Models to Study Gravitational Biology: CONCLUSIONS

CONCLUSIONS

As the International Space Station moves us closer to the reality of space colonization, it becomes increasingly important to understand the effects of altered gravity on mammalian reproductive physiology and function. Based on the existing data, there is evidence for hypo- and hypergravity-induced changes in male and female reproductive processes. However, additional research is needed to fill in the gaps in our current knowledge.

Models to Study Gravitational Biology: EFFECTS OF ALTERED GRAVITY

Ultimately, successful reproduction is the production of viable progeny. In only one study was mating capability in the space environment examined. Rats were described as having mated successfully in hypogravity, although no viable progeny were produced. It is unclear from the study design whether reproductive effects occurred in the males, the females, or both. Male spaceflight rats mated 5 days after flight to nonflight female rats bred successfully, but their offspring showed growth retardation and more frequent abnormalities, such as edema, hemorrhages, hydrocephaly, ectopic kidneys, and enlargement of the bladder.

Models to Study Gravitational Biology: EFFECTS OF HYPERGRAVITY(2)

HYPERGRAVITY(2)

Oyama et al. reported that pregnant rat dams centrifuged at 2.16 or 3.14 g had reduced numbers of survivors within their litters compared with 1-g controls. Furthermore, neonatal mortality in this study increased with increasing g load. Survival and development of neonates in hypergravity is partly dependent upon normal maternal behavior and mother-offspring interactions. Decreased plasma prolactin in rat dams centrifuged at 2.16 or 3.14 g has been suggested as a mechanism responsible for decreased neonatal survival because prolactin plays a key role in the expression of maternal behavior in rats.

Models to Study Gravitational Biology: EFFECTS OF HYPERGRAVITY(1)

Table 2 summarizes the effect of hypergravity on female reproduction. Hypergravity exposure of nonpregnant rats produced no differences in mating ability or gestation, but fewer pregnancies resulted. Hypergravity at moderate levels of 1.46 and 2.28 g disrupted the ovulatory cycle by inducing prolonged diestrus in rats, suggesting that the reduction in the number of pregnancies observed in centrifuged rats is due to changes in the ovulatory cycles. Pregnancy did not occur in mice chronically centrifuged at 3.5 g. Even centrifugation at relatively low speeds of 1.411.47 g resulted in an increased tendency to abort, especially during early pregnancy.

Models to Study Gravitational Biology: EFFECTS OF SIMULATED HYPOGRAVITY

 HYPOGRAVITY

Ground-based models have not been used frequently to study the effects of hypogravity on female reproduction. Women exposed to 17 days of 6° head-down tilt bed rest showed no changes in menstrual cycle length (Table 2). However, the duration of the study was too short to draw definitive conclusions. Rock and Fortney reported that women exposed to bed rest exhibited luteal phase deficiency, a condition that is related to HPG axis dysfunction. However, this study lacked controls. Clearly, more studies are needed to answer basic questions about female reproductive processes and to address concerns that fluid shifts associated with hypogravity may lead to retrograde menstruation or endometriosis.

Models to Study Gravitational Biology: FEMALE REPRODUCTION(3)

Table 2 summarizes the results of spaceflight on female reproduction. Despite speculation that headward fluid shifts, cardiovascular deconditioning, bone demineralization, and decreased red cells associated with hypogravity may affect the ability of rat dams to sustain their pregnancy, the results of spaceflight studies indicate that pregnant rat dams are able to successfully direct physiological resources to support fetal development in the space environment. In females, appropriate ratios of estrogen and progesterone are required for the establishment, maintenance, and termination of pregnancy. In view of the changes in male reproductive hormones following spaceflight, there is concern that spaceflight also may affect female reproductive hormones.

Models to Study Gravitational Biology: FEMALE REPRODUCTION(2)

FEMALE REPRODUCTION(2)

Plasma FSH was also elevated; however, there was no effect on pituitary FSH. These unequivocal results are likely due to the pulsatile secretion of LH and FSH. More meaningful results would require sequential blood sampling for LH and FSH.

Serova and Denisova reported that rats mated in hypogravity during spaceflight, indicating that female rats ovulated and cycled normally; however, no births resulted. Postflight laparotomies suggested that the fetuses were resorbed, but there is no clear indication of whether conception or implantation can proceed in the space environment. No systematic studies have examined the effect of spaceflight on early pregnancy. However, several spaceflight missions have included rat dams for varying durations between Days 9 and 19 of the 22-day gestation period.

Models to Study Gravitational Biology: FEMALE REPRODUCTION(1)

The number of female astronauts is growing, and the presence of women on long-duration spaceflights and at the International Space Station is also expected, yet relatively little is known about the effect of spaceflight on female reproduction. Environmental conditions can exert a number of adverse effects on the ovaries. To our knowledge, no researchers have examined the effect of the space environment on the ovaries of nonpregnant females. However, examination of the ovaries of postpartum rats flown in space during Days 9-20 of gestation showed no effect on ovarian weight or number of preovulatory or atretic follicles.

Models to Study Gravitational Biology: EFFECTS OF HYPERGRAVITY

HYPERGRAVITY

Centrifugation studies have enabled researchers to distinguish effects of acute versus chronic hypergravity exposure. Short-term centrifugation even at high forces of 4.1 g for 15 min had no detectable effect on the T levels of male rats. However, centrifugation at 4 g for 4 h resulted in reduced T levels, suggesting that duration of exposure is important. The hypergravity experienced at liftoff and re-entry is short term; therefore, it is unlikely that the reduced T in spaceflight rats was due to acute hypergravity.

Models to Study Gravitational Biology: EFFECTS OF SIMULATED HYPOGRAVITY(3)

Together, these results suggest that effects on testicular weight are due to simulated hypogravity rather than stress. Atrophy of testes in HLS rats was accompanied by significant reductions in plasma T compared with nonsuspended controls and an 85% loss of spermatogenic cells, indicating that both spermatogenesis and steroidogenesis were impaired in HLS rats.