Search Results (267)

Leptin (LEP) is an adipocyte-derived cytokine that integrates nutritional status, metabolism, and reproduction in cattle, with particular relevance for modern high-producing dairy cows. In ruminants, LEP and its receptors are widely expressed in metabolic and reproductive tissues, including adipose tissue, liver, hypothalamus, pituitary, ovary, uterus, and placenta, where LEP modulates energy homeostasis, neuroendocrine function, and local tissue responses. Changes in circulating LEP concentrations during the transition period reflect changes in body fat reserve, insulin and GH-IGF-1 dynamics, thyroid hormones, and inflammation and contribute to coordinated metabolic adaptations supporting the onset of lactation. At the reproductive level, LEP influences the hypothalamic–pituitary–gonadal axis, affects the pulsatility of luteinizing hormone (LH) under nutritional stress, and exerts direct effects on ovarian steroidogenesis, folliculogenesis, oocyte competence, embryo development, and uterine immune function. New evidence also links LEP profiles to major peripartum disorders, including subclinical ketosis, insulin resistance, postpartum ovarian inactivity, and uterine inflammatory diseases, and emphasises its potential as part of a panel evaluating the risk of metabolic and reproductive disorders. Furthermore, polymorphisms within the bovine LEP gene and its signalling network have been associated with milk production, feed efficiency, body condition, and fertility traits, suggesting opportunities to incorporate markers into genomic selection schemes aimed at improving robustness and reproductive performance. This review summarises current knowledge on LEP biology in cattle, with an emphasis on dairy cows, and discusses perspectives on translating this information into practical tools for nutritional management, health monitoring, and genetic improvement in bovine production systems. Full article

Background/Objectives: Ultrasound elastography (UE) is a non-invasive imaging technique that evaluates tissue stiffness and may complement conventional ultrasound in the assessment of uterine diseases. This systematic review aimed to summarize the current evidence on the role of strain elastography (SE) and shear wave elastography (SWE) in the diagnosis and management of benign and malignant uterine pathologies. Methods: A systematic literature search of MEDLINE (PubMed) and Embase was performed to identify studies published between January 2018 and February 2026. Original studies evaluating UE in adenomyosis, uterine fibroids, cervical lesions, and endometrial pathologies were included. Data were qualitatively synthesized according to pathology type and elastographic technique. Results: Twenty studies met the inclusion criteria. In benign myometrial disorders, adenomyosis and uterine fibroids generally showed higher stiffness than normal myometrium, although differentiation between these entities was not always consistent across studies. In cervical disease, malignant and high-grade lesions typically demonstrated increased stiffness compared with benign or low-grade lesions. In endometrial pathology, endometrial carcinoma was generally associated with higher stiffness values than benign lesions and elastography also showed potential in assessing myometrial invasion. Across studies, UE demonstrated promising diagnostic performance, but substantial heterogeneity was observed in acquisition methods, parameters, and reported thresholds. Conclusions: UE appears to be a promising adjunct to conventional ultrasound for the evaluation of uterine pathologies. However, further standardized, large-scale studies are needed to define reproducible protocols and clinically applicable diagnostic thresholds. Full article

Arthrogryposis multiplex congenita (AMC) is a diverse group of conditions characterized by multiple joint contractures. Although individually rare, these disorders are estimated to affect 1 in 3000–5000 live births. Their common pathophysiological mechanism is fetal akinesia, a sustained reduction of fetal movement that may arise from intrinsic disturbances—such as central nervous system malformations, motor neuronopathies, neuropathies, neuromuscular junction defects, congenital myopathies, muscular dystrophies, or metabolic diseases—or from extrinsic factors including uterine constraint, maternal illness, infections, or toxic exposures. Reduced fetal motion leads to relatively uniform clinical manifestations, known as the fetal akinesia deformation sequence (FADS), which is characterized by craniofacial anomalies, pulmonary hypoplasia, growth restriction, and contractures. Currently, AMC is classified by clinical features, such as distal arthrogryposis or lethal congenital contracture syndromes. However, advances in molecular genetics have shown wide variability among conditions classified into the same category. Prognosis is widely variable, ranging from lethal perinatal forms to non-progressive mild conditions. This review discusses AMC etiologies from a topographic standpoint, considering the different levels of the motor system involved, by combining current clinical, genetic, and pathophysiological information. Full article

Endometriosis is a chronic, estrogen-dependent inflammatory disorder characterized by the ectopic implantation and persistence of endometrial-like tissue outside the uterine cavity. Despite its high prevalence and significant impact on quality of life, the pathogenesis of endometriosis remains incompletely understood and involves a complex interplay between hormonal dysregulation, immune dysfunction, and chronic inflammation. In recent years, growing evidence has highlighted the role of the microbiota as a potential modulator of these interconnected pathways. This review proposes an integrative framework in which the microbiota acts as a central modulator of immune–endocrine interactions in endometriosis, while synthesizing current evidence on underlying biological mechanisms. We discuss how alterations in the gut, vaginal, and endometrial microbiota contribute to disease pathophysiology through multiple mechanisms, including disruption of intestinal barrier integrity, activation of pro-inflammatory signaling pathways, immune dysregulation, and modulation of estrogen metabolism via the estrobolome. Microbial β-glucuronidase activity and enterohepatic recirculation of estrogens are explored as key processes linking gut dysbiosis to the hyperestrogenic environment characteristic of endometriosis. Furthermore, we review current pharmacological treatments and highlight their limitations, emphasizing the need for novel therapeutic strategies targeting upstream disease mechanisms. Emerging approaches, including probiotics, postbiotics, short-chain fatty acids, and dietary interventions, are discussed as promising adjunctive therapies capable of modulating inflammation, immune responses, and metabolic pathways. Although current evidence remains heterogeneous and largely derived from preclinical and observational studies, the microbiota emerges not only as a potential therapeutic target but as a key integrative node linking endocrine, immune, and metabolic pathways in endometriosis. Future research should focus on well-designed clinical trials to validate microbiome-based interventions and to define their role in personalized management strategies for endometriosis. Full article

Syringa oblata Lindl. (SOL) has long been used in traditional medicine for inflammatory disorders, yet its molecular actions in reproductive tract inflammation remain poorly defined. This study investigated the phytochemical composition and anti-inflammatory mechanisms of an aqueous SOL leaf extract using murine and cellular models of endometritis. Ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) analysis revealed major constituents including rutin, salidroside, and esculetin. In a murine model of bacterial endometritis induced by Escherichia coli and Staphylococcus aureus, SOL markedly attenuated uterine edema, epithelial disruption, leukocyte infiltration, and bacterial burden. Mechanistic analyses demonstrated that SOL suppressed the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88) axis and decreased the uterine expression of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). In lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, SOL and its principal monomers significantly reduced nitric oxide (NO) and reactive oxygen species (ROS) production both in the presence and absence of the TLR4 inhibitor TAK-242, suggesting additional modulation of redox-responsive pathways beyond canonical TLR4 signaling. Moreover, SOL selectively decreased the M1 macrophage marker CD86 in uterine tissue without altering CD163, consistent with partial inhibition of pro-inflammatory macrophage polarization. Collectively, these findings indicate that SOL exerts potent antimicrobial, anti-inflammatory, and antioxidative effects through coordinated regulation of innate immune signaling and macrophage activation, supporting its potential as a natural therapeutic candidate for inflammation-associated reproductive disorders. Full article

Background/Objectives: Ciliated epithelial change in endometrial lesions is a recognized morphologic finding, but its immunophenotypic correlates and biological significance remain insufficiently defined. We investigated whether endometrial lesions with ciliated epithelial change show reproducible immunohistochemical alterations across benign, premalignant, and malignant diagnostic categories. Methods: We performed a retrospective immunohistochemical study of 315 formalin-fixed paraffin-embedded eutopic uterine endometrial specimens (no endometriotic/ectopic lesions included) collected between 2019 and 2024 and distributed equally across seven diagnostic categories (n = 45 each): normal endometrium, endometrial polyp, hyperplasia with cystic/disordered glands, hyperplasia with crowded glands, atypical hyperplasia/EIN, endometrioid carcinoma, and serous carcinoma. Marker expression was quantified by digital image analysis and compared between lesions with and without ciliated epithelial change, including lesions with ciliated epithelial change showing cytological atypia. Results: Ciliated epithelial change (CEC) was identified in 86/315 cases (27.3%), including 41 cases (13.0%) with atypical CEC. In benign categories, lesions with CEC showed lower E-cadherin expression and higher β-catenin expression, including more frequent nuclear β-catenin localization. In carcinomas, these patterns were not recapitulated and instead showed an opposite or attenuated profile, supporting a context-dependent rather than linear model. Vimentin was consistently reduced in lesions with CEC across diagnostic categories. p53 and CD44 showed heterogeneous findings and were less informative than the adhesion- and phenotype-related markers. Conclusions: Endometrial lesions with CEC show reproducible, context-dependent immunohistochemical alterations, most consistently involving E-cadherin, β-catenin, and vimentin. In particular, nuclear β-catenin reactivity in this setting should not be interpreted as evidence of canonical Wnt-pathway activation in the absence of CTNNB1 sequencing or validated downstream readouts, and the carcinoma findings cannot be assigned to a specific TCGA/ProMisE molecular subgroup using immunohistochemistry alone. The observations should therefore be regarded as exploratory and warrant validation in studies incorporating molecular classification, direct ciliogenesis markers (FOXJ1, acetylated α-tubulin, basal body markers), and outcome data. Full article

Recurrent intrauterine adhesions (IUA) and refractory thin endometrium are associated with impaired endometrial regeneration, reduced implantation, and poor live birth outcomes. Regenerative therapy using mesenchymal stromal cells (MSCs) has shown promising results; however, factors associated with reproductive success remain unclear. In this prospective, single-centre, single-arm uncontrolled observational study, 35 women with recurrent IUA and thin endometrium (<7 mm) unresponsive to standard surgical and hormonal therapy received combined subendometrial and systemic administration of placenta-derived MSCs. The primary endpoint was live birth. Secondary endpoints included clinical pregnancy rate, time to pregnancy, endometrial thickness changes, uterine blood flow (resistance index, RI), and anti-Müllerian hormone (AMH) levels. Univariable logistic regression was performed to identify factors associated with live birth. Clinical pregnancy occurred in 13/35 patients (37.1%), and live birth was achieved in 11/35 (31.4%). Median time to pregnancy was 7 (5–8) months. Shorter duration of infertility or prior pregnancy loss (OR 1.55 per year; 95% CI 1.10–2.57), AFS stage I adhesions (OR 6.8; 95% CI 1.1–42; p = 0.04), lower baseline RI in uterine, arcuate and radial arteries, and higher baseline AMH (OR 2.59 per doubling; 95% CI 1.15–6.89) were significantly associated with live birth. Endometrial thickness increased after therapy but was not significantly associated with live birth. No severe adverse events were observed. Placenta-derived MSC therapy was followed by live birth in 31.4% of women with recurrent IUA and refractory thin endometrium. A shorter duration of reproductive disorders, less severe adhesions, lower baseline RI in uterine, arcuate and radial arteries, and higher AMH levels were associated with live birth after treatment and may help identify patients with a more favourable reproductive prognosis in future controlled studies. Full article

Preeclampsia is a pregnancy-specific multisystem disorder and a major cause of maternal and perinatal morbidity and mortality worldwide. This narrative review summarizes current evidence on the principal risk factors and pathophysiological mechanisms involved in its development. The disease is best explained by the two-stage model: in stage 1, inadequate trophoblast invasion and incomplete spiral artery remodeling lead to placental hypoperfusion, hypoxia, and oxidative stress; in stage 2, the hypoxic placenta releases anti-angiogenic and pro-inflammatory factors, including soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), which trigger systemic endothelial dysfunction and the maternal clinical syndrome. The review highlights the central role of angiogenic imbalance, immune dysregulation, and chronic inflammation in disease progression. Particular emphasis is placed on maternal risk factors such as primiparity, advanced maternal age, obesity, diabetes mellitus, chronic hypertension, multiple pregnancy, prior preeclampsia, genetic susceptibility, and epigenetic regulation. We also emphasize the contribution of microRNAs in relation to placental hypoxia, trophoblast invasion, angiogenesis, endothelial injury and microchimerism to the development of preeclampsia. The review also examines the role of T helper 1 (Th1)/Th2/Th17/regulatory T cells (Treg) imbalance and uterine natural killer cell dysfunction at the maternal–fetal interface. Improved understanding of these interconnected mechanisms may support earlier diagnosis, better risk stratification, and the development of targeted preventive and therapeutic strategies. Full article

Background and Objectives: To evaluate maternal characteristics associated with placenta previa in comparison with breech cesarean controls, as well as maternal and neonatal outcomes. Materials and Methods: A retrospective case–control study was conducted at the Hospital of Lithuanian University of Health Sciences, Kaunas Clinics (2015–2022). A total of 150 cases of placenta previa were compared with a control group of participants who underwent cesarean delivery due to fetal breech presentation without placenta previa. Results: In multivariable analysis, higher parity, prior cesarean delivery, in vitro fertilization, prior surgical termination of pregnancy, and prior uterine surgery were independently associated with placenta previa compared with breech cesarean controls. Maternal complications were significantly more frequent in the placenta previa group and included placenta accreta spectrum disorders, second- and third-trimester hemorrhage, postpartum hemorrhage, and increased need for blood transfusion. The most severe outcomes, including cesarean hysterectomy, occurred exclusively in cases complicated by placenta accreta spectrum disorders. Neonatal outcomes in the placenta previa group were characterized by higher rates of preterm birth, low Apgar scores, and birth weight < 2500 g. Adverse neonatal outcomes were partly associated with earlier gestational age at delivery. However, placenta previa remained associated with low Apgar score after adjustment. Conclusions: Compared with breech cesarean controls, placenta previa was associated with multiple maternal characteristics, including higher parity, prior cesarean delivery, in vitro fertilization, prior surgical termination of pregnancy, and prior uterine surgery. The condition is linked to increased maternal hemorrhagic morbidity, particularly in cases complicated by placenta accreta spectrum disorders, as well as adverse neonatal outcomes mainly related to prematurity. These findings highlight the importance of careful antenatal monitoring and delivery planning in specialized centers. Full article

Background/Objective: Asherman syndrome is an acquired intrauterine adhesive disorder associated with menstrual abnormalities, infertility, recurrent pregnancy loss, and adverse reproductive outcomes. Data from Latin American tertiary referral centers remain limited. To characterize clinical history, classification, hysteroscopic management strategies, and anatomical and reproductive outcomes in a single cohort of Mexican women with Asherman syndrome. Methods: This retrospective cohort study included women identified through institutional electronic records between July 2016 and December 2023 with a diagnosis of Asherman syndrome and analyzable hysteroscopic records. Women were followed for twelve months. Recurrence was defined as hysteroscopic evidence of intrauterine adhesions during follow-up. Among women with follow-up hysteroscopy, two-sided Fisher’s exact tests were used to calculate odds ratios and 95% confidence intervals. Results: Fifty-four women were analyzed. A prior uterine procedure was documented in 44 women (81.5%), with sharp curettage in 35 (64.8%). The most common reasons for consultation were secondary infertility (29.6%), abnormal uterine bleeding (27.8%), primary infertility (20.4%), and recurrent pregnancy loss (13.0%). Disease severity was classified as mild in 30 women (55.6%), moderate in 11 (20.4%), and severe in 7 (13.0%). Hysteroscopic intervention was predominantly performed with cold knife adhesiolysis (83.3%). Twelve-month follow-up hysteroscopy was performed in 38 women (70.4%); recurrence was identified in 30 (55.6%). Among the 34 women with reproductive intent, 12 achieved a live birth, corresponding to a live birth rate of 35.3%. Conclusions: Prior uterine instrumentation, particularly sharp curettage, was the most frequent antecedent. Recurrence remained common despite surgical management, highlighting the need for standardized postoperative surveillance and preventive strategies. Full article

Female infertility affects millions of women worldwide and is frequently caused by ovulatory disorders and uterine pathologies. Among these, endometrial abnormalities play a central role, especially in cases of embryo implantation failure during assisted reproductive techniques (ARTs). Endometrial receptivity, the period during which the endometrium prepares to receive and support embryo implantation, is a complex process regulated by essential morphological, molecular, and immunological changes necessary for a successful pregnancy. This review examines the mechanisms that govern endometrial receptivity and investigates the dysfunctions that may compromise this phase. In particular, it focuses on key biomarkers of receptivity, such as estrogen receptor-alpha (ERα), integrins, and uterine immune cells, which are crucial for endometrial preparation. It provides an in-depth understanding of female reproductive physiology and the main indicators to optimize embryo transfer at the most opportune time during the menstrual cycle within medically assisted reproductive techniques. Furthermore, it explores innovative approaches, such as immunomodulation and mesenchymal stem cell therapy, which are opening new diagnostic and therapeutic horizons, offering hope to many couples facing reproductive challenges. Full article

Paroxetine, a selective serotonin reuptake inhibitor commonly used to treat various psychiatric disorders, may adversely affect female reproductive function. Although apigenin has been shown to ameliorate reproductive abnormalities and ovarian dysfunction, its effect on paroxetine-induced reproductive toxicity in females remains unclear. Therefore, this study investigated the potential protective effects of apigenin against paroxetine-induced reproductive alterations in female rats. Female rats with regular estrous cycles were randomly assigned to four groups (n = 9 per group): control, apigenin, paroxetine, and paroxetine + apigenin. The rats received saline, apigenin (20 mg/kg), paroxetine (10 mg/kg), or their combination by oral gavage once daily for about 29 consecutive days. Compared with paroxetine treatment alone, apigenin co-administration restored decreased serum anti-Müllerian hormone (AMH) levels, enhanced PAS reactivity in the zona pellucida, reduced ovarian iNOS immunoreactivity, increased follicle and corpus luteum numbers, and increased ovarian VEGF immunoreactivity. However, apigenin administration alone was associated with reduced testosterone levels and alterations in certain ovarian and uterine histological features in female rats. In conclusion, the findings suggest that apigenin may ameliorate paroxetine-induced reproductive alterations in female rats by modulating AMH levels, follicle and corpus luteum numbers, and ovarian histochemical and molecular parameters. Full article

Background/Objectives: Botanical supplements are increasingly investigated for their potential to address women’s health concerns. Compounds that modulate progesterone receptor (PR) signaling may help manage gynecologic disorders such as endometriosis, uterine hyperplasia, and preterm birth. Because PR ligands often cross-react with the glucocorticoid receptor (GR), this study examined two botanical compounds, paeoniflorin from Paeonia lactiflora (white peony root) and isoorientin from Vitex agnus-castus (chasteberry), that were identified as modulators of GR or PR signaling. Methods: Luciferase reporter assays were performed in OVCAR5, Ishikawa PR-B, and T47D A1-2 cells to evaluate GR and PR signaling. GR target gene expression was measured by qPCR. A receptor binding assay and computational docking were used to assess interaction with GR. Adipogenesis was evaluated in 3T3-L1 cells using Oil Red O staining and FABP4 protein expression by Western blot. Results: Paeoniflorin and isoorientin inhibited dexamethasone-induced GR signaling in OVCAR5 and Ishikawa PR-B cells. In T47D A1-2 cells, a variant of T47D engineered to express GR, both compounds blocked luciferase induction stimulated by progesterone; this effect was not observed in the parental line that expresses PR but lacks GR. In OVCAR5 cells, paeoniflorin or isoorientin combined with dexamethasone downregulated GILZ and DUSP1/MKP1 mRNA. Isoorientin directly bound GR, and computational analysis supported potential binding poses. Both compounds also reduced lipid accumulation during 3T3-L1 adipocyte differentiation and decreased FABP4 expression, consistent with GR antagonist activity and reduced adipogenesis. Conclusions: These findings identify paeoniflorin and isoorientin as botanical modulators that suppress GR signaling and limit GR-dependent adipogenic responses across multiple cell-based models under controlled in vitro conditions. Full article

Background and Objectives: Endometriosis is a chronic, estrogen-dependent disorder characterized by the presence of functional endometrial tissue, comprising both glandular and stromal components, located outside the uterine cavity, affecting approximately 6–10% of women of reproductive age and up to 30–50% of those with infertility. Increasing evidence indicates that endometriosis is not solely a localized gynecological condition but rather a systemic inflammatory and immune-mediated disease. Chronic inflammation and immune dysregulation contribute to disease progression and may impair reproductive function. This review aims to analyze the current evidence regarding the inflammatory and immunological mechanisms underlying endometriosis and to evaluate their impact on reproductive dysfunction and assisted reproductive technology (ART) outcomes. Materials and Methods: A comprehensive narrative review was conducted using major scientific databases, including PubMed, Scopus, and Web of Science. Relevant articles published in the last decade were selected using keywords such as “endometriosis”, “inflammation”, “immune response”, “cytokines”, and “ART outcomes”. Both clinical and experimental studies were included to assess the relationship between inflammatory markers, immune alterations, and reproductive performance. Results: Endometriosis is associated with elevated levels of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α), as well as increased oxidative stress and altered peritoneal microenvironment. Immune dysfunction is characterized by activated macrophages, decreased natural killer (NK) cell cytotoxicity, and an imbalance in T-cell populations. These alterations negatively affect oocyte quality, fertilization, embryo development, and endometrial receptivity. Emerging biomarkers such as IL-6, TNF-α, and CA-125 show potential in predicting disease severity and ART outcomes, although their clinical utility remains under investigation. Conclusions: Endometriosis should be regarded as a systemic immuno-inflammatory disorder with significant implications for reproductive health. The interaction between chronic inflammation and immune dysregulation plays a central role in infertility and suboptimal ART outcomes. Further research is required to validate reliable biomarkers and develop targeted therapeutic strategies to improve reproductive success in affected patients. Full article

Background/Objectives: Adenomyosis is a common disorder of the uterus in those of reproductive age. Robotic-assisted surgery has been adopted to address the technical challenges of adenomyomectomy. This systematic review evaluated the current evidence regarding the feasibility, safety, and clinical outcomes of robotic-assisted conservative surgery for uterine adenomyosis. Methods: A systematic review of literature was performed on five databases, from the beginning to 21 December 2025, to identify studies reporting robotic-assisted uterus-sparing surgical approaches to adenomyosis. Data were collected on patient characteristics, surgical techniques used, pre- and post-operative pain, fertility outcomes, and complications. Risk of bias was evaluated using the ROBINS-I framework. Results: A total of 514 articles were found; six studies met the inclusion criteria. Most included studies were small and retrospective. The operative time ranged from 279 to 147 min. Mean blood loss ranged between 25 and 296 mL with a low rate of conversion and perioperative complications. Dysmenorrhea improved after surgery as reflected by the post operative visual analog scale pain score and serum CA-125 level. Few reproductive data were collected about successive spontaneous pregnancies. Risk of bias was serious or moderate in all studies included. Conclusions: Robotic-assisted conservative surgery for adenomyosis may represent a feasible and safe option for women with symptomatic adenomyosis who wish preserve the uterus, with a positive impact on patients’ symptoms. Large prospective, multicenter studies with standardized protocols and long-term follow-up are needed to clarify the real impact of robotic surgery in adenomyosis management. Full article