Effects of 17β-estradiol, and its metabolite, 4-hydroxyestradiol on fertilization, embryo development and oxidative DNA damage in sand dollar (Dendraster excentricus) sperm

Abstract

Oxidative compounds have been demonstrated to decrease the fertilization capability and viability of offspring of treated spermatozoa. As estrogen and its hydroxylated metabolites readily undergo redox cycling, this study was undertaken to determine if estrogens and other oxidants could damage DNA and impair sperm function. Sperm was preexposed to either 17β-estradiol (E2), 4-hydroxyestradiol (4OHE2) or the oxidant t-butyl hydroperoxide (t-BOOH), and allowed to fertilize untreated eggs. The fertilization rates and development of the larvae were assessed, as well as the amount of 8-oxodeoxyguanosine (8-oxodG) as an indication of oxidative DNA damage. All compounds caused significant decreases in fertilization and increases in pathological abnormalities in offspring, with 4OHE2 being the most toxic. Treatment with 4OHE2 caused a significant increase of 8-oxodG, but E2 failed to show any effect. Pathological abnormalities were significantly correlated (r 2 = 0.44, p ≤ 0.05) with 8-oxodG levels in sperm treated with t-BOOH and 4OHE2, but not E2. 8-OxodG levels also were somewhat weakly correlated with impaired fertilization in 4OHE2-treated sperm (r 2 = 0.33, p ≤ 0.05). The results indicate that biotransformation of E2 to 4OHE2 enhances oxidative damage of DNA in sperm, which can reduce fertilization and impair embryonic development, but other mechanisms of action may also contribute to these effects.

Estrogen receptor-dependent and independent roles of benzo[a]pyrene in Ishikawa cells

“…PAHs have previously been shown to engender estrogenic activity in rodent models and breast cancer cell lines but not in human endometrial cells; thus this work is significant because it illustrates the estrogenic character of PAHs and their metabolites in these cells. It is noteworthy that B[a]P-7,8-dione can redox cycle to the corresponding catechol, and B[a]P-7,8-catechol has structural similarity to catechol estrogens, which have genotoxic properties (Rempel et al 2009, 2010, Fussell et al 2011. Thus B[a]P-7,8-dione formed may play a significant role in endometrial cell genotoxicity in addition to its estrogenic action.…”

Mechanisms of Estrogens’ Dose-Dependent Neuroprotective and Neurodamaging Effects in Experimental Models of Cerebral Ischemia

“…As aforementioned, estrogens have also been shown to increase oxidative stress, and thereby possibly augment ischemic damage ( Figure 1 ) [ 9 , 73 ]. The reported pro-oxidative effects include increased mitochondrial ROS production [ 74 , 75 ], oxidative DNA-damage in sperm and ovarian surface epithelium [ 76 , 77 ], reduced levels of anti-oxidant proteins in rat brain [ 78 ], promotion of oxidative damage in rat liver cells [ 79 ] and increased ROS-production from the estrogen metabolites 2-methoxyestradiol and 4-hydroxyestradiol [ 80 – 82 ]. However, these pro-oxidative effects of estrogens have mainly been reported from in vitro experiments and in other tissues than the brain, while studies on the nervous system almost uniformly have found estrogens to exert anti-oxidant properties [ 73 ].…”

Assessing reproductive and endocrine parameters in male largescale suckers (Catostomus macrocheilus) along a contaminant gradient in the lower Columbia River, USA

“…Sperm DNA integrity is essential for the accurate transmission of genetic information, and sperm chromatin abnormalities or DNA damage may result in male infertility (Agarwal and Said, 2003;Jenkins, 2011b;Rempel et al, 2009). In this study, site differences were noted in DNA fragmentation (P = 0.0016), where LV N SK = CC (Table 2; Fig.…”

“…Xenobiotics and biotransformation reactions play important roles in the mechanistic aspects of oxidative damage, of which DNA is a target (Rempel et al, 2009;Zharkov, 2013). Sperm DNA integrity is essential for the accurate transmission of genetic information, and sperm chromatin abnormalities or DNA damage may result in male infertility (Agarwal and Said, 2003;Jenkins, 2011b;Rempel et al, 2009).…”