The rat is commonly used as a model in studies on embryology and reproduction toxicology. Surprisingly, the current literature does not provide a comprehensive reference data set on placental development in rat. Therefore, we have evaluated morphological changes of the placenta and maternal blood parameters during pregnancy of the Sprague-Dawley rat. The morphologic data presented in this study may be useful as reference material. This study revealed that placental development in the rat is a well-defined process, characterized by key synchronized morphological events at specific points in time, convenient for laboratory practice and provides the toxicologist with a sensitive tool to distinguish between normal and abnormal placental development and to detect fetal and placental mismatches. During rat pregnancy, significant changes were observed in maternal blood parameters strongly reminiscent of those observed in pregnant women. These changes included: (a) decreased blood cell volume as a result of hemodilution, (b) increased white blood cell counts reflecting the response of the mother to the fetal allograft, (c) increased blood clotting values, (d) decreased plasma glucose and increased lipid content maximizing fetal glucose availability and maternal energy conservation, and (e) decreased electrolyte values reflecting plasma volume expansion. It was concluded that the combined data set on placental morphology and maternal blood parameters in pregnant rats provides powerful tools for recognition of abnormal pregnancies.

The authors describe a selection of normal findings and common naturally occurring lesions in the reproductive system of female macaques, including changes in the ovaries, uterus, cervix, vagina, and mammary glands. Normal features of immature ovaries, uteri, and mammary glands are described. Common non-neoplastic lesions in the ovaries include cortical mineralization, polyovular follicles, cysts, ovarian surface epithelial hyperplasia, and ectopic ovarian tissue. Ovarian neoplasms include granulosa cell tumors, teratomas, and ovarian surface epithelial tumors. Common non-neoplastic uterine findings include loss of features of normal cyclicity, abnormal bleeding, adenomyosis, endometriosis, epithelial plaques, and pregnancy-associated vascular remodeling. Hyperplastic and neoplastic lesions of the uterus include endometrial polyps, leiomyomas, and rarely endometrial hyperplasia and endometrial adenocarcinoma. Vaginitis is common. Cervical lesions include endocervical squamous metaplasia, polyps, and papillomavirus-associated lesions. Lesions in the mammary gland are most often proliferative and range from ductal hyperplasia to invasive carcinoma. Challenges to interpretation include the normal or pathologic absence of menstrual cyclicity and the potential misinterpretation of sporadic lesions, such as epithelial plaques or papillomavirus-associated lesions. Interpretation of normal and pathologic findings is best accomplished with knowledge of the life stage, reproductive history, and hormonal status of the animal.

The cynomolgus monkey (Macaca fascicularis) is widely used in regulatory toxicity studies. Especially in studies on male contraception, the male reproductive tract can be an important target system. The aim of the present paper is to describe a practical approach for morphological staging of spermatogenesis in routinely prepared paraffin sections. Results obtained using this approach could help to determine possible drug-related effects on spermatogenesis. As a guide to the investigators, photomicrographs of Bouin-fixed, paraffin-embedded and H&E or PAS stained sections from testis tissue are presented to illustrate the twelve successive morphological stages (cell associations) of normal spermatogenesis. Sexually immature or peripubertal monkeys sometimes are included in toxicity studies. Since the morphological features of the testes of such monkeys can be mistaken for treatment-related abnormalities, the morphologic characteristics of these testes are described and discussed briefly.

The melanophore-stimulating hormone (MSH) cells of the amphibian pars intermedia secrete the peptide a-melanophore-stimulating hormone (a-MSH), which induces pigment dispersion in dermal melanophores. The purpose of the present study was to determine (1) whether prolonged activation of the secretory activity of the pars intermedia is associated with hypertrophy, hyperplasia, or both and (2) whether the MSH cells function as a homo geneous or heterogeneous population in meeting the physiological demand for MSH. The demand for MSH was manipulated by adapting animals for at least 3 weeks to white, two shades of grey, or black backgrounds. Morphometric analysis showed that the intermediate lobe volume was positively correlated with the degree of pigment dispersion in the mela nophores. The number of MSH cells per lobe was not affected by the degree of pigment dispersion. Therefore, we conclude that enlargement of the tissue associated with MSH cell activation involves hypertrophy rather than hyperplasia. Ultrastructural examination indi cated that the majority of MSH cells in black-adapted animals are biosynthetically active, whereas the cells of white-adapted animals are relatively inactive and show granule storage. The pars intermedia of grey-adapted toads contained both active and inactive cells, indi cating that MSH cells respond as a heterogeneous cell population in meeting the endocrine demand imposed by background. © 1990 Academic Press, inc.In general, activation of endocrine cells may involve hypertrophy, hyperplasia, or both. Furthermore, two patterns of cell re sponses can be distinguished during activa tion: either all cells become activated or only subpopulations of cells become acti vated. An example of the former are the oxytocin-producing neuroendocrine cells that respond as a homogeneous population to the suckling stimulus (Poulain and Wakerley, 1982). An example of the latter are the vasopressin-producing neuroendocrine cells that respond as a heterogeneous pop ulation to osmotic stress (Poulain and Wakerley, 1982). Morphometric and biochemi cal evidence has been advanced that the rat gonadotropes and lactotropes (Lucque et al., 1986) as well as the p cells of the pancreatic islets (Schuit et al., 1988) and thyroid follicular cells in mice (Gerber et al., 1987) form heterogeneous populations with regard to their secretory response to demand for hormone.In the present investigation we studied the response of amphibian melanophorestimulating hormone (MSH)-producing cells to a physiological stimulus. Two major questions were addressed. First, does the activation of the pars intermedia involve hypertrophy, hyperplasia, or both? Second, do the endocrine cells of this tissue function as a homogeneous or as a heterogeneous cell population in response to a demand for MSH? The MSH cell of Xenopus laevis provides a good model to study these ques tions because the pars intermedia activity can be easily manipulated. The MSH cells of animals placed on a black background release a-MSH, which stimulates pigment ...

This quantitative ultrastructural immunocytochemical study demonstrates the coexistence of a catecholamine [dopamine (DA)], an amino acid (GABA), and a neuropeptide [neuropeptide Y (NPY)] in axon varicosities innervating the pars intermedia of Xenopus laevis. The varicosities are assumed to control the pars intermedia melanotrope cells, which regulate skin color during the physiological process of background adaptation. Varicosity profiles appear to abut melanotrope cells and folliculostellate cells, star-shaped cells that intimately contact the melanotropes. All varicosity profiles contain two morphological types of vesicle. Monolabeling studies on routinely fixed and freeze-substituted tissues showed that the small, electron-lucent vesicles store GABA, whereas DA and NPY occur in larger, electron-dense ones. Double and triple labeling experiments, in which the degree of immunoreactivity was quantified per varicosity profile and per vesicle, led to the conclusion that (1) DA, GABA, and NPY coexist within almost all varicosity profiles and (2) DA and NPY are costored within electron-dense vesicles. Varicosity profiles that abut melanotrope cells show a much higher ratio between the numbers of electron-lucent and electron-dense vesicles than varicosities contacting folliculostellate cells (15.8 and 3.3, respectively). This differential distribution is in line with the previous demonstration that, in contrast to GABA, NPY does not act directly on the melanotrope cells but indirectly, by controlling the activity of the folliculostellate cells.