Impact of Triclosan on Female Reproduction through Reducing Thyroid Hormones to Suppress Hypothalamic Kisspeptin Neurons in Mice

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.

Comprehensive insight into triclosan—from widespread occurrence to health outcomes

“…Endocrine disrupting properties of TCS were also examined in various animal models within a wide range of doses and dosing regimens, which makes the obtained results difficult to compare. For instance, administration of TCS in concentration up to 0.345 mmol/kg/day resulted in a decrease of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in female mice (Cao et al 2018), while at the higher oral dose (0.639 mmol/ kg/day), increased both FSH and LH were measured in Sprague Dawley rats (Abd-Elhakim et al 2018). However, a comparable reduction in thyroid hormones, T3 and T4, was observed in male Wistar albino rats (Taha et al 2020), female Sprague Dawley rats (Abd-Elhakim et al 2018) and female mice (Cao et al 2018).…”

Integrated Hypothalamic Transcriptome Profiling Reveals the Reproductive Roles of mRNAs and miRNAs in Sheep

“…Triclosan in mice was found to reduce the production of TRH and thyroid-stimulating hormone (TSH), and this decreased effect could further cause hyperprolactinemia. Hyperprolactinemia was suggested to cause a suppressive effect on kisspeptin expression, resulting in deficits in reproductive and endocrine function (Cao et al, 2018b). In addition, TRH can not only stimulate PRL release but also inhibit LH release, and this inhibitory effects may occur through prohibiting the release of GnRH (Araujo-Lopes et al, 2014).…”

Triclocarban, Triclosan, Bromochlorophene, Chlorophene, and Climbazole Effects on Nuclear Receptors: An in Silico and in Vitro Study

“…Triclosan up-regulated AR and ER in the placenta of pregnant rats, and decreased serum E2 and testosterone levels (Feng et al 2016). Although it is generally accepted that triclosan interferes with thyroid hormone-controlled gene expression and has effects in vivo, there are studies that show no effects with respect to TR agonist and antagonist activities, and some that claim triclosan is a TR antagonist (Cao et al 2018;Crofton et al 2007;Fort et al 2010Fort et al , 2011Paul et al 2010;Veldhoen et al 2006;Zhang et al 2018;Zhou et al 2017). The present study confirms that triclosan is a TR antagonist in the GH3.TRE-Luc reporter cell line, with an IC 50 of 3:61 lM.…”