Scintigraphic studies of uterine and placental growth and placental migration during pregnancy

Placental scintigraphy with 113mIn (Indium) combined with cervical marking with a shielded 57Co (Cobalt) radioactive source was used to study uterine and placental growth in human pregnancy and placental location and migration in a total of 176 patients. Uterine length measurements can be used for selecting growth retarded fetuses. There was an approximately constant ratio between placenta diameter and uterine length (0.68 +/- 0.03). When the placenta was located on the ventral uterine wall, low implantation occurred in 61%. The corresponding figure for low implantation when the placenta was located on the dorsal uterine wall was 30%. The difference was highly significant. Placental migration was studied in 20 patients. Significant migration occurred in 11 cases. The placental margin closest to the internal cervical os migrated outwards about 3 cm on average.     

Bovine placentomal heparanase and syndecan expression is related to placental maturation

IntroductionImpaired placental maturation has been associated with retention of fetal membranes, which is a major reproductive disease in cattle. This maturation includes alterations in all tissue compartments of the placenta, specifically of epithelial and stroma cells and extracellular matrix. It is believed to be controlled by hormones, adhesion molecules and proteolytic enzymes. To investigate if the proteolytic enzyme heparanase and its substrates, the syndecans (SDCs) could be involved in the release of fetal membranes, their expression in bovine placentomes was analyzed.MethodsPlacentomes were taken from gestational day 35 until term, directly after spontaneous parturition, after preterm caesarean section, and after chemically induced parturition. Heparanase and SDCs were localized by immunohistochemistry and the respective mRNAs were quantified by qRT-PCR. Heparanase expression was additionally quantified by Western blot.ResultsHeparanase, SDC1 and SDC4 displayed significant changes in expression and localization depending on gestational progress and mode of parturition. All three proteins showed an expression at the end of gestation, together with an altered, predominant localization in fetal and maternal epithelia. After physiological parturition, the placentomal tissue stained weaker for all syndecans. This change in staining pattern could not be observed after induced preterm parturition. SDC2 expression did not change during the course of gestation.DiscussionThe changing placental expression patterns of heparanase, SDC1 and SDC4 indicate that these molecules might be involved in fetomaternal communication and placental maturation in cattle. The matrix degrading properties of heparanase could assist in a timely reduction of fetomaternal adhesion and thus promote separation of the membranes after parturition.     

Arterial wall hyperplasia is increased in placental compared with myoendometrial radial uterine arteries from late-pregnant rats

OBJECTIVE: This study compared myoendometrial versus placental radial uterine arteries from late-pregnant rats to evaluate differences in passive mechanical properties and arterial wall hyperplasia. STUDY DESIGN: Myoendometrial and placental radial uterine arteries were dissected from late-pregnant (day 17-19) Sprague-Dawley rats (n = 21) for determination of the lumen diameter and passive distensibility. Arterial wall hyperplasia was evaluated by bromodeoxyuridine incorporation and histologic determination of mitotic indices of endothelial, smooth muscle, and adventitial cells. Nonpregnant radial uterine and mesenteric arteries were used as control cells. RESULTS: Both placental and myoendometrial uterine arteries were significantly larger than nonpregnant uterine arteries by 40% and 28%, respectively (P < .05). The lumen diameter of placental arteries was significantly (16%) larger than adjacent myoendometrial arteries (P < .05). In addition to the larger luminal diameter, placental arteries were significantly more distensible than myoendometrial arteries at all pressures that were studied, which demonstrates differential remodeling. Comparison of mitotic indices revealed that placental arteries had significantly increased cell division rates of both endothelial and smooth muscle significantly compared to myoendometrial arteries. Both types of arteries from pregnant animals had increased cell division rates compared with vessels from nonpregnant animals. The mitotic index of endothelial and smooth muscle cells for placental and myoendometrial arteries from late-pregnant and nonpregnant animals was 15.08% +/- 2.05% and 6.57% +/- 1.37%, 8.73% +/- 1.23%, and 3.04% +/- 0.48% (P < .05 vs placental), and 0.29% +/- 0.29% and 0.23% +/- 0.23% (P < .05 vs placental endothelial), respectively. Adventitial cell division was 10- to 15-fold higher in late-pregnant versus nonpregnant animals. CONCLUSION: These data demonstrate differential growth and remodeling of uterine arteries that supply the placenta versus the myoendometrium, which likely is facilitated by enhanced arterial wall hyperplasia in placental arteries.     

Temporal and regional regulation of major histocompatibility complex class I expression at the bovine uterine/placental interface

In most mammals trophoblast cells do not express major histocompatibility complex (MHC) antigens. This probably protects the placenta from immune attack. We have used immunohistochemistry to study the ontogeny of MHC class I expression by bovine trophoblast and endometrial epithelial cells. The interplacentomal, placentomal arcade and placentomal villous/crypt regions were studied. In the interplacentomal region a substantial proportion of trophoblast cells were class I positive from the sixth month on and about half of the endometrial epithelium was class I positive throughout pregnancy. In the arcade region trophoblast class I expression was first observed in the sixth month, increased slowly and peaked at term. Here there was no endometrial epithelial class I expression until term and then only a small percentage of cells were positive. In contrast, in the placentomal villous/crypt region both trophoblast and endometrial epithelium were class I negative throughout gestation. This study shows that cattle have extensive trophoblast class I expression. Moreover class I expression on placentomal, cryptal endometrial epithelium is shut down. Because binucleate trophoblast cells migrate and fuse with endometrial epithelial cells, total shut down of class I expression in areas of intimate interdigitation may be critical for avoidance of immunological rejection.     

Increased osteopontin expression is associated with progression from vulvar precancerous lesions to vulvar squamous cell carcinoma

Purpose

Vulvar squamous cell carcinoma (VSCC) contributes to about 3–5 % of all gynecological cancers. Vulvar intraepithelial neoplasia (VIN) and vulvar lichen sclerosus (VLS) are regarded as precancerous lesions. Early detection and treatment of precancerous lesions may prevent development of VSCC. Osteopontin (OPN) has been shown to be involved in many physiological and pathological processes, such as tumor progression, by promoting cancer cell invasion and metastasis. As a result of these findings, OPN has been described as a potential marker for tumor progression in some malignancies. In this study, we investigated the expression of OPN in vulvar tissue specimens and compared its expression between different histopathological grades.

Methods

In the present study, the expression patterns of OPN in 80 paraffin-embedded tissue specimens, including 25 VSCC samples, 21 VIN lesions and 21 VLS, in addition to 13 normal vulvar samples, were examined by the immunohistochemical method and chromogenic in situ hybridization.

Results

The intensity of OPN expression steadily increased according to the pathological grades. In addition, OPN staining was found in the extracellular matrix in VSCC.

Conclusions

Expression levels of OPN increased from VLS and VIN to VSCC, and steadily increased with the pathological stage of VSCC. Our results suggest that OPN may be associated with the progression of VSCC.     

Placental expression of the angiogenic placental growth factor is stimulated by both aldosterone and simulated starvation

Aldosterone is an important factor supporting placental growth and fetal development. Recently, expression of placental growth factor (PlGF) has been observed in response to aldosterone exposure in different models of atherosclerosis. Thus, we hypothesized that aldosterone up-regulates growth-adaptive angiogenesis in pregnancy, via increased placental PlGF expression.We followed normotensive pregnant women (n = 24) throughout pregnancy and confirmed these results in a second independent first trimester cohort (n = 36). Urinary tetrahydroaldosterone was measured by gas chromatography-mass spectrometry and corrected for creatinine. Circulating PlGF concentrations were determined by ELISA. Additionally, cultured cell lines, adrenocortical H295R and choriocarcinoma BeWo cells, as well as primary human third trimester trophoblasts were tested in vitro. PlGF serum concentrations positively correlated with urinary tetrahydroaldosterone corrected for creatinine in these two independent cohorts. This observation was not due to PlGF, which did not induce aldosterone production in cultured H295R cells. On the other hand, PlGF expression was specifically enhanced by aldosterone in the presence of forskolin (p < 0.01) in trophoblasts. A pronounced stimulation of PlGF expression was observed with reduced glucose concentrations simulating starvation (p < 0.001).In conclusion, aldosterone stimulates placental PlGF production, enhancing its availability during human pregnancy, a response amplified by reduced glucose supply. Given the crucial role of PlGF in maintaining a healthy pregnancy, these data support a key role of aldosterone for a healthy pregnancy outcome.     

Altered placental syncytin and its receptor ASCT2 expression in placental development and pre-eclampsia

OBJECTIVE: To investigate the alterations of syncytin, a fusogenic membrane protein involved in syncytiotrophoblastic layer formation, and its receptor ASCT2 expression in placental development and pre-eclampsia. DESIGN: Analyses of syncytin and ASCT2 expression in placentas from different stages of pregnancy and women with pre-eclampsia and in cytotrophoblasts cultured in normoxic and hypoxic conditions. SETTING: Placental samples were collected from a tertiary medical centre. POPULATION: Sixteen women with pre-eclampsia and 58 pregnant women presented as pregnancy (5-19 weeks of gestation) for elective termination, preterm birth, or normal term delivery. METHODS: The quantitative real-time polymerase chain reaction was used to study the syncytin and ASCT2 expression during placental development in 35 placentas from women without pre-eclampsia (ranged from 5 to 40 weeks of gestation) and the alterations of pre-eclamptic placentas (n=16) compared with gestational-age-matched controls (n=16). Western blot analysis was performed to study the protein level of syncytin in pre-eclamptic placentas and gestational-age-matched controls. The hypoxic effect on trophoblastic syncytin and ASCT2 expression was further studied in cytotrophoblasts cultured in 2% oxygen (n= 7). MAIN OUTCOME MEASURES: Syncytin and ASCT2 messenger RNA (mRNA) in placental tissue and cytotrophoblasts. RESULTS: The level of syncytin mRNA expression increased significantly since the first trimester of pregnancy until 37 weeks of gestation, when the level of syncytin expression was reduced. The ASCT2 mRNA expression was decreased significantly since the second trimester and was relatively stable since then to 40 weeks of gestation. Furthermore, a significant reduction in syncytin mRNA expression was observed in pre-eclamptic placentas and cytotrophoblasts cultured in hypoxia, but not a reduction in ASCT2 mRNA expression. Correlatively, the protein level of syncytin was decreased in pre-eclamptic placentas. CONCLUSIONS: A reduced placental expression of syncytin but not ASCT2 may contribute to altered cytotrophoblastic cell fusion processes and disturbed placental function in pre-eclampsia. Correspondingly, hypoxia decreases syncytin but not ASCT2 gene expression in cultured cytotrophoblasts.     

Fatty acid transporter expression and regulation is impaired in placental macrovascular endothelial cells in obese women

Objective: Fetal fatty acid (FA) delivery is ultimately controlled by placental transport. Focus has been the maternal-placental interface, but regulation at the feto-placental interface is unknown.

Methods: Placental macrovascular endothelial cells (EC) (n?=?4/group) and trophoblasts (TB) (n?=?5/group) were isolated from lean (pregravid BMI <25?kg/m²) and obese (body mass index (BMI)?>?30) women. Fatty acid transporters FAT/CD36, FABPpm, FATP4, FABP 3, 4 and 5, PLIN2 and PPARα, δ, γ expression, was measured in EC and TB. Transporter response to 24?h palmitate (PA) was assessed.

Results: mRNA expression of FABP3, 4, 5 and PPARγ was 2- to 3-fold reduced in EC of obese versus lean women (p?p?p?p?p?Conclusions: In obese women, FA transporter expression is lower in placental EC, but not TB, and less sensitive to saturated FA, compared to lean women. FA transport may be regulated at the feto-placental interface.     

Imbalance of expression of bFGF and PK1 is associated with defective maturation and antenatal placental insufficiency

Objective

Defective placental maturation is associated with restricted functional capacity and adverse perinatal fetal outcomes. The aim of the study was a comparative analysis of the role of mRNA expression of various angiogenic factors in placental maturation defects.

Study design

We examined the mRNA expression patterns of prokineticin 1 (PK1), its receptors (PKRs), basic-fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in tissue from third-trimester placentae that exhibited delayed or accelerated villous maturation.

Results

The expression of PK1 and PKR2 was elevated in placental tissue exhibiting accelerated maturation and a predominant differentiation of terminal villi. The opposite was found in tissue exhibiting delayed maturation and deficiency of the terminal villi. In addition, low expression of bFGF correlated with the predominant differentiation of terminal villi, whereas the opposite was observed when terminal villi were deficient. The expression of VEGF, PIGF, and PKR1 showed no significant differences between the groups.

Conclusion

Defective placental maturation is associated with an imbalance of expression of bFGF and PK1. Our results demonstrate an involvement of the PK1/PKR2-signalling pathway in the regulation of the functional adequate capillarization in late pregnancy. We propose the bFGF/PK1-ratio as a monitor of placental function and a possible indicator of latent clinical problems, such as placental dysfunction leading to fetal hypoxia.     

Cigarette smoking and pregnancy I: ovarian, uterine and placental effects.

This review examines the major observations and principal controversies relating to the effects of smoking and the constituents of tobacco on ovarian, uterine and placental tissues. Maternal exposure is assessed relative to specific tobacco-related chemicals and the feto-placental impact of mutagenic products, in addition to nicotine replacement as a pharmacological intervention for smoking cessation. Important new information is being learned from clinical in vitro fertilization and assisted reproduction technologies regarding the effects of smoking on fertility. Present evidence supports an adverse effect of smoking on ovarian function which is prolonged and dose-dependent, whereas there appear to be more reversible effects on implantation and ongoing pregnancy. The anti-oestrogenic effect of smoking is reviewed in terms of direct effects of nicotine, cadmium and polyaromatic hydrocarbons on oestrogen synthesis and metabolism, oocytes and granulosa-luteal function. Innovative new models provide evidence that smoking may alter fertility through effects on uterine-fallopian tube functions which mediate gamete and conceptus transport. It is of interest that smoking is associated with a decreased incidence of uterine fibroids, endometriosis and uterine cancer, which may reflect inhibitory effects of smoke constituents on uterine cell proliferation and extracellular matrix interactions. The increased miscarriage rate among mothers who smoke may be related to direct adverse effects of nicotine, cadmium and polyaromatic hydrocarbons on trophoblast invasion and proliferation. In this respect, alterations in trophoblast differentiation along invasive or proliferative pathways may explain the changes in endocrine function and vascular morphology that are observed in smokers. In summary, significant advances are being made in the understanding of cellular and molecular mechanisms which underlie the differential effects of cigarette smoking on reproductive tissues.     

Intrauterine haematoma and placental protein 5 in patients with uterine bleeding during pregnancy

The prognostic value of placental protein 5 (PP5) serum levels were compared with ultrasound in the clinical assessment of 26 patients with uterine bleeding at 12-33 weeks of pregnancy. An intrauterine haematoma was found by ultrasound in 16 patients (62%), and in those patients the duration of pregnancy was significantly shorter than in the 10 who did not have a haematoma. Placental abruption ensued in five patients with haematoma, and although the highest serum PP5 level occurred in such a patient, the levels were similar to those in the other patients in whom no abruption was identified. A clinically important finding was that, in placental abruption, a haematoma may accumulate between the fetal membranes and the uterine wall instead of in the retroplacental space. We conclude that ultrasound examination is more effective than PP5 measurement in the assessment of prognosis of patients who bleed during pregnancy.