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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 -
Journal of Clinical Medicine Apr 2020Placental lactogen (PL) is a peptide hormone secreted throughout pregnancy by both animal and human specialized endocrine cells. PL plays an important role in the... (Review)
Review
Placental lactogen (PL) is a peptide hormone secreted throughout pregnancy by both animal and human specialized endocrine cells. PL plays an important role in the regulation of insulin secretion in pancreatic β-cells, stimulating their proliferation and promoting the expression of anti-apoptotic proteins. Cases of pregnancy affected by metabolic conditions, including obesity and diabetes, are related to alterations in the PL secretion pattern. Whereas obesity is most often associated with lower PL serum concentrations, diabetes results in increased PL blood levels. Disruptions in PL secretion are thought to be associated with an increased prevalence of gestational complications, such as placental dysfunction, diabetic retinopathy, and abnormalities in fetal growth. PL is believed to be positively correlated with birth weight. The impaired regulation of PL secretion could contribute to an increased incidence of both growth retardation and fetal macrosomia. Moreover, the dysregulation of PL production during the intrauterine period could affect the metabolic status in adulthood. PL concentration measurement could be useful in the prediction of fetal macrosomia in women with normal oral glucose tolerance test (OGTT) results or in evaluating the risk of fetal growth restriction, but its application in standard clinical practice seems to be limited in the era of ultrasonography.
PubMed: 32316284
DOI: 10.3390/jcm9041142 -
Frontiers in Endocrinology 2022Placental lactogen (hPL) is a key hormone of pregnancy responsible for inducing maternal adaptations critical for a successful pregnancy. Low levels of placental...
Placental lactogen (hPL) is a key hormone of pregnancy responsible for inducing maternal adaptations critical for a successful pregnancy. Low levels of placental lactogen have been associated with lower birth weight as well as symptoms of maternal depression and anxiety. Lower placental lactogen has been reported in women with higher body mass index (BMI) but it is unclear whether prenatal health behaviours predict hPL levels or if hPL is associated with infant weight outcomes. This study utilised data from the longitudinal Grown in Wales cohort, based in South Wales. Participants were recruited at the pre-surgical appointment for an elective caesarean section. This study incorporates data from recruitment, post-delivery and a 12 month follow-up. Measures of maternal serum hPL were available for 248 participants. Analysis included unadjusted and adjusted linear and binary regression. Unadjusted, prenatal smoking and a Health Conscious dietary pattern were associated with hPL levels, however this was lost on adjustment for BMI at booking, Welsh Index of Multiple Deprivation (WIMD) score and placental weight. When stratified by maternal BMI at booking, a Health Conscious dietary pattern remained associated with increased hPL levels in women with a healthy BMI (p=.024, B=.59. 95% CI=.08,1.11) following adjustment for WIMD score and placental weight. When adjusted for a wide range of confounders, maternal hPL was also associated with increased custom birthweight centiles (CBWC) (p=.014, B=1.64. 95% CI=.33,2.94) and increased odds of large for gestational age deliveries (p=<.001, Exp(B)=1.42. 95% CI=1.17,1.72). This study identified that consuming a Health Conscious dietary pattern in pregnancy was associated with increased hPL, within women of a healthy BMI. Moreover, higher hPL levels were associated with increased CBWC and increased odds of delivering a large for gestational age infant. This improves the current limited evidence surrounding the nature of hPL in these areas.
Topics: Birth Weight; Cesarean Section; Female; Health Behavior; Humans; Placenta; Placental Lactogen; Pregnancy
PubMed: 36157466
DOI: 10.3389/fendo.2022.946539 -
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 -
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 Global Women's Health 2021Transition into motherhood involves profound physiological and behavioral adaptations that ensure the healthy development of offspring while maintaining maternal health.... (Review)
Review
Transition into motherhood involves profound physiological and behavioral adaptations that ensure the healthy development of offspring while maintaining maternal health. Dynamic fluctuations in key hormones during pregnancy and lactation induce these maternal adaptations by acting on neural circuits in the brain. Amongst these hormonal changes, lactogenic hormones (e.g., prolactin and its pregnancy-specific homolog, placental lactogen) are important regulators of these processes, and their receptors are located in key brain regions controlling emotional behaviors and maternal responses. With pregnancy and lactation also being associated with a marked elevation in the risk of developing mood disorders, it is important to understand how hormones are normally regulating mood and behavior during this time. It seems likely that pathological changes in mood could result from aberrant expression of these hormone-induced behavioral responses. Maternal mental health problems during pregnancy and the postpartum period represent a major barrier in developing healthy mother-infant interactions which are crucial for the child's development. In this review, we will examine the role lactogenic hormones play in driving a range of specific maternal behaviors, including motivation, protectiveness, and mother-pup interactions. Understanding how these hormones collectively act in a mother's brain to promote nurturing behaviors toward offspring will ultimately assist in treatment development and contribute to safeguarding a successful pregnancy.
PubMed: 34927138
DOI: 10.3389/fgwh.2021.767467 -
Journal of Medicine and Life 2021The purpose of the study was TO analyze the fetoplacental complex hormone levels and changes in their dynamics in pregnant women with miscarriage and the impact of these...
The purpose of the study was TO analyze the fetoplacental complex hormone levels and changes in their dynamics in pregnant women with miscarriage and the impact of these features on the subsequent course of pregnancy. Hormone levels were determined at different stages of gestation in 50 healthy women with a physiological course of pregnancy (control group) and 50 pregnant women with a history of miscarriage (main group). The women of the main group had a significantly slower rate of increase in hormones and a lag in quantitative indicators than the control group. The estradiol level indicators were 4.1 times (76.0%) and 2.89 times (65.5%) lower in women with miscarriage in the embryonic and late fetal period, respectively, compared to healthy women. Indicators of the level of placental lactogen and chorionic gonadotropin in the embryonic period in women with miscarriage were lower by 39.1% and 50.9%, respectively, compared to healthy women. In the late fetal period, the level of these hormones was lower by 72.9% and 35.4%, respectively. In the embryonic and late fetal periods, progesterone levels were lower by 67.4% and 68.4%, respectively, compared to the control group. The data obtained are evidence of a pronounced hormonal abnormality of the placenta, and hence a marker of fetoplacental dysfunction, which on the background of miscarriage develops at the early stages and continues to progress with the course of pregnancy.
Topics: Abortion, Spontaneous; Female; Hormones; Humans; Placenta; Placental Lactogen; Pregnancy; Pregnant Women; Progesterone
PubMed: 34621371
DOI: 10.25122/jml-2021-0089 -
Nutrients Mar 2023Folic acid (FA) food fortification in Australia has resulted in a higher-than-expected intake of FA during pregnancy. High FA intake is associated with increased insulin...
Elevated Maternal Folate Status and Changes in Maternal Prolactin, Placental Lactogen and Placental Growth Hormone Following Folic Acid Food Fortification: Evidence from Two Prospective Pregnancy Cohorts.
Folic acid (FA) food fortification in Australia has resulted in a higher-than-expected intake of FA during pregnancy. High FA intake is associated with increased insulin resistance and gestational diabetes. We aimed to establish whether maternal one-carbon metabolism and hormones that regulate glucose homeostasis change in healthy pregnancies post-FA food fortification. Circulating folate, B12, homocysteine, prolactin (PRL), human placental lactogen (hPL) and placental growth hormone (GH2) were measured in early pregnancy maternal blood in women with uncomplicated pregnancies prior to (SCOPE: N = 604) and post (STOP: N = 711)-FA food fortification. FA food fortification resulted in 63% higher maternal folate. STOP women had lower hPL (33%) and GH2 (43%) after 10 weeks of gestation, but they had higher PRL (29%) and hPL (28%) after 16 weeks. FA supplementation during pregnancy increased maternal folate and reduced homocysteine but only in the SCOPE group, and it was associated with 54% higher PRL in SCOPE but 28% lower PRL in STOP. FA food fortification increased maternal folate status, but supplements no longer had an effect, thereby calling into question their utility. An altered secretion of hormones that regulate glucose homeostasis in pregnancy could place women post-fortification at an increased risk of insulin resistance and gestational diabetes, particularly for older women and those with obesity.
Topics: Humans; Pregnancy; Female; Aged; Placental Lactogen; Folic Acid; Prolactin; Food, Fortified; Diabetes, Gestational; Insulin Resistance; Prospective Studies; Placenta; Growth Hormone; Glucose
PubMed: 37049394
DOI: 10.3390/nu15071553 -
Frontiers in Cell and Developmental... 2022Cytotrophoblasts are progenitor cells that proliferate and fuse to form the multinucleated syncytiotrophoblast layer, implicated in placental endocrine and transport...
Cytotrophoblasts are progenitor cells that proliferate and fuse to form the multinucleated syncytiotrophoblast layer, implicated in placental endocrine and transport functions. While membrane transporters play a critical role in the distribution of nutrients, hormones, and xenobiotics at the maternal-fetal interface, their selectivity to the syncytiotrophoblast layer is poorly characterized. We aimed to evaluate the regulation of placental transporters in response to trophoblast differentiation . Experiments were carried out in isolated primary human trophoblast cells before and after syncytialization. Gene expression of six molecular markers and thirty membrane transporters was investigated by qPCR analysis. Subsequently, functional expression was evaluated for proteins involved in the transplacental transfer of essential nutrients i.e., cholesterol (ABCA1, ABCG1), glucose (SLC2A1), leucine (SLC3A2, SLC7A5), and iron (transferrin receptor, TfR1). We identified that human chorionic gonadotropin, placental lactogen, endoglin, and cadherin-11 serve as optimal gene markers for the syncytialization process. We showed that trophoblast differentiation was associated with differential gene expression (mostly up-regulation) of several nutrient and drug transporters. Further, we revealed enhanced protein expression and activity of ABCG1, SLC3A2, SLC7A5, and TfR1 in syncytialized cells, with ABCA1 and GLUT1 displaying no change. Taken together, these results indicate that the syncytiotrophoblast has a dominant role in transporting essential nutrients cholesterol, leucine, and iron. Nonetheless, we present evidence that the cytotrophoblast cells may also be linked to transport functions that could be critical for the cell fusion processes. Our findings collectively yield new insights into the cellular functions associated with or altered by the trophoblast fusion. Importantly, defective syncytialization could lead to nutrient transfer imbalance, ultimately compromising fetal development and programming.
PubMed: 35273963
DOI: 10.3389/fcell.2022.820286 -
Biology of Sex Differences Nov 2021Current methods fail to accurately predict women at greatest risk of developing fetal growth restriction (FGR) or related adverse outcomes, including stillbirth. Sexual...
BACKGROUND
Current methods fail to accurately predict women at greatest risk of developing fetal growth restriction (FGR) or related adverse outcomes, including stillbirth. Sexual dimorphism in these adverse pregnancy outcomes is well documented as are sex-specific differences in gene and protein expression in the placenta. Circulating maternal serum microRNAs (miRNAs) offer potential as biomarkers that may also be informative of underlying pathology. We hypothesised that FGR would be associated with an altered miRNA profile and would differ depending on fetal sex.
METHODS
miRNA expression profiles were assessed in maternal serum (> 36 weeks' gestation) from women delivering a severely FGR infant (defined as an individualised birthweight centile (IBC) < 3rd) and matched control participants (AGA; IBC = 20-80th), using miRNA arrays. qPCR was performed using specific miRNA primers in an expanded cohort of patients with IBC < 5th (n = 15 males, n = 16 females/group). Maternal serum human placental lactogen (hPL) was used as a proxy to determine if serum miRNAs were related to placental dysfunction. In silico analyses were performed to predict the potential functions of altered miRNAs.
RESULTS
Initial analyses revealed 11 miRNAs were altered in maternal serum from FGR pregnancies. In silico analyses revealed all 11 altered miRNAs were located in a network of genes that regulate placental function. Subsequent analysis demonstrated four miRNAs showed sexually dimorphic patterns. miR-28-5p was reduced in FGR pregnancies (p < 0.01) only when there was a female offspring and miR-301a-3p was only reduced in FGR pregnancies with a male fetus (p < 0.05). miR-454-3p was decreased in FGR pregnancies (p < 0.05) regardless of fetal sex but was only positively correlated to hPL when the fetus was female. Conversely, miR-29c-3p was correlated to maternal hPL only when the fetus was male. Target genes for sexually dimorphic miRNAs reveal potential functional roles in the placenta including angiogenesis, placental growth, nutrient transport and apoptosis.
CONCLUSIONS
These studies have identified sexually dimorphic patterns for miRNAs in maternal serum in FGR. These miRNAs may have potential as non-invasive biomarkers for FGR and associated placental dysfunction. Further studies to determine if these miRNAs have potential functional roles in the placenta may provide greater understanding of the pathogenesis of placental dysfunction and the differing susceptibility of male and female fetuses to adverse in utero conditions.
Topics: Circulating MicroRNA; Female; Fetal Growth Retardation; Humans; Male; Placenta; Pregnancy; Pregnancy Outcome; Sex Factors
PubMed: 34789323
DOI: 10.1186/s13293-021-00405-z