Lack of effects of oxolinic acid on spermatogenesis in young adult and aged Wistar rats.

Prolonged treatment with oxolinic acid is known to elevate serum luteinizing hormone (LH) levels, resulting in induction of Leydig cell tumors in rats. In a carcinogenicity study of the compound, tubular atrophy of the testis was also increased, suggesting that oxolinic acid might affect spermatogenesis. The present study was therefore performed using rats of different ages with a particular focus on seminiferous tubule alteration and its relation to Leydig cell proliferation. Young adult (7 weeks of age) and aged (52 weeks of age) males of the Wistar strain were administered oxolinic acid at dietary concentrations of 0 (basal diet), 300, 1000 or 3000 ppm for 4 (all groups), 13 (0 and 3000 ppm groups), 26 (0 and 3000 ppm groups), or 52 weeks (0 and 3000 ppm groups of aged rats). Serum LH levels were elevated in both young adult and aged animals treated with 3000 ppm at most examined time points. While testosterone levels were also increased at the early time points in young adult, this was not the case in older animals. Elevation of the incidences of foci and/or focal hyperplasia of Leydig cells was noted but was only slight limited to aged rats treated with 3000 ppm after 26 weeks. Furthermore, it did not appear to be related to seminiferous tubular alteration. No treatment-related histopathological abnormalities could be detected in any treatment group, and morphometrical stage analysis of spermatogenesis conducted for the control and 3000 ppm-treated groups demonstrated no lesions. These results provide strong evidence that prolonged oxolinic treatment does not directly induce testicular toxicity or altered spermatogenesis in either young adult or aged rats, except for slight increase of Leydig cell proliferative lesions caused by elevated serum LH levels. Aged rats might have higher sensitivity than young adults to the effects of oxolinic acid on proliferative lesions of Leydig cells.

Recording of blood pressure, heart rate and aortic nerve activity during parabolic flight in the rat via radio-telemetry.

Exposure to microgravity induces cardiovascular deconditioning characterized by orthostatic hypotension when astronauts return to the earth. In order to understand the mechanism of cardiovascular deconditioning, it is necessary to clarify the changes in hemodynamics and the cardiovascular regulation system over the period of space flight. The telemetry system applied to freely moving animals will be a useful and appropriate technique for this kind of long term study of the cardiovascular system in the conscious animal during space flight. The purpose of the present study is twofold: firstly, to observe the detailed changes of arterial pressure and heart rate (HR) during microgravity elicited by the parabolic flight in order to study the acute effect of microgravity exposure on the cardiovascular system; and secondly, to test the feasibility of the telemetry system for recording blood pressure, HR and autonomic nervous activities continuously during space flight.

Mechanical tensile properties of the aortic wall in the premature rat exposed to the microgravity environment during space flight for 16 days.

Under microgravity environment, blood shifts headward and thereafter decrease in volume to adapt to the environment, which could affect cardiovascular hemodynamics and their regulatory mechanisms. Baroreceptor sensitivity is known to be reduced in newborn animals and to gradually increase with development. The baroreceptor is a stretch receptor; therefore its function is closely related to the rheological properties and fine structure of the aortic wall in which the baroreceptor lies. The mechanical and histological properties could be altered under microgravity conditions in the process of development with change in circulatory function. In the present study, we investigated the mechanical tensile characteristics and histological structure of the aortic wall in the proximal thoracic aorta of premature rats bred in the microgravity environment of the space shuttle for 16 days.

Estrogen receptor mRNA in uteri of normal estrous cycling and ovariectomized rats by in situ hybridization.

Biological effects of estrogen are mediated via its binding to the estrogen receptor (ER), the contents of its protein and mRNA varying during the estrous cycle. In the present study, the ERalpha mRNA expression in different cell components of the uterus was investigated in normal estrous cycling rats using nonisotopic in situ hybridization. Additionally, ovariectomized (OVX) rats treated with 17beta-estradiol (E2: 5 microg/kg, sc injection daily) were also investigated to clarify the effects of exogenous E2. At proestrus and diestrus, and especially the former, the luminal and glandular epithelial (LE and GE) cells were strongly positive, along with stromal cells beneath the luminal epithelium. At estrus, the expression was slightly diminished in LE cells, but almost completely lacking in GE cells. At metestrus, positive signals appeared again in GE cells. In the myometrium, ER mRNA was demonstrated to be constantly positive in all estrous cycle stages. OVX rat uteri underwent marked atrophy, but ER mRNA still remained in all cell types. After 2 consecutive days of E2 treatment, markedly increased intensity was observed, especially in LE and GE cells. The uteri of OVX rats treated with E2 for 14 days, however, showed slightly diminished expression, whereas the serum concentration of E2 was comparable to that in rats after 2 days. These results provide evidence that cell-type specific patterns of ER mRNA expression characterize the uteri of both normal estrous cycling rats and OVX rats after estrogen treatment.

Frequency distribution of axon diameters in the left aortic nerve of the rat raised in space--Neurolab Program.

INTRODUCTION: To study development of the aortic baroreflex mechanisms under conditions of microgravity, we carried out the various experiments in the neonate rats aged 25 days raised in microgravity for 16 days (flight: FLT group) in Neurolab program (STS-90, space shuttle Columbia, launch date: Apr 17, '98. Some results of the experiments were already reported. The results of histological examination of the aortic nerve which is the afferent of the aortic baroreflex showed that the number of unmyelinated fibers in FLT was significantly less in than those in two control groups and there was no difference between FLT and each control group in the analysis of myelin. In the present paper, the frequency distribution of axon diameters of the left aortic nerves in FLT was compared to that in two ground control groups to examine the growth of the aortic nerve fibers in space. METHODS: After breeding Sprague-Dawley rats for 16 days in the shuttle in space and in the animal center in the Kennedy space center, a total of 43 deeply anesthetized rats were perfused with 1% parahormaldehyde and 1% glutaraldehyde or 4% parahormaldehyde solution buffered at pH7.4 with 0.12 M phosphate solution. Concerning the control groups, one group was the asynchronous ground control (AGC) group in which the rats were housed in the same cages as those on the shuttle, and the other was the vivarium ground control (VIV) group in which the rats were housed in commercial cages. The cervical region of the left aortic nerve which is a branch of the vagus was cut off and stored in the same fixative as that used for perfusion, and postfixed in the solution of 1% OsO4, for 2 hours within 24 hours after the perfusion. The fixed specimens were embedded in epoxy resin blocks by the usual method for electron microscopy following dehydration. Electron microscopic montages of transverse sections of these nerve trunks were made from the five left aortic nerves in each group. The magnification of the montages was approximately 13400 times. The long and short axes (a and b) of the nerve fibers and the myelin thickness (T) were measured with a caliper and the axon diameters (R were calculated by following formula: R2=[(a-2T)2+(b-2T)2]/2.

Histological analysis of the aortic nerve in the rat raised in space (Rapid communication on Neurolab Project).

To study development of the aortic nerve baroreflex under conditions of microgravity, we examined the cross section of the left aortic nerve (LAN), which is the afferent of the baroreflex, in the neonate rats aged 25 days raised in microgravity on the space shuttle Columbia (flight:FLT group) for 16 days. In this paper, we report a part of the result obtained from the data of the myelinated fibers of LAN analyzed with an electron microscope. Two kind of ground control groups were compared to the FLT group; one was asynchronous ground control (AGC) group where the rats were housed in the same cage as that on the shuttle, and the other was vivarium(VIV) group where the rats were housed in a commercial cage. The LANs in each group were extirpated the from rats perfused with a fixative and embedded for histological analysis. We observed the transverse sections of LAN and took pictures of several areas (magnified to x 2K to x 200K). No irregular myelination was found in all fibers of FLT group when they were compared with two control groups. The thickness of myelin of the maximally myelinated fibers were 0.55 +/- 0.17 micrometer in FLT(n=5), 0.45 +/- 0.10 micrometer in AGC(n=5), and O.47 +/- 0.06 micrometer meter in VIV(n=5). There was no significant difference among three groups (unpared t-test). The results suggest that there is no effect of space environment on the myelin formation of each nerve fiber in the aortic nerve.