Abstract
Triclosan (TCS), a broad-spectrum antimicrobial agent, is widely used in clinical settings and various personal care products. The aim of this study was to evaluate the influence of TCS on reproductive endocrine and function. Here, we show that the exposure of adult female mice to 10 or 100 mg/kg/day TCS caused prolongation of diestrus, and decreases in antral follicles and corpora lutea within 2 weeks. TCS mice showed decreases in the levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and progesterone, and gonadotrophin-releasing hormone (GnRH) mRNA with the lack of LH surge and elevation of prolactin (PRL). TCS mice had lower kisspeptin immunoreactivity and kiss1 mRNA in anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). Moreover, the estrogen (E2)-enhanced AVPV-kisspeptin expression was reduced in TCS mice. In addition, the serum thyroid hormones (triiodothyronine (T3) and thyroxine (T4)) in TCS mice were reduced with increases in levels of thyroid stimulating hormone (TSH) and thyroid releasing hormone (TRH). In TCS mice, the treatment with Levothyroxine (L-T4) corrected the increases in PRL, TSH and TRH; the administration of L-T4 or type-2 dopamine receptors agonist quinpirole inhibiting PRL release could rescue the decline of kisspeptin expression in AVPV and ARC; the treatment with L-T4, quinpirole or the GPR45 agonist kisspeptin-10 recovered the levels of serum LH and FSH and progesterone, and GnRH mRNA. Furthermore, TCS mice treated with L-T4 or quinpirole resumed regular estrous cycling, follicular development and ovulation. Together, these results indicate that exposing adult female mice to TCS (≥10 mg/kg) reduces thyroid hormones causing hyperprolactinemia that then suppresses hypothalamic kisspeptin expression, leading to deficits in reproductive endocrine and function.
Highlights
Triclosan (2,4,4 -trichloro-2 -hydroxy-diphenyl ether, TCS) is a synthetic antibacterial compound largely utilized in personal and household products such as toothpastes, shampoos, cosmetics, antibacterial soaps, deodorants, kitchen utensils, bedding and clothing (Rodricks et al, 2010)
The results in the present study provides in vivo evidence that the exposure of adult female mice to TCS (≥10 mg/kg) reduces thyroid hormones, causing hyperprolactinemia which suppresses hypothalamic kisspeptin neurons, disrupting reproductive endocrine and function
The present data suggest that TCS-induced hypothyroidism presents the same scenario, as the elevated levels of serum PRL, thyroid stimulating hormone (TSH) and thyroid releasing hormone (TRH) in 10-TCS mice were corrected by L-T4 administration
Summary
Triclosan (2,4,4 -trichloro-2 -hydroxy-diphenyl ether, TCS) is a synthetic antibacterial compound largely utilized in personal and household products such as toothpastes, shampoos, cosmetics, antibacterial soaps, deodorants, kitchen utensils, bedding and clothing (Rodricks et al, 2010). A large body of evidence indicates that the exposure of female rats to TCS reduces the thyroid hormones (Stoker et al, 2010). The oral administration of TCS decreases dose-dependently the level of circulating thyroxine (T4) in weanling female rats (Witorsch, 2014). The treatment with TCS in pregnant rats decreases total serum triiodothyronine (T3) and T4 (Rodríguez and Sanchez, 2010). This decrease in thyroid hormone results in reduced negative feedback on the hypothalamus-pituitary axis enhances thyroid releasing hormone (TRH) secretion, which would in turn promote excess prolactin (PRL) secretion (Tohei et al, 2000). Hyperprolactinemia is a major neuroendocrine-related cause of reproductive disturbances in women
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