The uterine secretome initiates growth of gynecologic tissues in ectopic locations.

Endosalpingiosis (ES) and endometriosis (EM) refer to the growth of tubal and endometrial epithelium respectively, outside of their site of origin. We hypothesize that uterine secretome factors drive ectopic growth. To test this, we developed a mouse model of ES and EM using tdTomato (tdT) transgenic fluorescent mice as donors.

Gestational diabetes augments group B Streptococcus infection by disrupting maternal immunity and the vaginal microbiota.

Group B Streptococcus (GBS) is a pervasive perinatal pathogen, yet factors driving GBS dissemination in utero are poorly defined. Gestational diabetes mellitus (GDM), a complication marked by dysregulated immunity and maternal microbial dysbiosis, increases risk for GBS perinatal disease. Using a murine GDM model of GBS colonization and perinatal transmission, we find that GDM mice display greater GBS in utero dissemination and subsequently worse neonatal outcomes.

Role of adrenomedullin2/ intermedin in pregnancy induced vascular and metabolic adaptation in mice.

Adrenomedullin2 (AM2) shares its receptor with Calcitonin gene related peptide and adrenomedullin with overlapping but distinct biological functions. Goal of this study was to assess the specific role of Adrenomedullin2 (AM2) in pregnancy induced vascular and metabolic adaptation using AM2 knockout mice ( ). The mice were successfully generated using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Nuclease Cas nine system.

A novel model of gestational diabetes: Acute high fat high sugar diet results in insulin resistance and beta cell dysfunction during pregnancy in mice.

Gestational diabetes mellitus (GDM) affects 7-18% of all pregnancies. Despite its high prevalence, there is no widely accepted animal model. To address this, we recently developed a mouse model of GDM.

Conditional knockout of leptin receptor in the female reproductive tract reduces fertility due to parturition defects in mice.

Leptin is required for fertility, including initiation of estrous cycles. It is therefore challenging to assess the role of leptin signaling during pregnancy. Although neuron-specific transgene approaches suggest that leptin signaling in the central nervous system is most important, experiments with pharmacologic inhibition of leptin in the uterus or global replacement of leptin during pregnancy suggest leptin signaling in the reproductive tract may be required.

Adrenomedullin and its receptors are expressed in mouse pancreatic β-cells and suppresses insulin synthesis and secretion.

Gestational diabetes mellitus (GDM) is associated with defective pancreatic β-cell adaptation in pregnancy, but the underlying mechanism remains obscure. Our previous studies demonstrated that GDM women display increased plasma adrenomedullin (ADM) levels, and non-obese GDM mice show decreased serum concentrations of insulin and the number of β-cells in pancreas islets. The aims of this study is to examine if ADM and its receptors are expressed in female mouse pancreas, and if so, whether insulin secretion is regulated by ADM in mouse β-cell line, NIT-1 cells and isolated mouse pancreatic islets.

Brief high fat high sugar diet results in altered energy and fat metabolism during pregnancy in mice.

During pregnancy several maternal adaptations occur in order to support the growing fetus which are further exacerbated by gestational diabetes mellitus (GDM). Previously we developed a mouse model of GDM, however we did not evaluate alterations to energy and fat metabolism. We have also shown that alterations in lipid metabolism are mediated by adrenomedullin (ADM) in normal and GDM pregnancies.

Transcription Factor PLAGL1 Is Associated with Angiogenic Gene Expression in the Placenta.

During pregnancy, the placenta is important for transporting nutrients and waste between the maternal and fetal blood supply, secreting hormones, and serving as a protective barrier. To better understand placental development, we must understand how placental gene expression is regulated. We used RNA-seq data and ChIP-seq data for the enhancer associated mark, H3k27ac, to study gene regulation in the mouse placenta at embryonic day (e) 9.

Changes in excitability and ion channel expression in neurons of the major pelvic ganglion in female type II diabetic mice.

Bladder cystopathy and autonomic dysfunction are common complications of diabetes, and have been associated with changes in ganglionic transmission and some measures of neuronal excitability in male mice. To determine whether type II diabetes also impacts excitability of ganglionic neurons in females, we investigated neuronal excitability and firing properties, as well as underlying ion channel expression, in major pelvic ganglion (MPG) neurons in control, 10-week, and 21-week Lepr mice. Type II diabetes in Lepr animals caused a non-linear change in excitability and firing properties of MPG neurons.

Impact of adrenomedullin blockage on lipid metabolism in female mice exposed to high-fat diet.

Purpose: Adrenomedullin (ADM) levels are elevated in gestational and type 2 diabetic patients. ADM also stimulates lipolysis in vitro. Disturbed lipid metabolism has been implicated in the pathogenesis of diabetes.

In Utero and Postnatal Exposure to High Fat, High Sucrose Diet Suppressed Testis Apoptosis and Reduced Sperm Count.

Obesity affects male fertility and maternal diabetes affects the offspring sperm epigenome. However, the effects of in utero exposure to maternal glucose intolerance in combination with postnatal high fat, high sucrose (HFHS) diet consumption on offspring spermatogenesis is not clear. The present study was designed to test these effects.

Effects of acute exposure to a high-fat, high-sucrose diet on gestational glucose tolerance and subsequent maternal health in mice.

Gestational diabetes mellitus (GDM) is a common obstetric complication. Half of women who have GDM will go on to develop type 2 diabetes. Understanding the mechanisms by which this occurs requires an animal model of GDM without ongoing diabetes at conception.

Maternal Hyperleptinemia Is Associated with Male Offspring's Altered Vascular Function and Structure in Mice.

Children of mothers with gestational diabetes have greater risk of developing hypertension but little is known about the mechanisms by which this occurs. The objective of this study was to test the hypothesis that high maternal concentrations of leptin during pregnancy, which are present in mothers with gestational diabetes and/or obesity, alter blood pressure, vascular structure and vascular function in offspring. Wildtype (WT) offspring of hyperleptinemic, normoglycemic, Leprdb/+ dams were compared to genotype matched offspring of WT-control dams.

Maternal Hyperleptinemia Improves Offspring Insulin Sensitivity in Mice.

Maternal obesity and gestational diabetes are prevalent worldwide. Offspring of mothers with these conditions weigh more and are predisposed to metabolic syndrome. A hallmark of both conditions is maternal hyperleptinemia, but the role of elevated leptin levels during pregnancy on developmental programming is largely unknown.

Hyperleptinemia During Pregnancy Decreases Adult Weight of Offspring and Is Associated With Increased Offspring Locomotor Activity in Mice.

Pregnant women who are obese or have gestational diabetes mellitus have elevated leptin levels and their children have an increased risk for child and adult obesity. The goals of this study were to determine whether offspring weights are altered by maternal hyperleptinemia, and whether this occurs via behavioral changes that influence energy balance. We used 2 hyperleptinemic mouse models.

Placental changes caused by food restriction during early pregnancy in mice are reversible.

In a previous study, 50% calorie restriction in mice from d1.5 to 11.5 of pregnancy resulted in reduced placental weights and areas,relative sparing of labyrinth zone area compared to junctional zone area, and dramatic changes in global gene expression profiles.

Maternal exposure to bisphenol A and genistein has minimal effect on A(vy)/a offspring coat color but favors birth of agouti over nonagouti mice.

Reports that maternal diet influences coat color in mouse offspring carrying the agouti A(vy) allele have received considerable attention because the range, from pseudoagouti (brown) to yellow, predicts adult health outcomes, especially disposition toward obesity and diabetes, in yellower mice. Bisphenol A (BPA), an endocrine-disrupting compound with estrogenic properties, fed to a/a dams harboring A(vy)/a conceptuses has been reported to induce a significant shift toward yellower mice, whereas consumption of either genistein (G) alone or in combination with BPA led to greater numbers of healthy, brown offspring. Groups of C57/B6 a/a females, which are nonagouti, were fed either a phytoestrogen-free control diet or one of six experimental diets: diets 1-3 contained BPA (50 mg, 5 mg, and 50 μg BPA/kg food, respectively); diet 4 contained G (250 mg/kg food); diet 5 contained G plus BPA (250 and 50 mg/kg food, respectively); and diet 6 contained 0.

Leptin and the placental response to maternal food restriction during early pregnancy in mice.

Several studies have demonstrated that maternal undernutrition or overnutrition during pregnancy can have negative consequences for the health of children born to these pregnancies, but the physiological mechanisms by which this occurs are not completely understood. During periods of food restriction, concentrations of leptin decline, whereas leptin is elevated in obesity, suggesting that it may play a role in the response to altered nutrition during pregnancy. This study compares placental development and global placental gene expression profiles at Day 11.

Effect of food restriction and leptin supplementation on fetal programming in mice.

Metabolic disease is a significant global health and economic problem. In a phenomenon referred to as fetal programming, offspring of underweight or overweight mothers have an increased incidence of adulthood obesity and metabolic disease. Undernourished individuals have decreased levels of leptin, a regulator of energy balance, whereas obese people develop hyperleptinemia and leptin resistance.

The expression and potential function of bone morphogenetic proteins 2 and 4 in bovine trophectoderm.

Background: Bone morphogenetic proteins (BMPs) were first described for their roles in bone formation, but they now also are known to possess additional activities, including those relating to embryogenesis. The objectives of this work were to 1) determine if peri-attachment bovine conceptuses and bovine trophoblast cells (CT1) contain transcripts for BMP2 and 4, an innate inhibitor noggin (NOG), and BMP2/4 receptors (BMPRII, ACVR1, BMPR1A, BMPR1B), and 2) determine if BMP2 or 4 supplementation to CT1 cells affects cell proliferation, differentiation or trophoblast-specific gene expression.

Methods: RNA was isolated from day 17 bovine conceptuses and CT1 cells.

Isolation of primary mouse trophoblast cells and trophoblast invasion assay.

The placenta is responsible for the transport of nutrients, gasses and growth factors to the fetus, as well as the elimination of wastes. Thus, defects in placental development have important consequences for the fetus and mother, and are a major cause of embryonic lethality. The major cell type of the fetal portion of the placenta is the trophoblast.

Preeclampsia: multiple approaches for a multifactorial disease.

Preeclampsia is a pregnancy-specific disorder characterized by hypertension and excess protein excretion in the urine. It is an important cause of maternal and fetal morbidity and mortality worldwide. The disease is almost exclusive to humans and delivery of the pregnancy continues to be the only effective treatment.

Consequences of conceptus exposure to colony-stimulating factor 2 on survival, elongation, interferon-τ secretion, and gene expression.

Exposure of bovine conceptuses to colony-stimulating factor 2 (CSF2) from days 5 to 7 of development can increase the percentage of transferred conceptuses that develop to term. The purpose of this experiment was to understand the mechanism by which CSF2 increases embryonic and fetal survival. Conceptuses were produced in vitro in the presence or absence of 10  ng/ml CSF2 from days 5 to 7 after insemination, transferred into cows, and flushed from the uterus at day 15 of pregnancy.

Several fibroblast growth factors are expressed during pre-attachment bovine conceptus development and regulate interferon-tau expression from trophectoderm.

The trophectoderm-derived factor interferon tau (IFNT) maintains the uterus in a pregnancy-receptive state in cattle and sheep. Fibroblast growth factors (FGFs) are implicated in regulating IFNT expression and potentially other critical events associated with early conceptus development in cattle. The overall objectives of this work were to identify the various FGFs and FGF receptors (FGFRs) expressed in elongating pre-attachment bovine conceptuses and determine if these FGFs regulate conceptus development and/or mediate IFNT production.