-
BioFactors (Oxford, England) May 2024Angiopoietin-like protein 4 (ANGPTL4) is a secretory glycoprotein involved in regulating glucose homeostasis in non-pregnant subjects. However, its role in glucose...
Angiopoietin-like protein 4 (ANGPTL4) is a secretory glycoprotein involved in regulating glucose homeostasis in non-pregnant subjects. However, its role in glucose metabolism during pregnancy and the pathophysiology of gestational diabetes mellitus (GDM) remains elusive. Thus, this study aimed to clarify the relationship between ANGPTL4 and GDM and investigate the pathophysiology of placental ANGPTL4 in glucose metabolism. We investigated this issue using blood and placenta samples in 957 pregnant women, the human 3A-sub-E trophoblast cell line, and the L6 skeletal muscle cell line. We found that ANGPTL4 expression in the placenta was higher in obese pregnant women than in lean controls. Palmitic acid significantly induced ANGPTL4 expression in trophoblast cells in a dose-response manner. ANGPTL4 overexpression in trophoblast cells resulted in endoplasmic reticulum (ER) stress, which stimulated the expression and secretion of growth hormone-variant (GH2) but not human placental lactogen. In L6 skeletal muscle cells, soluble ANGPTL4 suppressed insulin-mediated glucose uptake through the epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinases 1/2 (ERK 1/2) pathways. In pregnant women, plasma ANGPTL4 concentrations in the first trimester predicted the incidence of GDM and were positively associated with BMI, plasma triglyceride, and plasma GH2 in the first trimester. However, they were negatively associated with insulin sensitivity index ISI in the second trimester. Overall, placental ANGPTL4 is induced by obesity and is involved in the pathophysiology of GDM via the induction of ER stress and GH2 secretion. Soluble ANGPTL4 can lead to insulin resistance in skeletal muscle cells and is an early biomarker for predicting GDM.
PubMed: 38760159
DOI: 10.1002/biof.2076 -
Endocrine Journal May 2024The placenta secretes a prolactin (PRL)-like hormone PRL3B1 (placental lactogen II), a luteotropic hormone essential for maintaining pregnancy until labor in mice. A...
The placenta secretes a prolactin (PRL)-like hormone PRL3B1 (placental lactogen II), a luteotropic hormone essential for maintaining pregnancy until labor in mice. A report from 1984 examined the secretion pattern of PRL3B1 in prepartum mice. In the current study, we found contradictory findings in the secretion pattern that invalidate the previous report. By measuring maternal plasma PRL3B1 and PRL every 4 hrs from gestational day 17 (G17), we newly discovered that maternal plasma PRL3B1 levels decrease rapidly in prepartum C57BL/6 mice. Interestingly, the onset of this decline coincided with the PRL surge at G18, demonstrating a plasma prolactin axis shift from placental to pituitary origin. We also found that maternal plasma progesterone regression precedes the onset of the PRL shift. The level of Prl3b1 mRNA was determined by RT-qPCR in the placenta and remained stable until parturition, implying that PRL3B1 peptide production or secretion was suppressed. We hypothesized that production of the PRL family, the 25 paralogous PRL proteins exclusively expressed in mice placenta, would decrease alongside PRL3B1 during this period. To investigate this hypothesis and to seek proteomic changes, we performed a shotgun proteome analysis of the placental tissue using data-independent acquisition mass spectrometry (DIA-MS). Up to 5,891 proteins were identified, including 17 PRL family members. Relative quantitative analysis between embryonic day 17 (E17) and E18 placentas showed no significant difference in the expression of PRL3B1 and most PRL family members except PRL7C1. These results suggest that PRL3B1 secretion from the placenta is suppressed at G18 (E18).
PubMed: 38749736
DOI: 10.1507/endocrj.EJ23-0724 -
Hormones and Behavior Jul 2024Previous studies support links among maternal-fetal attachment, psychological symptoms, and hormones during pregnancy and the post-partum period. Other studies connect...
Human placental lactogen (human chorionic somatomammotropin) and oxytocin during pregnancy: Individual patterns and associations with maternal-fetal attachment, anxiety, and depression.
Previous studies support links among maternal-fetal attachment, psychological symptoms, and hormones during pregnancy and the post-partum period. Other studies connect maternal feelings and behaviors to oxytocin and suggest that an increase in oxytocin during pregnancy may prime maternal-fetal attachment. To date, researchers have not examined a possible association between maternal-fetal attachment with human placental lactogen although animal models are suggestive. In the current study, we sought to describe oxytocin and human placental lactogen levels as related to psychological constructs across pregnancy. Seventy women participated in the study. At each of three time-points (early, mid, and late pregnancy), the women had their blood drawn to assess oxytocin and human placental lactogen levels, and they completed psychological assessments measuring maternal-fetal attachment, anxiety, and depression. Our results indicate that oxytocin levels were statistically similar across pregnancy, but that human placental lactogen significantly increased across pregnancy. Results did not indicate significant associations of within-person (comparing individuals to themselves) oxytocin or human placental lactogen levels with maternal-fetal attachment. Additionally, results did not show between-person (comparing individuals to other individuals) oxytocin or human placental lactogen levels with maternal-fetal attachment. Oxytocin levels were not associated with anxiety; rather the stage of pregnancy moderated the effect of the within-person OT level on depression. Notably, increasing levels of human placental lactogen were significantly associated with increasing levels of both anxiety and depression in between subject analyses. The current study is important because it describes typical hormonal and maternal fetal attachment levels during each stage of pregnancy, and because it suggests an association between human placental lactogen and psychological symptoms during pregnancy. Future research should further elucidate these relationships.
Topics: Humans; Female; Oxytocin; Pregnancy; Placental Lactogen; Adult; Anxiety; Depression; Maternal-Fetal Relations; Young Adult; Object Attachment
PubMed: 38723407
DOI: 10.1016/j.yhbeh.2024.105560 -
Cureus Jan 2024Gestational diabetes mellitus (GDM) is one of the most common endocrine disorders to occur during pregnancy due to the increase in circulating human placental lactogen... (Review)
Review
Gestational diabetes mellitus (GDM) is one of the most common endocrine disorders to occur during pregnancy due to the increase in circulating human placental lactogen (hPL) and possible beta-cell sensitivity. While GDM can be managed either with diet and exercise or pharmacological interventions, it is associated with significant maternal and neonatal complications. Maternal complications include short- and long-term conditions such as pre-eclampsia, preterm birth, arrest of labor, future development of type 2 diabetes mellitus (T2DM), and cardiovascular disorders. Neonates can develop hypoglycemia and hypocalcemia and have a large gestational age (LGA). New research has also highlighted another possible long-term complication for both mothers and offspring, which is the development of cancer. Cancer has various types of progression, but most cause systemic symptoms leading to a reduced quality of life. Cancer can be terminal and can affect the majority of the population; thus, significant effort is being employed to try and reduce its occurrence. This systematic review was conducted with adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using PubMed, ScienceDirect, and ProQuest databases. Initially, 136,019 publications were identified. Through the screening process, a total of 27 publications were finalized within the scope of this paper. Most studies observing maternal cancer with a history of GDM found that there was an association between the increased risk of cancer and GDM. Specifically, these studies identified the association of GDM with breast, ovarian, cervical, and uterine cancer, as well as other non-reproductive organs such as the thyroid and pancreas. Cancer development in the offspring also presented an association with mothers who developed GDM. The most prevalent cancer evaluated was leukemia, and it was specifically associated with a maternal history of GDM. With the consistent rise in the incidence of cancer, any attempts to reduce its development are imperative to assess. While GDM is essentially a temporary condition that resolves following pregnancy in most patients, the possibility of contributing to future conditions years after its occurrence creates a sense of urgency and necessity to reduce the incidence of GDM. Researchers should be able to identify other unknown biomarkers that contribute to the development of cancer in mothers who experienced GDM as well as their infants.
PubMed: 38435884
DOI: 10.7759/cureus.53328 -
The Journal of Veterinary Medical... Apr 2024In this study, we examined the morphological features of the placentas from 3 species of rorqual whales (Balaenopteridae), namely Bryde's (Balaenoptera brydei), sei (B....
In this study, we examined the morphological features of the placentas from 3 species of rorqual whales (Balaenopteridae), namely Bryde's (Balaenoptera brydei), sei (B. borealis), and common minke (B. acutorostrata) whales, and verified the secretion of 2 placental-specific peptide hormones, placental lactogen (PL) and chorionic gonadotropin (CG). The placentas were collected in the second phase of the Japanese Whale Research Program under a special permit in the North Pacific (JARPN II) between 2009 and 2010. For all three species of rorqual whales, as the fetus grew, the interdigitation between the maternal endometrial folds and chorionic villi became more complicated, and many blood capillaries of chorionic villi and endometrium became larger and infiltrated the trophoblast cells and endometrial epithelial cells, respectively. In the immunohistochemical examination, the trophoblast cells (except for areolar trophoblast cells) showed immunoreactivities for the PL and luteinizing hormone (LH) antibodies, and this phenomenon was similar in the placentas of all 3 rorqual whale species. Our results suggest that PL and LH-like CG play roles in regulating pregnancy in the placenta of cetacean.
Topics: Female; Pregnancy; Animals; Balaenoptera; Placenta; Peptide Hormones; Cetacea; Luteinizing Hormone; Chorionic Gonadotropin
PubMed: 38417877
DOI: 10.1292/jvms.23-0439 -
American Journal of Physiology.... May 2024We previously demonstrated impaired placental nutrient transfer in chorionic somatomammotropin (CSH) RNA interference (RNAi) pregnancies, with glucose transfer being the...
We previously demonstrated impaired placental nutrient transfer in chorionic somatomammotropin (CSH) RNA interference (RNAi) pregnancies, with glucose transfer being the most impacted. Thus, we hypothesized that despite experimentally elevating maternal glucose, diminished umbilical glucose uptake would persist in CSH RNAi pregnancies, demonstrating the necessity of CSH for adequate placental glucose transfer. Trophectoderm of sheep blastocysts (9 days of gestational age; dGA) were infected with a lentivirus expressing either nontargeting control (CON RNAi; = 5) or CSH-specific shRNA (CSH RNAi; = 7) before transfer into recipient sheep. At 126 dGA, pregnancies were fitted with vascular catheters and underwent steady-state metabolic studies (HO transplacental diffusion) at 137 ± 0 dGA, before and during a maternal hyperglycemic clamp. Umbilical glucose and oxygen uptakes, as well as insulin and IGF1 concentrations, were impaired ( ≤ 0.01) in CSH RNAi fetuses and were not rescued by elevated maternal glucose. This is partially due to impaired uterine and umbilical blood flow ( ≤ 0.01). However, uteroplacental oxygen utilization was greater ( ≤ 0.05) during the maternal hyperglycemic clamp, consistent with greater placental oxidation of substrates. The relationship between umbilical glucose uptake and the maternal-fetal glucose gradient was analyzed, and while the slope (CON RNAi, Y = 29.54X +74.15; CSH RNAi, Y = 19.05X + 52.40) was not different, the y-intercepts and elevation were ( = 0.003), indicating reduced maximal glucose transport during maternal hyperglycemia. Together, these data suggested that CSH plays a key role in modulating placental metabolism that ultimately promotes maximal placental glucose transfer. The current study demonstrated a novel, critical autocrine role for chorionic somatomammotropin in augmenting placental glucose transfer and maintaining placental oxidative metabolism. In pregnancies with CSH deficiency, excess glucose in maternal circulation is insufficient to overcome fetal hypoglycemia due to impaired placental glucose transfer and elevated placental metabolic demands. This suggests that perturbations in glucose transfer in CSH RNAi pregnancies are due to compromised metabolic efficiency along with reduced placental mass.
Topics: Pregnancy; Female; Animals; Sheep; Placenta; Glucose; RNA Interference; Placental Lactogen; Oxygen
PubMed: 38353640
DOI: 10.1152/ajpendo.00331.2023 -
Nigerian Journal of Physiological... Jun 2023Human placental lactogen (HPL) is a pregnancy-related hormone produced by the placenta. The overall functions of serum HPL impacts the developing fetus and placenta. The...
Human placental lactogen (HPL) is a pregnancy-related hormone produced by the placenta. The overall functions of serum HPL impacts the developing fetus and placenta. The objective of this study was to determine the relationship between maternal serum concentration of HPL and sonographic fetal growth parameters in pregnancy induced hypertension as a marker of placental function. This prospective cross-sectional study was conducted over a 9-month period in the University of Calabar Teaching Hospital, Calabar, Nigeria that involved 100 women with pregnancy induced hypertension. An obstetric ultrasound scan was done on all the subjects and their blood was collected for HPL evaluation using Enzyme-linked Immunosorbent Assay (ELISA). SPSS version 20 was used to analyze the data. Maternal serum HPL had a significant positive correlation with PLA (P=0.000), estimated gestational age (P=0.000), estimated fetal weight (P=0.000) and amniotic fluid index AFI (P=0.000) and a significant negative correlation with proteinuria (P=0.047), fetal heart rate (P=0.032) and HC/AC (P=0.000). It is concluded that maternal serum HPL concentration increases as pregnancy advances and causes a significant increase in placental thickness, fetal weight and amniotic fluid volume, however, its reduction is significantly associated with the onset of pre-eclampsia, fetal distress and asymmetrical intra-uterine growth restriction. Thus, the evaluation of maternal serum HPL concentration is a reliable marker of placental function in the second half of pregnancy.
Topics: Pregnancy; Humans; Female; Placental Lactogen; Placenta; Hypertension, Pregnancy-Induced; Fetal Weight; Prospective Studies; Cross-Sectional Studies
PubMed: 38243348
DOI: 10.54548/njps.v38i1.2 -
Doklady Biological Sciences :... Dec 2023Gestational diabetes mellitus (GDM) and preeclampsia (PE) are common pregnancy complications with similar risk factors. Although GDM is associated with PE, the exact...
Gestational diabetes mellitus (GDM) and preeclampsia (PE) are common pregnancy complications with similar risk factors. Although GDM is associated with PE, the exact mechanism underlying the association is unclear. The objective of this work was to study the morphofunctional and molecular changes in the placenta and peripheral blood in PE and GDM. Local and systemic changes in the production of several placental proteins were assessed along with markers of inflammation and metabolic disorders. Expression of placental lactogen, trophoblastic β1-glycoprotein, placental alpha-1-microglobulin, and proteinase 3 in villi was found to change in complicated pregnancy groups. Similarity of underlying pathogenic mechanisms was demonstrated for PE and GDM.
Topics: Pregnancy; Female; Humans; Diabetes, Gestational; Placenta; Pre-Eclampsia
PubMed: 38066383
DOI: 10.1134/S0012496623700722 -
Journal of Diabetes and Metabolic... Dec 2023Gestational diabetes mellitus (GDM) is a pathological condition in which the placenta releases a hormone called human placental lactogen that prevents maternal insulin... (Review)
Review
UNLABELLED
Gestational diabetes mellitus (GDM) is a pathological condition in which the placenta releases a hormone called human placental lactogen that prevents maternal insulin uptake. GDM is characterised by varying degrees of carbohydrate intolerance and is first identified during pregnancy. Around 5-17% of pregnancies are GDM pregnancies. Older or obese women have a higher risk of developing GDM during gestation. Hyperglycemia is a classic manifestation of GDM and leads to alterations in eNOS and iNOS expression and subsequently causes ROS and RNS overproduction. ROS and RNS play an important role in maintaining normal physiology, when present in low concentrations. Increased concentrations of ROS is harmful and can cause cellular and tissue damage. Oxidative stress is defined as an imbalance between pro-oxidant and antioxidant molecules that manifests due to hyperglycemia. miRNAs are short, non-coding RNAs that play a critical role in regulating gene expression. Studies have shown that the placenta expresses more than 500 miRNAs, which play a crucial role in trophoblast division, movement, and apoptosis. Latest research has revealed that hyperglycemic conditions and increased oxidative stress, characteristic of GDM, can lead to the dysregulation of miRNAs. The placenta also releases miRNAs into the maternal circulation. The secreted miRNAs are encapsulated in exosomes or vesicles. These exosomes interact with tissues and organs at distant sites, releasing their cargo intracellularly. This crosstalk between hyperglycemia, ROS and miRNA expression in GDM has detrimental effects on both foetal and maternal health. One of the complications of GDM is preterm labour. GDM induced iNOS expression has been implicated in cervical ripening, which in turn causes preterm birth. This article focuses on the speculations of oxidative and nitrative stress markers that lead to detrimental effects in GDM. We have also envisaged the role of non-coding miRNA interactions in regulating gene expression for oxidative damage.
GRAPHICAL ABSTRACT
. I)(A) Placenta as a metabolic organ that provides the foetus with nutrients, oxygen and hormones to maintain pregnancy. Human placental lactogen (hPL) is one such hormone that is released into maternal circulation. hPL is known to induce insulin resistance. (B) ß-cell dysfunction leads to reduced glucose sensing and insulin production. Insulin resistance, a characteristic of GDM, exacerbates insulin ß cell dysfunction leading to maternal hyperglycemia. Hyperglycemia leads to increased ROS and RNS production through several mechanisms. Consequently, GDM is characterised by increased oxidative and nitrative stress.II)Exposure to maternal hyperglycemia causes increased ROS and RNS production in trophoblast cells. Oxidative stress caused by hyperglycemia may lead to eNOS uncoupling, causing eNOS to behave as a superoxide producing enzyme. iNOS expression in trophoblast cells leads to increased NO production. iNOS-derived NO reacts with ROS to produce RNS, thereby increasing nitrosative stress. Expression of antioxidant defences are reduced. Hyperglycemia and oxidative stress may alter the expression of some miRNAs. Some miRNAs are upregulated while others are downregulated. Some miRNAs are secreted into maternal circulation in the form of exosomes. Oxidative stress markers, nitrative stress markers and circulating miRNAs are found to be increased in maternal circulation.
PubMed: 37975145
DOI: 10.1007/s40200-023-01232-2 -
Biology of Reproduction Feb 2024The intervillous space of human placenta is filled with maternal blood, and villous trophoblasts are constantly exposed to the shear stress generated by maternal blood...
The intervillous space of human placenta is filled with maternal blood, and villous trophoblasts are constantly exposed to the shear stress generated by maternal blood pressure and flow throughout the entire gestation period. However, the effects of shear stress on villous trophoblasts and their biological significance remain unknown. Here, using our recently established naïve human pluripotent stem cells-derived cytotrophoblast stem cells (nCTs) and a device that can apply arbitrary shear stress to cells, we investigated the impact of shear stress on early-stage trophoblasts. After 72 h of exposure to 10 dyn/cm2 shear stress, nCTs became fused and multinuclear, and mRNA expression of the syncytiotrophoblast (ST) markers, such as glial cell missing 1, endogenous retrovirus group W member 1 envelope, chorionic gonadotropin subunit beta 3, syndecan 1, pregnancy specific beta-1-glycoprotein 3, placental growth factor, and solute carrier family 2 member 1 were significantly upregulated compared to static conditions. Immunohistochemistry showed that shear stress increased fusion index, human chorionic gonadotropin secretion, and human placental lactogen secretion. Increased microvilli formation on the surface of nCTs under flow conditions was detected using scanning electron microscopy. Intracellular cyclic adenosine monophosphate significantly increased under flow conditions. Moreover, transcriptome analysis of nCTs subjected to shear stress revealed that shear stress upregulated ST-specific genes and downregulated CT-specific genes. Collectively, these findings indicate that shear stress promotes the differentiation of nCTs into ST.
Topics: Female; Pregnancy; Humans; Placenta; Induced Pluripotent Stem Cells; Placenta Growth Factor; Trophoblasts; Chorionic Gonadotropin; Cell Differentiation
PubMed: 37930227
DOI: 10.1093/biolre/ioad143