Hostname: page-component-cd9895bd7-7cvxr Total loading time: 0 Render date: 2024-12-18T19:49:23.640Z Has data issue: false hasContentIssue false

The transgenerational effect of maternal and paternal F1 low birth weight on bone health of second and third generation offspring

Published online by Cambridge University Press:  10 April 2018

K. Anevska
Affiliation:
Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, Australia Department of Physiology, The University of Melbourne, Parkville, Australia
J. D. Wark
Affiliation:
Department of Medicine, The University of Melbourne and Bone and Mineral Medicine, Royal Melbourne Hospital, Parkville, Australia
M. E. Wlodek
Affiliation:
Department of Physiology, The University of Melbourne, Parkville, Australia
T. Romano*
Affiliation:
Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, Australia
*
*Address for correspondence: Dr T. Romano, Lecturer, Department of Physiology, Anatomy and Microbiology, College of Science, Health and Engineering, La Trobe University, Bundoora, VIC 3086, Australia. E-mail: [email protected]

Abstract

Low birth weight programs diseases in adulthood, including adverse bone health. These diseases can have intergenerational and transgenerational origins, whereby transmission to subsequent generations occurs via both parental lines. Uteroplacental insufficiency surgery (Restricted) or sham surgery (Control) was performed on gestational day 18, in F0 Wistar–Kyoto rats. F1 Restricted males and females mated with breeders in order to generate F2 offspring of maternal and paternal lineages. F2 males and females were randomly selected for breeding to generate F3 offspring. F2 and F3 offspring did not have differences in birth weight irrespective of F1 low birth weight and parental line. Maternal line females had minor alterations to trabecular content and density at 6 months, these differences were not sustained at 12 months. Maternal line males had changes to trabecular content at 6 and 12 months; however, differences were no longer present at 16 months. Despite altered bone geometry at 12 and 16 months, bending strength remained unaffected at both ages. Bone health of paternal line females was not affected at 6 and 12 months. Paternal line males at 6 months had changes to trabecular and cortical content; cortical thickness, periosteal circumference and bending strength; however, these differences were no longer sustained at 12 and 16 months. Our data demonstrate that there is no transgenerational transmission of adverse bone health in F2 and F3 offspring, derived from low F1 birth weight females and males. Our results are novel, as bone health across generations and both parental lines has not been investigated in a model of low birth weight due to uteroplacental insufficiency.

Type
Original Article
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018. 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

Joint senior author.

References

1. Barker, DJP. The developmental origins of adult disease. J Am Coll Nutr. 2004; 23, 558S595S.Google Scholar
2. Barker, DJ. Fetal origins of coronary heart disease. Acta Pediatr Suppl. 1995; 311, 171174.Google Scholar
3. Barker, DJ, Winter, PD, Osmond, C, Margetts, B, Simmonds, SJ. Weight in infancy and death from ischaemic heart disease. Lancet. 1989; 2, 577580.Google Scholar
4. Cooper, C, Fall, C, Egger, P, et al. Growth in infancy and bone mass in later life. Ann Rheum Dis. 1997; 56, 1721.Google Scholar
5. Romano, T, Wark, JD, Owens, JA, Wlodek, ME. Prenatal growth restriction and postnatal growth restriction followed by accelerated growth independently program reduced bone growth and strength. Bone. 2009; 45, 132141.Google Scholar
6. Romano, T, Wark, JD, Wlodek, ME. Calcium supplementation does not rescue the programmed adult bone deficits associated with perinatal growth restriction. Bone. 2010; 47, 10541063.Google Scholar
7. Hanson, MA, Skinner, MK. Developmental origins of epigenetic transgenerational inheritance. Environ Epigenet. 2016; 2, dvw002dvw002.Google Scholar
8. Skinner, MK. What is an epigenetic transgenerational phenotype? F3 or F2. Reprod Toxicol. 2008; 25, 26.Google Scholar
9. Skinner, MK. Endocrine disruptor induction of epigenetic transgenerational inheritance of disease. Mol Cell Endocrinol. 2014; 398, 412.Google Scholar
10. Dickinson, H, Moss, TJ, Gatford, KL, et al. A review of fundamental principles for animal models of DOHaD research: an Australian perspective. J Dev Orig Health Dis. 2016; 7, 449472.Google Scholar
11. Painter, RC, Osmond, C, Gluckman, P, et al. Transgenerational effects of prenatal exposure to the Dutch famine on neonatal adiposity and health in later life. BJOG. 2008; 115, 12431249.Google Scholar
12. Roseboom, TJ, Van Der Meulen, JHP, Ravelli, ACJ, et al. Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Mol Cell Endocrinol. 2001; 185, 9398.Google Scholar
13. Jaquet, D, Swaminathan, S, Alexander, GR, et al. Significant paternal contribution to the risk of small for gestational age. BJOG. 2005; 112, 153159.Google Scholar
14. Alberman, E, Emanuel, I, Filakti, H, Evans, SJ. The contrasting effects of parental birthweight and gestational age on the birthweight of offspring. Paediatr Perinat Epidemiol. 1992; 6, 134144.Google Scholar
15. Emanuel, I, Filakti, H, Alberman, E, Evans, SJ. Intergenerational studies of human birthweight from the 1958 birth cohort. 1. Evidence for a multigenerational effect. Br J Obstet Gynaecol. 1992; 99, 6774.Google Scholar
16. Magnus, P, Gjessing, HK, Skrondal, A, Skjaerven, R. Paternal contribution to birth weight. J Epidemiol Community Health. 2001; 55, 873877.Google Scholar
17. Klebanoff, MA, Mednick, BR, Schulsinger, C, Secher, NJ, Shiono, PH. Father’s effect on infant birth weight. Am J Obstet Gynecol. 1998; 178, 10221026.Google Scholar
18. Tran, M, Gallo, LA, Hanvey, AN, et al. Embryo-transfer in rats cannot delineate between the maternal pregnancy environment and germ-line effects in the transgenerational transmission of disease in rats. Am J Physiol Regul Integr Comp Physiol. 2014; 306, R607R618.Google Scholar
19. Tran, M, Gallo, LA, Jefferies, AJ, Moritz, KM, Wlodek, ME. Transgenerational metabolic outcomes associated with uteroplacental insufficiency. J Endocrinol. 2013; 217, 105118.Google Scholar
20. Gallo, LA, Tran, M, Cullen-McEwen, LA, Denton, KM, Jefferies, AJ, Moritz, KM, Wlodek, ME. Transgenerational programming of fetal nephron deficits and sex-specific adult hypertension in rats. Reprod Fertil Dev. 2014; 26, 10321043.Google Scholar
21. Anevska, K, Gallo, LA, Tran, M, et al. Pregnant growth restricted female rats have bone gains during late gestation which contributes to second generation adolescent and adult offspring having normal bone health. Bone. 2015; 74C, 199207.Google Scholar
22. Romano, T, Wark, JD, Wlodek, ME. Developmental programming of bone deficits in growth-restricted offspring. Reprod Fertil Dev. 2014; 27, 823833.Google Scholar
23. Wlodek, ME, Westcott, KT, O’Dowd, R, et al. Uteroplacental restriction in the rat impairs fetal growth in association with alterations in placental growth factors including PTHrP. Am J Physiol Regul Integr Comp Physiol. 2005; 288, R1620R1627.Google Scholar
24. Wlodek, ME, Mibus, A, Tan, A, et al. Normal lactational environment restores nephron endowment and prevents hypertension after placental restriction in the rat. J Am Soc Nephrol. 2007; 18, 16881696.Google Scholar
25. O’Dowd, R, Kent, JC, Moseley, JM, Wlodek, ME. Effects of uteroplacental insufficiency and reducing litter size on maternal mammary function and postnatal offspring growth. Am J Physiol Regul Integr Comp Physiol. 2008; 294, R539R548.Google Scholar
26. Romano, T, Hryciw, DH, Westcott, KT, Wlodek, ME. Puberty onset is delayed following uteroplacental insufficiency and occurs earlier with improved lactation and growth for pups born small. Reprod Fertil Dev. 2017; 29, 307318.Google Scholar
27. Romano, T, Wark, JD, Wlodek, ME. Physiological skeletal gains and losses in rat mothers during pregnancy and lactation are not observed following uteroplacental insufficiency. Reprod Fertil Dev. 2013; 26, 385394.Google Scholar
28. Anevska, K, Cheong, JN, Wark, JD, Wlodek, ME, Romano, T. Maternal stress does not exacerbate long-term bone deficits in female rats born growth restricted, with differential effects on offspring bone health. Am J Physiol Regul Integr Comp Physiol. 2018; 314, R161R170.Google Scholar
29. Cheong, JN, Cuffe, JS, Jefferies, AJ, et al. Sex-specific metabolic outcomes in offspring of female rats born small or exposed to stress during pregnancy. Endocrinology. 2016; 157, 41044120.Google Scholar
30. Davison, KS, Siminoski, K, Adachi, JD, et al. Bone strength: the whole is greater than the sum of its parts. Semin Cell Biol. 2006; 36, 2231.Google Scholar
31. Ng, SF, Lin, RC, Laybutt, DR, et al. Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring. Nature. 2010; 467, 963966.Google Scholar
32. Fullston, T, Ohlsson Teague, EM, Palmer, NO, et al. Paternal obesity initiates metabolic disturbances in two generations of mice with incomplete penetrance to the F2 generation and alters the transcriptional profile of testis and sperm microRNA content. FASEB J. 2013; 27, 42264243.Google Scholar
33. Fullston, T, Shehadeh, H, Sandeman, LY, et al. Female offspring sired by diet induced obese male mice display impaired blastocyst development with molecular alterations to their ovaries, oocytes and cumulus cells. J Assist Reprod Genet. 2015; 32, 725735.Google Scholar
34. Orwoll, ES. Toward an expanded understanding of the role of the periosteum in skeletal health. J Bone Miner Res. 2003; 18, 949954.Google Scholar
35. Anway, MD, Cupp, AS, Uzumcu, M, Skinner, MK. Epigenetic transgenerational actions of endocrine distruptors and male fertility. Science. 2005; 308, 14661469.Google Scholar
36. Anway, MD, Leathers, C, Skinner, MK. Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease. Endocrinology. 2006; 147, 55155523.Google Scholar
Supplementary material: File

Anevska et al. supplementary material

Table S1

Download Anevska et al. supplementary material(File)
File 15.4 KB