Signaling Molecules Involved in IFN‐γ‐Inducible Nitric Oxide Synthase Expression in the Mouse Trophoblast

Leanza, Eduardo Cava; Hoshida, Mara Sandra; Costa, Ana Luiza Fontes de Azevedo; Fernandes, C.M.; Teixeira, Catarina; Bevilacqua, Estela

doi:10.1111/j.1600-0897.2007.00537.x

Cited by 9 publications

(10 citation statements)

References 49 publications

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“…Homodimers of phosphorylated STAT-1 translocate to the nucleus, activating specific gene program IFN-γ-dependent (Darnell et al, 1994). In support of this and as previously reported in macrophages, IFN-γ increases the gene expression of iNOS and STAT-1 in trophoblast cells, but not of STAT2, related to regulatory pathways other than IFN-γ (Leanza et al, 2007). Up-regulation of STAT1 is involved with the intensity of IFN-γ responses at inflammatory sites and thereby, considered an additional regulatory mechanism for IFN-γ-induced responses.…”

Section: Ifn-γ γ γsupporting

confidence: 73%

Trophoblast phagocytic program: roles in different placental systems

Bevilacqua

Hoshida²,

Amarante-Paffaro³

et al. 2010

Int. J. Dev. Biol.

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Section: Ifn-γ γ γsupporting

confidence: 73%

Trophoblast phagocytic program: roles in different placental systems

Bevilacqua

Hoshida²,

Amarante-Paffaro³

et al. 2010

Int. J. Dev. Biol.

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“…Signaling by type II IFNG involves activation of JAK1 and JAK2 constitutively associated with IFNGR1 and IFNGR2 subunits of type II IFNR respectively. IFNG stimulates autophosphorylation and subsequent tyrosine phosphorylation and homodimerization of STAT1 allowing STAT1 homodimers to translocate to the nucleus and bind GAS elements in promoter regions of IFNG-regulated genes (Leanza et al 2007). There is evidence that IFNs are expressed by human placentae (IFNA, IFNB, and IFNG), decidua (IFNA, IFNB, and IFNG) and fetal membranes (IFNA and IFNG), as well as conceptus trophectoderm of sheep (IFNT) and pig (IFND and IFNG), and rodent uteri and/or conceptuses (IFNA and IFNB; see Bazer et al 2008Bazer et al , 2009).…”

Section: Maternal Recognition Of Pregnancymentioning

confidence: 99%

Comparative aspects of implantation

Bazer

Spencer²,

Johnson³

et al. 2009

Reproduction

337

285

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Uterine receptivity to implantation of blastocysts in mammals includes hatching from zona pellucida, precontact with uterine luminal (LE) and superficial glandular (sGE) epithelia and orientation of blastocyst, apposition between trophectoderm and uterine LE and sGE, adhesion of trophectoderm to uterine LE/sGE, and, in some species, limited or extensive invasion into the endometrial stroma and induction of decidualization of stromal cells. These peri-implantation events are prerequisites for pregnancy recognition signaling, implantation, and placentation required for fetal-placental growth and development through the remainder of pregnancy. Although there is a range of strategies for implantation in mammals, a common feature is the requirement for progesterone (P 4 ) to downregulate expression of its receptors in uterine epithelia and P 4 prior to implantation events. P 4 then mediates its effects via growth factors expressed by stromal cells in most species; however, uterine luminal epithelium may express a growth factor in response to P 4 and/or estrogens in species with a true epitheliochorial placenta. There is also compelling evidence that uterine receptivity to implantation involves temporal and cell-specific expression of interferon (IFN)-stimulated genes that may be induced directly by an IFN or induced by P 4 and stimulated by an IFN. These genes have many roles including nutrient transport, cellular remodeling, angiogenesis and relaxation of vascular tissues, cell proliferation and migration, establishment of an antiviral state, and protection of conceptus tissues from challenges by the maternal immune cells.

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“…Aos sete DG, o hipotireoidismo aumentou a imunomarcação de iNOS e reduziu a imunoexpressão de MIF e a população de células uNK DBA + . O iNOS tem efeitos antiinflamatórios, e o seu aumento na interface materno-fetal está associado ao estresse oxidativo (Leanza et al, 2007). É importante ressaltar que, nesse período gestacional, é necessário um ambiente pró-inflamatório que permita o processo de implantação embrionária e migração trofoblástica (Koga et al, 2009), sendo que o aumento da expressão de iNOS observado nos animais hipotireoideos, nesse período gestacional, pode comprometer tais processos.…”

Section: Discussionunclassified

“…O IFNγ influencia diretamente a função das células uNKs que estão envolvidas tanto na imunidade quanto na dinâmica vascular placentária e decidual (Hu e Cross, 2010). Além disso, o IFNγ está relacionado à atividade fagocítica de macrófagos, importante para a diferenciação do trofoblasto durante o período de diferenciação do cone ectoplacentário (Leanza et al, 2007). Portanto, a expressão reduzida de Ifnγ pode ter sido a causa do subdesenvolvimento da decídua observado por Souza et al (2017) (Ashkar et al, 2000;Hu e Cross, 2010).…”

Section: Discussionunclassified

“…Aos 12 DG, nos animais hipotireoideos, foi observada redução da imunomarcação de IFNγ e iNOS e aumento de IL15, de MIF e da expressão gênica de iNos. Estudos anteriores demonstraram que o IFNγ, além de ativar macrófagos deciduais, na interface materno-fetal, também induz a síntese de iNOS pelos trofoblastos fetais (Hoshida et al, 2007). A redução de imunomarcação de iNOS em animais hipotireoideos foi observada aos 12, 14, e 19 DG e a redução da expressão gênica foi observada aos 10 DG.…”

Section: Discussionunclassified

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Efeito do hipotireoidismo materno na expressão espaço-temporal de mediadores imunológicos e população de células natural killers na decídua e na glândula metrial de ratas

Souza

Silva

Ocarino

et al. 2020

Arq. Bras. Med. Vet. Zootec.

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RESUMOEstudou-se o efeito do hipotireoidismo materno na expressão espaço-temporal de mediadores imunológicos e na população de células natural killers (NK) na decídua e na glândula metrial de ratas durante a gestação. Avaliou-se a detecção imunoistoquímica de interferon γ (IFNγ), do fator inibidor de migração (MIF), da interleucina 15 (IL15), do óxido nítrico sintase induzível (iNOS), a marcação com lectina DBA para evidenciação das células NK uterinas DBA + e a expressão gênica de Ifnγ e Nos2. O hipotireoidismo aumentou o iNOS aos sete dias, a IL15 e o MIF aos 10 e 12 dias, o IFNγ e o MIF aos 14 DG e a expressão dos transcritos gênicos para iNos aos 12 e 19 dias e para Ifnγ aos 14 DG. O hipotireoidismo reduziu a imunomarcação de MIF e lectina DBA aos sete dias, lectina DBA aos 10 e 14 DG, IFNγ aos 12 dias, e a expressão de Ifnγ aos 10 e 19 DG e de iNOS aos 12, 14 e 19 DG, bem como reduziu seus transcritos gênicos aos 10 e 14 DG. Conclui-se que o hipotireoidismo compromete o perfil imunológico na interface materno-fetal ao longo da gestação, particularmente por reduzir o fator anti-inflamatório iNOS e a população de células uNK DBA + . Palavras-chave: hipotireoidismo, decídua, glândula metrial, imunologia ABSTRACTThe goal of this study was to evaluate the effect of maternal hypothyroidism on the spatiotemporal expression of immunological mediators and population of Natural Killers cells in decidua and metrial gland of rats. Interferon gamma (IFNγ), migration inhibitory factor (MIF), interleukin 15 (IL15), inducible nitric oxide synthase (iNOS), and DBA-Lectin labeling for evidence of uNK DBA + cells in decidua and genetic expression of Ifnγ and iNos by real-time RT-PCR were evaluated. Hypothyroidism increased protein expression of iNOS at 7 days, IL15 and MIF at 10 and 12 days, IFNγ and MIF at 14 DG in the decidua and/or metrial gland and the gene transcripts for iNOS at 12 and 19 days and for Inf at 14 DG. In addition, hypothyroidism reduced the protein expression of MIF and DBA-Lectin at 7 days, DBA-Lectin at 10 and 14 DG, IFNγ at 12 days, and the gene transcript to Ifnγ at 10 and 19 DGs. Hypothyroidism also reduced the protein expression of iNOS at 12, 14 and 19 DG and reduced its gene transcripts at 10 and 14 DGs. It is concluded that hypothyroidism compromises the immunology profile at the maternal-fetal interface throughout pregnancy, particularly by reducing the anti-inflammatory factor iNOS and population of uNK DBA + cells.

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Signaling Molecules Involved in IFN‐γ‐Inducible Nitric Oxide Synthase Expression in the Mouse Trophoblast

Cited by 9 publications

References 49 publications

Trophoblast phagocytic program: roles in different placental systems

Trophoblast phagocytic program: roles in different placental systems

Comparative aspects of implantation

Efeito do hipotireoidismo materno na expressão espaço-temporal de mediadores imunológicos e população de células natural killers na decídua e na glândula metrial de ratas

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