In Vitro Effects of Bisphenol A and Tetrabromobisphenol A on Cell Viability and Reproduction-Related Gene Expression in Pituitaries from Sexually Maturing Atlantic Cod (Gadus morhua L.)

Abstract

Bisphenol A (BPA) and tetrabromobisphenol A (TBBPA) are widely used industrial chemicals, ubiquitously present in the environment. While BPA is a well-known endocrine disruptor and able to affect all levels of the teleost reproductive axis, information regarding TBBPA on this subject is very limited. Using primary cultures from Atlantic cod (Gadus morhua), the present study was aimed at investigating potential direct effects of acute (72 h) BPA and TBBPA exposure on cell viability and the expression of reproductive-relevant genes in the pituitary. The results revealed that both bisphenols stimulate cell viability in terms of metabolic activity and membrane integrity at environmentally relevant concentrations. BPA had no direct effects on gonadotropin gene expression, but enhanced the expression of gonadotropin-releasing hormone (GnRH) receptor 2a, the main gonadotropin modulator in Atlantic cod. In contrast, TBBPA increased gonadotropin transcript levels but had no effect on GnRH receptor mRNA. In conclusion, both anthropogenic compounds display endocrine disruptive properties and are able to directly interfere with gene expression related to reproductive function in cod pituitary cells at environmentally relevant concentrations in vitro.

Salmonid Pituitary Cells as a Test System for Identifying Endocrine‐Disrupting Compounds

“…Based on the results summarized in Figures 1 and 2, we concluded that the optimal protocol was to culture primary pituitary cells from previtellogenic rainbow trout and to expose cell cultures to chemical treatments with or without 3.7 nM (1 ng/mL) E2 for a period of 3 days. These test conditions were influenced by decades of in vitro experiments studying the effects of hormones on pituitary function in salmonids (see Luckenbach et al, 2010; Weil et al, 1986) and are generally consistent with studies examining hormone and EAC effects on primary pituitary cells from other cold water fish species (von Krogh et al, 2019a, 2019b). We found that pituitary cultures from previtellogenic trout were much more responsive to E2 stimulation than cells from vitellogenic trout, suggesting that understanding the hormonal milieu at pituitary collection is critical to the interpretation of primary cell culture results.…”

“…Primary pituitary cell cultures from asynchronous spawning fishes such as the marine medaka ( Oryzias melastigma ) have been used for rapid detection of endocrine‐disrupting activity for several well‐characterized chemicals including E2, 2,2′,4,4′‐tetrabromodiphenyl ether (BDE‐47), and 4‐NP (Tse et al, 2013). A more recent study used pituitary cells prepared from mixed‐sex Atlantic cod ( Gadus morphua , a group‐synchronous spawner) to evaluate bisphenol A (BPA) and tetrabromobisphenol A (TBBPA) effects on Gth expression (von Krogh et al, 2019b). These studies demonstrate the potential of primary pituitary cells as a contaminant screening tool.…”

A Review on Tetrabromobisphenol A: Human Biomonitoring, Toxicity, Detection and Treatment in the Environment

“…The reproductive ability in males can be reduced, as a result of increased concentrations of TBBPA, which can alter the mobility of sperm cells, sperm concentration, displace the lateral head, and angular displacement [ 91 , 92 ]. Loss of sexual desire, low sperm count and erectile disfunction was also noticed in males exposed to TBBPA [ 93 , 94 ].…”

Screening of halogenated phenolic compounds in plasma and serum from marine wildlife

“…Brominated phenolic compounds have been released to the environment via the use of brominated flame retardants (BFRs). Some BFRs are phenolic in their native configuration such as tetrabromobisphenol A (TBBPA), which has been shown to alter expression reproductive-relevant genes in fish (von Krogh et al 2019). Other BFRs may be converted to HPCs as a result of metabolism (Hakk and Letcher 2003).…”