Human fetal testis Leydig cell disruption by exposure to the pesticide dieldrin at low concentrations.
BACKGROUND
Declining human reproductive health over the last 60 years has been proposed to be due to effects of environmental chemicals, especially endocrine disrupting compounds, on fetal development. We investigated whether a model pesticide, dieldrin, at concentrations within both maternal circulation and environmental ranges (1 pmol/l = 0.0004 p.p.b. = 380.9 pg/l), could disrupt the human fetal testis.


METHODS
Human fetal testes were collected during the second trimester, a critical period of male sexual differentiation (development and masculinization). Testis explants were cultured for 24 h in the presence and absence of LH (10-1000 IU LH/l) and dieldrin (1 pmol and 1 nmol/l). Endocrine, immunohistological and proteome characteristics of the tissues were investigated.


RESULTS
Exposure to dieldrin reduced LH-induced testosterone secretion (P < 0.05) and tissue protein concentrations of LH receptor and steroid acute regulatory protein (P < 0.05). Dieldrin altered proteins associated with cancer, apoptosis, transcription and development. Wnt-2b was reduced 3-fold and immunolocalized to Leydig and Sertoli cells. Dieldrin also reversed some LH-induced changes in protein expression, supporting the conclusion that Leydig cell function is at risk from environmental chemicals.


CONCLUSIONS
Our findings indicate that exposure to very low, biologically relevant, concentrations of environmental chemicals could affect the fetal human Leydig cell, reducing testosterone secretion and potentially leading to subtle dysregulation of reproductive development and adult fecundity.
Fowler
Paul A
PA
Department of Obstetrics and Gynaecology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK. p.a.fowler@abdn.ac.uk
Abramovich
David R
DR
Haites
Neva E
NE
Cash
Phillip
P
Groome
Nigel P
NP
Al-Qahtani
Ahmed
A
Murray
Tessa J
TJ
Lea
Richard G
RG
D002478:Cells, Cultured; D004026:Dieldrin / Q000633:toxicity*; D005260:Female; D006062:Gonadotropins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007985:Leydig Cells / Q000166:cytology* / Q000187:drug effects*; D008297:Male; D010575:Pesticides / Q000633:toxicity*; D010750:Phosphoproteins / Q000096:biosynthesis; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D020543:Proteome; D013737:Testis / Q000187:drug effects* / Q000196:embryology*; D013739:Testosterone / Q000096:biosynthesis; D000098682:Steroidogenic Acute Regulatory Protein
D006062:Gonadotropins; D010575:Pesticides; D010750:Phosphoproteins; D020543:Proteome; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D004026:Dieldrin