The fetal ovary exhibits temporal sensitivity to a ‘real-life’ mixture of environmental chemicals

Abstract

The development of fetal ovarian follicles is a critical determinant of adult female reproductive competence. Prolonged exposure to environmental chemicals (ECs) can perturb this process with detrimental consequences for offspring. Here we report on the exposure of pregnant ewes to an environmental mixture of ECs derived from pastures fertilized with sewage sludge (biosolids): a common global agricultural practice. Exposure of pregnant ewes to ECs over 80 day periods during early, mid or late gestation reduced the proportion of healthy early stage fetal follicles comprising the ovarian reserve. Mid and late gestation EC exposures had the most marked effects, disturbing maternal and fetal liver chemical profiles, masculinising fetal anogenital distance and greatly increasing the number of altered fetal ovarian genes and proteins. In conclusion, differential temporal sensitivity of the fetus and its ovaries to EC mixtures has implications for adult ovarian function following adverse exposures during pregnancy.

Environmental influences on ovarian dysgenesis — developmental windows sensitive to chemical exposures

“…By exposing pregnant ewes during early, mid, late or the whole gestation period to a mixture of environmental chemicals, including EDCs, disrupted fetal folliculogenesis was induced in all exposure groups, likely due to effects on follicle assembly. At the molecular level, however, the most pronounced changes to gene and protein expression was observed in fetuses having been exposed during mid-late gestation 88 .…”

“…What complicates the picture even further, is that humans are continuously exposed to a large number of chemicals at any given time 119 , whereas controlled animal experiments typically involves the exposure of single chemicals during specific time windows. To overcome this hurdle, a series of studies were conducted exposing sheep on pastures before and during pregnancy to a mixture of environmental chemicals 88,120,121 . The studies focusing on female fetuses found that constant maternal exposure to a low-concentration mixture of chemicals can disrupt ovary development 120 , and that exposure during mid and late gestation was most detrimental 88 .…”

“…To overcome this hurdle, a series of studies were conducted exposing sheep on pastures before and during pregnancy to a mixture of environmental chemicals 88,120,121 . The studies focusing on female fetuses found that constant maternal exposure to a low-concentration mixture of chemicals can disrupt ovary development 120 , and that exposure during mid and late gestation was most detrimental 88 . It was also found that the preconception period is important in relation to effect outcomes on the offspring 121 .…”

A multidisciplinary investigation of the technical and environmental performances of TAML/peroxide elimination of Bisphenol A compounds from water

“…5,238,[251][252][253][254][255][256] This has led to a considerable literature of the effects on animals and their offspring that graze on pastureland amended with sludge containing multiple EDs. 95,[257][258][259][260][261][262][263][264][265][266][267] Since these studies mostly concern multi-ED exposures, we consider this area outside the scope of the current mini-reviews. Sludge is the primary source of 1a soil contamination.…”

Environmental mixture with estrogenic activity increases Hsd3b1 expression through estrogen receptors in immature rat granulosa cells

“…Owing to their complexity, environmental mixtures are virtually impossible to reproduce artificially, thus enabling investigations into the effect of the "whole mixture" exposure on biological functions (Lea et al, 2016). Sewage sludge fertilizer containing readily detectable levels of EDs has been used to investigate the effect of a "real-life" mixture on the ovarian (Lea et al, 2016), testicular (Paul et al, 2005), thyroid gland (Hombach-Klonisch et al, 2013), and hypothalamopituitary axis (Bellingham et al, 2010) development. Exposure to wastewater effluents, which also represent a source of various EDs, is associated with a range of reproductive effects, particularly in fish, such as lowered hormone levels (Folmar et al, 1996) and reduced gamete production and fertilization capabilities (Jobling et al, 2002).…”