Developmental exposure to Passiflora incarnata induces behavioural alterations in the male progeny
André D. Bacchi A , Bianca Ponte A , Milene L. Vieira A , Jaqueline C. C. de Paula A , Suzana F. P. Mesquita B , Daniela C. C. Gerardin A and Estefânia G. Moreira A CA Department of Physiological Sciences, State University of Londrina, 86051-980, Londrina, Paraná, Brazil.
B Department of Biology, State University of Londrina, 86051-980, Londrina, Paraná, Brazil.
C Corresponding author. Email: egmoreira@uel.br
Reproduction, Fertility and Development 25(5) 782-789 https://doi.org/10.1071/RD11307
Submitted: 12 December 2011 Accepted: 25 June 2012 Published: 8 August 2012
Abstract
Passiflora incarnata is marketed in many countries as a phytomedicine and is prescribed mainly as a sedative and anxiolytic. Even though the directions of most marketed phytomedicines recommend them to be used under medical supervision, reproductive and developmental studies are sparse and not mandatory for regulatory purposes. To evaluate the reproductive and developmental toxicity of P. incarnata, Wistar female rats were gavaged with 30 or 300 mg kg–1 of this herb from gestational Day (GD) 0 to postnatal Day (PND) 21. P. incarnata treatment did not influence dams’ bodyweight or food intake or their reproductive performance (post-implantation loss, litter size, litter weight). There was also no influence on the physical development of pups (bodyweight gain, day of vaginal opening or preputial separation) or their behaviour in the open-field at PND 22, 35 and 75. Sexual behaviour was disrupted in adult male pups exposed to 300 mg kg–1 of P. incarnata; in this group, only 3 out of 11 pups were sexually competent. This behavioural disruption was not accompanied by alterations in plasma testosterone levels, reproductive-related organs and glands weights or sperm count. It is hypothesised that aromatase inhibition may be involved in the observed effect.
Additional keywords: developmental toxicity, lactation, open-field, pregnancy, reproductive toxicity, sexual behaviour.
References
Agmo, A. (1997). Male rat sexual behavior. Brain Res. 1, 203–209.| 1:STN:280:DyaK1c%2FktVagsQ%3D%3D&md5=e5ad6c0384d1032efce35b10132a8f1aCAS |
Agmo, A. (2003). Lack of opioid or dopaminergic effects on unconditioned sexual incentive motivation in male rats. Behav. Neurosci. 117, 55–68.
| Lack of opioid or dopaminergic effects on unconditioned sexual incentive motivation in male rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXjtl2mur4%3D&md5=af5da4bd65aee885f6384f1dd298203eCAS | 12619908PubMed |
Aste, N., Honda, S., and Harada, N. (2003). Forebrain Fos responses to reproductively related chemosensory cues in aromatase knockout mice. Brain Res. Bull. 60, 191–200.
| Forebrain Fos responses to reproductively related chemosensory cues in aromatase knockout mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXjs1CqtL8%3D&md5=55d20d0531b70f1fe55572badfd45ee7CAS | 12754080PubMed |
Attila, M., Oksala, R., and Agmo, A. (2010). Sexual incentive motivation in male rats requires both androgens and oestrogens. Horm. Behav. 58, 341–351.
| Sexual incentive motivation in male rats requires both androgens and oestrogens.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXmslSgtbo%3D&md5=c153bf7cb2ca21bd944d5d344099708cCAS | 19769979PubMed |
Bakker, J., Brand, T., Van Ophemert, J., and Slob, A. K. (1993). Hormonal regulation of adult partner preference behavior in neonatally ATD-treated male rats. Behav. Neurosci. 107, 480–487.
| Hormonal regulation of adult partner preference behavior in neonatally ATD-treated male rats.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3szhvFKksw%3D%3D&md5=774a974f741364a22147054974a1260dCAS | 8329137PubMed |
Bakker, J., Van Ophemert, J., and Slob, A. K. (1996). Sexual differentiation of odour and partner preference in rat. Physiol. Behav. 60, 489–494.
| Sexual differentiation of odour and partner preference in rat.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XkvFSiu7g%3D&md5=470c74ac2df51e86fab85fa6bb94c340CAS | 8840910PubMed |
Barros, D., Amaral, O., Izquierdo, I., Geracitano, L., Raseira, M. C. B., Henriques, A. T., and Ramirez, M. R. (2006). Behavioural and genoprotective effects of Vaccinium berries intake in mice. Pharmacol. Biochem. Behav. 84, 229–234.
| Behavioural and genoprotective effects of Vaccinium berries intake in mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xns1GltLo%3D&md5=d006a301d0594cc55607f8962fa015a6CAS | 16797063PubMed |
Baum, M. J., Carroll, R. S., and Tobet, S. A. (1990). Steroidal control of behavioural, neuroendocrine and brain sexual differentiation. J. Neuroendocrinol. 2, 401–418.
| Steroidal control of behavioural, neuroendocrine and brain sexual differentiation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3cXlvVCrsrY%3D&md5=fca975ef7ca5307bb9f3f7f1c1c455ebCAS | 19215366PubMed |
Beyer, B. K., Chernoff, N., Danielsson, B. R., Davis-Bruno, K., Harrouk, W., and Hood, R. D. (2011). ILSI/HESI maternal toxicity workshop summary: maternal toxicity and its impact on study design and data interpretation. Birth Defects Res. B Dev. Reprod. Toxicol. 92, 36–51.
| ILSI/HESI maternal toxicity workshop summary: maternal toxicity and its impact on study design and data interpretation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhslKqur0%3D&md5=e171f2318f7223f481e2b5a9740cc4cdCAS | 21312321PubMed |
Booth, J. E. (1977). Sexual behaviour of neonatally castrated rats injected during infancy with oestrogen and dihydrotestosterone. J. Endocrinol. 72, 135–141.
| Sexual behaviour of neonatally castrated rats injected during infancy with oestrogen and dihydrotestosterone.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE2sXhvVelsLs%3D&md5=fac7c435e67794ad06eb8221ffb775aaCAS | 845532PubMed |
BRASIL (2008). Ministério da Saúde. Agência Nacional de Vigilância Sanitária. Resolução de Diretoria Colegiada no 95, de 11 de dezembro de 2008. Regulamenta o texto de bulas de medicamentos fitoterápicos. Available at http://189.28.128.100/dab/docs/legislacao/resolucao95_11_12_08.pdf [accessed September 2011].
Broadhurst, P. L. (1960). Experiments in psychogenetics. In ‘Experiments in Personality’. (Ed. H. J. Eysenk.) pp. 31–61. (Rutledge and Kegan Paul: London.)
Buratti, F. M., De Angelis, G., Ricceri, L., Venerosi, A., Calamandrei, G., and Testai, E. (2011). Foetal and neonatal exposure to chlorpyrifos: biochemical and metabolic alterations in the mouse liver at different developmental stages. Toxicology 280, 98–108.
| Foetal and neonatal exposure to chlorpyrifos: biochemical and metabolic alterations in the mouse liver at different developmental stages.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtlaktLc%3D&md5=028dedbe0e1d1e714ec27a7a7d170057CAS | 21129432PubMed |
Buttar, H. S., and Jones, K. L. (2003). What do we know about the reproductive and developmental risks of herbal and alternate remedies? Birth Defects Res. B Dev. Reprod. Toxicol. 68, 492–493.
| What do we know about the reproductive and developmental risks of herbal and alternate remedies?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXjvFSrtQ%3D%3D&md5=1a8a093659e3f9b7b9b1f102f9702ea0CAS | 14745983PubMed |
Dhawan, K., Kumar, S., and Sharma, A. (2002). Suppression of alcohol-cessation-oriented hyper-anxiety by the benzoflavone moiety of Passiflora incarnata Linneaus in mice. J. Ethnopharmacol. 81, 239–244.
| Suppression of alcohol-cessation-oriented hyper-anxiety by the benzoflavone moiety of Passiflora incarnata Linneaus in mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XktlyntLg%3D&md5=a4945c82af9befe87512fd5301d17912CAS | 12065157PubMed |
Dhawan, K., Dhawan, S., and Sharma, A. (2004). Passiflora: a review update. J. Ethnopharmacol. 94, 1–23.
| Passiflora: a review update.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXlsl2jsb4%3D&md5=781dc8715fbb1b76fef418a606794c34CAS | 15261959PubMed |
Feder, H. H., and Whalen, R. E. (1965). Feminine behaviour in neonatally castrated and oestrogen-treated male rats. Science 147, 306–307.
| Feminine behaviour in neonatally castrated and oestrogen-treated male rats.Crossref | GoogleScholarGoogle Scholar | 17788218PubMed |
Freeman, L. M., and Rissman, E. F. (1996). Neural aromatisation and the control of sexual behaviour. Trends Endocrinol. Metab. 7, 334–338.
| Neural aromatisation and the control of sexual behaviour.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28Xntl2hs78%3D&md5=826564130cf850532994ae1ecf05b780CAS | 18406768PubMed |
Gerardin, D. C. C., Piffer, R. C., Garcia, P. C., Moreira, E. G., and Pereira, O. C. M. (2008). Effects of maternal exposure to an aromatase inhibitor on sexual behaviour and neurochemical and endocrine aspects of adult male rat. Reprod. Fertil. Dev. 20, 557–562.
| Effects of maternal exposure to an aromatase inhibitor on sexual behaviour and neurochemical and endocrine aspects of adult male rat.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXmsFagu7s%3D&md5=4e610d7adfb3ea0e57cfb420f82f4b20CAS |
Grundmann, O., Wang, J., McGregor, G. P., and Butterweck, V. (2008). Anxiolytic activity of a phytochemically characterized Passiflora incarnata extract is mediated via the GABAergic system. Planta Med. 74, 1769–1773.
| Anxiolytic activity of a phytochemically characterized Passiflora incarnata extract is mediated via the GABAergic system.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXptVOlsw%3D%3D&md5=736f85a36c65661141979bcc8c7e1e0dCAS | 19006051PubMed |
ICH (2005). Detection of toxicity to reproduction for medicinal products & toxicity to male fertility S5(R2). International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.
Jones, M. E. E., Boon, W. C., Proietto, J., and Simpson, E. R. (2006). Of mice and men: the evolving phenotype of aromatase deficiency. Trends Endocrinol. Metab. 17, 55–64.
| Of mice and men: the evolving phenotype of aromatase deficiency.Crossref | GoogleScholarGoogle Scholar |
Koren, G., Dugoua, J. J., Magee, L., Vohra, S., Matsui, D., Bérard, A., Johnson, B., Moretti, M., and Einarson, A. (2008). Mother nature: establishing a Canadian research network for natural health products (NHPs) during pregnancy and lactation. J. Altern. Complement. Med. 14, 369–372.
| Mother nature: establishing a Canadian research network for natural health products (NHPs) during pregnancy and lactation.Crossref | GoogleScholarGoogle Scholar | 18466066PubMed |
Moreira, E. G., Vassilieff, I., and Vassilieff, V. S. (2001). Developmental lead exposure: behavioural alterations in the short and long term. Neurotoxicol. Teratol. 23, 489–495.
| Developmental lead exposure: behavioural alterations in the short and long term.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXot1Oltb8%3D&md5=4995c6d75eb1ac4b76bf1e759742b552CAS | 11711252PubMed |
Nordeng, H., and Havnen, G. C. (2005). Impact of socio-demographic factors, knowledge and attitude on the use of herbal drugs in pregnancy. Acta Obstet. Gynecol. Scand. 84, 26–33.
| 15603563PubMed |
Pellow, S., and File, S. E. (1986). Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol. Biochem. Behav. 24, 525–529.
| Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL28XhvVSisbc%3D&md5=62ff115c3cecebac2370ff2dd9f3b6c6CAS | 2871560PubMed |
Refuerzo, J. S., Blackwell, S. C., and Sokol, R. J. (2005). Use of over-the-counter medication and herbal remedies in pregnancy. Am. J. Perinatol. 22, 321–324.
| Use of over-the-counter medication and herbal remedies in pregnancy.Crossref | GoogleScholarGoogle Scholar | 16118721PubMed |
Robb, G. W., Amann, R. P., and Killian, G. J. (1978). Daily sperm production and epididymal sperm reserves of pubertal and adult rats. J. Reprod. Fertil. 54, 103–107.
| Daily sperm production and epididymal sperm reserves of pubertal and adult rats.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE1M%2FltVegtg%3D%3D&md5=fa5604eb2f607b2867cae0246087b069CAS | 712697PubMed |
Roselli, C. E., Cross, E., Poonyagariyagorn, H. K., and Stadelman, H. L. (2003). Role of aromatisation in anticipatory and consummatory aspects of sexual behaviour in male rats. Horm. Behav. 44, 146–151.
| Role of aromatisation in anticipatory and consummatory aspects of sexual behaviour in male rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXnt1anurY%3D&md5=ef794e7ea1d483c1d5020bd1afc1bd98CAS | 13129487PubMed |
Ruggy, G. H., and Smith, C. S. (1940). A pharmacological study of the active principle of Passiflora incarnata. J. Am. Pharm. Assoc. 29, 245–249.
| 1:CAS:528:DyaH3cXjs1Kmsg%3D%3D&md5=8ed4c25439e42ddc222d51bb0d26c936CAS |
Soulimani, R., Younos, C., Jarmouni, S., Bousta, D., Misslin, R., and Mortier, F. (1997). Behavioural effects of P. incarnata L. and its indole alkaloid and flavonoid derivatives and maltol in the mouse. J. Ethnopharmacol. 57, 11–20.
| Behavioural effects of P. incarnata L. and its indole alkaloid and flavonoid derivatives and maltol in the mouse.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXks1ans78%3D&md5=ca101eea13bfbd16a949768a8478528cCAS | 9234160PubMed |
Tiran, D. (2003). The use of herbs by pregnant and childbearing women: a risk–benefit assessment. Complement. Ther. Nurs. Midwifery 9, 176–181.
| The use of herbs by pregnant and childbearing women: a risk–benefit assessment.Crossref | GoogleScholarGoogle Scholar | 14556766PubMed |
Veenema, A. H., Bredewold, R., and Neumann, I. D. (2007). Opposite effects of maternal separation on inter-male and maternal aggression in C57BL/6 mice: link to hypothalamic vasopressin and oxytocin immunoreactivity. Psychoneuroendocrinology 32, 437–450.
| Opposite effects of maternal separation on inter-male and maternal aggression in C57BL/6 mice: link to hypothalamic vasopressin and oxytocin immunoreactivity.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXlsFKqu7s%3D&md5=75f58bad5b0a10ec5385a4ff841306e6CAS | 17433558PubMed |
Veríssimo, L.F., Bacchi, A.D., Zaminelli, T., De Paula, G.H.O., and Moreira, E.G. (2011). Herbs of interest to the Brazilian Federal Government: female reproductive and developmental toxicity studies. Rev. Bras. Farmacogn , .
| Herbs of interest to the Brazilian Federal Government: female reproductive and developmental toxicity studies.Crossref | GoogleScholarGoogle Scholar |
Vianna, M. R. M., Izquierdo, L. A., Barros, D. M., Souza, M. M., Rodrigues, C., Sant’Anna, M. K., Medina, J. H., and Izquierdo, I. (2001). Pharmacological differences between memory consolidation of habituation to an open field and inhibitory avoidance learning. Braz. J. Med. Biol. Res. 34, 233–240.
| Pharmacological differences between memory consolidation of habituation to an open field and inhibitory avoidance learning.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3M3gsV2quw%3D%3D&md5=b369b5ff4aa881904bf005ab0471c4aaCAS |
Yunes, R. A., and Calixto, J. B. (2001). ‘Plantas Medicinais: Sob a Ótica da Química Medicinal Moderna’. 1st edn. (Argos Editora Universitária: Chapecó.)
Zanoli, P., Avallone, R., and Baraldi, M. (2000). Behavioural characterisation of the flavonoids apigenin and chrysin. Fitoterapia 71, S117–S123.
| Behavioural characterisation of the flavonoids apigenin and chrysin.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXltlWmsrs%3D&md5=9c026531e46a0442d92825bfb832e235CAS | 10930722PubMed |