Bisphenol S Administered to Pregnant Ewes with Contrasted Metabolic Status Impaired the Ovarian Follicular Development of Fetuses and Lambs

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Téteau, Ophélie | Jarrier-Gaillard, Peggy | Lasserre, Olivier | Papillier, Pascal | Desmarchais, Alice | Vignault, Claire | Maillard, Virginie | Binet, Aurélien | Lebachelier de la Riviere, Marie-Emilie | Picard-Hagen, Nicole | Elis, Sébastien

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International audience. BACKGROUND-AIMThe size of the ovarian reserve, which is established by the number of primordial follicles, is defined before birth in ovine. The prenatal period is a critical window of sensitivity to environmental factors. Maternal metabolic status during gestation can influence fetal programming, and affect the ovarian reserve. Bisphenol A (BPA), a plasticizer used in food packaging, has deleterious effects on fetal folliculogenesis. It has been banned from the food industry and mainly replaced by bisphenol S (BPS). The objective of this study was to determine the effects of BPS 50 μg/kg/d in utero exposure on female fetuses and lambs from ewes with contrasted metabolic status on follicular population by ovarian histology.METHODSThis study was divided into two experiments performed on pregnant ewes exhibiting a contrasted metabolic status (lean versus well-fed). First, pregnant ewes were exposed to BPS by daily subcutaneous injection for 3 months, to analyze the ovarian development of the fetuses at 130 days of gestation. Second, pregnant ewes were exposed daily to BPS through food for 3 months and the lambs were then monitored up to 4 month-old (pre-puberty). Follicular population was characterized through follicle classification and counting on ovarian sections.RESULTSIn utero BPS exposure led to an increase in the number of pre-antral (p = 0.005) and antral follicles (p < 0.001) in fetuses and conversely to a decrease in 4 month-old lambs (p = 0.007). Besides, a significant interaction between maternal metabolic status and BPS exposure during gestation was reported for the number of primordial (p = 0.019), pre-antral (p = 0.003) and antral (p <0.001) follicles of fetuses. In offspring of fat mothers, the plasma anti- Mullerian hormone decreased in 1 and 2 month-old lambs (p < 0.001). In offspring of well-fed mothers, the body weight of the female fetuses increased (p < 0.001). Moreover, the body weight of female lambs that were in utero exposed to BPS increased compared to control (p = 0.040).CONCLUSIONSIn conclusion, bisphenol exposure during gestation had deleterious consequences on the body and folliculogenesis of the offspring. BPS effects also vary according to the maternal metabolic status. Further research will be needed to determine if these alterations will have deleterious effects on the ovarian reserve and on the reproductive function in adulthood.

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