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Reproduction, Fertility, and Development Oct 2021This study explored the molecular mechanism underlying the effects of dexamethasone (DEX, 1 µM) on glucose transporters (GLUT) in JEG-3 human placental...
Dexamethasone may inhibit placental growth by blocking glucocorticoid receptors via phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin and reactive oxygen species/AMP-activated protein kinase signalling pathways in human placental JEG-3 cells.
This study explored the molecular mechanism underlying the effects of dexamethasone (DEX, 1 µM) on glucose transporters (GLUT) in JEG-3 human placental choriocarcinoma cells. JEG-3 cells were treated with DEX, an expression plasmid encoding human glucocorticoid receptor α (GRα), pcDNA3.1-GRα, GRα short interference (si) RNA, LY294002, xanthine oxidase (XO)/hypoxanthine (HX), rapamycin, insulin-like growth factor (IGF) 1, N-acetylcysteine (NAC) or phosphatidic acid (PA), and cell proliferation, apoptosis, mitochondrial membrane potential (MMP), human chorionic gonadotrophin (hCG) content, human placental lactogen (hPL) content, glucose uptake, reactive oxygen species levels and signalling pathway modulation were evaluated. Treatment of JEG-3 cells with DEX (1 µM), GRα siRNA, LY294002 (50 µM), XO/HX (7.2 µM/36 nM) or rapamycin (80 nM) inhibited cell proliferation, induced apoptosis, significantly decreased MMP and hCG and hPL content and increased ROS levels. In addition, glucose uptake was decreased through downregulation of the mRNA and protein expression of GRα, GLUT1 and GLUT3. Treatment of JEG-3 cells with GRα siRNA, LY294002, XO/HX or rapamycin inhibited phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, glycogen synthase kinase 3 and mammalian target of rapamycin (mTOR) and induced the phosphorylation of AMP-activated protein kinase (AMPK) and tuberous sclerosis complex 2. The effects of GRα overexpression and IGF1 (100 nM), NAC (5 nM) or PA (100 µM) treatment on JEG-3 cells contrasted with those of DEX treatment. DEX blocked glucose uptake by downregulating GRα expression, which reduced GLUT1 and GLUT3 mRNA and protein expression, which, in turn, may have inhibited the PI3K/AKT/mTOR pathway and activated the ROS/AMPK pathway.
Topics: AMP-Activated Protein Kinases; Apoptosis; Cell Line; Dexamethasone; Female; Humans; Membrane Potential, Mitochondrial; Phosphatidylinositol 3-Kinases; Phosphorylation; Placenta; Pregnancy; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Receptors, Glucocorticoid; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 34399087
DOI: 10.1071/RD21048 -
Animal Reproduction 2021The chemotaxis of subsp. and subsp. was determined in the presence of bovine cervical mucus and bovine placental extract. Some reported substances and ion in those...
The chemotaxis of subsp. and subsp. was determined in the presence of bovine cervical mucus and bovine placental extract. Some reported substances and ion in those materials, such amino acids, ferrous iron, hormones, sugars and organic acids were also investigated. Bovine cervical mucus, bovine placenta extracts and some substances and ion of these materials namely L-fucose, L- aspartate, L-glutamate, L-serine, ferrous iron, fumarate, pyruvate and succinate were chemoattractants. The chemottraction was significantly larger in higher concentrations of the tested substances and ion and significant differences among tested strains were also observed. Meso-erythritol and hormones bovine placental lactogen, 17β-estradiol, and progesterone did not elicit chemotactical response. In conclusion, this chemotactic behavior may guide the navigation in the bovine host's genital tract and be an important cofactor of tissue tropism for this bacterium.
PubMed: 34394754
DOI: 10.1590/1984-3143-AR2021-0008 -
International Journal of Molecular... Jul 2021Deficiency of the placental hormone chorionic somatomammotropin (CSH) can lead to the development of intrauterine growth restriction (IUGR). To gain insight into the...
Deficiency of the placental hormone chorionic somatomammotropin (CSH) can lead to the development of intrauterine growth restriction (IUGR). To gain insight into the physiological consequences of CSH RNA interference (RNAi), the trophectoderm of hatched blastocysts (nine days of gestational age; dGA) was infected with a lentivirus expressing either a scrambled control or CSH-specific shRNA, prior to transfer into synchronized recipient sheep. At 90 dGA, umbilical hemodynamics and fetal measurements were assessed by Doppler ultrasonography. At 120 dGA, pregnancies were fitted with vascular catheters to undergo steady-state metabolic studies with the HO transplacental diffusion technique at 130 dGA. Nutrient uptake rates were determined and tissues were subsequently harvested at necropsy. CSH RNAi reduced ( ≤ 0.05) both fetal and uterine weights as well as umbilical blood flow (mL/min). This ultimately resulted in reduced ( ≤ 0.01) umbilical IGF1 concentrations, as well as reduced umbilical nutrient uptakes ( ≤ 0.05) in CSH RNAi pregnancies. CSH RNAi also reduced ( ≤ 0.05) uterine nutrient uptakes as well as uteroplacental glucose utilization. These data suggest that CSH is necessary to facilitate adequate blood flow for the uptake of oxygen, oxidative substrates, and hormones essential to support fetal and uterine growth.
Topics: Animals; Blastocyst; Female; Fetal Blood; Fetal Growth Retardation; Fetus; Gestational Age; Glucose; Hemodynamics; Insulin-Like Growth Factor I; Male; Nutrients; Placenta; Placental Lactogen; Pregnancy; RNA Interference; RNA, Small Interfering; Sheep; Signal Transduction; Ultrasonography, Doppler; Uterus
PubMed: 34360913
DOI: 10.3390/ijms22158150 -
International Journal of Molecular... Jul 2021Human placentation differs from that of other mammals. A suite of characteristics is shared with haplorrhine primates, including early development of the embryonic... (Review)
Review
Human placentation differs from that of other mammals. A suite of characteristics is shared with haplorrhine primates, including early development of the embryonic membranes and placental hormones such as chorionic gonadotrophin and placental lactogen. A comparable architecture of the intervillous space is found only in Old World monkeys and apes. The routes of trophoblast invasion and the precise role of extravillous trophoblast in uterine artery transformation is similar in chimpanzee and gorilla. Extended parental care is shared with the great apes, and though human babies are rather helpless at birth, they are well developed (precocial) in other respects. Primates and rodents last shared a common ancestor in the Cretaceous period, and their placentation has evolved independently for some 80 million years. This is reflected in many aspects of their placentation. Some apparent resemblances such as interstitial implantation and placental lactogens are the result of convergent evolution. For rodent models such as the mouse, the differences are compounded by short gestations leading to the delivery of poorly developed (altricial) young.
Topics: Animals; Biological Evolution; Female; Humans; Placenta; Placental Hormones; Placentation; Pregnancy; Primates; Uterine Artery
PubMed: 34360862
DOI: 10.3390/ijms22158099 -
Animal Reproduction May 2020Bovids have enjoyed great evolutionary success as evidenced by the large number of extant species. Several important domestic animals are from this family. They derive...
Bovids have enjoyed great evolutionary success as evidenced by the large number of extant species. Several important domestic animals are from this family. They derive from both subfamilies: cattle and their kin belong to Bovinae and sheep and goats to Antilopinae. The premise of this review, therefore, is that evolution of reproduction and placentation is best understood in a context that includes antelope-like bovines and antelopes. Many key features of placentation, including hormone secretion, had evolved before bovids emerged as a distinct group. Variation nevertheless occurs. Most striking is the difference in fusion of the binucleate trophoblast cell with uterine epithelium that yields a transient trinucleate cell in bovines and many antelopes, but a more persistent syncytium in wildebeest, sheep and goat. There is considerable variation in placentome number and villus branching within the placentome. Many antelopes have right-sided implantation in a bicornuate uterus whilst others have a uterus duplex. Finally, there has been continued evolution of placental hormones with tandem duplication of genes in cattle, differences in glycosylation of placental lactogen and the emergence of placental growth hormone in sheep and goats. The selection pressures driving this evolution are unknown though maternal-fetal competition for nutrients is an attractive hypothesis.
PubMed: 33936288
DOI: 10.21451/1984-3143-AR2018-00145 -
Frontiers in Microbiology 2021(), the etiological agent of Chagas Disease (CD), is transmitted to humans by infected kissing bugs, blood transfusion, organ transplantation, and from mother-to-child....
(), the etiological agent of Chagas Disease (CD), is transmitted to humans by infected kissing bugs, blood transfusion, organ transplantation, and from mother-to-child. Congenital transmission is now considered an important route of CD spread in non-endemic countries where no routine testing of pregnant women for the disease is implemented. The main cellular mechanisms that lead to fetal infection by , despite the presence of a placental barrier, remain unclear. Mother-to-child transmission most likely occurs when bloodstream trypomastigotes reach the placental intervillous space and interact with the large cellular surface provided by the syncytioptrophoblasts. These highly specialized cells not only function as a physical obstacle between mother and fetus, but also modulate immune responses against pathogen infections. To overcome the limitations associated with the use of human fetal tissues, we employed a three-dimensional (3D) cell culture model to recreate the human placenta environment. In this system, the trophoblast-derived JEG-3 cell line is co-cultured with human brain microvascular endothelial cells attached to microcarrier beads in a rotating bioreactor. Here, we report that 3D culture of JEG-3/HBMEC spheroids promote JEG-3 cells differentiation revealed by the formation of syncytia and production of β human chorionic gonadotropin and human placental lactogen (hPL). Under these growth conditions, we demonstrate that 3D-grown JEG-3 cells have reduced susceptibility to infection compared to JEG-3 cells grown in conventional tissue culture flasks. We also show that 3D-cultured JEG-3 cells release paracrine factors in the supernatant that prevent infection of non-trophoblastic cell lines. Our model of vertical transmission may help better understand the molecular processes by which parasites bypass the human placental barrier and could be exploited to evaluate therapeutics to reduce congenital CD.
PubMed: 33746919
DOI: 10.3389/fmicb.2021.626370 -
BMC Women's Health Mar 2021Studies have found an association between obesity and an increased risk for peripartum depression, which has also been linked to decreased placental lactogen levels. In...
BACKGROUND
Studies have found an association between obesity and an increased risk for peripartum depression, which has also been linked to decreased placental lactogen levels. In addition, women with obesity treated for gestational diabetes with insulin were found to have increased levels of placental lactogen. Treatment options exist for perinatal and postpartum depression however they pose a risk to the developing offspring. Thus, prevention as well as markers for early identification of peripartum depression are needed. Therefore, our study objective is to identify the association between insulin treatment in pregnancy and the risk of postpartum psychological distress (abbreviated here as PPD) among cohorts of women with and without obesity.
METHODS
Administrative health data (2002/03-2018/19) were used to identify a cohort of women (age 15+ years) who gave birth (N = 250,746) and had no pre-existing mood/anxiety disorders or diabetes (N = 222,863 excluded). Women were then divided into two groups: lean (N = 17,975) and with obesity (N = 9908), which was identified by a recorded maternal weight of > 38 to < 65.6 kg and ≥ 85 to < 186 kg (respectively). The risk of PPD within one year after delivery with and without insulin treatment was assessed by Poisson regression analysis. Models were adjusted for maternal age group (at pregnancy start date) and area-level income (at delivery).
RESULTS
The unadjusted risk of PPD was higher in the obesity group (8.56%; 95% CI 8.00-9.15) than in the lean group (6.93%; 95% CI 6.56-7.33). When no insulin treatment was given during pregnancy, mothers with obesity had a significantly higher risk of PPD than the lean group (aRR 1.27; 95% CI 1.17-1.39; p < 0.0001). However, when women with obesity and insulin treatment were compared to the lean group with no insulin treatment, no significant difference in the risk of PPD was observed between the groups (aRR 1.30; 95% CI 0.83-2.02; p = 0.248).
CONCLUSION
This is the first study to demonstrate a positive association between insulin treatment in pregnancy among women with obesity and reduced PPD rates, suggesting insulin as a possible preventative measure. However, the biological mechanism behind the observed positive effect of insulin on PPD rates remains to be investigated.
Topics: Adolescent; Depression, Postpartum; Female; Humans; Insulins; Obesity, Maternal; Placenta; Population Health; Postpartum Period; Pregnancy; Psychological Distress; Risk Factors
PubMed: 33743677
DOI: 10.1186/s12905-021-01261-0 -
BioEssays : News and Reviews in... Apr 2021The molecular evolution of pituitary growth hormone and prolactin in mammals shows two unusual features: episodes of markedly accelerated evolution and, in some species,...
Do some viruses use growth hormone, prolactin and their receptors to facilitate entry into cells?: Episodic evolution of hormones and receptors suggests host-virus arms races; related placental lactogens may provide protective viral decoys.
The molecular evolution of pituitary growth hormone and prolactin in mammals shows two unusual features: episodes of markedly accelerated evolution and, in some species, complex families of related proteins expressed in placenta and resulting from multiple gene duplications. Explanations of these phenomena in terms of physiological adaptations seem unconvincing. Here, I propose an alternative explanation, namely that these evolutionary features reflect the use of the hormones (and their receptors) as viral receptors. Episodes of rapid evolution can then be explained as due to "arms races" in which changes in the hormone lead to reduced interaction with the virus, and subsequent changes in the virus counteract this. Placental paralogues of the hormones could provide decoys that bind viruses, and protect the foetus against infection. The hypothesis implies that the extensive changes introduced into growth hormone, prolactin and their receptors during the course of mammalian evolution reflect viral interactions, not endocrine adaptations.
Topics: Animals; Female; Growth Hormone; Placenta; Placental Lactogen; Pregnancy; Prolactin; Viruses
PubMed: 33521987
DOI: 10.1002/bies.202000268 -
Clinica E Investigacion En... 2021During pregnancy there is a physiological increase in total cholesterol (TC) and triglycerides (TG) plasma concentrations, due to increased insulin resistance,...
During pregnancy there is a physiological increase in total cholesterol (TC) and triglycerides (TG) plasma concentrations, due to increased insulin resistance, oestrogens, progesterone, and placental lactogen, although their reference values are not exactly known, TG levels can increase up to 300mg/dL, and TC can go as high as 350mg/dL. When the cholesterol concentration exceeds the 95 percentile (familial hypercholesterolaemia (FH) and transient maternal hypercholesterolaemia), there is a predisposition to oxidative stress in foetal vessels, exposing the newborn to a greater fatty streaks formation and a higher risk of atherosclerosis. However, the current treatment of pregnant women with hyperlipidaemia consists of a diet and suspension of lipid-lowering drugs. The most prevalent maternal hypertriglyceridaemia (HTG) is due to secondary causes, like diabetes, obesity, drugs, etc. The case of severe HTG due to genetic causes is less prevalent, and can be a higher risk of maternal-foetal complications, such as, acute pancreatitis (AP), pre-eclampsia, preterm labour, and gestational diabetes. Severe HTG-AP is a rare but potentially lethal pregnancy complication, for the mother and the foetus, usually occurs during the third trimester or in the immediate postpartum period, and there are no specific protocols for its diagnosis and treatment. In conclusion, it is crucial that dyslipidaemia during pregnancy must be carefully evaluated, not just because of the acute complications, but also because of the future cardiovascular morbidity and mortality of the newborn child. That is why the establishment of consensus protocols or guidelines is essential for its management.
Topics: Cholesterol; Dyslipidemias; Female; Humans; Hypercholesterolemia; Hypertriglyceridemia; Infant, Newborn; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Triglycerides
PubMed: 33309071
DOI: 10.1016/j.arteri.2020.10.002 -
American Journal of Physiology.... Feb 2021Chorionic somatomammotropin (CSH) is one of the most abundantly produced placental hormones, yet its exact function remains elusive. Near-term [135 days of gestational...
Chorionic somatomammotropin (CSH) is one of the most abundantly produced placental hormones, yet its exact function remains elusive. Near-term [135 days of gestational age (dGA)], CSH RNA interference (RNAi) results in two distinct phenotypes: ) pregnancies with intrauterine growth restriction (IUGR), and ) pregnancies with normal fetal and placental weights. Here, we report the physiological changes in CSH RNAi pregnancies without IUGR. The trophectoderm of hatched blastocysts (9 dGA) were infected with lentiviral-constructs expressing either a scrambled control (Control RNAi) or CSH-specific shRNA (CSH RNAi), prior to transfer into synchronized recipient ewes. At 126 dGA, Control RNAi ( = 6) and CSH RNAi ( = 6) pregnancies were fitted with maternal and fetal catheters. Uterine and umbilical blood flows were measured at 132 dGA and nutrient uptakes were calculated by the Fick's principle. Control RNAi and CSH RNAi pregnancies were compared by analysis of variance, and significance was set at ≤ 0.05. Absolute (mL/min) and relative (mL/min/kg fetus) uterine blood flows were reduced ( ≤ 0.05) in CSH RNAi pregnancies, but umbilical flows were not impacted. The uterine artery-to-vein glucose gradient (mmol/L) was significantly ( ≤ 0.05) increased. The uteroplacental glucose uptake (μmoL/min/kg placenta) was increased ( ≤ 0.05), whereas umbilical glucose uptake (μmoL/min/kg fetus) was reduced. Our results demonstrate that CSH RNAi has significant physiological ramifications, even in the absence of IUGR, and comparing CSH RNAi pregnancies exhibiting both IUGR and non-IUGR phenotypes may help determine the direct effects of CSH and its potential impact on fetal development.
Topics: Animals; Biological Transport; Blood Flow Velocity; Female; Fetal Growth Retardation; Glucose; Oxygen; Placenta; Placental Lactogen; Pregnancy; RNA Interference; Sheep; Uterus
PubMed: 33146554
DOI: 10.1152/ajpregu.00223.2020