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Endocrinology Apr 2024The glycoprotein receptors, members of the large G protein-coupled receptor family, are characterized by a large extracellular domains responsible for binding their...
The glycoprotein receptors, members of the large G protein-coupled receptor family, are characterized by a large extracellular domains responsible for binding their glycoprotein hormones. Hormone-receptor interactions are traditionally analyzed by ligand-binding assays, most often using radiolabeling but also by thermal shift assays. Despite their high sensitivity, these assays require appropriate laboratory conditions and, often, purified plasma cell membranes, which do not provide information on receptor localization or activity because the assays typically focus on measuring binding only. Here, we apply bioluminescence resonance energy transfer in living cells to determine hormone-receptor interactions between a Gaussia luciferase (Gluc)-luteinizing hormone/chorionic gonadotropin receptor (LHCGR) fusion and its ligands (human chorionic gonadotropin or LH) fused to the enhanced green fluorescent protein. The Gluc-LHCGR, as well as other Gluc-G protein-coupled receptors such as the somatostatin and the C-X-C motif chemokine receptors, is expressed on the plasma membrane, where luminescence activity is equal to membrane receptor expression, and is fully functional. The chimeric enhanced green fluorescent protein-ligands are properly secreted from cells and able to bind and activate the wild-type LHCGR as well as the Gluc-LHCGR. Finally, bioluminescence resonance energy transfer was used to determine the interactions between clinically relevant mutations of the hormones and the LHCGR that show that this bioassay provides a fast and effective, safe, and cost-efficient tool to assist the molecular characterization of mutations in either the receptor or ligand and that it is compatible with downstream cellular assays to determine receptor activation/function.
Topics: Humans; Green Fluorescent Proteins; Protein Binding; Receptors, LH; Luciferases; Animals; Bioluminescence Resonance Energy Transfer Techniques; Chorionic Gonadotropin; HEK293 Cells; Recombinant Fusion Proteins; Energy Transfer; Glycoproteins; Luminescent Measurements
PubMed: 38679471
DOI: 10.1210/endocr/bqae052 -
International Journal of Molecular... Apr 2024Preeclampsia, a serious complication of pregnancy, involves intricate molecular and cellular mechanisms. Fetal microchimerism, where fetal cells persist within maternal... (Review)
Review
Preeclampsia, a serious complication of pregnancy, involves intricate molecular and cellular mechanisms. Fetal microchimerism, where fetal cells persist within maternal tissues and in circulation, acts as a mechanistic link between placental dysfunction and maternal complications in the two-stage model of preeclampsia. Hormones, complements, and cytokines play pivotal roles in the pathophysiology, influencing immune responses, arterial remodeling, and endothelial function. Also, soluble HLA-G, involved in maternal-fetal immune tolerance, is reduced in preeclampsia. Hypoxia-inducible factor 1-alpha (Hif-α) dysregulation leads to placental abnormalities and preeclampsia-like symptoms. Alterations in matrix metalloproteinases (MMPs), endothelins (ETs), chemokines, and cytokines contribute to defective trophoblast invasion, endothelial dysfunction, and inflammation. Preeclampsia's genetic complexity includes circRNAs, miRNAs, and lncRNAs. CircRNA_06354 is linked to early-onset preeclampsia by influencing trophoblast invasion via the hsa-miR-92a-3p/VEGF-A pathway. The dysregulation of C19MC, especially miR-519d and miR-517-5p, affects trophoblast function. Additionally, lncRNAs like IGFBP1 and EGFR-AS1, along with protein-coding genes, impact trophoblast regulation and angiogenesis, influencing both preeclampsia and fetal growth. Besides aberrations in CD31+ cells, other potential biomarkers such as MMPs, soluble HLA-G, and hCG hold promise for predicting preeclampsia and its complications. Therapeutic interventions targeting factors such as peroxisome PPAR-γ and endothelin receptors show potential in mitigating preeclampsia-related complications. In conclusion, preeclampsia is a complex disorder with a multifactorial etiology and pathogenesis. Fetal microchimerism, hormones, complements, and cytokines contribute to placental and endothelial dysfunction with inflammation. Identifying novel biomarkers and therapeutic targets offers promise for early diagnosis and effective management, ultimately reducing maternal and fetal morbidity and mortality. However, further research is warranted to translate these findings into clinical practice and enhance outcomes for at-risk women.
Topics: Female; Humans; Pregnancy; Biomarkers; Hormones; MicroRNAs; Placenta; Pre-Eclampsia; Trophoblasts
PubMed: 38674114
DOI: 10.3390/ijms25084532 -
Current Issues in Molecular Biology Apr 2024The glycoprotein hormones LH, FSH, TSH and chorionic gonadotropin consist of a common α-subunit and a hormone-specific β-subunit. The α-subunit is expressed in the...
The glycoprotein hormones LH, FSH, TSH and chorionic gonadotropin consist of a common α-subunit and a hormone-specific β-subunit. The α-subunit is expressed in the pituitary and the placental cells, and its expression is regulated by extracellular signal molecules. Much is known about the regulation of the α-subunit gene in the pituitary, but few studies have addressed the regulation of this gene in trophoblasts. The aim of this study was to characterize the molecular mechanism of stimulus-induced α-subunit gene transcription in JEG-3 cells, a cellular model for human trophoblasts, using chromatin-embedded reporter genes under the control of the α-subunit promoter. The results show that increasing the concentration of the second messengers cAMP or Ca, or expressing the catalytic subunit of cAMP-dependent protein kinase in the nucleus activated the α-subunit promoter. Similarly, the stimulation of p38 protein kinase activated the α-subunit promoter, linking α-subunit expression to stress response. The stimulation of a Gαq-coupled designer receptor activated the α-subunit promoter, involving the transcription factor CREB, linking α-subunit expression to hormonal stimulation and an increase in intracellular Ca. Deletion mutagenesis underscores the importance of a tandem cAMP response element within the glycoprotein hormone α-subunit promoter, which acts as a point of convergence for a multiple signaling pathway.
PubMed: 38666932
DOI: 10.3390/cimb46040202 -
Frontiers in Public Health 2024Recent evidence has revealed associations between endocrine-disrupting chemicals (EDCs) and placental insufficiency due to altered placental growth, syncytialization,...
Recent evidence has revealed associations between endocrine-disrupting chemicals (EDCs) and placental insufficiency due to altered placental growth, syncytialization, and trophoblast invasion. However, no epidemiologic study has reported associations between exposure to EDCs and asymmetric fetal growth restriction (FGR) caused by placenta insufficiency. The aim of this study was to evaluate the association between EDC exposure and asymmetric FGR. This was a prospective cohort study including women admitted for delivery to the Maternal Fetal Center at Seoul St. Mary's Hospital between October 2021 and October 2022. Maternal urine and cord blood samples were collected, and the levels of bisphenol-A (BPA), monoethyl phthalates, and perfluorooctanoic acid in each specimen were analyzed. We investigated linear and non-linear associations between the levels of EDCs and fetal growth parameters, including the head circumference (HC)/abdominal circumference (AC) ratio as an asymmetric parameter. The levels of EDCs were compared between fetuses with and without asymmetric FGR. Of the EDCs, only the fetal levels of BPA showed a linear association with the HC/AC ratio after adjusting for confounding variables ( = 0.003, < 0.05). When comparing the normal growth and asymmetric FGR groups, the asymmetric FGR group showed significantly higher maternal and fetal BPA levels compared to the normal growth group (maternal urine BPA, 3.99 μg/g creatinine vs. 1.71 μg/g creatinine [ < 0.05]; cord blood BPA, 1.96 μg/L vs. -0.86 μg/L [ < 0.05]). In conclusion, fetal exposure levels of BPA show linear associations with asymmetric fetal growth patterns. High maternal and fetal exposure to BPA might be associated with asymmetric FGR.
Topics: Humans; Female; Endocrine Disruptors; Prospective Studies; Pregnancy; Fetal Growth Retardation; Adult; Benzhydryl Compounds; Phenols; Maternal Exposure; Fetal Blood; Fluorocarbons; Phthalic Acids; Caprylates; Placental Insufficiency; Republic of Korea; Seoul
PubMed: 38665245
DOI: 10.3389/fpubh.2024.1351786 -
Clinical Endocrinology Apr 2024The aim of this study was to investigate the feasibility of different gonadotropin assays for determining total and intact luteinizing hormone (LH), and...
OBJECTIVE
The aim of this study was to investigate the feasibility of different gonadotropin assays for determining total and intact luteinizing hormone (LH), and follicle-stimulating hormone (FSH) immunoreactivity in urine (U-LH-ir and U-FSH-ir, respectively) during early infancy.
DESIGN, PATIENTS AND MEASUREMENTS
Morning urine samples were obtained from 31 infants, aged between 0 and 6 months, to study the age-related course of urinary gonadotropins. Additionally, we investigated bi-hourly urine samples of a 5-day-old male neonate for 24 h to observe the course of urinary gonadotropins during a daily cycle. We employed different immunofluorometric assays for measuring total and intact U-LH-ir, and U-FSH-ir.
RESULTS
In neonates up to 21 days of age, the U-LH-ir levels measured by the regular LH assay (also detecting hCG) were significantly higher than those determined by the total (specific) LH assays (p = .004). U-FSH-ir was higher in girls than boys during both the first and the next 5 months (p = .02 and p < .001, respectively), whereas total U-LH-ir was higher in boys until 6 months of age (p < .001). Total U-LH-ir/U-FSH-ir ratio was significantly higher in boys than girls across the first half-year (p < .001).
CONCLUSIONS
The assessment of total U-LH-ir and U-FSH-ir, and their respective ratio constitutes a noninvasive, practical and scalable tool to investigate sex-specific changes during early infancy, with the ratio being significantly higher in boys than girls. Only highly specific LH assays detecting beta-subunit and its core fragment in addition to intact LH should be used for determining U-LH-ir in the neonatal period to avoid potential cross-reactivity with hCG of placental origin.
PubMed: 38664930
DOI: 10.1111/cen.15064 -
The Journal of International Medical... Apr 2024We investigated the efficacy of a combination of laparoscopy and bilateral uterine artery occlusion (BUAO) for the treatment of type II cesarean scar pregnancy (CSP).
OBJECTIVE
We investigated the efficacy of a combination of laparoscopy and bilateral uterine artery occlusion (BUAO) for the treatment of type II cesarean scar pregnancy (CSP).
METHODS
Patients with type II CSP underwent laparoscopy + bilateral uterine artery embolization (control group) or laparoscopy + BUAO (study group). Data regarding the duration of surgery, intraoperative hemorrhage, postoperative complications, the duration of the hospital stay, and the costs of hospitalization were retrospectively collected. One year later, the time to the return of the β-human chorionic gonadotropin (β-hCG) concentration to normal and to the return of menstruation were compared.
RESULTS
The duration of surgery, time to the return of menstruation, and incidence of postoperative complications in the study group were significantly less than in the control group, but there was no significant difference in the time for β-hCG to return to normal or the volume of intraoperative hemorrhage. The duration of hospitalization and costs for the control group were higher than those for the study group.
CONCLUSION
Laparoscopy in combination with BUAO is associated with minimal trauma, rapid recovery, a short duration of surgery, low cost of hospitalization, and a low postoperative complication rate. Thus, it represents a useful new surgical treatment for type II CSP.
Topics: Humans; Female; Laparoscopy; Pregnancy; Adult; Cesarean Section; Retrospective Studies; Cicatrix; Uterine Artery Embolization; Pregnancy, Ectopic; Uterine Artery; Postoperative Complications; Length of Stay; Treatment Outcome; Chorionic Gonadotropin, beta Subunit, Human
PubMed: 38663910
DOI: 10.1177/03000605241241010 -
Journal of Perinatal Medicine Jun 2024We aimed to analyze trends in the rate of effective antenatal corticosteroid prophylaxis (ACS) administrations across a spectrum of typical diagnoses associated with...
OBJECTIVES
We aimed to analyze trends in the rate of effective antenatal corticosteroid prophylaxis (ACS) administrations across a spectrum of typical diagnoses associated with preterm birth.
METHODS
In this retrospective study we utilized delivery data after ACS from 2014 to 2020 at Charité Berlin, Germany. We evaluated the rate of effective ACS administrations defined as ≤10 days between last dose of ACS and delivery as well as the rate of post-ACS births on/after 37 + 0 weeks. We explored conditions associated with high rates of ineffective ACS administrations (>10 days before delivery). We analyzed the trend of ACS-effectiveness during the study period in the overall cohort and in placental dysfunction and cervical insufficiency diagnoses.
RESULTS
The overall rate of effective ACS administrations was 42 % (709/1,672). The overall percentage of deliveries after/at 37 + 0 weeks following ACS administration was 19 % (343). Placenta previa, twin pregnancy and isthmocervical insufficiency were associated with ineffective ACS (19-34 % effective i.e. ≤10 days before delivery). The overall ratio of effective ACS applications rose over time (p=0.002). Over the course of this study ACS effectiveness increased in placental dysfunction and isthmocervical insufficiency diagnoses (p=0.028; p=0.001).
CONCLUSIONS
Compared to a previous publication we found a decrease of post-ACS deliveries after/at 37 + 0 weeks (19 vs. 27 %). Ineffective ACS administrations are still frequent in patients with placenta previa, twin pregnancy and isthmocervical insufficiency. It remains to be investigated in future trials if the introduction of new diagnostic tools such as soluble Fms-like tyrosinkinase-1/placental growth factor (sFlt-1/PlGF) testing and placental alpha-microglobulin-1 (PAMG-1) testing directly led to an increased ACS effectiveness.
Topics: Humans; Female; Pregnancy; Retrospective Studies; Premature Birth; Adult; Adrenal Cortex Hormones; Prenatal Care; Infant, Newborn
PubMed: 38662540
DOI: 10.1515/jpm-2023-0353 -
Research Square Apr 2024Intrauterine factors can impact fetal and child growth and may underlie the developmental origins of childhood obesity. Sex steroid hormone exposure during pregnancy is...
OBJECTIVE
Intrauterine factors can impact fetal and child growth and may underlie the developmental origins of childhood obesity. Sex steroid hormone exposure during pregnancy is a plausible target because of the impact on placental vascularization, nutrient transportation, bone growth, adipogenesis, and epigenetic modifications. In this study we assessed maternal sex steroid hormones in each trimester in relation to birthweight, neonatal adiposity, and infant growth trajectories, and evaluate sensitive windows of development.
METHODS
Participants from a prospective pregnancy cohort who delivered at term were included in the analysis (n=252). Estrone, estradiol, and estriol, as well as total and free testosterone throughout gestation were assessed using high-performance liquid chromatography and tandem mass spectrometry. Path analyses were used to assess the direct associations of sex steroid hormones in each trimester with birth outcomes and infant growth trajectories (birth to 12 months) adjusting for covariates and considering moderation by sex.
RESULTS
The associations between prenatal sex steroid hormones and fetal/infant growth varied by sex and hormone assessment timing. First trimester estrone were associated with higher birthweight z-scores (β=0.37, 95%CI: 0.02, 0.73) and truncal skinfold thickness (TST) at birth (β=0.94, 95%CI: 0.34, 1.54) in female infants. Third trimester total testosterone was associated with higher TST at birth (β=0.61, 95%CI: 0.02, 1.21) in male infants. First trimester estrone/estradiol and first and third trimesters testosterone were associated with lower probabilities of high stable weight trajectory compared to low stable weight trajectory (Estrone: β=-3.87, 95%CI: -6.59, -1.16; First trimester testosterone: β=-3.53, 95%CI: -6.63, -0.43; Third trimester testosterone: β=-3.67, 95%CI: -6.66, -0.69) during infancy in male infants.
CONCLUSIONS
We observed associations between prenatal sex steroid hormone exposure and birthweight, neonatal adiposity and infant growth that were sex and gestational timing dependent. Our findings suggest further investigation on additional mechanisms linking prenatal sex steroid exposure and fetal/postnatal growth is needed.
PubMed: 38659862
DOI: 10.21203/rs.3.rs-4178000/v1 -
Animal Reproduction Science Jun 2024This study investigated the effect of hCG or GnRH on structural changes of the corpora lutea (CL) and the regulation of the expression of steroidogenic enzymes involved...
This study investigated the effect of hCG or GnRH on structural changes of the corpora lutea (CL) and the regulation of the expression of steroidogenic enzymes involved in P secretion in post-ovulatory (po-CL) and accessory CL (acc-CL). Sixty-four ewes were assigned to three groups receiving: 300 IU of hCG (hCG) or 4 µg Buserelin (GnRH) or 1 mL of saline solution (Control) on Day (d) 4 post artificial insemination (FTAI). Laparoscopic ovarian were performed on d 4, 14 and, 21 post-FTAI to determine the numbers of CL. Blood samples were collected for serum LH and P analysis. On d 14 post-FTAI, both CL were removed from the ovary to determine large luteal cell (LLC) number and to evaluate the expression of steroidogenic enzymes (HSD3B1, STAR, CYP11A1). Only hCG and GnRH treated ewes generated acc-CL. The LLC in both po- and acc-CL were significantly greater in the hCG group compared to GnRH and Control groups (P<0.05). Overall, hCG group showed the greatest immunodetection of HSD3B1and STAR in both po- and acc-CL (P<0.05). rnRNA expression of HSD3B1, STAR and CYP11A1 in the acc-CL tended to be greater in hCG group than in GnRH group (P<0.1). The LH concentration was increased in GnRH group (P<0.05) and P concentration was greater in hCG group compared to the other groups (P<0.05). In conclusion, administration of hCG has a notably impact on acc-CL development and the expression of steroidogenic enzymes compared to GnRH treatment in ewes. This leads to elevated P concentration and improved luteal function.
Topics: Animals; Female; Sheep; Corpus Luteum; Progesterone; Chorionic Gonadotropin; Gonadotropin-Releasing Hormone; Luteal Phase; Cholesterol Side-Chain Cleavage Enzyme; Luteinizing Hormone; Phosphoproteins
PubMed: 38657463
DOI: 10.1016/j.anireprosci.2024.107474 -
European Journal of Surgical Oncology :... Apr 2024Congenital tumors are rare, and malignant congenital tumors are uncommon. Benign tu,mors might be life-threatening, depending on the location and size of the tumor....
Congenital tumors are rare, and malignant congenital tumors are uncommon. Benign tu,mors might be life-threatening, depending on the location and size of the tumor. Different factors affect congenital tumors, such as maternal and placental hormones and environmental factors such as drugs, radiation, and infection. Developing fetal imaging methods and continuous follow-up during pregnancy are important factors in congenital tumor prognosis. Ultrasound is the most common method used for fetal evaluation. The complementary evaluation method is MRI. Both methods are helpful and widely spread for the detection of congenital tumors. These imaging methods help the medical team make a suitable decision about therapy. Some of these tumors regressed spontaneously, and some need surgical treatments. Treatment of tumors has developed rapidly, and recently molecular-targeted drugs have been used.
PubMed: 38653587
DOI: 10.1016/j.ejso.2024.108316