Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Reproductive hazards of space travel in women and men

An Author Correction to this article was published on 30 October 2019

This article has been updated

Abstract

Extended travel in deep space poses potential hazards to the reproductive function of female and male astronauts, including exposure to cosmic radiation, microgravity, increased gravity (hypergravity), psychological stress, physical stress and circadian rhythm disruptions. This Review focuses on the effects of microgravity, hypergravity and cosmic radiation. Cosmic radiation contains protons, helium nuclei and high charge and energy (HZE) particles. Studies performed on Earth in which rodents were exposed to experimentally generated HZE particles have demonstrated a high sensitivity of ovarian follicles and spermatogenic cells to HZE particles. Exposure to microgravity during space flight and to simulated microgravity on Earth disrupts spermatogenesis and testicular testosterone synthesis in rodents, whereas the male reproductive system seems to adapt to exposure to moderate hypergravity. A few studies have investigated the effects of microgravity on female reproduction, with findings of disrupted oestrous cycling and in vitro follicle development being cause for concern. Many remaining data gaps need to be addressed, including the effects of microgravity, hypergravity and space radiation on the male and female reproductive tracts, hypothalamic–pituitary regulation of reproduction and prenatal development of the reproductive system as well as the combined effects of the multiple reproductive hazards encountered in space.

Key points

  • Space travel exposes astronauts to multiple potential reproductive hazards, including cosmic radiation, microgravity and hypergravity.

  • Oocytes and their surrounding ovarian somatic cells as well as differentiating testicular spermatogenic cells are highly sensitive to destruction by high charge and energy particles typical of space radiation.

  • Exposure to high charge and energy particles results in accelerated depletion of the ovarian reserve and premature ovarian failure; by contrast, spermatogonial stem cells in the testis are fairly radioresistant, allowing spermatogenesis to recover.

  • Long-term exposure to microgravity during low Earth orbit and simulated microgravity on Earth decreased spermatogenesis; serum and testicular concentrations of testosterone were decreased in some studies and unchanged in others.

  • Exposure to microgravity during the second half of pregnancy does not cause major disruptions of fetal development or parturition in rodents.

  • Exposure to hypergravity during mating and through the neonatal period decreases pregnancy rates and neonatal offspring survival in rodents.

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Proposed mechanisms of HZE particle radiation-induced destruction of ovarian follicles.
Fig. 2: Proposed mechanisms of HZE particle radiation-induced destruction of testicular germ cells.

Change history

  • 30 October 2019

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

References

  1. 1.

    Evans, M. C. & Anderson, G. M. Integration of circadian and metabolic control of reproductive function. Endocrinology 159, 3661–3673 (2018).

    CAS  PubMed  Google Scholar 

  2. 2.

    Boden, M. J., Varcoe, T. J. & Kennaway, D. J. Circadian regulation of reproduction: from gamete to offspring. Prog. Biophys. Mol. Biol. 113, 387–397 (2013).

    CAS  PubMed  Google Scholar 

  3. 3.

    Sominsky, L. et al. Linking stress and infertility: a novel role for ghrelin. Endocr. Rev. 38, 432–467 (2017).

    PubMed  Google Scholar 

  4. 4.

    Nargund, V. H. Effects of psychological stress on male fertility. Nat. Rev. Urol. 12, 373–382 (2015).

    CAS  PubMed  Google Scholar 

  5. 5.

    Task Group on Radiation Protection in Space et al. ICRP, 123. Assessment of radiation exposure of astronauts in space. ICRP Publication 123. Ann. ICRP 42, 1–339 (2013).

    Google Scholar 

  6. 6.

    Slaba, T. C. et al. GCR Simulator Reference Field and a Spectral Approach for Laboratory Simulation. NASA Technical Publication, NASA/TP-2015-218698 (NASA, 2015).

  7. 7.

    Cucinotta, F. A. & Durante, M. Cancer risk from exposure to galactic cosmic rays: implications for space exploration by human beings. Lancet Oncol. 7, 431–435 (2006).

    CAS  PubMed  Google Scholar 

  8. 8.

    Spitz, D. R., Azzam, E. I., Li, J. J. & Gius, D. Metabolic oxidation/reduction reactions and cellular response to ionizing radiation: a unifying concept in stress response biology. Cancer Metastasis Rev. 23, 311–322 (2004).

    CAS  PubMed  Google Scholar 

  9. 9.

    Dayal, D., Martin, S. M., Limoli, C. L. & Spitz, D. R. Hydrogen peroxide mediates the radiation-induced mutator phenotype in mammalian cells. Biochem. J. 413, 185–191 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Sridharan, D. M., L.J., C., Whalen, M. K., Cucinotta, F. A. & Pluth, J. M. Defining the biological effectiveness of components of high-LET track structure. Radiat. Res. 184, 105–119 (2015).

    CAS  PubMed  Google Scholar 

  11. 11.

    Tokuyama, Y., Furusawa, Y., Ide, H., Yasui, A. & Terato, H. Role of isolated and clustered DNA damage and the post-irradiating repair process in the effects of heavy ion beam irradiation. J. Radiat. Res. 56, 446–455 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Sridharan, D. M. et al. Understanding cancer development processes after HZE-particle exposure: role of ROS, DNA damage repair and inflammation. Radiat. Res. 183, 1–26 (2015).

    CAS  PubMed  Google Scholar 

  13. 13.

    Steller, J. G., Alberts, J. R. & Ronca, A. E. Oxidative stress as cause, consequence, or biomarker of altered female reproduction and development in the space environment. Int. J. Mol. Sci. 19, 3729 (2018).

    PubMed Central  Google Scholar 

  14. 14.

    Aitken, R. J. & Roman, S. D. in Molecular Mechanisms in Spermatogenesis (ed C. Y. Cheng) Ch. 9, 154-171 (Landes Bioscience and Springer Science+Business Media, 2008).

  15. 15.

    Devine, P. J., Perreault, S. D. & Luderer, U. Roles of reactive oxygen species and antioxidants in ovarian toxicity. Biol. Reprod. 86, 27 (2012).

    PubMed  Google Scholar 

  16. 16.

    Zhu, H., Wang, H. & Liu, Z. Effects of real and simulated weightlessness on the cardiac and peripheral vascular functions of humans: a review. Int. J. Occup. Med. Environ. Health 28, 793–802 (2015).

    PubMed  Google Scholar 

  17. 17.

    Tanaka, K., Nishimura, N. & Kawai, Y. Adaptation to microgravity, deconditioning, and countermeasures. J. Physiol. Sci. 67, 271–281 (2017).

    PubMed  Google Scholar 

  18. 18.

    Ade, C. J., Broxterman, R. M. & Barstow, T. J. VO2max and microgravity exposure: convective versus diffusive O2 transport. Med. Sci. Sports Exerc. 47, 1351–1361 (2015).

    PubMed  Google Scholar 

  19. 19.

    Bergouignan, A. et al. Towards human exploration of space: the THESEUS review series on nutrition and metabolism research priorities. NPJ Microgravity 2, 16029 (2016).

    PubMed  PubMed Central  Google Scholar 

  20. 20.

    Vernikos, J. & Schneider, V. S. Space, gravity and the physiology of aging: parallel or convergent disciplines? A mini-review. Gerontology 56, 157–166 (2010).

    PubMed  Google Scholar 

  21. 21.

    Prisk, G. K. Microgravity and the respiratory system. Eur. Respir. J. 43, 1459–1471 (2014).

    PubMed  Google Scholar 

  22. 22.

    Herranz, R. et al. Ground-based facilities for simulation of microgravity: organism-specific recommendations for their use, and recommended terminology. Astrobiology 13, 1–17 (2013).

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Tou, J., Ronca, A., Grindeland, R. & Wade, C. Models to study gravitational biology of mammalian reproduction. Biol. Reprod. 67, 1681–1687 (2002).

    CAS  PubMed  Google Scholar 

  24. 24.

    Jennings, R. T. & Baker, E. S. Gynecological and reproductive issues for women in space: a review. Obstet. Gynecol. Surv. 55, 109–116 (2000).

    CAS  PubMed  Google Scholar 

  25. 25.

    Jain, V. & Wotring, V. E. Medically induced amenorrhea in female astronauts. NPJ Microgravity 2, 16008 (2016).

    PubMed  PubMed Central  Google Scholar 

  26. 26.

    Ronca, A. E. et al. Effects of sex and gender on adaptations to space: reproductive health. J. Womens Health 23, 967–974 (2014).

    Google Scholar 

  27. 27.

    Schatten, G., Simerly, C. & Schatten, H. Microtubule configurations during fertilization, mitosis, and early development in the mouse and the requirement for egg microtubule-mediated motility during mammalian fertilization. Proc. Natl Acad. Sci. USA 82, 4152–4156 (1985).

    CAS  PubMed  Google Scholar 

  28. 28.

    Souza, K. A., Black, S. D. & Wassersug, R. J. Amphibian development in the virtual absence of gravity. Proc. Natl Acad. Sci. USA 92, 1975–1978 (1995).

    CAS  PubMed  Google Scholar 

  29. 29.

    Aimar, C. et al. Microgravity and hypergravity effects on fertilization of the salamander Pleurodeles waltl (urodele amphibian). Biol. Reprod. 63, 551–558 (2000).

    CAS  PubMed  Google Scholar 

  30. 30.

    Ijiri, K. Development of space-fertilized eggs and formation of primordial germ cells in the embryos of Medaka fish. Adv. Space Res. 21, 1155–1158 (1998).

    CAS  PubMed  Google Scholar 

  31. 31.

    Serova, L. V. & Denisova, L. A. The effect of weightlessness on the reproductive function of mammals. Physiologist 25, S9–S12 (1982).

    CAS  PubMed  Google Scholar 

  32. 32.

    Serova, L. V., Denisova, L. A., Makeeva, V. F., Chelnaya, N. A. & Pustynnikova, A. M. The effect of microgravity on the prenatal development of mammals. Physiologist 27, S107–S110 (1984).

    Google Scholar 

  33. 33.

    Burden, H. W. et al. Effects of space flight on ovarian-hypophyseal function in postpartum rats. J. Reprod. Fertil. 109, 193–197 (1997).

    CAS  PubMed  Google Scholar 

  34. 34.

    Wong, A. M. & De Santis, M. Rat gestation during space flight: outcomes for dams and their offspring born after return to earth. Integr. Physiol. Behav. Sci. 32, 322–342 (1997).

    CAS  PubMed  Google Scholar 

  35. 35.

    Ronca, A. E. & Alberts, J. R. Physiology of a microgravity environment selected contribution: effects of spaceflight during pregnancy on labor and birth at 1 G. J. Appl. Physiol. 89, 849–854 (2000).

    CAS  PubMed  Google Scholar 

  36. 36.

    Burden, H. W., Zary, J. & Alberts, J. R. Effects of space flight on the immunohistochemical demonstration of connexin 26 and connexin 43 in the postpartum uterus of rats. J. Reprod. Fertil. 116, 229–234 (1999).

    CAS  PubMed  Google Scholar 

  37. 37.

    Burden, H. W., Poole, M. C., Zary, J., Jeansonne, B. & Alberts, J. R. The effects of space flight during gestation on rat uterine smooth muscle. J. Gravit. Physiol. 5, 23–29 (1998).

    CAS  PubMed  Google Scholar 

  38. 38.

    Fejtek, M. & Wassersug, R. Effects of laparotomy, cage type, gestation period and spaceflight on abdominal muscles of pregnant rodents. J. Exp. Zool. 284, 252–264 (1999).

    CAS  PubMed  Google Scholar 

  39. 39.

    Hirshfield, A. N. Overview of ovarian follicular development: considerations for the toxicologist. Environ. Mol. Mutagen. 29, 10–15 (1997).

    CAS  PubMed  Google Scholar 

  40. 40.

    Gougeon, A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr. Rev. 17, 121–155 (1996).

    CAS  PubMed  Google Scholar 

  41. 41.

    Zhang, S. et al. Simulated microgravity using a rotary culture system compromises the in vitro development of mouse preantral follicles. PLOS ONE 11, e0151062 (2016).

    PubMed  PubMed Central  Google Scholar 

  42. 42.

    Yang, H., Bhat, G. K. & Sridaran, R. Clinostat rotation induces apoptosis in luteal cells of the pregnant rat. Biol. Reprod. 66, 770–777 (2002).

    CAS  PubMed  Google Scholar 

  43. 43.

    Bhat, G. K., Yang, H. & Sridaran, R. Simulated conditions of microgravity suppress progesterone production by luteal cells of the pregnant rat. J. Gravit. Physiol. 8, 57–66 (2001).

    CAS  PubMed  Google Scholar 

  44. 44.

    Tou, J. C., Grindeland, R. E. & Wade, C. E. Effects of diet and exposure to hindlimb suspension on estrous cycling in sprague-dawley rats. Am. J. Physiol. 286, E425–E433 (2004).

    CAS  Google Scholar 

  45. 45.

    Ronca, A. E., Baer, L. A. & Wade, C. E. Hypergravity effects on pregnancy and parturition. J. Gravit. Physiol. 9, P203–P204 (2002).

    PubMed  Google Scholar 

  46. 46.

    Ronca, A. E., Baer, L. A., Daunton, N. G. & Wade, C. E. Maternal reproductive experience enhances early postnatal outcome following gestation and birth of rats in hypergravity. Biol. Reprod. 65, 805–813 (2001).

    CAS  PubMed  Google Scholar 

  47. 47.

    Oyama, J. & Platt, W. T. Reproduction and growth of mice and rats under conditions of simulated increased gravity. Am. J. Physiol. 212, 164–166 (1967).

    CAS  PubMed  Google Scholar 

  48. 48.

    Moore, J. & Duke, J. Effect of chronic centrifugation on mouse breeding pairs and their offspring. Physiologist 31, S120–S121 (1988).

    CAS  PubMed  Google Scholar 

  49. 49.

    Megory, E. & Oyama, J. Hypergravity induced prolactin surge in female rats. Aviat. Space Environ. Med. 56, 415–418 (1985).

    CAS  PubMed  Google Scholar 

  50. 50.

    Megory, E. & Oyama, J. Hypergravity effects on litter size, nursing activity, prolactin, TSH, T3, and T4 in the rat. Aviat. Space Environ. Med. 55, 1129–1135 (1984).

    CAS  PubMed  Google Scholar 

  51. 51.

    Megory, E., Konikoff, F., Ishay, J. S. & Lelyveld, J. Hypergravity: its effect on the estrous cycle and hormonal levels in female rats. Life Sci. Space Res. 17, 213–218 (1979).

    CAS  PubMed  Google Scholar 

  52. 52.

    Megory, E. & Ishay, J. S. Hypergravity induced prolonged diestrous in the rat can be prevented by bromergocryptine or by previous exposure to the same conditions - a “memory” effect. Life Sci. 27, 1503–1507 (1980).

    CAS  PubMed  Google Scholar 

  53. 53.

    Lintault, L. M. et al. In a hypergravity environment neonatal survival is adversely affected by alterations in dam tissue metabolism rather than reduced food intake. J. Appl. Physiol. 102, 2186–2193 (2007).

    CAS  PubMed  Google Scholar 

  54. 54.

    Wang, H. et al. Variation in commercial rodent diets induces disparate molecular and physiological changes in the mouse uterus. Proc. Natl Acad. Sci. USA 102, 9960–9965 (2005).

    CAS  PubMed  Google Scholar 

  55. 55.

    Wu, C. et al. Simulated microgravity compromises mouse oocyte maturation by disrupting meiotic spindle organization and inducing cytoplasmic blebbing. PLOS ONE 6, e22214 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Uva, B. M. et al. Morpho-functional alterations in testicular and nervous cells submitted to modelled microgravity. J. Endocrinol. Invest. 28, 84–91 (2005).

    CAS  PubMed  Google Scholar 

  57. 57.

    Wakayama, S. et al. Detrimental effects of microgravity on mouse preimplantation development in vitro. PLOS ONE 4, e6753 (2009).

    PubMed  PubMed Central  Google Scholar 

  58. 58.

    Wang, Y. et al. A major effect of simulated microgravity on several stages of preimplantation mouse development is lethality associated with elevated phosphorylated SAPK/JNK. Reprod. Sci. 16, 947–959 (2009).

    CAS  PubMed  Google Scholar 

  59. 59.

    Ronca, A. E. Studies toward birth and early mammalian development in space. Adv. Space Res. 32, 1483–1490 (2003).

    PubMed  Google Scholar 

  60. 60.

    La Tessa, C., Sivertz, M., Chiang, I. H., Lowenstein, D. & Rusek, A. Overview of the NASA Space Radiation Laboratory. Life Sci. Space Res. 11, 18–23 (2016).

    Google Scholar 

  61. 61.

    Pesty, A., Doussau, M., Lahaye, J.-B. & Lefèvre, B. Whole-body or isolated ovary 60Co irradiation: effects on in vivo and in vitro folliculogenesis and oocyte maturation. Reprod. Toxicol. 29, 93–98 (2010).

    CAS  PubMed  Google Scholar 

  62. 62.

    Mathur, S., Nandchahal, K. & Bhartiya, H. C. Radioprotection by MPG of mice ovaries exposed to sublethal gamma radiation doses at different postnatal ages. Acta. Oncol. 30, 981–983 (1991).

    CAS  PubMed  Google Scholar 

  63. 63.

    Nitta, Y. & Hoshi, M. Relationship between oocyte apoptosis and ovarian tumors induced by high and low LET radiations in mice. Int. J. Radiat. Biol. 79, 241–250 (2003).

    CAS  PubMed  Google Scholar 

  64. 64.

    Mishra, B., Ripperdan, R., Ortiz, L. & Luderer, U. Very low doses of heavy oxygen ion radiation induce premature ovarian failure. Reproduction 154, 123–133 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Mishra, B., Ortiz, L. & Luderer, U. Charged iron particles, components of space radiation, destroy ovarian follicles. Hum. Reprod. 31, 1816–1826 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66.

    Vanderhyden, B. C. Loss of ovarian function and the risk of ovarian cancer. Cell Tissue Res. 322, 117–124 (2005).

    PubMed  Google Scholar 

  67. 67.

    Salehi, F., Dunfield, L., Phillips, K. P., Krewski, D. & Vanderhyden, B. C. Risk factors for ovarian cancer: an overview with emphasis on hormonal factors. J. Toxicol. Environ. Health. B. Crit. Rev. 11, 301–321 (2008).

    CAS  PubMed  Google Scholar 

  68. 68.

    Mishra, B., Lawson, G. W., Ripperdan, R., Ortiz, L. & Luderer, U. Charged-iron-particles found in galactic cosmic rays are potent inducers of epithelial ovarian tumors. Radiat. Res. 190, 142–150 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. 69.

    Arrivé, L. et al. Radiation-induced uterine changes: MR imaging. Radiology 170, 55–58 (1989).

    PubMed  Google Scholar 

  70. 70.

    Larsen, E. C. et al. Radiotherapy at a young age reduces uterine volume of childhood cancer survivors. Acta Obstet. Gynecol. Scand. 83, 96–102 (2004).

    PubMed  Google Scholar 

  71. 71.

    Bath, L. E. et al. Ovarian and uterine characteristics after total body irradiation in childhood and adolescence: response to sex steroid replacement. Br. J. Obstet. Gynaecol. 106, 1265–1272 (1999).

    CAS  PubMed  Google Scholar 

  72. 72.

    Carabajal, E. et al. Radioprotective potential of histamine on rat small intestine and uterus. Eur. J. Histochem. 56, e48 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Critchley, H. O. & Wallace, W. H. Impact of cancer treatment on uterine function. J. Natl Cancer Inst. Monogr. 34, 64–68 (2005).

    Google Scholar 

  74. 74.

    Wood, D. H., Yochmowitz, M. G., Hardy, K. A. & Salmon, Y. L. Animal studies of life shortening and cancer risk from space radiation. Adv. Space Res. 6, 275–283 (1986).

    CAS  PubMed  Google Scholar 

  75. 75.

    Fanton, J. W. & Golden, J. G. Radiation-induced endometriosis in Macaca mulatta. Radiat. Res. 126, 141–146 (1991).

    CAS  PubMed  Google Scholar 

  76. 76.

    Palumbo, G. et al. Effect of space radiation on expression of apoptosis-related genes in endometrial cells: a preliminary study. Phys. Med. 17 (Suppl. 1), 241–246 (2001).

    PubMed  Google Scholar 

  77. 77.

    Strollo, F. et al. The effect of microgravity on testicular androgen secretion. Aviat. Space Environ. Med. 69, 133–136 (1998).

    CAS  PubMed  Google Scholar 

  78. 78.

    Smith, S. M., Heer, M., Wang, Z., Huntoon, C. L. & Zwart, S. R. Long-duration space flight and bed rest effects on testosterone and other steroids. J. Clin. Endocrinol. Metab. 97, 270–278 (2012).

    CAS  PubMed  Google Scholar 

  79. 79.

    Merrill, A. H. Jr., Wang, E., Mullins, R. E., Grindeland, R. E. & Popova, I. A. Analyses of plasma for metabolic and hormonal changes in rats flown aboard COSMOS 2044. J. Appl. Physiol. 73 (Suppl.2), 132S–135S (1992).

    CAS  PubMed  Google Scholar 

  80. 80.

    Amann, R. P. et al. Effects of microgravity or simulated launch on testicular function in rats. J. Appl. Physiol. 73 (Suppl. 2), 174S–185S (1992).

    CAS  PubMed  Google Scholar 

  81. 81.

    Sapp, W. J. et al. Effects of spaceflight on the spermatogonial population of rat seminiferous epithelium. FASEB J. 4, 101–104 (1990).

    CAS  PubMed  Google Scholar 

  82. 82.

    Masini, M. A. et al. The impact of long-term exposure to space environment on adult mammalian organisms: a study on mouse thyroid and testis. PLOS ONE 7, e35418 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. 83.

    Russell, L. D., Ettlin, R. A., Hikim, A. P. S. & Clegg, E. D. Histological and Histopathological Evaluation of the Testis (Cache River Press, 1990).

  84. 84.

    Sapp, W. J. et al. Comparative study of spermatogonial survival after x-ray exposure, high LET (HZE) irradiation or spaceflight. Adv. Space Res. 12, 179–189 (1992).

    CAS  PubMed  Google Scholar 

  85. 85.

    Tash, J. S. & Bracho, G. E. Microgravity alters protein phosphorylation changes during initiation of sea urchin sperm motility. FASEB J. 13, S43–S54 (1999).

    CAS  PubMed  Google Scholar 

  86. 86.

    Wakayama, S. et al. Healthy offspring from freeze-dried mouse spermatozoa held on the international space station for 9 months. Proc. Natl Acad. Sci. USA 114, 5988–5993 (2017).

    CAS  PubMed  Google Scholar 

  87. 87.

    Ferrando, A. A., Lane, H. W., Stuart, C. A., Davis-Street, J. & Wolfe, R. R. Prolonged bed rest decreases skeletal muscle and whole body protein synthesis. Am. J. Physiol. 270, E627–E633 (1996).

    CAS  PubMed  Google Scholar 

  88. 88.

    Deaver, D. R. et al. Effects of caudal elevation on testicular function in rats. Separation of effects on spermatogenesis and steroidogenesis. J. Androl. 13, 224–231 (1992).

    CAS  PubMed  Google Scholar 

  89. 89.

    Hadley, J. A., Hall, J. C., O'Brien, A. & Ball, R. Effects of a simulated microgravity model on cell structure and function in rat testis and epididymis. J. Appl. Physiol. 72, (748–759 (1992).

    Google Scholar 

  90. 90.

    Zirkin, B. R., Santulli, R., Awoniyi, C. A. & Ewing, L. L. Maintenance of advanced spermatogenic cells in the adult rat testis: quantitative relationship to testosterone concentration within the testis. Endocrinology 124, 3043–3049 (1989).

    CAS  PubMed  Google Scholar 

  91. 91.

    Tash, J. S., Johnson, D. C. & Enders, G. C. Long-term (6-wk) hindlimb suspension inhibits spermatogenesis in adult male rats. J. Appl. Physiol. 92, 1191–1198 (2002).

    Google Scholar 

  92. 92.

    Ricci, G., Esposito, R., Catizone, A. & Galdieri, M. Direct effects of microgravity on testicular function: analysis of hystological, molecular and physiologic parameters. J. Endocrinol. Invest. 31, 229–237 (2008).

    CAS  PubMed  Google Scholar 

  93. 93.

    Engelmann, U., Krassnigg, F. & Schill, W. B. Sperm motility under conditions of weightlessness. J. Androl. 13, 433–436 (1992).

    CAS  PubMed  Google Scholar 

  94. 94.

    Ikeuchi, T. et al. Human sperm motility in a microgravity environment. Reprod. Med. Biol. 4, 161–168 (2005).

    PubMed  PubMed Central  Google Scholar 

  95. 95.

    Kamiya, H. et al. Effect of simulated microgravity on testosterone and sperm motility in mice. J. Androl. 24, 885–890 (2003).

    CAS  PubMed  Google Scholar 

  96. 96.

    Usik, M. A. & Ogneva, I. V. Cytoskeleton structure in mouse sperm and testes after 30 days of hindlimb unloading and 12 hours of recovery. Cell. Physiol. Biochem. 51, 375–392 (2018).

    CAS  PubMed  Google Scholar 

  97. 97.

    Ortiz, R. M., Wade, C. E. & Morey-Holton, E. Urinary excretion of LH and testosterone from male rats during exposure to increased gravity: post-spaceflight and centrifugation. Proc. Soc. Exp. Biol. Med. 225, 98–102 (2000).

    CAS  PubMed  Google Scholar 

  98. 98.

    Veeramachaneni, D. N., Deaver, D. R. & Amann, R. P. Hypergravity does not affect testicular function. Aviat. Space Environ. Med. 69, A49–A52 (1998).

    CAS  PubMed  Google Scholar 

  99. 99.

    Gray, G. D., Smith, E. R., Damassa, D. A. & Davidson, J. M. Effects of centrifugation stress on pituitary-gonadal function in male rats. J. Appl. Physiol. 48, 1–5 (1980).

    CAS  PubMed  Google Scholar 

  100. 100.

    Alpen, E. L. & Powers-Risius, P. The relative biological effectiveness of high-Z, high-LET charged particles for spermatogonial killing. Radiat. Res. 88, 132–143 (1981).

    CAS  PubMed  Google Scholar 

  101. 101.

    Vaglenov, A., Fedorenko, B. & Kaltenboeck, B. RBE and genetic susceptibility of mouse and rat spermatogonial stem cells to protons, heavy charged particles, and 1.5 MeV neutrons. Adv. Space Res. 39, 1093–1101 (2007).

    CAS  Google Scholar 

  102. 102.

    Li, H. Y. et al. Simulated microgravity conditions and carbon ion irradiation induce spermatogenic cell apoptosis and sperm DNA damage. Biomed. Environ. Sci. 26, 726–734 (2013).

    CAS  PubMed  Google Scholar 

  103. 103.

    Li, H. et al. Proteomic analysis of testis for mice exposed to carbon ion radiation. Mutat. Res. 755, 148–155 (2013).

    CAS  PubMed  Google Scholar 

  104. 104.

    Zhao, Q. et al. 56Fe ion irradiation induced apoptosis through Nrf2 pathway in mouse testis. Life Sci. 157, 32–37 (2016).

    CAS  PubMed  Google Scholar 

  105. 105.

    Li, H. et al. Comparative proteomics reveals the underlying toxicological mechanism of low sperm motility induced by iron ion radiation in mice. Reprod. Toxicol. 65, 148–158 (2016).

    CAS  PubMed  Google Scholar 

  106. 106.

    Schatten, H. et al. Effects of spaceflight conditions on fertillization and embryogenesis in the sea urchin Lytechinus pictus. Cell Biol. Int. 23, 407–415 (1999).

    CAS  PubMed  Google Scholar 

  107. 107.

    Padmanabhan, V., Puttabyatappa, M. & Cardoso, R. in Encyclopedia of Reproduction: Volume 2 Female Reproduction 2nd edn (eds T. Spencer & J. Flaws) 121–129 (Elsevier, 2018).

  108. 108.

    Pepling, M. E. From primordial germ cell to primordial follicle: mammalian female germ cell development. Genesis 44, 622–632 (2006).

    CAS  PubMed  Google Scholar 

  109. 109.

    Juengel, J. L. & McNatty, K. P. The role of proteins of the transforming growth factor-β superfamily in the intraovarian regulation of follicular development. Hum. Reprod. Update 11, 144–161 (2005).

    Google Scholar 

  110. 110.

    Zheng, W., Nagaraju, G., Liu, Z. & Liu, K. Functional roles of the phosphatidylinositol 3-kinases (PI3Ks) signaling in the mammalian ovary. Mol. Cell. Endocrinol. 356, 24–30 (2012).

    CAS  PubMed  Google Scholar 

  111. 111.

    Hennebold, J. D. in Encyclopedia of Reproduction: Volume 2 Female Reproduction 2nd edn (eds T. E. Spencer & J. A. Flaws) 99–105 (Elsevier, 2018).

  112. 112.

    Abel, M. H. et al. Spermatogenesis and Sertoli cell activity in mice lacking Sertoli cell receptors for follicle-stimulating hormone. Endocrinology 149, 3279–3285 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. 113.

    Oduwole, O. O., Peltoketo, H. & Huhtaniemi, I. T. Role of follicle-stimulating hormone in spermatogenesis. Front. Endocrinol. 9, 763 (2018).

    Google Scholar 

  114. 114.

    Plakhuta-Plakutina, G. I., Serova, L. V., Dreval, A. A. & Tarabrin, S. B. Effect of 22-day space flight factors on the state of the sex glands and reproductive capacity of rats [Russian]. Kosm. Biol. Aviakosm. Med. 10, 40–47 (1976).

    CAS  PubMed  Google Scholar 

  115. 115.

    Serova, L. V., Denisova, L. A., Apanasenko, Z. I., Kuznetsova, M. A. & Meizerov, E. S. Reproductive function of the male rat after a flight on the Kosmos-1129 biosatellite [Russian]. Kosm. Biol. Aviakosm. Med. 16, 62–65 (1982).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge funding support from National Space Biomedical Research Institute (NSBRI) (B.M.), U.S. Department of Health & Human Services, NIH National Institute of Environmental Health Sciences (NIEHS, National Institutes of Health; grant number R01ES020454) (U.L.) and National Aeronautics and Space Administration (NASA; grant number NNX14AC50G) (U.L.).

Author information

Affiliations

Authors

Contributions

B.M. researched data for the article and reviewed and edited the manuscript before submission. U.L. researched data for the article, contributed to discussion of the content, wrote the article, and reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Ulrike Luderer.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Endocrinology thanks F. Strollo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Ionizing radiation

Radiation that carries sufficient energy to detach electrons from atoms or molecules, ionizing them.

Microgravity

Gravity near zero g; the condition in which people or objects appear to be weightless.

Hypergravity

Conditions in which the force of gravity exceeds that on Earth’s surface, which is 1 g.

Linear energy transfer

The amount of energy transferred from the charged particle as it traverses a cell or tissue per unit of path length.

Centrifugation

The application of centrifugal force to increase the effective gravitational force for experimental purposes.

Vaginal oestrus

Vaginal cytology consisting of keratinized epithelial cells; this cytology characterizes oestrus, the day of the rodent oestrous cycle when ovulation occurs.

Secondary follicle

The next stage of follicular development after primary follicles; characterized by more than one layer of cuboidal granulosa cells and theca cell layers outside the granulosa cell layers.

Zona pellucida

The layer of glycoprotein that surrounds the oocyte plasma membrane; during fertilization, the sperm binds to specific proteins within the zona pellucida.

Shear stress

The force acting on an object or surface parallel to the plane or slope in which it lies.

Preovulatory follicles

Mature ovarian follicles capable of ovulating in response to a luteinizing hormone surge.

Primordial follicles

Quiescent ovarian follicles that are arrested in the first meiotic prophase; characterized by an incomplete layer of squamous granulosa cells.

Primary follicles

The next stage of follicular development after primordial follicles; characterized by a single layer of cuboidal granulosa cells or a layer of mixed squamous and cuboidal granulosa cells.

Relative biological effectiveness

The ratio of absorbed dose of one type of radiation compared with the absorbed dose of another type of radiation that gives an identical biological effect.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mishra, B., Luderer, U. Reproductive hazards of space travel in women and men. Nat Rev Endocrinol 15, 713–730 (2019). https://doi.org/10.1038/s41574-019-0267-6

Download citation

Further reading

Search

Quick links