You are here:
Phthalate-Induced Pathology in the Foetal Testis Involves More Than Decreased Testosterone Production
Citation:
Veeramachaneni, D. AND G. Klinefelter. Phthalate-Induced Pathology in the Foetal Testis Involves More Than Decreased Testosterone Production. REPRODUCTION. BioScientifica Ltd., Bristol, Uk, 147(4):435-42, (2014).
Impact/Purpose:
This review is an extension of our recent study published last December in Reproduction. Subsequent to publication the work was invited for presentation at the recent Copenhagen Workshop on EDCs. Dr. Veeramachaneni presented. Subsequent to the workshop, we were invited to submit a manuscript. This manuscript attempts to summarize the current state of the science relating to phthalate exposures and dysgenesis in the fetal testis. Based on our research we have proposed an adverse outcome pathway that might better explain the existing data across species.
Description:
Foetal exposure to phthalates is known to adversely impact male reproductive development and function. Developmental anomalies of reproductive tract have been attributed to impaired testosterone synthesis. However, species differences in the ability to produce testosterone have been noted; e.g., following foetal exposure, abnormal clustering of Leydig cells or decreased production of testosterone that manifests in rats do not occur in mice or humans. Nonetheless, other facets of testicular dysgenesis do occur in both rats and mice as well as in some other species tested. We recently published a comprehensive evaluation of the foetal rat testis proteome following in utero exposure to diethylhexyl phthalate (DEHP), which revealed changes in individual proteins that are known to be factors in cellular differentiation and migration or related to the capacity of the foetal Leydig cell to produce T and fit a pathway network in which each is regulated directly or indirectly by oestradiol. Plasma oestradiol indeed was elevated ~two-fold in 19-day-old DEHP-exposed foetal male rats. In this brief review, we discuss our new findings vis-à-vis “oestrogen hypothesis” as a cause for testicular dysgenesis syndrome.