Endocrine-Disrupting Chemicals: Part 2

April 12, 2016

In the second half of this update from ENDO 2016, we look at how endocrine-disrupting chemicals affect the reproductive system and the gut microbiome.

UV filters interfere with sperm function

Some ultraviolet (UV) filters used in sunscreens are quickly absorbed in the skin and have been found in more than 95% of urine samples in the US, Spain, France, and Denmark and measured in plasma.

In a pilot study1 published in EMBO Reports, researchers found that various types of endocrine-disrupting chemicals can mimic the action of progesterone on the CatSper channel and thereby induce calcium signals in human sperm cells. Anders Rehfeld and colleagues, of the University of Copenhagen, Copenhagen, Denmark, sought to determine if UV filters mimicked the action of progesterone on the human sperm-specific CatSper calcium channel.

They examined 29 of the 31 UV filters found in sunscreens in the US or Europe (one filter could not be obtained and one could not be dissolved). Thirteen filters were found to induce calcium signals in human sperm. Researchers tested these UV filters at various doses and plotted the calcium signals.

4-MBC and 3-BC, the most efficient UV filters, induced calcium influxes at 10 µM (97% and 92%, respectively, of the maximal progesterone-induced calcium influx). Nine of the 13 UV filters induced a calcium influx by directly activating the CatSper channel (n=3). The 13 UV filters were also tested in a mixture of 100 NM each, and a small calcium signal was found.

In conclusion, 13 of 29 tested UV filters induced calcium signals at relevant doses. Nine UV filters activated the CatSper channel directly, thus mimicking the effect of progesterone. Some of the UV filters also interfered with vital sperm functions. Further studies are needed to learn if UV filters affect human fertility.

From material presented at The Endocrine Society Annual Meeting 2016, Boston, MA. OR04-6. Organic Ultraviolet Filters Mimic the Action of Progesterone on Human Sperm and Interfere with Sperm Functions.

Non-prescription antibiotic induces gut microbial dysbiosis

The gastrointestinal tract is primarily colonized with microbiota following birth and eventually stabilizes to a more adult-like profile. However, certain environmental exposures to things like prescription antibiotics can change this stabilization and lead to infectious disease in the short-term as well as immune disorders and obesity in later life. Prescription antibiotics are commonly prescribed during pregnancy as well as in the nursing period. Because of the fear of infectious disease during this time, explained presenter Rebekah Kennedy, there has also been an increase in non-prescription antimicrobial use.

Triclocarban (3,4,4′-trichlorocarbanilide; TCC) is an antimicrobial compound commonly found in bar soaps. People are primarily exposed when they use TCC-containing personal care products that are absorbed into the skin and then the bloodstream.

Kennedy and colleagues (University of Tennessee, Knoxville, TN and University of Colorado, Fort Collins, CO) previously demonstrated that TCC actually concentrated in the breast milk of rats exposed to TCC during pregnancy and the nursing period. Their offspring developed a distended abdomen as well as liquid, mustard-colored diarrhea, indicating that some gut microbial disturbance may be occurring.

The objective of this study was to characterize the effect of TCC exposure on microbiota compositional changes in the nursing offspring. During pregnancy and the nursing period, rats were given 0.1% of TCC through their food. Cecum was then collected from the nursing pups.

At day 3 there is not much definition between the treated and untreated groups of rats. At day 6 there is a reorganization of microbiota, but still not much definition between the groups. By day 12 the groups start to separate and by day 16, they are significantly different, indicating that TCC affects the colonization process. Researchers looked at the relative abundance at the family level. At day 3, there is a variety of bacteria families. At day 6 there is a reorganization and both samples are primarily composed of Enterobacteriaccae. At day 16 there is another reorganization and the untreated group is composed primarily of Bacteroidaccae and the TCC group is primarily composed of Enterobacteriaccae. This is important because in humans we see that an increased ratio of Enterobacteriaccae leads to food sensitivities later in life, which may indicate that TCC may have some later life health outcomes.

TCC exposure can actually drive microbial compositional changes during the nursing period. Kennedy stated that future investigations should focus on the health effects associated with non-prescription antimicrobial use during sensitive exposure windows.

From material presented at The Endocrine Society Annual Meeting 2016, Boston, MA. PP04-2. 3,4,4'-Trichlorocarbanilide Exposure Induces Gut Microbial Dysbiosis in Neonatal Rats.

 

References:

1. Schiffer C, et al. Direct action of endocrine disrupting chemicals on human sperm. EMBO Rep. 2014 Jul;15(7):758-765.