scholarly journals Abnormal Leydig Cell Aggregation in the Fetal Testis of Rats Exposed to Di (n-Butyl) Phthalate and Its Possible Role in Testicular Dysgenesis

Endocrinology ◽  
2005 ◽  
Vol 146 (2) ◽  
pp. 613-623 ◽  
Author(s):  
I. Kim Mahood ◽  
Nina Hallmark ◽  
Chris McKinnell ◽  
Marion Walker ◽  
Jane S. Fisher ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Cell Aggregation ◽  
Fetal Testis ◽  
Testicular Dysgenesis ◽  
Butyl Phthalate

scholarly journals Reconstitution of rat fetal testis during the masculinisation programming window induces focal dysgenesis consistent with testicular dysgenesis syndrome

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ellie Smart ◽  
Joni Macdonald ◽  
Lee B. Smith ◽  
Rod T. Mitchell
Keyword(s):  
Testicular Dysgenesis Syndrome ◽  
Fetal Testis ◽  
Specific Effects ◽  
Fetal Rat ◽  
Testicular Dysgenesis ◽  
Seminal Vesicle Weight ◽  
Consistent Feature ◽  
Butyl Phthalate ◽  
Testis Tissue

Abstract Focal dysgenesis is a consistent feature of testicular dysgenesis syndrome (TDS) in humans. Rodent studies show that perturbation of androgens (e.g. following phthalate exposure) during a fetal masculinisation programming window (MPW) predisposes to a TDS phenotype. This study aimed to determine whether dissociation and reconstitution of rat fetal testis tissue during the MPW can be used to model and manipulate seminiferous cord development, including induction of focal dysgenesis, as described in TDS. Dissociated fetal rat testes were xenotransplanted subcutaneously into recipient mice for 4 weeks. Transplanted mice were treated with vehicle or di-n-butyl-phthalate (DBP, a plasticising chemical known to induce testicular dysgenesis in vivo in rats). Testosterone production by the transplants was measured in recipient mice and immunofluorescence was performed on the retrieved transplants to identify features consistent with focal testicular dysgenesis. Re-aggregation of rat fetal testis tissue xenotransplants during the MPW results in reconstitution of seminiferous cords. Features of focal testicular dysgenesis were present in re-aggregated testis, including ectopic Sertoli cells and intratubular Leydig cells (ITLCs). DBP exposure of recipient mice reduced androgen-dependent seminal vesicle weight (8.3 vs 26.7 mg; p < 0.05), but did not enhance features of focal dysgenesis including number of ITLCs (0.07 vs 0.10 cells/mm2; p > 0.05). We conclude that seminiferous cord reformation during the MPW results in development of focal dysgenesis. The system may be used to separate specific effects (e.g. androgen suppression) of individual chemical exposures from other mechanisms that may be conserved in TDS.

scholarly journals Novel molecular targets associated with testicular dysgenesis induced by gestational exposure to diethylhexyl phthalate in the rat: a role for estradiol

Reproduction ◽  
2012 ◽  
Vol 144 (6) ◽  
pp. 747-761 ◽  
Author(s):  
Gary R Klinefelter ◽  
John W Laskey ◽  
Witold M Winnik ◽  
Juan D Suarez ◽  
Naomi L Roberts ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Semen Quality ◽  
Testicular Dysgenesis Syndrome ◽  
Pathway Network ◽  
Diethylhexyl Phthalate ◽  
Fetal Testis ◽  
Testosterone Production ◽  
Testicular Dysgenesis ◽  
Significant Research ◽  
Dehp Exposure

Significant research has been focused on phthalate-induced alterations in male reproductive development. Studies on rodents have prompted the notion that a syndrome exists in the human male which includes phenotypic alterations such as hypospadias, cryptorchidism, poor semen quality, and even testicular cancer. Each phenotype in this ‘testicular dysgenesis syndrome’ is predicated on reduction in testosterone production by the fetal Leydig cell. We sought to examine the relationship between dysgenesis and steroidogenic capacity in the fetal rat testis more stringently by incorporating lower exposures than those typically used, conducting a comprehensive, non-targeted quantitative evaluation of the fetal testis proteome, and relating alterations in individual proteins to the capacity of the fetal Leydig cell to produce testosterone, and histopathology of the fetal testis. Pregnant dams were dosed orally from gestation day (GD) 13–19 with 0, 10, or 100 mg diethylhexyl phthalate (DEHP)/kg body weight per day. Each endpoint was represented by 16 l. Clustering of Leydig cells occurred before any significant decrease in the capacity of the GD19 Leydig cell to produce testosterone. At 100 mg DEHP/kg, testosterone production was reduced significantly, Leydig cell clusters became quite large, and additional dysgenetic changes were observed in the fetal testis. Of 23 proteins whose expression was altered significantly at both DEHP exposure levels, seven were found to be correlated with and predictive of the quantified endpoints. None of these proteins have been previously implicated with DEHP exposure. Notably, pathway analysis revealed that these seven proteins fit a pathway network in which each is regulated directly or indirectly by estradiol.

scholarly journals Cellular origins of testicular dysgenesis in rats exposed in utero to di(n-butyl) phthalate

2006 ◽  
Vol 29 (1) ◽  
pp. 148-154 ◽  
Author(s):  
I. KIM MAHOOD ◽  
CHRIS MCKINNELL ◽  
MARION WALKER ◽  
NINA HALLMARK ◽  
HAYLEY SCOTT ◽  
...  
Keyword(s):  
In Utero ◽  
Testicular Dysgenesis ◽  
Butyl Phthalate

scholarly journals Do Phthalates Affect Steroidogenesis by the Human Fetal Testis? Exposure of Human Fetal Testis Xenografts to Di-n-Butyl Phthalate

2012 ◽  
Vol 97 (3) ◽  
pp. E341-E348 ◽  
Author(s):  
R. T. Mitchell ◽  
A. J. Childs ◽  
R. A. Anderson ◽  
S. van den Driesche ◽  
P. T. K. Saunders ◽  
...  
Keyword(s):  
Fetal Testis ◽  
Butyl Phthalate

In utero exposure to diisononyl phthalate caused testicular dysgenesis of rat fetal testis

2015 ◽  
Vol 232 (2) ◽  
pp. 466-474 ◽  
Author(s):  
Linxi Li ◽  
Tiao Bu ◽  
Huina Su ◽  
Zhichuan Chen ◽  
Yuyuan Liang ◽  
...  
Keyword(s):  
In Utero ◽  
In Utero Exposure ◽  
Fetal Testis ◽  
Testicular Dysgenesis ◽  
Diisononyl Phthalate

scholarly journals Comparative Effects of Di( n -Butyl) Phthalate Exposure on Fetal Germ Cell Development in the Rat and in Human Fetal Testis Xenografts

2015 ◽  
Vol 123 (3) ◽  
pp. 223-230 ◽  
Author(s):  
Sander van den Driesche ◽  
Chris McKinnell ◽  
Ana Calarrão ◽  
Laura Kennedy ◽  
Gary R. Hutchison ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Development ◽  
Germ Cell Development ◽  
Fetal Testis ◽  
Phthalate Exposure ◽  
Butyl Phthalate ◽  
Fetal Germ Cell

scholarly journals Effects of environmental Bisphenol A exposures on germ cell development and Leydig cell function in the human fetal testis

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0191934 ◽  
Author(s):  
Soria Eladak ◽  
Delphine Moison ◽  
Marie-Justine Guerquin ◽  
Gabriele Matilionyte ◽  
Karen Kilcoyne ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Germ Cell ◽  
Leydig Cell ◽  
Cell Function ◽  
Cell Development ◽  
Germ Cell Development ◽  
Fetal Testis ◽  
Leydig Cell Function

scholarly journals Effects ofin UteroExposure to Di(n-butyl) Phthalate for Estrogen Receptors α, β, and Androgen Receptor of Leydig Cell on Rats

2013 ◽  
Vol 42 (5) ◽  
pp. 877-887 ◽  
Author(s):  
Shin Wakui ◽  
Masaru Shirai ◽  
Masaya Motohashi ◽  
Tomoko Mutou ◽  
Noriko Oyama ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Estrogen Receptors ◽  
Leydig Cell ◽  
Butyl Phthalate

scholarly journals Differential Response to Abiraterone Acetate and Di-n-butyl Phthalate in an Androgen-Sensitive Human Fetal Testis Xenograft Bioassay

2013 ◽  
Vol 138 (1) ◽  
pp. 148-160 ◽  
Author(s):  
Daniel J. Spade ◽  
Susan J. Hall ◽  
Camelia M. Saffarini ◽  
Susan M. Huse ◽  
Elizabeth V. McDonnell ◽  
...  
Keyword(s):  
Differential Response ◽  
Abiraterone Acetate ◽  
Fetal Testis ◽  
Butyl Phthalate
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