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Is Gravity A Continuum? Investigations Of Mechanisms Mediating Gravity-Induced Change In Mammary Metabolism And Maternal Behavior In Pregnant And Lactating Rats (NNA05CP91A)
Principal Investigator
Research Area:
Developmental biology
Species Studied
Scientific Name: Rattus norvegicus Species: Rat Strain: Sprague-Dawley


Homeostasis, the dynamic state of physiological balance, is fundamentally changed in mammals exposed to either microgravity (spaceflight) or hypergravity (centrifugation). In pregnant and lactating mammals, failure to maintain homeostasis exerts pronounced effects on both mothers and their offspring. Our previous data, derived from pregnant rats exposed to either micro- or hypergravity, support: 1) decreased mammary metabolic activity with increased gravitational force; 2) changes in maternal and neonatal energy balance; 3) altered maternal care; and 4) neonatal mortality. The specific aims are:
1. To measure metabolic and hormonal changes in metabolism during hypergravity that may explain how gravitational forces alter whole body physiology during preganncy and lactation.
2. To measure behavioral changes that are coupled with physiological changes when animals are exposed to hypergravity and have the additional stress of pregnancy and lactation.

Further studies were designed to determine if: 1) the lactation defect was caused by changes in energy balance; 2) the lactation defect could be corrected by injections of prolactin or bromocryptine; or 3) global gene expression profiles would elucidate an alternate mechanism to explain the lactation defect that occurs in hypergravity. Studies supported by this grant demonstrated that Perturbations in PRL concentration were accompanied by a decrease in PRL receptor (PRLR) mRNA abundance. Further experiments were conducted to evaluate whether glucocorticoid supplementation could increase the PRLR in animals exposed to HG. Preliminary investigations utilizing across tissue gene enrichment analysis identified derangement in a unique set of genes pivotal to lipid synthesis in HG rats, particularly, in the lactating mammary gland. Therefore, investigations were extended to map-out other alterations in transcriptional crosstalk across key metabolic tissues induced by exposure to HG during the transition from pregnancy to lactation.

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Lintault LM, Zakrzewska EI, Maple RL, Baer LA, Casey TM, Ronca AE, Wade CE, Plaut K. "In a hypergravity environment neonatal survival is adversely affected by alterations in dam tissue metabolism rather than reduced food intake." J Appl Physiol. 2007 Jun;102(6):2186-93. [DOI]

Patel OV, Maple R, Bear L, Ronca A, Wade C, Plaut K. "Tissue-specific variation in expression of prolactin receptor gene subtypes in hypergravity-exposed rats." Journal of Gravitational Physiology 2007;14: 129-30.

Casey T, Zakrzewska EI, Maple RL, Lintault L, Wade CE, Baer LA, Ronca AE, Plaut K. (2012) "Hypergravity disruption of homeorhetic adaptations to lactation in rat dams include changes in circadian clocks" Biology Open, vol. 1, no. 6, 2012, pp. 570-581. [DOI]

Patel OV, Zakrzewska E, Maple RL, Baer LA, Ronca AE, Wade CE, Plaut K. "Lipogenesis impaired in periparturient rats exposed to altered gravity is independent of prolactin and glucocorticoid secretion." Eur J Appl Physiol. 2008 Nov;104(5):847-58. doi:10.1007/s00421-008-0840-5 [DOI]

Casey, T.; Patel, O.V.; and Plaut, K. (2015). "Transcriptomes reveal alterations in gravity impact circadian clocks and activate mechanotransduction pathways with adaptation through epigenetic change." Physiol Genomics, 47(4),113-128. [DOI]

Plaut K, Maple R, Vyas C, Munaim S, Darling A, Casey T, Alberts JR. The effects of spaceflight on mammary metabolism in pregnant rats. Proc Soc Exp Biol Med. 222: 85–89, 1999.

Patel OV, Casey T, Dover H, Plaut K. "Homeorhetic adaptation to lactation: comparative transcriptome analysis of mammary, liver, and adipose tissue during the transition from pregnancy to lactation in rats." Funct Integr Genomics. 2011 Mar;11(1):193-202. doi: 10.1007/s10142-010-0193-0. Epub 2010 Sep 18. [DOI]

Casey T, Patel O, Dykema K, Dover H, Furge K, Plaut K. "Molecular signatures reveal circadian clocks may orchestrate the homeorhetic response to lactation." PLoS One. 2009 Oct 9;4(10):e7395. doi: 10.1371/journal.pone.0007395 [DOI]

Alula KM, Resau JH, Patel OV. Chronic exposure to altered gravity during the pregnancy-to-lactation transition affects abundance of cytoskeletal proteins in the rat mammary gland. Gravit Space Res. 2018 Jul;6(1):58-72.

Data Information
Data Availability
Archive is complete. No data sets are available for this experiment. Please Contact LSDA if you know of available data for this investigation.

Mission/Study Information
Mission Launch/Start Date Landing/End Date Duration
STS-70 07/13/1995 07/22/1995 9 days

Additional Information
Managing NASA Center
Ames Research Center (ARC)
Responsible NASA Representative
Institutional Support
National Aeronautics and Space Administration (NASA)
Proposal Date
Proposal Source
2001 Space Biology 01-OBP