Testicular maldescent and maldevelopment in fetal rats prenatally exposed to nitrofen.
In the rat model of nitrofen-induced congenital diaphragmatic hernia, we found the testicles in a high abdominal position in many male animals, and undertook to investigate whether the teratogen interferes with testicular descent and development. Male fetuses from time-mated Wistar rats treated intragastrically with 100 mg nitrofen dissolved in oil on day 9.5 of gestation were compared with control fetuses from mothers receiving only vehicle. The litters were recovered by cesarean section on days 17, 19, and 21 of gestation; the position of the testicles in male animals was recorded, and their volume was measured prior to histological assessment of mean tubular diameter, number of germ cells per tubule, and degree of collagenization of the tunica albuginea. Testicular maldescent was present in 100% of nitrofen-exposed fetuses on the 17th gestational day, 77% of those recovered on day 19, and 41% of those near term (21st day), whereas all control animals but 1 had "descended" gonads on all three days. Testicular volume was significantly decreased in treated fetuses on the 21st gestational day, and the mean tubular diameter was significantly decreased in all three age groups. Experimental and control animals had similar numbers of germ cells per tubule. The albuginea layer had apparently normal collagen content in all groups. These findings suggest that prenatal exposure to nitrofen interferes with both transabdominal descent of the testicle (transinguinal descent is postnatal in the rodent) and its normal development. Previous evidence and the present results authorize speculation on the possible role of nitrofen-induced prenatal thyroid hypofunction in the pathogenesis of maldescent and maldevelopment in this model, since thyroid hormones act directly on Sertoli cells, which secrete müllerian inhibiting substance, which is likely responsible for transabdominal descent.
Department of Pediatric Surgery, Hospital "La Paz", Universidad Autónoma, P. de la Castellana 261, E-28046, Madrid, Spain.
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Qi
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Diez-Pardo
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Nistal
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Tovar