We used scanning electron microscopy to count the number of mucous gland openings in the tracheae and lower portion of the larynges of the rat, guinea pig, hamster, mouse and rabbit. Cells of the airway surface epithelium were removed by protease digestion better to visualise the gland openings. The distribution of glands was further studied by conventional histology and by PAS/Alcian blue staining of whole mounts. In all rodent species, gland openings in the larynx occurred with a frequency of 1–2 per mm2. Mice had no gland openings in their tracheae, and hamsters, only a handful. Rat tracheae contained 126±42 gland openings (±S.D.; n = 6) at a frequency of ∼ 0.6 per mm2 at the top of the trachea and ∼ 0.15 per mm2 at the bottom. Guinea pig tracheae contained 153±90 gland openings (±S.D.; n = 5), with 54% being in the top 40% of the trachea. In both rat and guinea pig, tracheal glands were found in the ventral aspect between the cartilaginous rings, and were absent from the dorsal membranous portion. Gland openings in most species were simple circles of ∼ 50 μm diameter. However, glands in the rat trachea generally opened obliquely into shallow (∼ 20 μm deep) oval troughs (∼ 150×75 μm), which had their long axes oriented from head to tail. In the rabbit, there was no evidence of tracheal or laryngeal glands histologically. However, the tracheal and laryngeal surfaces contained numerous pits (∼ 30 μm diameter) distributed evenly over and between cartilages at a frequency of ∼ 4 per mm2. These may correspond to the ‘nests’ of goblet cells described by others.

We investigated the immunohistochemical localisation of types II and X collagen as well as the cytochemical localisation of alkaline phosphatase in the developing condylar cartilage of the fetal mouse mandible on d 14–16 of pregnancy. On d 14 of pregnancy, although no immunostaining for types II and X collagen was observed, alkaline phosphatase activity was detected in all cells in the anlage of the future condylar process. On d 15 of pregnancy, immunostaining for both collagen types was simultaneously detected in the primarily formed condylar cartilage. Alkaline phosphatase activity was also detected in chondrocytes at this stage. By d 16 of pregnancy, the hypertrophic cell zone rapidly increased in size. These findings strongly support a periosteal origin for the condylar cartilage of the fetal mouse mandible, and show that progenitor cells for condylar cartilage rapidly or directly differentiate into hypertrophic chondrocytes.

This study examined the tissue level mineralisation density distribution in mandibles from 88 adult humans. Mandibles (19–96 y) were sectioned vertically in midline (MID), mental foramen (MF), and third molar (M3) regions. Surgical fragments from M3 were obtained from individuals aged 16–38 y. All specimens were cleaned, embedded in PMMA, micromilled and examined by digital 20 kV backscattered electron (BSE) stereology. Quantitation was based on rescaling image histograms to the signal range between a monobrominated (0) and a monoiodinated (255) dimethacrylate resin standard. Mineralisation density increased with age (r=0.70; P<0.0001): the mean for 39 individuals aged between 16 and 50 y was significantly lower (P<0.0001) than for 35 individuals over 51 y (mean (±S.E.M.): 158.20 (1.63) and 174.71 (1.27) normalised grey level units respectively). There was good correlation in mean mineralisation density between different sites in the same mandible, but MID was significantly less highly mineralised than the other sites: MID 173.90, MF 177.34, M3 177.11 (P<0.002 and 0.01 for MF and M3 respectively; paired t test), as was the alveolar bone density when compared with the bone of the inferior cortex (e.g. MID: 171.13 (1.53) and 174.46 (1.14) P<0.0001). No sex difference was found. Partially dentate mandibles generally had regions of higher mineralisation than fully dentate and edentulous mandibles. The lowest density bone occurred at the alveolar crest anteriorly and superolingually at M3, matching sites of net resorption following tooth loss. Highest densities were found inferolingually at MID, inferiorly at MF and buccally at M3, matching the sites thought to experience the highest functional strains. This stresses the importance that local factors may have in the remodelling of the edentulous mandible. Morphology showed that there is a preponderance of highly mineralised cement lines, and of packets containing dead, mineralised, osteocytes.

Compared with other joints, the ligaments of the ankle have not been studied in great detail; consequently relatively little literature exists. The positions of the 3 major bands of the lateral collateral ligament are well known and documented (Schafer et al. 1915; Sarrafian, 1983; McMinn, 1994; Palastanga et al. 1994; Williams et al. 1995). The detailed anatomy of the ligaments is, however, relatively complex with variations of the major bands and several minor additional bands being reported (Sarrafian, 1993; Burks & Morgan, 1994; Rosenberg et al. 1995).

This review covers a number of aspects of the behaviour of oligodendrocyte progenitors following transplantation into the adult CNS. First, an account is given of the ability of transplanted oligodendrocyte progenitors, grown in tissue culture in the presence of PDGF and bFGF, to extensively remyelinate focal areas of persistent demyelination. Secondly, we describe how transplanted clonal cell lines of oligodendrocyte progenitors will differentiate into astrocytes as well oligodendrocytes following transplantation into pathological environments in which both oligodendrocytes and astrocytes are absent, thereby manifesting the bipotentially demonstrable in vitro but not during development. Finally, a series of studies examining the migratory behaviour of transplanted oligodendrocyte progenitors (modelled using the oliodendrocyte progenitor cell line CG4) are described. These show that CG4 cells do not survive (or migrate) when transplanted into the normal adult CNS. However, if they are transplanted into CNS tissue that has previously been exposed to 40 Gy of x-irradiation then transplanted CG4 cells survive, divide and migrate over large distances. Moreover, within an x-irradiated environment, migrating transplanted CG4 cells are able to enter remotely located foci of demyelination and contribute to the remyelination of the demyelinated axons within. These studies demonstrate that although the normal adult CNS does not appear to support survival and migration of the CG4 cell line, it is possible to manipulate the environment in such a way that these nonpermissive properties of the environment can be overcome.

As part of a large comparative study on the development of reptilian skin, we provide the first ultrastructural description of differentiation of the epidermis of the carapace and plastron in the Chelonia, using the Australian pleurodiran turtle Emydura macquarii as a model. The epidermis is initially composed of an external flat peridermis and a basal layer of cuboidal cells. During differentiation, the peridermis darkens, flakes off and is partially lost before hatching. Four to 6 layers of flat cells containing lipids and mucus form from the basal layer beneath the external peridermis. Because such cells are found only during embryogenesis, we have referred to these layers as embryonic epidermis. They contain reticulate bodies made of a meshwork of coarse filaments similar to those described in the inner peridermis of lizard and bird embryos. In advanced embryos, cells of the embryonic epidermis condense into a thin dark stratum which is subsequently lost after hatching. The lowermost 2 layers of the embryonic epidermis keratinise, as for a typical lepidosaurian α-layer. A splitting zone is progressively formed beneath the α-layer to separate the embryonic epidermis from the underlying β-layer. Patterns of cytodifferentiation of the β-synthesising cells over the carapace and plastron essentially resemble those of the lepidosaurian epidermis. The β-keratin matrix initially accumulates among ribosomes as round bodies not clearly surrounded by a membrane. These bodies appear not to be derived from the Golgi apparatus. Melanosomes and other dark granules of uncertain nature are present among early differentiating β-cells. The round β-keratin bodies merge with the dense bodies to produce the definitive variegated pattern of the mature β-keratin layer. The histochemistry suggests that calcium combines with organic molecules within β-keratinising cells to harden the tissue. In contrast to the β-keratin cells of lizards and snakes, cells of the mature β-keratin layer of E. macquarii maintain their cell boundaries in part or completely, a characteristics shared with the β-keratin layer of Sphenodon and crocodilians.

There are limited data detailing the pattern of age and gender-related changes to the thoracic vertebral bodies and intervertebral discs. A retrospective MR investigation, involving T1-weighted midsagittal images from 169 cases, was undertaken to examine age influences on the anterior wedge (anteroposterior height ratio or Ha/Hp), biconcavity (midposterior height ratio or Hm/Hp), and compression indices (posterior height/anteroposterior diameter or Hp/D) of the thoracic vertebral bodies. Disc degenerative changes in the annulus, nucleus, end-plate and disc margin were noted on T2-weighted sagittal images for the 169 cases, based on a 3-level grading system. A linear age-related decline in the Ha/Hp and Hm/Hp indices was noted. The Hp/D index increased during the first few decades of life, then decreased gradually thereafter. The prevalence of abnormal findings in the annuli, nuclei and disc margins increased with increasing age, particularly in the mid and lower thoracic discs. Greater disc degenerative changes were observed in males. These findings provide further insight into the nature of thoracic vertebral shape changes across the lifespan, and the typical patterns of degeneration of the thoracic intervertebral discs.

The cellular events leading to the generation of Schwann cells from the neural crest have recently been clarified and it is now possible to outline a relatively simple model of the Schwann cell lineage in the rat and mouse. Neural crest cells have to undergo 3 main developmental transitions to become mature Schwann cells. These are the formation of Schwann cell precursors from crest cells, the formation of immature Schwann cells from precursors and, lastly, the postnatal and reversible generation of non-myelin- and myelin-forming Schwann cells. Axonal signals involving neuregulins are important regulators of these events, in particular of the survival, proliferation and differentiation of Schwann cell precursors.

The variation in frequency of the Inca bone was examined in major human populations around the world. The New World populations have generally high frequencies of the Inca bone, whereas lower frequencies occur in northeast Asians and Australians. Tibetan/Nepalese and Assam/Sikkim populations in northeast India have more Inca bones than do neighbouring populations. Among modern populations originally derived from eastern Asian population stock, the frequencies are highest in some of the marginal isolated groups. In Central and West Asia as well as in Europe, frequency of the Inca bone is relatively low. The incidence of the complete Inca bone is, moreover, very low in the western hemisphere of the Old World except for Subsaharan Africa. Subsaharan Africans show as a whole a second peak in the occurrence of the Inca bone. Geographical and ethnographical patterns of the frequency variation of the Inca bone found in this study indicate that the possible genetic background for the occurrence of this bone cannot be completely excluded. Relatively high frequencies of the Inca bone in Subsaharan Africans indicate that this trait is not a uniquely eastern Asian regional character.

The posterior hypothalamic nucleus has been implicated as an area controlling autonomic activity. The afferent input to the nucleus will provide evidence as to its role in autonomic function. In the present study, we aimed to identify the detailed anatomical projections to the posterior hypothalamic nucleus from cortical, subcortical and brainstem structures, using the horseradish peroxidase (HRP) retrograde axonal transport technique in the rat. Subsequent to the injection of HRP into the posterior hypothalamic nucleus, extensive cell labelling was observed bilaterally in various areas of the cerebral cortex including the cingulate, frontal, parietal and insular cortices. At subcortical levels, labelled cells were observed in the medial and lateral septal nuclei, the bed nucleus of stria terminalis, and various thalamic and amygdaloid nuclei. Also axons of the vertical and horizontal limbs of the diagonal band were labelled and labelled cells were localised at the CA1 and CA3 fields of the hippocampus and the dentate gyrus. The brainstem projections were from the medial, lateral and parasolitary nuclei, the intercalated nucleus of the medulla, the sensory nuclei of the trigeminal nerve, and various reticular, vestibular, raphe and central grey nuclei. The posterior hypothalamic nucleus also received projections from the lateral and medial cerebellar nuclei and from upper cervical spinal levels. The results are discussed in relation to the involvement of the posterior hypothalamic nucleus in autonomic function and allows a better understanding of how the brain controls visceral function.

The aim of this study was to investigate the developmental characteristics of the mandibular condyle in sequential phases at the gene level using in situ hybridisation. At d 14.5 of gestation, although no expression of type II collagen mRNA was observed, aggrecan mRNA was detected with type I collagen mRNA in the posterior region of the mesenchymal cell aggregation continuous with the ossifying mandibular bone anlage prior to chondrogenesis. At d 15.0 of gestation, the first cartilaginous tissue appeared at the posterior edge of the ossifying mandibular bone anlage. The primarily formed chondrocytes in the cartilage matrix had already shown the appearance of hypertrophy and expressed types I, II and X collagens and aggrecan mRNAs simultaneously. At d 16.0 of gestation, the condylar cartilage increased in size due to accumulation of hypertrophic chondrocytes characterised by the expression of type X collagen mRNA, whereas the expression of type I collagen mRNA had been reduced in the hypertrophic chondrocytes and was confined to the periosteal osteogenic cells surrounding the cartilaginous tissue. At d 18.0 of gestation before birth, cartilage-characteristic gene expression had been reduced in the chondrocytes of the lower half of the hypertrophic cell layer. The present findings demonstrate that the initial chondrogenesis for the mandibular condyle starts continuous with the posterior edge of the mandibular periosteum and that chondroprogenitor cells for the condylar cartilage rapidly differentiate into hypertrophic chondrocytes. Further, it is indicated that sequential rapid changes and reductions of each mRNA might be closely related to the construction of the temporal mandibular ramus in the fetal stage.

The process of wound healing begins with an inflammatory reaction that is principally dependent on cellular immune elements. Although the involvement in wound healing of leucocytes that mediate nonspecific immunity (e.g. neutrophils and macrophages) is well known, the participation of cells which prime the immune reaction, i.e. the lymphocytes, requires further investigation. This study was performed to examine the temporal sequence and kinetics of these cells during cutaneous wound repair. The model selected was a full-thickness skin excisional wound made on the flanks of female Wistar rats. At time points ranging from 3 h to 2 wk wound samples were processed for polyester wax-embedding. Target antigens were identified and monitored quantitatively in sections stained immunohistochemically. Monoclonal antibodies against neutrophils, macrophages, pan T cells and cytotoxic populations of lymphocytes were used. The results showed that these cells are involved in the process of wound healing in a distinctive dynamic pattern. The accumulation of CD3+ T lymphocytes in the wound bed was mainly associated with the phase of granulation tissue formation. Intraepithelial CD3+ T lymphocytes were detected in considerable numbers within the regenerating epidermis. The cytotoxic cell populations (OX8+ ) were classified morphologically into the cytotoxic/suppressor subset of T cells and NK cells. The OX8+ T cells were shown to have a kinetic pattern similar to CD3+ T lymphocytes but of a lower magnitude. The accumulation of OX8+ NK cells was confined to the early inflammatory phase of repair. It is concluded that CD3+ T lymphocytes as well as OX8+ cytotoxic populations of the immune system are involved in the process of cutaneous wound healing in temporal sequences which suggest that they may be involved in its modulation.

When the tibialis anterior muscle of the rabbit is progressively stretched during surgical limb distraction, the muscle fibres lengthen by addition of new serial sarcomeres, provided that stretch is carried out at an appropriate rate. However, in spite of the apparent adaptation to the new functional length, range of joint movement is greatly decreased. In this study we have first, made measurements of the passive tension developed by distracted muscles over the range of joint movement and secondly made quantitative measurements of endomysial and perimysial connective tissue content. It was found that at all ankle joint angles greater than 90°, the passive tension developed by the distracted muscles was greater than both contralateral and sham-operated controls. Image analysis showed that the ratio of collagen to contractile material was increased in distracted muscles compared with muscles from sham-operated controls, due to increased deposition of collagen type III. Scanning electron microscopy showed the presence of a dense perimysial weave surrounding the distracted muscle fibres. These quantitative and qualitative changes in the connective tissue component could account for the increased stiffness demonstrated by the physiological measurements. It would seem that in distracted muscle the connective tissue element adapts less readily than the contractile component, with prolonged stretch leading to damage to the perimysial and endomysial network, with subsequent fibrosis and loss of muscle compliance. Such changes could help explain the loss of range of movement noted in the distracted limbs of patients undergoing surgical limb-lengthening and in other conditions that result in muscle contractures.

The formation of the first epidermal generations and in particular of the shedding complex in the developing scales of the lizards Anolis lineatopus and Podarcis muralis was studied by electron microscopy. The initially linear and bilayered epidermis turned into symmetric papillae, which became asymmetric scales. The outer periderm was more electrondense than the following layer, provisionally named ‘inner periderm’ but probably derived from the basal layer. Coarse thick filaments progressively filled the cytoplasm of the inner periderm or formed reticulate bodies resembling avian peridermal granules. Peridermal cells cornified slightly and could be shed in ovo. From the basal layer various suprabasal epithelial layers were produced. The first layer contained keratohyalin-like granules and was identified as a clear layer. Beneath it a spinulated (Anolis) or serrated (Podarcis) oberhäutchen differentiated. The clear and ‘oberhäutchen’ layers constitute the first shedding complex. The first epidermal layers that were shed consisted of flaking periderm or periderm together with the clear layer. The differentiation of a mesos layer was under way before hatching, when the epidermal morphology resembled a stage 4–5 of the adult shedding cycle. Fibroblasts under the inner side of the scale made few contacts with the basement membrane and their cytoplasmic elongations were mostly oriented parallel to the dense lamina. Instead, fibroblasts under the basal layer of the outer scale surface (BLOS) made numerous contacts with the basement membrane, suggesting that more dermal–epidermal interactions take place on this side of the scale.

Classic ideas on mechanisms for axon sprouting and nerve regeneration from peripheral nerves suggest that there is a prominent role for neurotrophin support. There has been comparatively less attention towards features of the regenerative process that develop from the proximal nerve trunk without the support of target tissues or the denervated trunk of a peripheral nerve. We studied early (2–14 d) expression of local growth factors in proximal nerve stump tips of transected sciatic nerves in rats. Immunohistochemical labelling was used to address specific deposition of BDNF, NGF, NT-3, bFGF, CNTF and IGF-1. We observed a unique localisation of BDNF, and to a much lesser extent, NGF in mast cells of injured nerve trunks but they were also observed in intact uninjured nerves. Macrophages did not express either BDNF or NGF. CNTF and IGF-1 were expressed in Schwann cells of intact nerves and stumps. We did not observe bFGF or NT-3 expression in any of the samples we studied. Mast cells may represent an important reservoir of BDNF in peripheral nerves.

Anatomical and electromyographic studies point to regional differences in function in the human temporalis muscle. During chewing and biting the anterior portions of the muscle are in general more intensively activated and they are capable of producing larger forces than the posterior portions. It was hypothetised that this heterogeneity in function is reflected in the fibre type composition of the muscle. The composition and surface area of different fibre types in various anteroposterior portions of the temporalis muscle were investigated in 7 cadavers employing immunohistochemistry with a panel of monoclonal antibodies against different isoforms of myosin heavy chain. Pure slow muscle fibres, type I, differed strongly in number across the muscle. In the most posterior portion of the muscle there were 24% type I fibres, in the intermediate portion 57%, and in the most anterior portion 46%. The mean fibre cross-sectional area (m-fcsa) of type I fibres was 1849 μm2, which did not differ significantly across the muscle. The proportion of pure fast muscle fibres, type IIA and IIX, remained more or less constant throughout the muscle at 13% and 11% respectively ; their m-fcsa was 1309 μm2 and 1206 μm2, respectively, which did not differ significantly throughout the muscle. Pure type IIB fibres were not found. The relative proportion of hybrid fibres was 31% and did not differ significantly among the muscle portions. Fibre types I+IIA and cardiac α+I+IIA were the most abundant hybrid fibre types. In addition, 5% of the type I fibres had an additional myosin isoform which has only recently been described by means of electrophoresis and was named Ia. In the present study they were denoted as hybrid type I+Ia muscle fibres. It is concluded that intramuscular differences in type I fibre distribution are in accordance with regional differences in muscle function.

Connective tissues synthesise and secrete a family of matrix metalloproteinases (MMPs) which are capable of degrading most components of the extracellular matrix. Animal studies suggest that the MMPs play a role in bone turnover. Using specific polyclonal antisera, immunohistochemistry was used to determine the patterns of synthesis and distribution of collagenase (MMP-1), stromelysin (MMP-3), gelatinase A (MMP-2) and gelatinase B (MMP-9) and of the tissue inhibitor of metalloproteinases-1 (TIMP-1) within developing human osteophytic bone. The different MMPs and TIMP showed distinct patterns of localisation. Collagenase expression was seen at sites of vascular invasion, in osteoblasts synthesising new matrix and in some osteoclasts at sites of resorption. Chondrocytes demonstrated variable levels of collagenase and stromelysin expression throughout the proliferative and hypertrophic regions, stromelysin showing both cell-associated and strong matrix staining. Intense gelatinase B expression was observed at sites of bone resorption in osteoclasts and mononuclear cells. Gelatinase A was only weakly expressed in the fibrocartilage adjacent to areas of endochondral ossification. There was widespread but variable expression of TIMP-1 throughout the fibrous tissue, cartilage and bone. These results indicate that MMPs play a role in the development of human bone from cartilage and fibrous tissue and are likely to have multiple functions.

The development of the patella, its associated tendons, and suprapatella of the rabbit knee joint is described from the 17 d fetus to the mature adult. The patellar tendon (ligament) with the patella on its posterior surface is seen in the 17 d fetus and is fully developed by 1 postnatal wk. It is composed of bundles of types I and V collagens separated by endotenons of types III and V collagens. Anteriorly there is an epitenon of types III and V collagens while synovium and a fat pad cover its posterior surface. In the 25 d fetus, the patella is cartilaginous and is separated from the femoral condyles. The cartilage contains type II collagen, but types I, III and V collagens are found along the articular surface. Ossification starts 1 postnatal wk and at 6 wk only the articular cartilage remains. In addition to type II, types III and V collagens are located around the chondrocyte lacunae. The long anterior junction between the patella and its tendon is fibrocartilaginous at 1 wk, but as ossification proceeds this is replaced by bone. Types I and V collagens are found in this region. The suprapatella on the posterior surface of the quadriceps tendon is first seen 1 wk postnatally as an area of irregularly organised fibres and chondrocyte-like cells. Types I, II, III and V collagens are present from 3 wk onwards. It is compared with the fibrocartilage of other tendons that are under compression. The arrangement of the collagens in the patellar tendon is discussed in relation to its use as a replacement for injured anterior cruciate ligaments. It is suggested that the structural differences between the patellar tendon and anterior cruciate ligament preclude the translocated tendon acquiring mechanical strength similar to that of a normal cruciate ligament. The designation ‘patellar ligament’ as opposed to ‘patellar tendon’ is questioned. It is argued that the term patellar tendon reflects its structure more accurately than patellar ligament.

Recently, mutations of the alpha-synuclein gene were found to cause dominantly inherited Lewy-body Parkinson's disease (PD) and alpha-synuclein was identified as a major component of the Lewy body. However, the cause of the common form of PD, with a multifactorial rather than autosomal dominant inheritance pattern, remains unknown. Alpha-synuclein precipitates slowly and apparently spontaneously at high concentration in solution and the mutations that cause PD accelerate precipitation. Other dominantly inherited late-onset or adult-onset dominantly inherited neurodegenerative diseases are associated with precipitation of proteins. In Alzheimer disease, beta-amyloid and tau abnormalities are present and in prion disorders, prion proteins are found. In Huntington disease, a disorder with expanded CAG repeats, huntingtin precipitates occur. In dominantly inherited spinocerebellar ataxias, also expanded CAG repeat disorders, the corresponding ataxin protein precipitates are found. In multiple system atrophy, alpha- synuclein precipitates are encountered and in progressive supranuclear palsy, tau precipitates occur. In familial amyotrophic lateral sclerosis, a group of dominantly inherited disorders, SOD1 precipitates are found. Most of these disorders can involve the basal ganglia in some way.

Since similar processes seem to affect neurons of adults or older individuals and since a relatively limited group of proteins seems to be involved, each producing a form of neurodegeneration, it is possible that certain common features are present that affect this group of proteins. Candidates include a conformational shift, as in prions, an abnormality of the ubiquitin-proteosome pathway, as seen in PD, an abnormality of a pathway preventing precipitation (e.g. chaperonins), or potentiation of a pathway promoting precipitation (e.g. gamma-glutamyl-transpeptidase) or apoptosis. Elucidation of the pathways causing this protein insolubilisation is the first step towards approaching prevention and reversal in these late-onset neurodegenerative diseases.

Exposure of male Albino Swiss rats to the nonsteroidal antiandrogen flutamide during the period from gestational day (d) 10 to birth resulted in feminisation of the external genitalia and the suppression of growth of the male reproductive tract. In adulthood, testes were found to be located in diverse positions. True cryptorchidism occurred in 10% of cases, whereas 50% of testes descended to the scrotum and 40% were located in a suprainguinal ectopic region. Varying degrees of tubule abnormality were seen in the testes of flutamide-treated animals, ranging from completely normal tubules with full spermatogenesis (and the expected frequency of the stages of spermatogenesis) to severely abnormal tubules lined with Sertoli cells only. For each individual testis, the overall severity of tubule damage was strongly correlated with its adult location, with intra-abdominal testes worst affected and scrotally-located testes least; only the latter contained normal tubules. Similarly, intra-abdominal testes were the smallest in weight and contained the least testosterone. By contrast, postnatal treatment of male rats with flutamide from birth to postnatal d 14 did not impair development of the external genitalia, the process of testicular descent or adult spermatogenesis. These findings confirm that androgen blockade during embryonic development interferes with testicular descent but also demonstrate that (1) prenatal flutamide treatment per se has a detrimental effect on adult testis morphology but (2) the degree of abnormality of the testes is strongly influenced by location.