Maternal Progesterone Research Articles

Early pregnancy maternal progesterone administration alters pituitary and testis function and steroid profile in male fetuses

Maternal exposure to increased steroid hormones, including estrogens, androgens or glucocorticoids during pregnancy results in chronic conditions in offspring that manifest in adulthood. Little is known about effects of progesterone administration in early pregnancy on fetal development. We hypothesised that maternal early pregnancy progesterone supplementation would increase fetal progesterone, affect progesterone target tissues in the developing fetal reproductive system and be metabolised to other bioactive steroids in the fetus. We investigated the effects of progesterone treatment during early pregnancy on maternal and fetal plasma progesterone concentrations, transcript abundance in the fetal pituitary and testes and circulating steroids, at day 75 gestation, using a clinically realistic ovine model. Endogenous progesterone concentrations were lower in male than female fetuses. Maternal progesterone administration increased male, but not female, fetal progesterone concentrations, also increasing circulating 11-dehydrocorticosterone in male fetuses. Maternal progesterone administration altered fetal pituitary and testicular function in ovine male fetuses. This suggests that there may be fetal sex specific effects of the use of progesterone in early pregnancy, and highlights that progesterone supplementation should be used only when there is clear evidence of efficacy and for as limited time as necessary.

High, not low-dose of stanozolol (Anabolic – androgenic steroid) impedes embryo implantation by attenuating endometrial receptivity in the mouse, Mus musculus

The present investigation is aimed at evaluating the efficacy of one of the anabolic –androgenic steroids, stanozolol (ST), on establishment and maintenance of pregnancy in mice. A total of 40 female mice were assigned to three experimental groups. Stanozolol was dosed subcutaneously (low-dose, 0.5 mg/kg bwt; high-dose, 5.0 mg/kg bwt or 1% alcohol-baseline control) for 30 consecutive days. On the 31st day, treatment was withdrawn. The estrous cycle was disrupted in both treatment groups and its resumption was dose dependent. Following estrous resumption, mice were allowed to mate. Results reveal that the low-dose ST-treated mice maintained gestation until term with reduced litter size, while high-dose-treated mice divulged vaginal plug at frequent intervals, indicating conception failure. Because pregnancy failure was noticed in high-dose-treated mice, they were autopsied on GD1.5 and 4.5. Interestingly, neither dose of stanozolol affected early embryonic development or blastocyst hatching. A decrease in the number of corpora lutea in both treated groups suggests it affects either ovulation or recruitment of follicles that occurs in each cycle for maturation.In high-dose-treated mice, decreased serum levels of estradiol, progesterone and increased testosterone along with downregulated endometrial expression of ERα and PR suggest the deficiency of steroid hormones and their respective receptors. Decreased ovarian expression of ERα, hyperexpression of PRLR, AR and abated progesterone secretion led to luteal dysfunction, consequently attenuating endometrial receptivity. Therefore, in high-dose-treated mice, decreased maternal estradiol and progesterone levels and their receptors during implantation hindered signaling to LIF and Hoxa-10, resulting in pragmatic implantation failure.

Serum progesterone and serum b-HCG levels in first trimester threatened abortion

Background: Spontaneous threatened abortion is painful or painless vaginal bleeding from a closed cervix in the condition of positive embryo cardiac pulsations in the first 20 weeks of pregnancy. Most of pregnant women look for urgent obstetrician consultation in early pregnancy because of sudden abdominal pain with or without vaginal bleeding . Aim of the Work: aimed to declare the relation between maternal serum progesterone level and serum b HCG level in case of threatened abortion and their prediction role of the end result of that abortion. Patients and Methods: The study was carried out at El Hussien and Om El Masreen hospitals. 200 patients on the 5th - 12th week of gestation with first trimester threatened abortion were included in our study Results: Regarding patient`s age, GA, HB and BMI, there is showed no significant difference between the groups. In our study, b HCG and progesterone are markedly acceptable to anticipate abortion end result with a cutoff value of b-HCG and Progesterone which was (18153 mIU/ml ,23.5 ng/ml). The sensitivity, specificity for b_HCG at 18153 mIU/ml were 100% and 98.2%, respectively, for Progesterone at 23.5 ng/ml 83% and 89% respectively. Conclusion: In case of threatened abortion, using b HCG to anticipate the end result is more reliable than progesterone. Moreover, The assaying of b HCG and progesterone together does not add any benefits on sensitivity ,while specificity increased from 98.2% to 100%.

Maternal Progesterone Treatment Reduces Maternal Inflammation-Induced Fetal Brain Injury in a Mouse Model of Preterm Birth.

Maternal natural vaginal progesterone (nVP) administration has been shown to reduce the risk of preterm birth (PTB). The largest randomized trial of nVP for PTB (OPPTIMUM) noted a sonographic reduction in neonatal brain injury following nVP treatment. We investigated the neuroinflammatory protective effect of maternal nVP in a mouse model for maternal inflammation. Pregnant mice (n = 24) were randomized to nVP (1mg/day) or vehicle from days 13-16 of gestation. At days 15 and 16, lipopolysaccharide (30μg) or saline were administered. Mice were sacrificed 4h following the last injection. Fetal brains and placentas were collected. Levels of NF-κB, nNOS, IL-6, and TNFα were determined by Western blot. Maternal lipopolysaccharide significantly increased fetal brain levels of IL-6 (0.33 ± 0.02 vs. 0.11 ± 0.01u), TNFα (0.3 ± 0.02 vs. 0.10 ± 0.01u), NF-κB (0.32 ± 0.01 vs. 0.17 ± 0.01u), and nNOS (0.24 ± 0.04 vs. 0.08 ± 0.01u), and reduced the total glutathione levels (0.014 ± 0.001 vs. 0.026 ± 0.001pmol/μl; p < 0.01) compared with control. Maternal nVP significantly reduced fetal brain levels of IL-6 (0.14 ± 0.01 vs. 0.33 ± 0.02u), TNFα (0.2 ± 0.06 vs. 0.3 ± 0.02u), NF-κB (0.16 ± 0.01 vs 0.32 ± 0.01u), and nNOS (0.14 ± 0.01 vs 0.24 ± 0.04u), and prevented the reduction of fetal brain total glutathione levels (0.022 ± 0.001 vs. 0.014 ± 0.001pmol/μl; p < 0.01) to levels similar to controls. A similar pattern was demonstrated in the placenta. Maternal nVP for PTB may protect the fetal brain from inflammation-induced brain injury by inhibiting specific inflammatory and oxidative pathways in both brain and placenta.

Prediction of Spontaneous Abortion Risk by the Use of First Trimester Ultrasound Measurements and Maternal Serum Progesterone Level

Prediction of Spontaneous Abortion Risk by the Use of First Trimester Ultrasound Measurements and Maternal Serum Progesterone Level

Maternal Pregnancy Hormone Concentrations in Countries with Very Low and High Breast Cancer Risk.

Background: Breast cancer rates in Asia are much lower than in Europe and North America. Within Asia, rates are lower in Mongolia than in neighboring countries. Variation in pregnancy exposure to endogenous hormone concentrations may explain the differences, but data are lacking. Methods: We measured maternal serum progesterone, prolactin, estradiol and estrone concentrations in the second half of pregnancy in a cross-sectional study of urban (n = 143–194 depending on the analyte) and rural (n = 150–193) Mongolian women, and U.S. women from Boston (n = 66–204). Medical records provided information on maternal and perinatal factors. Geometric mean hormones were estimated from standard linear models with the log-hormone as the dependent variable and country as the independent variable adjusted for maternal and gestational age at blood draw. Results: Mean concentrations of prolactin (5722 vs. 4648 uIU/mL; p < 0.0001) and estradiol (17.7 vs. 13.6 ng/mL; p < 0.0001) were greater in Mongolian than U.S. women, while progesterone (147 vs. 201 ng/mL; p < 0.0001) was lower. Mean hormone concentrations were similar in rural and urban Mongolian women. Results were generally similar, with additional adjustment for gravidity, parity, height, body mass index at blood draw, education and alcohol use during pregnancy, and when stratified by offspring sex or parity. Conclusions: Mongolian women had greater concentrations of prolactin and estrogen and lower concentrations of progesterone than U.S. women, while hormone concentrations were similar in rural and urban Mongolian pregnancies. Impact: These data do not support the hypothesis that estrogen concentrations in pregnant women are lower in Mongolian compared with Caucasian women.

Glucosamine Supplementation in Premating Drinking Water Improves Within-Litter Birth Weight Uniformity of Rats Partly through Modulating Hormone Metabolism and Genes Involved in Implantation.

Within-litter birth weight variation in multiparous animals has become a big issue due to high incidence of low birth weight neonates, which gives rise to high preweaning mortality and morbidity. Foetus with various birth weights is the outcome of diverse embryos competence which is affected by oocyte quality. Glucosamine (GlcN) has been reported to be involved in oocyte maturation; however, its effect on pregnant outcomes remains unknown. The present study was conducted to investigate the effects of premating GlcN supplementation via drinking water on within-litter birth weight variation and its underlying mechanism. Fifty eight Sprague-Dawley female rats were randomly assigned to one of two groups with normal drinking water or drinking water supplemented with 0.5 mM GlcN from six to eight weeks old. Variation of within-litter birth weight in the GlcN group was 5.55%, significantly lower compared with 8.17% in the control group. Birth weight was significantly increased in the GlcN group (2.27 ± 0.06) compared with the control group (2.08 ± 0.04). Both absolute and relative weights of the ovary at the end of GlcN treatment were higher in the GlcN group than in the control group (P < 0.05). In the GlcN group, there were more successfully implanted blastocysts (13.38 ± 0.63 and 15.75 ± 0.59 in the control and treatment group, respectively) with more uniform distribution along the two uterine horns compared with the control group. Besides, gene expressions of Alk3 and Bmp2 were increased in the implantation sites, while IGF-1 and Mucin-1 were decreased significantly in rats administrated with GlcN. Maternal progesterone, estradiol, and IGF-1 concentrations on D 19.5 were significantly increased, while insulin and total cholesterol levels were significantly decreased in contrast with control dams. In summary, the administration of 0.5 mM GlcN solution before mating reduced within-litter birth weight variation, accompanied with increased fetal weight. Further investigation indicated that the improved outcome of pregnancy results at least partly from the increased ovary weights of the rats, the homogeneous embryo developmental competence, the enhanced receptivity of the uterine environment, and the adjusted maternal hormone levels.

PSXIII-35 Relationship between early gestation maternal plasma progesterone concentrations and within-litter birth weight variation from Yorkshire sired litters

Abstract The objective of this study was to determine if maternal plasma progesterone (P4) during early gestation influences within-litter birth weight variation in pigs. White crossbred females (n = 589) of mixed parity (1–4) were bred at standing estrus designated as day 0 of pregnancy and again 24 h later using single-sire semen from commercial Yorkshire genetics. At day 7 of pregnancy, a single blood sample from each female was collected, processed for plasma and P4 was analyzed using a validated RIA for swine. Dams were allowed to farrow under normal management procedures and standard litter statistics (e.g., number born alive, piglet birth weight, etc.) were recorded. Within-litter birth weight variation (BWV) was determined for each litter using the coefficient of variation of birth weight. Pearson correlation analysis illustrated there was a low (r = 0.0967) but significant (P = 0.0191) positive correlation between P4 and BWV. Linear regression demonstrated that for every ng/ml increase in P4 during early gestation, BWV increased 0.11 ± 0.04%. For this population, the mean BWV was 19.4% with a SD of 7.8%. When analyzing P4 concentrations from extreme groups of females with high or low BWV [i.e. females with 1 SD above, high group (&amp;gt;27.2%; n = 100); or below, low group (&amp;lt; 11.6%; n = 106) the mean BWV] by GLM procedures, high BWV group females had increased (P = 0.0473) concentrations of P4 during early gestation compared to low BWV group (13.9 ± 1.4 vs. 9.0 ± 1.7 ng/ml, respectively). These data demonstrate a positive relationship for early gestation plasma P4 concentrations with greater BWV; thereby, illustrating that high concentrations of P4 during early gestation influence within-litter birth weight variation in pigs. USDA is an equal opportunity provider and employer.

Maternal Pregnancy Hormone Concentrations in Countries with Very Low and High Breast Cancer Risk

Background: Breast cancer rates in Asia are much lower than in Europe and North America. Within Asia, rates are lower in Mongolia than in neighboring countries. Variation in pregnancy exposure to endogenous hormone concentrations may explain the differences, but data are lacking. Methods: We measured maternal serum progesterone, prolactin, estradiol and estrone concentrations in the second half of pregnancy in urban and rural Mongolian, and U.S. women from Boston. Medical records provided information on maternal and perinatal factors. Geometric mean hormones were estimated from standard linear models with the log-hormone as the dependent variable and country as the independent variable adjusted for maternal and gestational age at blood draw. Results: Mean concentrations of prolactin (5722 vs. 4648 uIU/mL; p<0.0001) and estradiol (17.7 vs. 13.6 ng/mL; p<0.0001) were greater in Mongolian than U.S. women, while progesterone (147 vs. 201 ng/mL; p<00001) was lower. Mean hormone concentrations were similar in rural and urban Mongolian women. Results were generally similar with additional adjustment for gravidity, parity, height, body mass index at blood draw, education and alcohol use during pregnancy, and when stratified by offspring sex or parity. Conclusions: Mongolian women had greater concentrations of prolactin and estrogen and lower concentrations of progesterone than US women, while hormone concentrations were similar in rural and urban Mongolian pregnancies. Funding Statement: This research was supported by funding from the intramural program at the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. Declaration of Interests: None of the authors has a conflict of interest. Ethics Approval Statement: The study was approved by ethical review boards at Mongolia’s Ministry of Health, the National University of Mongolia, and in the United States (U.S.) at the National Cancer Institute (National Institutes of Health), and the Harvard School of Public Health and Brigham and Women’s Hospital in Boston. All participants provided written, informed consent.

The Role of Maternal Progesterone and Estradiol Levels in Predicting the Success of Induction of Labour: A Preliminary Study

Objective: to evaluate whether maternal progesterone and estradiol levels could be used to predictthe success ofinduction of labour (IOL)&#x0D; Methods:This cross-sectional study was conducted at the Women’s Health Clinic as well as delivery suite of Dr. Cipto Mangunkusumo Hospital during the period of May 2016 to April 2017. Blood samples of term pregnant women who were indicated for IOL wereobtainedbefore birth.&#x0D; Results:A total 44 subject were recruited in this study.Of these, 24 subjects had successful IOL while the other 20 subjects had IOL failure. There was no significant difference of progesterone among both groups (66,7% vs 75%, p=0,55). The estradiol levels in subjects who successfully performed induction had an average of 16,916.28 ± 2,574.75 pg/mL which did not differ significantly from the failed of induction group with estradiol levels of 14,832.24 ± 2374.47 pg/mL (p = 0,65).&#x0D; Conclusion:We found no significant association between both maternal progesterone and estradiol levels and the success rate of IOL. Further studies with larger sample sizes are required to confirm whether progesterone and estradiol play pivotal roles in the success of IOL.&#x0D; Keywords: progesterone, estradiol, induction of labour&#x0D; &#x0D; Tujuan: mengevaluasi kadar progesteron dan estradiol ibu sebagai prediktor kesuksesan induksi persalinan&#x0D; Metode: Penelitian ini menggunakan desain potong lintang yang berlangsung pada bulan Mei 2016 hingga April 2017 di Poliklinik dan IGD Kebidanan Rumah Sakit Umum Pusat Rujukan Nasional Cipto Mangunkusumo. Pasien hamil aterm yang dilakukan induksi persalinan dan memenuhi kriteria penelitian akan diambil sampel darah sebelum persalinan.&#x0D; Hasil: Dari 44 subjek yang mengikuti penelitian, 24 subjek berhasil dilakukan induksi persalinan dan 20 subjek gagal.Tidakterdapatperbedaanbermaknapadakadarprogesterone&#x0D; Antarakeduagrup(66,7% vs 75%, p=0,55). Kadar estradiol padapasien yang berhasildilakukaninduksimemiliki rata-rata 16.916,28 + 2.574,75pg/mL yang tidakberbedajauhdengankadar estradiol pasien yang gagalinduksiyaitu 14.832,24 + 2374,47pg/mL (p = 0,65).&#x0D; Kesimpulan: Tidakterdapat perbedaan bermakna antara kadar progesteron dan estradiol maternal terhadap keberhasilan induksi persalinan. Penelitian lebih lanjut dengan jumlah sampel yang lebih besar dibutuhkan untuk mengkonfirmasi hubungan ini dengan lebih baik.&#x0D; Kata kunci: progesteron, estradiol, induksi persalinan

Influence of Low Protein Diet-Induced Fetal Growth Restriction on the Neuroplacental Corticosterone Axis in the Rat.

Objectives: Placental steroid metabolism is linked to the fetal hypothalamus-pituitary-adrenal axis. Intrauterine growth restriction (IUGR) might alter this cross-talk and lead to maternal stress, in turn contributing to the pathogenesis of anxiety-related disorders of the offspring, which might be mediated by fetal overexposure to, or a reduced local enzymatic protection against maternal glucocorticoids. So far, direct evidence of altered levels of circulating/local glucocorticoids is scarce. Liquid chromatography tandem-mass spectrometry (LC-MS/MS) allows quantitative endocrine assessment of blood and tissue. Using a rat model of maternal protein restriction (low protein [LP] vs. normal protein [NP]) to induce IUGR, we analyzed fetal and maternal steroid levels via LC-MS/MS along with the local expression of 11beta-hydroxysteroid-dehydrogenase (Hsd11b).Methods: Pregnant Wistar dams were fed a low protein (8%, LP; IUGR) or an isocaloric normal protein diet (17%, NP; controls). At E18.5, the expression of Hsd11b1 and 2 was determined by RT-PCR in fetal placenta and brain. Steroid profiling of maternal and fetal whole blood, fetal brain, and placenta was performed via LC-MS/MS.Results: In animals with LP-induced reduced body (p < 0.001) and placental weights (p < 0.05) we did not observe any difference in the expressional Hsd11b1/2-ratio in brain or placenta. Moreover, LP diet did not alter corticosterone (Cort) or 11-dehydrocorticosterone (DH-Cort) levels in dams, while fetal whole blood levels of Cort were significantly lower in the LP group (p < 0.001) and concomitantly in LP brain (p = 0.003) and LP placenta (p = 0.002). Maternal and fetal progesterone levels (whole blood and tissue) were not influenced by LP diet.Conclusion: Various rat models of intrauterine stress show profound alterations in placental Hsd11b2 gatekeeper function and fetal overexposure to corticosterone. In contrast, LP diet in our model induced IUGR without altering maternal steroid levels or placental enzymatic glucocorticoid barrier function. In fact, IUGR offspring showed significantly reduced levels of circulating and local corticosterone. Thus, our LP model might not represent a genuine model of intrauterine stress. Hypothetically, the observed changes might reflect a fetal attempt to maintain anabolic conditions in the light of protein restriction to sustain regular brain development. This may contribute to fetal origins of later neurodevelopmental sequelae.

Birth and Neonatal Transition in the Guinea Pig: Experimental Approaches to Prevent Preterm Birth and Protect the Premature Fetus

The guinea pig (Cavia porcellus) displays many features of gestational physiology that makes it the most translationally relevant rodent species. Progesterone production undergoes a luteal to placental shift as in human pregnancy with levels rising during gestation and with labor and delivery occurring without a precipitous decline in maternal progesterone levels. In contrast to other laboratory rodents, labor in guinea pigs is triggered by a functional progesterone withdrawal, which involves the loss of uterine sensitivity to progesterone like in women. In both species the amnion membrane is a major source of labor-inducing prostaglandins, which promote functional progesterone withdrawal by modifying myometrial progesterone receptor expression. These similar features appear to result from convergent evolution rather than closer evolutionally relationship to primates compared to other rodents. Nevertheless, the similarities in the production, metabolism and actions of progesterone and prostaglandins allow information gained in pregnant guinea pigs to be extended to pregnant women with confidence. This includes exploring the effects of pregnancy complications including growth restriction and the mechanisms by which stressful conditions increase the incidence of preterm labor. The relatively long gestation of the guinea pig and the maturity of the pups at birth particularly in brain development means that a greater proportion of brain development happens in utero. This allows adverse intrauterine conditions to make a sustained impact on the developing brain like in compromised human pregnancies. In addition, the brain is exposed to a protective neurosteroid environment in utero, which has been suggested to promote development in the guinea pig and the human. Moreover, in utero stresses that have been shown to adversely affect long term neurobehavioral outcomes in clinical studies, can be modeled successfully in guinea pigs. Overall, these parallels to the human have led to increasing interest in the guinea pig for translational studies of treatments and therapies that potentially improve outcomes following adverse events in pregnancy and after preterm birth.

Effect of body weight on early hormone levels in singleton pregnancies resulting in delivery after in vitro fertilization

To evaluate which clinical characteristics influence early maternal β-human chorionic gonadotropin (hCG) and progesterone levels in invitro fertilization (IVF) pregnancies. Retrospective cohort analysis. Academic medical center. Women with a live birth after single-blastocyst embryo transfer in either a fresh or frozen cycle between 2004 and 2017, comprising 1,282 pregnancies in 1,057 patients. None. The initial human chorionic gonadotropin concentration (β-hCG1) measured a mean of 10days (range: 9-12days) after embryo transfer, the rate of increase in β-hCG concentrations, and progesterone concentration, with all analyses controlled for number of days between the embryo transfer and the β-hCG1 measurement. The clinical factor that positively influenced the β-hCG1 level in the fresh cycle was the stimulation type (antagonist cycle higher than long agonist cycle). The clinical factors that negatively influenced both fresh and frozen cycle β-hCG1 were lower embryo quality and increasing body weight. Increasing weight negatively impacted progesterone levels in both fresh and frozen cycles. A 100 lb (45.4kg) difference in weight was associated with a 34.8% reduction in β-hCG1 for both fresh and frozen cycle pregnancies. The rate of increase in β-hCG was unaffected by body weight. A 100 lb (45.4kg) difference in weight was associated with a 53.3% and a 32.8% reduction in progesterone in fresh and frozen cycles, respectively. Increasing body weight is associated with significantly lower β-hCG and progesterone concentrations in early pregnancy after blastocyst single-embryo transfer in both fresh and frozen cycles. Clinicians should consider this when evaluating these hormone levels for prognostic and diagnostic purposes.

Sex steroids influence the plasma membrane transformation in the uterus of the fat-tailed dunnart (Sminthopsis crassicaudata, Marsupialia).

The uterine epithelium undergoes remodelling to become receptive to blastocyst implantation during pregnancy in a process known as the plasma membrane transformation. There are commonalities in ultrastructural changes to the epithelium, which, in eutherian, pregnancies are controlled by maternal hormones, progesterone and oestrogens. The aim of this study was to determine the effects that sex steroids have on the uterine epithelium in the fat-tailed dunnart Sminthopsis crassicaudata, the first such study in a marsupial. Females were exposed to exogenous hormones while they were reproductively quiescent, thus not producing physiological concentrations of ovarian hormones. We found that changes to the protein E-cadherin, which forms part of the adherens junction, are controlled by progesterone and that changes to the desmoglein-2 protein, which forms part of desmosomes, are controlled by 17β-oestradiol. Exposure to a combination of progesterone and 17β-oestradiol causes changes to the microvilli on the apical surface and to the ultrastructure of the uterine epithelium. There is a decrease in lateral adhesion when the uterus is exposed to progesterone and 17β-oestradiol that mimics the hormone environment of uterine receptivity. We conclude that uterine receptivity and the plasma membrane transformation in marsupial and eutherian pregnancies are under the same endocrine control and may be an ancestral feature of therian mammals.

Phenotypic variations in transferred progeny due to genotype of surrogate mother.

Does the genotype of the surrogate mother modulate the body composition and immunity of her offspring? C57BL/6J (B6) progenies carried by immunodeficient NOD SCID (NS) mothers had increased adaptive but decreased innate, immune responsiveness in comparison with the same genotype offspring carried by immunocompetent mothers, B6 and BALB/c (C); the B6 progenies carried by the same genotype mothers also showed higher body fat than the others. Differences in the major histocompatibility complex (MHC) genes between mother and foetus is considered as an important factor in prenatal embryo development, whereas the impact of such dissimilarity on the phenotype of the mature progeny is unclear. Transplantation of two-cell mouse embryos into recipient females of the different MHC (H2) genotypes was used as an approach to simulate three variants of the immunogenic mother-foetus interaction: (i) bidirectional immunogenic dialogue between B6 (H2b haplotype) embryos and C (H2d haplotype) surrogate mother; (ii) one-way immunogenic interaction between B6 embryos and immunodeficient NS (H2g7 haplotype) surrogate mother and (iii) reduced immunogenetic dialogue between embryos and surrogate mother of the same H2b haplotype resulting in only a maternal response to HY antigens of male foetuses. Delivered by Caesarean section, pups were fostered by lactating B6 females and weighed after weaning (n = 171). Body mass and composition and innate and adaptive immunity were assessed in selected progeny groups at 9-11 weeks of age. The study was performed on the specific pathogen-free mouse, inbred strains C57BL/6J, NOD SCID and BALB/c. Plasma progesterone in pregnant females was measured by enzyme-linked immunosorbent assay (ELISA). Body composition was determined by magnetic resonance spectroscopy using a low-field NMR spectrometer (EchoMRI, USA). To assess peritoneal macrophage responses (innate immunity) to anthrax, lactate dehydrogenase (LDH) and interleukin-1 (IL-1β) were measured in a culture medium 24 h after the addition of both anthrax-lethal factor and anthrax-protective antigen. To assess adaptive immunity, 9-10 males in experimental groups were infected with Helicobacter hepaticus. Faeces collected 2 and 4 weeks after infection was used for quantitative assessment of the H. hepaticus DNA by real-time polymerase chain reaction. IgA, interferon (IFN-γ), tumour necrosis factor (TNFα), interleukin-17 (IL-17) and interleukin-10 (IL-10) in colon tissue and IgG in serum were determined in samples collected 4 weeks after gavage with H. hepaticus using ELISA. For statistical analyses, ANCOVA, post hoc least significant difference (LSD) test, Student's t-test, Spearman rank correlations and χ2 test were performed. P-value <0.05 was considered as a statistically significant difference. ANCOVA with litter size and age as covariates revealed significant effects of the surrogate mother genotype on body mass and percent of fat in their adult progeny (F2149 = 15.60, P < 0.001 and F2149 = 5.02, P = 0.007, respectively). Adult B6 mice carried by B6 surrogate mothers were characterized by a higher percentage of body fat in comparison with offspring that were carried by NS and C females. In comparison with the male offspring carried by the B6 and C mothers, male B6 progenies carried by immunodeficient NS mothers had a higher humoral immune response (serum IgG) against oral infection with H. hepaticus, but lower in vitro macrophage IL-1β reaction to the anthrax. Four weeks after the infection of offspring, concentrations of serum IgG and colon IL-10 correlated positively with maternal progesterone on Day 4 after embryo transfer and negatively with DNA of H. hepaticus. One-way ANOVA confirmed a statistically significant impact of surrogate mother genotype on adaptive (IgG) and innate (IL-1β) immunity (F2.26 = 26.39, P < 0.001 and F2.27 = 5.89, P = 0.008, respectively). N/A. The main limitation of our study is the number of combinations of mother and foetus interactions, in particular, transfer of only one embryo genotype was used. Also, it is a descriptive study, which requires further analysis of the epigenetic mechanisms of the observed phenotypic effects of surrogate mother genotype. Our experimental data demonstrate that the transfer of inbred embryos to surrogate mothers of the different genotypes is a prospective experimental model for the study of epigenetic effects of the immunogenetic interactions between mother and foetus. The experimental approach tested in our study will be in demand for the development of criteria for choosing surrogate mothers. In particular, immunocompetence of the surrogate mother along with genetic distance of her MHC alleles to the transferred embryos have a significant impact on offspring development. This work was supported by the Russian FPI (6/099/2017), budget projects (0324-2016-0002 and 0324-2018-0016) and implemented using the equipment of the Centre for Genetic Resources of Laboratory Animals at ICG SB RAS, supported by the Ministry of Education and Science of Russia (Unique project identifier RFMEFI62117X0015). The authors report no conflicts of interest.

Antenatal placental assessment in the prediction of adverse pregnancy outcome after reduced fetal movement.

ObjectiveTo assess the value of in utero placental assessment in predicting adverse pregnancy outcome after reported reduced fetal movements (RFM).MethodA non-interventional prospective cohort study of women (N = 300) with subjective RFM at ≥28 weeks’ gestation in singleton non-anomalous pregnancies at a UK tertiary maternity hospital. Clinical, sonographic (fetal weight, placental size and maternal, fetal and placental arterial Doppler) and biochemical (maternal serum hCG, hPL, progesterone, PlGF and sFlt-1) assessment was conducted. Multiple logistic regression identified combinations of measurements (models) most predictive of adverse pregnancy outcome (perinatal mortality, birth weight <10th centile, five minute Apgar score <7, umbilical arterial pH <7.1 or base excess <-10, neonatal intensive care admission). Models were compared by test performance characteristics (ROC curve, sensitivity, specificity, positive/negative predictive value, positive/negative likelihood ratios) against baseline care (estimated fetal weight centile, amniotic fluid index and gestation at presentation).Results61 (20.6%) pregnancies ended in adverse outcome. Models incorporating PlGF/sFlt-1 ratio and umbilical artery free loop Doppler impedance demonstrated modest improvement in ROC area for adverse outcome (baseline care 0.69 vs. proposed models 0.73–0.76, p<0.05). However, there was little improvement in other test characteristics (baseline vs. best proposed model: sensitivity 21.7% [95% confidence interval 13.1–33.6] vs. 35.8%% [24.4–49.3], specificity 96.6% [93.4–98.3] vs. 94.7% [90.7–97.0], PPV 61.9% [40.9–79.3] vs. 63.3% [45.5–78.1], NPV 82.8% [77.9–86.8] vs. 85.2% [80.0–89.2], positive LR 6.3 [2.8–14.6] vs. 6.7 [3.4–3.3], negative LR 0.81 [0.71–0.93] vs. 0.68 [0.55–0.83]) and wide confidence intervals. Negative post-test probability remained high (16.7% vs. 14.0%).ConclusionAntenatal placental assessment may improve identification of RFM pregnancies at highest risk of adverse pregnancy outcome but further work is required to understand and refine currently available outcome definitions and diagnostic techniques to improve clinical utility.

Maternal estradiol and progesterone concentrations among singleton spontaneous pregnancies during the first trimester.

Pregnancy hormonal milieu represents a crucial determinant of fetal outcome. We aim to determine 17β-estradiol (E2) and progesterone (PGT) concentrations in spontaneous pregnancies during the first trimester. In addition, we aim to determine E2 concentrations as a function of gestational age (GA) and PGT. Between November 2015 and March 2017, 104 healthy women of at least 18years undergoing medical consultation for voluntary interruption of pregnancy were enrolled in an observational study at University Hospital ASST Fatebenefratelli Sacco, Milan, Italy. Only singleton pregnancies between 5+0 and 13+6 weeks of gestation were eligible. First trimester ultrasound scans were performed for dating and one fasting venous blood sample was collected for E2 and PGT determinations. E2 and PGT concentrations steadily increased according to GA. The correlation between E2 on a logarithmic scale and PGT concentrations was expressed by the following equation, explaining 12.6% of E2 variance: logE2 = 2.57 + 0.1 × PGT, (r = 0.34, p < 0.001). By performing a multivariable linear regression analysis adjusted for variables significantly correlated with E2 concentrations, we obtained a model explaining the 53.5% of E2 variance. The final equation to determine E2 concentrations among Caucasian women was: logE2 = 1.96 + 0.01 × GA + 0.004 × PGT. Gestational week-specific reference intervals are reported for maternal E2 and PGT concentrations during early pregnancy, further providing a model for E2 assessment in this period. This will represent a starting point for further evaluations between twin and ART pregnancies, as well as to potentially improve pregnancy outcome and future health of the offspring.

Clinical characteristics and risk factors of infantile hemangioma: a case-control study in Northwest China

Objective To investigate the clinical characteristics and risk factors of infantile hemangioma in Xinjiang Uygur Autonomous Region, China. Methods A total of 941 infants with infantile hemangioma were identified as subjects and matched with 941 infants of the same age without infantile hemangioma. Trained investigators used a standardized questionnaire to collect data from both groups, including demographic, prenatal, and perinatal characteristics. Univariate and multiple logistic regression models were used to screen risk factors. Results This study revealed that female (P<0.001, OR = 3.08, 95% CI = 2.54 - 3.74), maternal tea drinking (P<0.001, OR =1.86, 95% CI = 1.32 - 2.61), low birth-weight (P<0.001, OR = 3.01, 95% CI = 2.10 - 4.30), preterm (P<0.001, OR = 4.07, 95% CI = 2.73 - 6.09), gestational diabetes (P<0.001, OR = 2.03, 95% CI = 1.41 - 2.94 ), maternal progesterone use (P<0.001, OR = 2.44, 95% CI = 1.83 - 3.25) and a history of hemangiomas in first-degree relatives (P<0.001, OR = 1.80, 95% CI = 1.33 - 2.43) influenced the occurrence of infantile hemangioma. Female (P<0.001, OR = 2.82, 95% CI = 2.30 - 3.45 ), maternal progesterone use (P<0.001, OR = 14.64, 95% CI = 3.52 - 60.88) and a history of hemangiomas in first-degree relatives (P<0.001, OR = 0.011, 95% CI = 0.002 - 0.065) were independent risk factors for infantile hemangioma. Conclusions Female, maternal tea drinking, low birthweight, preterm, gestational diabetes, maternal progesterone use, and a history of hemangiomas in first-degree relatives may interact with each other leading to the occurrence of infantile hemangioma. Key words: Infantile hemangioma; Clinical characteristics; Risk factors; Case-control; Epidemiology

Temporal trends in prenatal risk factors for the development of infantile hemangiomas.

Specific maternal risk factors have recently been identified in the development of infantile hemangiomas (IH), including gestational diabetes (GDM), maternal antihypertensive medication use or gestational hypertension (GHTN), maternal progesterone use, and artificial reproductive technologies (ART). We sought to explore the change in incidence of these risk factors over time and determine their association with the increased incidence of hemangiomas over 35years, as previously reported. The charts of 869 mother and infant pairs (infants previously diagnosed with IH between January 1, 1976, and December 31, 2010) were reviewed for prenatal complications. Rates of the prenatal complications over the 35-year period in birth mothers of infants diagnosed with IH were determined and evaluated by year of diagnosis (1976-1990, 1991-2000, and 2001-2010). Over the 35-year period in which the incidence of IH was previously examined, maternal age at delivery, prepregnancy body mass index (BMI), use of ART, maternal progesterone use, placental abnormalities, and GDM also increased. GDM, ART, and maternal progesterone use increased over the past 35years, mirroring the previously reported trend of increasing incidence of IH. Maternal age and BMI also increased in mothers of infants with IH. Further exploration of this association may direct future research in the pathogenesis of infantile hemangiomas.

Serum progesterone distribution in normal pregnancies compared to pregnancies complicated by threatened miscarriage from 5 to 13 weeks gestation: a prospective cohort study

BackgroundProgesterone is a critical hormone in early pregnancy. A low level of serum progesterone is associated with threatened miscarriage. We aim to establish the distribution of maternal serum progesterone in normal pregnancies compared to pregnancies complicated by threatened miscarriage from 5 to 13 weeks gestation.MethodsThis is a single centre, prospective cohort study of 929 patients. Women from the Normal Pregnancy [NP] cohort were recruited from antenatal clinics, and those in the Threatened Miscarriage [TM] cohort were recruited from emergency walk-in clinics. Women with multiple gestations, missed, incomplete or inevitable miscarriage were excluded from the study. Quantile regression was used to characterize serum progesterone levels in the NP and TM cohorts by estimating the 10th, 50th and 90th percentiles from 5 to 13 weeks gestation. Pregnancy outcome was determined at 16 weeks of gestation. Subgroup analysis within the TM group compared progesterone levels of women who subsequently miscarried with those who had ongoing pregnancies at 16 weeks of gestation.ResultsMedian serum progesterone concentration demonstrated a linearly increasing trend from 57.5 nmol/L to 80.8 nmol/L from 5 to 13 weeks gestation in the NP cohort. In the TM cohort, median serum progesterone concentration increased from 41.7 nmol/L to 78.1 nmol/L. However, median progesterone levels were uniformly lower in the TM cohort by approximately 10 nmol/L at every gestation week. In the subgroup analysis, median serum progesterone concentration in women with ongoing pregnancy at 16 weeks gestation demonstrated a linearly increasing trend from 5 to 13 weeks gestation. There was a marginal and non-significant increase in serum progesterone from 19.0 to 30.3 nmol/L from 5 to 13 weeks gestation in women who eventually had a spontaneous miscarriage.ConclusionsSerum progesterone concentration increased linearly with gestational age from 5 to 13 weeks in women with normal pregnancies. Women with spontaneous miscarriage showed a marginal and non-significant increase in serum progesterone. This study highlights the pivotal role of progesterone in supporting an early pregnancy, with lower serum progesterone associated with threatened miscarriage and a subsequent complete miscarriage at 16 weeks gestation.