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Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Feb 2021Heterotopic pregnancies are rare and difficult to be diagnosed early. A patient with combined intrauterine pregnancy and cervical pregnancy was admitted in Qingdao...
Heterotopic pregnancies are rare and difficult to be diagnosed early. A patient with combined intrauterine pregnancy and cervical pregnancy was admitted in Qingdao Municipal Hospital in 2019. The patient complained of abnormal vaginal bleeding after menopause and was misdiagnosed as simple intrauterine pregnancy. She underwent artificial abortion and suffered intraoperative hemorrhage. To stop bleeding, she received the treatment of uterine artery embolization immediately. Afterwards, cervical residual pregnancy tissues started necrosis, blood β-human chorionic gonadotropin level and the cervix appearance gradually returned to normal. This report suggests that cervical heterotopic pregnancy inclines to be mis diagnosed. Correct diagnosis should be made as soon as possible. Selective uterine artery embolization is an effective measure to prevent and treat massive bleeding.
Topics: Chorionic Gonadotropin, beta Subunit, Human; Female; Humans; Pregnancy; Pregnancy, Heterotopic; Uterine Artery Embolization; Uterine Hemorrhage
PubMed: 33678661
DOI: 10.11817/j.issn.1672-7347.2021.190712 -
The Journal of Physiology Jul 2021Fetal glucagon concentrations are elevated in the setting of placental insufficiency, hypoxia and elevated stress hormones. Chronically elevated glucagon concentrations...
KEY POINTS
Fetal glucagon concentrations are elevated in the setting of placental insufficiency, hypoxia and elevated stress hormones. Chronically elevated glucagon concentrations in the adult result in profound decreases in amino acid concentrations and lean body mass. Experimental elevation of fetal glucagon concentrations in a late-gestation pregnant sheep results in lower fetal amino acid concentrations, lower protein accretion and lower fetal weight, in addition to decreased placental function. This study demonstrates a negative effect of glucagon on fetal protein accretion and growth, and also provides the first example of a fetal hormone that negatively regulates placental nutrient transport and blood flow.
ABSTRACT
Fetal glucagon concentrations are elevated in the setting of placental insufficiency and fetal stress. Postnatal studies have demonstrated the importance of glucagon in amino acid metabolism, and limited fetal studies have suggested that glucagon inhibits umbilical uptake of certain amino acids. We hypothesized that chronic fetal hyperglucagonaemia would decrease amino acid transfer and increase amino acid oxidation by the fetus. Late gestation singleton fetal sheep received a direct intravenous infusion of glucagon (GCG; 5 or 50 ng/kg/min; n = 7 and 5, respectively) or a vehicle control (n = 10) for 8-10 days. Fetal and maternal nutrient concentrations, uterine and umbilical blood flows, fetal leucine flux, nutrient uptake rates, placental secretion of chorionic somatomammotropin (CSH), and targeted placental gene expression were measured. GCG fetuses had 13% lower fetal weight compared to controls (P = 0.0239) and >28% lower concentrations of 16 out of 21 amino acids (P < 0.02). Additionally, protein synthesis was 49% lower (P = 0.0005), and protein accretion was 92% lower in GCG fetuses (P = 0.0006). Uterine blood flow was 33% lower in ewes with GCG fetuses (P = 0.0154), while umbilical blood flow was similar. Fetal hyperglucagonaemia lowered uterine uptake of 10 amino acids by >48% (P < 0.05) and umbilical uptake of seven amino acids by >29% (P < 0.04). Placental secretion of CSH into maternal circulation was reduced by 80% compared to controls (P = 0.0080). This study demonstrates a negative effect of glucagon on fetal protein accretion and growth. It also demonstrates that glucagon, a hormone of fetal origin, negatively regulates maternal placental nutrient transport function, placental CSH production and uterine blood flow.
Topics: Animals; Female; Fetal Development; Fetus; Glucagon; Placenta; Placental Insufficiency; Pregnancy; Sheep
PubMed: 33878802
DOI: 10.1113/JP281288 -
Archives of Gynecology and Obstetrics Feb 2021Labor is a complex process involving multiple para-, auto- and endocrine cascades. The interaction of cortisol, corticotropin-releasing hormone (CRH) and progesterone is...
PURPOSE
Labor is a complex process involving multiple para-, auto- and endocrine cascades. The interaction of cortisol, corticotropin-releasing hormone (CRH) and progesterone is essential. The action of cortisol on the human feto-placental unit is regulated by 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2/HSD11B2) that converts cortisol into inactive cortisone. The majority of studies on the assessment of placental 11β-HSD2 function determined indirect activity parameters. It remains elusive if indirect measurements correlate with enzymatic function and if these parameters are affected by potential confounders (e.g., mode of delivery). Thus, we compared determinants of indirect 11β-HSD2 tissue activity with its direct enzymatic turnover rate in placental samples from spontaneous births and cesarean (C)-sections.
METHODS
Using LC-MS/MS, we determined CRH, cortisol, cortisone, progesterone and 17-hydroxy(OH)-progesterone in human term placentas (spontaneous birth vs. C-section, n = 5 each) and measured the enzymatic glucocorticoid conversion rates in placental microsomes. Expression of HSD11B1, 2 and CRH was determined via qRT-PCR in the same samples.
RESULTS
Cortisol-cortisone ratio correlated with direct microsomal enzymatic turnover. While this observation seemed independent of sampling site, a strong influence of mode of delivery on tissue steroids was observed. The mRNA expression of HSD11B2 correlated with indirect and direct cortisol turnover rates in C-section placentas only. In contrast to C-sections, CRH, cortisol and cortisone levels were significantly increased in placental samples following spontaneous birth.
CONCLUSION
Labor involves a series of complex hormonal processes including activation of placental CRH and glucocorticoid metabolism. This has to be taken into account when selecting human cohorts for comparative analysis of placental steroids.
Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 2; Adult; Chromatography, Liquid; Corticotropin-Releasing Hormone; Cortisone; Female; Gene Expression; Glucocorticoids; Humans; Hydrocortisone; Labor, Obstetric; Placenta; Pregnancy; Progesterone; RNA, Messenger; Tandem Mass Spectrometry
PubMed: 32880710
DOI: 10.1007/s00404-020-05755-4 -
Reproduction & Fertility Jul 2022This study was carried out to investigate whether repeated controlled ovarian hyperstimulation (COH) affects ovarian reserve. For this reason, we aimed to show possible...
ABSTRACT
This study was carried out to investigate whether repeated controlled ovarian hyperstimulation (COH) affects ovarian reserve. For this reason, we aimed to show possible changes in the expression of PTEN and FOXO3, which are involved in preserving the over-reserve, after applying the COH protocol methods. For this purpose, 18 young Wistar albino female rats (8 weeks old) were randomly assigned as group 1 (control), group 2, and group 3 as 6 subjects in each group. Experimental groups were treated with 10 IU/0.1 mL pregnant mare's serum gonadotropin and a COH protocol consisting of 10 IU/0.1 mL human chorionic gonadotropin injection after 48 h. This procedure was applied three and five times to group 2 and group 3, respectively. For the control groups, the same procedures were performed with 0.1 mL of 0.9% sodium chloride solution. At the end of the experiment, the ovarium tissues were placed in a 10% neutral formaldehyde solution for light microscopic examinations. In histological sections stained with hematoxylin and eosin, the number of ovarian follicles was determined using the physical dissector method. However, the expression of PTEN, FOXO3, and LH-R molecules was evaluated by immunohistochemical methods. As a result of our study, it was concluded that COH administration reduces the expression levels of PTEN and FOXO3 proteins and LH-R, which are among the essential components of the PIK3 intracellular signaling pathway and also increased the levels of hormones such as follicle-stimulating hormone, estradiol, and luteinizing hormone, which are over-reserve markers, and causes adverse effects on the histological structure, oocyte morphology, and number of ovaries.
LAY SUMMARY
Today, approximately 10-15% of couples experience fertility problems. However, assisted reproductive techniques help people with fertility problems to get pregnant. The main purpose of these techniques is to put the sperm and egg together outside the woman's body where the eggs are fertilized and then to return the fertilized eggs (embryos) to the womb. During a woman's menstrual cycle, several hormones influence the growth of the eggs. This process can be mimicked by using various medications. Medication is given to increase the number of eggs that develop. However, this method is not the same as normal ovulation. Therefore, in our study, we wanted to examine the effect that developing multiple follicles has on the number and quality of eggs remaining for the future.
Topics: Animals; Female; Rats; Chorionic Gonadotropin; Follicle Stimulating Hormone; Ovarian Reserve; Ovulation Induction; PTEN Phosphohydrolase; Random Allocation; Rats, Wistar; Models, Animal
PubMed: 35972314
DOI: 10.1530/RAF-21-0075 -
Placenta Jan 2023Gestational diabetes (GDM) is traditionally thought to emerge from placental endocrine dysregulations, but recent evidence suggests that fetal sex can also impact GDM...
INTRODUCTION
Gestational diabetes (GDM) is traditionally thought to emerge from placental endocrine dysregulations, but recent evidence suggests that fetal sex can also impact GDM development. Understanding the molecular mechanisms through which sex modulates placenta physiology can help identify novel molecular targets for future clinical care. Thus, we investigated the nutrient-sensing O-GlcNAc pathway as a potential mediator of sex-specific placenta dysfunction in GDM.
METHODS
Expression levels of O-GlcNAc enzymes were measured in male and female (n = 9+/gender) human placentas based on the maternal diagnosis of GDM. We then simulated the observed differences in both BeWo cells and human syncytiotrophoblasts primary cells (SCT) from male and female origins (n = 6/gender). RNA sequencing and targeted qPCR were performed to characterize the subsequent changes in the placenta transcriptome related to gestational diabetes.
RESULTS
O-GlcNAc transferase (OGT) expression was significantly reduced only in male placenta collected from mothers with GDM compared to healthy controls. Similar downregulation of OGT in trophoblast-like BeWo male cells demonstrated significant gene expression deregulations that overlapped with known GDM-related genes. Notably, placental growth hormone (GH) production was significantly elevated, while compensatory factors against GH-related insulin resistance were diminished. Inflammatory and immunologic factors with toxic effects on pancreatic β cell mass were also increased, altogether leaning toward a decompensatory diabetic profile. Similar changes in hormone expression were confirmed in male human primary SCTs transfected with siOGT. However, down-regulating OGT in female primary SCTs did not impact hormone production.
CONCLUSION
Our study demonstrated the significant deregulation of placental OGT levels in mothers with GDM carrying a male fetus. When simulated in vitro, such deregulation impacted hormonal production in BeWo trophoblast cells and primary SCTs purified from male placentas. Interestingly, female placentas were only modestly impacted by OGT downregulation, suggesting that the sex-specific presentation observed in gestational diabetes could be related to O-GlcNAc-mediated regulation of placental hormone production.
Topics: Pregnancy; Female; Male; Humans; Placenta; Diabetes, Gestational; N-Acetylglucosaminyltransferases; Insulin
PubMed: 36442303
DOI: 10.1016/j.placenta.2022.11.006 -
International Journal of Molecular... Feb 2024Miscarriages affect 50-70% of all conceptions and 15-20% of clinically recognized pregnancies. Recurrent pregnancy loss (RPL, ≥2 miscarriages) affects 1-5% of...
Miscarriages affect 50-70% of all conceptions and 15-20% of clinically recognized pregnancies. Recurrent pregnancy loss (RPL, ≥2 miscarriages) affects 1-5% of recognized pregnancies. Nevertheless, our knowledge about the etiologies and pathophysiology of RPL is incomplete, and thus, reliable diagnostic/preventive tools are not yet available. Here, we aimed to define the diagnostic value of three placental proteins for RPL: human chorionic gonadotropin free beta-subunit (free-β-hCG), pregnancy-associated plasma protein-A (PAPP-A), and placental growth factor (PlGF). Blood samples were collected from women with RPL ( = 14) and controls undergoing elective termination of pregnancy ( = 30) at the time of surgery. Maternal serum protein concentrations were measured by BRAHMS KRYPTOR Analyzer. Daily multiple of median (dMoM) values were calculated for gestational age-specific normalization. To obtain classifiers, logistic regression analysis was performed, and ROC curves were calculated. There were differences in changes of maternal serum protein concentrations with advancing healthy gestation. Between 6 and 13 weeks, women with RPL had lower concentrations and dMoMs of free β-hCG, PAPP-A, and PlGF than controls. PAPP-A dMoM had the best discriminative properties (AUC = 0.880). Between 9 and 13 weeks, discriminative properties of all protein dMoMs were excellent (free β-hCG: AUC = 0.975; PAPP-A: AUC = 0.998; PlGF: AUC = 0.924). In conclusion, free-β-hCG and PAPP-A are valuable biomarkers for RPL, especially between 9 and 13 weeks. Their decreased concentrations indicate the deterioration of placental functions, while lower PlGF levels indicate problems with placental angiogenesis after 9 weeks.
Topics: Pregnancy; Female; Humans; Pregnancy-Associated Plasma Protein-A; Placenta Growth Factor; Pregnancy Trimester, First; Placenta; Pregnancy Proteins; Chorionic Gonadotropin, beta Subunit, Human; Biomarkers; Abortion, Habitual; Blood Proteins
PubMed: 38339143
DOI: 10.3390/ijms25031865 -
Journal of the Endocrine Society May 2021Adequate maternal thyroid hormone (TH) is necessary for fetal brain development. The role of placental human chorionic gonadotropin (hCG) in ensuring the production of...
Adequate maternal thyroid hormone (TH) is necessary for fetal brain development. The role of placental human chorionic gonadotropin (hCG) in ensuring the production of TH is less well understood. The objective of the study was to evaluate 1) associations of placental hCG and its subunits, and maternal TH in the second trimester, and 2) the single and joint effects of TH and placental hormones on cognitive development and communication at ages 1 and 3 years. Fifty individuals (5%) were selected from the CANDLE (Conditions Affecting Neurocognitive Development and Early Learning) pregnancy cohort in Memphis, Tennessee, with recruitment from 2006 to 2011, to equally represent male and female fetuses. Participants were 68% Black and 32% White. Hormones measured were maternal thyroid (thyrotropin [TSH] and free thyroxine [FT4]) and placental hormones (hCG, its hyperglycosylated form [hCG-h], and free α- [hCGα] and β-subunits [hCGβ]) in maternal serum (17-28 weeks). The primary outcome measurement was the Bayley Scales of Infant and Toddler Development. All forms of hCG were negatively associated with FT4 and not associated with TSH. hCGα was associated with cognitive development at age 1 year and jointly interacted with TSH to predict cognitive development at age 3 years. This pilot study added insight into the thyrotropic actions of hCG in the second trimester, and into the significance of this mechanism for brain development. More research is warranted to elucidate differences between hCGα, hCGβ, and hCG-h in relation to TH regulation and child brain function.
PubMed: 33928202
DOI: 10.1210/jendso/bvab027 -
European Thyroid Journal Dec 2019Thyroid hormone regulates vital processes in early brain development such as neuronal stem cell proliferation, migration, and myelination. The fetal thyroid is not fully... (Review)
Review
Thyroid hormone regulates vital processes in early brain development such as neuronal stem cell proliferation, migration, and myelination. The fetal thyroid is not fully functional until mid-pregnancy (18-20 weeks), so placental transfer of maternal thyroid hormones during early pregnancy is crucial, as is the maternal iodine status. The volume of chemical production has increased 300-fold since the 1970s. Thus, chemical exposure is ubiquitous; every child born today has dozens of man-made xenobiotic compounds in its blood. Increasing evidence from both epidemiological and animal or in vitro studies demonstrates that many of these chemicals have the potential to interfere with thyroid hormone availability and action at different physiological levels. These chemicals are found in numerous consumer products and include certain plastics, pesticides, perfluorinated compounds, and flame retardants. The last decades have seen exponential increases in neurodevelopmental disease including autism spectrum disorder and attention deficit/hyperactivity disorder. We hypothesize that prenatal exposure to mixtures of thyroid hormone-disrupting chemicals, with iodine deficiency potentially exacerbating the situation, has a strong probability of contributing to this increased incidence of neurodevelopmental disease, but could also entail a surreptitious, but socio-economically consequential, loss of IQ. Thyroid hormone receptor actions can modulate gene transcription, most often through epigenetic mechanisms. Thus, interference with epigenetic regulations is increasingly thought to link neurodevelopmental disease and IQ loss to thyroid hormone disruption.
PubMed: 31934553
DOI: 10.1159/000504668 -
Medical Science Monitor : International... Apr 2022BACKGROUND We aimed to insure the accuracy and reproducibility of alpha-fetoprotein (AFP), free beta-human chorionic gonadotropin (free ß-hCG), and unconjugated estriol...
External Quality Assessment of Maternal Serum Levels of Alpha-Fetoprotein, Free Beta-Human Chorionic Gonadotropin, and Unconjugated Estriol in Detecting Down Syndrome and Neural Tube Defects in the Second Trimester of 87 Maternal Serum Samples, Based on 105-139 Days.
BACKGROUND We aimed to insure the accuracy and reproducibility of alpha-fetoprotein (AFP), free beta-human chorionic gonadotropin (free ß-hCG), and unconjugated estriol (uE3) concentrations for the screening for trisomy 21 (T21) and neural tube defects (NTD) in the second trimester. We conducted an external quality assessment of 6 laboratories, using maternal serum specimens. MATERIAL AND METHODS Serum specimens collected from 87 women of singleton pregnancies (4 with T21, 5 with NTD, and 78 with normal fetuses) were divided into 6 equivalent-volume fractions and transported to 6 laboratories (A, B, C, D, E, and F). All laboratories used the time-resolved fluorescence analyzer and supporting reagents to measure concentrations of AFP, free ß-hCG, and uE3. The screening efficacies of T21 and NTD were compared with the certified or accredited status of the participants' quality systems. RESULTS Concentrations of AFP measured by laboratory F were low compared with those determined by the other 5 laboratories, and the differences were significant (P<0.01). There was no statistically significant difference in the free ß-hCG and uE3 concentrations measured by the 6 laboratories (P>0.05). The correlation coefficients for the 3 multiples of the median values were all >0.900. The McNemar paired chi-squared test showed the differences in the positivity and detection rates were not statistically significant (P=1.000). CONCLUSIONS AFP, free ß-hCG, and uE3 values measured by the other 5 laboratories were comparable with those of laboratory A, with good linear correlation. When used in the maternal prenatal screening of T21 and NTD, the test results met the clinical requirements.
Topics: Biomarkers; Chorionic Gonadotropin, beta Subunit, Human; Down Syndrome; Estriol; Female; Humans; Neural Tube Defects; Pregnancy; Pregnancy Trimester, Second; Prenatal Diagnosis; Reproducibility of Results; alpha-Fetoproteins
PubMed: 35414638
DOI: 10.12659/MSM.935573 -
International Journal of Molecular... Oct 2022In the ruminant placenta, glucose uptake and transfer are mediated by facilitative glucose transporters SLC2A1 (GLUT1) and SLC2A3 (GLUT3). SLC2A1 is located on the...
In the ruminant placenta, glucose uptake and transfer are mediated by facilitative glucose transporters SLC2A1 (GLUT1) and SLC2A3 (GLUT3). SLC2A1 is located on the basolateral trophoblast membrane, whereas SLC2A3 is located solely on the maternal-facing, apical trophoblast membrane. While SLC2A3 is less abundant than SLC2A1, SLC2A3 has a five-fold greater affinity and transport capacity. Based on its location, SLC2A3 likely plays a significant role in the uptake of glucose into the trophoblast. Fetal hypoglycemia is a hallmark of fetal growth restriction (FGR), and as such, any deficiency in SLC2A3 could impact trophoblast glucose uptake and transfer to the fetus, thus potentially setting the stage for FGR. By utilizing in vivo placenta-specific lentiviral-mediated RNA interference (RNAi) in sheep, we were able to significantly diminish ( ≤ 0.05) placental SLC2A3 concentration, and determine the impact at mid-gestation (75 dGA). In response to SLC2A3 RNAi ( = 6), the fetuses were hypoglycemic ( ≤ 0.05), exhibited reduced fetal growth, including reduced fetal pancreas weight ( ≤ 0.05), which was associated with reduced umbilical artery insulin and glucagon concentrations, when compared to the non-targeting sequence (NTS) RNAi controls ( = 6). By contrast, fetal liver weights were not impacted, nor were umbilical artery concentrations of IGF1, possibly resulting from a 70% increase ( ≤ 0.05) in umbilical vein chorionic somatomammotropin (CSH) concentrations. Thus, during the first half of gestation, a deficiency in SLC2A3 results in fetal hypoglycemia, reduced fetal development, and altered metabolic hormone concentrations. These results suggest that SLC2A3 may be the rate-limiting placental glucose transporter during the first-half of gestation in sheep.
Topics: Humans; Pregnancy; Female; Sheep; Animals; Placental Lactogen; Glucose Transporter Type 3; Glucagon; Glucose Transporter Type 1; Placenta; Fetal Growth Retardation; Fetal Weight; Glucose; Hypoglycemia; Hypoglycemic Agents; Insulins
PubMed: 36293384
DOI: 10.3390/ijms232012530