The placenta is an endocrine fetal organ, which secretes a plethora of steroid- and proteo-hormones, metabolic proteins, growth factors, and cytokines in order to adapt maternal physiology to pregnancy. Central to the growth of the fetus is the supply with nutrients, foremost with glucose. Therefore, during pregnancy, maternal insulin resistance arises, which elevates maternal blood glucose levels, and consequently ensures an adequate glucose supply for the developing fetus. At the same time, maternal β-cell mass and function increase to compensate for the higher insulin demand. These adaptations are also regulated by the endocrine function of the placenta. Excessive insulin resistance or the inability to increase insulin production accordingly disrupts physiological modulation of pregnancy mediated glucose metabolism and may cause maternal gestational diabetes (GDM). A growing body of evidence suggests that this adaptation of maternal glucose metabolism differs between pregnancies carrying a girl vs. pregnancies carrying a boy. Moreover, the risk of developing GDM differs depending on the sex of the fetus. Sex differences in placenta derived hormones and bioactive proteins, which adapt and modulate maternal glucose metabolism, are likely to contribute to this sexual dimorphism. This review provides an overview on the adaptation and maladaptation of maternal glucose metabolism by placenta-derived factors, and highlights sex differences in this regulatory network.

Preeclampsia is a frequent obstetric complication which affects the mother`s and the fetus’s health and can be life threatening. It also has an impact on psychological outcomes. There may be protective variables such as resilience shielding against psychosocial distress in women experiencing these pregnancy complications. The aim of this study was to examine differences in resilience in terms of quality of life, depression and post-traumatic stress symptoms in women after preeclampsia.

BACKGROUND: Preeclampsia is a severe hypertensive disorder in pregnancy that causes preterm delivery, maternal and fetal morbidity, mortality, and life-long sequelae. Understanding the pathogenesis of preeclampsia is a critical first step toward protecting mother and child from this syndrome and increased risk of cardiovascular disease later in life. However, effective early predictive tests and therapies for preeclampsia are scarce. METHODS: To identify novel markers and signaling pathways for early onset preeclampsia, we profiled human maternal-fetal interface units (fetal villi and maternal decidua) from early onset preeclampsia and healthy controls using single-nucleus RNA sequencing combined with spatial transcriptomics. The placental syncytiotrophoblast is in direct contact with maternal blood and forms the barrier between fetal and maternal circulation. RESULTS: We identified different transcriptomic states of the endocrine syncytiotrophoblast nuclei with patterns of dysregulation associated with a senescence-associated secretory phenotype and a spatial dysregulation of senescence in the placental trophoblast layer. Elevated senescence markers were validated in placental tissues of clinical multicenter cohorts. Importantly, several secreted senescence-associated secretory phenotype factors were elevated in maternal blood already in the first trimester. We verified the secreted senescence markers, PAI-1 (plasminogen activator inhibitor 1) and activin A, as identified in our single-nucleus RNA sequencing model as predictive markers before clinical preeclampsia diagnosis. CONCLUSIONS: This indicates that increased syncytiotrophoblast senescence appears weeks before clinical manifestation of early onset preeclampsia, suggesting that the dysregulated preeclamptic placenta starts with higher cell maturation resulting in premature and increased senescence-associated secretory phenotype release. These senescence-associated secretory phenotype markers may serve as an additional early diagnostic tool for this syndrome.

Background: Soluble FMS-like Tyrosine Kinase 1 (sFlt-1) and placental growth factor (PlGF) have been reported to be highly predictive several weeks before the onset of preeclampsia. Objective: To investigate longitudinal changes of serum levels sFlt-1 and PlGF in pregnant women at high risk for the development of preeclampsia and to reveal an impact of aspirin on maternal serum concentrations of sFlt-1 and PlGF. Methods: This was a prospective longitudinal study in 394 women with various risk factors for the development of preeclampsia (chronic hypertension, antiphospholipid syndrome/APS or systemic lupus erythematosus/SLE, thrombophilia, women with a history of preeclampsia, pathologic first trimester screening for preeclampsia) and 68 healthy women. Serum levels of sFlt-1 and PlGF were measured prospectively at 4-week intervals (from gestational weeks 12 until postpartum). Results: The sFlt-1/PlGF ratio was significantly higher in women with an adverse obstetric outcome compared to women with a normal pregnancy, starting between 20 and 24 weeks of gestation. There was no effect of aspirin on sFlt-1/PlGF ratio in women with chronic hypertension, APS/SLE, thrombophilia and controls. The use of aspirin showed a trend towards an improvement of the sFlt-1/PlGF ratio in women with preeclampsia in a previous pregnancy and a significant effect on the sFlt-1/PlGF ratio in women with a pathologic first trimester screening for preeclampsia. Conclusions: Our findings reveal an impact of aspirin on sFlt-1/PlGF ratio in women with a pathologic first trimester screening for preeclampsia, strongly supporting its prophylactic use.

Background/Objective: To examine maternal physical and mental health-related quality of life (HRQoL) and depression after early and late preterm and term births in the early postpartum period.Method: In a prospective pilot study, three groups of women whose newborns had to be treated in the neonatal ward during the immediate postpartum period were established and compared with each other: 20 women with extremely to very preterm birth, 20 with moderate to late preterm birth and 20 women with term birth. All participants completed the Short Form-12 Health Survey (SF-12) to measure HRQoL, and the Edinburgh Postnatal Depression Scale (EPDS) to detect depressive symptoms combined with independently developed questions to evaluate anxiety and psychological distress.Results: Maternal psychological HRQoL was significantly worse in the very preterm birth group compared to moderate to late preterm birth (p < 0.001) and full-term birth groups (p = 0.004). There were no differences between the birth groups in depressive symptoms (p = 0.083), anxiety (p = 0.238), perceived stress (p = 0.340) and the general psychological distress values (p = 0.755). In the EPDS, the depression screening instrument 30 to 65% were beyond the cut-off-value to detect major depression.Conclusions: During the early postpartum period, an extensive medical care focussing on acute stress, HRQoL parameters and depression may be a good step to improving maternal well-being.