Proposed mode of action for in utero effects of some phthalate esters on the developing male reproductive tract

David, RM

HERO ID

673617

Reference Type

Journal Article

Subtype

Review

Year

2006

Language

English

PMID

16698716

HERO ID 673617
Material Type Review
In Press No
Year 2006
Title Proposed mode of action for in utero effects of some phthalate esters on the developing male reproductive tract
Authors David, RM
Journal Toxicologic Pathology
Volume 34
Issue 3
Page Numbers 209-219
Abstract Phthalate esters containing a straight-chain backbone of 4-6 carbons have demonstrated testicular toxicity and infertility in adult and pre-adolescent rats, mice, hamsters, and ferrets. In recent years, these same phthalates have been shown to interfere with the normal development of the male reproductive tract in rodents and rabbits. The review presented here summarizes studies that provide evidence of a mode of action for these effects. The data indicate that C4-C6 phthalate esters inhibit processes in the Leydig cell, such as the synthesis of testosterone (T) and production of insulin-like factor 3 (insl3), both of which are required for normal development of male genitalia. A proposed secondary effect of reduced androgen production is on Sertoli cells, resulting in failure to proliferate and interference with cell-cell communication (gap-junction intracellular communication) leading to the development of large multinucleate gonocytes. The possibility that phthalates act directly on the Sertoli cells to interfere with intracellular communication is not excluded. The strength, consistency, and plausibility of the proposed mode of action and alternate modes of action are discussed.
Doi 10.1080/01926230600642625
Pmid 16698716
Wosid WOS:000237512800001
Is Certified Translation No
Dupe Override No
Comments Source: Web of Science WOS:000237512800001
Is Public Yes
Language Text English
Keyword Animals; Esters/toxicity; Female; Genitalia, Male/*drug effects/pathology; Humans; Leydig Cells/drug effects/metabolism; Male; *Maternal Exposure; Phthalic Acids/metabolism/*toxicity; Pregnancy; Sertoli Cells/drug effects/metabolism; Testosterone/metabolism; 0 (Esters); 0 (Phthalic Acids); 58-22-0 (Testosterone); 88-99-3 (phthalic acid)