Cytokines and cytokine receptors in fetal growth and development

2001 ◽  
Vol 29 (2) ◽  
pp. 33-37 ◽  
Author(s):  
M. E. Symonds ◽  
A. Mostyn ◽  
T. Stephenson

The cytokine receptors for growth hormone (GH), prolactin and leptin have a critical role in regulating embryo, placental and/or fetal development, which is dependent on stage of gestation and species. GH and prolactin receptors are detectable from conception, and alterations in the maternal hormonal environment may impact on placental growth from this early stage of gestation. Leptin is critical for conception, but its role in fetal growth remains elusive. During late gestation, when fetal growth accelerates and organ maturation occurs, prolactin and insulin-like growth factor-I may have interactive roles in regulating the growth of specific tissues, including adipose tissue. Prolactin, leptin and GH all have specific effects on fetal and neonatal energy balance, which are mediated in part through promoting lipolysis and/or enhancing the expression of uncoupling proteins. An increased understanding of these interactions is likely to have important implications for a number of potentially pathological conditions, including infection, obesity and hypertension.

1996 ◽  
Vol 270 (5) ◽  
pp. R1148-R1155 ◽  
Author(s):  
F. Lok ◽  
J. A. Owens ◽  
L. Mundy ◽  
J. S. Robinson ◽  
P. C. Owens

Insulin-like growth factor I (IGF-I) is required for normal fetal growth and skeletal maturation in late gestation, because null mutations of the IGF-I gene in mice reduce fetal weight and retard ossification of bones. To determine if, conversely, increased abundance of IGF-I promotes fetal growth and skeletal maturation, fetal sheep were infused intravascularly with recombinant human IGF-I (n = 7) (26 +/- 3 micrograms. h-1.kg-1) from 120 to 130 days gestation and compared with controls (n = 15). IGF-I infusion increased plasma IGF-I concentrations by 140% (P = 0.002) and weights of fetal liver, lungs, heart, kidneys, spleen, pituitary, and adrenal glands by 16-50% (P < 0.05). Weights and/or lengths of the fetus, placenta, gastrointestinal tract, individual skeletal muscles, and long bones were unchanged by IGF-I. However, IGF-I increased the percentage of proximal epiphyses of long bones present (P < 0.05) and their cross-sectional areas by 15 to 38% (P < 0.05). These results show that IGF-I promotes growth of major fetal organs, endocrine glands, and skeletal maturation in vivo, consistent with IGF-I actively controlling and not merely facilitating fetal growth. The variable response of different tissues may partly reflect tissue specificity in growth requirements for additional factors.


Reproduction ◽  
2007 ◽  
Vol 133 (3) ◽  
pp. 653-661 ◽  
Author(s):  
Christopher J McNeil ◽  
Margaret O Nwagwu ◽  
Angela M Finch ◽  
Kenneth R Page ◽  
Alan Thain ◽  
...  

Glucocorticoids play a critical role in fetal development, but inappropriate exposure is associated with reduced fetal growth. We investigated cortisol exposure and supply in a porcine model of differential fetal growth. This model compares the smallest fetus of a litter with an average-sized sibling at three stages of gestation. At day 45, small fetuses had reduced plasma cortisol (16.8 ± 3.4 ng/ml) relative to average fetuses (34.4 ± 3.4 ng/ml, P < 0.001). At day 65 levels had reduced in small and average fetuses to similar concentrations (5.7 ± 1.0 vs 4.8 ± 0.5 ng/ml, P = 0.128). By day 100, elevated levels were found in small fetuses (10.7 ± 1.5 vs 7.6 ± 0.7 ng/ml, P < 0.001). Maternal plasma cortisol was unchanged over gestation (day 45, 56.7 ± 21.6 ng/ml; day 65, 57.8 ± 14.4 ng/ml; day 100, 55.7 ± 6.5 ng/ml). We examined the cause of altered cortisol by investigating the fetal hypothalamic–pituitary–adrenal axis through the measurement of adrenocorticotropic hormone and assessing exposure to maternal cortisol by quantifying placental 11β-hydroxysteroid dehydrogenase-isoform 2 (11β HSD-2) gene expression. These data suggest that altered cortisol supply was of fetal origin. We examined organ glucocorticoid (GC) metabolism by the measurement of GC receptor (GR) and 11β-hydroxysteroid dehydrogenase-isoform 1 (11β HSD-1) gene expression. We found that fetal organs have different temporal patterns of 11β HSD-1 and GR expression, with the liver particularly sensitive to cortisol in late gestation. This study examines GC exposure in naturally occurring differential growth and simultaneously explores tissue GC sensitivity and handling, at three key stages of gestation.


Reproduction ◽  
2016 ◽  
Vol 151 (4) ◽  
pp. 443-453 ◽  
Author(s):  
Kun Tan ◽  
Zhuqing Wang ◽  
Zhenni Zhang ◽  
Lei An ◽  
Jianhui Tian

Increasing evidence indicates that IVF (IVF includes in vitro fertilization and culture) embryos and babies are associated with a series of health complications, and some of them show sex-dimorphic patterns. Therefore, we hypothesized that IVF procedures have sex-biased or even sex-specific effects on embryonic and fetal development. Here, we demonstrate that IVF-induced side effects show significant sexual dimorphic patterns from the pre-implantation to the prenatal stage. During the pre-implantation stage, female IVF embryos appear to be more vulnerable to IVF-induced effects, including an increased percentage of apoptosis (7.22±1.94 vs 0.71±0.76, P<0.01), and dysregulated expression of representative sex-dimorphic genes (Xist, Hprt, Pgk1 and Hsp70). During the mid-gestation stage, IVF males had a higher survival rate than IVF females at E13.5 (male:female=1.33:1), accompanied with a female-biased pregnancy loss. In addition, while both IVF males and females had reduced placental vasculogenesis/angiogenesis, the compensatory placental overgrowth was more evident in IVF males. During the late-gestation period, IVF fetuses had a higher sex ratio (male:female=1.48:1) at E19.5, and both male and female IVF placentas showed overgrowth. After birth, IVF males grew faster than their in vivo (IVO) counterparts, while IVF females showed a similar growth pattern with IVO females. The present study provides a new insight into understanding IVF-induced health complications during embryonic and fetal development. By understanding and minimizing these sex-biased effects of the IVF process, the health of IVF-conceived babies may be improved in the future.


2020 ◽  
Vol 21 (9) ◽  
pp. 846-859
Author(s):  
Mohd Saeed ◽  
Mohd Adnan Kausar ◽  
Rajeev Singh ◽  
Arif J. Siddiqui ◽  
Asma Akhter

Glycation refers to the covalent binding of sugar molecules to macromolecules, such as DNA, proteins, and lipids in a non-enzymatic reaction, resulting in the formation of irreversibly bound products known as advanced glycation end products (AGEs). AGEs are synthesized in high amounts both in pathological conditions, such as diabetes and under physiological conditions resulting in aging. The body’s anti-glycation defense mechanisms play a critical role in removing glycated products. However, if this defense system fails, AGEs start accumulating, which results in pathological conditions. Studies have been shown that increased accumulation of AGEs acts as key mediators in multiple diseases, such as diabetes, obesity, arthritis, cancer, atherosclerosis, decreased skin elasticity, male erectile dysfunction, pulmonary fibrosis, aging, and Alzheimer’s disease. Furthermore, glycation of nucleotides, proteins, and phospholipids by α-oxoaldehyde metabolites, such as glyoxal (GO) and methylglyoxal (MGO), causes potential damage to the genome, proteome, and lipidome. Glyoxalase-1 (GLO-1) acts as a part of the anti-glycation defense system by carrying out detoxification of GO and MGO. It has been demonstrated that GLO-1 protects dicarbonyl modifications of the proteome and lipidome, thereby impeding the cell signaling and affecting age-related diseases. Its relationship with detoxification and anti-glycation defense is well established. Glycation of proteins by MGO and GO results in protein misfolding, thereby affecting their structure and function. These findings provide evidence for the rationale that the functional modulation of the GLO pathway could be used as a potential therapeutic target. In the present review, we summarized the newly emerged literature on the GLO pathway, including enzymes regulating the process. In addition, we described small bioactive molecules with the potential to modulate the GLO pathway, thereby providing a basis for the development of new treatment strategies against age-related complications.


2021 ◽  
Vol 99 (Supplement_2) ◽  
pp. 25-26
Author(s):  
Sterling H Fahey ◽  
Sarah West ◽  
John M Long ◽  
Carey Satterfield ◽  
Rodolfo C Cardoso

Abstract Gestational nutrient restriction causes epigenetic and phenotypic changes that affect multiple physiological processes in the offspring. Gonadotropes, the cells in the anterior pituitary that secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH), are particularly sensitive to nutritional changes during fetal development. Our objective herein was to investigate the effects of gestational nutrient restriction on LH protein content and number of gonadotropes in the fetal bovine pituitary. We hypothesized that moderate nutrient restriction during mid to late gestation decreases pituitary LH production, which is associated with a reduced number of gonadotropes. Embryos were produced in vitro with X-bearing semen from a single sire then split to generate monozygotic twins. Each identical twin was transferred to a virgin dam yielding four sets of female twins. At gestational d 158, the dams were randomly assigned into two groups, one fed 100% NRC requirements (control) and the other fed 70% of NRC requirements (restricted) during the last trimester of gestation, ensuring each pair of twins had one twin in each group. At gestational d 265, the fetuses (n = 4/group) were euthanized by barbiturate overdose, and the pituitaries were collected. Western blots were performed using an ovine LH-specific antibody (Dr. A.F. Parlow, NIDDK). The total LH protein content in the pituitary tended to be decreased in the restricted fetuses compared to controls (P &lt; 0.10). However, immunohistochemistry analysis of the pituitary did not reveal any significant changes in the total number of LH-positive cells (control = 460±23 cells/0.5 mm2; restricted = 496±45 cells/0.5 mm2, P = 0.58). In conclusion, while maternal nutrient restriction during gestation resulted in a trend of reduced LH content in the fetal pituitary, immunohistological findings suggest that these changes are likely related to the individual potential of each gonadotrope to produce LH, rather than alterations in cell differentiation during fetal development.


1997 ◽  
Vol 273 (1) ◽  
pp. L227-L233 ◽  
Author(s):  
V. C. Venkatesh ◽  
H. D. Katzberg

Pulmonary epithelial Na+ channels (ENaC), composed of three distinct subunits (alpha, beta, and gamma), play a critical role in the regulation of fluid reabsorption from airspaces of late-gestation fetal lung. We studied the expression of ENaC subunit genes in cultured human fetal lung. All three mRNAs were expressed at low levels in second trimester lung (13-32% of adult values at 24 wk gestation). There was a spontaneous increase of approximately threefold over preculture values of all three subunits within 24 h of explant culture in serum-free Waymouth's medium. Dexamethasone (Dex) induced all three mRNAs by two- to threefold. Maximal induction was noted by 8 h with 30-100 nM Dex and half-maximal stimulation with 3-10 nM Dex. Cycloheximide decreased basal expression of all three subunits by 8 h but did not alter the response to Dex. Actinomycin D and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), inhibitors of RNA polymerase II, decreased the basal and the Dex-induced expression of all three subunits with a more marked effect on human hENaC-gamma than on hENaC-alpha or hENaC-beta. Under conditions where transcription was blocked by actinomycin D or DRB, Dex did not alter the stability of the three mRNAs. Triiodothyronine (T3) at low (2 nM) or high (100 nM) concentrations had no effect on the expression of the three subunits in the presence or absence of low (10 nM) or high (100 nM) concentrations of Dex for 8 or 24 h. Similarly, 8-bromoadenosine 3',5'-cyclic monophosphate (2 microM) had no effect on basal or Dex-induced increase in the three subunits. We conclude that the three Na+ channel subunit genes are expressed in second trimester human fetal lung and are coordinately upregulated by glucocorticoid hormones but not by T3 or adenosine 3',5'-cyclic monophosphate. Glucocorticoid induction is receptor mediated, is primarily transcriptional, and does not require the induction of an intermediate protein for transcriptional enhancement. We speculate that induction of lung ENaC may contribute to the beneficial effects of antenatal glucocorticoids in premature babies.


2019 ◽  
Vol 97 (Supplement_2) ◽  
pp. 13-13
Author(s):  
Joel M DeRouchey ◽  
Mike D Tokach ◽  
Robert D Goodband ◽  
Jason C Woodworth ◽  
Steve S Dritz ◽  
...  

Abstract Improvements in modern sow prolificacy have markedly increased the number of pigs weaned, thus the ability of sows to provide nutrients to support fetal growth and milk production has been enhanced. The goals of the gestation nutrition program consist of meeting the nutrient requirements for maintenance and growth and for adequate conceptus development, while managing body condition. Early gestation represents the best opportunity for replenishing body reserves, whereas in late gestation, both estimated protein deposition and energy requirement are exponentially increased and directed towards fetal growth and mammary development. Increased feed intake after breeding has been presumed to be detrimental to embryo survival; however, data with modern line sows demonstrates to feed thin sows to recover body condition as quickly as possible while avoiding feed deprivation immediately after breeding. Importance of body condition scoring remains unchanged: feed thin sows to bring back to adequate body condition and prevent over-conditioned sows at farrowing. A recent meta-analysis showed increasing late gestation feed intake seems to modestly improve piglet birth weight by 28 g per piglet in gilts and sows. Also, recent findings in gestating sows suggest modern genotypes have improved feed efficiency and propensity for growth. Therefore, increasing energy intake during late gestation has a modest effect on piglet birth weight and a negative effect on stillborn rate. Historically, lactation catabolism impacted subsequent reproductive performance of sows, particularly in first-parity. However, contemporary sows appear to be increasingly resistant to the negative effects of lactational catabolism. Even so, continued emphasis on maximizing lactation feed intake is critical to support milk production and prevent excessive lean tissue mobilization. Research data suggests that ad libitum feeding and offering lactation diets during the wean-to-estrus interval is not needed. Modern genetic sow lines appear to be more robust from a nutritional perspective than in the past.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chun-Ping Hao ◽  
Nan-Jue Cao ◽  
Yu-He Zhu ◽  
Wei Wang

AbstractDental implants are commonly used to repair missing teeth. The implant surface plays a critical role in promoting osseointegration and implant success. However, little information is available about which implant surface treatment technology best promotes osseointegration and implant stability. The aim of this network meta-analysis was to evaluate the osseointegration and stability of four commonly used dental implants (SLA, SLActive, TiUnite, and Osseotite). The protocol of the current meta-analysis is registered in PROSPERO (International Prospective Register of Systematic Reviews) under the code CRD42020190907 (https://www.crd.york.ac.uk). We conducted a systematic review following PRISMA and Cochrane Recommendations. Medline (PubMed), Cochrane Library, Embase, and the Web of Science databases were searched. Only randomized controlled trials were considered. Twelve studies were included in the current network meta-analysis, eleven studies were included concerning the osseointegration effect and five studies were included for stability analysis (four studies were used to assess both stability and osseointegration). Rank possibility shows that the SLActive surface best promoted bone formation at an early healing stage and TiUnite seemed to be the best surface for overall osseointegration. For stability, TiUnite seemed to be the best surface. The present network meta-analysis showed that the SLActive surface has the potential to promote osseointegration at an early stage. The TiUnite surface had the best effect on osseointegration regarding the overall healing period. The TiUnite surface also had the best effect in stability.


2021 ◽  
Vol 19 ◽  
Author(s):  
Yu Jin Jung ◽  
Han-Joon Kim ◽  
Sun Ha Paek ◽  
Beomseok Jeon

: Sleep-wake disturbances (SWD) are one of the most common non-motor symptoms in Parkinson's disease (PD) and can appear in the early stage even before the onset of motor symptoms. Deep brain stimulation (DBS) is an established treatment for the motor symptoms in patients with advanced PD. However, the effect of DBS on SWD and its specific mechanisms are not widely understood and remain controversial. In addition to the circuit-mediated direct effect, DBS may improve SWD by an indirect effect such as the resolution of nocturnal motor complications and a reduction of dopaminergic medication. Here, the authors review the recent literatures regarding the impact of DBS on SWD in patients with PD. Furthermore, the selection of the DBS targets and the specific effects of applying DBS to each target on SWD in PD are also discussed.


2018 ◽  
Vol 26 (9) ◽  
pp. 1287-1293 ◽  
Author(s):  
Yuri K. Sinzato ◽  
Estela M. Bevilacqua ◽  
Gustavo T. Volpato ◽  
Rogelio E. Hernandez-Pando ◽  
Marilza V. C. Rudge ◽  
...  

The diabetic syndrome affects pregnancy, contributing to placental functional and structural disruptions and impaired fetal development, with many reports indicating tobacco-associated morbidity and perinatal mortality. In our study, an experimental rat model of diabetes and cigarette smoke exposure in pregnant rats was used to determine the impact of the combination of diabetes and exposure to cigarette smoke during pregnancy on maternal oxidative stress biomarkers and placental and fetal development. Diabetes was induced by streptozotocin, and dams were exposed to cigarette smoke by mainstream smoke generated by a mechanical smoking device and delivered into a chamber. Four groups of dams were studied: nondiabetic (C, control) and diabetic (D) exposed to filtered air and nondiabetic (CS) and diabetic (DS) exposed to cigarette smoke prior to and during pregnancy. Maternal oxidative stress biomarkers, placental morphology, and fetal growth were determined close to term. The combination of diabetes and cigarette smoke resulted in elevated maternal blood glucose levels and increased number of small fetuses. Placentas from the DS group showed increased junctional zone and decreased labyrinthine area. The morphological alterations were characterized by extensive vascular congestion, thickness, and hyalinization of the vascular walls, numerous decidual cells with abundant glycogen, and macrophages with cytoplasmic inclusions of hemosiderin. Additionally, they showed increased glycogen accumulation and junctional zone structural derangement with ectopic giant cells. No alterations were observed in maternal oxidative stress status. Thus, our result suggests that diabetes makes pregnant rats more susceptible to the adverse effects of exposure to cigarette smoke on placental morphometry and fetal growth.


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