Tim-3 Coordinates Macrophage-Trophoblast Crosstalk via Angiogenic Growth Factors to Promote Pregnancy Maintenance.

T-cell immunoglobulin mucin-3 (Tim-3) is an important checkpoint that induces maternal-fetal tolerance in pregnancy. Macrophages (Mφs) play essential roles in maintaining maternal-fetal tolerance, remodeling spiral arteries, and regulating trophoblast biological behaviors. In the present study, the formation of the labyrinth zone showed striking defects in pregnant mice treated with Tim-3 neutralizing antibodies. The adoptive transfer of Tim-3+Mφs, rather than Tim-3-Mφs, reversed the murine placental dysplasia resulting from Mφ depletion. With the higher production of angiogenic growth factors (AGFs, including PDGF-AA, TGF-α, and VEGF), Tim-3+dMφs were more beneficial in promoting the invasion and tube formation ability of trophoblasts. The blockade of AGFs in Tim-3+Mφs led to the narrowing of the labyrinthine layer of the placenta, compromising maternal-fetal tolerance, and increasing the risk of fetal loss. Meanwhile, the AGFs-treated Tim-3-Mφs could resolve the placental dysplasia and fetal loss resulting from Mφ depletion. These findings emphasized the vital roles of Tim-3 in coordinating Mφs-extravillous trophoblasts interaction via AGFs to promote pregnancy maintenance and in extending the role of checkpoint signaling in placental development. The results obtained in our study also firmly demonstrated that careful consideration of reproductive safety should be taken when selecting immune checkpoint and AGF blockade therapies in real-world clinical care.

Antibody microarray analysis of amniotic fluid proteomes in women with cervical insufficiency and short cervix, and their association with pregnancy latency length.

INTRODUCTION: This study aimed to investigate amniotic fluid (AF) proteins that were differentially expressed between patients with cervical insufficiency (CI) and asymptomatic short cervix (SCX, ≤ 25 mm), and whether these proteins could be predictive of spontaneous preterm birth (SPTB) in these patients. METHOD: This was a retrospective cohort study of 129 singleton pregnant women with CI (n = 80) or SCX (n = 49) at 17 to 26 weeks who underwent amniocentesis. An antibody microarray was used to perform comparative proteomic profiling of AF from matched CI (n = 20) and SCX (n = 20) pregnancies. In the total cohort, an ELISA validation study was performed for 15 candidate proteins of interest. Subgroup analyses of patients with CI and SCX were conducted to evaluate the association between the 15 proteins and SPTB at < 32 weeks of gestation. RESULTS: Eighty-six proteins showed intergroup differences. ELISA validation confirmed significantly higher levels of AF EN-RAGE, IL-8, lipocalin-2, MMP-9, S100A8/A9, thrombospondin-2, and TNFR2 in patients with CI than in those with SCX. Multivariable analysis showed that increased AF levels of EN-RAGE, S100A8/A9, and uPA were independently associated with SPTB at < 32 weeks in patients with CI; whereas in patients with SCX, high AF levels of APRIL, EN-RAGE, LBP, and TNFR2 were independently associated with SPTB at < 32 weeks. CONCLUSIONS: Multiple AF proteins show altered expression in patients with CI compared with SCX controls. Moreover, several novel mediators involved in inflammation were identified as potential biomarkers for predicting SPTB after the diagnosis of CI and SCX. These results provide new insights into target-specific molecules for targeted therapies to prevent SPTB in patients with CI/SCX.

Non-invasive prenatal testing in the management of twin pregnancies.

Twin pregnancies are common and associated with pregnancy complications and adverse outcomes. Prenatal clinical management is intensive and has been hampered by inferior screening and less acceptable invasive testing. For aneuploidy screening, meta-analyses show that non-invasive prenatal testing (NIPT) through analysis of cell-free DNA (cf-DNA) is superior to serum and ultrasound-based tests. The positive predictive value for NIPT is driven strongly by the discriminatory power of the assay and only secondarily by the prior risk. Uncertainties in a priori risks for aneuploidies in twin pregnancies are therefore of lesser importance with NIPT. Additional information on zygosity can be obtained using NIPT. Establishing zygosity can be helpful when chorionicity was not reliably established early in pregnancy or where the there is a concern for one versus two affected fetuses. In dizygotic twin pregnancies, individual fetal fractions can be measured to ensure that both values are satisfactory. Vanishing twins can be identified by NIPT. Although clinical utility of routinely detecting vanishing twins has not yet been demonstrated, there are individual cases where cf-DNA analysis could be helpful in explaining unusual clinical or laboratory observations. We conclude that cf-DNA analysis and ultrasound have synergistic roles in the management of multiple gestational pregnancies.

Impact of exosome-mediated feto-maternal interactions on pregnancy maintenance and development of obstetric complications.

Pregnancy is an immunological paradox, a phenomenon in which the foetus and the placenta, containing foreign antigens to the mother, develop without inducing rejection by the maternal immune system. Cell-to-cell communication between the foetus and the mother is mediated by secreted factors such as cytokines, hormones and extracellular vesicles (EVs) for a successful pregnancy and to avoid rejection. Exosomes, the smallest of EVs, are released extracellularly, where they are taken up by proximal or distant recipient cells. Here, we discuss the role of EVs, especially exosomes in feto-maternal communication during pregnancy. This review will provide an overview of the functional roles exosomes may play during embryo implantation, modulating immune responses during pregnancy and the onset of labour. Moreover, we will discuss exosomal function in obstetric pathology, and the development of pregnancy-associated complications such as preeclampsia and preterm birth as well as the biomarker potential of exosomes for detecting such conditions.

Early pregnancy loss in 15-hydroxyprostaglandin dehydrogenase knockout (15-HPGD-/-) mice due to requirement for embryo 15-HPGD activity.

Prostaglandins (PGs) have critical signaling functions in a variety of processes including the establishment and maintenance of pregnancy, and the initiation of labor. Most PGs are non-enzymatically degraded, however, the two PGs most prominently implicated in the termination of pregnancy, including the initiation of labor, prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α), are enzymatically degraded by 15-hydroxyprostaglandin dehydrogenase (15-HPGD). The role of PG metabolism by 15-HPGD in the maintenance of pregnancy remains largely unknown, as direct functional studies are lacking. To test the hypothesis that 15-PGDH-mediated PG metabolism is essential for pregnancy maintenance and normal labor timing, we generated and analyzed pregnancy in 15-HPGD knockout mice (Hpgd-/-). We report here that pregnancies resulting from matings between 15-HPGD KO mice (Hpgd-/- X Hpgd-/-KO mating) are terminated at mid gestation due to a requirement for embryo derived 15-HPGD. Aside from altered implantation site spacing, pregnancies from KO matings look grossly and histologically normal at days post coitum (dpc) 6.5 and 7.5 of pregnancy. However, virtually all of these pregnancies are resorbed by dpc 8.5. This resorption is preceded by elevation of PGF2∝ but is not preceded by a decrease in circulating progesterone, suggesting that pregnancy loss is a local inflammatory phenomenon rather than a centrally mediated phenomena. This pregnancy loss can be temporarily deferred by indomethacin treatment, but treated pregnancies are not maintained to term and indomethacin treatment increases maternal mortality. We conclude that PG metabolism to inactive products by embryo derived 15-HPGD is essential for pregnancy maintenance in mice, and may serve a similar function during human pregnancy.

Providing Patient-Centered Perinatal Care for Transgender Men and Gender-Diverse Individuals: A Collaborative Multidisciplinary Team Approach.

BACKGROUND: Little is documented about the experiences of pregnancy for transgender and gender-diverse individuals. There is scant clinical guidance for providing prepregnancy, prenatal, intrapartum, and postpartum care to transgender and gender-diverse people who desire pregnancy. CASE: Our team provided perinatal care to a 20-year-old transgender man, which prompted collaborative advocacy for health care systems change to create gender-affirming patient experiences in the perinatal health care setting. CONCLUSION: Systems-level and interpersonal-level interventions were adopted to create gender-affirming and inclusive care in and around pregnancy. Basic practices to mitigate stigma and promote gender-affirming care include staff trainings and query and use of appropriate name and pronouns in patient interactions and medical documentation. Various factors are important to consider regarding testosterone therapy for transgender individuals desiring pregnancy.

[The relationship between inflammatory and immunological processes during pregnancy. Practical aspects]. / A gyulladásos és immunológiai folyamatok kapcsolata a várandósság alatt. Gyakorlati vonatkozások.

The aim of this review is to explore, in addition to revealing the biological background, new conceptual and therapeutic approaches for reproductive clinicians to provide better and more effective care for sterile and infertile couples. In humans, 75% of unsuccessful pregnancies are the result of failures of implantation, and implantation failure is the limiting factor for in vitro fertilization treatment. A modified "good" inflammation is necessary for implantation and parturition, but for most of pregnancy, inflammation threatens the continuation of pregnancy. During this period, maintaining the non-inflammatory condition is extremely important, enabling the maternal epigenetic effects to occur in the fetus, making it possible for the offspring to adapt as much as possible to the extrauterine life. In the maintenance of the non-inflammatory condition of pregnancy, a large amount of progesterone hormone produced by the placenta (after the luteo-placental shift) plays a crucial role. It has been reported that the role of inflammation during implantation is an ancestral response to the embryo as a foreign body. During normal pregnancy, this inflammation is initiated by the trophoblast and involves the suppression of neutrophil infiltration, the recruitment of natural killer cells to the site of implantation as well as the production of a range of proinflammatory cytokines. During the "implantation window", the uterus is primed to produce several inflammatory signals such as prostaglandin E2 and a range of proinflammatory cytokines, including TNF, IL6 and IFNγ. The feto-placental unit is a semi-foreign graft called a "semi allograft", and the recognition of pregnancy by the mother (host) and the resulting maternal immune tolerance is an essential part of successful pregnancy and the birth of a healthy fetus. Because of the functional or absolute reduction of circulating progesterone (due to the decreasing hormone production of the physiologically "aging" placenta after around the 36th week of pregnancy) progesterone effects become insufficient. Therefore it is unable to suppress the production of IL8 and other inflammatory cytokines and the term inflammation, leading to cervical ripening, uterus contractions and parturition ("good" inflammation). Orv Hetil. 2019; 160(32): 1247-1259.

New perspective on conceptus estrogens in maternal recognition and pregnancy establishment in the pig†.

The proposed signal for maternal recognition of pregnancy in pigs is estrogen (E2), produced by the elongating conceptuses between days 11 to 12 of pregnancy with a more sustained increase during conceptus attachment and placental development on days 15 to 30. To understand the role of E2 in porcine conceptus elongation and pregnancy establishment, a loss-of-function study was conducted by editing aromatase (CYP19A1) using CRISPR/Cas9 technology. Wild-type (CYP19A1+/+) and (CYP19A1-/-) fibroblast cells were used to create embryos through somatic cell nuclear transfer, which were transferred into recipient gilts. Elongated and attaching conceptuses were recovered from gilts containing CYP19A1+/+ or CYP19A1-/- embryos on day 14 and 17 of pregnancy. Total E2 in the uterine flushings of gilts with CYP19A1-/- embryos was lower than recipients containing CYP19A1+/+ embryos with no difference in testosterone, PGF2α, or PGE2 on either day 14 or 17. Despite the loss of conceptus E2 production, CYP19A1-/- conceptuses were capable of maintaining the corpora lutea. However, gilts gestating CYP19A1-/- embryos aborted between days 27 and 31 of gestation. Attempts to rescue the pregnancy of CYP19A1-/- gestating gilts with exogenous E2 failed to maintain pregnancy. However, CYP19A1-/- embryos could be rescued when co-transferred with embryos derived by in vitro fertilization. Endometrial transcriptome analysis revealed that ablation of conceptus E2 resulted in disruption of a number biological pathways. Results demonstrate that intrinsic E2 conceptus production is not essential for pre-implantation development, conceptus elongation, and early CL maintenance, but is essential for maintenance of pregnancy beyond 30 days .

Bone-marrow-derived endothelial progenitor cells contribute to vasculogenesis of pregnant mouse uterus†.

Angiogenesis is essential for cyclic endometrial growth, implantation, and pregnancy maintenance. Vasculogenesis, the formation of new blood vessels by bone marrow (BM)-derived endothelial progenitor cells (EPCs), has been shown to contribute to endometrial vasculature. However, it is unknown whether vasculogenesis occurs in neovascularization of the decidua during pregnancy. To investigate the contribution of BM-derived EPCs to vascularization of the pregnant uterus, we induced non-gonadotoxic submyeloablation by 5-fluorouracil administration to wild-type FVB/N female mice recipients followed by BM transplantation from transgenic mice expressing green fluorescent protein (GFP) under regulation of Tie2 endothelial-specific promoter. Following 1 month, Tie2-GFP BM-transplanted mice were bred and sacrificed at various gestational days (ED6.5, ED10.5, ED13.5, ED18.5, and postpartum). Bone-marrow-transplanted non-pregnant and saline-injected pregnant mice served as controls (n = 5-6/group). Implantation sites were analyzed by flow cytometry, immunohistochemistry, and immunofluorescence. While no GFP-positive EPCs were found in non-pregnant or early pregnant uteri of BM-transplanted mice, GFP-positive EPCs were first detected in pregnant uterus on ED10.5 (0.12%) and increased as the pregnancy progressed (1.14% on ED13.5), peaking on ED18.5 (1.42%) followed by decrease in the postpartum (0.9%). The percentage of endothelial cells that were BM-derived out of the total endothelial cell population in the implantation sites (GFP+CD31+/CD31+) were 9.3%, 15.8%, and 6.1% on ED13.5, ED18.5, and postpartum, respectively. Immunohistochemistry demonstrated that EPCs incorporated into decidual vasculature, and immunofluorescence showed that GFP-positive EPCs colocalized with CD31 in vascular endothelium of uterine implantation sites, confirming their endothelial lineage. Our findings indicate that BM-derived EPCs contribute to vasculogenesis of the pregnant mouse decidua.

Preparing for childbirth: women's look

Introduction: Childbirth preparation is a form of health intervention education per-formed by specialist nurses in maternal health and obstetrics aimed at promoting self-efficacy during labour. In planning an efficient childbirth education intervention, it is essential that nurses know the pregnant women's/couple's expectations on this specific issue. Objectives: To understand the pregnant women's expectations related to preparation for childbirth. Material and Methods: This was an exploratory, transversal study of qualitative nature where data was collected through interviews, after an informed consent was signed. The Bardin technique was applied to data analysis. A non-probability sample of 224 pregnant women was made, all over 20 years of age, with 28 weeks or more of gestation. The majority of participants possessed an advanced degree, were married or living in a marital situation, and were experiencing their first pregnancy. Results: From an analysis of the interviews, three categories emerged: knowledge, ability, and self-efficacy to deal with labour, and seven subcategories. These results corroborate findings of other researchers who have concluded that couples wish to be informed regarding how to prepare for labour, and that this preparation is relevant when the acquired knowledge helps the pregnant woman or couple make decisions and exercise control over their labour experience. Conclusion: The results enabled nurse-midwives to increase their knowledge and understanding of pregnant women's labour preparation expectations and preferences. Knowledge of this variety can assist these professionals in planning effective, quality interventions, which in turn can clearly contribute to gains in health

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Control prenatal del embarazo normal / Prenatal control of normal pregnancy

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Mechanisms for the establishment and maintenance of pregnancy: synergies from scientific collaborations.

Research on the functions of interferon tau (IFNT) led to the theory of pregnancy recognition signaling in ruminant species. But IFNT does much more as it induces expression of interferon regulatory factor 2 (IRF2) in uterine luminal (LE), superficial glandular (sGE), but not glandular (GE) epithelia. First, IRF2 silences transcription of the estrogen receptor alpha gene and, indirectly, transcription of the oxytocin receptor gene to abrogate development of the luteolytic mechanism to prevent regression of the corpus luteum and its production of progesterone for establishing and maintaining pregnancy. Second, IRF2 silences expression of classical interferon-stimulated genes in uterine LE and sGE; however, uterine LE and sGE respond to progesterone (P4) and IFNT to increase expression of genes for transport of nutrients into the uterine lumen such as amino acids and glucose. Other genes expressed by uterine LE and sGE encode for adhesion molecules such as galectin 15, cathepsins, and cystatins for tissue remodeling, and hypoxia-inducible factor relevant to angiogenesis and survival of blastocysts in a hypoxic environment. IFNT is also key to a servomechanism that allows uterine epithelia, particularly GE, to proliferate and to express genes in response to placental lactogen and placental growth hormone in sheep. The roles of secreted phosphoprotein 1 are also discussed regarding its role in implantation in sheep and pigs, as well as its stimulation of expression of mechanistic target of rapamycin mRNA and protein which is central to proliferation, migration, and gene expression in the trophectoderm cells.

Influencia del apoyo psicológico grupal en la calidad de vida, continuidad y tasas de embarazo, en tratamientos de fecundación in Vitro / The influence of group psychological support on quality of life, discontinuation and pregnancy rates in In vitro fertilization treatments

Pregunta del estudio. ¿La intervención psicológica grupal antes y durante los ciclos de Fecundación in vitro (FIV), es una herramienta eficaz para mejorar la calidad de vida, la continuidad y las tasas de embarazo? Resumen. Las mujeres que participan en un grupo de apoyo psicológico logran una mejor gestión de sus emociones durante los tratamientos, aumentando la tolerabilidad y continuidad frente a los mismos. Así mismo los grupos de apoyo han logrado una influencia positiva en las tasas de embarazo. Lo que ya se conoce. Los tratamientos de Reproducción Asistida afectan negativamente en la calidad de vida de las pacientes en general. El motivo principal de abandono de los tratamientos es el estrés, la afectación en la pareja, y los síntomas de ansiedad y depresión. Por otra parte, las modalidades de intervención psicológica grupal han logrado influir positivamente tanto en el estado emocional como en las tasas de embarazo. Diseño del estudio, tamaño y duración. Estudio de cohorte, prospectivo, 95 mujeres que inician un ciclo de Fecundación Asistida en una clínica privada de la ciudad de Sevilla (España). El proyecto se diseñó en dos etapas. 1ª Etapa: Primer ciclo de fecundación asistida, F1: inicio, F2: final. 2ª Etapa: transferencia de los embriones congelados o nuevo ciclo para aquellas mujeres que no lograron el embarazo en el primer ciclo, F3: inicio, F4: final. El estudio se llevó a cabo desde agosto 2012 hasta agosto 2013. Participantes/materiales, composición y métodos. Mujeres entre 25 y 40 años, que inician un ciclo de FIV. Las pacientes fueron captadas principalmente por vía telefónica; siendo asignadas al grupo control (CG) o al grupo de apoyo (SG). La totalidad de la muestra cumplimentó el Cuestionario de Calidad de Vida en Fertilidad (FertiQol), en el inicio (F1/F3) y tras finalización de cada ciclo realizado o transferencia de embriones congelados (F2/F4). El seguimiento se realizó durante un año y/o dos intentos. Las mujeres del SG participaron durante el primer ciclo en un Programa de Apoyo psicológico realizado en 8 sesiones grupales, de frecuencia semanal cuyo objetivo fue el ajuste emocional, la adopción de recursos adaptativos y de afrontamiento y técnicas de relajación para reducir el estrés durante el tratamiento. Resultados principales. No existen diferencias significativas entre las mujeres participantes de este estudio en cuanto a la edad o en las variables clínicas. Las mujeres del CG tienen un mayor porcentaje de tasas de abandono que las mujeres que recibieron el programa de intervención psicológica, 38 % vs. 8 %, p=0,046. La calidad de vida intergrupal al comienzo del ciclo revela diferencias estadísticamente significativas en el Core FertiQol y en cada una de las subescalas (p=0,001), obteniendo el CG valores más elevados en su calidad de vida inicial. La variación en la calidad de vida durante el transcurso del primer ciclo (F1 vs. F2), en el SG evidencia una tendencia en aumento, presentando diferencias significativas en Core FertiQol y las subescalas Emocional y Mente/Cuerpo, p=0,032, p=0,005, p=0,039, respectivamente. En tanto que en el CG se observa una tendencia a la disminución en Core Fertiqol y en cada una de las cuatro subescalas. En cuanto a la Calidad del Cuidado se observa una tendencia al aumento para el SG en el Módulo de Tratamiento (Treatment FertiQol) y la subescala Entorno con una diferencia significativa en Tolerabilidad, (p=0,001.). La tasa de embarazo logrado para el SG asciende al 64 % mientras que la tasa de embarazo logrado para el CG asciende al 48 % (p=0,668). En la primer fase del estudio las pacientes del SG presentaron tasas superiores de embarazo con respecto al CG, 48 % vs 38 % (p=0,793). La misma tendencia se observa en la segunda fase, 35 % vs. 22 % respectivamente. Limitaciones. Dadas las condiciones del estudio (ajuste temporal y sesiones grupales semanales) la asignación a un grupo u otro fue a voluntad de las participantes. Por esta misma razón la muestra se limitó a 95 mujeres, siendo de interés que futuros estudios puedan extender nuestros resultados a una población mayor. Implicaciones del hallazgo. El Cuestionario FertiQol es un cuestionario validado internacionalmente y sus resultados se pueden analizar en una perspectiva amplia e internacional. Observamos que el apoyo psico-emocional puede mejorar la calidad de vida antes y durante los tratamientos de Fecundación Asistida y disminuir a su vez las tasas de abandono. Financiación del estudio/conflicto de intereses. Este trabajo fue apoyado por Fundación Ginemed en su interés por mejorar la calidad asistencial de sus centros. No hay conflictos de intereses

Study question: Is attending a psychological support group before and during an assisted in In Vitro Fertilization (IVF) treatment a useful tool in, improving quality of life, continued participation and pregnancy rates? Summary answer: Women who participate in a support group improve their quality of life, continue with their treatment and a higher percentage achieve a pregnancy. What is known already: Assisted reproduction treatments negatively affect patients´ quality of life. The principal cause of treatment discontinuation is stress, relational strain and symptoms associated with anxiety and depression. However, psychological intervention in the form of support groups has been demonstrated to have a positive influence on both emotional wellbeing as well as pregnancy rates. Study design, size, duration: Cohort Study, Pilot, 95 women who are beginning an assisted reproduction cycle in a private clinic in Seville (Spain). The project was designed in two stages. 1st Stage: first cycle of IVF (F1 start, F2: end). 2nd Stage: transfer frozen embryos transfer (FET) or new cycle of IVF, for women who failed pregnancy in the first cycle (F3: start, F4: end).The study was undertaken from August 2012 to August 2013. Participants/materials, setting, methods: Women between 25 and 40 years old, who are commencing an IVF cycle. The patients were primarily recruited by telephone; they were assigned to a control group (CG) or to a support group (SG) according to their availability. All of the members of the sample group completed the Fertility Quality of Life Questionnaire (FertiQol) at the beginning (F1/F3) and end of each cycle or frozen embryos transfer (F2/F4). The follow-up took place over a one-year period and/or two attempts. The women from the SG took part, during the first cycle, in a psychological support programme, which took the form of eight group sessions, which took place on a weekly basis and the emphasis of which was emotional well-being, the adoption of behaviour modification and coping strategies, and relaxation techniques aimed at stress reduction. Main results and the role of chance: The ages and clinical variables of the women who participated in the study did not differ significantly. The women from the CG ha a higher drop-out rate than those who took part in the psychological support programme, 38% vs. 8%, p=0.046. The between-group comparison from the initial Quality of Life assessment reveals statistically significant differences in the Core FertiQol and in each of the subscales (p=0.001), with the CG initially obtaining higher quality of life scores. The quality of life of the SG tended to increase over the course of the first cycle (F1 vs. F2), with significant differences being found in the Core FertiQol and in the Emotional and Mind-Body subscales, p=0.032, p=0.005, p=0.039, respectively. Equally, the scores in the Core FertiQol and the four subscales of the CG tended to decrease. In terms of Quality of Care, in the SG a tendency towards an increase is observed in the Treatment FertiQol and the Environment subscale with a significant difference visible in the Treatment Tolerability, p=0.001. This suggests that psychological support improves the patients´ ability to manage their emotions and affords a greater ability to tolerate the burden of the treatment on daily life. Core FertiQol and Total FertiQol for the second cycle IVF or FET reveal similar trends in both groups. In this second cycle or frozen embryo transfer, neither of the groups received psychological support. The total number of pregnancies from both attempts among the group of patients who received the eight psychological support sessions increases to 65%, while the women from the control group obtained a pregnancy rate of 48%, p=0.668. The patients from the SG also achieved superior pregnancy rates during the first fertility treatment in comparison to those from the CG, 49% vs. 39%, p=0.793. Limitations, reasons for caution: Given the conditions of the study (time constraints and weekly group sessions), the participants were able to decide whether they were assigned to one group or the other. The average quality of life from the initial questionnaire (FertiQol) of those who agreed to participate in the SG was significantly lower in comparison to those from the CG. These findings might lead us to believe that those women who perceive psychological distress are more receptive to receiving additional support. Nonetheless, later evaluations also indicate that those patients, who began with an optimal state of mind, experienced a fall in their quality of life during the treatment and had a higher discontinuation rate. Wider implications of the findings: Given that FertiQol is an internationally validated questionnaire, these results can be evaluated within a broad and international perspective. On the other hand, it is interesting to observe how patients, who are at a higher risk of emotional problems can benefit from psychological support, and how those patients who initially do not appear to be at risk of developing emotional problems, but are then unsuccessful in their treatment have high drop-out rates. This could indicate the importance of psychological-emotional support being integrated into assisted reproduction clinical practice. Study funding/competing interest: The Ginemed Foundation, in accordance with their objective to improve the quality of the care available in their centres, funded this study. There are no competing interests

Embryo-maternal communication during the first 4 weeks of equine pregnancy.

The first month of equine pregnancy covers a period of rapid growth and development, during which the single-cell zygote metamorphoses into an embryo with a functional circulation and precursors of many important organs, enclosed within extraembryonic membranes responsible for nutrient uptake and gaseous exchange. After exiting the oviduct, the conceptus must influence uterine physiology to ensure adequate nutrition and preparation for implantation, while continued development results in the chorioallantois superseding the yolk sac as the primary interface for maternal interaction and exchange. Throughout the first month, pregnancy maintenance depends absolutely on progesterone secreted by the primary corpus luteum. However, although extension of luteal life span via maternal recognition of pregnancy is clearly essential, it is still not known how the horse conceptus signals its presence. On the other hand, our understanding of how luteolytic prostaglandin F2α release from the endometrium is averted has improved, and we are increasingly aware of the biological and practical significance of various events characteristic of early horse pregnancy, such as selective oviductal transport, the formation and dissolution of the blastocyst capsule, and prolonged intrauterine conceptus migration. It is also increasingly clear that embryo-maternal dialog during the first month is essential not only to conceptus survival but also has more profound and long-lasting implications. In this latter respect, it is now accepted that the maternal environment (e.g., metabolic or health status) may epigenetically alter gene expression capacity of the developing embryo and thereby permanently influence the health of the resulting foal right through adulthood.

Hormonal Physiology of Childbearing, an Essential Framework for Maternal-Newborn Nursing.

Knowledge of the hormonal physiology of childbearing is foundational for all who care for childbearing women and newborns. When promoted, supported, and protected, innate, hormonally driven processes optimize labor and birth, maternal and newborn transitions, breastfeeding, and mother-infant attachment. Many common perinatal interventions can interfere with or limit hormonal processes and have other unintended effects. Such interventions should only be used when clearly indicated. High-quality care incorporates salutogenic nursing practices that support physiologic processes and maternal-newborn health.

Up-regulation of lymphocyte antigen 6 complex expression in side-population cells derived from a human trophoblast cell line HTR-8/SVneo.

The continual proliferation and differentiation of trophoblasts are critical for the maintenance of pregnancy. It is well known that the tissue stem cells are associated with the development of tissues and pathologies. It has been demonstrated that side-population (SP) cells identified by fluorescence-activated cell sorting (FACS) are enriched with stem cells. The SP cells in HTR-8/SVneo cells derived from human primary trophoblast cells were isolated by FACS. HTR-8/SVneo-SP cell cultures generated both SP and non-SP (NSP) subpopulations. In contrast, NSP cell cultures produced NSP cells and failed to produce SP cells. These SP cells showed self-renewal capability by serial colony-forming assay. Microarray expression analysis using a set of HTR-8/SVneo-SP and -NSP cells revealed that SP cells overexpressed several stemness genes including caudal type homeobox2 (CDX2) and bone morphogenic proteins (BMPs), and lymphocyte antigen 6 complex locus D (LY6D) gene was the most highly up-regulated in HTR-8/SVneo-SP cells. LY6D gene reduced its expression in the course of a 7-day cultivation in differentiation medium. SP cells tended to reduce its fraction by treatment of LY6D siRNA indicating that LY6D had potential to maintain cell proliferation of HTR-8/SVneo-SP cells. On ontology analysis, epithelial-mesenchymal transition (EMT) pathway was involved in the up-regulated genes on microarray analysis. HTR-SVneo-SP cells showed enhanced migration. This is the first report that LY6D was important for the maintenance of HTR-8/SVneo-SP cells. EMT was associated with the phenotype of these SP cells.

The childhood obesity epidemic as a result of nongenetic evolution: the maternal resources hypothesis.

Over the past century, socioenvironmental evolution (eg, reduced pathogenic load, decreased physical activity, and improved nutrition) led to cumulative increments in maternal energy resources (ie, body mass and adiposity) and decrements in energy expenditure and metabolic control. These decrements reduced the competition between maternal and fetal energy demands and increased the availability of energy substrates to the intrauterine milieu. This perturbation of mother-conceptus energy partitioning stimulated fetal pancreatic ß-cell and adipocyte hyperplasia, thereby inducing an enduring competitive dominance of adipocytes over other tissues in the acquisition and sequestering of nutrient energy via intensified insulin secretion and hyperplastic adiposity. At menarche, the competitive dominance of adipocytes was further amplified via hormone-induced adipocyte hyperplasia and weight-induced decrements in physical activity. These metabolic and behavioral effects were propagated progressively when obese, inactive, metabolically compromised women produced progressively larger, more inactive, metabolically compromised children. Consequently, the evolution of human energy metabolism was markedly altered. This phenotypic evolution was exacerbated by increments in the use of cesarean sections, which allowed both the larger fetuses and the metabolically compromised mothers who produced them to survive and reproduce. Thus, natural selection was iatrogenically rendered artificial selection, and the frequency of obese, inactive, metabolically compromised phenotypes increased in the global population. By the late 20th century, a metabolic tipping point was reached at which the postprandial insulin response was so intense, the relative number of adipocytes so large, and inactivity so pervasive that the competitive dominance of adipocytes in the sequestering of nutrient energy was inevitable and obesity was unavoidable.

Progesterone receptor signaling in the initiation of pregnancy and preservation of a healthy uterus.

Infertility and reproductive-associated disease are global problems in the world today affecting millions of women. A successful pregnancy requires a healthy uterus ready to receive and support an implanting embryo. As an endocrine organ, the uterus is dependent on the secretions of the ovarian hormones estrogen and progesterone which signal via their cognate receptors, the estrogen and progesterone receptors. The progesterone receptor not only functions using classical nuclear receptor signaling, but also participates in non-genomic signaling at the cellular membrane. The complexity of progesterone signaling is further enhanced by the existence of multiple isoforms and post-translational regulation via kinases and transcription coregulators. This dynamic means of regulation of the progesterone receptor is evidenced in its necessary role in a successful pregnancy. Within early pregnancy, the progesterone receptor elicits activation of its target genes in a spatiotemporal manner in order to allow for successful embryo attachment and uterine decidualization. Additionally, appropriate progesterone signaling is important for the prevention of uterine disease such as endometrial cancer, endometriosis, and leiomyoma. The utilization of progesterone receptor modulators in the treatment of these devastating uterine diseases is promising. This review presents a general overview of progesterone receptor structure, function, and regulation and highlights its important role in the establishment of pregnancy and as a therapeutic target in uterine disease.

Role of sulphate in development.

Sulphate contributes to numerous processes in mammalian physiology, particularly during development. Sulphotransferases mediate the sulphate conjugation (sulphonation) of numerous compounds, including steroids, glycosaminoglycans, proteins, neurotransmitters and xenobiotics, transforming their biological activities. Importantly, the ratio of sulphonated to unconjugated molecules plays a significant physiological role in many of the molecular events that regulate mammalian growth and development. In humans, the fetus is unable to generate its own sulphate and therefore relies on sulphate being supplied from maternal circulation via the placenta. To meet the gestational needs of the growing fetus, maternal blood sulphate concentrations double from mid-gestation. Maternal hyposulphataemia has been linked to fetal sulphate deficiency and late gestational fetal loss in mice. Disorders of sulphonation have also been linked to a number of developmental disorders in humans, including skeletal dysplasias and premature adrenarche. While recognised as an important nutrient in mammalian physiology, sulphate is largely unappreciated in clinical settings. In part, this may be due to technical challenges in measuring sulphate with standard pathology equipment and hence the limited findings of perturbed sulphate homoeostasis affecting human health. This review article is aimed at highlighting the importance of sulphate in mammalian development, with basic science research being translated through animal models and linkage to human disorders.