Submitted July 4, 2007
Returned for revision August 7, 2007
Accepted September 28, 2007
Testis
Sertoli Cell Development and Function in an Animal Model of Testicular Dysgenesis Syndrome in the Rat
Gary R. Hutchison ,
Hayley M. Scott ,
Marion Walker ,
Chris McKinnell ,
Diana Ferrara ,
I. Kim Mahood ,
and
Richard M. Sharpe *
* To whom correspondence should be addressed. E-mail: r.sharpe{at}hrsu.mrc.ac.uk.
Abstract
Pregnancy exposure to di(n-butyl) phthalate (DBP) in rats induces a testicular dysgenesis-like syndrome (TDS) in male offspring. Earlier studies suggested altered Sertoli cell (SC) development/maturation may result, especially in testes that become cryptorchid. This study quantitatively assessed SC numerical and functional development in DBP-exposed rats, and compared (unilaterally) cryptorchid and scrotal testes. Pregnant rats were gavaged with 500mg/kg/day DBP or corn oil from E13.5-21.5. Male offspring were sampled on E21.5 or postnatal day 6, 10, 15, 25 or 90. SC number in DBP-exposed males was reduced by ~50% at E21.5 but recovered to normal by days 25-90, accompanied by significant changes in plasma Inhibin B and testosterone levels. SC maturational development in DBP-exposed males, assessed using 5 protein markers (anti-mullerian hormone, cytokeratin, androgen receptor, CDKN1B and Nestin), was largely normal with some evidence of delayed maturation. However, in adulthood, SC in areas lacking germ cells (SCO tubules) often exhibited immature features, especially in cryptorchid testes. SC in DBP-exposed animals supported fewer germ cells during puberty, but this normalised in scrotal testes by adulthood. Scrotal, and especially cryptorchid, testes from DBP-exposed animals exhibited abnormalities (SCO tubules, focal dysgenetic areas) at all postnatal ages. Cryptorchid testes from DBP-exposed animals exhibited more SC abnormalities at day 25 compared with scrotal testes, perhaps indicating more severe underlying SC malfunction in these testes. Our findings support the concept of altered SC development in TDS, especially in cryptorchid testes, but show that maturational defects in SC in adulthood most commonly reflect secondary dedifferentiation in absence of germ cells.
Key words:
Rat •
Sertoli cell number •
Testis development •
di(n-butyl) phthalate (DBP) •
testicular dysgenesis syndrome (TDS)
