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1.
Prog Lipid Res ; 91: 101222, 2023 07.
Article in English | MEDLINE | ID: mdl-36746351

ABSTRACT

This review is about the role of arachidonic acid (ArA) in foetal and early growth and development. In 1975 and '76, we reported the preferential incorporation of ArA into the developing brain of rat pups, its conservation as a principal component in the brains of 32 mammalian species and the high proportion delivered by the human placenta for foetal nutrition, compared to its parent linoleic acid (LA). ArA is quantitatively the principal acyl component of membrane lipids from foetal red cells, mononuclear cells, astrocytes, endothelium, and placenta. Functionally, we present evidence that ArA, but not DHA, relaxes the foetal mesenteric arteries. The placenta biomagnifies ArA, doubling the proportion of the maternal level in cord blood. The proportions of ArA and its allies (di-homo-gamma-linolenic acid (DGLA), adrenic acid and ω6 docosapentaenoic acid) are similar or higher than the total of ω3 fatty acids in human milk, maintaining the abundant supply to the developing infant. Despite the evidence of the importance of ArA, the European Food Standard Agency, in 2014 rejected the joint FAO and WHO recommendation on the inclusion of ArA in infant formula, although they recommended DHA. The almost universal dominance of ArA in the membrane phosphoglycerides during human organogenesis and prenatal growth suggests that the importance of ArA and its allies in reproductive biology needs to be re-evaluated urgently.


Subject(s)
Docosahexaenoic Acids , Linoleic Acid , Pregnancy , Female , Humans , Animals , Rats , Arachidonic Acid/metabolism , Docosahexaenoic Acids/metabolism , Linoleic Acid/metabolism , Infant Formula , Glycerophospholipids , Mammals/metabolism
2.
Clin Nutr ; 35(3): 608-14, 2016 06.
Article in English | MEDLINE | ID: mdl-26091965

ABSTRACT

BACKGROUND & AIMS: Gestational diabetes mellitus (GDM) compromises the level of docosahexaenoic acid (DHA) in phospholipids of maternal and fetal red blood cells and fetal plasma. This is of some concern because of the importance of DHA for fetal neuro-visual development. We have investigated whether this abnormality could be rectified by supplementation with DHA-enriched formula. METHODS: Women with GDM (n = 138) recruited from Newham University Hospital, London received two capsules of DHA-enriched formula (active-group) or high oleic acid sunflower seed oil (placebo-group) from diagnosis until delivery. Maternal (baseline and delivery) and fetal (cord blood) red blood cell and plasma phospholipid fatty acid composition, and neonatal anthropometry were assessed. RESULTS: One hundred and fourteen women (58 active, 56 placebo) completed the trial. The active-group compared with the placebo-group had significantly enhanced level of DHA in plasma phosphatidylcholine (4.5% vs 3.8%, P = 0.011), red blood cell phosphatidylcholine (2.7% vs 2.2%, P = 0.022) and phosphatidylethoanolamine (9.5% vs 7.6%, P = 0.002). There was no difference in cord plasma and red blood cell phospholipid DHA between the two groups. The neonates of the two groups of women had comparable anthropometric measurements at birth. CONCLUSION: Daily supplementation of 600 mg DHA enhances maternal but not fetal DHA status in pregnancy complicated by GDM. The inefficacy of the supplement to improve fetal status suggests that the transfer of DHA across the placenta maybe impaired in women with the condition. Regardless of the mechanisms responsible for the impairment of the transfer, the finding has implications for the management of neonates of women with GDM because they are born with a reduced level of DHA and the condition is thought to be associated with a risk of neuro-developmental deficits. We suggest that babies of women with GDM, particularly those not suckling, similar to the babies born prematurely require formula milk fortified with a higher level of DHA.


Subject(s)
Diabetes, Gestational/diet therapy , Dietary Supplements , Docosahexaenoic Acids/therapeutic use , Fetal Development , Hypoglycemic Agents/therapeutic use , Intestinal Absorption , Maternal Nutritional Physiological Phenomena , Adult , Diabetes, Gestational/blood , Dietary Supplements/analysis , Docosahexaenoic Acids/blood , Docosahexaenoic Acids/metabolism , Double-Blind Method , Female , Fetal Blood/chemistry , Humans , Hypoglycemic Agents/blood , Hypoglycemic Agents/metabolism , Infant, Newborn , London , Lost to Follow-Up , Male , Maternal-Fetal Exchange , Nutritional Status , Patient Dropouts , Pregnancy , Sunflower Oil/analysis , Sunflower Oil/metabolism , Sunflower Oil/therapeutic use , Young Adult
3.
J Assist Reprod Genet ; 31(10): 1337-47, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25117646

ABSTRACT

With the advent of assisted reproductive technology in the past three decades, the clinical importance of fallopian tubes has been relatively overlooked. However, successful spontaneous conception requires normal function of the tube to provide not only a conduit for the gametes to convene and embryo to reach the uterine cavity, but also a physiologically optimized environment for fertilization and early embryonic development. In this review, after a brief description of normal human tubal anatomy and histology, we will discuss tubal transport and its principal effectors, including ciliary motion, muscular contractility and tubal fluid. Furthermore, we will discuss the ciliary ultrastructure and regulation of ciliary beat frequency by ovarian steroids, follicular fluid, angiotensin system, autonomic nervous system and other factors such as adrenomedullin and prostaglandins. In the last section, we describe the adverse impact of various pathological conditions, such as endometriosis, infection and smoking on tubal function and ciliary motility.


Subject(s)
Fallopian Tubes/pathology , Fallopian Tubes/physiology , Germ Cells/pathology , Germ Cells/physiology , Animals , Female , Humans , Reproductive Techniques, Assisted , Uterus/pathology , Uterus/physiology
4.
Hear Res ; 268(1-2): 114-22, 2010 Sep 01.
Article in English | MEDLINE | ID: mdl-20685243

ABSTRACT

This study investigates whether physiological variations in ovarian hormones during the ovarian cycle (OC) are associated with changes in auditory function. Sixteen women with normal hearing underwent auditory tests and simultaneous measurements of the hormone levels four times during OC. The auditory tests included recording of otoacoustic emissions (OAEs), the medial olivocochlear (MOC) suppression and auditory brainstem responses (ABRs). The OC was defined by oestradiol and progesterone serum levels and menstrual cycle dating. A significant spontaneous OAE frequency shift [F(3,114.6)=15.8, p<0.001], with the greatest shift in the late follicular phase (highest oestrogen levels), was observed. Transient evoked OAE levels showed a consistent tendency in an increase in all frequency bands in the late follicular/early luteal stage and a decrease in the late follicular stage; TEOAE inter-session comparison indicated very small statistical differences. The MOC suppression changed significantly during OC [F(3,33.8)=3.2, p=0.036], with significant inter-session difference, lower in session 2 than in session 1 (p=0.019) and lower in session 4 than in session 1 (p=0.007). The ABR wave V absolute latency changed significantly during OC [F(3,33)=3.3, p=0.03], longer in the late follicular phase. There was also a significant positive correlation of TEOAEs and ABR (wave V latency and III-V interval) and significant negative correlation of MOC suppression with oestradiol levels in the follicular phase. The results of this study reflect very small changes in auditory function during OC, and they are suggestive of an increased hearing sensitivity around the time of ovulation.


Subject(s)
Auditory Pathways/physiology , Menstrual Cycle/physiology , Acoustic Impedance Tests , Acoustic Stimulation , Adult , Audiometry, Pure-Tone , Auditory Threshold , Biomarkers/blood , Cochlea/physiology , Estradiol/blood , Evoked Potentials, Auditory, Brain Stem , Female , Humans , Menstrual Cycle/blood , Middle Aged , Neural Inhibition , Olivary Nucleus/physiology , Otoacoustic Emissions, Spontaneous , Progesterone/blood , Reaction Time , Young Adult
5.
Nutr Health ; 20(2): 167-85, 2009.
Article in English | MEDLINE | ID: mdl-19835110

ABSTRACT

Preterm neonates are more susceptible to infection than term neonates. Arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) are biologically active components of cell membrane phospholipids. Arachidonic acid is a substrate for the synthesis of eicosanoids, potent regulators of immune function. Preterm babies may have a deficiency of arachidonic acid and docosahexaenoic acid, but the impact of this deficit on maturation of the immune system is unknown. To address this we explored links between placental provision of fatty acids to cord blood mononuclear cell (CBMC) membranes using gas chromatography (GC), and maturation of the immune response with gestational age by analysing lymphocyte subsets by flow cytometry. This is the first study to examine the lipid profile of the phosphatidylcholine (PC) and phosphatidylethanolamine (PE) fractions of CBMC membranes from preterm neonates. The long chain polyunsaturated fatty acid (LCPUFA) composition of CBMC membranes was dominated by arachidonic acid in both PE (34%) and PC (15%) fractions in healthy term neonates (> or =37 weeks, n=9), whilst in healthy preterm neonates (<37 weeks, n=10) the level of arachidonic acid was significantly lower at 28.8% and 12.5% respectively (p<0.05). Preterm neonates (<37 weeks, n=23) also had significantly lower absolute numbers of CD4+ (p<0.05) leukocytes and CD4+ (p<0.01) and CD8+ (p<0.05) naïve T-cells than term (> or =37 weeks, n=24) neonates that correlated with gestational age (p<0.01-0.05).


Subject(s)
Arachidonic Acid/immunology , Cell Membrane/immunology , Docosahexaenoic Acids/immunology , Immunity, Cellular/immunology , Infant, Premature/immunology , Lipids/deficiency , Adult , Arachidonic Acid/blood , Arachidonic Acid/deficiency , Cell Membrane/chemistry , Chromatography, Gas , Docosahexaenoic Acids/blood , Female , Fetal Blood/immunology , Flow Cytometry , Gestational Age , Humans , Infant, Newborn , Infant, Premature/blood , Lipids/blood , Lipids/immunology , Lymphocytes/immunology , Male , Young Adult
6.
Lipids ; 41(4): 341-6, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16808147

ABSTRACT

In previous studies, we reported that neonates of women with gestational diabetes mellitus (GDM) have reduced blood levels of arachidonic acid (AA) and docosahexaenoic acid (DHA) that were unrelated to maternal status. Since both AA and DHA are selectively transferred from maternal to fetal circulation by the placenta, we have investigated whether the FA composition of the placenta is altered by GDM. Thirty-six women, 11 with and 25 without GDM, were recruited from Newham General Hospital, London. The women with GDM had higher levels of di-homo-gamma-linolenic (P < 0.05), docosatetraenoic (n-6 DTA; P< 0.0001), docosapentaenoic n-6 (P< 0.005), total n-6 (P < 0.005), docosapentaenoic (n-3 DPA; P < 0.005), and total n-3 (P < 0.01) FA, as well as higher levels of AA (P < 0.05) and DHA (P < 0.01), in placental choline phosphoglycerides (CPG) compared with the healthy women who served as controls. Similarly, the women with GDM had elevated n-6 DTA (P < 0.005), AA, total n-6 metabolites (P < 0.05), DHA, total n-3 metabolites, and total n-3 FA (P < 0.005) in ethanolamine phosphoglycerides (EPG). In contrast to CPG and EPG, the placental TG of the women with GDM had higher linoleic acid (P< 0.05) and lower AA, n-6 metabolites, and n-3 DPA (P < 0.01). The placenta is devoid of desaturase activity, and it is thought to be reliant on maternal circulation for both AA and DHA. Hence, the enhanced levels of the two FA in the placenta of the GDM group suggests that these FA are taken up from the maternal circulation and retained after esterification into phosphoglycerides instead of being transferred to the fetus. Further study is needed to elucidate the mechanism involved and the effect of the phenomenon on postnatal growth and development of the offspring.


Subject(s)
Arachidonic Acid/metabolism , Diabetes, Gestational/metabolism , Docosahexaenoic Acids/metabolism , Phospholipids/metabolism , Placenta/metabolism , Adult , Case-Control Studies , Diabetes, Gestational/pathology , Ethanolamine/metabolism , Fatty Acids/metabolism , Female , Glycerophospholipids/metabolism , Humans , Organ Size , Placenta/chemistry , Pregnancy
7.
J Nutr ; 135(11): 2566-71, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16251612

ABSTRACT

The aim of this study was to determine whether the high concentration of arachidonic acid (AA) in term placentae accumulates during pregnancy or is an inherent characteristic of placental lipids. We investigated the lipid content and fatty acid composition of the human placental phospholipids at 2 gestational periods, early in pregnancy (8-14 wk, n = 48) and at term (38-41 wk of gestation, n = 19). The subjects were healthy, normotensive, and free of medical and obstetric complications. The lipid concentration of placentae increased from 0.8% in early gestation to 1.4% at term (P < 0.0001). The mean proportions of AA were lower in the choline (P < 0.05), inositol (P < 0.0001), and ethanolamine (P < 0.0001) phosphoglycerides of the term compared with the early placenta. In contrast, the proportions of the immediate precursor of AA, dihomo-gamma-linolenic acid (DGLA), were higher in the term placenta, particularly in the inositol and serine phosphoglycerides (P < 0.0001). In sphingomyelin, the percentage of lignoceric acid was increased and that of nervonic acid was reduced at term (P < 0.01). The dominance of AA, particularly in the early placenta, suggests that it has an important role for placental development, i.e., organogenesis and vascularization. There was no evidence of an accumulation of AA in the placenta toward term, which might be a trigger for parturition. In contrast, the increased proportion of DGLA (precursor of the vasorelaxant and anticoagulant prostaglandin E(1)) at term is more consistent with a profile favoring optimal blood flow to nourish the fetal growth spurt.


Subject(s)
Arachidonic Acid/analysis , Cell Membrane/chemistry , Gestational Age , Glycerophospholipids/chemistry , Placenta/chemistry , Adolescent , Adult , Body Mass Index , Female , Humans , Labor, Obstetric , Phosphatidylcholines/chemistry , Phosphatidylethanolamines/chemistry , Phosphatidylinositols/chemistry , Phosphatidylserines/chemistry , Phospholipids/chemistry , Pregnancy , Sphingomyelins/chemistry
8.
Lancet ; 360(9341): 1221-2, 2002 Oct 19.
Article in English | MEDLINE | ID: mdl-12401250

ABSTRACT

Endometriosis and infertility are known to be associated, but it is unclear whether endometriosis causes infertility. We used contrast analogue enhancement to study the effect of peritoneal fluid from women with early stage endometriosis on the ciliary beat frequency of human fallopian tube epithelium. We obtained peritoneal fluid from six women with early stage endometriosis and from six fertile women with no evidence of endometriosis to use as controls. Fallopian tubes from hysterectomy specimens were collected from 17 women. The difference in ciliary beat frequency between fallopian tubes exposed to peritoneal fluids of women with and without endometriosis increased with the duration of incubation (mean difference at 24 h 1.35 Hz, 95% CI 0.94-1.75, p=0.01). At 24 h, ciliary beat frequency was significantly lower in the incubations with peritoneal fluid from women with endometriosis than controls (4.29 [0.15] vs 5.64 Hz [0.15], respectively, p=0.001). Impairment of ciliary action in women with endometriosis might reduce fertility.


Subject(s)
Ascitic Fluid , Cilia , Endometriosis/complications , Fallopian Tubes , Infertility, Female/etiology , Adult , Analysis of Variance , Case-Control Studies , Endometriosis/physiopathology , Female , Humans , Infertility, Female/physiopathology , Middle Aged , Time Factors
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