Skip to main content
Top
Published in: Reproductive Biology and Endocrinology 1/2019

Open Access 01-12-2019 | Intrauterine Growth Restriction | Research

Impact of uteroplacental insufficiency on ovarian follicular pool in the rat

Authors: Valentina Pampanini, Kirsi Jahnukainen, Lena Sahlin, Daniela Germani, Antonella Puglianiello, Stefano Cianfarani, Olle Söder

Published in: Reproductive Biology and Endocrinology | Issue 1/2019

Login to get access

Abstract

Background

A low oxygen supply to the fetus causes intrauterine growth restriction and can affect gonadal development of the offspring, having a potential impact on fertility. We investigated histology and gene expression in the postnatal rat ovary after fetal hypoxia induced by uterine artery ligation.

Methods

Sprague-Dawley rats underwent uterine artery ligation at day 19 of gestation. Offspring were sacrificed at 5, 20 and 40 days post-partum. Follicles were counted and classified in hematoxylin-eosin stained sections. Gene expression of 90 genes was analyzed by TaqMan® Low Density Array.

Results

A significantly lower number of total and primordial follicles was detected in 20 days post-partum intrauterine growth restricted animals. Follicle density was not different at 40 days post-partum, suggesting that compensatory mechanisms occurred during the pre-pubertal window. Uterine artery ligation modified the expression of 24 genes involved in different cellular functions, among which proliferation, apoptosis and metabolism.

Conclusion

Ovarian follicle pool was affected by fetal hypoxia in early life, but this effect did not persist in puberty. Genes involved in cellular processes were affected at all ages, potentially implying long-term genetic alterations. Further analyses are needed to elucidate later effects of fetal hypoxia on ovarian function and fertility.
Appendix
Available only for authorised users
Literature
1.
go back to reference Barker DJ. The fetal and infant origins of adult disease. BMJ. 1990;301(6761):1111.CrossRef Barker DJ. The fetal and infant origins of adult disease. BMJ. 1990;301(6761):1111.CrossRef
2.
go back to reference Barker DJ, Bull AR, Osmond C, Simmonds SJ. Fetal and placental size and risk of hypertension in adult life. BMJ. 1990;301(6746):259–62.CrossRef Barker DJ, Bull AR, Osmond C, Simmonds SJ. Fetal and placental size and risk of hypertension in adult life. BMJ. 1990;301(6746):259–62.CrossRef
3.
go back to reference Barker DJ. Fetal origins of coronary heart disease. BMJ. 1995;311(6998):171–4.CrossRef Barker DJ. Fetal origins of coronary heart disease. BMJ. 1995;311(6998):171–4.CrossRef
4.
go back to reference Barker DJ. The fetal and infant origins of disease. Eur J Clin Investig. 1995;25(7):457–63.CrossRef Barker DJ. The fetal and infant origins of disease. Eur J Clin Investig. 1995;25(7):457–63.CrossRef
5.
go back to reference Fall CH, Osmond C, Barker DJ, Clark PM, Hales CN, Stirling Y, et al. Fetal and infant growth and cardiovascular risk factors in women. BMJ. 1995;310(6977):428–32.CrossRef Fall CH, Osmond C, Barker DJ, Clark PM, Hales CN, Stirling Y, et al. Fetal and infant growth and cardiovascular risk factors in women. BMJ. 1995;310(6977):428–32.CrossRef
6.
go back to reference Barker DJ, Martyn CN, Osmond C, Hales CN, Fall CH. Growth in utero and serum cholesterol concentrations in adult life. BMJ. 1993;307(6918):1524–7.CrossRef Barker DJ, Martyn CN, Osmond C, Hales CN, Fall CH. Growth in utero and serum cholesterol concentrations in adult life. BMJ. 1993;307(6918):1524–7.CrossRef
7.
go back to reference Hales CN, Barker DJ. The thrifty phenotype hypothesis. Br Med Bull. 2001;60:5–20.CrossRef Hales CN, Barker DJ. The thrifty phenotype hypothesis. Br Med Bull. 2001;60:5–20.CrossRef
8.
go back to reference Cianfarani S, Agostoni C, Bedogni G, Berni Canani R, Brambilla P, Nobili V, et al. Effect of intrauterine growth retardation on liver and long-term metabolic risk. Int J Obes. 2012;36(10):1270–7.CrossRef Cianfarani S, Agostoni C, Bedogni G, Berni Canani R, Brambilla P, Nobili V, et al. Effect of intrauterine growth retardation on liver and long-term metabolic risk. Int J Obes. 2012;36(10):1270–7.CrossRef
9.
go back to reference Ibanez L, de Zegher F. Puberty and prenatal growth. Mol Cell Endocrinol. 2006;254-255:22–5.CrossRef Ibanez L, de Zegher F. Puberty and prenatal growth. Mol Cell Endocrinol. 2006;254-255:22–5.CrossRef
10.
go back to reference Hernandez MI, Mericq V. Impact of being born small for gestational age on onset and progression of puberty. Best Pract Res Clin Endocrinol Metab. 2008;22(3):463–76.CrossRef Hernandez MI, Mericq V. Impact of being born small for gestational age on onset and progression of puberty. Best Pract Res Clin Endocrinol Metab. 2008;22(3):463–76.CrossRef
11.
go back to reference Hokken-Koelega AC. Timing of puberty and fetal growth. Best Pract Res Clin Endocrinol Metab. 2002;16(1):65–71.CrossRef Hokken-Koelega AC. Timing of puberty and fetal growth. Best Pract Res Clin Endocrinol Metab. 2002;16(1):65–71.CrossRef
12.
go back to reference Ibanez L, Potau N, de Zegher F. Ovarian hyporesponsiveness to follicle stimulating hormone in adolescent girls born small for gestational age. J Clin Endocrinol Metab. 2000;85(7):2624–6.CrossRef Ibanez L, Potau N, de Zegher F. Ovarian hyporesponsiveness to follicle stimulating hormone in adolescent girls born small for gestational age. J Clin Endocrinol Metab. 2000;85(7):2624–6.CrossRef
13.
go back to reference Ibanez L, Valls C, Cols M, Ferrer A, Marcos MV, De Zegher F. Hypersecretion of FSH in infant boys and girls born small for gestational age. J Clin Endocrinol Metab. 2002;87(5):1986–8.CrossRef Ibanez L, Valls C, Cols M, Ferrer A, Marcos MV, De Zegher F. Hypersecretion of FSH in infant boys and girls born small for gestational age. J Clin Endocrinol Metab. 2002;87(5):1986–8.CrossRef
14.
go back to reference Verkauskiene R, Petraitiene I, Albertsson Wikland K. Puberty in children born small for gestational age. Horm Res Paediatr. 2013;80(2):69–77.CrossRef Verkauskiene R, Petraitiene I, Albertsson Wikland K. Puberty in children born small for gestational age. Horm Res Paediatr. 2013;80(2):69–77.CrossRef
15.
go back to reference Persson I, Ahlsson F, Ewald U, Tuvemo T, Qingyuan M, von Rosen D, et al. Influence of perinatal factors on the onset of puberty in boys and girls: implications for interpretation of link with risk of long term diseases. Am J Epidemiol. 1999;150(7):747–55.CrossRef Persson I, Ahlsson F, Ewald U, Tuvemo T, Qingyuan M, von Rosen D, et al. Influence of perinatal factors on the onset of puberty in boys and girls: implications for interpretation of link with risk of long term diseases. Am J Epidemiol. 1999;150(7):747–55.CrossRef
16.
go back to reference Ghirri P, Bernardini M, Vuerich M, Cuttano AM, Coccoli L, Merusi I, et al. Adrenarche, pubertal development, age at menarche and final height of full-term, born small for gestational age (SGA) girls. Gynecol Endocrinol. 2001;15(2):91–7.PubMed Ghirri P, Bernardini M, Vuerich M, Cuttano AM, Coccoli L, Merusi I, et al. Adrenarche, pubertal development, age at menarche and final height of full-term, born small for gestational age (SGA) girls. Gynecol Endocrinol. 2001;15(2):91–7.PubMed
17.
go back to reference Bhargava SK, Ramji S, Srivastava U, Sachdev HP, Kapani V, Datta V, et al. Growth and sexual maturation of low birth weight children: a 14 year follow up. Indian Pediatr. 1995;32(9):963–70.PubMed Bhargava SK, Ramji S, Srivastava U, Sachdev HP, Kapani V, Datta V, et al. Growth and sexual maturation of low birth weight children: a 14 year follow up. Indian Pediatr. 1995;32(9):963–70.PubMed
18.
go back to reference Ibanez L, Potau N, Enriquez G, de Zegher F. Reduced uterine and ovarian size in adolescent girls born small for gestational age. Pediatr Res. 2000;47(5):575–7.CrossRef Ibanez L, Potau N, Enriquez G, de Zegher F. Reduced uterine and ovarian size in adolescent girls born small for gestational age. Pediatr Res. 2000;47(5):575–7.CrossRef
19.
go back to reference Ibanez L, Potau N, Ferrer A, Rodriguez-Hierro F, Marcos MV, De Zegher F. Anovulation in eumenorrheic, nonobese adolescent girls born small for gestational age: insulin sensitization induces ovulation, increases lean body mass, and reduces abdominal fat excess, dyslipidemia, and subclinical hyperandrogenism. J Clin Endocrinol Metab. 2002;87(12):5702–5.CrossRef Ibanez L, Potau N, Ferrer A, Rodriguez-Hierro F, Marcos MV, De Zegher F. Anovulation in eumenorrheic, nonobese adolescent girls born small for gestational age: insulin sensitization induces ovulation, increases lean body mass, and reduces abdominal fat excess, dyslipidemia, and subclinical hyperandrogenism. J Clin Endocrinol Metab. 2002;87(12):5702–5.CrossRef
20.
go back to reference Ibanez L, Potau N, Ferrer A, Rodriguez-Hierro F, Marcos MV, de Zegher F. Reduced ovulation rate in adolescent girls born small for gestational age. J Clin Endocrinol Metab. 2002;87(7):3391–3.CrossRef Ibanez L, Potau N, Ferrer A, Rodriguez-Hierro F, Marcos MV, de Zegher F. Reduced ovulation rate in adolescent girls born small for gestational age. J Clin Endocrinol Metab. 2002;87(7):3391–3.CrossRef
21.
go back to reference Murdoch WJ, Van Kirk EA, Vonnahme KA, Ford SP. Ovarian responses to undernutrition in pregnant ewes, USA. Reprod Biol Endocrinol. 2003;1:6.CrossRef Murdoch WJ, Van Kirk EA, Vonnahme KA, Ford SP. Ovarian responses to undernutrition in pregnant ewes, USA. Reprod Biol Endocrinol. 2003;1:6.CrossRef
22.
go back to reference Bernal AB, Vickers MH, Hampton MB, Poynton RA, Sloboda DM. Maternal undernutrition significantly impacts ovarian follicle number and increases ovarian oxidative stress in adult rat offspring. PLoS One. 2010;5(12):e15558.CrossRef Bernal AB, Vickers MH, Hampton MB, Poynton RA, Sloboda DM. Maternal undernutrition significantly impacts ovarian follicle number and increases ovarian oxidative stress in adult rat offspring. PLoS One. 2010;5(12):e15558.CrossRef
23.
go back to reference Rae MT, Palassio S, Kyle CE, Brooks AN, Lea RG, Miller DW, et al. Effect of maternal undernutrition during pregnancy on early ovarian development and subsequent follicular development in sheep fetuses. Reproduction. 2001;122(6):915–22.CrossRef Rae MT, Palassio S, Kyle CE, Brooks AN, Lea RG, Miller DW, et al. Effect of maternal undernutrition during pregnancy on early ovarian development and subsequent follicular development in sheep fetuses. Reproduction. 2001;122(6):915–22.CrossRef
24.
go back to reference Pampanini V, Germani D, Puglianiello A, Stukenborg JB, Reda A, Savchuk I, et al. Impact of uteroplacental insufficiency on postnatal rat male gonad. J Endocrinol. 2017;232(2):247–57.CrossRef Pampanini V, Germani D, Puglianiello A, Stukenborg JB, Reda A, Savchuk I, et al. Impact of uteroplacental insufficiency on postnatal rat male gonad. J Endocrinol. 2017;232(2):247–57.CrossRef
25.
go back to reference Engelbregt MJ, van Weissenbruch MM, Popp-Snijders C, Delemarre-van de Waal HA. Delayed first cycle in intrauterine growth-retarded and postnatally undernourished female rats: follicular growth and ovulation after stimulation with pregnant mare serum gonadotropin at first cycle. J Endocrinol. 2002;173(2):297–304.CrossRef Engelbregt MJ, van Weissenbruch MM, Popp-Snijders C, Delemarre-van de Waal HA. Delayed first cycle in intrauterine growth-retarded and postnatally undernourished female rats: follicular growth and ovulation after stimulation with pregnant mare serum gonadotropin at first cycle. J Endocrinol. 2002;173(2):297–304.CrossRef
26.
go back to reference Wigglesworth JS. Experimental growth retardation in the Foetal rat. J Pathol Bacteriol. 1964;88:1–13.CrossRef Wigglesworth JS. Experimental growth retardation in the Foetal rat. J Pathol Bacteriol. 1964;88:1–13.CrossRef
27.
go back to reference Picut CA, Dixon D, Simons ML, Stump DG, Parker GA, Remick AK. Postnatal ovary development in the rat: morphologic study and correlation of morphology to neuroendocrine parameters. Toxicol Pathol. 2015;43(3):343–53.CrossRef Picut CA, Dixon D, Simons ML, Stump DG, Parker GA, Remick AK. Postnatal ovary development in the rat: morphologic study and correlation of morphology to neuroendocrine parameters. Toxicol Pathol. 2015;43(3):343–53.CrossRef
28.
go back to reference Dean A, van den Driesche S, Wang Y, McKinnell C, Macpherson S, Eddie SL, et al. Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences. Sci Rep. 2016;6:19789.CrossRef Dean A, van den Driesche S, Wang Y, McKinnell C, Macpherson S, Eddie SL, et al. Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences. Sci Rep. 2016;6:19789.CrossRef
29.
go back to reference Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr Rev. 1996;17(2):121–55.CrossRef Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr Rev. 1996;17(2):121–55.CrossRef
30.
go back to reference Gougeon A. Human ovarian follicular development: from activation of resting follicles to preovulatory maturation. Ann Endocrinol (Paris). 2010;71(3):132–43.CrossRef Gougeon A. Human ovarian follicular development: from activation of resting follicles to preovulatory maturation. Ann Endocrinol (Paris). 2010;71(3):132–43.CrossRef
31.
go back to reference Rosendahl M, Ernst E, Rasmussen PE, Andersen CY. True ovarian volume is underestimated by two-dimensional transvaginal ultrasound measurement. Fertil Steril. 2010;93(3):995–8.CrossRef Rosendahl M, Ernst E, Rasmussen PE, Andersen CY. True ovarian volume is underestimated by two-dimensional transvaginal ultrasound measurement. Fertil Steril. 2010;93(3):995–8.CrossRef
32.
go back to reference Jones KP, Walker LC, Anderson D, Lacreuse A, Robson SL, Hawkes K. Depletion of ovarian follicles with age in chimpanzees: similarities to humans. Biol Reprod. 2007;77(2):247–51.CrossRef Jones KP, Walker LC, Anderson D, Lacreuse A, Robson SL, Hawkes K. Depletion of ovarian follicles with age in chimpanzees: similarities to humans. Biol Reprod. 2007;77(2):247–51.CrossRef
33.
go back to reference Miller PB, Charleston JS, Battaglia DE, Klein NA, Soules MR. Morphometric analysis of primordial follicle number in pigtailed monkey ovaries: symmetry and relationship with age. Biol Reprod. 1999;61(2):553–6.CrossRef Miller PB, Charleston JS, Battaglia DE, Klein NA, Soules MR. Morphometric analysis of primordial follicle number in pigtailed monkey ovaries: symmetry and relationship with age. Biol Reprod. 1999;61(2):553–6.CrossRef
34.
go back to reference Wallace WH, Kelsey TW. Human ovarian reserve from conception to the menopause. PLoS One. 2010;5(1):e8772.CrossRef Wallace WH, Kelsey TW. Human ovarian reserve from conception to the menopause. PLoS One. 2010;5(1):e8772.CrossRef
35.
go back to reference Broer SL, Broekmans FJ, Laven JS, Fauser BC. Anti-Mullerian hormone: ovarian reserve testing and its potential clinical implications. Hum Reprod Update. 2014;20(5):688–701.CrossRef Broer SL, Broekmans FJ, Laven JS, Fauser BC. Anti-Mullerian hormone: ovarian reserve testing and its potential clinical implications. Hum Reprod Update. 2014;20(5):688–701.CrossRef
36.
go back to reference Shalom-Paz E, Weill S, Ginzberg Y, Khatib N, Anabusi S, Klorin G, et al. IUGR induced by maternal chronic inflammation: long-term effect on offspring's ovaries in rat model-a preliminary report. J Endocrinol Investig. 2017;40(10):1125–31.CrossRef Shalom-Paz E, Weill S, Ginzberg Y, Khatib N, Anabusi S, Klorin G, et al. IUGR induced by maternal chronic inflammation: long-term effect on offspring's ovaries in rat model-a preliminary report. J Endocrinol Investig. 2017;40(10):1125–31.CrossRef
37.
go back to reference de Bruin JP, Dorland M, Bruinse HW, Spliet W, Nikkels PG, Te Velde ER. Fetal growth retardation as a cause of impaired ovarian development. Early Hum Dev. 1998;51(1):39–46.CrossRef de Bruin JP, Dorland M, Bruinse HW, Spliet W, Nikkels PG, Te Velde ER. Fetal growth retardation as a cause of impaired ovarian development. Early Hum Dev. 1998;51(1):39–46.CrossRef
38.
go back to reference Ibanez L, Potau N, Enriquez G, Marcos MV, de Zegher F. Hypergonadotrophinaemia with reduced uterine and ovarian size in women born small-for-gestational-age. Hum Reprod. 2003;18(8):1565–9.CrossRef Ibanez L, Potau N, Enriquez G, Marcos MV, de Zegher F. Hypergonadotrophinaemia with reduced uterine and ovarian size in women born small-for-gestational-age. Hum Reprod. 2003;18(8):1565–9.CrossRef
39.
go back to reference Zheng W, Zhang H, Gorre N, Risal S, Shen Y, Liu K. Two classes of ovarian primordial follicles exhibit distinct developmental dynamics and physiological functions. Hum Mol Genet. 2014;23(4):920–8.CrossRef Zheng W, Zhang H, Gorre N, Risal S, Shen Y, Liu K. Two classes of ovarian primordial follicles exhibit distinct developmental dynamics and physiological functions. Hum Mol Genet. 2014;23(4):920–8.CrossRef
40.
go back to reference Zheng W, Zhang H, Liu K. The two classes of primordial follicles in the mouse ovary: their development, physiological functions and implications for future research. Mol Hum Reprod. 2014;20(4):286–92.CrossRef Zheng W, Zhang H, Liu K. The two classes of primordial follicles in the mouse ovary: their development, physiological functions and implications for future research. Mol Hum Reprod. 2014;20(4):286–92.CrossRef
41.
go back to reference Mork L, Maatouk DM, McMahon JA, Guo JJ, Zhang P, McMahon AP, et al. Temporal differences in granulosa cell specification in the ovary reflect distinct follicle fates in mice. Biol Reprod. 2012;86(2):37.CrossRef Mork L, Maatouk DM, McMahon JA, Guo JJ, Zhang P, McMahon AP, et al. Temporal differences in granulosa cell specification in the ovary reflect distinct follicle fates in mice. Biol Reprod. 2012;86(2):37.CrossRef
42.
go back to reference Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature. 2004;428(6979):145–50.CrossRef Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature. 2004;428(6979):145–50.CrossRef
43.
go back to reference Johnson J, Skaznik-Wikiel M, Lee HJ, Niikura Y, Tilly JC, Tilly JL. Setting the record straight on data supporting postnatal oogenesis in female mammals. Cell Cycle. 2005;4(11):1471–7.CrossRef Johnson J, Skaznik-Wikiel M, Lee HJ, Niikura Y, Tilly JC, Tilly JL. Setting the record straight on data supporting postnatal oogenesis in female mammals. Cell Cycle. 2005;4(11):1471–7.CrossRef
44.
go back to reference White YA, Woods DC, Takai Y, Ishihara O, Seki H, Tilly JL. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med. 2012;18(3):413–21.CrossRef White YA, Woods DC, Takai Y, Ishihara O, Seki H, Tilly JL. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med. 2012;18(3):413–21.CrossRef
45.
go back to reference Horan CJ, Williams SA. Oocyte stem cells: fact or fantasy? Reproduction. 2017;154(1):R23–35.CrossRef Horan CJ, Williams SA. Oocyte stem cells: fact or fantasy? Reproduction. 2017;154(1):R23–35.CrossRef
46.
go back to reference Kalich-Philosoph L, Roness H, Carmely A, Fishel-Bartal M, Ligumsky H, Paglin S, et al. Cyclophosphamide triggers follicle activation and “burnout”; AS101 prevents follicle loss and preserves fertility. Sci Transl Med. 2013;5(185):185ra62.CrossRef Kalich-Philosoph L, Roness H, Carmely A, Fishel-Bartal M, Ligumsky H, Paglin S, et al. Cyclophosphamide triggers follicle activation and “burnout”; AS101 prevents follicle loss and preserves fertility. Sci Transl Med. 2013;5(185):185ra62.CrossRef
47.
go back to reference Wang J, Chen L, Li P, Li X, Zhou H, Wang F, et al. Gene expression is altered in piglet small intestine by weaning and dietary glutamine supplementation. J Nutr. 2008;138(6):1025–32.CrossRef Wang J, Chen L, Li P, Li X, Zhou H, Wang F, et al. Gene expression is altered in piglet small intestine by weaning and dietary glutamine supplementation. J Nutr. 2008;138(6):1025–32.CrossRef
Metadata
Title
Impact of uteroplacental insufficiency on ovarian follicular pool in the rat
Authors
Valentina Pampanini
Kirsi Jahnukainen
Lena Sahlin
Daniela Germani
Antonella Puglianiello
Stefano Cianfarani
Olle Söder
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2019
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-019-0453-3

Other articles of this Issue 1/2019

Reproductive Biology and Endocrinology 1/2019 Go to the issue