Reduced oocyte quality and exacerbation of the maternal age effect are enduring consequences of low-level atrazine exposure in mouse

Abstract

BACKGROUNDEgg development has unique features that render it vulnerable to environmental perturbation. The herbicide atrazine is an endocrine disruptor shown to have detrimental effects on reproduction across a number of vertebrate species. OBJECTIVESTo determine whether exposure to low levels of atrazine impairs meiosis in female mammals using a mouse model; in particular, whether and how the fidelity of oocyte chromosome segregation is affected, and whether the aging-related aneuploidy is exacerbated. METHODSFemale C57BL/6J mice were exposed to two levels of atrazine in drinking water, with the lower level corresponding to detected environmental contamination. To model exposure during development, atrazine was ingested by pregnant females at 0.5 days post coitum and continued until pups were weaned at 21 days post-partum. For adult exposure, 2-month-old females ingested atrazine for 3 months. For each exposure group, various indicators of oocyte quality were determined, including developmental capacity and chromosomal abnormalities during the two meiotic divisions. RESULTSDevelopmental exposure caused only minor effects on the fetal events of meiotic prophase-I and establishment of initial follicle pools. However, ovulation was enhanced while oocyte quality was significantly reduced. At the chromosome level, misalignment and numerical and structural abnormalities were increased at both meiotic divisions. Furthermore, fertilization efficiency was impaired in vitro, and apoptosis was elevated in blastocysts derived from the eggs of atrazine-exposed females. Similar levels of chromosomal defects were seen in oocytes following both developmental and adult exposure regimens suggesting that quiescent primordial follicles may be the consequential targets of atrazine. Importantly, defects were observed long after exposure was terminated. Moreover, dramatic increases in chromosomally abnormal oocytes were seen in older mice indicating that atrazine exposure during development exacerbates the effects of maternal aging on oocyte quality. Indeed, analogous to the effects of maternal age, atrazine exposure resulted in weakened cohesion between sister chromatids. CONCLUSIONLow-level atrazine exposure causes persistent changes to the female mammalian germline with potential consequences for reproductive lifespan and congenital disease.