title: Impact of low molecular weight phthalates in inducing reproductive malfunctions in male mice: Special emphasis on Sertoli cell functions.
abstract: Phthalates are commonly used as plasticizers in a variety of products. Since they have been identified as endocrine-disrupting chemicals (EDCs), effect of phthalates on human health is a major concern. In this study, we evaluated individual as well as combined mixture effects of three low molecular weight phthalates on the reproductive system of male mice, specifically on the Sertoli cell structure and function. In order to analyze the blood testes barrier (BTB) dynamics, primary culture of Sertoli cells from 3-weeks old male mice was used for mimicking typical tight junction structures. Male mice were exposed to long-term (45 days) and combined mixture of three phthalates, diethyl phthalate (DEP), diphenyl phthalate (DPP), and dimethyl isophthalate (DMIP) between pre-pubertal to adult stage. Our data showed significant decrease (p < 0.05) in the rates of transcription of certain prominent Sertoli cell specific genes like transferrin, testin and occludin. Moreover, we also observed significant decreases in the expression of proteins like 3β-HSD, connexin-43 and occludin in testicular lysates of treated animals (p < 0.05). The transmission electron microscopic analysis revealed that the test compounds significantly altered the structural integrity of Sertoli cells. The significant changes of Sertoli cell tight junction structure by test compounds were associated with phosphorylation of ERK. Taken together, our study suggests that low molecular weight phthalates may affect male fertility by altering both structural and functional integrity of Sertoli cells in testes.
authors.affiliation: Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand, India.
authors.forename: Narender
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Srivastava
authors.affiliation: Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand, India. Electronic address: paroyfbs@iitr.ac.in.
authors.forename: Partha
authors.initials: P
authors.lastname: Roy
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D007124:Immunoenzyme Techniques; D007248:Infertility, Male / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008970:Molecular Weight; D010795:Phthalic Acids / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D013737:Testis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013739:Testosterone / Q000097:blood; D019108:Tight Junctions / Q000187:drug effects*
chemical_list: D010795:Phthalic Acids; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013739:Testosterone; C032279:phthalic acid
keywords: Anti-androgenicity; Blood testes barrier; Mixture effects; Phthalates; Sertoli cell junctions