title: Molecular feminization of mouse seminal vesicle by prenatal exposure to diethylstilbestrol: altered expression of messenger RNA.
abstract: Exposure to estrogens during critical stages of development has been reported to cause irreversible changes in estrogen target tissues such as the reproductive tract. In fact, recent studies using mice describe prenatal estrogen exposure resulting in the expression of the major estrogen-inducible uterine secretory protein, lactoferrin (LF), by the seminal vesicles of the male offspring. Thus, we have studied the role of estrogens in abnormal and normal gene expression in the developing male reproductive tract using LF and seminal vesicle secretory protein IV (SVS IV), an androgen-regulated murine seminal vesicle secretory protein, as markers. Lactoferrin and SVS IV protein and mRNA expression were studied in histological samples by using the techniques of in situ hybridization (ISH) and immunohistochemistry (IHC). Seminal vesicle secretory protein IV was expressed in all (100%) epithelial cells of the control seminal vesicle, but this protein was decreased by castration. However, LF expression was undetectable by ISH or IHC in control seminal vesicle epithelium. Lactoferrin was inducible in 2% of the seminal vesicle epithelial cells from adult castrated mice treated with estradiol 17 beta (E2; 20 micrograms/kg/day for 3 days), indicating that a small percentage of the seminal vesicle cells could be induced to secrete LF after modification of the endocrine environment. Prenatal DES treatment (100 micrograms./kg. maternal body weight on days 9 through 16 of gestation) resulted in the male offspring exhibiting constitutive expression of LF in 5% of the seminal vesicle epithelial cells, while expression of the androgen-regulated protein SVS IV was slightly decreased. The maximal contrast between LF and SVS IV expression was observed in prenatally DES-treated mice that were subsequently castrated as adults and further treated with E2; LF was detected in 40% of the epithelial cells in these mice. Double immunostaining techniques revealed that epithelial cells which were making LF had ceased production of SVS IV. Since a large percentage of the epithelial cells in the intact prenatal DES exposed male was capable of expressing the normal gene product, SVS IV, it was concluded that DES treatment during prenatal development appears to imprint or induce estrogenic sensitivity in the adult seminal vesicle, causing increased production of LF. The results suggest that this altered protein response may be an example of atypical gene expression in male reproductive tract tissues following hormonal manipulation early in development.
authors.affiliation: Developmental Endocrinology and Pharmacology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
authors.forename: W C
authors.initials: WC
authors.lastname: Beckman
authors.forename: R R
authors.initials: RR
authors.lastname: Newbold
authors.forename: C T
authors.initials: CT
authors.lastname: Teng
authors.forename: J A
authors.initials: JA
authors.lastname: McLachlan
mesh_terms: D000818:Animals; D004054:Diethylstilbestrol / Q000633:toxicity*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007781:Lactoferrin / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009919:Orchiectomy; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D029584:Prostatic Secretory Proteins; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D029589:Seminal Plasma Proteins; D012669:Seminal Vesicles / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D029584:Prostatic Secretory Proteins; D011506:Proteins; D012333:RNA, Messenger; D029589:Seminal Plasma Proteins; C043076:beta-microseminoprotein; D004958:Estradiol; D004054:Diethylstilbestrol; D007781:Lactoferrin