Space Developmental Biology- Review Reading
Eran Schenker, MD* and David M. Warmflash, M.D.#
*Israel Aerospace Medicine Institute and, Department of Obstetric & Gynecology, Hadassah
University Hospitals Mt. Scopus Jerusalem Israel; #NASA Johnson Space Center, Houston, TX,
77058.
Introduction
The space environment impacts most of the systems of all species. The data concerning the effects
of weightlessness on the reproductive function in most species and particularly mammalian are still
limited and controversial. Human long duration space flight on the international space station (ISS),
colonization of the Moon, exploration of Mars and other new space frontiers will ultimately depend
on ability of plants, animals and humans to function and reproduce in the space environment.
It is commonly believed that some species make use of Earth's gravitational field as a positioning
cue during early embryogenesis. Until now, there have been no studies that have looked at the entire
process of reproduction in any animal species in space environment.
This type of investigation will be critical in understanding and preventing the problems that may
affect reproduction in space. New approaches to experimental investigation in this area are needed.
It is important to emphasize the need to study fertilization and the early stages of development
during space flight, as understanding these processes should be the first step in understanding the
entire process of reproduction. It is important to determine whether or not embryos can develop
normally without gravitational cues, to determine if any stages of early embryogenesis are adversely
affected by weightlessness and at which point the affected stages regulate back to producing normal
embryos.
On 4 October 1957, the Soviets launched Sputnik 1 into Earth orbit. This heralded the beginning of
the space age. A month later, the Soviets launched Sputnik 2, which carried a female dog named
Laika. The cabin contained systems for air regeneration and thermal regulation. The correct
functioning of the dog’s life support system (LSS) was monitored from Earth by telemetry. Vital
signs such as heart rate, respiration, and blood pressure were also monitored throughout the 1-week
flight, until the dog died from lack of oxygen. This flight provided the first evidence that a mammal,
fairly similar physiologically to a human, could withstand the rigors of launch and remain alive in
space.
Thereafter, a series of five Korabl Sputnik flights served as precursors to the first human mission.
On 10 August 1960 Sputnik-S was launched, which carried two dogs, two rats, forty mice and a
number of flies. This was the first time that living beings had been sent into space and subsequently
returned safely to Earth. On 12 April 1961, 27 year-old Senior Lieutenant Yuri Gagarin completed
the first human spaceflight in the spacecraft Vostok-l. His mission lasted only 108 minutes.
Although the Sputnik flights had indicated that normal bodily functions could be maintained during
spaceflight, scientists were still unclear about the various effects of weightlessness upon the body.
Consequently, Gagarin was very heavily instrumented, and medical monitoring included continuous
measurement of heart rate, respiration, electroencephalogram (EEG), electrooculogram (EOG)
electromyogram (EHG), electrocardiogram (ECG), thermography, and galvanic skin response.
Gagarin wore a pressurized suit throughout the flight. He ejected from his capsule at an altitude of
22,000 feet to complete the final stages of his descent by parachute. His flight proved to the world
that man could be sent into space and then returned safely to Earth.
The American program, initially called HISS and subsequently changed to Project Mercury, had in
the meantime developed the capability to repeat Gagarin’s feat. On 5 May 1961, Alan Shepard
completed a suborbital flight in the spacecraft Mercury MR-3, which lasted only 15 minutes.
From here onwards the duration of spaceflights have progressed steadily to those lasting more than
365 days. Today there are several Cosmonauts who have individually accumulated more than 500
man-days in space. Mankind’s insatiable curiosity and quest for knowledge will continue to grow.
This quest will be carried out by future space explorers who will embark upon routine missions
lasting several years.
Travel to and colonization of other habitable planets will eventually become inevitable. It is obvious
that mankind’s exploration and colonization of the frontier of space will ultimately depend on men’s
and women’s ability to live, work and reproduce in the space environment.
Much knowledge has been gained in the field of Space Medicine since the Vostok and Mercury
flights. Weightlessness, radiation, altered pressures and breathing partial pressures, potential
toxicological exposure, and exposure to harmful electromagnetic fields are some of the factors of
the space environment that may limit our ability to reproduce. The various effects upon
reproduction by these factors have been studied in animals, from microorganisms to mammals. Due
to current operational constraints data on actual human reproductive physiology in the space
environment are limited.
A 26-year-old ex-factory worker named Valentina Tereshkova was the first woman in space. On 16
June 1963 she piloted the Vostok 6 mission which lasted 70 hrs 50 min.. Later that year in the
month of November she married Cosmonaut Andrian Nikolayev, the pilot of the 94hr 22min Vostok
3 mission. A year later Cosmonaut Valentina Tereshkova gave birth to a healthy baby girl. This
provides us with the first evidence of post-flight normal pregnancy; at least as far as short duration
space flights are concerned.
Currently, several women are flying as Mission/Payload specialists or pilots on board Space Shuttle
flights. This includes.
Margaret Rhea Seddon (who first flew on the SLS-1 mission) is married to Navy Capt. Robert L.
(“Hoot”) Gibson, the pilot commander of several space missions (STS 6-C and STS 27 of January
1986 and December 1988 respectively) including the 50th U.S. space shuttle mission, Spacelab J
(12, 71). This mission included an astronaut couple, Dr. N. Jan Davis (37) and Lt. Col. Mark Lee
(39) who are the first married couple to fly in space together.
It is noteworthy to add that like Valentina Tereshkova, Rhea Seddon conceived and gave birth to a
healthy baby after being in space, which suggests that short duration space missions apparently
cause no permanent harmful effects to the reproductive system in human beings. Despite all this,
most of the knowledge gained so far has been implied from animal experiments.
Human gamete production, menstrual cycles, fertilization, fetal development, pregnancy and
delivery are similar in many ways to those of other animals. So far, it has been impossible to study
long term effects on human beings due to the present time limitations of space missions. Related
issues, such as sexual intercourse and contraception, need to be evaluated as well. Key areas in
which there will be limitations to men’s and women’s reproductive ability need to be identified. In
the subsequent chapters of this review reading suitable recommendations with a view to future
survivability of mankind as a species will be discussed.
There is little doubt that gravity provides a potential constraint on virtually all phases of
reproduction. Similarly, shielding of radiation by the atmosphere prevents the occurrence of lethal
genetic mutations on Earth. Even simple organisms such as the slime mold Dictyostelium display
genetically distinct specified adaptations to gravity. Their stalks synthesize an extracellular matrix
that allows the organism to exhibit a negative geotrophic growth pattern, which facilitates spore
dispersal. Pollard speculated in 1965 that exposure to zero gravity might significantly impact
nuclear and cellular division in both plants and animals.
Medaka Fish as a Model
The Life and Microgravity Spacelab (LMS) Space Tissue Loss-B (STL-B) hardware was developed
to test the hypothesis that gravity is required for normal embryo development. Investigators are
conducting systematic evaluation of vertebrate development and growth using the fish Medaka as a
model (Crotty, DA).
The Medaka is particularly suited to this experiment since it is a hardy fish, whose embryos tolerate
reduced temperatures well, allowing researchers to subject the embryos to low temperatures and
slow embryonic development. This provides more time to study each stage of vertebrate
development and maximizes the effects of weightlessness on each stage. Also, the embryos are
optically clear, which allows investigators to visually examine molecular markers and the
development of the internal organ systems.
The STL-B hardware has flown experiments on the Shuttle on two separate occasions. The first,
STS-59, was considered a hardware flight test. In addition, good video images of the developing
embryos during space flight were obtained. The second flight, STS-70, provided the opportunity for
histological examinations that the effects weightlessness might have on the development of the
Medaka. These analyses are currently underway (Crotty, DA).
One of the direct molecular genetic studies was cloning of the Medaka homeobox-containing gene
Hoxa-4. The Hoxa-4 gene as a marker of embryonic development for analyzing the effect of
weightlessness stress on embryonic segmentation. The next series of experiments, in the near future
on Medaka, will examine the Medaka Hoxa-4 gene which have showed several sequences
conserved in mouse and chicken, suggesting a role in the regulation of Hoxa-4 pattern of expression
(Wolgemuth, DJ).
Sea Urchins
During 1996, sea urchins were flown aboard a KC-135 and fertilization rates equivalent to those on
Earth have been obtained in the first 24 seconds of weightlessness although sperm movement was
somewhat slower (Chakrabarti, A).
Previous work has shown that ultraviolet (UV) space irradiation of fertilized frog eggs yields
embryos that lack dorsal and anterior structures. The eggs fail to undergo the cortical/cytoplasmic
rotation that specifies dorsoventral polarity, and they lack an array of parallel microtubules
associated with the rotation (Elinson, RP).
Drosophila Melanogaster
The results obtained during the last successful flight of the Challenger Shuttle, in early November
1985, indicate that oogenesis and embryonic development of Drosophila melanogaster are altered in
the absence of gravity. Two hundred forty females and ninety males, wild type Oregon R Drosophila
melanogaster flies were flown in the Space Shuttle. The results showed an increase in oocyte
production and size, a significant decrease in the number of larvae hatched from the embryonic
cuticles in weightlessness and alterations in the deposition of yolk (Vernos, I).
In connection with these results, at least 25% of the living embryos recovered from space failed to
develop into adults. Studies of the larval cuticles and those of the late embryos indicate the
existence of alterations in the anterior, head and thoracic regions of the animals. There was a delay
in the development into adults of the embryos and larvae that had been subjected to weightlessness
and recovered from the Space Shuttle at the end of the flight.
No significant accumulation of lethal mutations in any of the experimental conditions was detected
as measured through the male to female ratio in the descendant generation. It seems that even
Drosophila melanogaster flies are able to sense and respond to the absence of gravity, changing
several developmental processes even during very short space flights. The results suggest that
weightlessness interferes with the distribution and/or deposition of the maternal components
involved in the specification of the anterioposterior axis of the embryo.
Xenopus Fertilized Eggs
The cytoplasm of Xenopus fertilized eggs appears to be organized into three major compartments
based primarily on the uneven distribution of yolk platelets. There is a shift of these yolk
compartments during the first cell cycle that is thought to be involved in the dorsal/ventral
morphogenesis of the embryo. The involvement of gravity in Xenopus cytoplasmic organization and
in compartment shifts was studied by Smith, RC.
The cytoplasmic organization into yolk compartments was found to be maintained, and the
asymmetric movements of compartments still occurred in eggs that developed on the clinostat.
Smith, RC suggests that the organization of Xenopus egg cytoplasm into discrete compartments
relies on forces other than those involving gravity and that the compartment shifts that take place
during the first cell cycle are active movements (Smith, RC).
Recent intriguing work suggests that there are subtle developmental changes in the Xenopus laevis
embryos subjected to novel gravitational fields. These changes include the position of the third
cleavage plane, the dorsal lip of the blastopore and the size of the head and eyes.
Huang, S. investigated the early changes in development caused by gravitational alterations at the
cellular and molecular levels. Huang tried to define the periods and durations of exposure from
which embryos can recover and this has lead to studies of which types of exposure embryos cannot
tolerate. Defining this critical developmental window will contribute to NASA's research goals by
providing basic information important to raising animals in space (Huang, S).
The unfertilized frog egg appears to be radially symmetric about its animal-vegetal (AV) axis.
Establishment of bilateral symmetry, dorsal-ventral (DV) axis specification, requires a 30 degree
rotation of the vegetal yolk mass relative to the egg surface during the first cell cycle.
One well-known external influence on frog eggs is gravity. When fertilized eggs are tilted from their
usual orientation, gravity-driven internal rearrangements result in rotation directions different from
those specified by the SEP. Endogenous cues may also be present in the unfertilized egg. For
example, parthenogenetically activated eggs exhibit a normal rotation, even though they have not
been fertilized. There are observations that eggs of the frog Xenopus laevis tilted 90 degrees offaxis during in vitro maturation do not have true radial symmetry.
There are at least two major controllers of development in the early stages of embryonic
development that are of concern: gravity and the primitive steak. Gravity, probably acting through
the distribution of yolk and its components, lays down the initial plans for polarity. The primitive
streak, controls the orderly ingressions of the cells and imposes a pattern on the developing tissues
(Bellairs, R).
To test whether gravity is required for normal amphibian development, Xenopus laevis females
were induced to ovulate aboard the orbiting Space Shuttle (Souza, KA). Eggs were fertilized in
vitro, and although early embryonic stages showed some abnormalities, the embryos were able to
regulate and produce nearly normal larvae. These results demonstrate that a vertebrate can ovulate
in the virtual absence of gravity and that the eggs can develop to a free-living stage (Souza, KA).
On the Spacelab J mission the results where the same: “normal development can proceed in
weightlessness” (Danilchik, MV).
Avian Development
Preliminary results indicate no adverse effects of vibration and g force (launch profile of the shuttle)
on avian development. Only five quail embryos have survived weightlessness and only one of these
embryos survived to the latter stages of development (15 days of incubation). Results of flight
experiments indicate that gravity may be needed during the earliest stages of avian embryogenesis,
but is not important for the latter stages of development.
An egg incubator within a centrifuge in space can allow us to determine if lack of gravity is the
reason for the death of young avian embryos in space, as has occurred on one of the previous
studies. The results indicate that chick embryos are more adversely affected by lack of turning than
quail eggs and that they need to be turned at least 4 times daily or more for improved rate of hatch
(Hester, PY).
On future space flights there are three objectives designed to determine the effect of weightlessness
on embryonic development initiated after the launch; the fecundity of adult quail during orbit and
the assessment of their hormones and reproductive tissues after orbit; and the regeneration potential
of quail in weightlessness based on primordial germ cell migration and differentiation,
gametogenesis, ovulation, fertilization, embryonic development, and hatching (Bernard, CW).
These experiments will provide substantial basic information about the effects of weightlessness on
embryonic differentiation and development, as well as important information about adult quail
endocrinology and physiology. Many aspects of the proposed work will focus on reproduction since
this is the only path for successful animal bioregeneration in space.
On the Mir-19 flight there was a demonstrated adequate procedure for the delivery of fertile egg to
the Mir Space Lab. Crew tasking for incubator monitoring, embryo fixation and return of the fixed
eggs by either Soyuz or Shuttle was shown to be practical.
Additionally ground experiments are being conducted to determine at 1 g the effect of no turning
verses turning eggs 1800 every four hours from embryogenesis through to hatching.
The results of the space flight consisted of early embryonic death with only two embryos living to
the 16th day of incubation. Interpretations of the results were made more difficult by the fact the
synchronous control showed a similar lack of viability. Retrospective analysis of onboard flight
recording data suggests that the incubator temperature control malfunctioned and the eggs were
being incubated at 42 C instead of the programmed 37.5 C.
Preliminary histological evaluation of the embryonic reproductive organs of the viable inflight
embryos suggests normal development. Critical stages of development from heat stressed embryos
appear to be at days 1, 3, and 5.
These experiments were designed to foster reproduction in space weightlessness. Additionally, we
expect to gather substantial information on basic embryonic developmental processes. The outcome
of such studies will have a direct bearing on the understanding of embryogenesis and reproduction.
Furthermore from such studies we can develop a better interpretation of the role Earth gravity and
space weightlessness play in cell and tissue migration during embryo development and
differentiation. Embryonic cell migration is a primary reproductive interest. In all vertebrates the
germinal cells (future sperm and eggs) must migrate from outside the embryo to the gonads where
they proliferate and differentiate to form spermatogonia and oogonia. Some information may be
forthcoming on the need for controlled turning during avian embryonic development (Bernard,
CW).
Mammals and Developmental Biology
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 the Apollo-17 mission, (BIOCORE: Biological
Cosmic Ray Experiment), pocket mice, Perognathus longimembris, were subjected to HZE
radiation. The results showed that in two out of the three surviving male flight mice,
spermatogenesis was advanced to the same degree as in ground control mice at the same season.
Another experiment done by the Soviets produced the same results.
In a simultaneous Soviet study, on board the Cosmos 1129 biosatellite, male rats were allowed to
mate with non-flight females 5, 75 and 90 days post-flight. Litters of the 5 days post-flight 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 matings showed no differences in both samples (5 versus 75 and 90 days post-flight samples),
thereby suggesting that only the mature spermatozoa were affected during the flight.
In addition to the above, male and female rats were allowed to mate in space. No pregnancies
resulted, but post-flight 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.
Ground based experiments have shown decreased number of embryos and increased embryo
mortality in immobilized rats. In the clinostat experiment very few oocytes reached the second
meiotic division.
In rats that had been subjected to 1.02-2.28 G centrifugal force, hormonal analysis showed that
the progesterone levels were elevated due to a prolonged diestrous phase. The uterus however did
not show any decidual reaction to this pseudopregnancy response. The investigators have implicated
stimulation of the hypothalamus in hypergravity situations as a possible cause.
In another experiment, pregnant rats were subjected to centrifugal forces up to 3 Gs for 3 hours a
day. In the first and second days of pregnancy oocytes were not found in the oviduct. 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.
Studies have also been conducted on primates. In one large experiment, 2 year old primates, Macaca
mulatta, were subjected to varying levels of proton irradiation. Seventeen years later mortality
studies were conducted. The investigators determined that one of the leading causes of increased
mortality was a significant (48% in irradiated females compared to 0% in controls) increase in the
incidence of endometriosis.
In a similar experiment done by Wood et al, female rhesus monkeys were given total body
exposures of protons of varying energies. The doses and energies of the radiation received were
within the range that could be received by an astronaut traveling in low-Earth-orbit (LEO) during a
random solar flare event. The frequency of developing endometriosis was highly significant in the
irradiated group versus the non-irradiated controls. The minimum latency period was found to be 7
years. The scientists concluded that the risk of endometriosis cannot be ignored when weighing the
importance of a mission versus the risk of delayed radiation effects in female astronauts. Other
scientists too have the same opinion after having obtained similar results in their experiments.
The mouse testis has also been widely used as a model for stem-cell survival using a wide range of
endpoints following exposure to ionizing radiation. It is now well known that exposure to ionizing
radiation can cause damage to the spermatogonia.
Rats on Space Flight Experiment
Previous space flight experiments on female rats have shown that fetuses can grow and develop
when the maternal organism is exposed to weightlessness (Serova, LV).
In the 7-day space flight of Cosmos 1667, the Russians observed and concluded that short-term
space flight produces no effect on the reproductive system of white rats. No differences between
flight rats and synchronous and vivarium controls were detected with respect to such parameters as
the testis and epididymis weight, testicular content of spermatogonia, spermatocytes, spermatids,
spermatozoa, Leydig's cells and Sertoli's cells, and the number of normal and atypical spermatozoa
in the epididymis. Nuclei of Sertoli's cells were similar in size in the flight and control rats
(Denisova, LA).
On Cosmos 1514 the results where less clear. The flown rats had 0.9% reciprocal translocations
while the ground-based synchronous controls showed 0.5%. Exposure to space flight factors in
combination had a mutagenic effect on gonocytes. However, the adverse effect of weightlessness
per se was not demonstrated unambiguously according to the researcher (Benova, DK ).
Baikova found that stressogenic conditions produce stronger changes in reproductive organs than
space flight stress per se. (Baikova, OV). Another study on the reproductive function of the male
rat was performed after the space flight of the Cosmos 1129 biosatellite. The results of mating of 5
days postflight rats that were exposed to weightlessness were studied. The mature stage of the
space flight group lagged behind that of the ground control group vis-à-vis growth and development
during the first postnatal month (Serova, LV).
The offspring of male rats that were exposed to 22-day weightlessness did not differ from the
controls with respect to the number of the newborns, weight at birth, or weight gain during the first
postnatal month. (Plakhuta, PG)
Another experiment involving pregnant rats attempted to determine the effect of space flight on
ovarian antral follicles, corpora lutea, and pituitary content of hormones. These studies provided
insight into the role of gravity in hypophyseal-ovarian function and fecundity on Earth. All ovaries
have been serially sectioned and stained, and ovarian morphometric analyses have been completed.
Pituitary LH and FSH content has been measured. The analysis of plasma concentrations of LH and
FSH is complete. There was no effect of space flight observed during the post-implantation period
on any of the ovarian morphometric parameters evaluated, nor on vaginal birth or fecundity. As a
follow up to these studies, it seems imperative to investigate whether space flight initiated during
the pre-implantation period has any effect on embryonic survival and fecundity (Burden, HW).
Female germ cells (oocytes) are contained in ovarian follicles. The fate of over 99% of ovarian
follicles and their oocytes is a degenerative process known as atresia. A study designed to examine
the effects of space flight on atresia of antral follicles was performed as well. It appears that space
flight during the post-implantation phases of pregnancy does not alter this important ovarian
regulatory process. Additionally, space flight, during this period of pregnancy, does not alter the
rate of fetal wastage (Burden, HW).
Human and Mammalian Spermatozoa
Makler, A. investigated in real time how natural gravity affects rates of swim-up and swim-down
of human spermatozoa. Samples of motile or immobilized spermatozoa in a sealed mini-chamber
were placed vertically on a 90 degrees tilted microscope. Gravity causes the sperm heads to turn
downward after which the oriented spermatozoa continue to move down by their own tail
movements, causing accumulation of motile spermatozoa at the bottom. This may explain why in
some recent studies the swim-down procedure was superior to the swim-up procedure during sperm
separation by self-migration. Based on this study one can only speculate on what would happen with
no gravity effect. (Makler, A).
There is strong evidence that gravity influences sperm motility. The amount of progressively motile
spermatozoa, including all spermatozoa with a velocity > 20 microns/second, increased significantly
from 24% (+/- 9.5%) to 49% (+/- 7.6%) in the weightlessness test. (Engelmann, U).
In another study, seminiferous tubules in maturation stage from five animals revealed 4% fewer
spermatogonia in flight testes compared with synchronous controls and 11% fewer spermatogonia in
flight samples compared with vivarium controls (Sapp, WJ).
Plans for long term space habitation raise the question of whether the normal fertilization produces
might be altered under weightlessness conditions. Earlier unmanned weightlessness experiments, in
fact, demonstrated that motility of bull sperm is altered significantly in weightlessness.
Weightlessness experiments will expand these studies to determine whether the reported changes in
sperm motility under weightlessness correlate with alterations in the intracellular messenger
pathways and protein phosphorylation targets that regulate motility. Since sperm expend
considerable levels of the biochemical energy supply to produce motility, these studies are also
relevant to bioenergetics under weightlessness conditions. Results of these experiments will not
only expand our knowledge of the basic biological process of sperm function, but will also address
an area of biology relevant to extended habitation in weightlessness (Bracho, GE).
The objective of a continuos current project is to determine whether second messenger signal
transduction pathways in sperm are altered in weightlessness as compared to Earth-normal gravity.
A previous unmanned experiment, which examined a limited number of sperm movement
parameters, demonstrated that bovine sperm motility is altered significantly in weightlessness.
Prior to that study, exposure of sperm to hypergravity was found to produce a dramatic decline in
the content of ATP and a rise in ADP in sperm. Motility in these experiments was not determined.
In this study, sperm able to swim against a 1g force were found to contain higher levels of ATP.
Since ATP is critical to the maintenance of sperm motility, it is likely that weightlessness may
produce changes in sperm motility. Sperm motility is regulated by the content of cAMP, calcium
(Ca2+), and the state of protein phosphorylation modulated by these second messengers. Whether
these components are altered during changes in gravitational forces are not known (Bracho, GE).
The project will also yield information regarding biochemical mechanisms underlying the
alterations in movement produced by alterations in gravity. Results from these experiments will
greatly expand on previous data regarding the effects of altered gravity on sperm function. These
studies will yield information relevant to plans for habitation and survival during long-term space
flight.
Tests have demonstrated that the sperm will survive in the Biorack H/W extremely well under
launch scrub conditions as long as 72 hr with no significant deterioration in cell viability and as long
as 96 hr with only a slight reduction in viability. The initial timeline discussions indicated that the
experiment will be conducted at ~30 hr | 12 EMT which is well within the limits of optimal cell
viability.
In order for fertilization to occur, sperm must become motile and undergo a process termed
capacitation prior to being able to fertilize the egg. Some male factors correlate with a decreased
ability to undergo changes in sperm motility associated with capacitation. This area of sperm
function has been studied for a long time under Earth gravity conditions and is of particular
relevance to male infertility.
A new and interesting area involves the development and function of the central nervous system
(CNS) in weightlessness. The overall goal of these studies is to identify and evaluate sensitive
molecular and cellular markers of vertebrate morphogenesis in order to assess the effects of the
altered environment of space flight on embryonic and post-embryonic development. The hypothesis
to be examined is that embryonic development (and neural development in particular) will be
affected, potentially in a subtle but biologically significant manner, by exposure of the animals to
the environment of space and further and that this response will be different at different stages of
embryonic and post-natal development of the animal (Murashov, AK).
The success of developmental processes including fertilization, embryonic development and
maturation determines the ability of a species to survive in a certain environment. The space flight
environment includes several potential hazards such as radiation, alterations in atmospheric
pressure, prolonged toxic exposure and weightlessness that may affect developmental processes.
The impact of this research on the common man will be an increased awareness and comprehension
of the importance of the effects of altered environments on life as we know it today. Space flight
and space basic science provide a unique opportunity to evaluate the role of gravity in normal
physiology and metabolism. The investigation of the influence of the space flight environment on
developmental processes is very important when considering human survival in space.
(Murashov, AK).
Alberts, JR studed the fetal and postnatal development of rats to verify the hypothesis that
weightlessness reduces stimulation of the developing fetal vestibular system and alters early
function. His studies emphasize the behavior and physiology that are known to contribute to
successful pregnancy, labor, delivery and the onset of postnatal care, especially lactation (Alberts,
JR).
During the STS-80 Columbia space flight mission, forty-nine mice embryos at the 2-cell stage were
launched on the CMIX-5 Payload of ITA Inc. None of the forty-nine mice embryos showed any
development and all of the embryos degenerated (Schenker and Forkheim).
Labor and Vaginal Deliveries in Space
Alberts, JR provides quantitative data showing that labor and vaginal deliveries of flight rats and
ground control rats share many important parameters. Labors begin at the same time and last the
same amount of time, birth is achieved after the same time period, and the pup-to-pup intervals are
equivalent. These findings combine nicely with equivalence in number and size of the offspring.
Nevertheless, in contrast to this picture of equivalence in the birth process, we have found that flight
mothers display twice as many labor contractions as do synchronous control groups. This contrasts
with the expectations of many researchers that rat dams can sustain successful vaginal deliveries
after spending half of their pregnancy in weightlessness (Renegar, RH).
Some findings have been quite unexpected and many of these are important as validations of what
"ought" to happen, but had never been tested. The basic processes under consideration relate to the
ability of the body of an adult female mammal to tolerate space flight and maintain normal
gestation, followed by vaginal delivery during 1-g re-adaptation .
One practical aspect of this work applies to the utilization of the upcoming international space
station. Most plans for the life sciences laboratories on space station include reproductive and
developmental studies.
As we learn more about female mammals’ adaptive responses to space flight, we can better plan the
facilities needed for developmental research in a long duration facility such as the ISS. The Renegar
experiment will use pregnant rats to determine the effect of weightlessness on the development of
the rat placenta. Ten pregnant rats will be aboard the Space Shuttle during an 11-day mission.
Upon return to Earth, the rat uteruses and placentas will be examined. Morphological, biochemical
and endocrine variables of these tissues will be analyzed to determine whether the cells involved
have retained their structure and are operating correctly. These studies could identify factors that
regulate pregnancy and provide valuable insight into the role that gravity plays in pregnancy on
Earth.
Morphological and biochemical aspects of the above task have been completed. Analysis of
hormone expression is partially completed. Results indicate that space flight of pregnant animals
beginning after embryo implantation does not affect placental structure and selected biochemical
parameters. Hormonal analysis will be completed as proposed. An important question generated by
this study is whether space flight influences embryo implantation, which is a critical event
governing reproductive success.
Infertility is a health problem that can lead to significant psychological and economic stress for
many couples. This malady may result from problems associated with gamete fertilization, embryo
implantation, or placental insufficiency. Space studies may exam the role of gravity in placental
growth and development. It has been hypothesized that the correct vectoral movement of cells
during embryo implantation and placental development is dependent upon gravitational forces.
Additionally, hemodynamic changes associated with weightlessness have been postulated to
adversely influence placental development and function (Renegar, RH).
Conclusions
The course of early mammalian development and the possible roles of gravity still remain obscure.
Axis formation is of particular interest, since the factors determining axial polarity in mammalian
embryos is still unclear. It is suggested that embryos that are not heavily yolk-laden, or otherwise
polarized so that they naturally exhibit a gravity orientation, are likely to prosper in weightlessness.
The implantation of the embryo in the mammalian uterus, however, is not symmetrical, and the
subsequent orientation of the axis may be correlated with this asymmetry. House embryos grown in
vitro during the period of axis formation bend over as they elongate, and the primitive streak that
marks the onset of axis formation seems preferentially to develop along the upper side of the
cylindrical structure. Thus gravity could provide a possible directional signal both in vivo and in
vitro.
Such information needs to be confirmed under actual weightlessness conditions in order to
determine the possible limitations of human embryogenesis. Since the average mammalian
pregnancy period is so long, compared to current spaceflights, investigations of such nature present
formidable problems that need to be solved in such a way as to ensure the health of the animals
without jeopardizing astronaut safety.
It is necessary to know the effect of space flight on reproductive processes at this time in order to
determine if studies of mammalian biology, requiring stable animal colonies aboard an orbiting
laboratory, should be planned. Also, a better understanding of reproductive processes will facilitate
management of human proliferation in face of a finite supply of resources on Earth.
Acknowledgment: The literature review was conducted in collaboration with many investigators
including Prof.’ J.G. Schenker (Hadassah Medical Center Jerusalem Israel) and Prof.’ Stanley
Mohler (Wright State University, OH, USA). We are grateful to all of the collaborators for their
helpful advice and discussion. We are also grateful to Dr. Jennings, Dr Santy and Dr. Sahiar, upon
whose works in the areas of reproduction and the space environment of which this review is based
on.
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