Exposure to bisphenol A at physiological concentrations observed in Chinese children promotes primordial follicle growth through the PI3K/Akt pathway in an ovarian culture system

Zhao, Qian; Ma, Yan; Sun, Ning; Wang, Hongzhi; Zhang, Qing; Sun, Shuhan; Xu, Chen; Wang, Fang; Li, Wen

doi:10.1016/j.tiv.2014.07.009

Cited by 30 publications

(20 citation statements)

References 48 publications

(46 reference statements)

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“…In this study, although the concentration of the inhibitor (50 µM LY294002) is higher than most of the other studies (Keating et al, 2009;Sobinoff et al, 2012;Zhang et al, 2014;Zhao et al, 2017), our findings support the idea that this concentration was not toxic because it did not reduce the percentage of normal follicles compared to the treatment without the inhibitor. Moreover, the PI3K pathway inhibition decreased the spontaneously ovine primordial follicle activation observed after culture in the control medium, which is in agreement with previous results (rat : Keating et al, 2009;mouse: Sobinoff et al, 2012;Zhao et al, 2014). However, surprisingly, our results also provide evidence that EGF is nonessential in engaging the PI3K pathway to regulate the activation.…”

Section: Discussionsupporting

confidence: 94%

“…Some studies have demonstrated that pharmacological manipulation of the PI3K pathway, using PI3K inhibitors such as LY294002 (Granville et al, 2006), could potentially give a better understanding of the function and regulatory mechanisms of this pathway on Anim. Reprod., v.14, (Suppl.1), p.1298-1306, 2017 1299 follicular activation (Keating et al, 2009;Sobinoff et al, 2012;Zhao et al, 2014). However, it remains to be seen whether PI3K or its inhibitor LY294002 can be used to maintain morphologically normal follicles and to promote follicle activation in sheep ovaries cultured in vitro.…”

Section: Introductionmentioning

confidence: 99%

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Blocking the PI3K pathway or the presence of high concentrations of EGF inhibits the spontaneous activation of ovine primordial follicles in vitro

Santos¹,

Santos²,

Menezes³

et al. 2017

Anim Reprod

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The aims of this study were to verify the effects of Epidermal Growth Factor (EGF) on the morphology, primordial follicle activation, growth and proliferation of granulosa cells of ovine follicles cultured in situ, as well as the effect of a PI3K inhibitor on the follicular activation. Ten ovine ovaries were divided into fragments, being one fixed for histological analysis (fresh control). The remaining fragments were cultured for 7 days in control medium (α-MEM + ) alone or supplemented with EGF (1, 10, 50, 100 or 200 ng/mL). Follicles were classified as normal or atretic, as primordial or growing, and the oocyte and follicle diameters were measured. PCNA immunohistochemistry was performed in the fresh control and in treatment that showed the best results for follicular activation. Pharmacologic inhibition of PI3K activity was performed through pretreatment in media added with 50 µM LY294002 for 1 h. The percentage of normal follicles decreased (P < 0.05) after 7 days of culture in all treatments compared to the fresh control. A significant reduction in the percentage of primordial follicles and an increase (P < 0.05) in the growing ones were observed in all treatments compared to fresh control. Furthermore, both the control medium and 1 ng/mL EGF promoted an increase (P < 0.05) in follicular activation compared to other EGF treatments. The PCNA-positive cells in the EGF treatment were higher (P < 0.05) than in fresh control and α-MEM + . Pretreatment of ovarian tissue with PI3K inhibitor significantly inhibited (P < 0.05) α-MEM + -stimulated primordial follicle activation, but had no effect on EGF-stimulated activation (P > 0.05). In conclusion, PI3K pathway mediates the in vitro spontaneous activation of sheep primordial follicles. Moreover, EGF may act indirectly on follicular activation by promoting granulosa cell proliferation at 1 ng/mL, and EGF inhibited follicle activation in concentrations similar or higher than 10 ng/mL.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Blocking the PI3K pathway or the presence of high concentrations of EGF inhibits the spontaneous activation of ovine primordial follicles in vitro

Santos¹,

Santos²,

Menezes³

et al. 2017

Anim Reprod

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“…In mice, in vitro studies of isolated neonatal ovaries indicate that high dose BPA exposure inhibited germ cell nest breakdown and accelerated primordial follicle recruitment compared to controls (99, 100), similar to some of the observations in in vivo studies. Specifically, BPA exposure decreased levels antigen KI-67 ( Ki67 ), tumor necrosis factor receptor superfamily member 6 ( Fas ), and caspases ( Casp3 and 8 ) (99, 100).…”

Section: Resultssupporting

confidence: 76%

“…Specifically, BPA exposure decreased levels antigen KI-67 ( Ki67 ), tumor necrosis factor receptor superfamily member 6 ( Fas ), and caspases ( Casp3 and 8 ) (99, 100). Further, BPA increased levels of Bcl2 and factors related to the phosphatidylinositol 3-kinase/thymoma viral proto-oncogene (PI3K/Akt) signaling pathway (99, 100).…”

Section: Resultsmentioning

confidence: 99%

Evidence for bisphenol A-induced female infertility: a review (2007–2016)

Ziv‐Gal

Flaws

2016

Fertility and Sterility

195

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We summarized the scientific literature published from 2007 to 2016 on the potential effects of bisphenol A (BPA) on female fertility. We focused on overall fertility outcomes (e.g., ability to become pregnant, number of offspring), organs that are important for female reproduction (i.e., oviduct, uterus, ovary, hypothalamus, and pituitary), and reproductive related processes (i.e., estrous cyclicity, implantation, and hormonal secretion). The reviewed literature indicates that BPA may be associated with infertility in women. Potential explanations for this association can be generated from experimental studies. Specifically, BPA may alter overall female reproductive capacity by affecting the morphology and function of the oviduct, uterus, ovary, and hypothalamus-pituitary-ovarian axis in animal models. Additionally, BPA may disrupt estrous cyclicity and implantation. Nevertheless, further studies are needed to better understand the exact mechanisms of action and to detect potential reproductive toxicity at earlier stages.

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“…Studies using culture of murine ovarian tissue demonstrate that, at exposure levels found in Chinese children, BPA may lead to a premature activation of folliculogenesis ultimately leading to a reduced follicular pool (388). Similar studies have been performed in vivo using mice, rats, sheep, and monkeys (see TABLE 7); however, there is limited data available on the effects of BPA on ovarian development and early folliculogenesis in humans (125).…”

Section: Influences On Follicular Development and Ovulationmentioning

confidence: 91%

Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics

Hart

2016

Physiological Reviews

168

119

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Across the Western World there is an increasing trend to postpone childbearing. Consequently, the negative influence of age on oocyte quality may lead to a difficulty in conceiving for many couples. Furthermore, lifestyle factors may exacerbate a couple's difficulty in conceiving due mainly to the metabolic influence of obesity; however, the negative impacts of low peripheral body fat, excessive exercise, the increasing prevalence of sexually transmitted diseases, and smoking all have significant negative effects on fertility. Other factors that impede conception are the perceived increasing prevalence of the polycystic ovary syndrome, which is further exacerbated by obesity, and the presence of uterine fibroids and endometriosis (a progressive pelvic inflammatory disorder) which are more prevalent in older women. A tendency for an earlier sexual debut and to have more sexual partners has led to an increase in sexually transmitted diseases. In addition, there are several genetic influences that may limit the number of oocytes within the ovary; consequently, by postponing attempts at childbearing, a limitation of oocyte number may become evident, whereas in previous generations with earlier conception this potentially reduced reproductive life span did not manifest in infertility. Environmental influences on reproduction are under increasing scrutiny. Although firm evidence is lacking however, dioxin exposure may be linked to endometriosis, phthalate exposure may influence ovarian reserve, and bisphenol A may interfere with oocyte development and maturation. However, chemotherapy or radiotherapy is recognized to lead to ovarian damage and predispose the woman to ovarian failure.

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Exposure to bisphenol A at physiological concentrations observed in Chinese children promotes primordial follicle growth through the PI3K/Akt pathway in an ovarian culture system

Cited by 30 publications

References 48 publications

Blocking the PI3K pathway or the presence of high concentrations of EGF inhibits the spontaneous activation of ovine primordial follicles in vitro

Blocking the PI3K pathway or the presence of high concentrations of EGF inhibits the spontaneous activation of ovine primordial follicles in vitro

Evidence for bisphenol A-induced female infertility: a review (2007–2016)

Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics

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