Abstract
Environmental factors are implicated in increased incidence of human testicular germ-cell cancer (TGCC). TGCC has foetal origins and may be one component of a testicular dysgenesis syndrome (TDS). Certain phthalates induce TDS in rats, including effects on foetal germ cells (GC). As humans are widely exposed to phthalates, study of the effects of phthalates on foetal rat GC could provide an insight into the vulnerability of foetal GC to disruption by environmental factors, and thus to origins of TGCC. This study has therefore characterized foetal GC development in rats after in utero exposure to di(n-butyl) phthalate (DBP) with emphasis on GC numbers/proliferation, differentiation and time course for inducing effects. Pregnant rats were treated orally from embryonic day 13.5 (e13.5) with 500 mg/kg/day DBP for varying periods. GC number, proliferation, apoptosis, differentiation (loss of OCT4, DMRT1 expression, DMRT1 re-expression, GC migration) and aggregation were evaluated at various foetal and postnatal ages. DBP exposure reduced foetal GC number by ∼60% by e15.5 and prolonged GC proliferation, OCT4 and DMRT1 immunoexpression; these effects were induced in the period immediately after testis differentiation (e13.5–e15.5). In contrast, DBP-induced GC aggregation stemmed from late gestation effects (beyond e19.5). Foetal DBP exposure delayed postnatal resumption of GC proliferation, leading to bigger deficits in numbers, and delayed re-expression of DMRT1 and radial GC migration. Therefore, DBP differentially affects foetal GC in rats according to stage of gestation, effects that may be relevant to the human because of their nature (OCT4, DMRT1 effects) or because similar effects are demonstrable in vitro on human foetal testes (GC number). Identification of the mechanisms underlying these effects could give a new insight into environment-sensitive mechanisms in early foetal GC development that could potentially be relevant to TGCC origins.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
