Perinatal exposure to low dose bisphenol A (BPA) or diethylstilbestrol (DES) have similar and yet unique effects on adult gene expression in experimental endometriosis while reducing the ovarian follicle reserve. — ASN Events

Perinatal exposure to low dose bisphenol A (BPA) or diethylstilbestrol (DES) have similar and yet unique effects on adult gene expression in experimental endometriosis while reducing the ovarian follicle reserve. (#280)

John J Bromfield 1 , Katherine E Pelch 2 , Susan C Nagel 1
  1. University of Missouri, Columbia, MO, United States
  2. National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA

Endocrine disrupting chemicals (EDCs) have a significant impact on the female reproductive tract. Developmental exposure to EDCs disrupts adult gene expression in the endometrium, increases the incidence of endometriosis and disrupts development of male and female gametes. Using a rodent model of low dose perinatal exposure to BPA or DES, we examined the impact of these chemicals on the susceptibility to experimental endometriosis and the ovarian follicle reserve. Mice at gestational day 11 were administered 100 ng/kg/day DES or 10 μg/kg/day BPA via mini-osmotic pumps implanted in dams until postnatal day 12. Offspring exposed to EDCs underwent surgical induction of endometriosis at 8 weeks of age. Uterus, endometriosis lesion and ovary were collected after 28 days of induced endometriosis for global gene expression analysis and ovarian follicle reserve assessment. Global gene expression of uterine tissue and endometriosis lesion revealed a significant dysregulation of gene expression in animals with perinatal BPA or DES exposure compared to vehicle treated controls. Gene ontology analysis revealed disruption of similar pathways between BPA and DES animals in the uterus, including membrane transport, metalloproteases and transcriptional activity. However dramatic differences in gene expression profiles of endometriosis lesion were apparent when comparing BPA to DES animals. DES animals (79 genes) revealed the greatest dysregulation of gene expression in the endometriosis lesion compared to BPA animals (38 genes) with changes to membrane transport, transcription, translation, cell-cell communication and apoptosis. Assessment of the ovarian reserve in animals exposed to BPA or DES revealed a significant reduction in the total ovarian follicle reserve (16.9% and 21.9%, respectively), due to a reduction in the primordial follicle pool and a dramatic increase in atretic follicle number. These findings suggest that exposure to EDCs during the perinatal period may lead to increased risk of endometriosis and premature ovarian failure in adulthood.

@ESASRB