Ann G. Clarke

The thymus in pregnancy: the interplay of neural, endocrine and immune influences.

This article discusses the dramatic events that accompany thymic involution during pregnancy, and traces the possible immune, neural and endocrine interactions that may occur. Ann Clarke and Marion Kendall present accumulating evidence that activity, not inactivity, is a feature of the thymus at this time. Whilst the cortex shrinks, the medulla enlarges and rearranges to create a microenvironment containing increased numbers of mature thymocytes. It is suggested that these recently derived T cells may contribute to the unique populations of cells with suppressive function that appear during pregnancy, and thereby contribute to the immune suppression of the mother to paternal and fetal antigens. In addition, the pregnancy-associated cortical involution of the thymus may reflect the deletion of clones with potential reactivity to paternal and/or fetal antigens.

The thymus in the mouse changes its activity during pregnancy: a study of the microenvironment.

The mouse thymus changes dramatically during pregnancy. It shrinks in size, and the cortex is extensively reduced from midpregnancy onwards. Despite this, there is surprisingly little evidence for any increase in apoptosis, and considerable evidence that mitosis of thymocytes continues throughout pregnancy. In spite of overall involution the thymic medulla actually expands in midpregnancy due to a combination of mitosis of epithelial cells and an accumulation of lymphocytes. The extent and nature of these changes are examined in this study at the ultrastructural level. The epithelial cells of the subcapsular cortex (type 1 cells) become wrinkled and exhibit powers of phagocytosis, whilst the other cortical epithelial cells are relatively unchanged, although the formation of epithelial/thymocyte rosettes and thymic nurse cells is more clearly seen in midpregnancy than usual. Other changes associated with pregnancy involve the medullary epithelial cells that undergo an increased level of mitosis. Their greater numbers surround accumulations of lymphocytes to form the characteristic medullary epithelial rings. Cell movement through blood vessel walls was clearly observed in midpregnancy, but not at other times. Interdigitating cells in the medulla become more conspicuous as pregnancy proceeds and the cells become phagocytic. The endoplasmic reticulum in plasma cells becomes expanded, indicating increased secretory activity. These results highlight the active nature of the thymus in pregnancy in spite of its involution. This picture contradicts the conventional notion that an involuted thymus is inactive.

Cryobanking of viable biomaterials: implementation of new strategies for conservation purposes

Cryobanking, the freezing of biological specimens to maintain their integrity for a variety of anticipated and unanticipated uses, offers unique opportunities to advance the basic knowledge of biological systems and their evolution. Notably, cryobanking provides a crucial opportunity to support conservation efforts for endangered species. Historically, cryobanking has been developed mostly in response to human economic and medical needs — these needs must now be extended to biodiversity conservation. Reproduction technologies utilizing cryobanked gametes, embryos and somatic cells are already vital components of endangered species recovery efforts. Advances in modern biological research (e.g. stem cell research, genomics and proteomics) are already drawing heavily on cryobanked specimens, and future needs are anticipated to be immense. The challenges of developing and applying cryobanking for a broader diversity of species were addressed at an international conference held at Trier University (Germany) in June 2008. However, the magnitude of the potential benefits of cryobanking stood in stark contrast to the lack of substantial resources available for this area of strategic interest for biological science — and society at large. The meeting at Trier established a foundation for a strong global incentive to cryobank threatened species. The establishment of an Amphibian Ark cryobanking programme offers the first opportunity for global cooperation to achieve the cryobanking of the threatened species from an entire vertebrate class.

The effects of pregnancy on the mouse thymic epithelium

Changes in the murine thymus during pregnancy were studied using immunocytochemistry with monoclonal antibodies against thymic epithelial, neuroendocrine, and thymulin-producing cells, fibroblasts, blood vessels and connective tissue components. Extensive alterations occur in mid-pregnancy. The medulla was greatly enlarged in the involuted thymus, and there were greater numbers of epithelial cells. These epithelial cells had an altered distribution forming large structures surrounding spherical masses of mononulear cells, lacked epithelial cells and often contained a central blood vessel with fibroblasts and connective tissue. We have called these structures ‘medullary epithelial rings’ (MERs). To our knowledge these structures have not been described before. Late in pregnancy the loss of the central mononuclear cells leaves collapsed structures in a smaller medulla that nevertheless retains many epithelial cells. In virgins and early-pregnancy, there are cortical channels free of epithelial cells that are very infrequent later in pregnancy. This may reflect the loss of steroid-sensitive thymocytes from the cortex. The influence of sex-steroids neurological impulses and immune activity in causing the changes are discussed, as are the possible consequences in pregnancy of a reduced, thymocyte-depleted cortex and an enlarged medulla that shows great complexity and activity.

IMMUNOLOGICAL STUDIES ON PREGNANCY IN THE MOUSE

This chapter discusses immunological studies on pregnancy in the mouse. An understanding of the immune changes in pregnancy has gained from studies of inbred and congeneic strains of mice. The use of such animals has recently clarified the extent of the antigenicity of the mouse embryo, and they are now helping to unravel the details of responses to discrete antigenic differences between mother and fetus. Studies carried out sequentially through the whole course of pregnancy show that many of the maternal responses fluctuate greatly during gestation, and that quite large changes can occur over a very short period of time. There is also evidence that cellular and humoral immunity do not necessarily go hand in hand. The chapter also discusses nonimmunological factors that influence the immune responses in pregnancy.

GENETIC AND IMMUNOLOGICAL ASPECTS OF LITTER SIZE IN THE MOUSE

The effects of antigenic differences between mother and fetus on implantation number and on post‐implantation mortality were studied. No evidence was found to support the hypothesis that these two measurements were affected by such antigenic differences or by prior immunization of the mother to paternal antigens.

C1q-binding activity of serum from allogeneically and syngeneically pregnant mice

C1q-binding activity of serum during allogeneic and syngeneic pregnancy in mice was measured using the direct [125I]C1q-binding assay. In both strains there was an initial tendency for levels to rise in very early pregnancy (Days 2 and 4) followed by a progressive fall in C1q binding to a level significantly lower than that found in non-pregnant animals. The changes were present in both syngeneic and allogeneic pregnancies but the later changes were more pronounced in the latter. The presence of changes associated with syngeneic pregnancy suggests that these profiles are at least in part independent of genetic differences between mother and embryo.

Structural and Cellular Changes in the Mouse Thymus During Pregnancy

During pregnancy in all mammals, including man, there is a massive loss of lymphocytes from the thymus. This is reflected in an excessive involution, with decreases in weight and in the numbers of thymocytes. At the end of pregnancy in the mouse, the thymus has lost 75% of its weight and cells. Involution continues during lactation, after which the thymus regenerates, becomes repopulated with lymphocytes, and regains its original size.