Mammalian Reproduction and Development on the International Space Station (ISS): Proceedings of the Rodent Mark III Habitat Workshop
, , oraz | 01 lip 2013
O artykule
Article Category: Review
Data publikacji: 01 lip 2013
Zakres stron: 107 - 123
DOI: https://doi.org/10.2478/gsr-2013-0009
© 2013 April E. Ronca et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.
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Concerns, Risks, and Knowledge Gaps from the Workshop Discussion on Breeding. Birthing, and Postnatal Development in Space
| Subcategory | Basic Science (S) / Hardware (H) / Enabling Science (ES) | Risk (R) / Concern (C) / Gap (G) | Concerns, Risks, & Knowledge Gaps | Risk Mitigation Approaches |
|---|---|---|---|---|
| Cross-cutting issues | S | G, R | What are the changes in endocrine status, including HPG axis and prolactin during spaceflight? | |
| S | G, R | Are there fertilization issues during spaceflight? | Artificial Insemination | |
| S | G | Does the elevated radiation level affect reproduction or fetal/neonatal development? | Localized dosimetry at or near (or that closely resembles the shielding characteristics of) the habitat and any exposure from DXA machine. | |
| H, ES | C, G | Information is needed to enable the understanding of behavior and of experiment failures. | Video and monitoring of key parameters | |
| H, ES | C, G | Does the environment (i.e., air circulation, noise) within the habitat impede acoustic and olfactory communication between neonates and dam? | Define and measure indices of survivability and thrivability | |
| H | C, G | Required crew access to animals should inform cage design and procedures (science, safety, etc), see SRED. | ||
| H | C | Cage design will play an important role in promoting or inhibiting success of all categories of reproduction and development. | Wall surface texture and grip; dimensions of birthing space; space for the young to huddle and suckle; temperature control | |
| ES | C, G | Does the current diet present any nutritional deficiencies impeding aspects of reproduction? | Pair feeding. Measure food and water intake. | |
| ES | C, G | What are the enrichment requirements for Breeders? | ||
| ES | G | What is the acclimation period before harems are ready to mate? | Generate data from a Mark I experiment. | |
| ES | C, G | How long have prior foodbar tests/studies been performed? Are there any foodbar inadequacy or stability issues with long-term use of the foodbar? | ||
| ES | C | Most of the knowledge is from studies using rats. Issues can emerge from extrapolation to mice. | Continue using rats to plan validation flight study and to test new hypothesis. Replicate some of the earlier rat-studies with mice in a stepwise fashion. | |
| Mating Behavior | S | G, R | Is copulation affected by space flight? | Selection of proven breeders or breeding pairs |
| S | G, R | Is estrous cycling altered by space flight? | ||
| H, ES | G, R | Are pre-mating behaviors and courtship affected by space flight or the habitat design? | Selection of proven breeders or breeding pairs | |
| Lactation | S | G, R | What are the changes in endocrine status during spaceflight, including HPG axis and prolactin? | Observing through skin: milk bands (acquiring milk); tooth eruption. Gauging milk let-downs through video |
| S | G, R | Is the quality and quantity of milk altered during space flight? | Pre- vs. during- flight comparison | |
| S | G, R | Do changes in immune function (antibody status in milk; absorption) affect lactation? | ||
| H, S | G, R | Are nursing behaviors of the dam and pup, including suckling and retrieving, altered during space flight? | Consider cage design to promote these behaviors. Use video to analyze behaviors. Also, apply a pre-flight candidate selection filter of the dam (define whether she is a gatherer, or not, and define the quality of her milk). | |
| ES | C, G | Is the foodbar adequate for lactation? | ||
| Pre-Fertilization | S | G, R | Are gonad and gametogenesis and their functions compromised during space flight? | |
| S | G, R | Is the endocrine status, including HPG axis, altered by spaceflight environment? | ||
| S | G, R | Are post-gonad gamete formation, function, and maturation compromised? | ||
| Fertilization | S, ES | G | Does the current diet present any nutritional deficiencies impeding aspects of fertilization? | Pair feeding. Measure food and water intake. |
| S | G, R | Are sperm-egg signaling and interactions compromised? | ||
| S | G, R | Is pre-implantation development compromised in the dam? | Consider results of STS-131, -133, -135 for underlying mechanisms in mouse. | |
| S | G, R | Is signaling in the fertilized egg compromised by mechanisms including altered gene regulation and DNA damage? | ||
| Implantation | S | G, R | Does mating trigger proper signaling to prepare uterine epithelium for implantation? | |
| S | G, R | Are adhesion and implantation gravity dependent? | ||
| S | G, R | Are uterine epithelial health and stem cells compromised? | ||
| Placentation | S | G, R | Does decreased connexin-43 levels affect placentation during spaceflight? | |
| S | G, R | During spaceflight, does placentation depend on changes in vascular tone? | ||
| S | G, R | Are the signals for placental formation intact? | ||
| S | G, R | During spaceflight, does placentation depend on changes in the immune system? | ||
| S | G, R | What are the statuses of prolactins and other pro-placentation endocrine signals during spaceflight? | ||
| Organogenesis | S | G, R | Are organ formation, maturation, and function compromised during spaceflight? | |
| S | G, R | Are the endocrine-driven fetal-development phases that define the sex of offspring altered during spaceflight? | ||
| Birth (also see cross-cutting) | S | R | Will reduced strength in abdominal musculature affect birth? | Caesarean section |
| S | C, R | Will altered uterine contraction strength affect birth? | Cage design - wall surface texture and grip; dimensions of birthing space | |
| S | G, R | Does the likelihood of a successful birth depend on genetic strain of rat? | ||
| H, S | G, R | Is the maternal care pattern at birth intact? | 1 hour of pup cooling - temperature regulation; Video and temperature monitoring; space for the young | |
| ES | C | With regards to testosterone formation, the temperature exposure of male pups should be closely monitored and potentially regulated. | Include capability for thermography of the pups within the habitat. | |
| Perinatal Development (PND 0-8) | H, S | G, R | Are the pups receiving milk in similar manner as ground controls? | Observing through skin: milk bands (acquiring milk); tooth eruption. Gauging milk-let downs through video |
| H, ES | G | Is the amount or quality of sleep that the neonates receive affected by spaceflight or cage design? | Video | |
| H, ES | C | In case of cannibalism, how to quantify the number of pups that were initially born? | Video. Count # that are born. Higher frequency of monitoring around key milestones. | |
| ES | C | How will individual pups be identified for further monitoring? | Ink in footpad or tail tatoo/marking, toe-clipping. Crew access. ANG; coat color. | |
| ES | C | Body mass shall be recorded 2x/week. | Repeated measurement of body mass is important during the first few weeks post-natal to assess growth. | |
| Infant Development (PND 8-14) | S | G | Do changes in the development of ovaries and testes occur during spaceflight? | |
| H, S | G, C | Is the amount or quality of sleep that the neonates receive affected by spaceflight or cage design? | Video | |
| H, ES | C | Huddle formation needs to be considered during cage design, as it is an integral aspect of neonatal development. | Cage design (artificial nest) | |
| H, ES | G | Does the relative humidity need to be regulated within a specific range for neonates? | ||
| H, ES | G | Are there thermal-regulation requirement differences between pups and mother? | Cage design (compartments with unique thermal regulation). Thermography capability needed. | |
| Pre-Weaning (PND 15-21) | S | G | Do changes in the development of ovaries and testes occur during spaceflight? | |
| S | C | Milestone: Independent ingestion should occur around PND15 (Neurolab). | ||
| Adolescence (PND 28-35) | ES | C, R | Consider the risk of impregnation of siblings at sexual maturity when establishing age to separate the litter. | Male-female separation Mice: approx. 21-35 days Rats: approx. 45-80 days |
Examples of relevant flight experiments requiring a RH Mark III Habitat.
| Multigenerational survival comprises a cycle of lifespan functional milestones at the multiple levels: Whole animal, organ and endocrine systems, and cell
A failure or deficit in any milestone compromises species survival |
| Does male and female sexual definition and development proceed normally in the space environment?
Gonad development, maturation and health Gamete production, maturation and health |
| Are patterns of social behavior and mating affected by the space environment?
Ex-gonad gamete maturation in the female reproductive tract Fertilization, conceptus, placentation, fetal development Support of pregnancy, birth, lactation, nursing, weaning Post-weaning growth, puberty, acquisition of sexual maturity |
| Is the neural architecture of the brain, particularly the gravity sensing system, shaped by gravity?
Morphology of the neurovestibular system |
| Are vestibular mediated behaviors shaped by gravity, and are these correlated with changes in vestibular morphology? |
| Is development of the motor system dependent upon gravitational input?
Emergence of fine motor control of locomotion and gait may require gravitational input during development |
| Are there critical periods during pre- and/or postnatal life during which gravity exerts formative effects? |
| Does lack of gravitational input to the vestibular macular sensory organs, beginning prior to conception and continuing into adulthood, ‘developmentally program’ circadian and homeostatic processes across the lifespan and generations? |
| Is there epigenetic (non-genomic) cross-generational heritability of early life programming by gravity?
Identifiable epigenetic changes in DNA methylation patterns may be associated with development in microgravity (a direct effect) distinct from indirect maternal contributions to epigenetic programming of offspring phenotype |
| For animals born in space and undergoing development, growth and aging are there critical periods of development and growth that require gravity?
On-orbit, temporal, noninvasive bone density and shape measurements, body weight to assess growth, temporal muscle diameter and length measurements, tissue acquisition and preservation of bone, cartilage, and muscle at key time points. Intact sample return for earth-based analyses |
| Is stem cell production (myoblasts, osteoblasts, osteoclasts, bone marrow cells) reduced during prolonged spaceflight?
Quantify stem cell 1G to evaluate reloading injury and the capacity for repair that is dependent on stem cell participation. 1G restores stem cell deficiency or reveals permanent deficiencies |
| General Physiology & Immunology
Altered regulation (System to Genome) Adaptive capabilities (i.e., 0->1G) |
| CNS Function
Covered by Neuroscience & Behavior Group Role in altered sensory signaling, esp. Central (Vestibular) sensing, in altering genome |
| Musculoskeletal System
Covered by Musculoskeletal Group |
| Growth, Body Size and Composition
Sex, Health |
| Endocrinology |
| Metabolism
Energetics, Nutrition, Gastrointestinal |
| Cardiovascular & Blood (i.e., Oxygen transport) |
| Temperature Regulation |
| Circadian Biology |
| Immune Function |
| External Stimuli
Exercise, Centrifugation |
| Number one application is drug or gene therapy testing (interpretations/contingency with off-target effects), in particular, where disease models would apply to young children (e.g., muscular dystrophy, myopathies) |
| Use of transgenic models would be likely. |
| Neonates: Model of severe disuse conditions for children |
| Dam: Model of pregnancy and delivery during conditions of disuse |
List of Participants
| Participant | Affiliation |
|---|---|
| Jeffrey Alberts, PhD ( |
Indiana University, Bloomington |
| Joshua S. Alwood, PhD Executive Secretary | Oak Ridge Associated Universities |
| Ted A. Bateman, PhD | University of North Carolina |
| Shawn G. Bengtson | McGowan Institute, University of Pittsburgh |
| Allison Brown | LifeSource Biomedical, LLC |
| Kristin D. Evans, PhD, DVM | University of California, Davis |
| Charles A. Fuller, PhD | University of California, Davis |
| Ruth K. Globus, PhD | NASA Lead, NASA Ames Research Center |
| Mike Hines | NASA Ames Research Center |
| Danny A. Riley, PhD | Medical College of Wisconsin |
| April E. Ronca, PhD, Workshop Co-Chair | Wake Forest School of Medicine |
| Stephanie Solis, DVM | LifeSource Biomedical, LLC |
| Kenneth A. Souza, Workshop Co-Chair | Logyx, LLC |
| Marianne Steele, PhD | Lockheed Martin |
| Louis S. Stodieck, PhD | BioServe Space Technologies, University of Colorado at Boulder |
| Joseph S. Tash, PhD | University of Kansas Medical Center |