Although mammalian cell cultures are more difficult to maintain, they are, nevertheless, essential to space biology. Human cell lines from muscle, bone, lymphoid, kidney, liver, and other tissues can help us understand, at the molecular and cellular levels, the tissue degradation observed in previous spaceflights.

Laboratory rats and mice have long been used for studying normal and disease processes in the human, primarily because of an extensive body of knowledge of rodent physiological mechanisms, a significant number of rat models that mimic human diseases, the ease of breeding, and the ability to generate inbred congenic rat strains. Rodents are very close to humans in terms of their genome and more than 90% of proteins identified so far show similarities to known human proteins. The mouse genome has been sequenced which brings research one step further toward elucidating mechanisms underlying physiological changes experienced by astronauts during spaceflight (Figure 2-08).

When investigations address human adaptation to spaceflight and its health implications, the use of mammalian species often becomes necessary when humans are not appropriate subjects. The rat is the mammal employed most frequently for space research. Its well-demonstrated biochemical and structural similarity with humans makes the rat an appropriate subject with which to test new drugs and investigate many disorders experienced by astronauts during and after spaceflight. Because of their phylogenetic proximity to humans, nonhuman primates, such as Rhesus monkeys, have occasionally served as research subjects in space biology, but only when the need has been clearly demonstrated (Souza et al. 2000).

Figure 2-08. The Mars Gravity Biosatellite is a project from MIT to study the effects of Mars gravity on mammals. A 400-kg biosatellite carrying will rotate about its central axis, providing 0.38 g outwards against a curved floor. After 5 weeks in tow Earth orbit, the re-entry capsule will separate from the primary spacecraft to return the mice safely to a landing zone in the Australian desert. The biosatellite provides autonomous life support capabilities and data telemetry or storage from onboard experiments. Credit:

When working with higher organisms, such as mammals, stress caused by unfamiliar conditions can impact science results. To prevent this, the animals must be habituated to their flight habitat, life support hardware, and biosensors. Some animals, such as rats and rhesus monkeys, must be trained to use inflight feeding and watering devices. When performance and behavior is studied, as is sometimes the case with rhesus monkeys, the animals must be trained to perform particular tasks in response to automated stimuli.

Also, when mammals are used as research subjects, microbiological testing of the animals is mandatory to ensure that they are free of pathogens that could be transmitted to crewmembers. Organisms that are part of the science payloads must be isolated from the humans onboard so that possible contaminants and odors do not affect crew health, comfort, or performance. Hardware for housing the experiment subjects is typically custom-built for this purpose and kept sealed or filtered for the duration of the mission.

As in the case of amphibians and zebrafish, a genome project is proceeding for mice, genetic information related to developmental mutations is available, there is a great deal of homology developmental patterns. Mice also have a short developmental cycle (21-day gestation) and short life cycle (4 months). Additionally, since adults are small, habitats take less space than those of other mammals. Mice are typically used in experiments requiring large numbers of individuals. On the other hand, rats are used in experiments requiring a minimum of six individuals per treatment. However, this number of 6 can increase to 12 or 24 with additional requirements, such as the need for an onboard 1-g centrifuge control group, or the need for sacrificing the animals inflight.

Rats have a developmental cycle similar to mice and, as in the case of mice, some flight data are available and a genome project has begun. Additionally, some well-developed rat models for human disease and pathophysiology are available as is a significant rat database of maternal fetal behavior.

The results of reproductive studies done on mammals in the space environment are probably the best ones from which to extrapolate in order to estimate human limitations in this area. In one of the early experiments conducted on board the Soviet Cosmos biosatellites, flown male rats were allowed to mate with non-flight females 5, 75, and 90 days postflight. Litters of the 5 days postflight rats had a significant increase in the number of abnormalities as compared to the controls. These abnormalities were mainly in the development of the various organs. Some of the offspring also showed growth retardation though the overall infant mortality was same as the controls. Later postflight mating showed no differences in both samples (5 versus 75 and 90 days postflight samples), thereby suggesting that only the mature spermatozoa were affected during the flight (Serova 1989).

In addition to the above, male and female rats were allowed to mate in space. No pregnancies resulted, but postflight laparotomy showed that the ovulation and fertilization did occur in the rats, though for some reason embryogenesis did not proceed in the normal way. Later, the same rats were mated with nonflight rats and all the litters were found to be normal (Denisova et al. 1989).

Ground-based experiments have shown decreased number of embryos and increased embryo mortality in immobilized female rats. In the clinostat experiment, very few oocytes reached the second meiotic division. Similarly, oocytes were not found in the oviduct of female rats that had been subjected to centrifugal forces up to 3 g for 3 hours a day during the first and second days of pregnancy. However, samples that were subjected to the centrifugal force during the fifth and sixth day of pregnancy showed developed embryos but most of these were found to be morphologically abnormal.

Video footage of adult animals during centrifugation indicates that behavioral activity within the environment is reduced and limited in range. However, the behavior of animal subjects in microgravity has not been investigated, and the influence of activity-dependent stimulation on development is presumably important (Alberts and Ronca 1999). For example, neonate rats flew on board several Space Shuttle flights. The results involved losses of animals or compromised weight gain, presumably related to inadequate maternal care and limited nursing interactions with the dams. Results from these studies also suggest altered motor behavior and neuromuscular development during spaceflight.

Figure 2-09. Haplopappus gracilis has been utilized in space to test whether the normal cell division in the root tip can be sustained in microgravity, and to determine whether the fidelity of chromosome partitioning is maintained during and after spaceflight.

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