Bisphenol S Alters the Steroidome in the Preovulatory Follicle, Oviduct Fluid and Plasma in Ewes With Contrasted Metabolic Status

Abstract

Bisphenol A (BPA), a plasticizer and endocrine disruptor, has been substituted by bisphenol S (BPS), a structural analogue that had already shown adverse effects on granulosa cell steroidogenesis. The objective of this study was to assess the effect of chronic exposure to BPS, a possible endocrine disruptor, on steroid hormones in the ovary, oviduct and plasma using the ewe as a model. Given the interaction between steroidogenesis and the metabolic status, the BPS effect was tested according to two diet groups. Eighty adult ewes were allotted to restricted (R) and well-fed (WF) groups, that were further subdivided into two subgroups. Ewes were exposed to 50 µg BPS/kg/day in their diet (R50 and WF50 groups) or were unexposed controls (R0 and WF0 groups). After at least 3 months of BPS exposure, preovulatory follicular fluid, oviduct fluid and plasma were collected and steroid hormones were analyzed by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). A deleterious effect of restricted diet on the volume of oviduct fluid and numbers of pre-ovulatory follicles was observed. Exposure to BPS impaired estradiol concentrations in both follicular and oviduct fluids of well-fed ewes and progesterone, estradiol and estrone concentrations in plasma of restricted ewes. In addition, a significant interaction between metabolic status and BPS exposure was observed for seven steroids, including estradiol. In conclusion, BPS acts in ewes as an endocrine disruptor with differential actions according to metabolic status.

Impact of food restriction on the medio‐basal hypothalamus of intact ewes as revealed by a large‐scale transcriptomics study

“…All animals used in the current study were involved in a protocol aimed at investigating the impact of a chronic low exposure to the environmental pollutant bisphenol S (BPS) upon the quality of in vitro embryo production and the steroidomic changes in plasma, follicular fluid and oviductal fluid according to the metabolic status in the ewe. Data pertaining to this aspect have already been published 21,22 . Below, we briefly summarize the experimental design.…”

“…This goal was not met; ewes of the WF ewes ended up with a BW of 66.0 ± 0.7 kg and a BCS of 3.14 ± 0.05 and ewes of the FRes group ended up with a BW of 54.3 ± 0.7 kg and a BCS of 2.12 ± 0.04. The difference between the groups was, however, highly significant, both for BW and BCS (p < .001 for both; see 21,22 ). For each year, the 60 ewes were killed in batches of either seven (Expt 1) or six (Expt 2) animals, with a variable number of animals from each of the six experimental groups (see Figure S1…”

“…Data pertaining to this aspect have already been published. 21,22 Below, we briefly summarize the experimental design. A total of 120 young primiparous ( Among the WF and FRes groups, ewes were supplemented with various BPS doses for at least 3 months (0, 4 or 50 μg/kg/day), therefore generating six experimental groups of 10 ewes (WF-0, WF-4, WF-50 and FRes-0, FRes-4, FRes-50; see Figure S1).…”

Bisphenol A and bisphenol S both disrupt ovine granulosa cell steroidogenesis but through different molecular pathways

“…The effect of BPS on the pre-ovulatory follicular fluid steroidome varied according to the metabolic status of the animal. Indeed, a stimulatory effect of BPS on the oestradiol level was observed only in well-fed ewes [58]. From this perspective, it could be assumed that the difference in sensitivity to bisphenols and variation in steroidogenesis of ovine GC could be influenced by either the metabolic status of the ewes -the donors of GC and/or the oestrus season.…”

Oral exposure to bisphenol S is associated with alterations in the oviduct proteome of an ovine model, with aggravated effects in overfed females

“…Sheep represent a good model to study the impact of endocrine disruptors in interaction with body mass index on human reproduction as it has already been used in previous toxicology studies [14,27], and because of its similarities in the anatomy of the oviducts and kinetics of ovogenesis and folliculogenesis with women [28,29].…”