Abstract
Mono-(2-ethylhexyl) phthalate (MEHP) and genistein have been classified as endocrine-disrupting chemicals (EDCs) which interfere with the differentiation and development of the male reproductive system. However, how these two EDCs would affect fetal rat testis development at a low dose was rarely studied. In this study, we established the organ culture system and applied it to evaluate testicular effects following multiple EDC exposure at a low dose. 15.5 days postcoitum fetal rat testes were dissected, cultured, and exposed to vehicle (control), GEN (1 μmol/L, G), MEHP (1 μmol/L, M), or GEN (1 μmol/L)+MEHP (1 μmol/L, G+M). Testicular cell markers, testosterone concentration, redox state, testicular histology, and testicular ultrastructure were evaluated. Our results showed that a low dose of MEHP suppressed the development of Sertoli cells, Leydig cells, and gonocytes by triggering oxidative injuries, which was consistent with the ultrastructural findings. However, coadministration of genistein at a low dose could partially attenuate MEHP-induced fetal testis damage through antioxidative action. Cotreatment of genistein at a low dose may have a promising future on its protecting role for attenuating other EDC-induced reproductive disorders during early life. Based on the results, it can be speculated that dietary intake of isoflavones may make the fetal testis less susceptible to phthalate-induced injury.
Highlights
In the last two decades, there have been growing concerns on endocrine-disrupting chemical- (EDC-) related male reproductive system disorder
Exposure to mono-(2-ethylhexyl) phthalate (MEHP) caused a significant decrease in Sohlh2, Hsp90, and Pdgfrβ expression compared with control (P < 0:05), while the combined exposure of MEHP and genistein showed an increase in Hsp90 expression compared to MEHP single exposure (P < 0:05), which manifests that genistein may exert its protective role in fetal germ cell development
Amh was downregulated after MEHP exposure for 4 days compared with the control group (P < 0:05) while the combined exposure to MEHP and genistein showed no significant difference with the control group (P > 0:05)
Summary
In the last two decades, there have been growing concerns on endocrine-disrupting chemical- (EDC-) related male reproductive system disorder. Multiple evidences suggested that EDCs can interfere with the production, release, transport, metabolism, binding action, or elimination of the natural hormones in the body, exhibiting potentially deleterious effects on the development of the male reproductive system [1]. Several common EDCs, including derivatives of paints, plastics, and natural soy-derived phytoestrogens, have been detected in amniotic fluid, cord blood, and breast milk [2,3,4], indicating that humans and animals are exposed to a myriad of potentially harmful substances in early life. Genistein (GEN), a kind of soy isoflavones commonly present in the Asian diet [6], and mono-(2-ethylhexyl) phthalate (MEHP), the metabolite of the widely used plasticizer di(2-ethylhexyl) phthalate (DEHP), are two kinds of the most prevalent EDCs which act via different mechanisms [7].
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