Gestational protein restriction delays prostate morphogenesis in male rats
Cristiane F. Pinho A , Mariana A. Ribeiro A , Jaqueline C. Rinaldi A , Sergio L. Felisbino B , Patricia F. Pinheiro C , Raquel F. Domeniconi C , Ricardo A. Fochi D , Patrícia A. Boer B and Wellerson R. Scarano B E
+ Author Affiliations
- Author Affiliations
A Graduate Program in Applied and General Biology, Institute of Biosciences, University Est. Paulista, UNESP, Botucatu, SP 18618-970, Brazil.
B Department of Morphology, Institute of Biosciences, University Est. Paulista, UNESP, Botucatu, SP 18618-970, Brazil.
C Department of Anatomy, Institute of Biosciences, University Est. Paulista, UNESP, Botucatu, SP 18618-970, Brazil.
D Graduate Program in Structural and Cell Biology, UNICAMP, Campinas, SP 13083-862, Brazil.
E Corresponding author. Email: scarano@ibb.unesp.br
Reproduction, Fertility and Development 26(7) 967-973 https://doi.org/10.1071/RD13132
Submitted: 3 May 2013 Accepted: 19 June 2013 Published: 7 August 2013
Abstract
Maternal malnutrition due to a low-protein diet is associated with functional disorders in adulthood, which may be related to embryonic development failures. The effects of gestational protein restriction on prostate morphogenesis in male offspring were investigated. Pregnant rat dams were divided into normoprotein (NP; fed a normal diet containing 17% protein) and hypoprotein (LP; fed a diet containing 6% protein) groups. On the day of birth (PND1), anogenital distance and bodyweight were measured in male pups. Seven males per experimental group (one male per litter) were killed, and the pelvic urethra was evaluated. LP offspring showed a significant reduction in bodyweight and anogenital distance on PND1. On three-dimensional reconstruction of the prostate, the number of prostatic buds was lower in LP than in NP males. Mesenchymal cells surrounding the buds were androgen-receptor positive, and the quantity and intensity of nucleus immunoreactivity was decreased in LP. The proliferation index was lower in LP than in NP prostatic buds. Immunoreactivity for α-actin in mesenchymal cells and that for epidermal growth factor receptor in epithelial cells was higher in NP than in LP. Our findings demonstrate that maternal protein restriction delays prostatic morphogenesis, probably because of considerable disruption in the epithelium–mesenchyme interaction.
Additional keywords: epithelium–mesenchyme interaction, fetal programming.
References
Barker, D. J. (2000). In utero programming of cardiovascular disease. Theriogenology 53, 555–574.| In utero programming of cardiovascular disease.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3c7pvFahtw%3D%3D&md5=658d5fc6dee30454484fdf22a5213e67CAS | 10735050PubMed |
Cónsole, G. M., Jurado, S. B., Oyhenart, E., Ferese, C., Pucciarelli, H., and Gómez Dumm, C. L. (2001). Morphometric and ultrastructural analysis of different pituitary cell populations in undernourished monkeys. Braz. J. Med. Biol. Res. 34, 65–74.
| Morphometric and ultrastructural analysis of different pituitary cell populations in undernourished monkeys.Crossref | GoogleScholarGoogle Scholar | 11151030PubMed |
Cooke, P. S., Young, P., and Cunha, G. R. (1991). Androgen receptor expression in developing male reproductive organs. Endocrinology 128, 2867–2873.
| Androgen receptor expression in developing male reproductive organs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3MXkt1amtr0%3D&md5=a0786943a206ab6779bdbc0378f46961CAS | 2036966PubMed |
Cunha, G. R., Alarid, E. T., Turner, T., Donjacour, A. A., Boutin, E. L., and Foster, B. A. (1992). Normal and abnormal development of the male urogenital tract: role of androgens, mesenchymal–epithelial interactions and growth factors. J. Androl. 13, 465–475.
| 1:STN:280:DyaK3s7os1CqtA%3D%3D&md5=18e19a9c8263d90bc12af6b717666e94CAS | 1293128PubMed |
Cunha, G. R., Foster, B., Thomson, A., Sugimura, Y., Tanji, N., Tsuji, M., Terada, N., Finch, P. W., and Donjacour, A. A. (1995). Growth factors as mediators of androgen action during the development of the male urogenital tract. World J. Urol. 13, 264–276.
| Growth factors as mediators of androgen action during the development of the male urogenital tract.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK287jt1SjsA%3D%3D&md5=fa9f0f1870fba086a0cc8b7039859addCAS | 8580997PubMed |
da Silva Faria, T., Da Fonte Ramos, C., and Sampaio, F. J. (2004). Puberty onset in the female offspring of rats submitted to protein or energy restricted diet during lactation. J. Nutr. Biochem. 15, 123–127.
| Puberty onset in the female offspring of rats submitted to protein or energy restricted diet during lactation.Crossref | GoogleScholarGoogle Scholar | 14972352PubMed |
Desai, M., Crowther, N. J., Lucas, A., and Hales, C. N. (1996). Organ-selective growth in the offspring of protein-restricted mothers. Br. J. Nutr. 76, 591–603.
| Organ-selective growth in the offspring of protein-restricted mothers.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28Xnt1Kiur0%3D&md5=1bf09a9c86620b3aa54845e85d49632aCAS | 8942365PubMed |
Fagundes, A. T., Moura, E. G., Passos, M. C. F., Oliveira, E., Toste, F. P., Bonomo, I. T., Trevenzoli, I. H., Garcia, R. M. G., and Lisboa, P. C. (2007). Maternal low-protein diet during lactation programmes body composition and glucose homeostasis in the adult rat offspring. Br. J. Nutr. 98, 922–928.
| Maternal low-protein diet during lactation programmes body composition and glucose homeostasis in the adult rat offspring.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtlSktLbL&md5=94753f402bf47bedfa43317db47e1f03CAS | 17524178PubMed |
Gardner, D. S., Ozanne, S. E., and Sinclair, K. D. (2009). Effect of the early-life nutritional environment on fecundity and fertility of mammals. Philos. Trans. R. Soc. Lond. B Biol. Sci. 364, 3419–3427.
| Effect of the early-life nutritional environment on fecundity and fertility of mammals.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD1MnpsFalsA%3D%3D&md5=2bba7a0dd6e11a486ae9ed0f7b5d0e4cCAS | 19833652PubMed |
Gosby, A. K., Stanton, L. M. L., Maloney, C. A., Thompson, M., Briody, J., Baxter, R. C., Bryson, J. M., Denyer, G. S., and Caterson, I. D. (2009). Postnatal nutrition alters body composition in adult offspring exposed to maternal protein restriction. Br. J. Nutr. 101, 1878–1884.
| Postnatal nutrition alters body composition in adult offspring exposed to maternal protein restriction.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXos1Cqsb8%3D&md5=69771979d68636b57dfa89cea1c1b610CAS | 19055852PubMed |
Graham, S., and Gandelman, R. (1986). The expression of anogenital distance data in the mouse. Physiol. Behav. 36, 103–104.
| The expression of anogenital distance data in the mouse.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL287kvFOrtg%3D%3D&md5=2e93f5acfdd3db0a44b98181c6363218CAS | 3952167PubMed |
Hayashi, N., Sugimura, Y., Kawamura, J., Donjacour, A. A., and Cunha, G. R. (1991). Morphological and functional heterogeneity in the rat prostatic gland. Biol. Reprod. 45, 308–321.
| Morphological and functional heterogeneity in the rat prostatic gland.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK387ltl2mug%3D%3D&md5=730095eae40657d1d7a5b272dfbf7125CAS | 1786296PubMed |
Lucas, A. (1998). Programming by early nutrition: an experimental approach. J. Nutr. 128, 401S–406S.
| 1:CAS:528:DyaK1cXpsVGiuw%3D%3D&md5=2a00fe8488d030019678c771d5749f8dCAS | 9478036PubMed |
Marker, P. C., Donjacour, A. A., Dahiya, R., and Cunha, G. R. (2003). Hormonal, cellular and molecular control of prostatic development. Dev. Biol. 253, 165–174.
| Hormonal, cellular and molecular control of prostatic development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXmt1Sruw%3D%3D&md5=b24578529b6159d1145f787e15fbcc5dCAS | 12645922PubMed |
McMillen, I. C., Maclaughlin, S. M., Muhlhausler, B. S., Gentili, S., Duffield, J. L., and Morrison, J. L. (2008). Developmental origins of adult health and disease: the role of periconceptional and foetal nutrition. Basic Clin. Pharmacol. Toxicol. 102, 82–89.
| Developmental origins of adult health and disease: the role of periconceptional and foetal nutrition.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhvF2gsrg%3D&md5=f50e3aac875dae4e681250b23817ee43CAS | 18226059PubMed |
Page, K. C., Sottas, C. M., and Hardy, M. P. (2001). Prenatal exposure to dexamethasone alters Leydig cell steroidogenic capacity in immature and adult rats. J. Androl. 22, 973–980.
| 1:CAS:528:DC%2BD3MXotlynsr4%3D&md5=515655961d9c63b29e1c9d699ce9d9fcCAS | 11700862PubMed |
Prins, G. S., and Birch, L. (1995). The developmental pattern of androgen receptor expression in rat prostate lobes is altered after neonatal exposure to oestrogen. Endocrinology 136, 1303–1314.
| The developmental pattern of androgen receptor expression in rat prostate lobes is altered after neonatal exposure to oestrogen.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXjvFCjtbo%3D&md5=a5cff2caf11c4d2da7209c5e2250ebddCAS | 7867585PubMed |
Prins, G. S., Cooke, P. S., Birch, L., Donjacour, A. A., Yalcinkaya, T. M., Siiteri, P. K., and Cunha, G. R. (1992). Androgen receptor expression and 5a-reductase activity along the proximal–distal axis of the rat prostatic duct. Endocrinology 130, 3066–3073.
| Androgen receptor expression and 5a-reductase activity along the proximal–distal axis of the rat prostatic duct.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38XisVyrsb0%3D&md5=0c046a8ba824f89b194a24d28899d94bCAS | 1572313PubMed |
Prins, G. S., Birch, L., Habermann, H., Chang, W. Y., Tebeau, C., Putz, O., and Bieberich, C. (2001). Influence of neonatal oestrogens on rat prostate development. Reprod. Fertil. Dev. 13, 241–252.
| Influence of neonatal oestrogens on rat prostate development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XlslE%3D&md5=8b00ac8a565f8f95fbc503674ed30e1eCAS | 11800163PubMed |
Puchtler, H., Waldrop, F. S., Meloan, S. N., Terry, M. S., and Conner, H. M. (1970). Methacarn (methanol-carnoy) fixation: practical and theoretical considerations. Histochemie 21, 97–116.
| Methacarn (methanol-carnoy) fixation: practical and theoretical considerations.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE3cXhtFygtbk%3D&md5=b3cfbadbd3073e1865d61e4a9b6eef9bCAS | 4907154PubMed |
Reeves, P. G., Nielsen, F. H., and Fahey, G. C. (1993). AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition Ad Hoc Writing Committee on the reformulation of the AIN-76 rodent diet. J. Nutr. 123, 1939–1951.
| 1:CAS:528:DyaK2cXltlegsw%3D%3D&md5=c16e1f984b11a244e77c7ded678489fbCAS | 8229312PubMed |
Rinaldi, J. C., Justulin, L. A., Lacorte, L. M., Sarobo, C., Boer, P. A., Scarano, W. R., and Felisbino, S. L. (2013). Implications of intrauterine protein malnutrition on prostate growth, maturation and aging. Life Sci. 92, 763–774.
| Implications of intrauterine protein malnutrition on prostate growth, maturation and aging.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXks1SisLw%3D&md5=82103e5b0c5edff28388f67d03b3857bCAS | 23439325PubMed |
Santos, F. C. A., Leite, R. P., Custódio, A. M. G., Carvalho, K. P., Monteiro-Leal, L. H., Santos, A. B., Goes, R. M., Carvalho, H. F., and Taboga, S. R. (2006). Testosterone stimulates growth and secretory activity of the female prostate in the adult gerbil (Meriones unguiculatus). Biol. Reprod. 75, 370–379.
| Testosterone stimulates growth and secretory activity of the female prostate in the adult gerbil (Meriones unguiculatus).Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XovVWmtbg%3D&md5=4a3ffe82fc1af9d0fc3dac3f6070688eCAS |
Scarano, W. R., Toledo, F. C., Guerra, M. T., Campos, S. G. P., Justulin, L. A., Felisbino, S. L., Anselmo-Franci, J. A., Taboga, S. R., and Kempinas, W. G. (2009). Long-term effects of developmental exposure to di-n-butyl-phthalate (DBP) on rat prostate: proliferative and inflammatory disorders and a possible role of androgens. Toxicology 262, 215–223.
| Long-term effects of developmental exposure to di-n-butyl-phthalate (DBP) on rat prostate: proliferative and inflammatory disorders and a possible role of androgens.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXptlSqsLk%3D&md5=c41f18cd2575a395eea7c6ff2b762d48CAS | 19549552PubMed |
Sugimura, Y., Cunha, G. R., and Donjacour, A. A. (1986). Morphogenesis of ductal networks in the mouse prostate. Biol. Reprod. 34, 961–971.
| Morphogenesis of ductal networks in the mouse prostate.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL283ntVansw%3D%3D&md5=9a087401cd88e85b4297a0b41b31534cCAS | 3730488PubMed |
Swan, S. H., Main, K. M., Liu, F., Stewart, S. L., Kruse, R. L., Calafat, A. M., Mao, C. S., Redmon, J. B., Ternand, C. L., Sullivan, S., and Teague, J. L. (2005). Decrease in ano-genital distance among male infants with prenatal phthalate exposure. Environ. Health Perspect. 113, 1056–1061.
| Decrease in ano-genital distance among male infants with prenatal phthalate exposure.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXpslSku74%3D&md5=13522c9d640e29676af21c76351ea07dCAS | 16079079PubMed |
Thomson, A. A. (2001). Role of androgens and fibroblast growth factors in prostatic development. Reproduction 121, 187–195.
| Role of androgens and fibroblast growth factors in prostatic development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXhslSisLs%3D&md5=02b833984e8dd8335bf53f817e9bfaf4CAS | 11226043PubMed |
Thomson, A. A., and Cunha, G. R. (1999). Prostatic growth and development are regulated by FGF10. Development 126, 3693–3701.
| 1:CAS:528:DyaK1MXlvFSjsr8%3D&md5=e73637f09ad5bcac81fb3b4ff8e2daa9CAS | 10409514PubMed |
Timms, B. G. (2008). Prostate development: a historical perspective. Differentiation 76, 565–577.
| Prostate development: a historical perspective.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtVSrsLbK&md5=70763571f770eb6b47e0671c4c3d3b4aCAS | 18462432PubMed |
Timms, B. G., Mohs, T. J., and Didio, L. J. (1994). Ductal budding and branching patterns in the developing prostate. J. Urol. 151, 1427–1432.
| 1:STN:280:DyaK2c3htVKltQ%3D%3D&md5=fe4eff3206af2138f01ac31d020e578dCAS | 8158800PubMed |
Vilamaior, P. S. L., Taboga, S. R., and Carvalho, H. F. (2006). Postnatal growth of the ventral prostate in Wistar rats: a stereological and morphometrical study. Anat. Rec. A Discov. Mol. Cell. Evol. Biol. 288A, 885–892.
| Postnatal growth of the ventral prostate in Wistar rats: a stereological and morphometrical study.Crossref | GoogleScholarGoogle Scholar |
Wang, Y., Hayward, S., Cao, M., Thayer, K., and Cunha, G. R. (2001). Cell differentiation lineage in the prostate. Differentiation 68, 270–279.
| Cell differentiation lineage in the prostate.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD38%2Fks1KqsQ%3D%3D&md5=540457fa3f35f435a9d51f8003fcd4a2CAS | 11776479PubMed |
Woodham, C., Birch, L., and Prins, G. S. (2003). Neonatal oestrogen down-regulates prostatic androgen receptor through a proteosome-mediated protein degradation pathway. Endocrinology 144, 4841–4850.
| Neonatal oestrogen down-regulates prostatic androgen receptor through a proteosome-mediated protein degradation pathway.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXoslertb0%3D&md5=ca9f9a855432d7db92d6466462914825CAS | 12960060PubMed |
Zambrano, E., Rodrigez-González, G. L., Guzmán, C., García-Becerra, R., Boeck, L., Díaz, L., Menjivar, M., Larrea, F., and Nathanielsz, P. W. (2005). A maternal low-protein diet during pregnancy and lactation in the rat impairs male reproductive development. J. Physiol. 563, 275–284.
| A maternal low-protein diet during pregnancy and lactation in the rat impairs male reproductive development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXitVSnuro%3D&md5=49bf3b6c639552aa63a7a030624b6b4fCAS | 15611025PubMed |
