Effects of Hyperbaric Oxygen on Rat Embryos

Abstract

The aim of the study was to investigate the toxic effects of hyperbaric oxygen (HBO) on rat embryos. Two groups of Fischer pregnant rats were exposed to oxygen at pressures of 324 and 426 kPa for 90 min per day for 5 consecutive days (8–12 days of gestation). The third group was exposed to normobaric oxygen for 12 h on the eighth day of gestation. Two control groups were used; the first was comprised of intact and the second of sham-treated animals. The HBO treatment did not significantly affect maternal weight gain or reduce litter size, nor did it induce any embryonic abnormalities. However, the fetal body weight was reduced and the placental weight increased in the groups exposed to HBO at pressures of 324 and 426 kPa. When female fetuses which had been exposed to oxygen at 324 or 426 kPa were compared to the intact control group, a reduction in wet weights of 9.2 (p < 0.05) and 12.1 % (p < 0.01), respectively, was noted. Male fetuses exposed to oxygen at 324 and 426 kPa displayed a reduced body weight of 11.7 (p < 0.01) and 16.6% (p < 0.01), respectively. Placental weight was increased by 18.9 (p < 0.01) and 23.6% (p < 0.01) in the groups exposed to oxygen at 324 and 426 kPa, respectively. These data suggest that HBO, either at 324 or 426 kPa, is not potent at inducing malformations and that the largest embryotoxic effects are upon fetal body weight and placental weight. However, the histological examination of placentas revealed alterations in labyrinthine blood vessels and a statistically significant thickening of the placental barrier. In conclusion, this study suggests that transient interference with normal placentation is probably sufficient to cause permanent maldevelopment of the placenta and embryo.

Narrative minireview of the current status of hyperbaric oxygen therapy for pregnant women

“…23 No previous report has described the benefits and adverse effects of HBOT for healthy pregnant women and, in particular, their fetuses. Sapunar et al 34 reported the effects of HBOT on rat embryos. They found that HBOT did not induce malformations at either 3.3 or 4.3 ATA and that the largest embryotoxic effects involved decreasing the fetal body weight and increasing the placental weight.…”

Maternal exposure to hyperbaric oxygen at the preimplantation stages increases apoptosis and ectopic Cdx2 expression and decreases Oct4 expression in mouse blastocysts via Nrf2‐Notch1 upregulation and Nf2 downregulation

“…17,[95][96][97] The use of HBOT in pregnant women is limited due to potential risks such as fetal weight decrease and congenital malformations. 15,17,96 However, there are potential benefits of HBOT in treating certain conditions during pregnancy, including threatened abortion, fetal hypoxia, toxemias of pregnancy, late gestation, diabetes, heart disease, CO intoxication, air embolism, and status epilepticus. 96 It is important to note that HBOT is not yet approved by the US FDA for these conditions except in cases of CO poisoning and air embolism.…”

“…Furthermore, the impaired lineage specification and increased cell apoptosis in the ICM of the HBO-exposed blastocysts may contribute to the reduced fetal weights and multiple congenital malformations observed in previous studies involving pregnant rabbits, mice, and Fischer rats exposed to HBO at pressures exceeding 2 ATA. 17,[95][96][97] The use of HBOT in pregnant women is limited due to potential risks such as fetal weight decrease and congenital malformations. 15,17,96 However, there are potential benefits of HBOT in treating certain conditions during pregnancy, including threatened abortion, fetal hypoxia, toxemias of pregnancy, late gestation, diabetes, heart disease, CO intoxication, air embolism, and status epilepticus.…”

“…17 Compared to control groups, HBO resulted in a 9.2-16.6% reduction in fetal body weights and an 18.9-23.6% increase in placental weights. 17 While the adverse phenotypic effects of HBO on embryogenesis have been observed, the precise molecular mechanisms linking prolonged HBO exposure to teratogenic abnormalities have yet to be fully elucidated. In addition, there have not been any precedent studies investigating the effects of HBO exposures on the preimplantation instead of postimplantation mammalian embryos.…”

“…The findings revealed that during the late blastula stage, the embryos in the high‐pressure oxygen group experienced hindered development, characterized by a lack of formation of epithelial cells or larvae 16 . In the Sapunar's study, two groups of Fischer pregnant rats were exposed to 100% O 2 at pressures of 3.2 or 4.2 atm for a duration of 90 min per day from gestational day 8 to gestational day 12 17 . Compared to control groups, HBO resulted in a 9.2–16.6% reduction in fetal body weights and an 18.9–23.6% increase in placental weights 17 .…”