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Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Jul 2023Tumor markers have been widely used clinically. Detection of serum CA125 is one of the commonly used clinical methods for early screening and early diagnosis of...
OBJECTIVES
Tumor markers have been widely used clinically. Detection of serum CA125 is one of the commonly used clinical methods for early screening and early diagnosis of epithelial ovarian cancer, but it is difficult to diagnose epithelial ovarian cancer with a single specific tumor marker. In this study, the combinatorial tumor marker detection method was used to compare the value of each tumor marker alone and different combinations in the diagnosis of epithelial ovarian cancer.
METHODS
The clinical data of patients with epithelial ovarian cancer (=65) and ovarian benign disease (=29) were collected. Multiple tumor marker protein chip was used to detect cancer antigen 125 (CA125), carbohydrate antigen 242 (CA242), alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-HCG), carcinoembryonic antigen (CEA), cancer antigen 199 (CA199), neuron-specific enolase (NSE), Ferritin, cancer antigen 153 (CA153), and human growth hormone (HGH) serum levels, and to compare the differences between the benign and malignant ovarian tumors. The correlation between tumor markers and clinicopathologic features for ovarian epithelial carcinoma was analyzed by χ test. Spearman rank analysis showed the correlation between CA125 expression level and other tumor markers in epithelial ovarian cancer and the correlation between age and the above 10 tumor markers. Sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and diagnostic efficiency were used to evaluate the diagnostic value of single tumor marker and the combination of tumor markers.
RESULTS
The levels of β-HCG, NSE, CA153, and CA125 in the epithelial ovarian cancer group were higher than those in the ovarian benign disease group. The level of NSE in the serum of patients with epithelial ovarian cancer was related to the clinical stage of patients. In addition, the levels of CA242, β-HCG, CEA, NSE, Ferritin, CA153 in the serum of patients with epithelial ovarian cancer were positively correlated with CA125 (=0.497, <0.001; =0.612, <0.001; =0.358, =0.003; =0.680, <0.001; =0.322, =0.009; =0.609, <0.001, respectively), and the levels of β-HCG, Ferritin, CA153 were positively correlated with the patient's age (=0.256, =0.040; =0.325, =0.008; =0.249, =0.046, respectively). In the diagnosis of epithelial ovarian cancer, the sensitivity, Youden index, and diagnostic efficiency of CA125 detection alone were higher than the results of the other 9 separate detections. When CA153, CA199, CA242, Ferritin, and CEA were combined with CA125, the sensitivity of the combined detection of different combinations was higher than that of CA125 alone. The combined detection sensitivities of CA125+CEA and CA125+Ferritin+CEA were 89.2% and 90.8%, respectively, and the diagnostic efficiencies were both 84.1%, which were higher than those of other combinations. The Youden index of CA125+CEA joint detection was 0.616, which was higher than those of other combinations.
CONCLUSIONS
CA125 has a high diagnostic value in the diagnosis of epithelial ovarian cancer. The detection of combined tumor markers in serum has higher sensitivity and specificity in epithelial ovarian cancer.
Topics: Humans; Female; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Ovarian Epithelial; Clinical Relevance; Chorionic Gonadotropin, beta Subunit, Human; Ovarian Neoplasms; Ferritins
PubMed: 37724407
DOI: 10.11817/j.issn.1672-7347.2023.230090 -
Frontiers in Endocrinology 2023Gonadotropin-releasing hormone (GnRH1) and its receptor (GnRHR1) drive reproduction by regulating gonadotropins. Another form, GnRH2, and its receptor (GnRHR2), also... (Review)
Review
Gonadotropin-releasing hormone (GnRH1) and its receptor (GnRHR1) drive reproduction by regulating gonadotropins. Another form, GnRH2, and its receptor (GnRHR2), also exist in mammals. In humans, and genes are present, but coding errors in the gene are predicted to hinder full-length protein production. Nonetheless, mounting evidence supports the presence of a functional GnRHR2 in humans. GnRH2 and its receptor have been identified throughout the body, including peripheral reproductive tissues like the ovary, uterus, breast, and prostate. In addition, GnRH2 and its receptor have been detected in a wide number of reproductive cancer cells in humans. Notably, GnRH2 analogues have potent anti-proliferative, pro-apoptotic, and/or anti-metastatic effects on various reproductive cancers, including endometrial, breast, placental, ovarian, and prostate. Thus, GnRH2 is an emerging target to treat human reproductive cancers.
Topics: Female; Humans; Male; Germ Cells; Gonadotropin-Releasing Hormone; Receptors, LHRH; Urogenital Neoplasms
PubMed: 38260130
DOI: 10.3389/fendo.2023.1341162 -
Fertility and Sterility Dec 2023To study sperm parameters recovery and fertility outcomes in men with azoospermia or severe oligospermia caused by anabolic steroid use who underwent a standardized...
OBJECTIVE
To study sperm parameters recovery and fertility outcomes in men with azoospermia or severe oligospermia caused by anabolic steroid use who underwent a standardized treatment regimen for spermatogenesis recovery.
DESIGN AND SUBJECTS
A retrospective analysis of a cohort of men with a prior history of anabolic steroid use and infertility complaints (between 2018 and 2022) was conducted.
EXPOSURE
The standardized treatment approach involved discontinuing testosterone replacement therapy and administering a combination regimen of clomiphene citrate and human chorionic gonadotropin for a minimum of 3 to 6 months.
MAIN OUTCOME MEASURES
The main outcome measures included changes in sperm parameters, predominantly sperm concentration, and subsequent pregnancy outcomes.
RESULTS
A total of 45 men (median age 37 years, IQR 32-45) met the inclusion criteria for this analysis. Median duration of prior T use was 4 years (IQR 1.3-10), with the 2 most common modalities consisting of injection therapy (43.5%) and oral therapy (34.8%). The median initial sperm concentration was 0 million/cc (IQR 0-1.15), and 23 (51.1%) men initially presented with azoospermia. The median duration of combination human chorionic gonadotropin/clomid therapy was 5 months (IQR 3-12). In initially azoospermic men (N: 23), 5 were lost to follow-up, 6 (33.3%) progressed to severe oligospermia (<5 million/cc), 6 (33.3%) to oligospermia (<15 million/cc), 1 (5.6%) to normozoospermia (>15 million/cc), and 5 (27.8%) remained azoospermic after medical treatment for 6 months. Among the 24 couples who responded to the follow-up call, a total of 9 (37.5%) achieved a successful subsequent pregnancy. Of these, 33.3% (3 couples) used assisted reproductive technology, whereas 66.7% (6 couples) conceived naturally. On logistic regression analysis, no significant predictors for improved sperm parameters or successful pregnancy were identified.
CONCLUSION
Despite appropriate treatment regimens, a significant proportion of men with a prior history of anabolic steroid use continue to exhibit severe oligospermia, with more than half showing limited improvement in semen parameters after 6 months of treatment. Only a fraction of men achieves normozoospermia after treatment. Further research is needed to explore predictors for improved sperm parameters and successful pregnancy outcomes in men with a history of anabolic steroid use.
Topics: Pregnancy; Female; Humans; Male; Adult; Oligospermia; Azoospermia; Anabolic Androgenic Steroids; Testosterone; Retrospective Studies; Semen; Chorionic Gonadotropin; Clomiphene; Fertility
PubMed: 37769866
DOI: 10.1016/j.fertnstert.2023.09.016 -
Frontiers in Immunology 2024The transition from oviparity to viviparity and the establishment of feto-maternal communications introduced the placenta as the major anatomical site to provide... (Review)
Review
The transition from oviparity to viviparity and the establishment of feto-maternal communications introduced the placenta as the major anatomical site to provide nutrients, gases, and hormones to the developing fetus. The placenta has endocrine functions, orchestrates maternal adaptations to pregnancy at different periods of pregnancy, and acts as a selective barrier to minimize exposure of developing fetus to xenobiotics, pathogens, and parasites. Despite the fact that this ancient organ is central for establishment of a normal pregnancy in eutherians, the placenta remains one of the least studied organs. The first step of pregnancy, embryo implantation, is finely regulated by the trophoectoderm, the precursor of all trophoblast cells. There is a bidirectional communication between placenta and endometrium leading to decidualization, a critical step for maintenance of pregnancy. There are three-direction interactions between the placenta, maternal immune cells, and the endometrium for adaptation of endometrial immune system to the allogeneic fetus. While 65% of all systemically expressed human proteins have been found in the placenta tissues, it expresses numerous placenta-specific proteins, whose expression are dramatically changed in gestational diseases and could serve as biomarkers for early detection of gestational diseases. Surprisingly, placentation and carcinogenesis exhibit numerous shared features in metabolism and cell behavior, proteins and molecular signatures, signaling pathways, and tissue microenvironment, which proposes the concept of "cancer as ectopic trophoblastic cells". By extensive researches in this novel field, a handful of cancer biomarkers has been discovered. This review paper, which has been inspired in part by our extensive experiences during the past couple of years, highlights new aspects of placental functions with emphasis on its immunomodulatory role in establishment of a successful pregnancy and on a potential link between placentation and carcinogenesis.
Topics: Humans; Pregnancy; Female; Placenta; Animals; Placentation; Endometrium; Neoplasms; Embryo Implantation
PubMed: 38707901
DOI: 10.3389/fimmu.2024.1385762 -
The Science of the Total Environment Apr 2024Endocrine disrupting chemicals (EDCs) possess the capability to interfere with the endocrine system by binding to hormone receptors, for example on immune cells....
Endocrine disrupting chemicals (EDCs) possess the capability to interfere with the endocrine system by binding to hormone receptors, for example on immune cells. Specific effects have already been described for individual substances, but the impact of exposure to chemical mixtures during pregnancy on maternal immune regulation, placentation and fetal development is not known. In this study, we aimed to investigate the combined effects of two widespread EDCs, bisphenol A (BPA) and benzophenone-3 (BP-3), at allowed concentrations on crucial pregnancy processes such as implantation, placentation, uterine immune cell populations and fetal growth. From gestation day (gd) 0 to gd10, female mice were exposed to 4 μg/kg/d BPA, 50 mg/kg/d BP-3 or a BPA/BP-3 mixture. High frequency ultrasound and Doppler measurements were used to determine intrauterine fetal development and hemodynamic parameters. Furthermore, uterine spiral artery remodeling and placental mRNA expression were studied via histology and CHIP-RT-PCR, respectively. Effects of EDC exposure on multiple uterine immune cell populations were investigated using flow cytometry. We found that exposure to BP-3 caused intrauterine growth restriction in offspring at gd14, while BPA and BPA/BP-3 mixture caused varying effects. Moreover, placental morphology at gd12 and placental efficiency at gd14 were altered upon BP-3 exposure. Placental gene transcription was altered particularly in female offspring after in utero exposure to BP-3. Flow cytometry analyses revealed an increase in uterine T cells and NK cells in BPA and BPA/BP-3-treated dams at gd14. Doppler measurements revealed no effect on uterine hemodynamic parameters and spiral artery remodeling was not affected following EDC exposure. Our results provide evidence that exposure to BPA and BP-3 during early gestation affects fetal development in a sex-dependent manner, placental function and immune cell frequencies at the feto-maternal interface. These results call for inclusion of studies addressing pregnancy in the risk assessment of environmental chemicals.
Topics: Pregnancy; Female; Mice; Animals; Placentation; Placenta; Benzhydryl Compounds; Fetal Development; Benzophenones; Phenols
PubMed: 38431166
DOI: 10.1016/j.scitotenv.2024.171386 -
Biology of Reproduction Dec 2023The placenta is a dynamic organ that must perform a remarkable variety of functions during its relatively short existence in order to support a developing fetus. These...
The placenta is a dynamic organ that must perform a remarkable variety of functions during its relatively short existence in order to support a developing fetus. These functions include nutrient delivery, gas exchange, waste removal, hormone production, and immune barrier protection. Proper placenta development and function are critical for healthy pregnancy outcomes, but the underlying genomic regulatory events that control this process remain largely unknown. We hypothesized that mapping sites of transcriptional enhancer activity and associated changes in gene expression across gestation in human placenta tissue would identify genomic loci and predicted transcription factor activity related to critical placenta functions. We used a suite of genomic assays [i.e., RNA-sequencing (RNA-seq), Precision run-on-sequencing (PRO-seq), and Chromatin immunoprecipitation-sequencing (ChIP-seq)] and computational pipelines to identify a set of >20 000 enhancers that are active at various time points in gestation. Changes in the activity of these enhancers correlate with changes in gene expression. In addition, some of these enhancers encode risk for adverse pregnancy outcomes. We further show that integrating enhancer activity, transcription factor motif analysis, and transcription factor expression can identify distinct sets of transcription factors predicted to be more active either in early pregnancy or at term. Knockdown of selected identified transcription factors in a trophoblast stem cell culture model altered the expression of key placental marker genes. These observations provide a framework for future mechanistic studies of individual enhancer-transcription factor-target gene interactions and have the potential to inform genetic risk prediction for adverse pregnancy outcomes.
Topics: Humans; Female; Pregnancy; Placentation; Placenta; Enhancer Elements, Genetic; Transcription Factors; Gene Expression Regulation
PubMed: 37694817
DOI: 10.1093/biolre/ioad119 -
Acta Obstetricia Et Gynecologica... Sep 2023Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin (hCG) are often treated with methotrexate (MTX), but expectant management with close monitoring is a feasible alternative. Studies comparing the two treatments have not shown a statistically significant difference in uneventful resolution of ectopic pregnancy, but these studies were too small to define whether certain subgroups could benefit more from either treatment.
MATERIAL AND METHODS
We performed a systematic review and individual participant data meta-analysis (IPD-MA) of randomized controlled trials comparing systemic MTX and expectant management in women with tubal ectopic pregnancy and low hCG (<2000 IU/L). A one-stage IPD-MA was performed to assess overall treatment effects of MTX and expectant management to generate a pooled intervention effect. Subgroup analyses and exploratory multivariable analyses were undertaken according to baseline serum hCG and progesterone levels. Primary outcome was treatment success, defined as resolution of clinical symptoms and decline in level of serum hCG to <20 IU/L, or a negative urine pregnancy test by the initial intervention strategy, without any additional treatment. Secondary outcomes were need for blood transfusion, surgical intervention, additional MTX side-effects and hCG resolution times.
TRIAL REGISTRATION NUMBER
PROSPERO: CRD42021214093.
RESULTS
1547 studies reviewed and 821 remained after duplicates removed. Five studies screened for eligibility and three IPD requested. Two randomized controlled trials supplied IPD, leading to 153 participants for analysis. Treatment success rate was 65/82 (79.3%) after MTX and 48/70 (68.6%) after expectant management (IPD risk ratio [RR] 1.16, 95% confidence interval [CI] 0.95-1.40). Surgical intervention rates were not significantly different: 8/82 (9.8%) vs 13/70 (18.6%) (RR 0.65, 95% CI 0.23-1.14). Mean time to success was 19.7 days (95% CI 17.4-22.3) after MTX and 21.2 days (95% CI 17.8-25.2) after expectant management (P = 0.25). MTX specific side-effects were reported in 33 MTX compared to four in the expectant group.
CONCLUSIONS
Our IPD-MA showed no statistically significant difference in treatment efficacy between MTX and expectant management in women with tubal ectopic pregnancy with low hCG. Initial expectant management could be the preferred strategy due to fewer side-effects.
Topics: Pregnancy; Humans; Female; Methotrexate; Watchful Waiting; Pregnancy, Tubal; Pregnancy, Ectopic; Chorionic Gonadotropin; Abortifacient Agents, Nonsteroidal; Retrospective Studies
PubMed: 37345445
DOI: 10.1111/aogs.14617 -
Climacteric : the Journal of the... Feb 2024We summarize convincing evidence that future cardiovascular disease (CVD) risk increases one-fold to four-fold for women with a history of pregnancy complicated by... (Review)
Review
We summarize convincing evidence that future cardiovascular disease (CVD) risk increases one-fold to four-fold for women with a history of pregnancy complicated by hypertensive disorders, gestational diabetes, fetal growth restriction, placental abruption and preterm birth. A concomitant occurrence of two or more complications in the same pregnancy further potentiates the risk. These women should be informed of their future CVD risks during the postpartum check-up taking place after delivery, and also, if needed, treated, for example, for persisting high blood pressure. In these women with high blood pressure, check-up should take place within 7-10 days, and if severe hypertension, within 72 h. Women without diagnostic signs and symptoms should be examined for the first time 1-2 years postpartum and then at intervals of 2-3 years for a complete CVD risk profile including clinical and laboratory assessments. Women should be informed for future CVD risks and their effective prevention with healthy lifestyle factors. Combined oral contraceptives should be avoided or used with caution. If laboratory or other clinical findings indicate, then vigorous treatments consisting of non-medical and medical (antihypertensives, statins, antidiabetic and anti-obesity therapies) interventions should be initiated early with liberal indications and with ambitious therapeutic goals. Low-dose aspirin and menopausal hormone therapy should be used in selected cases. Active control and treatment policies of these women with pregnancy-related risks will likely result in decreases of CVD occurrence in later life.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Cardiovascular Diseases; Premature Birth; Placenta; Hypertension; Risk Factors
PubMed: 38174425
DOI: 10.1080/13697137.2023.2287628 -
Current Heart Failure Reports Jun 2024The purpose of this review is to provide an overview of recent evidence on female-specific risk factors related to reproductive status or pregnancy. (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to provide an overview of recent evidence on female-specific risk factors related to reproductive status or pregnancy.
RECENT FINDINGS
Pregnancy-related factors, including hypertensive disorders and gestational diabetes, increase the risk of heart failure in women, while breastfeeding and hormone therapy may offer protection. Hypertensive disorders of pregnancy, gestational diabetes, polycystic ovarian syndrome, placental abruption, younger maternal age at first live birth, younger maternal age at last live birth, number of stillbirths, number of pregnancies, onset of menstruation before 12 years of age, shorter reproductive age, ovariectomy, and prolonged absence of ovarian hormones may increase the risk of heart failure in women. Conversely, breastfeeding status and hormone therapy (for menopause or contraception) may serve as protective factors, while fertility treatments have no discernible effect on the risk of heart failure.
Topics: Humans; Female; Heart Failure; Pregnancy; Risk Factors; Global Health
PubMed: 38507017
DOI: 10.1007/s11897-024-00657-x -
Environmental Research Oct 2023Bisphenols and Perfluoroalkyls are chemical compounds widely used in industry known to be endocrine disruptors (EDs). Once ingested through contaminated aliments, they...
Bisphenols and Perfluoroalkyls are chemical compounds widely used in industry known to be endocrine disruptors (EDs). Once ingested through contaminated aliments, they mimic the activity of endogenous hormones leading to a broad spectrum of diseases. Due to the extensive use of plastic in human life, particular attention should be paid to antenatal exposure to Bisphenols and Perfluoroalkyls since they cross the placental barrier and accumulates in developing embryo. Here we investigated the effects of Bisphenol-A (BPA), Bisphenol-S (BPS), perfluorooctane-sulfonate (PFOS) and perfluorooctanoic-acid (PFOA), alone or combined, on human-induced pluripotent stem cells (hiPSCs) that share several biological features with the stem cells of blastocysts. Our data show that these EDs affect hiPSC inducing a great mitotoxicity and dramatic changes in genes involved in the maintenance of pluripotency, germline specification, and epigenetic regulation. We also evidenced that these chemicals, when combined, may have additive, synergistic but also negative effects. All these data suggest that antenatal exposure to these EDs may affect the integrity of stem cells in the developing embryos, interfering with critical stages of early human development that might be determinant for fertility. The observation that the effects of exposure to a combination of these chemicals are not easily foreseeable further highlights the need for wider awareness of the complexity of the EDs effects on human health and of the social and economic burden attributable to these compounds.
Topics: Humans; Female; Pregnancy; Epigenesis, Genetic; Placenta; Infertility; Fertility; Benzhydryl Compounds; Fluorocarbons; Endocrine Disruptors
PubMed: 37419196
DOI: 10.1016/j.envres.2023.116487