Effects of mono-(2-ethylhexyl) phthalate on fetal and neonatal rat testis organ cultures

Hui Li; Kwan Hee Kim

doi:10.1095/biolreprod.103.018895

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Effects of mono-(2-ethylhexyl) phthalate on fetal and neonatal rat testis organ cultures

Journal article

Open access

Peer reviewed

Effects of mono-(2-ethylhexyl) phthalate on fetal and neonatal rat testis organ cultures

Hui Li and Kwan Hee Kim

Biology of reproduction, Vol.69(6), pp.1964-1972

12/2003

DOI: https://doi.org/10.1095/biolreprod.103.018895

Handle:

https://hdl.handle.net/2376/115771

PMID: 12904314

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Abstract

Organ Culture Techniques - methods

RNA Helicases - metabolism

Apoptosis - drug effects

Glycoproteins - metabolism

Male

Glycoproteins - drug effects

Sertoli Cells - pathology

Sertoli Cells - drug effects

Testis - drug effects

Transcription Factors - drug effects

DNA-Binding Proteins - metabolism

Dose-Response Relationship, Drug

RNA Helicases - drug effects

Testis - embryology

Testicular Hormones - metabolism

Anti-Mullerian Hormone

Diethylhexyl Phthalate - toxicity

Diethylhexyl Phthalate - analogs & derivatives

Female

Animals, Newborn

Sertoli Cells - metabolism

DEAD-box RNA Helicases

GATA4 Transcription Factor

Testis - cytology

DNA-Binding Proteins - drug effects

Rats

Testis - growth & development

Rats, Sprague-Dawley

Cell Division - drug effects

Transcription Factors - metabolism

Animals

Di-(2-ethylhexyl) phthalate (DEHP) and its active metabolite, mono-(2-ethylhexyl) phthalate (MEHP), have been shown to cause reproductive toxicity in both developing and adult animals. In this study, we used organ cultures of fetal and neonatal rat testes to assess the in vitro effect of MEHP on seminiferous cord formation in Embryonic Day 13 (E13) testes and on the development of E18 and Postnatal Day 3 (P3) testes. Interestingly, MEHP had no effect on cord formation in the organ cultures of E13 testes, indicating that it has no effect on sexual differentiation of the indifferent gonad to testis. Consistently, the expression of a Sertoli cell-specific protein, mullerian inhibiting substance (MIS), or the number of gonocytes did not change in E13 testes after MEHP treatment. In contrast, MEHP decreased the levels of MIS and GATA-4 proteins in Sertoli cells and impaired Sertoli cell proliferation in the organ cultures of E18 and P3 testes. These results suggest that MEHP negatively influences proliferation and differentiation of Sertoli cells in both fetal and neonatal testes. In addition, MEHP treatment did not alter the number of gonocytes in E18 testes, whereas the number of gonocytes in P3 testes decreased in a dose-dependent manner, apparently due to enhanced apoptosis. These results suggest that MEHP adversely affects the gonocytes, which are mitotically active and undergoing migration and differentiation in neonatal testes, but it has no effect on fetal gonocytes that are mitotically quiescent.

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Title: Effects of mono-(2-ethylhexyl) phthalate on fetal and neonatal rat testis organ cultures
Creators: Hui Li - School of Molecular Biosciences, Center for Reproductive Biology, Washington State University, Pullman, Washington 99164, USA
Kwan Hee Kim
Publication Details: Biology of reproduction, Vol.69(6), pp.1964-1972
Publisher: United States
Grant note: ES09978 / NIEHS NIH HHS
Identifiers: 99900548073201842
Language: English
Resource Type: Journal article