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Biochimica Et Biophysica Acta.... Jun 2024The mechanisms that underly reproductive hormone effects on cognition, neuronal plasticity, and AD risk, particularly in relation to gonadotropin LH receptor (LHCGR)...
The mechanisms that underly reproductive hormone effects on cognition, neuronal plasticity, and AD risk, particularly in relation to gonadotropin LH receptor (LHCGR) signaling, remain poorly understood. To address this gap in knowledge and clarify the impact of circulating steroid hormones on the therapeutic effects of CNS LHCGR activation, we delivered the LHCGR agonist human chorionic gonadotropin (hCG) intracerebroventricularly (ICV) and evaluated functional, structural, plasticity-related signaling cascades, Aβ pathology, and transcriptome differences in reproductively intact and ovariectomized (OVX) APP/PS1 AD female mice. Here we demonstrate that CNS hCG delivery restored function to wild-type levels only in OVX APP/PS1 mice. Spine density was increased in all hCG treated groups independently of reproductive status. Notably, increases in BDNF signaling and cognition, were selectively upregulated only in the OVX hCG-treated group. RNA sequencing analyses identified a significant increase in peripheral myeloid and pro-inflammatory genes within the hippocampi of the OVX group that were completely reversed by hCG treatment, identifying a potential mechanism underlying the selective therapeutic effect of LHCGR activation. Interestingly, in intact mice, hCG administration mimicked the effects of gonadectomy. Together, our findings indicate that CNS LHCGR agonism in the post-menopausal context is beneficial through trophic and immune mechanisms. Our findings also underscore the presence of a steroid-LHCGR mechanistic interaction that is unexplored yet potentially meaningful to fully understand "post-menopausal" brain function and CNS hormone treatment response.
Topics: Animals; Female; Alzheimer Disease; Mice; Chorionic Gonadotropin; Receptors, LH; Disease Models, Animal; Mice, Transgenic; Ovariectomy; Amyloid beta-Protein Precursor; Humans; Reproduction; Presenilin-1; Brain-Derived Neurotrophic Factor; Hippocampus; Signal Transduction; Cognition
PubMed: 38653355
DOI: 10.1016/j.bbadis.2024.167165 -
Diabetes & Metabolic Syndrome Apr 2024Gestational diabetes mellitus (GDM) is a prevalent condition with an unclear pathogenesis. B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL)... (Observational Study)
Observational Study
Serum BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand) levels in the first trimester may predict the future development of gestational diabetes mellitus.
BACKGROUND
Gestational diabetes mellitus (GDM) is a prevalent condition with an unclear pathogenesis. B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are potential key players in GDM.
PARTICIPANTS, MATERIALS, AND METHODS
In a longitudinal observational study, we monitored women from the first trimester through 24-28 weeks of gestation, focusing on the development of GDM. Serum levels of BAFF and APRIL, as well as their mRNA expression, were evaluated in both the first and third trimesters. Furthermore, we assessed cytokines, adipokines, and placental hormones in the serum.
RESULTS
In the first trimester, participants who later developed GDM exhibited elevated serum BAFF and reduced serum APRIL levels, although the mRNA expression of these molecules was similar to controls. Serum BAFF exhibited significant positive correlations with metabolic markers and placental hormones. Conversely, serum APRIL was negatively correlated with insulin resistance and inflammatory markers but positively correlated with adiponectin. In the early third trimester, GDM participants continued to display higher serum BAFF levels and lower serum APRIL levels than controls. There was no significant difference in mRNA expression of BAFF between GDM and control groups. Conversely, APRIL mRNA expression was significantly lower in the GDM group. The predictive potential of first-trimester BAFF and APRIL levels for future GDM development was explored, with both molecules demonstrating strong predictive capability.
DISCUSSION AND CONCLUSION
This study suggests that elevated serum BAFF and reduced serum APRIL levels during pregnancy may be associated with the development of GDM. These biomarkers can serve as potential early predictors for GDM.
Topics: Humans; B-Cell Activating Factor; Female; Pregnancy; Diabetes, Gestational; Tumor Necrosis Factor Ligand Superfamily Member 13; Adult; Pregnancy Trimester, First; Biomarkers; Longitudinal Studies; Prognosis; Follow-Up Studies; Case-Control Studies
PubMed: 38653036
DOI: 10.1016/j.dsx.2024.103019 -
Urology Journal Jun 2024We aimed to evaluate the diagnostic sensitivity and specificity of the miRNA-371a-3p for the primary diagnosis of germ cell tumors (GCT) and to investigate its...
PURPOSE
We aimed to evaluate the diagnostic sensitivity and specificity of the miRNA-371a-3p for the primary diagnosis of germ cell tumors (GCT) and to investigate its relationship with pathological factors and clinical stage in the Turkish population.
MATERIALS AND METHODS
In this prospective study, a total of 60 patients with GCTs, and 40 healthy male controls were examined for serum levels of miRNA-371a-3p before orchiectomy and again two weeks after surgery. The miRNA-371a-3p, alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin (bHCG) levels in the preoperative and postoperative periods were compared at different clinical stages. Receiver operating characteristics curve analyses were performed to determine the sensitivity and specificity of miRNA-371a-3p. Clinical and pathological factors such as clinical stage (CS), tumor size, histology, rete testis invasion, and lymphovascular invasion, potentially impacting miRNA-371a-3p expression levels (relative quantity, RQ), were evaluated statistically.
RESULTS
The sensitivity of miR-371a-3p in GCT patients was 98.3%, and the specificity was 95% (AUC = 0.997 [95%Cl:0.99-1], p < .001). miR-371a-3p expression was not detected in two patients with teratoma. The median miR-371a-3p RQ was 489 times in GCT and 2.2 times in the Control group (p < .001). In the postoperative period, there was a significant decrease in AFP and bHCG levels in all CS-1 (p = .01) and 30% of the other CS (p = .3). Throughout this time there was a decrease of 19 times at the miR-371a-3p RQ in CS-1(p < .001) and 1.6 times in the other CS (p < .001). The miR-371a-3p RQs were correlated with tumor size and CS.
CONCLUSION
The miR-371a-3p seems to have higher diagnostic accuracy than classical serum tumor markers in GCT.
Topics: Humans; Male; Testicular Neoplasms; Neoplasms, Germ Cell and Embryonal; Prospective Studies; Case-Control Studies; Adult; MicroRNAs; Turkey; Biomarkers, Tumor; Sensitivity and Specificity; alpha-Fetoproteins; Young Adult; Middle Aged; Chorionic Gonadotropin, beta Subunit, Human; Neoplasm Staging
PubMed: 38629199
DOI: 10.22037/uj.v20i.8002 -
Reproductive Biology and Endocrinology... Apr 2024Intra-uterine infusion treatments were reported to be beneficial to embryo implantation and pregnancy outcomes, and considered as potential therapies for infertile... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intra-uterine infusion treatments were reported to be beneficial to embryo implantation and pregnancy outcomes, and considered as potential therapies for infertile patients with recurrent implantation failure (RIF). Nevertheless, their efficiencies were controversial and there lack of consensus on which intrauterine treatment is the most effective.
METHODS
All prospective trials (in Chinese or English) were searched in Databases PubMed, Cochrane, Web of Science, and CNKI from July 2013 to July 2023. We included studies that investigated various uterine infusions, including chorionic gonadotropin, granulocyte colony-stimulating factor, monocytes, platelet-rich plasma, etc. during IVF treatment and reported subsequent pregnancy outcomes.
RESULTS
We finally included 56 researches, including 40 randomized controlled trials, 14 non-randomized controlled trials, and 3 prospective cohort studies. This study included a total of 11 uterine perfusion methods: Placebo, Human Chorionic Gonadotropin (HCG), Granulocyte Colony-Stimulating Factor (G-CSF), platelet-rich plasma (PRP), Peripheral Blood Mononuclear Cell (PBMC), Growth hormone (GH), dexamethasone (DEX), Embryo culture supernatant (ESC), PRP combined with G-CSF (PRP + G-CSF), RPR combined with subcutaneous injection of G-CSF (RPR + G-CSFsc), G-CSF combined with subcutaneous injection of AXaIU (G-CSF + AXaIUsc). Intrauterine infusion of HCG, PBMC, G-CSF, and PRP significantly improves pregnancy outcomes in patients with repeated implantation failure compared with blank controls or placebo, and PRP improved the clinical pregnancy and live birth most. GH and ESC infusion might improve the pregnancy outcomes, but uterine infusion of DEX was shown with high miscarriage. The combination therapy did not show a significant advantage over the mono-therapy.
CONCLUSIONS
Intrauterine infusion of HCG, PBMC, G-CSF, and PRP are promising strategies for improving pregnancy outcomes for infertile patients with recurrent implantation failure. Among these treatments, PRP may be the best. More researches are required to explore the effect of drug combinations and less commonly used drugs as well.
TRIAL REGISTRATION
Our study was registered in PROSPERO and the ID was CRD42023467188.
Topics: Pregnancy; Female; Humans; Prospective Studies; Leukocytes, Mononuclear; Network Meta-Analysis; Embryo Implantation; Chorionic Gonadotropin; Infertility, Female; Granulocyte Colony-Stimulating Factor; Pregnancy Rate
PubMed: 38627790
DOI: 10.1186/s12958-024-01221-x -
Environmental Health Perspectives Apr 2024Per- and polyfluoroalkyl substances (PFAS) are widely detected in pregnant women and associated with adverse outcomes related to impaired placental function. Human...
BACKGROUND
Per- and polyfluoroalkyl substances (PFAS) are widely detected in pregnant women and associated with adverse outcomes related to impaired placental function. Human chorionic gonadotropin (hCG) is a dimeric glycoprotein hormone that can indicate placental toxicity.
OBJECTIVES
Our aim was to quantify the association of serum PFAS with placental hCG, measured as an intact molecule (hCG), as free alpha-() and beta-subunits (), and as a hyperglycosylated form (h-hCG), and evaluate effect measure modification by social determinants and by fetal sex.
METHODS
Data were collected from 326 pregnant women enrolled from 2015 to 2019 in the UPSIDE study in Rochester, New York. hCG forms were normalized for gestational age at the time of blood draw in the first trimester [multiple of the median (MoM)]. Seven PFAS were measured in second-trimester maternal serum. Multivariate imputation by chained equations and inverse probability weighting were used to evaluate robustness of linear associations. PFAS mixture effects were estimated by Bayesian kernel machine regression.
RESULTS
Perfluorohexane sulfonic acid (PFHxS) [: 0.29 log MoM units per log PFHxS; 95% confidence interval (CI): 0.08, 0.51] and perfluorodecanoic acid (PFDA) (hCG: ; 95% CI: , ) were associated with hCG in the single chemical and mixture analyses. The PFAS mixture was negatively associated with and positively with . Subgroup analyses revealed that PFAS associations with hCG differed by maternal race/ethnicity and education. Perfluoropentanoic acid (PFPeA) was associated with only in Black participants (; 95% CI: , ) and in participants with high school education or less (; 95% CI: , ); conversely, perfluorononanoic acid (PFNA) was negatively associated with only in White participants (; 95% CI: , ) and with only in participants with a college education or greater (; 95% CI: , ). These findings were robust to testing for selection bias, confounding bias, and left truncation bias where PFAS detection frequency was . Two associations were negative in male (and null in female) pregnancies: Perfluoroundecanoic acid (PFUnDA) with , and PFNA with h-hCG.
CONCLUSIONS
Evidence was strongest for the association between PFHxS and PFDA with hCG in all participants and for PFPeA and PFNA within subgroups defined by social determinants and fetal sex. PFAS mixture associations with and differed, suggesting subunit-specific types of toxicity and/or regulation. Future studies will evaluate the biological, clinical and public health significance of these findings. https://doi.org/10.1289/EHP12950.
Topics: Humans; Female; Male; Pregnancy; Placenta; New York; Bayes Theorem; Chorionic Gonadotropin; Fluorocarbons; Environmental Pollutants; Alkanesulfonic Acids; Decanoic Acids; Fatty Acids; Pentanoic Acids
PubMed: 38625811
DOI: 10.1289/EHP12950 -
Biosensors & Bioelectronics Jul 2024Lateral flow immunoassays (LFIAs) are an essential and widely used point-of-care test for medical diagnoses. However, commercial LFIAs still have low sensitivity and...
Lateral flow immunoassays (LFIAs) are an essential and widely used point-of-care test for medical diagnoses. However, commercial LFIAs still have low sensitivity and specificity. Therefore, we developed an automatic ultrasensitive dual-color enhanced LFIA (DCE-LFIA) by applying an enzyme-induced tyramide signal amplification method to a double-antibody sandwich LFIA for antigen detection. The DCE-LFIA first specifically captured horseradish peroxidase (HRP)-labeled colored microspheres at the Test line, and then deposited a large amount of tyramide-modified signals under the catalytic action of HRP to achieve the color superposition. A limit of detection (LOD) of 3.9 pg/mL and a naked-eye cut-off limit of 7.8 pg/mL were achieved for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein. Additionally, in the inactivated virus detections, LOD equivalent to chemiluminescence (0.018 TCID/mL) was obtained, and it had excellent specificity under the interference of other respiratory viruses. High sensitivity has also been achieved for detection of influenza A, influenza B, cardiac troponin I, and human chorionic gonadotrophin using this DCE-LFIA, suggesting the assay is universally applicable. To ensure the convenience and stability in practical applications, we created an automatic device. It provides a new practical option for point-of-care test immunoassays, especially ultra trace detection and at-home testing.
Topics: Immunoassay; Humans; SARS-CoV-2; Biosensing Techniques; Limit of Detection; COVID-19; Horseradish Peroxidase; Troponin I; Point-of-Care Testing; Coronavirus Nucleocapsid Proteins; Chorionic Gonadotropin; Influenza A virus; Phosphoproteins
PubMed: 38621340
DOI: 10.1016/j.bios.2024.116262 -
Journal of Clinical Medicine Mar 2024Adverse childhood experiences (ACEs) are extremely prevalent in the United States population. Although ACEs occurs in childhood, exposure to them has been associated...
Adverse childhood experiences (ACEs) are extremely prevalent in the United States population. Although ACEs occurs in childhood, exposure to them has been associated with adverse future pregnancy outcomes and an increased risk of poorer social determinants of health, which further drive the risk of negative pregnancy outcomes. In addition, maternal ACE exposure has been linked to poor infant and child outcomes, highlighting the intergenerational transmission of risk from mother to child. While alterations along the Maternal-Placental-Fetal Hypothalamic-pituitary-adrenal (HPA) axis is hypothesized to be involved, the exact biological pathway underlying this intergenerational passage of risk is mostly unknown. This present work will highlight what is known about pregnancy-related stress hormone physiology, discuss the potential mechanisms of action of ACEs on cortisol regulation, and suggest opportunities for further clinical and translational studies.
PubMed: 38610785
DOI: 10.3390/jcm13072020 -
The Journal of Maternal-fetal &... Dec 2024Noninvasive prenatal testing (NIPT) is the most common method for prenatal aneuploidy screening. Low fetal fraction (LFF) is the primary reason for NIPT failure....
BACKGROUND
Noninvasive prenatal testing (NIPT) is the most common method for prenatal aneuploidy screening. Low fetal fraction (LFF) is the primary reason for NIPT failure. Consequently, factors associated with LFF should be elucidated for optimal clinical implementation of NIPT.
METHODS
In this study, NIPT data from January 2019 to December 2022 from the laboratory records and obstetrical and neonatal data from the electronic medical records were collected and analyzed. Subjects with FF >3.50% were assigned to the control group, subjects with FF <3.50% once were assigned to the LFF group, and subjects with FF <3.50% twice were assigned to the repetitive low fetal fraction (RLFF) group. Factors, including body mass index (BMI), gestational age, maternal age, twin pregnancy, and fertilization (IVF) known to be associated with LFF were assessed by Kruskal-Wallis test and logistic regression. Clinical data on first trimester pregnancy-associated plasma protein-A (PAPP-A), beta-human chorionic gonadotropin (β-hCG), gestational age at delivery, birth weight at delivery, and maternal diseases were obtained from the hospital's prenatal and neonatal screening systems (twin pregnancy was not included in the data on gestational age at delivery and the control group did not include data on maternal diseases.), and were analyzed using Kruskal-Wallis test and Chi-square test.
RESULTS
Among the total of 63,883 subjects, 63,605 subjects were assigned to the control group, 197 subjects were assigned to the LFF group, and 81 subjects were assigned to the RLFF group. The median of BMI in the three groups was 22.43 kg/m (control), 25.71 kg/m (LFF), and 24.54 kg/m (RLFF). The median gestational age in the three groups was 130 days (control), 126 days (LFF), and 122/133 days (RLFF). The median maternal age in the three groups was 29 (control), 29 (LFF), and 33-years-old (RLFF). The proportion of twin pregnancies in the three groups was 3.3% (control), 10.7% (LFF), and 11.7% (RLFF). The proportion of IVF in the three groups was 4.7% (control), 11.7% (LFF), and 21.3% (RLFF). The factors significantly associated with LFF included BMI [2.18, (1.94, 2.45), < 0.0001], gestational age [0.76, (0.67, 0.87), < 0.0001], twin pregnancy [1.62, (1.02, 2.52), = 0.0353], and IVF [2.68, (1.82, 3.86), < 0.0001]. The factors associated with RLFF included maternal age [1.54, (1.17, 2.05), = 0.0023] and IVF [2.55, (1.19, 5.54), = 0.016]. Multiples of the median (MOM) value of β-hCG and pregnant persons' gestational age at delivery were significantly decreased in the LFF and RLFF groups compared to the control group.
CONCLUSION
According to our findings based on the OR value, factors associated strongly with LFF include a high BMI and the use of IVF. Factors associated less strongly with LFF include early gestational age and twin pregnancy, while advanced maternal age and IVF were independent risk factors for a second LFF result.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Noninvasive Prenatal Testing; Cell-Free Nucleic Acids; Chorionic Gonadotropin, beta Subunit, Human; Prenatal Diagnosis; Pregnancy Trimester, First; DNA; Pregnancy-Associated Plasma Protein-A
PubMed: 38604949
DOI: 10.1080/14767058.2024.2338440 -
Cellular and Molecular Life Sciences :... Apr 2024Biological sex is a key variable influencing many physiological systems. Disease prevalence as well as treatment success can be modified by sex. Differences emerge...
Biological sex is a key variable influencing many physiological systems. Disease prevalence as well as treatment success can be modified by sex. Differences emerge already early in life and include pregnancy complications and adverse birth outcomes. The placenta is a critical organ for fetal development and shows sex-based differences in the expression of hormones and cytokines. Epigenetic regulation, such as DNA methylation (DNAm), may underlie the previously reported placental sexual dimorphism. We associated placental DNAm with fetal sex in three cohorts. Individual cohort results were meta-analyzed with random-effects modelling. CpG-sites differentially methylated with sex were further investigated regarding pathway enrichment, overlap with methylation quantitative trait loci (meQTLs), and hits from phenome-wide association studies (PheWAS). We evaluated the consistency of findings across tissues (CVS, i.e. chorionic villus sampling from early placenta, and cord blood) as well as with gene expression. We identified 10,320 epigenome-wide significant sex-differentially methylated probes (DMPs) spread throughout the epigenome of the placenta at birth. Most DMPs presented with lower DNAm levels in females. DMPs mapped to genes upregulated in brain, were enriched for neurodevelopmental pathways and significantly overlapped with meQTLs and PheWAS hits. Effect sizes were moderately correlated between CVS and placenta at birth, but only weakly correlated between birth placenta and cord blood. Sex differential gene expression in birth placenta was less pronounced and implicated genetic regions only marginally overlapped with those associated with differential DNAm. Our study provides an integrative perspective on sex-differential DNAm in perinatal tissues underscoring the possible link between placenta and brain.
Topics: Infant, Newborn; Humans; Pregnancy; Female; Male; DNA Methylation; Placenta; Epigenesis, Genetic; Sex Characteristics; Fetal Development
PubMed: 38600394
DOI: 10.1007/s00018-024-05208-0 -
Current Opinion in Obstetrics &... Jun 2024Identify the most recent and significant evidence regarding the ovulation trigger within the framework of a multicycle approach through DuoStim, providing valuable... (Review)
Review
PURPOSE OF REVIEW
Identify the most recent and significant evidence regarding the ovulation trigger within the framework of a multicycle approach through DuoStim, providing valuable insights for improving treatment strategies in patients with a poor prognosis.
RECENT FINDINGS
The trigger method plays a pivotal role in optimizing in-vitro fertilization (IVF) stimulation, influencing oocyte retrieval and maturation rates, as well as follicle recruitment in consecutive ovarian stimulations such as double stimulation. Decision-making involves multiple factors and, while guidelines exist for conventional stimulation, specific recommendations for the multicycle approach are not well established.
SUMMARY
The different methods for inducing oocyte maturation underscore the need for personalization of IVF protocols. The GnRH agonist trigger induces rapid luteolysis and establishes favorable hormonal conditions that do not adversely affect the recruitment of consecutive follicular waves in the context of DuoStim. It serves as a valid alternative to hCG in freeze-all cycles. This strategy might enhance the safety and flexibility of ovarian stimulations with no impact on oocyte competence and IVF efficacy.
Topics: Humans; Ovulation Induction; Female; Gonadotropin-Releasing Hormone; Fertilization in Vitro; Oocyte Retrieval; Pregnancy; Fertility Agents, Female; Prognosis; Triptorelin Pamoate; Pregnancy Rate; Chorionic Gonadotropin
PubMed: 38597577
DOI: 10.1097/GCO.0000000000000947