Methoxychlor induces atresia by altering Bcl2 factors and inducing caspase activity in mouse ovarian antral follicles in vitro

Abstract

Methoxychlor (MXC) is an organochlorine pesticide widely used in many countries against various species of insects that attack crops and domestic animals. MXC reduces fertility by increasing atresia (death) of antral follicles in vivo. MXC also induces atresia of antral follicles after 96 h in vitro. The current work tested the hypothesis that MXC induces morphological atresia at early time points (24 and 48 h) by altering pro-apoptotic (Bax, Bok, Casp3, and caspase activity) and anti-apoptotic (Bcl2 and Bcl-xL) factors in the follicles. The results indicate that at 24 h, MXC increased Bcl-xL and Bax mRNA levels and increased the ratio of Bax/Bcl2. At 48–96 h, MXC induced morphological atresia. At 24–96 h, MXC increased caspase activities. These data suggest that MXC may induce atresia by altering Bcl2 factors and inducing caspase activities in antral follicles.

Co-treatment of mouse antral follicles with 17β-estradiol interferes with mono-2-ethylhexyl phthalate (MEHP)-induced atresia and altered apoptosis gene expression

“…The selected genes included Bax, Bok, Bid , and Bcl2 [27, 31–33]. In a preliminary study, we compared mRNA expression in vehicle-treated antral follicles and MEHP-treated follicles using an apoptosis-specific qPCR array (data not shown).…”

“…MEHP treatment for 48 h resulted in decreased expression of Bok mRNA, a pro-apoptotic factor, previously shown to be up-regulated in response to methoxychlor which induces antral follicle atresia in mice [31]. No other published studies have evaluated the effect of MEHP on Bok expression in ovarian cells; however, one study reported that exposure to BPA decreased the expression of Bok mRNA in the human ovarian carcinoma cell line OVCAR-3 [44].…”

“…These observations were unexpected since these genes were selected based on evidence showing that their expression is altered by other chemicals that cause atresia in mouse antral follicles [27, 31–33]. Previous studies have also reported that MEHP increases Bax and decreases Bcl2 mRNA expression in histiocytic lymphoma U937 cells (300 µM for 20 h; [50] and mouse antral follicles (36 µM for 96 h) [25].…”

Methoxychlor exposure induces oxidative stress and affects mouse oocyte meiotic maturation

“…Here we examined the toxic effects of MXC, a representative EDC, on mouse oocyte maturation, using a range of concentrations (0–200 µM) previously reported to induce damage in mouse ovaries (Gupta et al, ; Basavarajappa et al, ,). We found that this same dose range increased levels of superoxide radicals and other ROS in mouse oocytes, had toxic effects on meiotic spindles, interfered with mitochondrial function, and elevated lipid peroxidation; a slightly higher concentration of MXC (500 µM) induced DNA DSBs (Fig.…”

Effects of phyto‐oestrogen quercetin on productive performance, hormones, reproductive organs and apoptotic genes in laying hens

“…Bcl-2 family protein-triggered mitochondrial membrane depolarization and caspase cascade activation were involved in apoptosis, and caspases were activated via death receptor pathway and mitochondrial pathway (Hilmi et al, 2008). In various animals, expression of caspase-3 is mainly found in granulosa cells of atretic antral follicles, and procaspase-3 is present at all stages of follicular development (Basavarajappa, Karman, Wang, Gupta, & Flaws, 2012). It implies that atresia of follicles at earlier developmental stage could be activated through caspase-3-independent pathway (Glamoclija, Vilovic, Saraga-Babic, Baranovic, & Sapunar, 2005).…”