Prospective Cohort Study of Congenital Cytomegalovirus Infection during Pregnancy with Fetal Growth Restriction: Serologic Analysis and Placental Pathology.

OBJECTIVE: To investigate prospectively the prevalence of congenital cytomegalovirus (CMV) infection and the pathologic features of the placenta in cases of fetal growth restriction (FGR). STUDY DESIGN: Forty-eight pregnant women who were diagnosed with FGR during pregnancy were enrolled for 15 months. Maternal CMV serologic tests, pathologic examinations of the placenta, and newborn urinary CMV-DNA polymerase chain reaction tests were performed in all the cases. The clinical characteristics and laboratory findings of the pregnant women and their newborns were collected. Biomarkers for inflammation, angiogenesis, and placental hormones were measured in the maternal serum at FGR diagnosis or in the neonatal urine at birth. RESULTS: One of the 48 cases with FGR was a congenital CMV infection. CMV antigen was detected in the placenta of 7 cases with FGR. The change rate of the estimated fetal body weight was significantly lower in FGR cases with placental CMV detection. Placental villitis was observed more frequently in FGR cases with placental CMV detection. Human placental lactogen was significantly decreased in FGR cases with placental CMV detection. Increased C-reactive protein and serum amyloid A levels in the maternal serum were observed more frequently in FGR cases with placental CMV detection. Newborn urine ß-2 microglobulin levels were significantly higher in FGR cases with placental CMV detection. CONCLUSIONS: Serologic tests for maternal CMV, the change rate of the estimated fetal body weight, analysis of several biomarkers, and placental pathologic examinations might be helpful in comprehensively predicting the possibility of congenital CMV infection.

Placental contribution to the endocrinology of gestation and parturition.

In addition to many other functions, the placenta is a source of a vast number of autocrine, paracrine and endocrine factors. However, the spectrum of placental regulatory factors, their concentrations, gestational profiles and roles may differ considerably even between phylogenetically closely related species. Depending on the species, placental regulatory factors of a broad range of molecule classes have been found including (glyco-)proteins, peptides, steroids and prostaglandins. Local placental regulatory factors are especially important for the dialogue between the fetal and the maternal compartment immediately at the feto-maternal borderline and for the control of growth, differentiation and functions of the placenta itself. Moreover, placental hormones in a proper sense may also have effects in more remote targets within the maternal compartment, serving functions such as pregnancy-specific adaptations of maternal circulation, provision of hemotrophe to the fetus or the development and function of the mammary gland. Functions of placental hormones in the fetus proper are less clear but may be especially important before the establishment of a functional fetal endocrine system and near term within the highly species-specific networks of signals preparing and initiating parturition. This review takes a comparative view on the situation in different domestic animals focusing on ruminants and on placental hormones occurring at significant concentrations in the maternal circulation.

Placental contribution to the endocrinology of gestation and parturition

In addition to many other functions, the placenta is a source of a vast number of autocrine, paracrine and endocrine factors. However, the spectrum of placental regulatory factors, their concentrations, gestational profiles and roles may differ considerably even between phylogenetically closely related species. Depending on the species, placental regulatory factors of a broad range of molecule classes have been found including (glyco- )proteins, peptides, steroids and prostaglandins. Local placental regulatory factors are especially important for the dialogue between the fetal and the maternal compartment immediately at the feto-maternal borderline and for the control of growth, differentiation and functions of the placenta itself. Moreover, placental hormones in a proper sense may also have effects in more remote targets within the maternal compartment, serving functions such as pregnancy-specific adaptations of maternal circulation, provision of hemotrophe to the fetus or the development and function of the mammary gland. Functions of placental hormones in the fetus proper are less clear but may be especially important before the establishment of a functional fetal endocrine system and near term within the highly species-specific networks of signals preparing and initiating parturition. This review takes a comparative view on the situation in different domestic animals focusing on ruminants and on placental hormones occurring at significant concentrations in the maternal circulation.(AU)

Hiperplasia fibroepitelial mamária felina (HFMF): novas perspectivas de regulação endócrina / Feline mammary fibroepithelial hyperplasia (FMFH): new perspectives of endocrine control

O controle da mamogênese, que inicia na fase embrionária e continua ao longo das várias etapas reprodutivas da fêmea, ainda não foi totalmente elucidado. Pesquisas nessa área geralmente são conduzidas com espécies produtoras de leite para fins comerciais, mas podem auxiliar nas investigações sobre a patogenia da hiperplasia fibroepitelial mamária felina (HFMF). Caracterizada como um fenômeno de crescimento anabólico que ocorre somente em algumas gatas, com proliferação celular nas estruturas alveolares, tanto no epitélio luminal quanto no mioepitélio, a HFMF pode exacerbar ao ponto de romper a pele e expor o parênquima mamário. Do ponto de vista endócrino, observa-se o envolvimento da progesterona, tanto endógena quanto exógena, aliada a uma sinergia com Hormônio do Crescimento (GH) e Fator de crescimento semelhante a insulina-1 (IGF-1). Todavia, a interação com outros hormônios envolvidos na mamogênese ainda é um campo aberto à pesquisa. Objetiva-se com esta revisão discorrer sobre os hormônios e fatores de crescimento celular relacionados à mamogênese e ocorrência de HFMF.(AU)

The control of mamogenesis, which starts on embryonic phase and continues throughout many female reproductive phases, was not fully understood. Researches on this field are commonly performed with dairy species, but support investigations focused on Feline mammary fibroepithelial hyperplasia (FMFH) pathogenesis. Characterized as a phenomenon of anabolic growth that occurs in few female cats, with alveolar proliferation in both luminal and myoepithelial cells, the FMFH can exacerbated and expose mammary parenchyma due to skin disruption. Endocrinologically it is observed participation of endogenous and exogenous progesterone, associated to synergism with Growth hormone (GH) and Insulin like growth factor-1 (IGF-1). However, interaction with other hormones enrolled on mammogenesis remains an open field to research. The goal of this review is to discuss about hormones and cellular growth factors related to mammogenesis and FMFH occurrence.(AU)

Placental contribution to the endocrinology of gestation and parturition

In addition to many other functions, the placenta is a source of a vast number of autocrine, paracrine and endocrine factors. However, the spectrum of placental regulatory factors, their concentrations, gestational profiles and roles may differ considerably even between phylogenetically closely related species. Depending on the species, placental regulatory factors of a broad range of molecule classes have been found including (glyco- )proteins, peptides, steroids and prostaglandins. Local placental regulatory factors are especially important for the dialogue between the fetal and the maternal compartment immediately at the feto-maternal borderline and for the control of growth, differentiation and functions of the placenta itself. Moreover, placental hormones in a proper sense may also have effects in more remote targets within the maternal compartment, serving functions such as pregnancy-specific adaptations of maternal circulation, provision of hemotrophe to the fetus or the development and function of the mammary gland. Functions of placental hormones in the fetus proper are less clear but may be especially important before the establishment of a functional fetal endocrine system and near term within the highly species-specific networks of signals preparing and initiating parturition. This review takes a comparative view on the situation in different domestic animals focusing on ruminants and on placental hormones occurring at significant concentrations in the maternal circulation.

Hiperplasia fibroepitelial mamária felina (HFMF): novas perspectivas de regulação endócrina / Feline mammary fibroepithelial hyperplasia (FMFH): new perspectives of endocrine control

O controle da mamogênese, que inicia na fase embrionária e continua ao longo das várias etapas reprodutivas da fêmea, ainda não foi totalmente elucidado. Pesquisas nessa área geralmente são conduzidas com espécies produtoras de leite para fins comerciais, mas podem auxiliar nas investigações sobre a patogenia da hiperplasia fibroepitelial mamária felina (HFMF). Caracterizada como um fenômeno de crescimento anabólico que ocorre somente em algumas gatas, com proliferação celular nas estruturas alveolares, tanto no epitélio luminal quanto no mioepitélio, a HFMF pode exacerbar ao ponto de romper a pele e expor o parênquima mamário. Do ponto de vista endócrino, observa-se o envolvimento da progesterona, tanto endógena quanto exógena, aliada a uma sinergia com Hormônio do Crescimento (GH) e Fator de crescimento semelhante a insulina-1 (IGF-1). Todavia, a interação com outros hormônios envolvidos na mamogênese ainda é um campo aberto à pesquisa. Objetiva-se com esta revisão discorrer sobre os hormônios e fatores de crescimento celular relacionados à mamogênese e ocorrência de HFMF.

The control of mamogenesis, which starts on embryonic phase and continues throughout many female reproductive phases, was not fully understood. Researches on this field are commonly performed with dairy species, but support investigations focused on Feline mammary fibroepithelial hyperplasia (FMFH) pathogenesis. Characterized as a phenomenon of anabolic growth that occurs in few female cats, with alveolar proliferation in both luminal and myoepithelial cells, the FMFH can exacerbated and expose mammary parenchyma due to skin disruption. Endocrinologically it is observed participation of endogenous and exogenous progesterone, associated to synergism with Growth hormone (GH) and Insulin like growth factor-1 (IGF-1). However, interaction with other hormones enrolled on mammogenesis remains an open field to research. The goal of this review is to discuss about hormones and cellular growth factors related to mammogenesis and FMFH occurrence.

Intrauterine Growth Retardation (IUGR) as a Novel Condition of Insulin-Like Growth Factor-1 (IGF-1) Deficiency.

Insulin-like growth factor 1 (IGF-1) is an anabolic hormone with several biological activities, such as proliferation, mitochondrial protection, cell survival, tissue growth and development, anti-inflammatory, antioxidant, antifibrogenic and antiaging. This hormone plays an important role in embryological and postnatal states, being essential for normal foetal and placental growth and differentiation. During gestation, the placenta is one of the major sources of IGF-1, among other hormones. This intrauterine organ expresses IGF-1 receptors and IGF-1 binding proteins (IGFBPs), which control IGF-1 activities. Intrauterine growth restriction (IUGR) is the second most frequent cause of perinatal morbidity and mortality, defined as the inability to achieve the expected weight for gestational age. Different studies have revealed that IUGR infants have placental dysfunction and low circulating levels of insulin, IGF-1, IGF-2 and IGFBPs. Such data suggest that IGF-1 deficiency in gestational state may be one of the major causes of foetal growth retardation. The aim of this review is to study the epidemiology, physiopathology and possible causes of IUGR. Also, it intends to study the possible role of the placenta as an IGF-1 target organ. The purpose is to establish if IUGR could be considered as a novel condition of IGF-1 deficiency and if its treatment with low doses of IGF-1 could be a suitable therapeutic strategy.

Identification of messenger RNA of fetoplacental source in maternal plasma of women with normal pregnancies and pregnancies with intrauterine growth restriction / Identificacion de RNA mensajero de origen fetoplacentario en plasma materno de mujeres con embarazos normales y gestantes con restriccion de crecimiento intrauterino

Objective: to quantify placenta-specific RNA in plasma of women carrying foetuses with intrauterine growth restriction and pregnant women with normal pregnancies. Materials and methods: 8 pregnant women with foetuses with intrauterine growth restriction were studied as well as 18 women with uncomplicated pregnancies in the third pregnancy trimester. Total free RNA was quantified in maternal plasma by spectrophotometry and the gene expression of hPL (Human Placental Lactogen) at the messenger RNA level through technical Real Time-Chain Reaction Polymerase. Results: plasma RNA of fetoplacental origin was successfully detected in 100% of pregnant women. There were no statistically significant differences between the values of total RNA extracted from plasma (p = 0.5975) nor in the messenger RNA expression of hPL gene (p = 0.5785) between cases and controls. Conclusion: messenger RNA of fetoplacental origin can be detected in maternal plasma during pregnancy.(AU)Objective: to quantify placenta-specific RNA in plasma of women carrying foetuses with intrauterine growth restriction and pregnant women with normal pregnancies. Materials and methods: 8 pregnant women with foetuses with intrauterine growth restriction were studied as well as 18 women with uncomplicated pregnancies in the third pregnancy trimester. Total free RNA was quantified in maternal plasma by spectrophotometry and the gene expression of hPL (Human Placental Lactogen) at the messenger RNA level through technical Real Time-Chain Reaction Polymerase.Results: plasma RNA of fetoplacental origin was successfully detected in 100% of pregnant women. There were no statistically significant differences between the values of total RNA extracted from plasma (p = 0.5975) nor in the messenger RNA expression of hPL gene (p = 0.5785) between cases and controls.Conclusion: messenger RNA of fetoplacental origin can be detected in maternal plasma during pregnancy

Objetivo: cuantificar RNA específico de placenta en el plasma de mujeres con embarazos con fetos con Restricción de Crecimiento Intrauterino y gestantes con embarazos normales. Materiales y métodos: se estudiaron 8 mujeres con embarazos con fetos con Restricción de Crecimiento Intrauterino y 18 mujeres con embarazos sin complicaciones, en el tercer trimestre de embarazo. Se cuantificó el RNA total libre en plasma materno por espectrofotometría y la expresión del gen hPL (Lactógeno Placentario Humano) a nivel de RNA mensajero por medio de la técnica Reacción en Cadena de la Polimerasa en Tiempo Real. Resultados: se logró detectar RNA en plasma de origen fetoplacentario en el 100% de las gestantes. No se encontraron diferencias estadísticamente significativas entre los valores de RNA total extraído de plasma (p=0,5975) ni en la expresión del RNA mensajero del gen hPL (p=0,5785) entre casos y controles. Conclusión: es posible detectar RNA mensajero de origen fetoplacentario en plasma materno durante el embarazo.

Identification of messenger RNA of fetoplacental source in maternal plasma of women with normal pregnancies and pregnancies with intrauterine growth restriction.

OBJECTIVE: to quantify placenta-specific RNA in plasma of women carrying foetuses with intrauterine growth restriction and pregnant women with normal pregnancies. METHODS: 8 pregnant women with foetuses with intrauterine growth restriction were studied as well as 18 women with uncomplicated pregnancies in the third pregnancy trimester. Total free RNA was quantified in maternal plasma by spectrophotometry and the gene expression of hPL (Human Placental Lactogen) at the messenger RNA level through technical Real Time-Chain Reaction Polymerase. RESULTS: plasma RNA of fetoplacental origin was successfully detected in 100% of pregnant women. There were no statistically significant differences between the values of total RNA extracted from plasma (p= 0.5975) nor in the messenger RNA expression of hPL gene (p= 0.5785) between cases and controls. CONCLUSION: messenger RNA of fetoplacental origin can be detected in maternal plasma during pregnancy.

OBJETIVO: cuantificar RNA específico de placenta en el plasma de mujeres con embarazos con fetos con Restricción de Crecimiento Intrauterino y gestantes con embarazos normales. MÉTODOS: se estudiaron 8 mujeres con embarazos con fetos con Restricción de Crecimiento Intrauterino y 18 mujeres con embarazos sin complicaciones, en el tercer trimestre de embarazo. Se cuantificó el RNA total libre en plasma materno por espectrofotometría y la expresión del gen hPL (Lactógeno Placentario Humano) a nivel de RNA mensajero por medio de la técnica Reacción en Cadena de la Polimerasa en Tiempo Real. RESULTADOS: se logró detectar RNA en plasma de origen fetoplacentario en el 100% de las gestantes. No se encontraron diferencias estadísticamente significativas entre los valores de RNA total extraído de plasma (p= 0.5975) ni en la expresión del RNA mensajero del gen hPL (p= 0.5785) entre casos y controles. CONCLUSIÓN: es posible detectar RNA mensajero de origen fetoplacentario en plasma materno durante el embarazo.

Relative Concentrations of Placental Lactogen II and PRL-Like Protein-A in Stressed Rats Placenta / Concentraciones del Lactógeno Placentario II y la Proteína A Ligada a Prolactina en Placentas de Ratas Estresadas

The chronic stress induces functional adaptations in the hypothalamo-pituitary- adrenocortical (HPA) and in the sympathetic-medullary-adrenal axis (SAM). Both axis are considered vital regulators of the homeostasis in vertebrates (Seyle, 1936; Ostrandrer et al, 2006. On the other hand, the placenta provides highly specialized functions during gestation that are critical for the normal development of the embryo/fetus (Soares et al., 1991). We hypothesized that the chronic immobilization (IMO) stress in pregnancy rats produces alterations in prolactin concentrations in placental tissue and also changes in the response of SAM axis. Chronic stress by IMO was applied on days 12, 17 and 21 of pregnancy rats. Relative concentrations and localization of placental lactogen-II (PL-II) and the PRL- like protein A (PLP-A) in chorioalantoic placenta were estimated by Immunoblotting and Immunocytochemical analysis. The levels of catecholamines metabolite, acid 3-metoxi 4-hidroximandélico (VMA), were analyzed in stressed rats urines on 6,12,17,21 days of pregnancy, by HPLC, in order to determine the response of SAM axis. During the days of the pregnancy studied, chronic stress did not induce any changes neither in the localization nor in placental concentrations of PL-II and PLP-A. The VMA values in stressed mothers urines increased on the day 6 respecting the control ones at the same time of pregnancy. VMA values in stressed rats at 21 days of pregnancy are smaller than the respective controls. We conclude that the chronic stressed mothers activated the SAM axis at the beginning of pregnancy and then they diminished the metabolites catecholamines that were interpreted as a stress adaptation coincident with normal concentrations of both placentary prolactines at this stage of the pregnancy.

El estrés crónico induce adaptaciones funcionales en los ejes hipotálamo-pituitario-adrenal (UPA) y en el simpático médulo adrenal (SAM). Ambos ejes son considerados reguladores vitales de la homeostasis en los vertebrados (Seyle, 1936; Ostrandrereí al., 2006). Por otro lado, el desarrollo y crecimiento fetal de los mamíferos dependen en gran medida del buen funcionamiento de la placenta (Soares, 1991). Nosotros hipotetizamos que el estrés crónico por inmovilización (IMO) aplicado a las ratas gestantes produce alteraciones en las concentraciones de las prolactinas en el tejido placentario y cambios en la respuesta del eje SAM. Se le aplicó estrés crónico por IMO a las hembras en los días 12, 17 y 21 de la preñez y se analizó por inmunocitoquímica e inmunoblotting la localización y concentraciones del lactógeno placentario dos (PL-II) y la proteína A ligada a la prolactina (PLP-A) en la placenta. Se analizaron por HPLC, en las orinas de ratas preñadas (6,12,17,21 días), los niveles del metabolito de las catecolaminas, (ácido 3-metoxi 4-hidroximandélico) (VMA), a fin de determinar la respuesta del eje SAM al tratamiento. El estrés crónico no indujo cambios tanto en la localización como en las concentraciones de PL-II y PLP-A en las placentas en los días de la preñez estudiados. Los valores de VMA en las orinas de las madres estresadas se incrementaron en el día 6 con respecto al control del mismo tiempo de preñez. Mientras que a los 21 días los valores de VMA de las ratas estresadas son menores que los controles respectivos. Concluimos que en las madres estresadas crónicamente, no se alteraron las concentraciones de ambas prolactinas placentarias. En cambio se activó el eje SAM al comienzo de la preñez ante el primer estímulo estresante y luego una reducción de la respuesta del eje ante el estrés crónico, a medida que avanza la preñez.