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NASA NTRS2002

Models to study gravitational biology of Mammalian reproduction

Mammalian reproduction evolved within Earth's 1-g gravitational field. As we move closer to the reality of space habitation, there is growing scientific interest in how different gravitational states influence reproduction in mammals. Habitation of space and extended spaceflight missions require prolonged exposure to decreased gravity (hypogravity, i.e., weightlessness). Lift-off and re-entry of the spacecraft are associated with exposure to increased gravity (hypergravity). Existing data suggest that spaceflight is associated with a constellation of changes in reproductive physiology and function. However, limited spaceflight opportunities and confounding effects of various nongravitational factors associated with spaceflight (i.e., radiation, stress) have led to the development of ground-based models for studying the effects of altered gravity on biological systems. Human bed rest and rodent hindlimb unloading paradigms are used to study exposure to hypogravity. Centrifugation is used to study hypergravity. Here, we review the results of spaceflight and ground-based models of altered gravity on reproductive physiology. Studies utilizing ground-based models that simulate hyper- and hypogravity have produced reproductive results similar to those obtained from spaceflight and are contributing new information on biological responses across the gravity continuum, thereby confirming the appropriateness of these models for studying reproductive responses to altered gravity and the underlying mechanisms of these responses. Together, these unique tools are yielding new insights into the gravitational biology of reproduction in mammals.

Review, Tutorial↗

NASA NTRS1996

Cardiovascular effects of a fractional -Gz force during a relatively prolonged exposure

Artificial hypogravity was created by having subjects remain in a supine position while undergoing rotation in an artificial gravity simulator. Various cardiovascular variables, such as heart rate, cardiac output, thoracic electric impedance, and blood pressure were measured. Results indicated that the hypogravity force produced a headward fluid shift, as seen by a decrease in thoracic impedance, which triggers regulatory neuroendocrine mechanisms. These findings are presented and discussed.

Non-NASA Center↗

NASA NTRS1980

Piracetam and fish orientation during parabolic aircraft flight

Goldfish were flown in parabolic Keplerian trajectories in a KC-135 aircraft to assay both the effectiveness of piracetam as an antimotion sickness drug and the effectiveness of state-dependent training during periods of oscillating gravity levels. Single-frame analyses of infrared films were performed for two classes of responses - role rates in hypogravity or hypogravity orienting responses (LGR) and climbing responses in hypergravity or hypergravity orienting responses (HGR). In Experiment I, preflight training with the vestibular stressor facilitated suppression of LGR by the 10th parabola. An inverse correlation was found between the magnitudes of LGR and HGR. Piracetam was not effective in a state-dependent design, but the drug did significantly increase HGR when injected into trained fish shortly before flight. In Experiment II, injections of saline, piracetam, and modifiers of gamma-aminobutyric acid - aminooxyacetic acid (AOAA) and isonicotinic acid did not modify LGR. AOAA did significantly increase HGR. Thus, the preflight training has a beneficial effect in reducing disorientation in the fish in weightlessness, but the drugs employed were ineffective.

Hoffman, R. B.↗

NASA NTRS1980

Evaluation of biological models using Spacelab

Biological models of hypogravity effects are described, including the cardiovascular-fluid shift, musculoskeletal, embryological and space sickness models. These models predict such effects as loss of extracellular fluid and electrolytes, decrease in red blood cell mass, and the loss of muscle and bone mass in weight-bearing portions of the body. Experimentation in Spacelab by the use of implanted electromagnetic flow probes, by fertilizing frog eggs in hypogravity and fixing the eggs at various stages of early development and by assessing the role of the vestibulocular reflex arc in space sickness is suggested. It is concluded that the use of small animals eliminates the uncertainties caused by corrective or preventive measures employed with human subjects.

Tollinger, D.↗

NASA NTRS1981

Growth and development of cultured carrot cells and embryos under spaceflight conditions

Morphogenetically competent proembryonic cells and well-developed somatic embryos of carrot at two levels of organization were exposed for 18.5 days to a hypogravity environment aboard the Soviet Biosatellite Cosmos 1129. It was confirmed that cultured totipotent cells of carrot can give rise to embryos with well-developed roots and minimally developed shoots. It was also shown that the space hypogravity environment could support the further growth of already-organized, later somatic embryonic stages and give rise to fully developed embryo-plantlets with roots and shoots.

Krikorian, A. D.↗

NASA NTRS1985

Space-flight simulations of calcium metabolism using a mathematical model of calcium regulation

The results of a series of simulation studies of calcium matabolic changes which have been recorded during human exposure to bed rest and space flight are presented. Space flight and bed rest data demonstrate losses of total body calcium during exposure to hypogravic environments. These losses are evidenced by higher than normal rates of urine calcium excretion and by negative calcium balances. In addition, intestinal absorption rates and bone mineral content are assumed to decrease. The bed rest and space flight simulations were executed on a mathematical model of the calcium metabolic system. The purpose of the simulations is to theoretically test hypotheses and predict system responses which are occurring during given experimental stresses. In this case, hypogravity occurs through the comparison of simulation and experimental data and through the analysis of model structure and system responses. The model reliably simulates the responses of selected bed rest and space flight parameters. When experimental data are available, the simulated skeletal responses and regulatory factors involved in the responses agree with space flight data collected on rodents. In addition, areas within the model that need improvement are identified.

Brand, S. N.↗

NASA NTRS1985

Localization of calcium stimulated adenosine triphosphatase activity in blood vessels of the skeleton

Alkaline phosphatase is an enzyme found in bone forming cells which decreases in certain bones as a result of hypogravity or non-weight bearing. This enzyme can also hydrolyze adenosine triphosphate. Therefore, an effort was made to localize calcium-stimulated ATPase by cytochemistry to determine whether altered bone cell activity might be related to changing calcium levels which occur during hypogravity. The results indicate that Ca(++)-ATPase is largely found along the endothelium and basal lamina of blood vessels, and not found in bone forming cells. This suggests that calcium regulation in the vicinity of bone formation may be modulated by the vasculature of the area.

Doty, S. B.↗

NASA NTRS1989

Do the design concepts used for the space flight hardware directly affect cell structure and/or cell function ground based simulations

The use of clinostats and centrifuges to explore the hypogravity range between zero and 1 g is described. Different types of clinostat configurations and clinostat-centrifuge combinations are compared. Some examples selected from the literature and current research in gravitational physiology are presented to show plant responses in the simulated hypogravity region of the g-parameter (0 is greater than g is greater than 1). The validation of clinostat simulation is discussed. Examples in which flight data can be compared to clinostat data are presented. The data from 3 different laboratories using 3 different plant species indicate that clinostat simulation in some cases were qualitatively similar to flight data, but that in all cases were quantitatively different. The need to conduct additional tests in weightlessness is emphasized.

Chapman, David K.↗

NASA NTRS1990

Effects of microgravity on rat bone, cartlage and connective tissues

The response to hypogravity by the skeletal system was originally thought to be the result of a reduction in weight bearing. Thus a reduced rate of new bone formation in the weight-bearing bones was accepted, when found, as an obvious result of hypogravity. However, data on non-weight-bearing tissues have begun to show that other physiological changes can be expected to occur to animals during spaceflight. This overview of the Cosmos 1887 data discusses these results as they pertain to individual bones or tissues because the response seems to depend on the architecture and metabolism of each tissue under study. Various effects were seen in different tissues from the rats flown on Cosmos 1887. The femur showed a reduced bone mineral content but only in the central region of the diaphysis. This same region in the tibia showed changes in the vascularity of bone as well as some osteocytic cell death. The humerus demonstrated reduced morphometric characteristics plus a decrease in mechanical stiffness. Bone mineral crystals did not mature normally as a result of flight, suggesting a defect in the matrix mineralization process. Note that these changes relate directly to the matrix portion of the bone or some function of bone which slowly responds to changes in the environment. However, most cellular functions of bone are rapid responders. The stimulation of osteoblast precursor cells, the osteoblast function in collagen synthesis, a change in the proliferation rate of cells in the epiphyseal growth plate, the synthesis and secretion of osteocalcin, and the movement of water into or out of tissues, are all processes which respond to environmental change. These rapidly responding events produced results from Cosmos 1887 which were frequently quite different from previous space flight data.

Doty, S.↗

NASA NTRS1990

Fluid and electrolyte homeostasis during spaceflight: Elucidation of mechanisms in a primate

Although it is now well accepted that exposure to the hypogravic environment of space induces a shift of fluid from the lower extremities toward the upper body, the actual physiological responses to this central volume expansion have not been well characterized. Because it is likely that the fluid and electrolyte response to hypogravity plays a critical role in the development of Cardiovascular Deconditioning, elucidation of these mechanisms is of critical importance. The goal of flight experiment 223, scheduled to fly on SLS-2, is the definition of the basic renal, fluid and electrolyte response to spaceflight in four instrumented squirrel monkeys. The studies were those required to support the development of flight hardware and optimal inflight procedures, and to evaluate a ground-based model for weightlessness, lower body positive pressure (LBPP).

Churchill, Susanne↗

NASA NTRS1992

Understanding the organization of the amphibian egg cytoplasm - Gravitational force as a probe

A combination of hypergravity (centrifugation) and hypogravity (clinostat) studies have been carried out on amphibian (frog, Xenopus) eggs. The results reveal that the twinning caused by centrifugation exhibits substantial spawning to spawning variation. That variation can be attributed to the apparent viscosity of the egg's internal cytoplasm. Simulated hypogravity results in a relocation of the egg's third (horizontal) cleavage furrow, toward the equator. Substantial egg-to-egg variation is also observed in this 'cleavage effect'. For interpreting spaceflight data and for using G-forces as probes for understanding the egg's architecture the egg variation documented herein should be considered.

Neff, Anton W.↗

NASA NTRS1996

Some Pecularities of the Graviresponse in Vaucheria

The growth and position of nuclei in the siphonaceous alga Vaucheria sessilis were investigated under conditions of hypergravity and hypogravity. Under hypergravity conditions, active sporogenesis was observed. The accumulation of nuclei in the apical and branching zone preceeded the sporogenesis. The anti-microtubular agent, colchicine inhibits sporogenesis and the response of Vaucheria to hypergravity. Under hypogravity conditions, the quantity of nuclei increased throughout the whole branch. Colchicine prevents the migration of nuclei from the apical zone to the basal part of the branch. The anti-actin agent phalloidin prevents the formation of an actin network, and phalloidin-poisoned cells lose a cluster of nuclei in the apical zone. However, the gravity dependent response is less pronounced. It is supposed that, in Vaucheria sessilis, the primary stages of the reception and translation of gravitational signals coincide with those for light signals and active division of nuclei in the growth zone is an integral part of the graviresponse.

Gavrilova, O. V.↗

NASA NTRS1978

Effects of Radiation on Rat Retina after 18 days of Space Flight

Although cumulative effects an retina from low-dose radiation during prolonged spaceflight are not known, ary impairment of vision could set limits for spaceflight duration. Cosmic rays are now considered to be the cause of the "light flashes" seen during spaceflight by activating retina cells as they pass through the photoreceptors. Previous studies have also shown retinal cellular alterations and cell necrosis from high-energy, particle (HZE) radiation. Ten rats, 5 centrifuged during flight (FC) to simulate gravity and 5 in-flight stationary (FS) experiencing hypogravity, orbited Earth for 18.5 days on Cosmos 936. The animals were sacrificed 25 days post-recovery and the eyes flown to Ames Res. Ctr. The pattern of cell necrosis in the retinas from the FC group showed the same response to radiation as the FS. This would indicate that hypogravity was not a factor in the observed results. Also the cellular response in the retinas exposed in the Berkeley accelerator again matched both the FC and FS eyes. Thus all three conditions provide comparable changes and indicate HZE particles as the possible cause of the cellular alterations, channels, and breakdown.

Philpott, D.↗

NASA NTRS2005

Artificial Gravity Research Project

Protecting the health, safety, and performance of exploration-class mission crews against the physiological deconditioning resulting from long-term weightlessness during transit and long-term hypogravity during surface operations will require effective, multi-system countermeasures. Artificial gravity (AG), which would replace terrestrial gravity with inertial forces generated by rotating the transit vehicle or by a human centrifuge device within the transit vehicle or surface habitat, has long been considered a potential solution. However, despite its attractiveness as an efficient, multi-system countermeasure and its potential for improving the environment and simplifying operational activities (e.g., WCS, galley, etc.), much still needs to be learned regarding the human response to rotating environments before AG can be successfully implemented. This paper will describe our approach for developing and implementing a rigorous AG Research Project to address the key biomedical research questions that must be answered before developing effective AG countermeasure implementation strategies for exploration-class missions. The AG Research Project will be performed at JSC, ARC, extramural academic and government research venues, and international partner facilities maintained by DLR and IMBP. The Project includes three major ground-based human research subprojects that will lead to flight testing of intermittent short-radius AG in ISS crewmembers after 201 0, continuous long-radius AG in CEV crews transiting to and from the Moon, and intermittent short-radius AG plus exercise in lunar habitats. These human ground-based subprojects include: 1) a directed, managed international short-radius project to investigate the multi-system effectiveness of intermittent AG in human subjects deconditioned by bed rest, 2) a directed, managed long-radius project to investigate the capacity of humans to live and work for extended periods in rotating environments, and 3) a focused, investigator-initiated project to investigate system-specific adaptation to and from rotating environments. The AG Research Project also includes two major animal research subprojects: 1) a directed, managed ground-based subproject using rodents and, possibly, sub-human primates, to address mechanistic issues that cannot be studied in humans, to rapidly develop higher sample numbers than can be achieved in the human subprojects, and to establish feasible parameter operating bands to reduce the breadth of the human subprojects, and 2) a flight subproject using rodents to estimate the physiological effects of long term exposure to hypogravity and to investigate the effects of contamination by terrestrial gravity in estimating AG effectiveness. The animal flight subproject would be performed aboard ISS using the CAM module in approximately the 2008-201 1 timeframe. The paper will first present an overview of the key biomedical research questions to be answered. It will then describe the overall approaches to be utilized in developing and implementing the AG Research Project, including definition of the intended scientific research, management and development approaches, identification of roles and responsibilities, risk management, and definition of project deliverables. The primary focus of the paper will be on the first of the three ground-based human research subprojects, since it is the only one currently in development and is scheduled to start active subject investigations in April of 2005.

Kamman, Michelle R.↗

NASA NTRS2006

Response of Ambulatory Human Subjects to Artificial Gravity (Short Radius Centrifugation)

Prolonged exposure to microgravity results in significant adaptive changes, including cardiovascular deconditioning, muscle atrophy, bone loss, and sensorimotor reorganization, that place individuals at risk for performing physical activities after return to a gravitational environment. Planned missions to Mars include unprecedented hypogravity exposures that would likely result in unacceptable risks to crews. Artificial gravity (AG) paradigms may offer multisystem protection from the untoward effects of adaptation to the microgravity of space or the hypogravity of planetary surfaces. While the most effective AG designs would employ a rotating spacecraft, perceived issues may preclude their use. The questions of whether and how intermittent AG produced by a short radius centrifuge (SRC) could be employed have therefore sprung to the forefront of operational research. In preparing for a series of intermittent AG trials in subjects deconditioned by bed rest, we have examined the responses of several healthy, ambulatory subjects to SRC exposures.

Paloski, William H.↗

NASA NTRS1995

Gravitropic responses of the Avena coleoptile in space and on clinostats. II. Is reciprocity valid?

Experiments were undertaken to determine if the reciprocity rule is valid for gravitropic responses of oat coleoptiles in the acceleration region below 1 g. The rule predicts that the gravitropic response should be proportional to the product of the applied acceleration and the stimulation time. Seedlings were cultivated on 1 g centrifuges and transferred to test centrifuges to apply a transverse g-stimulation. Since responses occurred in microgravity, the uncertainties about the validity of clinostat simulation of weightlessness was avoided. Plants at two stages of coleoptile development were tested. Plant responses were obtained using time-lapse video recordings that were analyzed after the flight. Stimulus intensities and durations were varied and ranged from 0.1 to 1.0 g and from 2 to 130 min, respectively. For threshold g-doses the reciprocity rule was obeyed. The threshold dose was of the order of 55 g s and 120 g s, respectively, for two groups of plants investigated. Reciprocity was studied also at bending responses which are from just above the detectable level to about 10 degrees. The validity of the rule could not be confirmed for higher g-doses, chiefly because the data were more variable. It was investigated whether the uniformity of the overall response data increased when the gravitropic dose was defined as (gm x t) with m-values different from unity. This was not the case and the reciprocity concept is, therefore, valid also in the hypogravity region. The concept of gravitropic dose, the product of the transverse acceleration and the stimulation time, is also well-defined in the acceleration region studied. With the same hardware, tests were done on earth where responses occurred on clinostats. The results did not contradict the reciprocity rule but scatter in the data was large.

Flight Experiment↗

NASA NTRS1995

Gravitropic responses of the Avena coleoptile in space and on clinostats. I. Gravitropic response thresholds

We conducted a series of gravitropic experiments on Avena coleoptiles in the weightlessness environment of Spacelab. The purpose was to test the threshold stimulus, reciprocity rule and autotropic reactions to a range of g-force stimulations of different intensities and durations The tests avoided the potentially complicating effects of earth's gravity and the interference from clinostat ambiguities. Using slow-speed centrifuges, coleoptiles received transversal accelerations in the hypogravity range between 0.l and 1.0 g over periods that ranged from 2 to 130 min. All responses that occurred in weightlessness were compared to clinostat experiments on earth using the same apparatus. Characteristic gravitropistic response patterns of Atuena were not substantially different from those observed in ground-based experiments. Gravitropic presentation times were extrapolated. The threshold at 1.0 g was less than 1 min (shortest stimulation time 2 min), in agreement with values obtained on the ground. The least stimulus tested, 0.1 g for 130 min, produced a significant response. Therefore the absolute threshold for a gravitropic response is less than 0.1 g.

Flight Experiment↗

NASA NTRS1974

Medical legacy of Apollo

Since Apollo crews enjoyed freedom of movement and experienced many of the same problems as earlier crews, confinement had to be ruled out in the etiology of space flight-related changes. Apollo was a mission of physiological firsts: the first inflight illnesses were reported, and a series of cardiac arrhythmias occurred. The most important physiological changes were decreased cardiovascular responsiveness, reduced red blood cell mass, and musculoskeletal deterioration. Vestibular-related problems were also noted for the first time. Crewmen lost weight as a result of a hypocaloric regimen inflight and a tendency to lose body tissue under hypogravic conditions. Aldosterone production increased causing some intracellular fluid loss. Very few of the crewmen experienced any psychological problems after Apollo.

Berry, C. A.↗