In utero exposure to low doses of environmental pollutants disrupts fetal ovarian development in sheep

Abstract

Epidemiological studies of the impact of environmental chemicals on reproductive health demonstrate consequences of exposure but establishing causative links requires animal models using ‘real life’ in utero exposures. We aimed to determine whether prolonged, low-dose, exposure of pregnant sheep to a mixture of environmental chemicals affects fetal ovarian development. Exposure of treated ewes (n = 7) to pollutants was maximized by surface application of processed sewage sludge to pasture. Control ewes (n = 10) were reared on pasture treated with inorganic fertilizer. Ovaries and blood were collected from fetuses (n = 15 control and n = 8 treated) on Day 110 of gestation for investigation of fetal endocrinology, ovarian follicle/oocyte numbers and ovarian proteome. Treated fetuses were 14% lighter than controls but fetal ovary weights were unchanged. Prolactin (48% lower) was the only measured hormone significantly affected by treatment. Treatment reduced numbers of growth differentiation factor (GDF9) and induced myeloid leukaemia cell differentiation protein (MCL1) positive oocytes by 25–26% and increased pro-apoptotic BAX by 65% and 42% of protein spots in the treated ovarian proteome were differently expressed compared with controls. Nineteen spots were identified and included proteins involved in gene expression/transcription, protein synthesis, phosphorylation and receptor activity. Fetal exposure to environmental chemicals, via the mother, significantly perturbs fetal ovarian development. If such effects are replicated in humans, premature menopause could be an outcome.

Medicating the environment: assessing risks of pharmaceuticals to wildlife and ecosystems

“…In the terrestrial environment, pharmaceuticals can also be taken up into plants [36,46] or remain bound to the external surfaces of leaves following biosolids or waste water application, thus potentially exposing herbivores to associated contaminants [47]. Predicting bioavailability of drugs in soils and also sediments is complicated by the fact that many compounds are ionizable and those that form cations may become bound to negatively charged clay particles [35,36].…”

Epigenetics and developmental programming of welfare and production traits in farm animals

“…There are welldocumented actions of EDCs on the morphology and development of the sheep ovary during fetal and early postnatal life. SS exposure alters ovarian dynamics in 110-day fetuses, reducing oocyte density, advancing follicle development and increasing a pro-apoptotic protein (Bax) key to normal ovarian development (Fowler et al 2008). Similarly, exposure to PCB 118 and PCB 153 throughout gestation altered follicular dynamics in prepubertal animals 60 days after birth.…”

Neonatal exposure to xenoestrogens impairs the ovarian response to gonadotropin treatment in lambs

“…The lamb ovary is sensitive to disruption by EDC exposure during intrauterine life (Adams et al 1988, Adams 1995, Savabieasfahani et al 2006, Fowler et al 2008 or during early postnatal life (Rivera et al 2011). In sheep, a precocial species, we have previously demonstrated that low doses of s.c. BPA or DES injections from birth to postnatal day 14 (PND14) cause a decline in the stock of primordial follicles by stimulating follicular development and increasing follicular atresia (Rivera et al 2011).…”