Very low doses of heavy oxygen ion radiation induce premature ovarian failure

Abstract

Astronauts are exposed to charged particles during space travel, and charged particles are also used for cancer radiotherapy. Premature ovarian failure is a well-known side-effect of conventional, low linear energy transfer (LET) cancer radiotherapy, but little is known about the effects of high LET charged particles on the ovary. We hypothesized that lower LET (16.5 keV/µm) oxygen particles would be less damaging to the ovary than we previously found for iron (LET=179 keV/µm). Adult female mice were irradiated with 0, 5, 30, or 50 cGy oxygen ions or 50 cGy oxygen plus dietary supplementation with the antioxidant alpha lipoic acid (ALA). 6h after irradiation, percentages of ovarian follicles immunopositive for γH2AX, a marker of DNA double strand breaks, 4-HNE, a marker of oxidative lipid damage, and PUMA, a proapoptotic BCL-2 family protein, were dose-dependently increased in irradiated mice compared to controls. One week after irradiation, numbers of primordial, primary, and secondary follicles per ovary were dose-dependently decreased, with complete absence of follicles in the 50 cGy groups. The ED50 for primordial follicle destruction was 4.6 cGy for oxygen compared to 27.5 cGy for iron in our previous study. Serum FSH and LH concentrations were significantly elevated in 50 cGy groups at 8wk. Supplementation with ALA mitigated the early effects, but not the ultimate depletion of ovarian follicles. In conclusion, oxygen charged particles are even more potent inducers of ovarian follicle depletion than charged iron particles, raising concern for premature ovarian failure in astronauts exposed to both particles during space travel.

Identification of Plasma Lipidome Changes Associated with Low Dose Space-Type Radiation Exposure in a Murine Model

“…Plasma levels of lipids such as PC(20:4), PC(18:2), PC(20:5), PC (38:5), LysoPC(18:3), LysoPC(20:3) and LysoPC(22:6) were significantly (+ 2 fold, p value ≤ 0.05) increased at 14 days after exposure to 0.1 Gy 16 O. These results are in agreement with previous reports in which 16 O exhibited a higher degree of change in lipids compared to 1 H [28,29]. An increase in overall plasma PC levels with a concomitant rise in LysoPCs levels is suggestive of oxidative stress and inflammation upon exposure to 16 O [30].…”

Effect of transcutaneous electrical acupoint stimulation on protecting against radiotherapy- induced ovarian damage in mice

“…Our results found the exhaustion of the primordial follicle and the reduction of primary and secondary follicles after irradiation. These results agreed with the study that reported that exposure to radiotherapy causes increased recruitment of primordial follicles, finally leading to the excessive expenditure of the primordial follicle pool and to premature ovarian failure/insufficiency (POF/POI) [37, 38]. Moreover, the primordial follicle count in the group treated with TEAS 2-days post irradiation showed a significant increase compared with the untreated group.…”

Obesity or Overweight, a Chronic Inflammatory Status in Male Reproductive System, Leads to Mice and Human Subfertility

“…On the other hand, there is much evidence showing that obesity reduces sperm quality and then impairs male fertility (Teerds et al, 2011 ; Hammiche et al, 2012 ; Liu and Ding, 2017 ), whereas metabolic syndrome, hyperlipidemia, and a pro-inflammatory state are independently linked with male subfertility (Klöting and Blüher, 2014 ). However, it is unclear how obesity elicits its effects on sperm morphology or function.…”