bioeconomic sustainability initiatives and climate change mitigation. Plants and plant extracts are one of the most underused biomass and bioactive ingredients resources. Moreover, nowadays crop loss is one of the main problems that the world faces, together with the depletion of natural resources, increasing population and limited arable land, leading to increased food scarcity and demand. To correctly attribute/use plant-based bioresources or to rapidly decide which farming operations should be performed before crop loss, we should be able to properly characterize plants or plant-based resources by the desired useful characteristics, such as (bio)chemical characteristics, rather than simply observing physical traits of plants (because, when these traits become visible, it may be too late for crop loss mitigation). Plant crops could be optimized, for example, using electrochemical methods that assess the nutrient uptake and nutrient use efficiency (NUE) or the oxidative stress burst encountered before crop loss, in order to improve crop yields and crop quality. Other different important analytes (such as hormones, pathogens, metabolites, etc.) or plant characteristics (such as genus, species, phylogenetic analysis, etc.) can be evaluated with these electrochemical sensors and methods. In the present review, we focus on the application of nanomaterials/nanotechnologies for the development of fast, accurate, accessible, cost-effective, sensitive and selective analytical electrochemical methods for the detection of different relevant biomolecules in plants or plant-related samples (plant extracts, plant cells, plant tissues, and/or plant-derived natural drinks/foods, as well as entire plants/plant parts), both in vivo vs. ex vivo and in situ vs. ex situ. This review systematically presents and critically discusses the outcomes of current electrochemical methods (both applied in the lab or as wearable/implantable sensors) and the future perspectives of these nanotechnology-based sensors, with an accent on wearable sensors for smart and precision agriculture, as real-world sensing technologies with significant practical impact. The novelty of this article is the abundance of electrochemical analytical parameters gathered and discussed, for such a large number of analyte categories. Full article

Background/Objectives: Progress in diagnostic and therapeutic strategies has resulted in an increasing prevalence of adults with congenital heart disease (ACHD), including those involving genetically determined syndromes. This study aimed to characterize prevalence, congenital phenotypes, heart failure (HF) stages, comorbidity burden, and current medical management of ACHD and concomitant genetically determined syndromes enrolled in a prospective HF-focused registry. Methods: The PATHFINDER-CHD Registry is a German-based (est. 2022) multicenter observational registry. This web-based platform consecutively tracks ACHD patients across the heart failure spectrum, including those with current or prior HF, as well as those at high structural or functional risk. HF stage was classified using a modified ACC/AHA scheme adapted for CHD; functional capacity was graded according to the Perloff classification. Baseline demographics, CHD anatomy, prior surgical/interventional treatment, cardiac and extracardiac comorbidities, and medication were collected from medical records. Results: Among 1987 enrolled ACHD, 107 (5.4%) had a genetic syndrome (n = 65, 60.7% women; mean age 33.5 ± 9.4 years; range 18–68). Most common syndromes were trisomy 21 (n = 49; 45.8%) and 22q11.2 deletion (n = 27; 25.2%); 31 patients (30.0) had rarer syndromes. Predominant CHD diagnoses were atrioventricular septal defect (n = 42, 39.3%), tetralogy of Fallot (n = 19, 17.8%), and pulmonary atresia with ventricular septal defect (n = 7, 6.5%). A systemic left ventricle was present in 102 (95.3%); 40 (37.4%) had primarily cyanotic CHD, and 7 (6.5%) an Eisenmenger physiology. Most patients (n = 71; 66.4%) had undergone definite surgical repair; 25 patients (23.3%) had at least one catheter intervention, including transcatheter valve implantation in 17 cases (15.9%). HF stage was mainly B (n = 30, 28.0%) or C (n = 75, 70.1%). Perloff functional class I/II was present in 97 (90.7%). Leading cardiac comorbidities included intrinsic aortopathy (n = 49, 45.8%), pulmonary arterial hypertension (n = 12, 11.2%), and arrhythmias (n = 10, 9.3%). Frequent extracardiac comorbidities were thyroid dysfunction (n = 34, 31.8%), kidney disease (n = 16, 15.0%), hyperuricemia (n = 13, 12.1%), and depression (n = 15, 14.0%). Pharmacotherapy was used in 66 patients (61.7%). Beta-blockers (n = 25, 23.4%) were common, while ACEi/ARB (n = 9, 8.4%), diuretics (n = 10, 9.3%), MRAs (n = 8, 7.5%), and SGLT2 inhibitors (n = 3; 2.8%) were infrequently prescribed; no patient received ARNI or digitalis. For targeted treatment of pulmonary arterial hypertension, phosphodiesterase-5 inhibitors (n = 7, 6.5%), endothelin receptor antagonists (n = 6, 5.6%), or prostacyclin analogues (n = 1, 0.9%) were used. As oral anticoagulants, vitamin K antagonists or direct oral anticoagulants (DOACs) were prescribed in 17 cases (15.9%). Forty-one patients (38.3%) received thyroid hormone replacement. Conclusions: Syndromic ACHD constitute a small but clinically high-risk subgroup within an HF-oriented registry, marked by complex CHD, substantial cardio–extracardiac multimorbidity (notably aortopathy, PAH, thyroid disease, renal dysfunction, depression), and low utilization of contemporary HF therapies. These data support specialized, interdisciplinary, longitudinal care pathways and prospective studies addressing outcomes and evidence-based HF management in syndromic ACHD. Full article

Endometriosis is a hormone-dependent gynecological disease manifested by cyclic pelvic pain and female infertility. Although many studies have shown that neoangiogenesis plays an essential role in the development of early endometriosis, the underlying pathophysiological mechanisms remain unclear. Recent evidence suggests that macrophages play an important role in the pathogenesis of endometriosis and that the hypoxia-inducible factor-1alpha (HIF-1α) may be involved, but when and how are largely unknown. Herein, we explore the role of macrophages in the early development of endometriosis using an in vivo subcutaneous implantation murine model. Upon depletion of macrophages, the subcutaneous injection of syngeneic endometrial material resulted in significant reduction in oxidative stress, endometriotic lesion size, and neovascularization. Likewise, inactivation of the lipid peroxidative gene Alox15 induced similar reduction in oxidative stress, lesion growth, and angiogenesis. Since HIF-1α is an important trigger of neoangiogenesis, we further administered a HIF-1α-specific inhibitor (PX-478) to our endometriotic model and further confirmed the same effects on the lesions. Taken together, these data suggest that an intact Alox15 pathway and HIF-1α signaling may play important roles in the macrophage-mediated oxidative stress and neovascularization of endometriosis in the early stages, suggesting anti-inflammation and antioxidation as potential therapeutic targets for the development of endometriosis. Full article