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19 pages, 6853 KiB  
Article
Metabolomic and Molecular Mechanisms of Glycerol Supplementation in Regulating the Reproductive Function of Kazakh Ewes in the Non-Breeding Season
by Ying Nan, Baihui Jiang, Xingdong Qi, Cuifang Ye, Mengting Xie and Zongsheng Zhao
Animals 2025, 15(15), 2291; https://doi.org/10.3390/ani15152291 - 5 Aug 2025
Abstract
The activation mechanism of the reproductive axis in Kazakh ewes during the non-breeding season was explored by supplementation with glycerol complex (7% glycerol + tyrosine + vitamin B9). The experiment divided 50 ewes into five groups (n = 10). After 90 days [...] Read more.
The activation mechanism of the reproductive axis in Kazakh ewes during the non-breeding season was explored by supplementation with glycerol complex (7% glycerol + tyrosine + vitamin B9). The experiment divided 50 ewes into five groups (n = 10). After 90 days of intervention, it was found that significant changes in serum DL-carnitine, N-methyl-lysine and other differential metabolites were observed in the GLY-Tyr-B9 group (p < 0.05, “p < 0.05” means significant difference, “p < 0.01” means “highly significant difference”). The bile acid metabolic pathway was specifically activated (p < 0.01). The group had a 50% estrus rate, ovaries contained 3–5 immature follicles, and HE staining showed intact granulosa cell structure. Serum E2/P4 fluctuated cyclically (p < 0.01), FSH/LH pulse frequency increased (p < 0.01), peak Glu/INS appeared on day 60 (p < 0.05), and LEP was negatively correlated with body fat percentage (p < 0.01). Molecular mechanisms revealed: upregulation of hypothalamic kiss-1/GPR54 expression (p < 0.01) drove GnRH pulses; ovarian CYP11A1/LHR/VEGF synergistically promoted follicular development (p < 0.05); the HSL of subcutaneous fat was significantly increased (p < 0.05), suggesting involvement of lipolytic supply. Glycerol activates the reproductive axis through a dual pathway—L-carnitine-mediated elevation of mitochondrial β-oxidation efficacy synergizes with kisspeptin/GPR54 signalling enhancement to re-establish HPO axis rhythms. This study reveals the central role of metabolic reprogramming in regulating seasonal reproduction in ruminants. Full article
(This article belongs to the Section Small Ruminants)
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15 pages, 357 KiB  
Article
Apalutamide Monotherapy in Metastatic Hormone-Sensitive Prostate Cancer: A Viable Alternative to First-Generation Anti-Androgen Agents to Avoid the Flare Phenomenon and an Effective Treatment for Achieving Early PSA Response
by Gaetano Facchini, Andrea D’Arienzo, Antonella Nicastro, Fabiano Flauto, Michela Izzo, Liliana Montella, Filippo Riccardo, Giovanni Maria Fusco, Francesco Trama, Giovanni Di Lauro, Giuseppe Di Costanzo, Anna Giacoma Tucci, Francesca Iasiello, Lorena Di Lorenzo, Salvatore Maddaluno, Carmela Liguori, Rita Assante di Cupillo, Paola Coppola, Angela Minissale, Maria Teresa Di Nardo, Luigi Formisano, Erika Martinelli, Giuliana Ciappina, Salvatore Pisconti, Massimiliano Berretta and Chiara Barracoadd Show full author list remove Hide full author list
Cancers 2025, 17(15), 2573; https://doi.org/10.3390/cancers17152573 - 5 Aug 2025
Viewed by 25
Abstract
Background/Objectives: Androgen deprivation therapy (ADT) is the mainstay of prostate cancer treatment, especially in advanced disease. In particular, the gonadotropin-releasing hormone agonists (aGnRH) reduce the production of gonadotropin and, therefore, of testosterone. In about 10% of patients, the non-pulsatile stimulation of GnRH receptor [...] Read more.
Background/Objectives: Androgen deprivation therapy (ADT) is the mainstay of prostate cancer treatment, especially in advanced disease. In particular, the gonadotropin-releasing hormone agonists (aGnRH) reduce the production of gonadotropin and, therefore, of testosterone. In about 10% of patients, the non-pulsatile stimulation of GnRH receptor initially causes a surge in LH and testosterone, defined as the “flare-up phenomenon”, leading to increased bone pain, spinal cord compression, bladder outlet obstruction and cardiovascular issues. To mitigate this effect, combining a first-generation antiandrogen agent (FGA) with aGnRH is recommended. However, second-generation anti-androgens, such as apalutamide, bind selectively and irreversibly to the androgen receptor (AR), exhibiting a more efficient inhibition of the AR pathway. Methods: This is a descriptive retrospective study of 27 patients (pts) with mHSPC, treated at a single center (“Santa Maria delle Grazie” Hospital in Pozzuoli, ASL Napoli 2 Nord, Italy) between June 2022 and April 2024. Patients received apalutamide monotherapy for 14 days followed by continuous combination with aGnRH plus apalutamide. Serum PSA and testosterone levels were measured at baseline, at day 14 (after 13 days of apalutamide monotherapy), at day 28 (after an additional 15 days of apalutamide plus a aGnRH), and at day 60. Results: PSA levels decreased from a mean of 45.2 (±63.1) ng/mL at baseline to a mean of 12.6 (±23.4) ng/mL at day 14 and to 3.3 ng/mL (±6.0) at day 28 of treatment. After 14 days of apalutamide monotherapy, 21 patients (77.8%) achieved a >50% PSA reduction and 4 (14.8%) a >90% PSA reduction. The number of patients with undetectable PSA was one (3.7%) at day 14, two (7.4%) at day 28, and nine (33.3%) at day 60. The mean serum testosterone levels were 6.56 (±4.46) ng/mL at baseline, 6.58 (±4.42) ng/mL at day 14, and 2.40 (± 3.38) ng/mL at day 28. No significant difference in PSA and testosterone level reduction during treatment emerged between subgroups of patients with low- vs. high-volume disease. Conclusions: Apalutamide alone is a viable option for mitigating the flare-up phenomenon, avoiding first generation anti-androgen therapy, and it can achieve rapid and deep biochemical control. Full article
(This article belongs to the Special Issue Advances in Therapeutic Strategies for Prostate Cancer)
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21 pages, 1359 KiB  
Article
Diagnostic Accuracy of Radiological Bone Age Methods for Assessing Skeletal Maturity in Central Precocious Puberty Girls from the Canary Islands
by Sebastián Eustaquio Martín Pérez, Isidro Miguel Martín Pérez, Ruth Molina Suárez, Jesús María Vega González and Alfonso Miguel García Hernández
Endocrines 2025, 6(3), 39; https://doi.org/10.3390/endocrines6030039 - 5 Aug 2025
Viewed by 178
Abstract
Background: Central precocious puberty (CPP), defined as the onset of secondary sexual characteristics before age 8 in girls, is increasingly prevalent worldwide. CPP is often caused by early activation of the HPG axis, leading to accelerated growth and bone maturation. However, the diagnostic [...] Read more.
Background: Central precocious puberty (CPP), defined as the onset of secondary sexual characteristics before age 8 in girls, is increasingly prevalent worldwide. CPP is often caused by early activation of the HPG axis, leading to accelerated growth and bone maturation. However, the diagnostic accuracy of standard bone age (BA) methods remains uncertain in this context. Objective: To compare the diagnostic accuracy of the Greulich–Pyle atlas (GPA) and Tanner–Whitehouse 3 (TW3) methods in estimating skeletal age in girls with CPP and to assess the predictive value of serum hormone levels for estimating chronological age (CA). Methods: An observational, cross-sectional diagnostic study was conducted, involving n = 109 girls aged 6–12 years with confirmed CPP (Ethics Committee approval: CHUC_2023_86; 13 July 2023). Left posteroanterior hand–wrist (PA–HW) radiographs were assessed using the GPA and TW3 methods. Anthropometric measurements were recorded, and serum concentrations of estradiol, LH, FSH, DHEA-S, cortisol, TSH, and free T4 were obtained. Comparisons between CA and BA estimates were conducted using repeated-measures ANOVA, and ANCOVA was applied to examine the hormonal predictors of CA. Results: Both GPA and TW3 overestimated CA between 7 and 12 years, with the GPA showing larger deviations (up to 4.8 months). The TW3 method provided more accurate estimations, particularly at advanced pubertal stages. Estradiol (η2p = 0.188–0.197), LH (η2p = 0.061–0.068), and FSH (η2p = 0.008–0.023) emerged as the strongest endocrine predictors of CA, significantly enhancing the explanatory power of both radiological methods. Conclusions: The TW3 method demonstrated superior diagnostic accuracy over GPA in girls with CPP, especially between 7 and 12 years. Integrating estradiol, LH, and FSH into BA assessment significantly improved the accuracy, supporting a more individualized and physiologically grounded diagnostic approach. Full article
(This article belongs to the Section Pediatric Endocrinology and Growth Disorders)
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14 pages, 397 KiB  
Article
Combination of Continuous Use of Oral Clomiphene Citrate with Injectable Gonadotropins for Ovarian Stimulation: A Single-Center Study
by Adamantia Kontogeorgi, Gkalia Tsangkalova, Panagiota Ambatzi, Ioannis Boutas, Eleftherios Meridis, Ioannis Gryparis, Dimitrios Kalaitzis, Angeliki Fenga, Melpomeni Peppa, Sophia Kalantaridou, Antonios Makrigiannakis and Minas Paschopoulos
Life 2025, 15(8), 1235; https://doi.org/10.3390/life15081235 - 4 Aug 2025
Viewed by 241
Abstract
Objective: This retrospective observational study evaluated the efficacy and safety of an ovarian stimulation protocol for embryo banking that involves continuous administration of clomiphene citrate (CC) in combination with gonadotropins, without the use of GnRH antagonists. Methods: Conducted at the Serum [...] Read more.
Objective: This retrospective observational study evaluated the efficacy and safety of an ovarian stimulation protocol for embryo banking that involves continuous administration of clomiphene citrate (CC) in combination with gonadotropins, without the use of GnRH antagonists. Methods: Conducted at the Serum IVF Clinic in Athens, Greece, the study included 250 women aged 25–45 who underwent IVF for embryo banking. The protocol involved administering 150 mg of CC daily from day 2 of the menstrual cycle until the day before hCG trigger, alongside 150 IU/day of Meriofert. Outcomes assessed included oocyte yield, fertilization rates, incidence of ovarian hyperstimulation syndrome (OHSS), and hormonal correlations. Comparative and regression analyses explored differences between age groups and predictors of success. Results: The protocol demonstrated a favorable safety profile with no cases of OHSS and yielded a mean of 10.25 oocytes per patient. Group analysis showed significantly more oocytes retrieved in women under 40 (mean: 12.5) versus those over 40 (mean: 8.43), while fertilization rates were paradoxically higher in the older cohort (59.16% vs. 30.68%, p < 0.0001). Regression models revealed basal FSH to be a significant inverse predictor of oocyte yield, but it was positively associated with fertilization rate. Continuous CC use effectively suppressed premature LH surges without compromising oocyte or embryo quality, allowing flexible and cost-effective stimulation with minimal monitoring. Conclusions: Continuous administration of clomiphene citrate in combination with gonadotropins presents a promising, antagonist-free ovarian stimulation protocol for embryo banking. The approach is economically efficient, reduces monitoring requirements, and maintains safety and effectiveness and is particularly notable in women over 40. Further studies are warranted to validate these findings and refine protocol mechanisms. Full article
(This article belongs to the Section Reproductive and Developmental Biology)
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17 pages, 1857 KiB  
Systematic Review
Effects of Pomegranate Juice on Androgen Levels, Inflammation and Lipid Profile in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis
by Vitória Silveira, Pamela Braz, Antonio Jose Grande, Tamy Colonetti, Maria Laura Rodrigues Uggioni, Gabriele da Silveira Prestes, Leonardo Roever, Valdemira Santina Dagostin and Maria Inês da Rosa
J. Clin. Med. 2025, 14(15), 5458; https://doi.org/10.3390/jcm14155458 - 3 Aug 2025
Viewed by 171
Abstract
Background/Objectives: Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder frequently associated with metabolic and inflammatory disturbances. Due to its antioxidant and anti-inflammatory properties, pomegranate juice has been proposed as a potential adjunctive therapy in managing PCOS. To evaluate the effects of pomegranate [...] Read more.
Background/Objectives: Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder frequently associated with metabolic and inflammatory disturbances. Due to its antioxidant and anti-inflammatory properties, pomegranate juice has been proposed as a potential adjunctive therapy in managing PCOS. To evaluate the effects of pomegranate juice on hormonal, inflammatory, and lipid parameters and body mass index (BMI) in women with PCOS. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted following PRISMA guidelines. Comprehensive searches were performed in electronic databases including Medline, Scopus, Web of Science, Cochrane CENTRAL, and Embase from inception to July 2025, using keywords and MeSH terms related to “polycystic ovary syndrome” and “pomegranate juice” without language restrictions. The primary outcomes were changes in serum testosterone, luteinizing hormone (LH), high-sensitivity C-reactive protein (hs-CRP), lipid profile parameters (HDL, LDL, triglycerides, and total cholesterol), and body mass index (BMI). Results: Four RCTs published between 2020 and 2023, encompassing 128 women with PCOS, were included. The meta-analysis revealed significant reductions in testosterone (MD: −0.05; 95% CI: −0.07 to −0.03; p < 0.0001; I2 = 0%, two studies, 85 participants) and hs-CRP (SMD: −0.85; 95% CI: −1.35 to −0.35; p = 0.0009; I2 = 20%, two studies, 85 participants), along with increases in HDL (MD: 6.21; 95% CI: 2.43 to 10.00; p = 0.001; I2 = 0%, two studies, 85 participants) and reductions in triglycerides (MD: −23.30; 95% CI: −45.19 to −1.42; p = 0.04; I2 = 0%, two studies, 85 participants). No significant changes were observed in LH, LDL, total cholesterol, or BMI. Conclusions: Pomegranate juice demonstrates promising effects as an adjunctive intervention in women with PCOS, improving androgen levels, inflammatory markers, and certain lipid parameters. Further long-term studies are needed to confirm these findings. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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17 pages, 3184 KiB  
Article
Polyphenol-Rich Extract of Chrysanthemum × morifolium (Ramat) Hemsl. (Hangbaiju) Prevents Obesity and Lipid Accumulation Through Restoring Intestinal Microecological Balance
by Xinyu Feng, Jing Huang, Lin Xiang, Fuyuan Zhang, Xinxin Wang, Anran Yan, Yani Pan, Ping Chen, Bizeng Mao and Qiang Chu
Plants 2025, 14(15), 2393; https://doi.org/10.3390/plants14152393 - 2 Aug 2025
Viewed by 245
Abstract
Chrysanthemum × morifolium (Ramat) Hemsl. (Hangbaiju), which has been widely consumed as a herbal tea for over 3000 years, is renowned for its biosafety and diverse bioactivities. This study investigates the impact of polyphenol-rich Hangbaiju extracts (HE) on high-fat diet-induced obesity in mice. [...] Read more.
Chrysanthemum × morifolium (Ramat) Hemsl. (Hangbaiju), which has been widely consumed as a herbal tea for over 3000 years, is renowned for its biosafety and diverse bioactivities. This study investigates the impact of polyphenol-rich Hangbaiju extracts (HE) on high-fat diet-induced obesity in mice. HE contains phenolic acids and flavonoids with anti-obesity properties, such as apigenin, luteolin-7-glucoside, apigenin-7-O-glucoside, kaempferol 3-(6″-acetylglucoside), etc. To establish the obesity model, mice were randomly assigned into four groups (n = 8 per group) and administered with either HE or water for 42 days under high-fat or low-fat dietary conditions. Administration of low (LH) and high (HH) doses of HE both significantly suppressed body weight growth (by 16.28% and 16.24%, respectively) and adipose tissue enlargement in obese mice. HE significantly improved the serum lipid profiles, mainly manifested as decreased levels of triglycerides (28.19% in LH and 19.59% in HH) and increased levels of high-density lipoprotein cholesterol (44.34% in LH and 54.88% in HH), and further attenuated liver lipid deposition. Furthermore, HE significantly decreased the Firmicutes/Bacteroidetes ratio 0.23-fold (LH) and 0.12-fold (HH), indicating an improvement in the microecological balance of the gut. HE administration also elevated the relative abundance of beneficial bacteria (e.g., Allobaculum, norank_f__Muribaculaceae), while suppressing harmful pathogenic proliferation (e.g., Dubosiella, Romboutsia). In conclusion, HE ameliorates obesity and hyperlipidemia through modulating lipid metabolism and restoring the balance of intestinal microecology, thus being promising for obesity therapy. Full article
(This article belongs to the Special Issue Functional Components and Bioactivity of Edible Plants)
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19 pages, 428 KiB  
Article
Irisin Concentrations in Children and Adolescent Cancer Survivors and Their Relation to Metabolic, Bone, and Reproductive Profile: A Pilot Case–Control Study
by Despoina Apostolaki, Katerina Katsibardi, Vasiliki Efthymiou, Charikleia Stefanaki, Aimilia Mantzou, Stavroula Papadodima, George P. Chrousos, Antonis Kattamis and Flora Bacopoulou
J. Clin. Med. 2025, 14(14), 5098; https://doi.org/10.3390/jcm14145098 - 17 Jul 2025
Viewed by 306
Abstract
Background/Objectives: Childhood cancer survivors (CCS) experience chronic health problems and significant metabolic burden. Timely identification of CCS at higher metabolic risk requires novel biomarkers. Irisin, a novel myokine/adipokine has been associated with metabolic, bone and reproductive diseases, but its role in the [...] Read more.
Background/Objectives: Childhood cancer survivors (CCS) experience chronic health problems and significant metabolic burden. Timely identification of CCS at higher metabolic risk requires novel biomarkers. Irisin, a novel myokine/adipokine has been associated with metabolic, bone and reproductive diseases, but its role in the health of CCS is unknown. The aim of this study was to examine irisin concentrations in children and adolescent CCS (vs. controls) and their association with metabolic, bone and hormonal parameters. Methods: Children and adolescent CCS, aged 8–18 years, as well as healthy controls, underwent a detailed physical, body composition, biochemical, hormonal and serum irisin assessment at least 6 months post-treatment. Results: A total of 59 children and adolescents (36 CCS, 23 controls; mean age ± SD 12.8 ± 2.9 years; 10 prepubertal, 49 pubertal) participated in the study. Serum irisin concentrations (ng/mL) were significantly lower in CCS than controls [median (IQR) 6.54 (4.12) vs. 11.70 (8.75) ng/mL, respectively, p < 0.001]. In the total study sample, serum irisin was correlated negatively with LH (rs = −0.314, p < 0.05), CRP (rs = −0.366, p < 0.005), age (rs = −0.323, p < 0.05) and positively with ALP (rs = 0.328, p < 0.05). Serum irisin was also positively correlated with ApoB and Lpa (rs = 0.410 and 0.421, respectively, p < 0.05) in CCS, and with PTH (r = 0.542, p < 0.005) in controls. Multivariate linear regression analysis indicated parathyroid hormone (PTH) as the only independent variable affecting irisin concentrations. Conclusions: Study results reinforce the irisin–PTH interplay hypothesis. Future studies are needed to clarify the potential role of irisin as a bone biomarker of CCS in childhood and adolescence. Full article
(This article belongs to the Section Clinical Pediatrics)
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12 pages, 508 KiB  
Article
Retrospective Analysis of Vitamin D Levels in Girls with Idiopathic Central Precocious Puberty: A Potential Role in Pubertal Activation?
by Giorgio Sodero, Luigi Antonio Moscogiuri, Anna Camporeale, Aniello Meoli, Fabio Comes, Paola Passoforte, Giacomo Perrone, Antonietta Villirillo and Marilea Lezzi
Endocrines 2025, 6(3), 33; https://doi.org/10.3390/endocrines6030033 - 7 Jul 2025
Viewed by 315
Abstract
Objective: To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and clinical, hormonal, and auxological features in girls with idiopathic central precocious puberty (CPP). Methods: This retrospective study included 122 girls diagnosed with idiopathic CPP. Participants were stratified into three groups based [...] Read more.
Objective: To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and clinical, hormonal, and auxological features in girls with idiopathic central precocious puberty (CPP). Methods: This retrospective study included 122 girls diagnosed with idiopathic CPP. Participants were stratified into three groups based on serum 25(OH)D concentrations: deficient (<20 ng/mL), insufficient (20–30 ng/mL), and sufficient (>30 ng/mL). Clinical and hormonal parameters were compared across groups. Spearman’s correlation and multiple linear regression analyses were used to explore the relationship between vitamin D levels and peak luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH) stimulation. Results: No significant differences were observed among the vitamin D groups in terms of age at diagnosis, body mass index (BMI), or other auxological measures. However, serum 25(OH)D levels showed a weak but significant positive correlation with LH peak values (rho = 0.23, p = 0.037). In multivariable regression analysis, vitamin D levels remained an independent predictor of LH peak (β = 0.125, p = 0.036), whereas BMI standard deviations (SDS), growth velocity SDS, and age at diagnosis did not show significant associations. Conclusions: Higher serum vitamin D levels are independently associated with greater LH peak responses in girls with idiopathic CPP. These findings support a potential modulatory role of vitamin D in the neuroendocrine mechanisms underlying pubertal onset and warrant further prospective studies to clarify its clinical relevance. Full article
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18 pages, 864 KiB  
Article
Urinary Glyphosate Concentrations and Serum Sex Hormones in a Nationally Representative U.S. Sample: NHANES 2017–2018
by Wen-Yang Wu, Du-Sheng Wang, Hsuan-Cheng Lin, Chikang Wang and Chien-Yu Lin
Life 2025, 15(7), 1024; https://doi.org/10.3390/life15071024 - 27 Jun 2025
Viewed by 439
Abstract
Glyphosate and glyphosate-based herbicides (GBHS) are the most widely used herbicides worldwide, yet their potential endocrine-disrupting effects in humans remain inadequately studied. We analyzed data from 1532 participants aged ≥6 years in the 2017–2018 National Health and Nutrition Examination Survey (NHANES). Serum sex [...] Read more.
Glyphosate and glyphosate-based herbicides (GBHS) are the most widely used herbicides worldwide, yet their potential endocrine-disrupting effects in humans remain inadequately studied. We analyzed data from 1532 participants aged ≥6 years in the 2017–2018 National Health and Nutrition Examination Survey (NHANES). Serum sex hormones assessed included follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), androstenedione, estrone, estradiol, estrone sulfate, 17α-hydroxyprogesterone, progesterone, and sex hormone-binding globulin (SHBG). We found that higher urinary glyphosate levels were significantly associated with lower concentrations of AMH (β = −0.140, p < 0.05), androstenedione (β = −0.134, p < 0.001), estradiol (β = −0.185, p < 0.05), estrone (β = −0.132, p < 0.05), estrone sulfate (β = −0.196, p < 0.001), 17α-hydroxyprogesterone (β = −0.097, p < 0.05), and progesterone (β = −0.212, p < 0.05). SHBG was positively associated (β = 0.080, p < 0.05). FSH and LH showed no significant associations. These associations were generally linear and showed modification by age. Subgroup analyses revealed stronger negative associations in adult males, while SHBG increased in females. In conclusion, we observed that higher urinary glyphosate levels were significantly associated with alterations in multiple serum sex hormones. Although the cross-sectional design precludes causal inference, these findings underscore the need for longitudinal research to determine temporal relationships and underlying mechanisms. Full article
(This article belongs to the Section Medical Research)
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12 pages, 754 KiB  
Article
Effects of Two Hormonal Protocols for FTAI on the Fertility of Repeat Cows
by Luis Miguel Vargas Ortiz, Verónica Cristina Andrade Yucailla, Juan Ramón García Díaz, Néstor Vicente Acosta Lozano, Ramón Gonzalo Aragadvay Yungán and Raciel Lima Orozco
Int. J. Mol. Sci. 2025, 26(12), 5499; https://doi.org/10.3390/ijms26125499 - 8 Jun 2025
Viewed by 438
Abstract
This study, carried out from January to July 2022 in three provinces of Ecuador, aimed to evaluate the effect of two hormonal protocols for fixed-time artificial insemination (FTAI) on the follicular dynamics, hormonal profile and fertility of dairy cows affected by repeat cow [...] Read more.
This study, carried out from January to July 2022 in three provinces of Ecuador, aimed to evaluate the effect of two hormonal protocols for fixed-time artificial insemination (FTAI) on the follicular dynamics, hormonal profile and fertility of dairy cows affected by repeat cow syndrome (RCS). Two groups of Holstein cows with RCS were formed, G1 (conventional) and G2 (J-Sinch), with 26 and 24 animals, respectively. Gynaecological examinations and hormonal determinations in blood serum were carried out. Follicular diameter and concentrations of FSH, LH and P4 were compared by t-Student test for independent samples, estrus and pregnancy were compared by binomial comparison of proportions, and factors associated with pregnancy were determined by a model of logistic regression (LR). In G1, the diameter of the dominant follicle was greater (p < 0.05) in the left ovary on day 7 following intravaginal device implantation. However, it was similar (p > 0.05) in the right ovary on days 7, 8 and 9. The estradiol and LH concentrations at the time of FTAI and the P4 concentrations 15 days after FTAI, as well as the pregnancy rate, were higher in G1 (p < 0.05). The LR model explained 60.91% of pregnancies (p < 0.001), and the concentrations of estradiol, LH and P4 and the absence of estrus at the time of FTAI had an influence on the pregnancy rate (p < 0.05). It was concluded that the inclusion of estradiol benzoate increased the dominant follicle diameter and the concentrations of estradiol, LH and P4 and the pregnancy rate at the first FTAI. Full article
(This article belongs to the Special Issue Molecular Insights into Reproductive Biology and Related Diseases)
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12 pages, 920 KiB  
Article
Decoding the Relationship Between Polycystic Ovary Syndrome and Hormonal Dependencies of Anti-Müllerian Hormone and Other Markers
by Dominika Gałczyńska, Jakub Daniluk, Aleksandra Buczek-Kutermak, Paweł Pruś and Dagmara Pluta
Biomedicines 2025, 13(6), 1341; https://doi.org/10.3390/biomedicines13061341 - 30 May 2025
Cited by 2 | Viewed by 595
Abstract
Background: The objective of this study was to evaluate the influence of polycystic ovary syndrome (PCOS) on various laboratory measurements, especially hormonal and metabolic parameters, as well as clinical measurements including hirsutism and acne assessment, with consideration of different PCOS phenotypes. This study [...] Read more.
Background: The objective of this study was to evaluate the influence of polycystic ovary syndrome (PCOS) on various laboratory measurements, especially hormonal and metabolic parameters, as well as clinical measurements including hirsutism and acne assessment, with consideration of different PCOS phenotypes. This study was focused mainly on the correlation between anti-Müllerian hormone (AMH) levels and other hormonal measurements. Methods: This single-center retrospective study included 296 patients with diagnosed PCOS according to the Rotterdam criteria. All participants of this study underwent blood tests between the 2nd and the 6th day of their menstrual cycle. Results: In statistical analysis, a strong significant correlation of AMH with androstenedione (r = 0.48, p < 0.0001), luteinizing hormone (LH) (r = 0.45, p < 0.0001), total testosterone (r = 0.34, p < 0.0001), 17-hydroxyprogesterone (r = 0.31, p < 0.0001), and cortisol after dexamethasone (r = 0.15, p = 0.011) was observed. In addition, significant negative correlations were found with follicle-stimulating hormone (FSH) (r = −0.21, p < 0.0001), weight (r = −0.15, p = 0.010), glucose 0′ (r = −0.14, p = 0.014), hip circumference (r = −0.14, p = 0.017), and body mass index (BMI) (r = −0.14, p = 0.018). A weak correlation with waist circumference of p = 0.06 was also observed. Conclusions: AMH serum levels showed a positive correlation with hyperandrogenism and a negative correlation with metabolic factors, although its relationship with BMI is more complex. There were no significant differences in AMH levels across the four PCOS phenotypes or when categorized into hyperandrogenic and normoandrogenic subtypes. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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11 pages, 4522 KiB  
Article
Evaluation of Ovarian Stromal Microvascularity and Clinical-Hormonal Associations in Reproductive-Aged Women with Polycystic Ovary Morphology
by Hakan Baş and Süleyman Filiz
Diagnostics 2025, 15(11), 1376; https://doi.org/10.3390/diagnostics15111376 - 29 May 2025
Viewed by 495
Abstract
Background/Objectives: This study aims to assess ovarian stromal vascularity using microvascular imaging in reproductive-aged women with polycystic ovarian morphology (PCOM) and to explore its associations with endocrine parameters and polycystic ovary syndrome (PCOS) phenotypes. Methods: We conducted a retrospective, single-center study between January [...] Read more.
Background/Objectives: This study aims to assess ovarian stromal vascularity using microvascular imaging in reproductive-aged women with polycystic ovarian morphology (PCOM) and to explore its associations with endocrine parameters and polycystic ovary syndrome (PCOS) phenotypes. Methods: We conducted a retrospective, single-center study between January 2021 and November 2023. Women aged 18–49 who met the PCOM criteria (≥20 follicles measuring 2–9 mm or an ovarian volume >10 cm3 in at least one ovary) were included. Pelvic ultrasound with MV-Flow Doppler imaging was used to quantify the stromal vascularity index (VI). On the same day, serum levels of FSH, LH, total and free testosterone, DHEAS, and estradiol were measured. PCOS phenotypes (A, C, D, and non-PCOS) were classified according to the Rotterdam criteria. Statistical analysis involved interobserver agreement using intraclass correlation coefficients (ICCs), correlation analysis for hormonal associations, and group comparisons using ANOVA. Results: A total of 111 women (mean age: 27.4 ± 6.1 years) were evaluated. The mean VI was 43.88 ± 19.84, with good interobserver agreement (ICC = 0.79; 95% CI: 0.65–0.88). VI was highest in Phenotype A (61.36 ± 10.11), followed by Phenotype C (42.57 ± 3.59), Phenotype D (26.47 ± 4.24), and Non-PCOS individuals (9.95 ± 5.44; p < 0.001). VI showed strong positive correlations with total testosterone (r = 0.797) and free testosterone (r = 0.778), and a moderate negative correlation with DHEAS (r = −0.483; p < 0.001). Conclusions: Microvascular imaging is a promising tool for quantifying ovarian stromal vascularity in PCOM. Its strong correlation with androgen levels, especially in hyperandrogenic phenotypes, highlights its potential role in enhancing diagnostic precision and deepening our understanding of PCOS pathophysiology. Full article
(This article belongs to the Special Issue Advanced Ultrasound Techniques in Diagnosis)
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17 pages, 1687 KiB  
Article
Sex Hormones and Iron-Related Biomarkers Associate with EMT Features and Tumor Stage in Colorectal Cancer: A Serum- and Tissue-Based Analysis
by Rosanna Squitti, Anastasia De Luca, Altea Severino, Gianluca Rizzo, Federica Marzi, Luca Emanuele Amodio, Gabriella Vicano, Antonio Focaccio, Vincenzo Tondolo and Mauro Rongioletti
Int. J. Mol. Sci. 2025, 26(11), 5163; https://doi.org/10.3390/ijms26115163 - 28 May 2025
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Abstract
Sex steroid hormones and systemic iron metabolism are emerging as modulators of colorectal cancer (CRC) development and progression. However, information linking systemic factors to tumor characteristics and epithelial–mesenchymal transition (EMT) is limited, particularly in a sex-specific context. We measured serum levels of sex [...] Read more.
Sex steroid hormones and systemic iron metabolism are emerging as modulators of colorectal cancer (CRC) development and progression. However, information linking systemic factors to tumor characteristics and epithelial–mesenchymal transition (EMT) is limited, particularly in a sex-specific context. We measured serum levels of sex hormones [testosterone, estradiol, progesterone, Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), Carcinoembryonic antigen (CEA)] and iron-related biomarkers (iron, transferrin, ferritin, % transferrin saturation, ceruloplasmin, and the ceruloplasmin/transferrin ratio) in 82 CRC patients and 31 healthy controls. EMT-related proteins [mediator of ErbB2-driven cell motility 1 (MEMO1), E-cadherin, fibronectin, vimentin, and vinculin] were quantified by Western blotting in tumor and adjacent normal mucosa. Non-parametric tests and Spearman correlations were applied, stratified by sex and corrected for age and anemia where appropriate. Progesterone levels were significantly lower in male CRC patients (median 0.17 ng/mL vs. 0.20 ng/mL, p = 0.04) and higher in female patients (0.17 ng/mL vs. 0.10 ng/mL, p = 0.0077) compared with controls. The iron-related biomarkers indicated a pattern of iron deficiency, including in non-anemic patients, with reduced % transferrin saturation (p < 0.01) and an elevated ceruloplasmin/transferrin ratio (p = 0.02). Correlations were found between iron status, tumor stage, and hormonal levels. Progesterone correlated with EMT protein expression in healthy mucosa (e.g., fibronectin in females: ρ = 0.567, p = 0.014; vimentin in males: ρ = −0.446, p = 0.007), but not in tumor tissue. In the healthy mucosa of male patients, ceruloplasmin/transferrin correlated with MEMO1 (ρ = 0.419, p = 0.04), vinculin (ρ = 0.299, p = 0.041), and vimentin (ρ = 0.394, p = 0.07); transferrin levels inversely correlated with MEMO1 expression (ρ = −0.392, p = 0.032), and vimentin showed a positive correlation with serum iron (ρ = 0.350, p = 0.043). Furthermore, fibronectin expression inversely correlated with iron in the sole tumor tissue of female patients (ρ = −0.366, p = 0.040). These findings support the role of sex hormones and iron metabolism in CRC biology, suggesting that EMT might be accompanied by altered iron uptake and redox remodeling, which can enhance cellular motility and the metastatic potential. Full article
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19 pages, 3614 KiB  
Article
Immunoenhancement Function of the Novel Hexapeptide (LVVLGH) from Thick-Shelled Mussel (Mytilus coruscus) on Immunodeficient Mice by Activating the NF-κB/MAPK Pathway
by Xu Yang, Yu Zeng, Fandi Que, Shiqing Fu, Li Xu, Fangmiao Yu and Bin Wang
Foods 2025, 14(11), 1865; https://doi.org/10.3390/foods14111865 - 24 May 2025
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Abstract
A novel hexapeptide LVVLGH (LH-6) from the thick-shelled mussel (Mytilus coruscus) demonstrated potent immune-enhancing effects in RAW264.7 cells in vitro, but its immunological activity in vivo is unclear. As a result, the present study was designed to investigate the in vivo [...] Read more.
A novel hexapeptide LVVLGH (LH-6) from the thick-shelled mussel (Mytilus coruscus) demonstrated potent immune-enhancing effects in RAW264.7 cells in vitro, but its immunological activity in vivo is unclear. As a result, the present study was designed to investigate the in vivo effects of LH-6 on cyclophosphamide-induced immunodeficient mice. The results demonstrate that LH-6 promoted the growth and development of immunodeficient mice in a concentration-dependent manner, remarkably elevated the immune organ index, and relieved the pathological characteristics of the spleen and thymus. Additional experiments also revealed that LH-6 effectively promoted the multiplication of splenic lymphocytes and natural killer activity, enhanced the function of abdominal macrophages, and apparently recovered delayed-type hypersensitivity in immunodeficient mice. The secretion of IgA, IgG, IgM, TNF-α, IL-1β, IL-6, and serum hemolysin were remarkably improved by LH-6, suggesting that LH-6 can synergistically strengthen cellular and humoral immunity. In addition, LH-6 promoted the phosphorylation of IκBα and nuclear translocation of p65, which correspondingly increased the phosphorylation levels of p38, JNK, and ERK; activated the NF-κB and MAPK pathways; and exerted in vivo immunomodulatory activities. Docking results show that LH-6 has favorable binding energies to candidate proteins in the NF-κB and MAPK pathways. To summarize, this research further demonstrated that LH-6 possesses in vivo immunomodulatory activity, which provides a possibility for the subsequent development of immune-enhancing functional foods. Full article
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15 pages, 4722 KiB  
Article
Effects of Lead Exposure on 1573 Male Workers’ Sex Hormones in China
by Ping Wang, Zhiling Wu, Ju Li, Yue Li, Xuefeng Wang, Mengya Ma, Wenkai Wei, Yijun Wang, Yi Liu, Yi Sun, Ling Tao, Yanyan Yang, Ziyuan Zhou, Jingchao Ren, Jia Cao and Guanghui Zhang
Toxics 2025, 13(5), 415; https://doi.org/10.3390/toxics13050415 - 21 May 2025
Viewed by 1134
Abstract
Lead (Pb) is recognized as an environmental pollutant with male reproductive toxicity, but its effects on sex hormones remain unclear. This study investigated the relationship between male blood lead levels (BLLs) and the sex hormones of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and [...] Read more.
Lead (Pb) is recognized as an environmental pollutant with male reproductive toxicity, but its effects on sex hormones remain unclear. This study investigated the relationship between male blood lead levels (BLLs) and the sex hormones of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL), as well as testosterone (T), estrogen (E2), and progesterone (PROG). Observational and experimental data from 1573 Pb-exposed workers (712 had also been surveyed in the previous year) and 35 Pb-poisoned patients (before and after Pb chelation therapy) were analyzed. Results from a cross-sectional study showed a nonlinear relationship between BLLs and LH/FSH, and a linear relationship between BLLs and serum T. After Pb chelation therapy, the BLLs in patients decreased from 61.7 to 36.3 (μg/dL), serum T and FSH decreased significantly (p < 0.001), and serum LH also decreased but without a significant change, while PRL and PROG increased significantly (p < 0.01). The data indicate that Pb may disturb male sex hormones by including LH, T, and FSH, and this needs further research. Full article
(This article belongs to the Special Issue Environmental Contaminants and Human Health—2nd Edition)
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