Oocyte Development and Quality in Young and Old Mice following Exposure to Atrazine

Egg 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 several vertebrate species.

This study was designed to determine whether exposure to low levels of atrazine impairs meiosis in female mammals, using a mouse model; in particular, the study's researchers sought to determine whether and how the fidelity of oocyte chromosome segregation may be affected and whether aging-related aneuploidy is exacerbated.

Female C57BL/6J mice were exposed to two levels of atrazine in drinking water: The higher level equaled aqueous saturation, and the lower level corresponded to detected environmental contamination. To model developmental exposure, atrazine was ingested by pregnant females at 0.5 d post coitum and continued until pups were weaned at 21 d postpartum. For adult exposure, 2-month-old females ingested atrazine for 3 months. Following exposure, various indicators of oocyte development and quality were determined, including: a) chromosome synapsis and crossing over in fetal oocytes using immunofluorescence staining of prophase-I chromosome preparations; b) sizes of follicle pools in sectioned ovaries; c) efficiencies of in vitro fertilization and early embryogenesis; d) chromosome alignment and segregation in cultured oocytes; e) chromosomal errors in metaphase-I and -II (MI and MII) preparations; and f) sister-chromatid cohesion via immunofluorescence intensity of cohesin subunit REC8 on MI-chromosome preparations, and measurement of interkinetochore distances in MII preparations.

Mice exposed to atrazine during development showed slightly higher levels of defects in chromosome synapsis, but sizes of initial follicle pools were indistinguishable from controls. However, although more eggs were ovulated, oocyte quality was lower. At the chromosome level, frequencies of spindle misalignment and numerical and structural abnormalities were greater at both meiotic divisions. In vitro fertilization was less efficient, and there were more apoptotic cells in blastocysts derived from eggs of atrazine-exposed females. Similar levels of chromosomal defects were seen in oocytes following both developmental and adult exposure regimens, suggesting quiescent primordial follicles may be a consequential target of atrazine. An important finding was that defects were observed long after exposure was terminated. Moreover, chromosomally abnormal eggs were very frequent in older mice, implying that atrazine exposure during development exacerbates effects of maternal aging on oocyte quality. Indeed, analogous to the effects of maternal age, weaker cohesion between sister chromatids was observed in oocytes from atrazine-exposed animals.

Low-level atrazine exposure caused persistent changes to the female mammalian germline in mice, with potential consequences for reproductive lifespan and congenital disease. https://doi.org/10.1289/EHP11343.