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Biomedical subjects

R G Lea

Publications and source records attributed to R G Lea.

At least 19 recordsLinked to original sources
PubMed2006

Effects of maternal undernutrition during early pregnancy on apoptosis regulators in the ovine fetal ovary.

This study aimed to determine whether reduced fetal ovary folliculogenesis in ewes undernourished during early/midpregnancy is associated with altered ovarian cell proliferation and/or the expression of apoptosis-regulating genes. Groups of ewes (n = 11-19) were fed either 100% (high; H) or 50% (low; L) of metabolisable energy requirements for live-weight maintenance during selected windows of gestation. All animals were killed at days 50, 65 or 110 of gestation. Between mating and slaughter, control animals were fed the H ration, while animals of other subgroups were fed the L ration from (a) mating to slaughter at 50, 65 or 110 days; (b) 0 to 30 days; (c) 31 to 50 or 65 days; or (d), in the day 110 slaughter group only, from 66 to 110 days. Bouin's-fixed fetal ovaries were examined for (a) Ki67 immunoexpression (proliferation) and (b) Bax and Mcl-1 (apoptosis-regulating genes) expression by in situ hybridisation (day 110) and immunohistochemistry (days 50, 65 and 110). At day 50, maternal nutrition had no effect on Ki67, predominant in germ cells, or Bax and Mcl-1, predominant in the oocytes. Restricted maternal food intake from 0 to 30 days significantly reduced staining for Ki67 in germ cells at day 65 (P < 0.05) but increased staining in granulosa cells at day 110 (P < 0.05). In animals fed the L ration for 110 days, primordial follicle Bax and Mcl-1 were significantly increased (Bax: P < 0.01; Mcl-1: P < 0.05). Granulosa cell Bax was also increased (P < 0.05). When the L ration was fed from 66 to 110 days, granulosa cell Bax (P < 0.05) and primordial follicle Mcl-1 (P < 0.01) were also significantly increased. In the fetal ovarian vasculature, animals underfed for 0-110 days had significantly elevated perivascular Mcl-1 (P < 0.001) and endothelial Bax expression (P < 0.05). Moreover, at day 110, endothelial Mcl-1 was increased by underfeeding from 0 to 30 days (P < 0.05). These data indicate that maternal undernutrition alters proliferation and the expression of apoptosis-regulating genes in the developing fetal ovary. The precise mechanism depends on the window of maternal food restriction.

Animal Nutritional Physiological Phenomena↗
PubMed2001

Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro.

Maternal iron deficiency during pregnancy induces anaemia in the developing fetus; however, the severity tends to be less than in the mother. The mechanism underlying this resistance has not been determined. We have measured placental expression of proteins involved in iron transfer in pregnant rats given diets with decreasing levels of iron and examined the effect of iron deficiency on iron transfer across BeWo cell layers, a model for placental iron transfer. Transferrin receptor expression was increased at both mRNA and protein levels. Similarly, expression of the iron-responsive element (IRE)-regulated form of the divalent metal transporter 1 (DMT1) was also increased. In contrast, the non-IRE regulated isoform showed no change in mRNA levels. Protein levels of DMT1 increased significantly. Iron efflux is thought to be mediated by the metal transporter protein, IREG1/ferroportin1/MTP1, and oxidation of Fe(II) to Fe(III) prior to incorporation into fetal transferrin is carried out by the placental copper oxidase. Expression of IREG1 was not altered by iron deficiency, whereas copper oxidase activity was increased. In BeWo cells made iron deficient by treatment with desferrioxamine ('deferioxamine'), iron accumulation from iron-transferrin increased, in parallel with increased expression of the transferrin receptor. At the same time, iron efflux also increased, showing a higher flux of iron from the apical to the basolateral side. The data show that expression of placental proteins of iron transport are up-regulated in maternal iron deficiency, resulting in an increased efficiency of iron flux and a consequent minimization of the severity of fetal anaemia.

Anemia, Iron-Deficiency↗
PubMed2001

Leptin expression in placental and fetal tissues: does leptin have a functional role?

Leptin is expressed in the placenta and in certain fetal tissues; however, little is known with regard to the function of this hormone in these tissues. To date, most evidence suggests that placental and/or fetal leptin acts as a fetal growth factor, but this is far from clear. Leptin may also have physiological effects on the placenta, including angiogenesis, growth and immunomodulation. The effects of placental leptin, if any, on the mother may contribute to endocrine-mediated alterations in energy balance, such as the mobilization of maternal fat, which occurs during the second half of pregnancy. In this review we will address these and other issues related to the expression of both placental and fetal leptin.

Animals↗
PubMed2001

Effect of maternal undernutrition during pregnancy on early ovarian development and subsequent follicular development in sheep fetuses.

Gonad development in female sheep fetuses is thought to occur in a number of key stages. The aim of this study was to determine the effects of maternal undernutrition, applied at one or more of these critical stages, on fetal ovarian development. Groups of ewes (n = 11-19) were fed rations providing either 100% (high; H) or 50% (low; L) of energy requirements for live weight maintenance during selected 'windows' during gestation. Control ewes (HH and HHH) were fed the H ration from mating until they were killed at days 50, 65 (HH) or 110 (HHH) of gestation, whereas ewes of other groups were fed the L ration for the periods between day 0 and day 30 of gestation (LH and LHH), day 31 and day 50 or 65 of gestation (HL and HLH), day 65 and day 110 of gestation (HHL) or day 0 of gestation until the animals were killed (LL and LLL). At day 50 of gestation, there was no effect of nutritional treatment on mean fetal mass but compared with HH animals, mean fetal ovarian mass was significantly lower in HL (P < 0.05) and LL (P < 0.001) animals. At day 65 of gestation, there were significantly fewer germ cells (P < 0.05) at the resting, diplotene stage of initial meiosis in LL animals than there were in HH animals, indicating delayed germ cell maturation and onset of meiosis. Qualitative assessment of proliferative cell nuclear antigen immunostaining indicated that, at day 50 of gestation, staining was located predominantly in the germ cells, whereas by day 65 of gestation, staining was confined predominantly to somatic cells. Undernutrition in each one of these windows was associated with delayed ovarian follicular development (P < 0.05-0.001) as measured by development of the granulosa cell layer at day 110 of gestation. This study demonstrates that undernutrition before and during folliculogenesis can delay fetal follicular development.

Analysis of Variance↗
PubMed2001

Endocrine disrupting chemicals: effects on human male reproductive health.

There is now considerable evidence that male reproductive function is declining in human and wildlife populations. This is coincident with the increasing use and prevalence of man-made chemicals in the environment over the last fifty years. Certain chemicals have subsequently been shown to disturb the developing fetal endocrine system of laboratory animals in utero. In these experiments, treatment caused similar male reproductive problems in offspring as those already observed in wildlife and human populations. In addition, both the human DES data and rodent studies have shown that there are specific windows of gestation when the developing fetal gonad is highly sensitive to small endocrine changes. Animal in vivo and human in vitro studies have identified EDC sensitive genes. Consequently, hypotheses are being generated concerning mechanism of action e.g. disturbed testicular apoptosis and altered hepatic biotransformation of steroids. While animal studies provide us with valuable insights into the range of effects that can be attributed to in utero EDC exposure, varying maternal doses employed by different research groups make relation of the results to human observations difficult. The EDC concentration representative of fetal exposure levels is uncertain. Confounding factors include: (a) the vast number of chemicals termed EDCs, (b) the ability of chemicals to bioaccumulate in body lipid, (c) the metabolism of body lipid during pregnancy releasing the mothers lifetime EDC legacy into circulation and (d) the poorly understood kinetics of EDC transfer across the placenta. Thus, the level of fetal exposure can only be crudely estimated at present. This highlights the need for large animal models of EDC in utero exposure where the partitioning of EDCs between the mother and fetus and transfer across the placenta can be studied in detail. Despite considerable effort the mechanisms by which these endocrine disrupting chemicals exert their effects are still largely unknown. Further studies of the mechanism of action, and consequences, of EDCs in fetal development must be done in order to elucidate how EDCs exert their effects. This can only be achieved using a combined approach whereby animal models are used in combination with in vitro human studies. In conclusion however, there are now sufficient animal model data to prove that EDCs can adversely affect reproductive development and function in the male. Our further understanding of the mechanisms involved may allow intervention strategies whereby we can at least prevent a further decline in male as well as female reproductive health.

Animals↗
PubMed2000

Ontogeny of the expression of leptin and its receptor in the murine fetus and placenta.

Leptin is a 167-amino acid protein that is secreted from adipose cells and expressed in placental tissues. It is important nutritionally in the regulation of energy balance, but also has other functions such as a role in reproduction. To investigate the function of the leptin system in fetal development we examined, primarily by in-situ hybridization and immunohistochemistry, the expression (both mRNA and protein) of leptin and its receptor (including the signalling splice variant) in tissues from 11.5, 13.5, 16.5 and 18.5 d postcoitus murine fetuses and associated placentas. We detected leptin mRNA (at low levels) and protein predominantly in the cytotrophoblasts of the labyrinth part of the placenta, an area of nutrient exchange between the developing fetus and the placenta, and in the trophoblast giant cells situated in the junctional zone at the maternal interface. In addition, leptin was strongly expressed in the fetal cartilage-bone and at a lower level in the hair follicles, heart, and liver of the murine fetus at differing stages of development. The leptin receptor, including the signalling splice variant, was also identified in specific fetal tissues. The physiological importance of expression of both leptin and the leptin receptor (OB-R and OB-Rb) in the placenta remains to be determined. In addition, the high levels of expression of leptin and its receptor in discrete areas of the murine fetus suggest that leptin has a critical role in fetal development.

Animals↗
PubMed2000

The effect of ceruloplasmin on iron release from placental (BeWo) cells; evidence for an endogenous Cu oxidase.

The mechanism of iron release from the placenta into the fetal circulation is not well understood. Ceruloplasmin, a plasma ferroxidase, has been implicated in iron efflux from a variety of cell types. The hypothesis is that circulating ceruloplasmin facilitates iron efflux by oxidizing the released Fe(II) to Fe(III) for incorporation into transferrin. We tested whether this mechanism mediates iron release from placental cells into the fetal circulation, using the BeWo cell line, a choriocarcinoma which can differentiate into a syncytium.(59)Fe release from undifferentiated or differentiated cells and from cells grown on porous filters was not stimulated by extracellular ceruloplasmin. Instead, we found that BeWo cells express an endogenous ferroxidase. The protein is membrane bound and cross-reacts with an anti-ceruloplasmin antibody, but has a different size; 100 and 140 kDa. Similar immunoreactivity was identified in first- and third-trimester human placentae. In BeWo cells, the protein has a perinuclear localization but does not entirely co-localize with markers for the endoplasmic reticulum or Golgi apparatus. We propose that this oxidase performs the same function as serum ceruloplasmin and is involved in iron release into the fetal circulation.

Ceruloplasmin↗
PubMed2000

Placental leptin in normal, diabetic and fetal growth-retarded pregnancies.

Leptin expression in third trimester placenta (p) and leptin concentrations in umbilical cord blood (cb) were investigated in normal pregnancies [n = 10 (p), 31 (cb)] and abnormal pregnancies complicated with (i) maternal insulin-dependent diabetes [IDDM: n = 3 (p), 13 (cb)], (ii) gestational diabetes [GD: n = 2 (p), 10 (cb)] and (iii) fetal growth retardation [FGR: n = 5 (p), 5 (cb)]. By in-situ hybridization and immunohistochemistry, placental leptin mRNA and protein were co-localized to the syncytiotrophoblast and villous vascular endothelial cells. Leptin receptor was immunolocalized to the syncytiotrophoblast. Relative to controls, the FGR group was characterized by low concentrations of placental and cord blood leptin. In a twin pregnancy, the normal-sized infant exhibited more placental and cord blood leptin than its growth-retarded twin. In contrast, both diabetic groups exhibited high concentrations of placental leptin mRNA and protein. The IDDM group exhibited the highest concentrations of leptin in cord blood. No change was observed in the expression of the leptin receptor in either the growth-retarded or diabetic pregnancies. In conclusion, the localization of placental leptin suggests that it may be released into both maternal and fetal blood. Furthermore, in fetal growth-retarded and diabetic pregnancies, the changes in leptin expression in the placenta and in leptin concentrations in umbilical cord blood appear to be related.

Carrier Proteins↗
PubMed2000

Human fetal testis: second trimester proliferative and steroidogenic capacities.

The period of Leydig cell hyperplasia (14-18 weeks gestation) in human fetal testis is crucial for normal gonad development. We have studied the spatio-temporal distribution of key developmental and functional markers in human fetal testis between 13-19 weeks gestation. Proliferating cell nuclear antigen-positive cells were immunolocalized to both interstitium and tubules. Image analysis confirmed an increase in positive interstitial cells during Leydig cell hyperplasia (P: < 0.05). c-Myc was localized to the interstitium with no gestational changes. The steroidogenic enzymes 3beta-hydroxysteroid dehydrogenase (protein) and cytochrome P450 17alpha-hydroxylase/C(17-20)-lyase (P450c17; messenger ribonucleic acid and protein) were confined to the Leydig cells. The number of immunopositive cells increased between 13 and 19 weeks (P: < 0.001). P450c17 mRNA (in situ hybridization) and protein were localized to the same population of interstitial Leydig cells. Androgen receptor and Bcl-2 protein (anti-apoptotic) were gradually restricted to the peritubular myoid cells as gestation progressed. Conversely, Bax protein (pro-apoptotic) was predominantly localized to the tubule Sertoli cells, whereas the germ cells were Bax immunonegative. In conclusion, human fetal Leydig cell hyperplasia is characterized by increasing numbers of proliferating cells and increased expression of steroidogenic enzymes. The Bcl-2-positive, Bax-negative status of the peritubular myoid cells may be a strategy for cell survival.

3-Hydroxysteroid Dehydrogenases↗
PubMed2000

Placental leptin.

Placental tissues from humans, rodents and farm animals contain leptin and its receptor. Leptin produced by the human placenta has the same size, charge and immunoreactivity as leptin produced by adipose tissue. However, the expression of human placental leptin appears to be regulated by a placenta-specific upstream enhancer. In this review the occurrence of leptin and its receptor in a range of species and placental types is described, and its significance during pregnancy discussed. Placental leptin contributes to the increase in maternal circulating concentrations of leptin during late pregnancy when it is likely to have an endocrine role in regulating maternal energy balance. Placental leptin may have angiogenic and immunomodulatory activities, which affect the placenta in an autocrine or paracrine manner. It also appears to affect fetal growth and development by binding to leptin receptors present in fetal organs.

Adipose Tissue↗
PubMed1999

Role of inflammatory mediators in human endometrium during progesterone withdrawal and early pregnancy.

The role of progesterone (P4) in the regulation of inflammatory mediators interleukin-8 (IL-8), monocyte chemoattractant protein-1, and cyclooxygenase-2 (COX-2) and in the recruitment of leukocyte subpopulations in the endometrium has been examined, by employing a model of P4 withdrawal and maintenance in vivo. Messenger RNA and protein expression have been investigated in endometrial biopsies: 1) during the midsecretory phase (LH+8 to 10); during the maintained luteal phase (P4 administered vaginally for 4 days from LH+8) and biopsies collected 2) 24 h and 3) 48 h post withdrawal of P4; and 4) during pseudo pregnancy (lifespan of corpus luteum extended by 7 days with CG; (decidua collected from women with 5) an ectopic gestation and 6) from women undergoing first-trimester termination of pregnancy). CD56+ large granular lymphocytes remain the major leukocyte subtype, both 24 and 48 h after P4 withdrawal, and in decidua (CG supported or ectopic). Higher numbers (P < 0.05) of macrophages (CD68+) were present in endometrium 48 h post P4 withdrawal and in pseudo pregnant endometrium, compared with normal decidua. Significantly more macrophages (P < 0.01) were present in decidua from an ectopic pregnancy. A significant elevation of IL-8 (P < 0.01) and COX-2 (P < 0.05) messenger RNA was detected 48 h post P4 withdrawal. Evidence is provided for up-regulation of IL-8 and COX-2 in response to P4 withdrawal.

Chemokine CCL2↗
PubMed1999

Cytokines and the regulation of apoptosis in reproductive tissues: a review.

PROBLEM: To determine the role of apoptosis-regulating genes bax and bcl-2 in reproduction. METHOD OF STUDY: Review of literature and current data. RESULTS: The bcl-2 family of apoptotic regulatory gene products interact and form dimers of anti- and pro-apoptotic proteins (e.g., bcl-2 and bax respectively), the ratio of which determines cell death or survival. Menses is associated with increased apoptosis in the glands, a change in bcl-2:bax ratio and increased levels of the pro-apoptotic cytokine TNFalpha. Apoptosis occurs in all placental cell types and increases from first to third trimester. Placental apoptosis is induced by TNFalpha in vitro and increased levels in utero characterize most failing pregnancies, intra-uterine growth restriction (IUGR) and labour. An increased bcl-2:bax ratio and apoptosis in the syncytiotrophoblast characterizes failing first trimester pregnancies. Apoptosis in the syncytiotrophoblast is also associated with IUGR. In a rat model, maternal vitamin A deficiency perturbs fetal development. This is associated with a placental infiltrate of TNFalpha positive neutrophils (day 20) and increased placental apoptosis in areas of infiltration. A similar infiltrate occurs in a mouse model of early pregnancy loss. In the fetal membranes, clusters of bcl-2 negative chorion trophoblast cells undergo apoptosis. This may allow passage of myometrial stimulatory factors that induce labour. CONCLUSION: The ratio of bcl-2:bax is crucial in the regulation of apoptosis, particularly in the human placenta. Changes in trophoblast apoptosis characterize (1) early pregnancy failure, (2) IUGR and (3) pre-term and term labour. Regardless of gestational age, TNFalpha plays a major role in the induction of placental apoptosis.

Animals↗
PubMed1998

Tumor necrosis factor-alpha mRNA-positive cells in spontaneous resorption in rodents.

PROBLEM: It has been proposed that high rates of resorption/spontaneous abortion may result from interaction in the decidua of gamma-interferon-producing natural killer (NK) cells and tumor necrosis factor (TNF)-alpha-producing macrophages. An increased release of TNF-alpha from placental tissue of resorptions has been reported, but macrophages producing TNF-alpha have so far not been demonstrated at the feto-maternal interface. Therefore, we have sought to identify TNF-alpha-producing cells by in situ hybridization at the feto-maternal interface in two inbred, well-characterized, and stable strains of laboratory rodents with high and low resorption rates. METHOD OF STUDY: Pregnant DBA/2-mated CBA/J mice with a resorption rate of 20% to 30% (dependent on NK cells and macrophages) and diabetes-resistant Bio-Breeding/Edinburgh (DR-BB/E) rats with low resorption rates (presumed to result from chromosomal abnormalities) were studied. AsialoGM1+ cells were detected by immunohistochemistry, and TNF-alpha mRNA+ cells were detected by in situ hybridization. RESULTS: TNF-alpha mRNA+ cells were detected in DBA/2-mated CBA/J mice at the time of resorption but only at the trophoblast-decidual junction. AsialoGM1+ cells were present in decidua, as assessed by immunohistochemistry, but few if any gave a positive signal for TNF-alpha. In rat resorptions, TNF-alpha mRNA-positive cells were present within the yolk sac and in contact with the trophoblast, but not at the trophoblast-decidual junction. In neither species did a significant accumulation of detectable TNF-alpha mRNA+ cells occur before the usual time of onset of resorption. CONCLUSIONS: In the DBA/2-mated CBA/J mouse, the removal of the placenta is associated with removal of a thin rim of adherent decidua similar to the location of the TNF-alpha mRNA+ cells detected in this study. Our data suggest that increased TNF-alpha in tissues associated with failing feto-placental units may arise from infiltration/activation of scavenger cells from decidua that are likely to be macrophages. Local TNF-alpha production in decidua, which occurs as a prelude to resorption in the CBA x DBA/2 model, could not be detected due to the insensitivity of the TNF-alpha probe we used; the release of TNF-alpha from decidual tissue left after the removal of the placenta does not differ between resorbing and healthy implant sites. AsialoGM1+ cells did not seem to be major producers of TNF-alpha. TNF-alpha mRNA+ cells in a low rate of resorption (rat) model were only found on the fetal side of the trophoblast, and they may also represent a macrophage response (to dying embryo tissue) derived from a nondecidual source. The location of TNF-alpha mRNA+ cells may identify distinct and different mechanisms of resorption in rodents.

Abortion, Veterinary↗
PubMed1998

Effects of maternal vitamin A status on fetal heart and lung: changes in expression of key developmental genes.

Vitamin A is required during pregnancy for fetal lung development. These experiments monitored fetal lung morphology in normal and vitamin A-deficient rats. The expression of elastin and the growth arrest-specific gene 6 (gas6) in fetal and neonatal hearts and lungs was assessed by Northern blotting. In normal-fed rats, elastin and gas6 were expressed in the fetal lung and heart from day 19 of gestation up to day 2 postnatally. Maternal vitamin A deficiency altered fetal lung development. On day 20, the bronchial passageways were less developed and showed reduced staining for elastic fibers, and in the neonates, the relative air space and the size of the sacculi were reduced. In the fetal lung, the mRNAs for elastin and gas6 were reduced to 56 and 68% of the control values, respectively. In the fetal heart, the mRNA for elastin was reduced to 64% of the control value, whereas gas6 was increased twofold. In the neonate, there was no change in elastin expression in the lung or heart, but gas6 expression in the heart was increased twofold. These results suggest that, in the pregnant rat, vitamin A deficiency may retard fetal lung development or influence the differentiation of critical cell lines. The changes in elastin and gas6 expression may be used to identify the cell types affected.

Animals↗
PubMed1997

The immunolocalization of bcl-2 at the maternal-fetal interface in healthy and failing pregnancies.

Programmed cell death by apoptosis occurs in both fetal and maternal tissues during early pregnancy. To investigate a role for apoptosis at the maternal-fetal interface, we have immunolocalized the bcl-2 protein in formalin-fixed decidual and placental tissue collected from women undergoing surgical termination of pregnancy (n = 22), from women undergoing a sporadic miscarriage (n = 16) and from women with a history of recurrent pregnancy loss (more than three consecutive pregnancy losses; n = 22) undergoing a further miscarriage. In all three groups, bcl-2+ cells were found in aggregates and dispersed in the stroma, and immunoreactivity was observed in glandular epithelium. Double immunostaining revealed that a majority of stromal bcl-2+ cells were CD56+ large granular lymphocytes. A computerized image analysis revealed no significant differences in percentage area of bcl-2 or CD56+ immunostaining. Significantly more biopsies from the surgical termination group (4/10) had > 20% positive immunostaining for CD56 compared with 0% in the other two groups combined (0/20; P < 0.05). Bcl-2 immunoreactivity was observed in the villi syncytiotrophoblast, and staining intensity was consistently greater in the surgical termination group. The possible roles of bcl-2 at the maternal-fetal interface are discussed.

Abortion, Habitual↗
PubMed1997

Deficient syncytiotrophoblast tumour necrosis factor-alpha characterizes failing first trimester pregnancies in a subgroup of recurrent miscarriage patients.

Pregnancy failure in mice has been associated with increased placental concentrations of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha). To investigate the role of uterine TNF-alpha in human first trimester miscarriage, we have collected human decidual and trophoblast tissue from women (i) undergoing surgical termination of pregnancy (n = 27), (ii) undergoing a sporadic miscarriage (n = 20) and (iii) with a history of recurrent pregnancy loss [>3 consecutive pregnancy losses (n = 26)] undergoing a further miscarriage. Formalin fixed tissues were examined for TNF-alpha mRNA (in-situ hybridization) and protein (immunohistochemistry). In decidua from all three groups, TNF-alpha protein and mRNA were co-localized to the decidual stroma, the luminal surface of some maternal vessels and to the glandular epithelium. Chorionic villi from the normal pregnancy and the sporadic miscarriage group exhibited co-localized TNF-alpha protein and mRNA in the syncytiotrophoblast and cytotrophoblast. In the recurrent miscarriage group, however, 63.6% of the biopsies showed positive immunostaining in only the cytotrophoblast, compared with 4.0% of women undergoing surgical termination of pregnancy and 0.0% of women with a sporadic failed pregnancy (P < 0.001). TNF-alpha mRNA was also localized exclusively to this layer. This may be a secondary effect caused by a different mechanism of pregnancy loss unique to this subgroup.

Abortion, Habitual↗
PubMed1996

Sex steroid regulation of leukocyte traffic in human decidua.

Endometrial leukocyte subpopulations vary over the reproductive cycle, but no data exist on the mechanism regulating their recruitment into uterine tissue. This study has evaluated the role of progesterone in the recruitment of selected leukocyte populations in early pregnancy decidua. Decidua was collected from women in early pregnancy at the time of vacuum aspiration of the uterus 6, 12, 24 and 36 h after taking 200 mg mifepristone (RU486). Standard immunohistochemical techniques were employed to demonstrate the selected leukocyte populations in decidual tissue and these were analysed using imaged analysis. Fresh decidua was incubated in medium for 24 h and supernatants assayed for interleukin (IL-8) (neutrophil chemotactic factor) and MCP-1 (monocyte chemoattractant protein-1) content. Analysis of variance demonstrated a significant increase in tissue monocyte number in decidua 12-36 h after mifepristone administration. No significant changes in other leukocyte subpopulations were observed. Decidua IL-8 concentrations were significantly increased (P = 0.019) 6 h after mifepristone and decidual MCP-1 concentration rose (non-significant) and fell significantly (P = 0.029) between 6 and 12 h after mifepristone. Progesterone withdrawal may initiate a local cascade of events involving inflammatory mediators which in turn are responsible for the influx of monocytes. This influx may be essential in the process of shedding of endometrium or decidua since monocytes and neutrophils are important sources of proteases and collagenases. Furthermore, these cells are potential local sources of immunomodulatory cytokines.

Decidua↗