RESUMO
Maternal metabolic adaptations during pregnancy ensure appropriate nutrient supply to the developing fetus. This is facilitated by reductions in maternal peripheral insulin sensitivity, which enables glucose to be available in the maternal circulation for transfer to the fetus for growth. To balance this process and avoid excessive hyperglycaemia and glucose intolerance in the mother during pregnancy, maternal pancreatic ß-cells undergo remarkable changes in their function including increasing their proliferation and glucose-stimulated insulin secretion. In this review we examine how placental and maternal hormones work cooperatively to activate several signalling pathways, transcription factors and epigenetic regulators to drive adaptations in ß-cell function during pregnancy. We also explore how adverse maternal environmental conditions, including malnutrition, obesity, circadian rhythm disruption and environmental pollutants, may impact the endocrine and molecular mechanisms controlling ß-cell adaptations during pregnancy. The available data from human and experimental animal studies highlight the need to better understand how maternal ß-cells integrate the various environmental, metabolic and endocrine cues and thereby determine appropriate ß-cell adaptation during gestation. In doing so, these studies may identify targetable pathways that could be used to prevent not only the development of pregnancy complications like gestational diabetes that impact maternal and fetal wellbeing, but also more generally the pathogenesis of other metabolic conditions like type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Gestacional/induzido quimicamente , Feminino , Feto/fisiologia , Glucose/metabolismo , Humanos , Placenta/metabolismo , GravidezRESUMO
Increased basal glucocorticoid secretion and a reduced glucocorticoid response during acute stress, despite only minor changes in the secretion of the major secretagogue adrenocorticotropic hormone (ACTH), have been documented in the peripartum period in several species. We recently showed that the adrenal gland, the site of glucocorticoid synthesis, undergoes substantial postpartum-associated plasticity in the rat at mid-lactation. Here, we asked the question whether adrenal changes already take place around parturition in the rat and in another species, namely the mouse. After demonstrating that several components of the adrenal machinery mediating cholesterol supply for steroidogenesis, including protein levels of hormone-sensitive lipase, low-density lipoprotein receptor (LDLR) and scavenger receptor class-B type-1 (SRB1), are upregulated, while hydroxymethylglutaryl coenzyme A reductase (HMGCR) is downregulated in the lactating rat one day after delivery, as previously observed at mid-lactation, we demonstrated profound changes in the mouse. In detail, protein expression of LDLR, SRB1, HMGCR and adrenal lipid store density were increased in the mouse adrenal one day after parturition as tested via western blot analysis and oil-red lipid staining, respectively. Moreover, using in vitro culture techniques, we observed that isolated adrenal explants from lactating mice secreted higher levels of corticosterone under basal conditions, but showed impaired responsiveness to ACTH, mimicking the in vivo scenario. These results suggest that mechanisms of adaptation in the maternal adrenal after delivery, namely increased cholesterol availability and decreased ACTH sensitivity, are crucial for the basal increase in circulating glucocorticoids and maternal stress hyporesponsiveness that are typical of this period.
Assuntos
Glândulas Suprarrenais/metabolismo , Corticosterona/metabolismo , Lactação/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Animais , Colesterol/metabolismo , Feminino , Hidroximetilglutaril-CoA Redutases/metabolismo , Camundongos , Fosfoproteínas/metabolismo , Período Pós-Parto/metabolismo , Ratos , Receptores da Corticotropina/metabolismo , Receptores de LDL/metabolismo , Receptores Depuradores Classe B/metabolismo , Esterol Esterase/metabolismoRESUMO
OBJECTIVE: The objective of the study was to define maternal tissue adaptations in pregnancy associated with uncomplicated spontaneous vaginal delivery using anatomical and biological outcomes. STUDY DESIGN: Nulliparous gravidas were prospectively enrolled in the first trimester at 2 institutions. Demographic and delivery data were chart abstracted. Vaginal elastase activity (units per milligram of protein) and Pelvic Organ Prolapse Quantification measurements of pelvic organ support were obtained in the first and third trimesters. A subset underwent 3-dimensional ultrasound measures of levator hiatus. Uncomplicated spontaneous vaginal delivery (VD) was defined as no cesarean, forceps, vacuum, shoulder dystocia, third- or fourth-degree perineal laceration, or prolonged second stage labor. RESULTS: We enrolled 173 women in their first trimester, 50 of whom had ultrasounds. Mean age was 25.5 ± 5.5 years with a body mass index of 28.0 ± 7.3 kg/m(2). Sixty-seven percent were white/Caucasian, 27% black/African American, and 6% Hispanic/Latina. Mean delivery gestational age was 38.5 ± 2.9 weeks, with 23% delivering by cesarean and 59% achieving uncomplicated spontaneous VD. Vaginal support changed significantly over trimesters with posterior vaginal and hiatal relaxation, vaginal lengthening, and increased levator hiatus area during strain. Women achieving uncomplicated spontaneous VD demonstrated significantly greater relaxation on third-trimester Pelvic Organ Prolapse Quantification for anterior, apical, and hiatal measures than those without uncomplicated spontaneous VD. Higher first-trimester vaginal elastase activity was strongly associated with uncomplicated spontaneous VD (geometric mean activity 0.289 ± 0.830 U/mg vs -0.029 ± 0.585 U/mg, P = .009). Higher first-trimester elastase, younger age, lower first-trimester body mass index, and more third-trimester vaginal support laxity in points C and GH were predictive of VD success. CONCLUSION: Significant maternal adaptations occur in the vagina during pregnancy, presumably in preparation for vaginal delivery. Greater adaptation, including vaginal descent and higher first-trimester elastase activity, is associated with an increased likelihood of uncomplicated spontaneous VD.
Assuntos
Adaptação Fisiológica/fisiologia , Parto Obstétrico/estatística & dados numéricos , Parto/fisiologia , Diafragma da Pelve/fisiologia , Gravidez/fisiologia , Vagina/fisiologia , Adulto , Cesárea/estatística & dados numéricos , Extração Obstétrica/estatística & dados numéricos , Feminino , Humanos , Imageamento Tridimensional , Elastase Pancreática/metabolismo , Diafragma da Pelve/diagnóstico por imagem , Primeiro Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Estudos Prospectivos , Ultrassonografia , Vagina/diagnóstico por imagem , Vagina/metabolismo , Adulto JovemRESUMO
During pregnancy, the mother must adapt her body systems to support nutrient and oxygen supply for growth of the baby in utero and during the subsequent lactation. These include changes in the cardiovascular, pulmonary, immune and metabolic systems of the mother. Failure to appropriately adjust maternal physiology to the pregnant state may result in pregnancy complications, including gestational diabetes and abnormal birth weight, which can further lead to a range of medically significant complications for the mother and baby. The placenta, which forms the functional interface separating the maternal and fetal circulations, is important for mediating adaptations in maternal physiology. It secretes a plethora of hormones into the maternal circulation which modulate her physiology and transfers the oxygen and nutrients available to the fetus for growth. Among these placental hormones, the prolactin-growth hormone family, steroids and neuropeptides play critical roles in driving maternal physiological adaptations during pregnancy. This review examines the changes that occur in maternal physiology in response to pregnancy and the significance of placental hormone production in mediating such changes.