Di‐(2‐ethylhexyl) phthalate and bisphenol A exposure impairs mouse primordial follicle assembly in vitro

Abstract

Bisphenol-A (BPA) and diethylhexyl phthalate (DEHP) are estrogenic compounds widely used in commercial plastic products. Previous studies have shown that exposure to such compounds have adverse effects on various aspects of mammalian reproduction including folliculogenesis. The objective of this study was to examine the effects of BPA and DEHP exposure on primordial follicle formation. We found that germ cell nest breakdown and primordial follicle assembly were significantly reduced when newborn mouse ovaries were exposed to 10 or 100 μM BPA and DEHP in vitro. Moreover, BPA and DEHP exposure increased the number of TUNEL positive oocytes and the mRNA level of the pro-apoptotic gene Bax in oocytes. These effects were associated with decreased expression of oocyte specific genes such as LIM homeobox 8 (Lhx8), factor in the germline alpha (Figla), spermatogenesis and oogenesis helix-loop-helix (Sohlh2), and newborn ovary homeobox (Nobox). Interestingly, BPA and DEHP exposure also prevented DNA demethylation of CpG sites of the Lhx8 gene in oocytes, a process normally associated with folliculogenesis. Finally, folliculogenesis was severely impaired in BPA and DEHP exposed ovaries after transplantation into the kidney capsules of immunodeficient mice. In conclusion, BPA and DEHP exposures impair mouse primordial follicle assembly in vitro.

Activin A Accelerates the Progression of Fetal Oocytes Throughout Meiosis and Early Oogenesis in the Mouse

“…At the end of the culturing, the ovarian tissues were collected and washed three times with PBS for the indicated analyses. Oocytes were isolated from the cultured ovarian tissues as previously described [23][24][25][26][27].…”

Bisphenol S instead of bisphenol A: a story of reproductive disruption by regretable substitution - a review

“…Especially in the area of reproduction in both animal models and in humans, a wide range of negative influences of BPA have been observed (Kwintkiewicz et al 2010;Trapphoff et al 2013;Zhang et al 2014). BPA has varied and complex mechanisms of action that may interfere with normal reproductive development and functions.…”

Sohlh2 inhibits the apoptosis of mouse primordial follicle oocytes via C-kit/PI3K/Akt/Foxo3a signalling pathway

“…Sohlh2 is a member of tissue-specific basic helix-loophelix transcription factor superfamily and plays critical roles in early development of germ cells (Barrios et al, 2012;Jagarlamudi and Rajkovic, 2012;Lim and Choi, 2012;Qin et al, 2014;Suzuki et al, 2012;Zhang et al, 2014). In Sohlh2-deficient ovaries, oocytes were rapidly lost whereas apoptosis of oocytes increased (Choi et al, 2008).…”