Gestational hypoxia modulates expression of corticotropin-releasing hormone and arginine vasopressin in the paraventricular nucleus in the ovine fetus

Myers, Dean A.; Singleton, Krista; Kenkel, Christy; Kaushal, Kanchan M.; Ducsay, Charles A.

doi:10.14814/phy2.12643

Cited by 7 publications

(5 citation statements)

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“…Image analysis was performed using NIH ImageJ (Wayne Rasband, NIH) based in part on our published methods for quantification of neuronal numbers and structural volume in the CNS ([75, 76]). Original ICC or IF images were deconvoluted using ImageJ to separate individual colors (Red, green, blue) using identical parameters for each section (minimum, maximum, brightness), then for each color, converted to 16 bit greyscale images.…”

Section: Methodsmentioning

confidence: 99%

Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon

et al. 2019

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Zika virus (ZIKV) infection during pregnancy in humans is associated with an increased incidence of congenital anomalies including microcephaly as well as fetal death and miscarriage and collectively has been referred to as Congenital Zika Syndrome (CZS). Animal models for ZIKV infection in pregnancy have been developed including mice and non-human primates (NHPs). In macaques, fetal CZS outcomes from maternal ZIKV infection range from none to significant. In the present study we develop the olive baboon (Papio anubis), as a model for vertical transfer of ZIKV during pregnancy. Four mid-gestation, timed-pregnant baboons were inoculated with the French Polynesian ZIKV isolate (104 ffu). This study specifically focused on the acute phase of vertical transfer. Dams were terminated at 7 days post infection (dpi; n = 1), 14 dpi (n = 2) and 21 dpi (n = 1). All dams exhibited mild to moderate rash and conjunctivitis. Viremia peaked at 5–7 dpi with only one of three dams remaining mildly viremic at 14 dpi. An anti-ZIKV IgM response was observed by 14 dpi in all three dams studied to this stage, and two dams developed a neutralizing IgG response by either 14 dpi or 21 dpi, the latter included transfer of the IgG to the fetus (cord blood). A systemic inflammatory response (increased IL2, IL6, IL7, IL15, IL16) was observed in three of four dams. Vertical transfer of ZIKV to the placenta was observed in three pregnancies (n = 2 at 14 dpi and n = 1 at 21 dpi) and ZIKV was detected in fetal tissues in two pregnancies: one associated with fetal death at ~14 dpi, and the other in a viable fetus at 21 dpi. ZIKV RNA was detected in the fetal cerebral cortex and other tissues of both of these fetuses. In the fetus studied at 21 dpi with vertical transfer of virus to the CNS, the frontal cerebral cortex exhibited notable defects in radial glia, radial glial fibers, disorganized migration of immature neurons to the cortical layers, and signs of pathology in immature oligodendrocytes. In addition, indices of pronounced neuroinflammation were observed including astrogliosis, increased microglia and IL6 expression. Of interest, in one fetus examined at 14 dpi without detection of ZIKV RNA in brain and other fetal tissues, increased neuroinflammation (IL6 and microglia) was observed in the cortex. Although the placenta of the 14 dpi dam with fetal death showed considerable pathology, only minor pathology was noted in the other three placentas. ZIKV was detected immunohistochemically in two placentas (14 dpi) and one placenta at 21 dpi but not at 7 dpi. This is the first study to examine the early events of vertical transfer of ZIKV in a NHP infected at mid-gestation. The baboon thus represents an additional NHP as a model for ZIKV induced brain pathologies to contrast and compare to humans as well as other NHPs.

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Section: Methodsmentioning

confidence: 99%

Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon

et al. 2019

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“…The animals are at altitude from~40 days of gestational age (dGA) onward resulting in a maintained fetal PO 2 of 18 mmHg (normal~23-25 mmHg) at~140 dGA (term 148 dGA) (1,235,707). In marked contrast to this activational function of acute or prolonged hypoxia when initiated during the final third of gestation, the HPA axis of the fetus adapts divergently when development occurs under conditions of LTH from day 40 of gestation onward (235,709,712). Indeed, LTH fetal sheep do not deliver early and are not growth restricted, reflective of the ability to maintain normal basal cortisol production.…”

Section: Chronic Hypoxiamentioning

confidence: 99%

Gestational Hypoxia and Developmental Plasticity

Ducsay

Goyal

Pearce

et al. 2018

Physiological Reviews

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145

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Hypoxia is one of the most common and severe challenges to the maintenance of homeostasis. Oxygen sensing is a property of all tissues, and the response to hypoxia is multidimensional involving complicated intracellular networks concerned with the transduction of hypoxia-induced responses. Of all the stresses to which the fetus and newborn infant are subjected, perhaps the most important and clinically relevant is that of hypoxia. Hypoxia during gestation impacts both the mother and fetal development through interactions with an individual's genetic traits acquired over multiple generations by natural selection and changes in gene expression patterns by altering the epigenetic code. Changes in the epigenome determine "genomic plasticity," i.e., the ability of genes to be differentially expressed according to environmental cues. The genomic plasticity defined by epigenomic mechanisms including DNA methylation, histone modifications, and noncoding RNAs during development is the mechanistic substrate for phenotypic programming that determines physiological response and risk for healthy or deleterious outcomes. This review explores the impact of gestational hypoxia on maternal health and fetal development, and epigenetic mechanisms of developmental plasticity with emphasis on the uteroplacental circulation, heart development, cerebral circulation, pulmonary development, and the hypothalamic-pituitary-adrenal axis and adipose tissue. The complex molecular and epigenetic interactions that may impact an individual's physiology and developmental programming of health and disease later in life are discussed.

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“…Although a non-invasive measure of fetal hypoxia would be useful, yet we are not aware of any known maternal biomarker of fetal hypoxia. Myers et al reported that arginin vasopressin (AVP) is a hormone produced by hypothalamus in fetal hypoxia [8]. Copeptin is a precursor of preprovasopressin which is secreted in an equimolar ratio to AVP in situations of high plasma osmolality, low blood pressure, and hypoxia [9].…”

Section: Discussionmentioning

confidence: 99%

The correlation of maternal serum and cord blood copeptin levels with intrapartum fetal distress

Ulu¹,

Çekmez²,

Gülşen³

et al. 2018

Clin. Exp. Obstet. Gynecol.

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Aim: Fetal distress (FD) is mostly an important sign of fetal hypoxia. The hypothalamic-pituitary-adrenal axis is an important limb of acute stress response. Copeptin is a hormone of endogenous stress. The authors aimed to investigate whether the level of copeptin correlates with FD or not. Material and Methods:Twenty-four pregnant women and their babies with the diagnosis of FD confirmed by category III fetal heart rate (FHR) pattern were compared with 20 uncomplicated pregnant women and their babies who were delivered by elective cesarean section. Results: The mean maternal serum copeptin level showed no significant difference between the mothers of control group and the mothers of FD group (p > 0.05). The mean umbilical cord serum copeptin level showed no significant difference between the groups (p > 0.05). Conclusion: The authors revealed that copeptin is not correlated with the presence of FD, thus further studies are needed to discover new biomarkers.

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Gestational hypoxia modulates expression of corticotropin-releasing hormone and arginine vasopressin in the paraventricular nucleus in the ovine fetus

Cited by 7 publications

References 50 publications

Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon

Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon

Gestational Hypoxia and Developmental Plasticity

The correlation of maternal serum and cord blood copeptin levels with intrapartum fetal distress

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