A pilot study on polycystic ovarian syndrome caused by neonatal exposure to tributyltin and bisphenol A in rats

Yang, Zhibing; Shi, Jonathan; Guo, Zhizhun; Chen, Mingyue; Wang, Chonggang; He, Chengyong; Zuo, Zhenghong

doi:10.1016/j.chemosphere.2019.05.129

Cited by 32 publications

(26 citation statements)

References 51 publications

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“…The state of endometrium and subsequent pregnancy preparation would be affected by changes in uterine morphology, which accounts for the mechanism of inference of uterus development by BPA. Other studies have pointed that irregular estrus cycles in adult rats are caused by BPA exposure, resulting in higher rate of rutting [48,49]. We observed that a more irregular estrus cycle following BPA treatment, especially in proestrus period.…”

Section: Discussionsupporting

confidence: 58%

Oral Bisphenol-A Regulates The Development and Function of Reproductive System through Differential Expression of METTL3

Zhang¹,

Wang²,

Zhu³

et al. 2020

Preprint

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Endocrine-disrupting chemicals (EDCs), which have a profound impact on the reproductive system, can cause endocrine and reproductive disorders, such as polycystic ovary syndrome (PCOS). Bisphenol-A (BPA) is a common endocrine disruptor which can affect the function of the reproductive system. However, the mechanism by which this molecule disrupts normal reproduction is still unclear. In this study, we hypothesized that oral BPA would have a effect on the structure and function of the reproductive system in adolescent female rats, and we would explore a kind of feasible mechanism for this effect. 4-week-old Sprague-Dawley (SD) rats were intragastrically treated for 10 weeks, which were divided into blank group (n = 8), control group (soybean oil, n = 8), three BPA-treatment groups (0.5 mg/kg BPA + soybean oil, 5 mg/kg BPA + soybean oil, 50 mg/kg BPA + soybean oil, n = 8). The results showed that 0.5 mg/kg oral BPA increased the coefficient of uteri, and oral BPA increased the length of uteri in rats without causing hyperandrogenism and ovarian polycystic changes. Oral BPA disturbed the expression of CYP17A1, CYP11A1 and METTL3 in ovaries. Our results suggested that oral BPA might partially interfere uterine morphology and the level of androgen synthetases with RNA methylation by disturbing the expression level of METTL3. RNA methylation might be a new way to explain the interference mechanism of BPA.

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Section: Discussionsupporting

confidence: 58%

Oral Bisphenol-A Regulates The Development and Function of Reproductive System through Differential Expression of METTL3

Zhang¹,

Wang²,

Zhu³

et al. 2020

Preprint

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“…On the other hand, the developmental programming by androgen excess can preferably lead to metabolic disorders, such as obesity, type 2 diabetes mellitus (DM), and insulin resistance in women [22]. Some papers have suggested that endocrine disrupting chemicals may affect PCOS development [23,24]. The exposure of pregnant rats to chemical mixtures caused PCOS-like symptoms as far as the third generation [25], while polychlorinated biphenyl exposure was associated with menstrual cycle abnormalities and the failure of implantation in in vitro fertilization (IVF) procedures [26].…”

Section: Polycystic Ovary Syndrome (Pcos)mentioning

confidence: 99%

Inositols’ Importance in the Improvement of the Endocrine–Metabolic Profile in PCOS

Wojciechowska

Osowski

Jóźwik

et al. 2019

IJMS

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Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility and metabolic problems among women of reproductive age. The mechanism of PCOS is associated with concurrent alterations at the hormonal level. The diagnosis assumes the occurrence of three interrelated symptoms of varying severity, namely ovulation disorders, androgen excess, or polycystic ovarian morphology (PCOM), which all require a proper therapeutic approach. The main symptom seems to be an increased androgen concentration, which in turn may contribute to different metabolic disorders. A number of papers have demonstrated the significant role of inositol therapy in PCOS. However, there is a lack of detailed discussion about the importance of myo-inositol (MI) and d-chiro-inositol (DCI) in reference to particular symptoms. Thus, the aim of this review is to present the effectiveness of MI and DCI treatment for PCOS symptoms. Moreover, the review is focused on analyzing the use of inositols, taking into account their physiological properties, together with the mechanism of individual PCOS symptom formation.

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“…BPA level in plasma is significantly elevated in obese women compared with normal nonobese women, which is positively correlated with serum androgen levels 16,17 . Our previous study also found that BPA (50 μg/kg bw/d) exposure to neonatal female rats led to disorder of adult estrous cycle, increase of serum testosterone (T) and luteinizing hormone (LH), and ovarian polycysticization 18 …”

Section: Introductionmentioning

confidence: 66%

“…Numerous studies have shown that BPA can induce PCOS‐like symptoms 8,10 . In our recent study, female SD rats were exposed to BPA (50 μg/kg bw/d) in the adult stage, and the SD rats experienced the disorder of estrous cycle, serum T increased, and ovarian polycysticization 18 . In this in vitro study, the P and E2 levels were decreased, and the E2/T value was significantly lower than that in the control group.…”

Section: Discussionmentioning

confidence: 93%

The interference effects of bisphenol A on the synthesis of steroid hormones in human ovarian granulosa cells

Shi

Liu

Chen

et al. 2020

Environmental Toxicology

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Numerous studies have shown that endocrine‐disrupting chemicals are one of the important pathogenic factors in women with polycystic ovary syndrome. Our previous study has revealed that bisphenol A (BPA) can cause steroid hormone imbalance, polycystic ovary, and estrus cycle disorder. In this study, we aimed to explore the effect of BPA, a typical environmental estrogen, on the synthesis of steroid hormones in human ovarian granulosa KGN cells. Exposure of KGN cells to BPA (0.5, 5, 50, and 500 μg/L) resulted in the decrease of progesterone (P), estradiol (E2), and the ratio of estradiol to testosterone (E2/T). BPA affected the expression of genes related to steroid hormone synthesis in KGN cells, including the decreased expression of the steroidogenic acute regulatory protein, ferredoxin, and ferredoxin reductase genes during progesterone synthesis; upregulating the expression of cytochrome p450 oxidoreductase gene associated with E2 and T synthesis; and the downregulated cytochrome P450 family 1 subfamily A member 1 and cytochrome P450 family 1 subfamily B member 1 in E2 degradation. BPA also reduced the expression of stimulatory G proteins (GS) in follicle‐stimulating hormone receptor (FSHR)/GS/adenylate cyclase (AC) signaling pathway. In summary, our research has demonstrated that environment‐relevant level of BPA exposure leads to steroid hormone synthesis disorder in human ovarian granulosa cells, which might cause the reduction of gene expression in hormone synthesis and the suppression of the FSHR/GS/AC signaling pathway.

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A pilot study on polycystic ovarian syndrome caused by neonatal exposure to tributyltin and bisphenol A in rats

Cited by 32 publications

References 51 publications

Oral Bisphenol-A Regulates The Development and Function of Reproductive System through Differential Expression of METTL3

Oral Bisphenol-A Regulates The Development and Function of Reproductive System through Differential Expression of METTL3

Inositols’ Importance in the Improvement of the Endocrine–Metabolic Profile in PCOS

The interference effects of bisphenol A on the synthesis of steroid hormones in human ovarian granulosa cells

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