An ultrastructural study of mouse and rat embryo implantation sites was undertaken to determine whether the uterine luminal epithelial cells surrounding the blastocyst exhibited the morphologic characteristics of apoptotic or necrotic cell death. In both species the epithelial cells exhibited all of the characteristics of apoptosis, including surface blebbing, shrinkage and fragmentation of the cells, condensation of chromatin, and indentation and fragmentation of nuclei. Cytoplasmic organelles remained morphologically intact, and the cytoplasm maintained normal or increased staining density. Also, the epithelial cells and cell fragments were phagocytosed by the adjacent trophoblast cells. The epithelial cells did not exhibit the characteristics of necrotic cell death, such as swollen cells and mitochondria, damaged surface membranes, and disintegrated cytoplasmic organelles. We conclude that uterine epithelial cells surrounding mouse and rat embryos during implantation undergo apoptotic cell death leading to their phagocytosis by trophoblast cells.

We investigated the role of interferon gamma (IFN-gamma) in a mouse model of immunity to vaginal infection by herpes simplex virus type 2 (HSV-2). Within 8 h after immune mice were challenged intravaginally with HSV-2, IFN-gamma concentrations in vaginal secretions reached levels that can be antiviral in vitro. This rapid synthesis of IFN-gamma occurred in immune-challenged mice but not in nonimmune-challenged mice, indicating that it required memory T cells. Immunostaining and in situ hybridization revealed that the IFN-gamma was synthesized by cells whose morphological appearance suggested that they were lymphocytes and macrophage-like cells in the mucosa. The presence of IFN-gamma in vaginal secretions was correlated with upregulation of MHC class II antigens in the epithelium and with vigorous (30-fold) recruitment of T and B lymphocytes into the vagina. In vivo administration of anti-IFN-gamma to immune mice 17 h before virus challenge blocked the subsequent appearance of IFN-gamma in vaginal secretions, blocked upregulation of class II antigens, blocked adherence of T cells to endothelium and their recruitment into the vagina, and markedly reduced immunity against reinfection of the vaginal epithelium.

SUMMARYWe compared nasal and vaginal immunizations using attenuated herpes simplex virus type-2 (HSV-2) for protection against vaginal infection with wild-type HSV-2. Mice were immunized once intranasally, intravaginally after progestin (DP) treatment, or intravaginally with scari®cation after oestradiol treatment. Compared with vaginal immunizations, nasal immunization did not increase immunoglobulin A (IgA) plasma cell numbers in the vagina or elicit a higher antiviral IgA titre in vaginal secretions. Both types of vaginal immunizations increased the number of immunoglobulin G (IgG) plasma cells in the vagina and the secretion/serum titre ratio of IgG antiviral antibody, indicating local production of virus-speci®c IgG in these groups. Cell-mediated immunity in the vagina, as indicated by memory T-cell secretion of interferon-c (IFN-c) in situ 20 hr after HSV-2 challenge, was essentially equivalent in the vaginally immunized groups but signi®cantly lower in the nasal group, while lymphocyte recruitment to the vagina was similar in all three groups. All three immunizations protected all mice from neurological disease after challenge, but vaginal DP immunization induced the greatest immunity against reinfection of the vaginal epithelium.

Immunization in the vagina can lead to the production of specific antibodies in the luminal fluid of this organ. To help understand the immune mechanisms involved in this process, we have studied the occurrence of Langerhans cells (LCs), macrophages, natural killer cells, and T and B lymphocytes in the murine vagina and cervix during the estrous cycle. LCs in the epithelia expressed Ia, F4/80, NLDC-145, and CD45, but not Mac-1, Moma-1, and Moma-2; double-labeling demonstrated phenotypic heterogeneity in this population Ia+, NLDC-145+; Ia+, NLDC-145-; Ia+, F4/80+; Ia+, F4/80-; Ia- F4/80+. T lymphocytes of both helper and cytotoxic/suppressor types were also present in the epithelia, sometimes in close association with LCs, but natural killer cells were not observed. The stroma of the vagina and cervix contained LCs (or interdigitating cells) and macrophages but few T lymphocytes and no B lymphocytes, natural killer cells, or lymphoid nodules. These observations confirm and extend previous reports that the murine vagina and cervix contain epithelial LCs and T lymphocytes and support the suggestion that antigens in the vagina and cervix, as in the epidermis, may be recognized and presented to the immune system by epithelial LCs. However, the paucity of T cells and the absence of B cells and lymphoid nodules from the stroma suggest that antigen presentation may not occur locally but at another site such as in the draining lymph nodes.

The evolution of the reproductive process has resulted in the development of elaborate adaptive mechanisms to ensure the survival of the offspring. In viviparous animals such adaptations include the development of complex and diverse forms of implantation and placentation in order to support the attachment and development of embryos in utero. The implantation process exhibits remarkable diversity among species, most prominently in the extent of trophoblastic invasion into the uterus. Yet the general aim of implantation is accomplished in all species: to attach the embryo to the uterine wall and to establish an intimate union between maternal and fetal tissues so that an exchange of nutrients and waste products can occur. The details of the earliest interactions between the blastocyst and endometrium have been the focus of extensive study. It is our purpose to summarize some of the more important developments in this field since the publication of Finn's fine review of the subject in the second edition of this book (Finn, 1977). In this chapter we have chosen to discuss four aspects of the implantation process: (1) adhesion of the trophoblast to the uterine epithelium; (2) increased vascular permeability at implantation sites; (3) the decidual cell reaction; and (4) loss of epithelial cells surrounding the implanting blastocyst. Our discussion is based primarily on the results of investigations using common laboratory animals, namely, the rat, mouse, and rabbit. In addition, other recent reviews and symposia may be of interest to the reader (Weitlauf