Bisphenol A and S impaired ovine granulosa cell steroidogenesis

Abstract

Bisphenols, plasticisers used in food containers, can transfer to food. Bisphenol A (BPA) has been described as an endocrine disruptor and consequently banned from the food industry in several countries. It was replaced by a structural analogue, Bisphenol S (BPS). BPA action on the steroidogenesis is one of the mechanisms underlying its adverse effects on the efficiency of female reproduction. This study aimed to determine whether BPS is a safe alternative to BPA regarding GC functions. Antral follicles (2–6 mm), of approximatively 1000 adult ewe ovaries, were aspired and GC purified. For 48 h, ovine GC were treated with BPA or BPS (from 1 nM to 200 µM) and the effects on cell viability, proliferation, steroid production, steroidogenic enzyme expression and signalling pathways were investigated. Dosages at and greater than 100 μM BPA and 10 µM BPS decreased progesterone secretion by 39% (P < 0.001) and 22% (P = 0.040), respectively. BPA and BPS 10 μM and previously mentioned concentrations increased oestradiol secretion two-fold (P < 0.001 and P = 0.082, respectively). Only 100 µM BPA induced a decrease (P < 0.001) in gene expression of the enzymes of steroidogenesis involved in the production of progesterone. BPA reduced MAPK3/1 phosphorylation and ESR1 and ESR2 gene expression, effects that were not observed with BPS. BPA and BPS altered steroidogenesis of ovine GC. Thus, BPS does not appear to be a safe alternative for BPA. Further investigations are required to elucidate BPA and BPS mechanisms of action.

Bisphenol S Impaired Human Granulosa Cell Steroidogenesis in Vitro

“…On the contrary, HGC are similar in terms of sensitivity to progesterone secretion with ewe GC. In ovine granulosa cells, progesterone declined by 22% and 32% after 10 µM and 50 µM BPS treatment, respectively [44], data that are similar to the results obtained in the present paper. These findings confirm that the ewe is a relevant model to study human reproductive function in terms of effects and sensitivity of cells [48][49][50].…”

“…The highest BPS concentration significantly reduced oestradiol secretion. This result is inconsistent with previous data in animal models, where BPS exposure increases oestradiol secretion in rat GC [43], ewe GC [44] and cow GC [42]. Nevertheless, as mentioned above, the fact that HGC were only collected from pre-ovulatory follicle (contrary to other animal models) could explain the observed discrepancies.…”

“…MAPK3/1 signalling pathway is involved in granulosa cell steroidogenesis [54]. Difference between the BPA and BPS effect on the MAPK3/1 signalling pathway were evidenced in ovine granulosa cells [44]. Nevertheless, these data suggest that the BPS effect on steroidogenesis is likely independent of the MAPK3/1 pathway, as it was reported in ovine GC.…”

“…This effect is consistent with previous data from animal models. Indeed, BPS exposure (5 mg/kg body weight) decreases plasma progesterone in rats [43] and progesterone secretion in ewe GC and cumulus cells [44,45]. However, discrepancies among species or tested doses can occur.…”

Bisphenol A and Bisphenol S Oxidative Effects in Sheep Red Blood Cells: An In Vitro Study

“…The sheep model represents a valuable tool in studying the effects of xenobiotics on animals and humans also at different development stages [17]. As an example, sheep was used to help understand BPs' effects and mechanism of action in a pregnancy model [18][19][20]. Another author used sheep blood for his work, and in particular, he studied sheep blood contaminated with BPA that was detected in both plasma and red blood cells (RBC) (10 times lower than in plasma), indicating that BPA could have migrated from plasma into RBC [21].…”