Critical windows in development of the rodent immune system

Abstract

<jats:p> The immune system of rodents, like that in humans, develops from a population of pluripotential hematopoietic stem cells (HSC) that are generated early in gestation from uncommitted mesenchymal stem cells in the intra-embryonic splanchnoplure surrounding the heart. This early population of HSC gives rise to all circulating blood cell lineages, including cells of the innate and acquired immune system. To access the impact of chemical exposure on the developing immune system and establish developmental windows of potential vulnerability to these exposures, it is essential to first consider the anatomical development of hematopoietic and lymphopoietic tissues and the sequence of appearance of cells that give rise to the immune system. This is particularly true in embryonic development because, after they initially appear in intra-embryonic mesenchyme early in gestation, HSC migrate through an orderly series of tissues before establishing residence in the bone marrow and thymus. The effect of exposure to chemical insults in utero, then, may differ depending on the specific timing of exposure and anatomical location of hematopoiesis. Mechanisms and consequences of developmental immunotoxicity in experimental animals will need to be considered in that context. This review presents an overview of developmental hematopoiesis and a working hypothesis of critical developmental windows of vulnerability of this developmental system to toxic insult by chemical exposure. </jats:p>

Gestation under chronic constant light leads to extensive gene expression changes in the fetal rat liver

“…In particular, the rat liver is the primary hematopoietic organ during the second half of gestation, playing a key role in development of the innate and adaptive immune system (23,50). Based on global transcriptome changes, both hematopoiesis and infectious disease were predicted to be activated under constant gestational light.…”

Neonatal lipopolysaccharide exposure induces sexually dimorphic sickness behavior in adult rats.

“…The reason to specifically treat rats on PND2 was because the period immediately after birth in rodents is the last critical period for immune system development (Landreth, 2002). The control groups consisted of male and female pups that received only sterile saline (.9% NaCl) with the same treatment schedule as the LPS animals.…”

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example

“…Immune development is relatively delayed in rodents compared with humans; some rodent postnatal events occur prenatally in humans (Landreth, 2002;West, 2002). Human T cells can respond to several mitogenic and allogeneic stimulatory challenges prenatally, whereas significant responses in rodents usually appear after birth.…”

“…The immune "windows", along with developmental windows for the respiratory system, were identified at a workshop sponsored by the USEPA and the March of Dimes (see Dietert et al, 2000;Holladay & Smialowicz, 2000;Landreth, 2002). They include 1) initiation of haematopoiesis, 2) migration and expansion of stem cell populations, 3) colonization events, including bone marrow colonization, pre-T cell seeding to the thymus, T cell education, T cell repertoire establishment, then seeding of the periphery by mature T cells, 4) acquisition of immunocompetence, and, finally, 5) the capacity to develop immunological memory.…”

“…There is an immune developmental period in which the capacity of low-level lead exposure to modulate T cell response in the offspring appears to be the greatest. This period of increased sensitivity (compared with adult-induced immunotoxicity) corresponds to the developmental period during which stem cells migrate, progenitor cell populations expand, and the bone marrow and thymus are colonized Landreth, 2002).…”