(300) Transgenerational Effects of Spaceflight on Mammalian Offspring: Behavioral and Metabolic Outcomes

Transgenerational Effects of Spaceflight on Mammalian Offspring: Behavioral and Metabolic Outcomes

Fereshteh Dalouchi¹, Stephanie A. Puukila², April E. Ronca³, E. Matthew Morris¹, John Prom¹,
Michael Ponte¹, Xiaoman Hong¹, Joshua S. Alwood⁴, Lane K. Christenson¹

1. Department of Cell Biology and Physiology, University of Kansas School of Medicine, Kansas City, USA

2. Blue Marble Space Institute of Science, Moffett Field, CA, USA,

3. Wake Forest School of Medicine, North Carolina, USA
4. NASA ARC, Moffett Field, CA, USA

Abstract Text: Reproductive health is an essential issue for prolonged space flight, as germ cell integrity and early developmental programming are particularly vulnerable to environmental stressors. Microgravity and radiation exposure during crucial phases of follicular development may cause defects in the maturation of oocytes and the follicular dynamics, which can affect the health of future generations. This research investigates the impact of maternal spaceflight exposure on F1 and F2 offspring, emphasizing behavioral, metabolic, and reproductive consequences. Twenty adult C57BL/6J (11 weeks of age) female mice were launched on the NASA Rodent Research 20 mission and spent 42 days aboard the International Space Station (ISS). Contemporary habitat and vivarium ground control dams (HGC; VGC) were exposed to similar environmental conditions (minus microgravity) as FLT dams with HGC females maintained in the same habitat as on the ISS while vivarium dams were maintained in standard cages. Upon return FLT females were mated to DBA/2J males after a 5-day period on Earth. Flight (FLT-F1), HGC-F1 and VGC-F1 offspring were subjected to behavioral assessments including locomotion analysis (Force Plate Actimeter), anxiety testing (Elevated Plus Maze), compulsive behavior examination (Marble Burying Test), and neuromotor screening (SHIRPA). To generate F2 offspring, FLT-F1 males and FLT-F1 females (similar for HGC and VGC) were mated and the resultant F2 offspring were subjected to similar behavior analyses. Furthermore, F2 offspring were exposed to high-fat diet (HFD) or a low-fat diet (LFD) for a duration of 8-weeks to evaluate metabolic responses in response to this dietary stressor. FLT-F1 females exhibited diminished locomotion and decreased compulsive behavior. Conversely, male FLT-F1 offspring displayed few behavioral variations, except for heightened risk-taking tendencies, spending more time in the open arms of the Elevated Plus Maze compared to control groups. Evaluations of F2 offspring revealed no major behavioral or locomotor differences across the 3 groups. With respect to metabolic differences, FLT-F1 offspring had reduced weights at 5, 10, 15 and 21 days of age compared to control F1 offspring.  At maturity F1 offspring (~90 days of age), FLT-F1 females exhibited differences in Echo measurements and body weight compared to controls, while no differences were seen in F1 males across the 3 groups. All F2 offspring fed the HFD experienced increased weight gain over their LFD-fed counterparts, with male FLT-HFD offspring demonstrating a significant increase over the HGC- and VGC-HFD males. Moreover, as expected blood glucose levels for male and female HFD groups were elevated over those of LFD for the HGC and VGC, while in FLT-F2 animals the LFD were same as the HFD, indicative of a preexisting difference in the FLT animals. In summary, maternal spaceflight experience impacted their offspring when compared to contemporary controls.  Moreover, this work presents new evidence that maternal exposure to spaceflight causes behavioral and metabolic alterations across two generations, with sex-specific effects observed both in F1 and F2 offspring. These findings emphasize the possible long-term impacts of spaceflight on future generations and stress the necessity for additional epigenetic and metabolic research to elucidate underlying mechanisms. As space missions progress beyond Earth's orbit, it is imperative to address these transgenerational issues to safeguard the reproductive health and welfare of future astronauts and their descendants.