An Immunohistochemical Study of the Secretory Immune System in Human Fetal Membranes and Decidua of the First Trimester of Pregnancy

Gurevich, Pavel; Elhayany, Asher; Ben‐Hur, Herzl; Moldavsky, Moisey; Szvalb, Sergio; Zandbank, Judit; Shperling, I. D.; Zusman, Itshak

doi:10.1034/j.1600-0897.2003.01201.x

Cited by 25 publications

(19 citation statements)

References 15 publications

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“…Other important immune effectors present in the placenta include immunoglobulins (e.g., IgG, IgA, and IgM), which play multiple important roles in regulating the course of a normal pregnancy [67, 68]. In the maternal part of the placenta, immunoglobulins protect the mother against paternal antigens present in the fetus, while in the fetal part, immunoglobulins protect the fetus against macromolecules and infectious agents originating from the mother [67].…”

Section: Pondering the Two Hypothesesmentioning

confidence: 99%

A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome

et al. 2017

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After more than a century of active research, the notion that the human fetal environment is sterile and that the neonate’s microbiome is acquired during and after birth was an accepted dogma. However, recent studies using molecular techniques suggest bacterial communities in the placenta, amniotic fluid, and meconium from healthy pregnancies. These findings have led many scientists to challenge the “sterile womb paradigm” and propose that microbiome acquisition instead begins in utero, an idea that would fundamentally change our understanding of gut microbiota acquisition and its role in human development. In this review, we provide a critical assessment of the evidence supporting these two opposing hypotheses, specifically as it relates to (i) anatomical, immunological, and physiological characteristics of the placenta and fetus; (ii) the research methods currently used to study microbial populations in the intrauterine environment; (iii) the fecal microbiome during the first days of life; and (iv) the generation of axenic animals and humans. Based on this analysis, we argue that the evidence in support of the “in utero colonization hypothesis” is extremely weak as it is founded almost entirely on studies that (i) used molecular approaches with an insufficient detection limit to study “low-biomass” microbial populations, (ii) lacked appropriate controls for contamination, and (iii) failed to provide evidence of bacterial viability. Most importantly, the ability to reliably derive axenic animals via cesarean sections strongly supports sterility of the fetal environment in mammals. We conclude that current scientific evidence does not support the existence of microbiomes within the healthy fetal milieu, which has implications for the development of clinical practices that prevent microbiome perturbations after birth and the establishment of future research priorities.

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Section: Pondering the Two Hypothesesmentioning

confidence: 99%

A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome

et al. 2017

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“…In the nonpregnant state, high levels of innate immunity also exist within the endometrium in the form of secreted antimicrobials and IgA from the mucosal surface (Hickey et al 2011; Wira et al 2011). This mucosal immune function is maintained in the decidua throughout pregnancy (Gurevich et al 2003; King et al 2007). Other factors, such as seminal fluid, also appear to play a role in priming the endometrial epithelium, muting the inflammatory reaction, and recruiting the necessary uterine immune cells to facilitate reproductive success (Schjenken and Robertson 2014).…”

Section: Why Does the Human Uterus Only Support A Pregnancy For Nine mentioning

confidence: 99%

Molecular Regulation of Parturition: The Role of the Decidual Clock

Norwitz

Bonney

Snegovskikh

et al. 2015

Cold Spring Harb Perspect Med

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The timing of birth is a critical determinant of perinatal outcome. Despite intensive research, the molecular mechanisms responsible for the onset of labor both at term and preterm remain unclear. It is likely that a “parturition cascade” exists that triggers labor at term, that preterm labor results from mechanisms that either prematurely stimulate or short-circuit this cascade, and that these mechanisms involve the activation of proinflammatory pathways within the uterus. It has long been postulated that the fetoplacental unit is in control of the timing of birth through a “placental clock.” We suggest that it is not a placental clock that regulates the timing of birth, but rather a “decidual clock.” Here, we review the evidence in support of the endometrium/decidua as the organ primarily responsible for the timing of birth and discuss the molecular mechanisms that prime this decidual clock.

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“…It is generally believed that the conceptus does not generate appreciable levels of IgG Jauniaux et al, 1995;Gurevich et al, 2003b) and therefore any IgGs detected in embryonic, extraembryonic, or fetal compartments are presumed to be of maternal origin. It is generally believed that the conceptus does not generate appreciable levels of IgG Jauniaux et al, 1995;Gurevich et al, 2003b) and therefore any IgGs detected in embryonic, extraembryonic, or fetal compartments are presumed to be of maternal origin.…”

Section: Placental Transfer In Humansmentioning

confidence: 99%

Placental Transfer of Fc‐Containing Biopharmaceuticals across Species, an Industry Survey Analysis

Bowman

Breslin

Connor³

et al. 2013

Birth Defects Research Pt B

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Embryonic (before the end of organogenesis) exposure was assessed in one molecule each in rabbit, rat, and mouse, but detectable levels were present only in rodents. In rodents, fetal levels remained relatively constant from gestation day (GD) 16 and 17 until the end of gestation, while maternal levels decreased or remained constant in rat and decreased in mice. In rabbits, following a last dose on GD 19, fetal levels increased markedly in late gestation while maternal levels decreased. In the cynomolgus monkey, fetal levels increased substantially from GD 50 to 100 and were maintained relatively constant through parturition (approximately GD 165). Based on available data of both the monkey and rabbit, IgG1 molecules appeared to transfer more readily than other isotypes in late gestation. Across all species, there was no differential transfer based on pharmacologic target being soluble or membrane bound. Within each species there was a correlation between maternal and fetal exposure, suggesting it may be possible to predict fetal exposures from maternal exposure data. These nonclinical data (both temporal and quantitative aspects) are discussed in a comparative context relative to our understanding of IgG placental transfer in humans.

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An Immunohistochemical Study of the Secretory Immune System in Human Fetal Membranes and Decidua of the First Trimester of Pregnancy

Cited by 25 publications

References 15 publications

A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome

A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome

Molecular Regulation of Parturition: The Role of the Decidual Clock

Placental Transfer of Fc‐Containing Biopharmaceuticals across Species, an Industry Survey Analysis

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