Evidence of prenatal toxicity of herbal based indigenous formulations for sex selection in rat models

10.1016/j.jtcme.2019.09.005

Sutapa Bandyopadhyay Neogi；Dilip Kumar Roy；Anand Kamal Sachdeva；Rashmi Sharma；Rakesh Gupta；Abhijit Ganguli

Indigenous preparations ； Herbal ； Sex selection ； Toxicity ； Animal models ； Prenatal

Journal of Traditional and Complementary Medicine

11卷1期（2021 / 01 / 01）

9 - 15

英文

Indigenous preparations(IPs) for a male child is reported from some parts of India. The present study aims to explore the effects of IPs for sex selection or sex selection drugs (SSDs) on pregnancy outcomes in rat models. SSDs contain Bryonia laciniosa, Quercus infectoria and Putranjiva roxburghii along with other ingredients. Methods: An experimental design with successfully mated female rats were randomized into control and treatment groups. Phase 1 had 2 interventional arms while phase 2 had 3 interventional arms (12 rats/ arm) besides control arm. In phase-1, pregnant females were dosed two SSDs(1000 mg/kg) on gestation days 1-5 whereas, in phase-2, on gestation days 6-19 to correlate the effect of the SSDs (500/1000/ 1500 mg/kg) consumption during different stages of pregnancy. Pregnant females were observed for clinical signs following treatment. The rats were sacrificed one day before expected day of delivery for evaluation. Pregnancy rate, gestation index, number of corpora lutea, and litter size were assessed. Foetuses were examined for sex, skeletal and soft tissue alterations. Discussion and conclusion: In phase 1, no appreciable findings were there with SSD exposure. In phase 2, intrauterine growth and survival of foetuses were affected when SSDs were administered during organogenesis period. Decreased number of live foetuses and increased incidence of early and late resorption, reduced fetal growth with significant alteration in skeleton and viscera were found in treatment groups in a dose-dependent manner. This correlates well with findings from observational studies in pregnant women. However, such treatment at any dose did not effect sex differentiation.

1. Bandyopadhyay, S,Singh, A(2007).Sex Selection through traditional drugs in rural north India.Indian J Community Med,32,32-34.
2. Benzie, IFF(ed.),Wachtel-Galor, S(ed.)(2011).Herbal Medicine: Biomolecular and Clinical Aspects.Boca Raton (FL).:
3. Bhagat, N,Laskar, A,Sharma, N(2012).Women's perception about sex selection in an urban slum in Delhi.J Reprod Infant Psychol,30(1),92.
4. Blumenthal, M,Goldberg A, B J.(2000).Herbal Medicine: Expanded Commission E Monographs.Boston:
5. Byard, RW,Musgrave, I,Maker, G,Bunce, M(2017).What risks do herbal products pose to the Australian community?.Med J Aust,206(2),86-90.
6. Ganguli, A,Rai, P,Balachandran, S,Gupta, R,Sharma, R,Neogi, SB(2018).Heavy Metals in Indigenous Preparations Used for Sex Selection during Pregnancy in India.Biological Trace Element Research
7. Jefferson, W,Patisaul, H,Williams, C(2012).Reproductive consequences of developmental phytoestrogen exposure.Reproduction,143(3),247-260.
8. Kazemipoor, M,Radzi, CW,Cordell, GA,Y, I(2012).Safety, efficacy and metabolism of traditional medicinal plants in the management of obesity: a review.International Journal of Chemical Engineering and Applications,3(4),288-292.
9. Leung, PC(2007).The efficacy of Chinese medicine for SARS: a review of Chinese publications after the crisis.Am J Chin Med.,35(4),575-581.
10. Liang, B,Li, L,Tang, LY,Wu, Q,Wu, XK,Wang, CC(2015).Safety of Chinese herbal medicines during pregnancy.J Appl Toxicol,35(5),447-458.
11. Manchanda, S,Saikia, B,Gupta, N,Chowdhary, S,Puliyel, J(2011).Sex ratio at birth in India, its relation to birth order, sex of previous children and use of indigenous medicine.PLoS One,6(6),e20097.
12. McClain, RM,Wolz, E,Davidovich, A,Edwards, J,Bausch, J(2007).Reproductive safety studies with genistein in rats.Food Chem Toxicol : Int. J.Publ.Br.Ind.Biol.Res.Assoc,45(8),1319-1332.
13. Neogi, S,Negandhi, P,Ganguli, A(2015).Consumption of indigenous medicines by pregnant women in North India for selecting sex of the foetus: what can it lead to?.BMC Pregnancy Childbirth,15(1),208.
14. Neogi, SB,Negandhi, P,Chopra, S(2016).Risk factors for stillbirth: findings from a population-based case-control study, Haryana, India.Paediatric and perinatal epidemiology,30(1),56-66.
15. Neogi, SB,Negandhi, PH,Sandhu, N(2015).Indigenous medicine use for sex selection during pregnancy and risk of congenital malformations: a population-based case-control study in Haryana, India.India. Drug Saf,38(9),789-797.
16. OECD(2001).OECD. OECD Guidelines for The Testing of Chemicals. vol. 414. 2001. USA..
17. Rai, P,Mishra, S,Shanker, K(2019).Chemical Evaluation of Dietary Herbal Formulations Consumed by Pregnant Women for Sex Selection of Offspring.Quality Assurance and Safety of Crops & Foods
18. Rai, P,Rajasekharan, S,Ganguli, A(2019).Indigenous preparations of Bryonia laciniosa, Quercus infectoria, Putranjiva roxburghii and Mesua ferrea induces developmental toxicity in C. elegans.Proc Natl Acad Sci India Sect B Biol Sci
19. Rhees, RW,Kirk, BA,Sephton, S,Lephart, ED(1997).Effects of prenatal testosterone on sexual behavior, reproductive morphology and LH secretion in the female rat.Dev Neurosci,19(5),430-437.
20. Romero, V,Dela Cruz, C,Pereira, O(2008).Reproductive and toxicological effects of isoflavones on female offspring of rats exposed during pregnancy.Anim Reprod,5(3/4),83-89.
21. Shulman, LP(2015).Walking the fine line between science and culture.Drug Saf,38(9),769-771.
22. Singh, A,Sinha, S.(2016).Risk factors of congenital malformations in north India: a case control study.J Postgrad Med Educ Res,50(1),22-27.
23. Smith, AJ,Clutton, RE,Lilley, E,Hansen, KEA,Brattelid, T(2018).PREPARE: guidelines for planning animal research and testing.Lab Anim,52(2),135-141.
24. Tilburt, JC,Kaptchuk, TJ(2008).Herbal medicine research and global health: an ethical analysis.Bull World Health Organ,86(8),594-599.
25. Wang, CC,Li, L,Tang, LY,Leung, PC(2012).Safety evaluation of commonly used Chinese herbal medicines during pregnancy in mice.Hum Reprod,27(8),2448-2456.
26. WHO(2013).WHO Traditional Medicine Strategy 2014-2023.Geneva, Switzerland:
27. Wolf, CJ,Hotchkiss, A,Ostby, JS,LeBlanc, GA,Gray, Jr, LE(2002).Effects of prenatal testosterone propionate on the sexual development of male and female rats: a dose-response study.Toxicol Sci,65(1),71-86.
28. Wood, RI,FJP, Ebling,I'Anson, H,Bucholtz, DC,Yellon, SM,Foster, DL(1991).Prenatal androgens time neuroendocrine sexual maturation*.Endocrinology,128(5),2457-2468.