The Treatment of Illnesses Arising in Pregnancy.

BACKGROUND: The treatment of pregnant women who have illnesses unrelated to pregnancy can cause uncertainty among physicians. METHODS: We searched the PubMed database and specialty guidelines from Germany and abroad (the guidelines of the German Society for Gynecology and Obstetrics, the American Congress of Obstetri cians and Gynecologists, and the Royal College of Obstetricians and Gynaecologists) over the period 2007-2016 for information on standards for the diagnosis and treatment of five illnesses that can arise in pregnancy: bronchial asthma, migraine, hypothyroidism, hyperthyroidism, and varicose veins. RESULTS: Any diagnostic tests that are carried out in pregnant women should be simple and goal-directed. The choice of drugs that can be used is limited. For many drugs, no embryotoxic or teratogenic effect is suspected, but the level of evidence is low. CONCLUSION: When illnesses unrelated to pregnancy arise in pregnant women, attention must be paid to potential diver gences from the typical disease course and to pos sible drug side effects on the fetus in order to prevent serious complications for both mother and child.

Can the Rate of C-sections Performed in a Level I Perinatal Center Be Reduced? - An Analysis of the University Gynecology Clinic Rostock, 2008 - 2014.

INTRODUCTION: In Germany the rate of deliveries by cesarean section is continually increasing. Many different reasons have been put forward to explain this trend. The aim of this study was to examine how the C-section rate developed at the University Gynecology Clinic Rostock, one of the biggest maternity hospitals and level I perinatal centers in Germany, based on various maternal and neonatal parameters. The aim was also to identify potential risk factors for C-sections. MATERIAL AND METHOD: Various obstetric parameters were obtained from the birth cohort (2008 to 2014; n = 20 091) of the University Gynecology Clinic Rostock. The data was used to calculate parameter-specific C-section rates. Potential risk factors for C-section were identified by regression analysis. RESULTS: The C-section rate dropped from 26.24% to 23.57%. The rate of repeat C-sections also declined. The mean age of the pregnant women increased. Nevertheless, the frequency of cesarean sections in pregnant women aged more than 35 years declined. Rates of being overweight or obese preconception increased. C-section rates increased as BMI values preconception increased. There was a perceptible trend towards attempting the vaginal delivery of children in breech presentation and of twins. The frequency of depressed neonates after vaginal delivery and after C-section decreased. Rates for mild and advanced acidosis increased after both C-sections and vaginal deliveries. Previous C-section, older maternal age, overweight and obesity prior to conception, breech presentation and multiple pregnancies all increased the risk of cesarean sections. CONCLUSION: This study showed that reducing the rates of C-sections without a deterioration in neonatal outcomes can be achieved even in a large maternity hospital that cares for many high-risk pregnancies.

Non-invasive spectroscopic determination of the antioxidative status of gravidae and neonates.

Pregnancy and postpartum adaptation cause an increased formation of free radicals. This is associated with various perinatological diseases, e.g. necrotising enterocolitis. The human body has developed a protective system in the form of the antioxidative potential. The present study was the first to investigate the kinetics of the cutaneous antioxidative status in pregnant women and newborns using a non-invasive spectroscopic method. Eighteen pregnant women and their babies took part in the study. A light-emitting diode-based compact scanner system was used for quick non-invasive measurements of carotenoid antioxidants in human skin based on reflection spectroscopy. It could be shown that the antioxidative status of the expectant mothers significantly declined during labour (p < 0.001) and on day 1 after delivery (p < 0.01). Compared to the mothers, the newborns exhibited a significantly higher cutaneous carotenoid concentration on both day 1 (p < 0.01) and 5 (p < 0.01) after delivery. These results suggest that the oxidative stress due to postpartum adaptation is counteracted by an enhanced reservoir of carotenoid antioxidants in the subcutaneous fatty tissue. The peripartum cutaneous carotenoid level of mothers declines continuously, whereas term newborns show very high cutaneous antioxidant values.

Progranulin shows cytoprotective effects on trophoblast cells in vitro but does not antagonize TNF-α-induced apoptosis.

AIMS: The glycoprotein progranulin directly binds to TNF-receptors and thereby can antagonize the inflammatory effects of TNF-α. Here we analyzed the impact of both cytokines on cytotoxicity and viability of trophoblast cells. METHODS: Isolated villous first trimester human trophoblast cells and the human choriocarcinoma cell line BeWo were treated with recombinant human progranulin and TNF-α. Analyses were performed by LDH- and MTT-assay and measurement of caspase-8-activity. RESULTS: Progranulin treatment showed some cytoprotective effects on isolated trophoblast cells. However, TNF-α-induced apoptosis was not antagonized by addition of progranulin. Effects were similar, but more pronounced in BeWo cells. CONCLUSION: The cytoprotective activity of progranulin on trophoblast cells in vitro was only weak and of doubtful biologic relevance. It was not able to antagonize TNF-α. Future studies should focus on possible paracrine activities of progranulin.

Effects of phytoestrogen extracts isolated from pumpkin seeds on estradiol production and ER/PR expression in breast cancer and trophoblast tumor cells.

Phytoestrogens have a controversial effect on hormone-dependent tumours. Herein, we investigated the effect of the pumpkin seed extract (PSE) on estradiol production and estrogen receptor (ER)-α/ER-ß/progesterone receptor (PR) status on MCF7, Jeg3, and BeWo cells. The PSE was prepared and analyzed by mass spectrometry. MCF7, Jeg3, and BeWo cells were incubated with various concentrations of PSE. Untreated cells served as controls. Supernatants were tested for estradiol production with an ELISA method. Furthermore, the effect of the PSE on ER-α/ER-ß/PR expression was assessed by immunocytochemistry. The PSE was found to contain both lignans and flavones. Estradiol production was elevated in MCF7, BeWo, and Jeg3 cells in a concentration-dependent manner. In MCF7 cells, a significant ER-α downregulation and a significant PR upregulation were observed. The above results after properly designed animal studies could highlight a potential role of pumpkin seed's lignans in breast cancer prevention and/or treatment.

An ethanolic extract of Linum usitatissimum caused cell lethality and inhibition of cell vitality/ - proliferation of MCF-7 and BT20 mamma carcinoma cells in vitro.

PURPOSE: Flaxseeds were shown to have anticancerogenic properties on breast cancer. In this work, an extract of roots of Linum usitatissimum was tested on MCF-7 and BT20 mamma carcinoma cells in vitro. METHODS: The extract was produced by an ethanolic extraction method and its chemical composition was afterwards analysed by pyrolysis field ionization mass spectrometry. The extract was tested in concentrations from 0.01 to 1,000 µg/mL. Its effects were detected by measuring the influence on cell lethality, viability and proliferation. RESULTS: The extract was shown to contain mainly sterols and triterpenes (21.4 %), free fatty acids (17.8 %), lignin dimers (12.2 %) and lipids (7.7 %). High concentrations of the extract caused significant cell lethality and suppression of cell vitality and proliferation. CONCLUSIONS: In this study, it was shown for the first time that an extract made of flaxroots caused different anticancerogenic effects on MCF-7 and BT20 cells in vitro. The extract supposably acts as a plantal multicomponent mixture, whereas the main active agents are not yet indentified and can only be suggested. Summarized, roots of flax may contain potential agents in the therapy of mamma carcinomas. Further investigations have to be carried out.

Trophoblastic progranulin expression is upregulated in cases of fetal growth restriction and preeclampsia.

AIMS: The expression of the anti-inflammatory glycoprotein progranulin and the hypoxia-induced transcription factor 1α (HIF-1α) in the villous trophoblast was compared between placentae from patients with preeclampsia (PE), fetal growth restriction (FGR), and normal controls. STUDY DESIGN: Matched pairs analysis of third trimester placentae specimens (mean gestational age 36+2) was performed by semiquantitative measurements of the immunohistochemical staining intensities for progranulin and HIF-1α expression (PE n=13, FGR n=9 and controls n=11). Further, placental progranulin mRNA expression was analyzed by qRT-PCR on term placentae (n=3 for each group). RESULTS: Compared to controls, villous trophoblast revealed a significantly higher expression of progranulin in cases of PE (P<0.05) and FGR (P<0.01). Similar results were shown for HIF-1α expression (P<0.01 for PE and <0.05 for FGR). The increase of the progranulin protein was not accompanied by an increase of the progranulin mRNA in term placentae. CONCLUSIONS: Increased expression of progranulin protein in villous trophoblast cells in cases of PE and FGR may result from disturbed placental development and, therefore, may be of pathogenetic importance. The increase was correlated to HIF-1α expression. Further evaluation of this potential mechanism of regulation is required.

Antiproliferative activity of lignans against the breast carcinoma cell lines MCF 7 and BT 20.

PURPOSE: Phytoestrogens are plant-derived, non-steroidal phytochemicals with anticarcinogenic potential. The major structural classes are the isoflavones and lignans. The aim of this study was to compare the effect of the plant-derived lignans secoisolariciresinol and matairesinol with the human lignans enterodiol and enterolactone as well as with 17ß estradiol and tamoxifen on cell proliferation of breast carcinoma cell lines. METHODS: The influence of the lignans, 17ß estradiol and tamoxifen on cell proliferation was determined using the BrdU test in MCF 7 and BT 20 cell lines. RESULTS: Enterodiol and enterolactone induced a stronger inhibition of cell growth in MCF 7 and BT 20 cells than secoisolariciresinol and matairesinol. The inhibition effects were less expressed in the BT 20 than in the MCF 7 cells. CONCLUSIONS: The human lignans enterodiol and enterolactone are more biologically active than their precursors secoisolariciresinol and matairesinol, and may be defined as the real drugs in cancer prevention.

Effects of elm bark extracts from Ulmus laevis on human chorion carcinoma cell lines.

PURPOSE: The potential of substances from elm bark extracts to affect cancer has been described in several studies. In this study, the anticancer effects of extracts from Ulmus laevis bark were tested in hormone-dependent gynecological tumours using human chorion carcinoma cell lines. METHODS: The molecular-chemical composition of the bark extract was analysed by pyrolysis-field ionisation mass spectrometry. The influence of the extracts was determined on cell vitality and cytotoxicity in the human chorion carcinoma cell lines Jeg3 and BeWo in comparison with primary trophoblast cells. RESULTS: The elm bark extract was mainly composed of triterpenes, phytosterols, free fatty acids and suberins with lower amounts of dilignols and lipids. The elm bark extract significantly inhibited the vitality of Jeg3 and BeWo cells but increased the vitality of primary trophoblast cells. CONCLUSIONS: Substances extracted from elm bark might have beneficial effects for the prevention of hormone-dependent tumours.

The effects of different lignans and isoflavones, tested as aglycones and glycosides, on hormone receptor-positive and -negative breast carcinoma cells in vitro.

PURPOSE: Phytooestrogens are known to cause anti-cancer effects on mamma carcinoma cells. In this study, the effects of the lignan secoisolariciresinol and the isoflavone glycosides and aglycones genistein, genistin, daidzein and daidzin were tested on MCF-7 and BT20 cells in vitro. METHODS: First, the cellular expression of hormone receptors was examined by immunohistochemical procedures. The effects of the phytooestrogens on the cells were detected by using three different assays measuring cell letality, viability and proliferation. The phytooestrogens were tested in concentrations of 1, 5, 10 and 50 µg/mL, respectively. 17ß-oestradiol and tamoxifen were used as controls, respectively, in the same concentrations as the phytooestrogens. RESULTS: The immunohistochemistry showed evidence of oestrogen- and progesterone receptors at the MCF-7 cell line, whereas no expression could be seen at the BT20 cells. Among the phytooestrogens, genistein and secoisolariciresinol showed various anti-cancerogenic effects on both cell lines, respectively, but only in the highest concentration. Regarding the controls, tamoxifen showed a stronger antivital and anti-proliferative effect on BT20 than on MCF-7. Oestradiol caused sporadic anti-cancer effects on both cell lines, respectively, at its highest concentration. CONCLUSIONS: Genistein and Secoisolariciresinol have anti-cancer properties on MCF-7 and BT20 in vitro. There are differences in the effects of isoflavones depending on the glycolysation status. The role of the oestrogen receptors in the mechanisms of action of both the phytooestrogens and controls is of less importance. Further investigations have to be carried out, especially concerning the mechanisms of action. Phytooestrogens may be potential substances in the therapy of mamma carcinomas.

Expression pattern of progranulin in the human placenta and its effect on cell proliferation in the choriocarcinoma cell line BeWo.

Expression of the glycoprotein progranulin has been recently identified in rodent trophoblast cells during early embryonic development. The aim of our study was to describe the expression pattern of progranulin in human placental tissue specimens by immunostaining. We further analyzed the influence of progranulin on invasion and migration of isolated first trimester villous trophoblast cells. The effect of progranulin on cell proliferation was investigated using the human choriocarcinoma derived cell lines BeWo and Jeg-3. Cells were tested with recombinant human progranulin at various concentrations (0.1, 0.2 and 1.0 µg/ml). The strongest expression of progranulin was observed in the villous trophoblast cells, particularly in the syncytiotrophoblast. The intensity of staining in these cells was higher in the first trimester than in the third trimester. In contrast, the staining of the extravillous trophoblast cells and of the villous and decidual stroma was only weak. Using an ELISA technique, we also detected progranulin in amniotic fluid of the early second trimester. Isolated human first trimester trophoblast cells also expressed and secreted progranulin. Progranulin significantly stimulated the cell proliferation of BeWo cells, but it did not influence the amount of trophoblast cell migration and invasion in vitro. Furthermore, it did not promote the cell proliferation of Jeg-3 cells. Our results suggested that progranulin, although it is mainly synthesized and secreted by villous trophoblast cells, may not primarily act on the villous trophoblast cells in a paracrine or autocrine manner. The observed effect of progranulin on cell proliferation in BeWo cells may indicate a growth stimulating effect also on the small part of proliferating extravillous trophoblast cells during placental development.

Perioperative complications of breast cancer surgery in elderly women (≥80 years).

PURPOSE: There has been much controversy regarding the optimal management of breast cancer in very elderly women. Some clinicians are reluctant to offer surgical treatment for women older than aged 80 years because of the assumed higher operative risk associated with advanced age. This study was designed to investigate the perioperative complications of breast cancer surgery in women of this age group. METHODS: Data were reviewed of all women ≥80 years of age who underwent breast cancer surgery at a university clinic during the period 1990-2005. Symptoms, comorbidities, preoperative risk assessment, type of operation, postoperative histological diagnosis, hospital stay, morbidity, and mortality were documented and analyzed. RESULTS: During this 16-year period, 140 operations for breast cancer were performed in 129 women. The majority of the patients (37.9%) underwent a modified radical mastectomy, 32.1% underwent a simple mastectomy, 24.3% underwent breast-conserving therapy, and 5.7% underwent an axillary lymph node dissection. Complications occurred in 37.1% of the cohort: 31.4% were minor complications and only 5.7% were major. Intraoperative morbidity was 18.6% and postoperative morbidity was 20%. Late complications occurred in 5% of patients. The most common complications were associated with the wound region (50%). The perioperative mortality in this group of elderly women was zero. CONCLUSIONS: Breast cancer surgery has acceptable perioperative morbidity and mortality in women aged ≥80 years. Surgery is the cornerstone of breast cancer treatment and should be offered as first-line treatment for all patients regardless of their age.

Does primary breast cancer in older women (≥80 years) have unfavorable histological characteristics?

INTRODUCTION: Although the majority of breast cancer patients are older than 65 years, limited data exist regarding the pathological features in very elderly patients. The aim of this study was to evaluate the histological characteristics of breast cancer in women aged over 80 years. METHODS: The histological data were reviewed for 137 women aged 80 years and older who were diagnosed with primary breast carcinoma at a university clinic during the period 1990-2005. RESULTS: Although it is believed that older women have more advanced tumor, the majority of the tumors were assessed as stage I (35%) and II (32.9%). Mucinous, papillary, medullary, tubular, and cribriform histological subtypes have been demonstrated often in this age group (16.8%). In 49.7 and 70.6% of cases, respectively, there were no regional lymph node metastases and no distant metastases. The frequency of ER-positive (72%) and PR-positive (56%) tumors in these patients is high. CONCLUSIONS: An accurate prognostic evaluation at the time of initial diagnosis is of high importance for older patients, since this could avoid unnecessary and risky therapies. As an increasing number of women ≥80 years old may be diagnosed with breast cancer in the coming years, treatment in this specific age group should be individualized to the patient and tumor factors.

Efficacy and tolerability of a local acting antiseptic agent in the treatment of vaginal dysbiosis during pregnancy.

OBJECTIVE: In the present study, the efficacy and tolerability of the local acting antiseptic octenidine hydrochloride/phenoxyethanol (OHP) for the treatment of vaginal dysbiosis (VD) and/or bacterial vaginosis (BV) in pregnancy and its potential influence on preterm births and low-weight newborns were examined. METHODS: One-hundred nine pregnant women with increased pH values (>4.5) and BV characteristic symptoms were treated with OHP for 7 days and a second time in case of a recurrent pH increase. pH values were continuously controlled by women's self-measurements. RESULTS: pH decreased to ≤ 4.5 in 67.9% of patients. Seven of 12 women (58.3%) treated again with OHP due to a recurrent pH increase finally reached the pH target (pH ≤ 4.5). No preterm birth occurred in the OHP group; no newborn had a birth weight <2,000 g. Rates of preterm births and low-weight newborns were comparable between OHP group and pregnant women without VD/BV. CONCLUSIONS: OHP is effective and well tolerated in the treatment of VD/BV also in pregnancy without side effects and the occurrence of resistances. It could be an additional therapeutic option in the prevention of the multifactorial disease pattern 'preterm birth' with all their consequences.

Risks of pregnancy and birth in obese primiparous women: an analysis of German perinatal statistics.

PURPOSE: To compare risks of pregnancy and birth in obese (body mass index, BMI ≥ 30) and normal weight women (BMI 18.5-24.99) giving birth to their first child. METHODS: We analysed data of 243,571 pregnancies in primiparous women from the German perinatal statistics of 1998-2000. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) for selected pregnancy and birth risks. ORs were adjusted for the confounding factors age, smoking status, single mother status, and maternal education. RESULTS: Obesity during pregnancy is common in primiparous women (n = 19,130; 7.9% of all cases) and it is significantly associated with a number of risks of pregnancy and birth, including diabetes [OR 3.71 (95% CI 2.93; 4.71); p < 0.001], hypertension [OR 8.44 (7.91; 9.00); p < 0.001], preecalmpsia/eclampsia [OR 6.72 (6.30; 7.17); p < 0.001], intraamniotic infection [OR 2.33 (2.05; 2.64); p < 0.001], birth weight ≥ 4,000 g [OR 2.16 (2.05; 2.28); p < 0.001], and an increased rate of Caesarean section [OR 2.23 (2.15; 2.30); p < 0.001]. Some risks were less frequent in the obese such as cervical incompetence [OR 0.55 (0.48; 0.63); p < 0.001] and preterm labour [OR 0.47 (0.43; 0.51); p < 0.001]. CONCLUSIONS: Obesity during pregnancy is an important clinical problem in primiparous women because it is common and it is associated with a number of risks of pregnancy and birth. Because of these increased risks, obese women need special attention clinically during the course of their first pregnancy. Weight reduction before the first pregnancy is generally indicated in obese women to prevent the above-mentioned complications of pregnancy and birth.

Birth weight percentile charts based on daily measurements for very preterm male and female infants at the age of 154-223 days.

OBJECTIVE: Birth weight percentiles based on weekly measurements are used to assess the nutritional status of preterm infants. However, as preterm infants exhibit a rapid growth rate (up to 20 g/kg/day), their body weight can increase by 15% per week. We calculated birth weight percentiles based on daily measurements, to more precisely classify very preterm infants (gestational age of 154-223 days). METHODS: Data of 23,864 (10,720 females and 13,144 males) very preterm singleton infants with a gestational age of 154-223 days (22-31 completed weeks) were retrieved from the German perinatal statistics of 1995-2000. Percentile curves based on the empirical birth weight data were subjected to three statistical smoothing procedures: cubic regression, local regression (LOESS smoothing), and the LMS method. RESULTS: Smoothing of the birth weight percentiles using cubic regression produced the smallest residual variance. CONCLUSION: Birth weight percentiles based on daily averages allow a more precise assessment of the somatic development of preterm infants.

Morbid obesity: pregnancy risks, birth risks and status of the newborn.

In perinatal medicine, severe obesity of the mother occurs in approximately 1% of cases. This is a problem of increasing importance because of the rising prevalence of juvenile obesity. Our retrospective cohort study aimed at characterising high-risk pregnancies associated with morbid obesity (body mass index [BMI]> or =40). This is of interest not only from an epidemiological perspective and for developing guidelines for clinical care but also from an anthropological point of view. We analysed the German perinatal statistics of the years 1998-2000 with data from more than 500,000 pregnancies. Pregnant women with coexistent morbid obesity were compared to a normal weight reference sample with regard to gestational, perinatal and neonatal risks. Birth weight percentiles were used to classify the neonates according to size (hypotrophy if <10th, hypertrophy/foetal macrosomia if >90th). The obtained risk profile for morbidly obese pregnant women primarily showed pregnancy related diseases, such as hypertension, pre-eclampsia and gestational diabetes. Hypertension and signs of foetal hypoxaemia occurred at higher frequencies with morbid obesity. Hypertrophic neonates were born 3.3 times more often to obese mothers than to mothers of the normal weight. At a BMI> or =40 the rates of complications such as pre-eclampsia, gestational diabetes, impending foetal hypoxaemia, foetal macrosomia, as well as neonatal infections and hyperbilirubinaemia were significantly higher. Obesity and maternal comorbidities, accounted for a higher rate of caesarean sections of up to 38.4% at a BMI> or =45. All differences were highly significant. Preconceptionally, the therapeutic approach should be weight reduction.

Investigation of the association of Apgar score with maternal socio-economic and biological factors: an analysis of German perinatal statistics.

PURPOSE: To examine the relationship of 5-min Apgar score with maternal socio-economic and biological factors. METHODS: We analyzed data from 465,964 singleton pregnancies (37-41 weeks' gestation) from the German perinatal statistics of 1998-2000. Using a logistic regression model we analyzed the incidence of low (0-6) 5-min Apgar scores in relation to these maternal factors: body mass index (BMI), age, previous live births, country of origin, occupation, single mother status, working during pregnancy, and smoking. RESULTS: A low Apgar score was more common in overweight [adjusted odds ratio (OR) 1.24; 95% confidence interval (CI) 1.10-1.40; P < 0.001] and obese [OR 1.92 (95% CI 1.67-2.20); P < 0.001] compared to normal weight women. A low Apgar score was also more common for women aged >35 years compared to those aged 20-35 years [OR 1.35 (95% CI 1.16-1.58); P < 0.001]. Furthermore, odds of a low Apgar score were higher for women with no previous live births compared to those with one or more previous live births [OR 1.52 (95% CI 1.37-1.70); P < 0.001]. Socio-economic factors did not convincingly influence Apgar scores. CONCLUSIONS: There was an influence of the biological maternal factors age, BMI, and parity on the 5-min Apgar score. There was no convincing effect of socio-economic factors on Apgar score in our study population. Possible reasons for this are discussed.

Inhibitory effects of bark extracts from Ulmus laevis on endometrial carcinoma: an in-vitro study.

Anti-inflammatory effects of elm tree have been shown in several studies. Besides this, protective effects of components of elm bark on damaged tissue have also been described. This study was carried out to investigate the antitumour potential of an ethanolic extract isolated from Ulmus laevis in the hormone-dependent endometrial carcinoma cell line RL95-2. A range of 2.5-500 microg/ml of elm bark extract was used as standard concentrations. The molecular-chemical composition of the bark extract was analysed by pyrolysis-field ionization mass spectrometry. The influence of the bark extracts was determined on cell vitality [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test], cell proliferation (5-bromo-2-deoxyuridine test) and cytotoxicity (lactate dehydrogenase test) in the human endometrial carcinoma cell line RL 95-2. By pyrolysis-field ionization mass spectrometry, the main substance classes of the extract as a composition of sterols/triterpenes, free fatty acids and a group of phenols, lignin monomers and flavonoids was identified. Our study showed a significant inhibition of cell vitality and proliferation measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test up to 5 microg/ml extract and up to 100 microg/ml according to the 5-bromo-2-deoxyuridine test. Concentrations of 500 microg/ml induced a significant inhibition of cell vitality up to 80% and cell proliferation up to 81.5%. A significant cytotoxity was not observed. The results lead to the assumption that the bark extract from Ulmus laevis has antiproliferation and anticancer potential in hormone-dependent endometrial carcinoma cells.

Effects of phytoestrogens genistein and daidzein on progesterone and estrogen (estradiol) production of human term trophoblast cells in vitro.

OBJECTIVE: Phytoestrogens are a diverse group of nonsteroidal plant compounds that occur naturally in many plants. Because they possess a ring system similar to estrogens they are able to bind on estrogen receptors alpha and beta in humans. The effects of the phytoestrogens genistein and daidzein on the production of progesterone and estrogen in isolated human term trophoblast cells in vitro were tested in this study. MATERIAL AND METHODS: Cytotrophoblast cells were isolated from human term placentas. Phytoestrogens genistein and daidzein were incubated in different concentrations with trophoblast cells. Untreated cells were used as controls. After 24 h aliquots were removed and tested for progesterone and estrogen production. RESULTS: The production of the steroid hormones progesterone and estrogen are influenced by phytoestrogens genistein and daidzein in human term trophoblast cells. A strong inhibition effect of both phytoestrogens tested in the production of progesterone was demonstrated. In addition, a significant stimulating effect on estrogen production by genistein and daidzein was observed. CONCLUSION: Results obtained with this study show that phytoestrogens (genistein and daidzein) sufficiently reduce progesterone production in human term trophoblast cells. Because blockade of progesterone is a possible mechanism involved in initiation of labor, we may speculate that high doses of phytoestrogens at the feto-maternal interphase could play a negative role in maintenance of pregnancy. Stimulation of estrogen production by genistein and daidzein in trophoblast cells is probably due to estrogen receptor blocking effects of both phytoestrogens. Trophoblast cells seem to compensate blocking of its estrogen receptors by higher estrogen production.