Fetal and Maternal Serum Levels of Steroid Sulfates, Unconjugated Steroids, and Prolactin at Term Pregnan and in Early Spontaneous Labor*

Laatikainen, Timo; Pelkonen, J.; Apter, Dan; Ranta, Tapio

doi:10.1210/jcem-50-3-489

Cited by 48 publications

(10 citation statements)

References 32 publications

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“…Estriol production rises toward the end of gestation, but uptake of 16␣-OH DHEAS via OAT4 seems not to be completely saturated, even at the end of gestation, because 16␣-OH DHEAS concentration in umbilical artery at term (10 M) (35,46) is similar to the K m of OAT4-mediated uptake of 16␣-OH DHEAS (7.4 M; Figure 3D). Therefore, it appears that OAT4-mediated uptake is functionally able to supply the increasing demand for 16␣-OH DHEAS in placental syncytiotrophoblasts toward the end of gestation.…”

Section: Discussionmentioning

confidence: 96%

Role of OAT4 in Uptake of Estriol Precursor 16α-Hydroxydehydroepiandrosterone Sulfate Into Human Placental Syncytiotrophoblasts From Fetus

et al. 2015

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Estriol biosynthesis in human placenta requires the uptake of a fetal liver-derived estriol precursor, 16α-hydroxydehydroepiandrosterone sulfate (16α-OH DHEAS), by placental syncytiotrophoblasts at their basal plasma membrane (BM), which faces the fetal circulation. The aim of this work is to identify the transporter(s) mediating 16α-OH DHEAS uptake at the fetal side of syncytiotrophoblasts by using human placental BM-enriched vesicles and to examine the contribution of the putative transporter to estriol synthesis at the cellular level, using choriocarcinoma JEG-3 cells. Organic anion transporter (OAT)-4 and organic anion transporting polypeptide 2B1 proteins were enriched in human placental BM vesicles compared with crude membrane fraction. Uptake of [(3)H]16α-OH DHEAS by BM vesicles was partially inhibited in the absence of sodium but was significantly increased in the absence of chloride and after preloading glutarate. Uptake of [(3)H]16α-OH DHEAS by BM vesicles was significantly inhibited by OAT4 substrates such as dehydroepiandrosterone sulfate, estrone-3-sulfate, and bromosulfophthalein but not by cyclosporin A, tetraethylammonium, p-aminohippuric acid, or cimetidine. These characteristics of vesicular [(3)H]16α-OH DHEAS uptake are in good agreement with those of human OAT4-transfected COS-7 cells as well as forskolin-differentiated JEG-3 cells. Estriol secretion from differentiated JEG-3 cells was detected when the cells were incubated with 16α-OH DHEAS for 8 hours but was inhibited in the presence of 50 μM bromosulfophthalein. Our results indicate that OAT4 at the BM of human placental syncytiotrophoblasts plays a predominant role in the uptake of 16α-OH DHEAS for placental estriol synthesis.

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Section: Discussionmentioning

confidence: 96%

Role of OAT4 in Uptake of Estriol Precursor 16α-Hydroxydehydroepiandrosterone Sulfate Into Human Placental Syncytiotrophoblasts From Fetus

et al. 2015

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“…Although there are indications that concentrations differ between arterial and venous cord blood samples (55,56), there is sufficient data that measurements in mixed cord blood do not differ significantly (27,57).…”

Section: Discussionmentioning

confidence: 99%

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome

Caanen

Kuijper

Hompes

et al. 2016

European Journal of Endocrinology

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Objective: Little is known about the aetiology of polycystic ovary syndrome (PCOS). Some suggest that elevated maternal androgens during gestation play a causative role. This implies placental passage of androgens during pregnancy. The aim of this study is to compare androgen and estrogen concentrations in maternal serum during pregnancy and in umbilical cord blood, between mothers with PCOS and their offspring compared to controls. Design: Prospective case-control study. Methods: Maternal blood samples were collected around 20 weeks of gestation and at delivery. Umbilical cord blood was also taken at delivery. Androgens (testosterone (T), androstenedione (ADION), dehydroepiandrostenedione (DHEA)) and estrogens (estrone (E 1 ), estradiol (E 2 ), estriol (E 3 )) were measured using the liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. Results: At 20 weeks of gestation: T (PZ0.019) and ADION (PZ0.034) were higher in the PCOS mothers (pregnant with a girl), whereas DHEA, E 1 , E 2 , and E 3 were not different. Maternal concentration at birth: T (PZ0.004) and ADION (PZ0.009) were also higher in the subgroup of PCOS mothers that were pregnant with a girl compared to the girl pregnancy controls. DHEA, E 1 , E 2 and E 3 were not different. In umbilical cord blood, no differences were found for T, ADION, DHEA, E 2 , E 3 , and AMH between the PCOS mothers and the controls respectively. E 1 was lower in girls from PCOS mothers (PZ0.007). Conclusions: Despite elevated maternal androgen concentrations during pregnancy in PCOS mothers, offspring showed no signs of elevated androgen concentrations in cord blood at birth using the latest highly specific LC-MS/MS methods.

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“…While we have confirmed that our samples are not contaminated by maternal blood, the relative proportion of umbilical arterial and venous blood is unknown and, in theory, may be altered by factors such as mode of delivery, gestational age, placental architecture and fetal hemodynamics. Studies which have compared UA∶UV differences in cord blood steroids suggest that UV concentrations of TT, A4 and DHEA are approximately 20%, 40% and 50–75% lower than UA levels [20], [33], representing the differential effects of placental metabolism. Hence, variations in relative proportions of UA and UV blood could have significant confounding effects which we are unable to control for in this study.…”

Section: Discussionmentioning

confidence: 99%

“…In one of these studies, assay sensitivity was a significant limitation (7), while only two of these studies described cord blood concentrations of the weak androgens Δ 4 -androstenedione (A4) and dehydroepiandrosterone (DHEA) [7], [33]. However, irrespective of assay methodology, previously published studies of cord androgens have suffered from a lack of power [6], [7], [17], [19], [33], or insufficient control over potential fetal and obstetric confounders such as fetal sex [20], [33], presence and duration of labor [7], [22], [36], [38], gestational age at delivery and maternal factors such as ethnicity, age, parity and smoking status [5], [7], [20], [24], [26], [40]. Fetal adrenal steroid production changes with gestational age and labor, while levels of steroid metabolizing enzymes in the placenta are regulated by factors known to be associated with labor and delivery such as glucocorticoids, pro-inflammatory cytokines and exposure to reactive oxygen species [41].…”

Section: Introductionmentioning

confidence: 99%

Androgen Concentrations in Umbilical Cord Blood and Their Association with Maternal, Fetal and Obstetric Factors

et al. 2012

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The aim of this study was to measure umbilical blood androgen concentrations in a birth cohort using a highly specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay and assesses the effects of sex, labor, and gestational age on fetal androgen levels at birth. We performed a prospective cohort study of androgen concentrations in mixed arterial and venous umbilical cord serum from 803 unselected singleton pregnancies from a general obstetric population in Western Australia. Total testosterone (TT), Δ4-androstenedione, and dehydroepiandrosterone were extracted from archived cord serum samples and measured using LC-MS/MS. SHBG was measured by ELISA; free testosterone (FT) and bioavailable testosterone (BioT) values were also calculated. Median values for all three androgens were generally lower than previously published values. Levels of TT, FT, BioT, and SHBG were significantly higher in male verses female neonates (P<0.0001), while dehydroepiandrosterone levels were higher in females (P<0.0001). Labor was associated with a significant (∼15–26%) decrease in median cord blood TT and FT levels (both sexes combined), but a modest (∼16–31%) increase in SHBG, Δ4-androstenedione, and dehydroepiandrosterone concentrations. TT and FT were significantly negatively correlated with gestational age at delivery, while SHBG, Δ4-androstenedione, and dehydroepiandrosterone were positively correlated. Antenatal glucocorticoid administration also had a significant effect in the multiple regression models. This is the first study to report umbilical cord androgen levels in a large unselected population of neonates using LC-MS/MS. Our findings suggest that previous studies have over-estimated cord androgen levels, and that fetal, maternal, and obstetric factors influence cord androgen levels differentially. Caution should be exercised when interpreting previously-published data that have not taken all of these factors into account.

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Fetal and Maternal Serum Levels of Steroid Sulfates, Unconjugated Steroids, and Prolactin at Term Pregnan and in Early Spontaneous Labor*

Cited by 48 publications

References 32 publications

Role of OAT4 in Uptake of Estriol Precursor 16α-Hydroxydehydroepiandrosterone Sulfate Into Human Placental Syncytiotrophoblasts From Fetus

Role of OAT4 in Uptake of Estriol Precursor 16α-Hydroxydehydroepiandrosterone Sulfate Into Human Placental Syncytiotrophoblasts From Fetus

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome

Androgen Concentrations in Umbilical Cord Blood and Their Association with Maternal, Fetal and Obstetric Factors

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