Long-term effects of intrauterine exposure to mono-n-butyl phthalate on the reproductive function of postnatal rats.
OBJECTIVE
Although it is well known that phthalate esters induce testicular dysfunction in both adult and immature rats, there have been few reports on the long-term effect of phthalate esters on the testicular function of male rats exposed to phthalate esters in utero. This study was designed to assess the long-term effects of the mono-n-butyl phthalate (MBP) ester on the testicular function of neonatal and adult rat offspring from pregnant dams exposed to phthalate esters during gestation.


METHODS
Pregnant rats were administered MBP [0.5 g/(kg body weight/.d); 4 days] by gavage from the 15th to the 18th gestational day. Rats administered solvent only were used as control subjects. After the rats' puberty, using male pups whose testes descended normally, the authors examined their fertility while also measuring their testicular weights, mean seminiferous tubular diameter, and the developmental grade of the germ cells (Johnsen score) in their testes. Next, in neonatal rats, the authors measured the testicular concentration of the Mullerian inhibiting substance (MIS) protein using enzyme-linked immunoassay and the expression level of the MIS messenger RNA using the quantitative polymerase chain reaction method as a marker of the Sertoli cells' function. Next the concentration of testosterone protein using a radioimmunoassay as a marker of the Leydig cells' function was measured.


RESULTS
The pregnancy rate of the female rats coupled with MBP-treated male rats decreased significantly in comparison with that of the female rats coupled with control male rats (P < .01). Both the testicular weight and the Johnsen score in the MBP-treated group were decreased significantly more than those of the control group (P < .05). Neither the concentration of the MIS protein nor the expression level of the MIS messenger RNA in the MBP-treated neonatal testes differed from those of the control testes, whereas the concentration of testosterone protein in the neonate testes decreased significantly in the MBP-treated group in comparison with that of the control group (P < .01).


CONCLUSIONS
A prenatal short-time exposure to MBP induces a long-term effect on postnatal rats and impairs reproductive function in male offspring probably by inhibiting the Leydig cells' rather than Sertoli cells' function in the fetal period.
Kai
Hiroki
H
Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Shono
Takeshi
T
Tajiri
Tatsuro
T
Suita
Sachiyo
S
D000818:Animals; D054304:Anti-Mullerian Hormone; D005260:Female; D006023:Glycoproteins / Q000032:analysis / Q000096:biosynthesis; D007150:Immunohistochemistry; D007248:Infertility, Male / Q000139:chemically induced*; D007985:Leydig Cells / Q000187:drug effects; D008297:Male; D010795:Phthalic Acids / Q000633:toxicity*; D010968:Plasticizers / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D012708:Sertoli Cells / Q000187:drug effects; D013735:Testicular Hormones / Q000032:analysis / Q000096:biosynthesis; D013737:Testis / Q000737:chemistry / Q000187:drug effects* / Q000503:physiopathology; D013739:Testosterone / Q000032:analysis
D006023:Glycoproteins; D010795:Phthalic Acids; D010968:Plasticizers; D012333:RNA, Messenger; D013735:Testicular Hormones; D013739:Testosterone; D054304:Anti-Mullerian Hormone; C028577:monobutyl phthalate