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Environmental Science and Pollution... Jun 2024
PubMed: 38941053
DOI: 10.1007/s11356-024-34101-3 -
Frontiers in Bioscience (Landmark... Jun 2024Hormone receptors exert their function through binding with their ligands, which results in cellular signaling activation mediated by genomic or non-genomic mechanisms....
BACKGROUND
Hormone receptors exert their function through binding with their ligands, which results in cellular signaling activation mediated by genomic or non-genomic mechanisms. The intrinsic molecular communication of tick and its host comprises an endocrine regulation involving hormones. In the present study, we performed a molecular and analysis of a Membrane Associated Progesterone Receptor in (RmMAPRC).
METHODS
The RmMAPRC protein sequence was analyzed with bioinformatics tools, and its structure was characterized by three-dimensional (3D) modeling and molecular docking. A semi-quantitative reverse transcription and polymerase chain reaction (sqRT-PCR) assessed the gene presence and relative expression in tick organs and embryonic cells.
RESULTS
relative expression in salivary glands, ovaries, and embryonic cells showed overexpression of 3%, 13%, and 24%, respectively. Bioinformatic analysis revealed that RmMAPRC corresponded to a Progesterone Receptor Membrane Component 1 (RmPGRMC1) of ~23.7 kDa, with an N-terminal transmembrane domain and a C-terminal Cytochrome b5-like heme/steroid binding domain. The docking results suggest that RmPGRMC1 could bind to progesterone (P4), some progestins, and P4 antagonists. The phylogenetic reconstruction showed that spp. MAPRC receptors were clustered in a clade that includes , , and (RmMAPRC), and mammals and helminths MAPRC receptors clustered in two separated clades away from ticks.
CONCLUSIONS
The presence of RmPGRMC1 highlights the importance of transregulation as a conserved adaptive mechanism that has succeeded for arthropod parasites, making it a target for tick control.
Topics: Animals; Rhipicephalus; Receptors, Progesterone; Progesterone; Cattle; Molecular Docking Simulation; Host-Parasite Interactions; Female; Amino Acid Sequence; Protein Binding; Phylogeny
PubMed: 38940045
DOI: 10.31083/j.fbl2906238 -
Acta Endocrinologica (Bucharest,... 2023More and more couples are postponing their desire to have children until later periods in life. This is accompanied by a variety of both, medical and social problems. It...
More and more couples are postponing their desire to have children until later periods in life. This is accompanied by a variety of both, medical and social problems. It is known that fertility in women begins to decline gradually from the age of 25 and decreases rapidly from the age of 35. On the other hand, many couples in the fourth decade of life are significantly involved in their careers and are sometimes even physically separated. This means that the probability of conception is inherently reduced, because sexual intercourse cannot take place regularly on fertile days. We report on a 35-year-old patient in whom we programmed the cycle with the progestin pill drospirenone, which resulted in a spontaneous conception and the birth of a healthy child.
PubMed: 38933246
DOI: 10.4183/aeb.2023.505 -
International Journal of Molecular... Jun 2024The objective of the study was to evaluate the profile and diagnostic significance of serum autoantibodies in infertile patients with premature ovarian insufficiency...
The objective of the study was to evaluate the profile and diagnostic significance of serum autoantibodies in infertile patients with premature ovarian insufficiency (POI). The pilot study included 26 patients of reproductive age with POI and diminished ovarian reserve who received complex treatment using new surgical technologies (Group 1) and 18 patients without POI (Group 2). The profile of serum autoantibodies, including anti-ovarian antibodies, antibodies against thyroid peroxidase (TPO), steroidogenic enzymes, and steroid and gonadotropic hormones, was studied using modified ELISAs and human recombinant steroidogenic enzymes (CYP11A1, CYP19A1, CYP21A2). Patients in Group 1 had higher levels of IgG autoantibodies against steroidogenic enzymes, estradiol, progesterone, and TPO than those in Group 2. Tests for IgG antibodies against CYP11A1, CYP19A1, and CYP21A2 exhibited high sensitivity (65.4-76.9%), specificity (83.3-89.9%), and AUC values (0.842-0.910) for POI, the highest in the first test. Three-antibodies panel screening showed higher diagnostic accuracy (84.1% versus 75-79.6%). The levels of these antibodies correlated with menstrual irregularities and a decrease in the antral follicle count. Thus, antibodies against CYP11A1, CYP19A1, and CYP21A2 have a high diagnostic value for POI. Three-antibody panel screening may improve the accuracy of POI diagnosis and be useful for identifying high-risk groups, early stages of the disease, and predicting POI progression.
Topics: Humans; Female; Autoantibodies; Primary Ovarian Insufficiency; Adult; Infertility, Female; Cholesterol Side-Chain Cleavage Enzyme; Aromatase; Steroid 21-Hydroxylase; Iodide Peroxidase; Pilot Projects; Immunoglobulin G; Biomarkers; Progesterone; Estradiol
PubMed: 38928251
DOI: 10.3390/ijms25126545 -
Nature Reviews. Endocrinology Jun 2024
PubMed: 38926499
DOI: 10.1038/s41574-024-01013-8 -
Scientific Reports Jun 2024Previously, we demonstrated the expression of visfatin in porcine reproductive tissues and its effect on pituitary endocrinology. The objective of this study was to...
Previously, we demonstrated the expression of visfatin in porcine reproductive tissues and its effect on pituitary endocrinology. The objective of this study was to examine the visfatin effect on the secretion of steroid (P, E) and prostaglandin (PGE, PGF), the mRNA and protein abundance of steroidogenic markers (STAR, CYP11A1, HSD3B, CYP19A1), prostaglandin receptors (PTGER2, PTGFR), insulin receptor (INSR), and activity of kinases (MAPK/ERK1/2, AKT, AMPK) in the porcine corpus luteum. We noted that the visfatin effect strongly depends on the phase of the estrous cycle: on days 2-3 and 14-16 it reduced P, while on days 10-12 it stimulated P. Visfatin increased secretion of E on days 2-3, PGE on days 2-3 and 10-12, reduced PGF release on days 14-16, as well as stimulated the expression of steroidogenic markers on days 10-12 of the estrous cycle. Moreover, visfatin elevated PTGER mRNA expression and decreased its protein level, while we noted the opposite changes for PTGFR. Additionally, visfatin activated ERK1/2, AKT, and AMPK, while reduced INSR phosphorylation. Interestingly, after inhibition of INSR and signalling pathways visfatin action was abolished. These findings suggest a regulatory role of visfatin in the porcine corpus luteum.
Topics: Animals; Corpus Luteum; Female; Swine; Nicotinamide Phosphoribosyltransferase; Estrous Cycle; Receptor, Insulin; Progesterone; Receptors, Prostaglandin; Dinoprost
PubMed: 38926439
DOI: 10.1038/s41598-024-65102-4 -
Reproduction in Domestic Animals =... Jun 2024Understanding the normal physiology of the canine mammary gland (CMG) is crucial, as it provides a foundational reference for understanding canine mammary neoplasms. The...
Understanding the normal physiology of the canine mammary gland (CMG) is crucial, as it provides a foundational reference for understanding canine mammary neoplasms. The relation between the Proliferation Index (PI) indicated by Ki-67 expression, along with the Apoptotic Index (AI) determined through Caspase-3 expression during the oestrous cycle, is inadequately documented in existing literature. This study seeks to offer insights into the interplay between PI and AI in the CMG across oestrous cycle phases. An extensive investigation was conducted on a diverse case series of bitches (n = 18). Oestrous cycle stages were determined through vaginal cytology, histological examination of the reproductive tract and serum progesterone and oestradiol concentrations. The entire mammary chain was histologically examined, and proliferation and apoptosis were assessed via double immunohistochemistry employing anti-Ki-67 and Caspase-3 antibodies. PI and AI were evaluated through a systematic random sampling approach, counting a minimum of 200 cells for each cell type. There was a significantly higher PI during early dioestrus in all mammary gland components, with a greater proportion of positive cells observed in epithelial cells compared to stromal cells. The highest PI was detected in epithelial cells within the end buds. Significant differences were found in Ki-67 labelling across the cranial mammary glands. A positive and strong correlation was noted between progesterone concentration and PI in epithelial cells. The AI remained consistently low throughout the oestrous cycle, with few differences observed across histological components. Caspase-3 labelling displayed the highest positivity in caudal mammary pairs. A negative and moderate correlation was identified between progesterone concentration and AI in interlobular mesenchymal cells. This study highlights the influence of endocrine regulation on cell proliferation indices in mammary tissue, emphasizing the need to consider these hormonal variations in toxicopathological studies involving canine mammary gland.
Topics: Animals; Female; Ki-67 Antigen; Dogs; Apoptosis; Mammary Glands, Animal; Caspase 3; Cell Proliferation; Estrous Cycle; Progesterone; Estradiol; Epithelial Cells
PubMed: 38924202
DOI: 10.1111/rda.14655 -
Reproduction in Domestic Animals =... Jun 2024The cervix is an important organ that has to dilate sufficiently at delivery to allow the foetus to transition to extrauterine life. Insufficient dilatation of the...
The cervix is an important organ that has to dilate sufficiently at delivery to allow the foetus to transition to extrauterine life. Insufficient dilatation of the cervix (IDC) is a frequent cause of dystocia in cattle. The mechanisms underlying cervical opening and the pathogenesis of IDC are still widely unclear. Systematic studies on the relationship between IDC and steroid hormones have been limited and have yielded inconsistent findings. This study aimed to measure oestrogen and progesterone (P4) concentrations in intrapartum cows presented with dystocia due to IDC and in a comparison (C) group of cows with eutocic delivery. Before any obstetrical procedures, and right after the initial evaluation, blood samples were taken from IDC and C animals. Concentrations of P4, oestradiol-17β (E2), free total oestrogens (FTE) and conjugated total oestrogens (CTE) were measured by established radioimmunoassays. Concentrations of P4 (p = .538), FTE (p = .065) and CTE (p = .605) were not statistically different between C and IDC groups. However, E2 levels in group C were significantly lower when compared to those in the IDC group (p = .013), which is inconsistent with the function of oestrogens in cervical dilatation. The correlation analysis demonstrated significant positive correlations between the pairs P4 versus FTE, P4 versus E2 and FTE versus E2 in group C and between the pair FTE versus E2 in group IDC. In conclusion, the results suggest that local activities of steroids relevant to the aetiology of IDC are not reflected by concentrations in the systemic circulation or that other factors are clearly more important.
Topics: Animals; Female; Cattle; Progesterone; Pregnancy; Cervix Uteri; Estrogens; Dystocia; Estradiol; Cattle Diseases
PubMed: 38923054
DOI: 10.1111/rda.14656 -
Clinical Cancer Research : An Official... Jun 2024Nonsurgical treatment options are increasingly needed for endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC). Despite promising initial...
BACKGROUND
Nonsurgical treatment options are increasingly needed for endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC). Despite promising initial response rates, prospective long-term data and determinants for relapse are limited.
METHODS
Follow-up data from patients in our prospective phase II trial of LIUD for AH/G1EEC were collected from medical records. Spatial transcriptomics (Nanostring GeoMX digital spatial profiling) with in silico cell type deconvolution and pathway analyses were employed on longitudinal biopsy samples from five patients across pre-treatment, on-treatment, and relapse.
RESULTS
Of 43 participants exhibiting initial response to LIUD, 41 had follow-up data. Sixteen (39%) experienced relapse. Clinical factors associated with shorter response duration included younger age, initial diagnosis of G1EEC, lack of response at six months, premenopausal status, and Hispanic ethnicity (p<0.05), but only six-month response status remained a significant predictor in a multivariate model (p=0.023). LIUD increased abundance of NK cells (DMCP-counter score=46.13, FDR=0.004) and cytotoxic lymphocytes (DMCP-counter score=277.67, FDR=0.004), as well as lymphocyte cytotoxicity markers PRF1 (log2FC=1.62, FDR=0.025) and GZMA (log2FC=2.47, FDR=0.008). NK cells were reduced at relapse (DMCP-counter score=-55.96, FDR=0.02). Immune-related pathways (IFNα-response and TGFβ-signaling) were enriched at relapse (FDR<0.05). IDO1 expression, reflecting immune exhaustion, was upregulated at relapse (FDR<0.05).
CONCLUSIONS
Upfront resistance and relapse after initial response to LIUD for AH/G1EEC impacts nearly half of patients, remaining a major hurdle for non-surgical treatment of AH/G1EEC. Molecular studies evaluating longitudinal biopsies from a small cohort implicate immune mechanisms at relapse, including reversal of progestin-related immunomodulation and increased immune exhaustion.
PubMed: 38922360
DOI: 10.1158/1078-0432.CCR-24-0362 -
World Journal of Surgical Oncology Jun 2024This study aimed to evaluate the oncological and reproductive outcomes of fertility-preserving re-treatment in progestin-resistant endometrial carcinoma (EC) and...
OBJECTIVE
This study aimed to evaluate the oncological and reproductive outcomes of fertility-preserving re-treatment in progestin-resistant endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) women who desire to maintain their fertility.
METHODS
Our study included 61 progestin-resistant EC/AEH patients. These patients underwent treatment with gonadotropin-releasing hormone agonist (GnRHa) solely or a combination of GnRHa with levonorgestrel-releasing intrauterine system (LNG-IUD) or aromatase inhibitor (AI). Histological evaluations were performed every 3-4 months. Upon achieving complete remission (CR), we recommended maintenance treatments including LNG-IUD, cyclical oral contraceptives, or low-dose cyclic progestin until they began attempting conception. Regular follow-up was conducted for all patients. The chi-square method was utilized to compare oncological and fertility outcomes, while the Cox proportional hazards regression analysis helped identify risk factors for CR, recurrence, and pregnancy.
RESULTS
Overall, 55 (90.2%) patients achieved CR, including 90.9% of AEH patients and 89.7% of EC patients. The median re-treatment time was 6 months (ranging from 3 to 12 months). The CR rate for GnRHa alone, GnRHa + LNG-IUD and GnRHa + AI were 80.0%, 91.7% and 93.3%, respectively. After a median follow-up period of 36 months (ranging from 3 to 96 months), 19 women (34.5%) experienced recurrence, 40.0% in AEH and 31.4% in EC patients, with the median recurrence time of 23 months (ranging from 6 to 77 months). Among the patients who achieved CR, 39 expressed a desire to conceive, 20 (51.3%) became pregnant, 11 (28.2%) had successfully deliveries, 1 (5.1%) was still pregnant, while 8 (20.5%) suffered miscarriages.
CONCLUSION
GnRHa-based fertility-sparing treatment exhibited promising oncological and reproductive outcomes for progestin-resistant patients. Future larger multi-institutional studies are necessary to confirm these findings.
Topics: Humans; Female; Endometrial Neoplasms; Adult; Retrospective Studies; Fertility Preservation; Endometrial Hyperplasia; Progestins; Follow-Up Studies; Pregnancy; Drug Resistance, Neoplasm; Gonadotropin-Releasing Hormone; Levonorgestrel; Middle Aged; Prognosis; Intrauterine Devices, Medicated; Neoplasm Recurrence, Local; Pregnancy Rate; Aromatase Inhibitors; Antineoplastic Agents, Hormonal
PubMed: 38918837
DOI: 10.1186/s12957-024-03439-w