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Clinical Reviews in Allergy & Immunology

Published in:

15-01-2022 | Fertility

Role of Inflammaging on the Reproductive Function and Pregnancy

Authors: Alice Zavatta, Francesca Parisi, Chiara Mandò, Chiara Scaccabarozzi, Valeria M. Savasi, Irene Cetin

Published in: Clinical Reviews in Allergy & Immunology | Issue 2/2023

Abstract

During female lifetime and pregnancy, inflammation and cellular senescence are implicated in physiological processes, from ovulation and menstruation, to placental homeostasis and delivery. Several lifestyles, nutritional, and environmental insults, as well as long-lasting pregestational inflammatory diseases may lead to detrimental effects in promoting and sustaining a chronic excessive inflammatory response and inflammaging, which finally contribute to the decay of fertility and pregnancy outcome, with a negative effect on placental function, fetal development, and future health risk profile in the offspring. Maladaptation to pregnancy and obstetric disease may in turn increase maternal inflammaging in a feedback loop, speeding up aging processes and outbreak of chronic diseases. Maternal inflammaging may also impact, through transgenerational effects, on future adult health. Hence, efficacious interventions should be implemented by physicians and healthcare professionals involved in prevention activities to reduce the modifiable factors contributing to the inflammaging process in order to improve public health.

Franceschi C, Bonafè M, Valensin S et al (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254. https://doi.org/10.1111/j.1749-6632.2000.tb06651.xCrossRefPubMed

Huang Y, Hu C, Ye H et al (2019) Inflamm-aging: a new mechanism affecting premature ovarian insufficiency. J Immunol Res 2019:8069898. https://doi.org/10.1155/2019/8069898CrossRefPubMedPubMedCentral

Weiss G, Goldsmith LT, Taylor RN et al (2009) Inflammation in reproductive disorders. Reprod Sci 16:216–229. https://doi.org/10.1177/1933719108330087CrossRefPubMed

Shirasuna K, Iwata H (2017) Effect of aging on the female reproductive function. Contracept Reprod Med 2:23. https://doi.org/10.1186/s40834-017-0050-9CrossRefPubMedPubMedCentral

Storer M, Mas A, Robert-Moreno A et al (2013) Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell 155:1119–1130. https://doi.org/10.1016/j.cell.2013.10.041CrossRefPubMed

Manna S, McCarthy C, McCarthy FP (2019) Placental ageing in adverse pregnancy outcomes: telomere shortening, cell senescence, and mitochondrial dysfunction. Oxid Med Cell Longev 2019:3095383. https://doi.org/10.1155/2019/3095383CrossRefPubMedPubMedCentral

Pantham P, Aye ILMH, Powell TL (2015) Inflammation in maternal obesity and gestational diabetes mellitus. Placenta 36:709–715. https://doi.org/10.1016/j.placenta.2015.04.006CrossRefPubMedPubMedCentral

Ingvorsen C, Brix S, Ozanne SE et al (2015) The effect of maternal Inflammation on foetal programming of metabolic disease. Acta Physiol (Oxf) 214:440–449. https://doi.org/10.1111/apha.12533CrossRefPubMed

Segovia SA, Vickers MH, Gray C et al (2014) Maternal obesity, inflammation, and developmental programming. Biomed Res Int 2014:418975. https://doi.org/10.1155/2014/418975CrossRefPubMedPubMedCentral

10.

Larbi A, Franceschi C, Mazzatti D et al (2008) Aging of the immune system as a prognostic factor for human longevity. Physiology (Bethesda) 23:64–74. https://doi.org/10.1152/physiol.00040.2007CrossRefPubMed

11.

Parisi F, Milazzo R, Savasi VM et al (2021) Maternal low-grade chronic inflammation and intrauterine programming of health and disease. Int J Mol Sci 22. https://doi.org/10.3390/ijms22041732

12.

Gregor MF, Hotamisligil GS (2011) Inflammatory mechanisms in obesity. Annu Rev Immunol 29:415–445. https://doi.org/10.1146/annurev-immunol-031210-101322CrossRefPubMed

13.

Weisberg SP, McCann D, Desai M et al (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808. https://doi.org/10.1172/JCI19246CrossRefPubMedPubMedCentral

14.

Chawla A, Nguyen KD, Goh YPS (2011) Macrophage-mediated inflammation in metabolic disease. Nat Rev Immunol 11:738–749. https://doi.org/10.1038/nri3071CrossRefPubMedPubMedCentral

15.

Cani PD, Amar J, Iglesias MA et al (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56:1761–1772. https://doi.org/10.2337/db06-1491CrossRefPubMed

16.

Raetz CRH, Whitfield C (2002) Lipopolysaccharide endotoxins. Annu Rev Biochem 71:635–700. https://doi.org/10.1146/annurev.biochem.71.110601.135414CrossRefPubMed

17.

Lee JY, Sohn KH, Rhee SH et al (2001) Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J Biol Chem 276:16683–16689. https://doi.org/10.1074/jbc.M011695200CrossRefPubMed

18.

Bailey MA, Holscher HD (2018) Microbiome-mediated effects of the mediterranean diet on inflammation. Adv Nutr 9:193–206. https://doi.org/10.1093/advances/nmy013CrossRefPubMedPubMedCentral

19.

Franzago M, Fraticelli F, Stuppia L et al (2019) Nutrigenetics, epigenetics and gestational diabetes: consequences in mother and child. Epigenetics 14:215–235. https://doi.org/10.1080/15592294.2019.1582277CrossRefPubMedPubMedCentral

20.

Cetin I, Mandò C, Calabrese S (2013) Maternal predictors of intrauterine growth restriction. Curr Opin Clin Nutr Metab Care 16:310–319. https://doi.org/10.1097/MCO.0b013e32835e8d9cCrossRefPubMed

21.

Doherty SP, Grabowski J, Hoffman C et al (2009) Early life insult from cigarette smoke may be predictive of chronic diseases later in life. Biomarkers 14(Suppl 1):97–101. https://doi.org/10.1080/13547500902965898CrossRefPubMed

22.

World Health Organization (‎2012)‎ Possible developmental early effects of endocrine disrupters on child health. World Health Organization. https://apps.who.int/iris/handle/10665/75342

23.

Alavian-Ghavanini A, Rüegg J (2018) Understanding epigenetic effects of endocrine disrupting chemicals: from mechanisms to novel test methods. Basic Clin Pharmacol Toxicol 122:38–45. https://doi.org/10.1111/bcpt.12878CrossRefPubMed

24.

Hu J, Ly J, Zhang W et al (2019) Microbiota of newborn meconium is associated with maternal anxiety experienced during pregnancy. Dev Psychobiol 61:640–649. https://doi.org/10.1002/dev.21837CrossRefPubMedPubMedCentral

25.

Bolten MI, Wurmser H, Buske-Kirschbaum A et al (2011) Cortisol levels in pregnancy as a psychobiological predictor for birth weight. Arch Womens Ment Health 14:33–41. https://doi.org/10.1007/s00737-010-0183-1CrossRefPubMed

26.

Xu K, Wei Y, Giunta S et al (2021) Do inflammaging and coagul-aging play a role as conditions contributing to the co-occurrence of the severe hyper-inflammatory state and deadly coagulopathy during COVID-19 in older people? Exp Gerontol 151:111423. https://doi.org/10.1016/j.exger.2021.111423CrossRefPubMedPubMedCentral

27.

Baltacıoğlu E, Kehribar MA, Yuva P et al (2014) Total oxidant status and bone resorption biomarkers in serum and gingival crevicular fluid of patients with periodontitis. J Periodontol 85:317–326. https://doi.org/10.1902/jop.2013.130012CrossRefPubMed

28.

Zambon M, Mandò C, Lissoni A et al (2018) Inflammatory and oxidative responses in pregnancies with obesity and periodontal disease. Reprod Sci 25:1474–1484. https://doi.org/10.1177/1933719117749758CrossRefPubMed

29.

Franceschi C, Garagnani P, Parini P et al (2018) Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol 14:576–590. https://doi.org/10.1038/s41574-018-0059-4CrossRefPubMed

30.

Mor G, Cardenas I, Abrahams V et al (2011) Inflammation and pregnancy: the role of the immune system at the implantation site. Ann N Y Acad Sci 1221:80–87. https://doi.org/10.1111/j.1749-6632.2010.05938.xCrossRefPubMedPubMedCentral

31.

Gomez CR, Boehmer ED, Kovacs EJ (2005) The aging innate immune system. Curr Opin Immunol 17:457–462. https://doi.org/10.1016/j.coi.2005.07.013CrossRefPubMed

32.

Castle SC (2000) Clinical relevance of age-related immune dysfunction. Clin Infect Dis 31:578–585. https://doi.org/10.1086/313947CrossRefPubMed

33.

Gavazzi G, Krause K-H (2002) Ageing and infection. Lancet Infect Dis 2:659–666. https://doi.org/10.1016/s1473-3099(02)00437-1CrossRefPubMed

34.

Bjornsson HT, Sigurdsson MI, Fallin MD et al (2008) Intra-individual change over time in DNA methylation with familial clustering. JAMA 299:2877–2883. https://doi.org/10.1001/jama.299.24.2877CrossRefPubMedPubMedCentral

35.

Phillippe M (2015) Cell-Free Fetal DNA, Telomeres, and the spontaneous onset of parturition. Reprod Sci 22:1186–1201. https://doi.org/10.1177/1933719115592714CrossRefPubMed

36.

Wang Y, Wang X, Flores ER et al (2016) Dysfunctional telomeres induce p53-dependent and independent apoptosis to compromise cellular proliferation and inhibit tumor formation. Aging Cell 15:646–660. https://doi.org/10.1111/acel.12476CrossRefPubMedPubMedCentral

37.

Chen J-H, Hales CN, Ozanne SE (2007) DNA damage, cellular senescence and organismal ageing: causal or correlative? Nucleic Acids Res 35:7417–7428. https://doi.org/10.1093/nar/gkm681CrossRefPubMedPubMedCentral

38.

Hemann MT, Strong MA, Hao L-Y et al (2001) The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell 107:67–77. https://doi.org/10.1016/s0092-8674(01)00504-9CrossRefPubMed

39.

Zhang J, Rane G, Dai X et al (2016) Ageing and the telomere connection: an intimate relationship with inflammation. Ageing Res Rev 25:55–69. https://doi.org/10.1016/j.arr.2015.11.006CrossRefPubMed

40.

Coppé J-P, Patil CK, Rodier F et al (2008) Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 6:2853–2868. https://doi.org/10.1371/journal.pbio.0060301CrossRefPubMed

41.

Kirkland JL, Tchkonia T (2017) Cellular senescence: a translational perspective. EBioMedicine 21:21–28. https://doi.org/10.1016/j.ebiom.2017.04.013CrossRefPubMed

42.

Lee HW, Blasco MA, Gottlieb GJ et al (1998) Essential role of mouse telomerase in highly proliferative organs. Nature 392:569–574. https://doi.org/10.1038/33345CrossRefPubMed

43.

Liu L, Franco S, Spyropoulos B et al (2004) Irregular telomeres impair meiotic synapsis and recombination in mice. Proc Natl Acad Sci U S A 101:6496–6501. https://doi.org/10.1073/pnas.0400755101CrossRefPubMedPubMedCentral

44.

Butts S, Riethman H, Ratcliffe S et al (2009) Correlation of telomere length and telomerase activity with occult ovarian insufficiency. J Clin Endocrinol Metab 94:4835–4843. https://doi.org/10.1210/jc.2008-2269CrossRefPubMedPubMedCentral

45.

Cheng E-H, Chen S-U, Lee T-H et al (2013) Evaluation of telomere length in cumulus cells as a potential biomarker of oocyte and embryo quality. Hum Reprod 28:929–936. https://doi.org/10.1093/humrep/det004CrossRefPubMed

46.

Broekmans FJ, Soules MR, Fauser BC (2009) Ovarian aging: mechanisms and clinical consequences. Endocr Rev 30:465–493. https://doi.org/10.1210/er.2009-0006CrossRefPubMed

47.

Lliberos C, Liew SH, Zareie P et al (2021) Evaluation of inflammation and follicle depletion during ovarian ageing in mice. Sci Rep 11:278. https://doi.org/10.1038/s41598-020-79488-4CrossRefPubMedPubMedCentral

48.

Zhang Z, Schlamp F, Huang L et al (2020) Inflammaging is associated with shifted macrophage ontogeny and polarization in the aging mouse ovary. Reproduction 159:325–337. https://doi.org/10.1530/REP-19-0330CrossRefPubMedPubMedCentral

49.

Briley SM, Jasti S, McCracken JM et al (2016) Reproductive age-associated fibrosis in the stroma of the mammalian ovary. Reproduction 152:245–260. https://doi.org/10.1530/REP-16-0129CrossRefPubMedPubMedCentral

50.

Tanikawa N, Ohtsu A, Kawahara-Miki R et al (2017) Age-associated mRNA expression changes in bovine endometrial cells in vitro. Reprod Biol Endocrinol 15:63. https://doi.org/10.1186/s12958-017-0284-zCrossRefPubMedPubMedCentral

51.

Burnum KE, Hirota Y, Baker ES et al (2012) Uterine deletion of Trp53 compromises antioxidant responses in the mouse decidua. Endocrinology 153:4568–4579. https://doi.org/10.1210/en.2012-1335CrossRefPubMedPubMedCentral

52.

Fortin CS, Leader A, Mahutte N et al (2019) Gene expression analysis of follicular cells revealed inflammation as a potential IVF failure cause. J Assist Reprod Genet 36:1195–1210. https://doi.org/10.1007/s10815-019-01447-4CrossRefPubMedPubMedCentral

53.

Brouillet S, Boursier G, Anav M et al (2020) C-reactive protein and ART outcomes: a systematic review. Hum Reprod Update 26:753–773. https://doi.org/10.1093/humupd/dmaa012CrossRefPubMed

54.

Burnik Papler T, Vrtačnik Bokal E, Maver A et al (2015) Specific gene expression differences in cumulus cells as potential biomarkers of pregnancy. Reprod Biomed Online 30:426–433. https://doi.org/10.1016/j.rbmo.2014.12.011CrossRefPubMed

55.

Hamel M, Dufort I, Robert C et al (2008) Identification of differentially expressed markers in human follicular cells associated with competent oocytes. Hum Reprod 23:1118–1127. https://doi.org/10.1093/humrep/den048CrossRefPubMed

56.

Hamel M, Dufort I, Robert C et al (2010) Identification of follicular marker genes as pregnancy predictors for human IVF: new evidence for the involvement of luteinization process. Mol Hum Reprod 16:548–556. https://doi.org/10.1093/molehr/gaq051CrossRefPubMed

57.

Gebhardt KM, Feil DK, Dunning KR et al (2011) Human cumulus cell gene expression as a biomarker of pregnancy outcome after single embryo transfer. Fertil Steril 96:47-52.e2. https://doi.org/10.1016/j.fertnstert.2011.04.033CrossRefPubMed

58.

Azkargorta M, Escobes I, Iloro I et al (2018) Differential proteomic analysis of endometrial fluid suggests increased inflammation and impaired glucose metabolism in non-implantative IVF cycles and pinpoints PYGB as a putative implantation marker. Hum Reprod 33:1898–1906. https://doi.org/10.1093/humrep/dey274CrossRefPubMed

59.

Palumbo A, Ávila J, Naftolin F (2016) The ovarian renin-angiotensin system (OVRAS): a major factor in ovarian function and disease. Reprod Sci 23:1644–1655. https://doi.org/10.1177/1933719116672588CrossRefPubMed

60.

Vloeberghs V, Peeraer K, Pexsters A et al (2009) Ovarian hyperstimulation syndrome and complications of ART. Best Pract Res Clin Obstet Gynaecol 23:691–709. https://doi.org/10.1016/j.bpobgyn.2009.02.006CrossRefPubMed

61.

Sahin A, Engin-Ustun Y, Tokmak A et al (2018) Serum levels of transforming growth factor β1 and C-reactive protein as possible markers of intra uterine insemination outcome. Eur Cytokine Netw 29:121–126. https://doi.org/10.1684/ecn.2018.0418CrossRefPubMed

62.

Robinson S, Pemberton P, Laing I et al (2008) Low grade inflammation, as evidenced by basal high sensitivity CRP, is not correlated to outcome measures in IVF. J Assist Reprod Genet 25:383–388. https://doi.org/10.1007/s10815-008-9253-yCrossRefPubMedPubMedCentral

63.

Almagor M, Hazav A, Yaffe H (2004) The levels of C-reactive protein in women treated by IVF. Hum Reprod 19:104–106. https://doi.org/10.1093/humrep/deh036CrossRefPubMed

64.

Sacks GP, Trew G, Lavery S (2004) C-reactive protein in women treated by IVF. Hum Reprod 19:1677; author reply 1677-8. https://doi.org/10.1093/humrep/deh242

65.

Wunder DM, Kretschmer R, Bersinger NA (2005) Concentrations of leptin and C-reactive protein in serum and follicular fluid during assisted reproductive cycles. Hum Reprod 20:1266–1271. https://doi.org/10.1093/humrep/deh767CrossRefPubMed

66.

Yildizfer F, Donma O, Yen M et al (2015) In vitro fertilization, levels of pro-inflammatory factors and lipid peroxidation. Int J Fertil Steril 9:277–284. https://doi.org/10.22074/ijfs.2015.4541

67.

Buyuk E, Asemota OA, Merhi Z et al (2017) Serum and follicular fluid monocyte chemotactic protein-1 levels are elevated in obese women and are associated with poorer clinical pregnancy rate after in vitro fertilization: a pilot study. Fertil Steril 107:632-640.e3. https://doi.org/10.1016/j.fertnstert.2016.12.023CrossRefPubMed

68.

Thiele K, Diao L, Arck PC (2018) Immunometabolism, pregnancy, and nutrition. Semin Immunopathol 40:157–174. https://doi.org/10.1007/s00281-017-0660-yCrossRefPubMed

69.

Romero R, Gotsch F, Pineles B et al (2007) Inflammation in pregnancy: its roles in reproductive physiology, obstetrical complications, and fetal injury. Nutr Rev 65:S194-202. https://doi.org/10.1111/j.1753-4887.2007.tb00362.xCrossRefPubMed

70.

Diceglie C, Anelli GM, Martelli C et al (2021) Placental antioxidant defenses and autophagy-related genes in maternal obesity and gestational diabetes mellitus. Nutrients 13. https://doi.org/10.3390/nu13041303

71.

Mandò C, Anelli GM, Novielli C et al (2018) Impact of obesity and hyperglycemia on placental mitochondria. Oxid Med Cell Longev 2018:2378189. https://doi.org/10.1155/2018/2378189CrossRefPubMedPubMedCentral

72.

Mandò C, de Palma C, Stampalija T et al (2014) Placental mitochondrial content and function in intrauterine growth restriction and preeclampsia. Am J Physiol Endocrinol Metab 306:E404-13. https://doi.org/10.1152/ajpendo.00426.2013CrossRefPubMed

73.

Menon R (2014) Oxidative stress damage as a detrimental factor in preterm birth pathology. Front Immunol 5:567. https://doi.org/10.3389/fimmu.2014.00567CrossRefPubMedPubMedCentral

74.

Bianchi C, Taricco E, Cardellicchio M et al (2021) The role of obesity and gestational diabetes on placental size and fetal oxygenation. Placenta 103:59–63. https://doi.org/10.1016/j.placenta.2020.10.013CrossRefPubMed

75.

Mandò C, Calabrese S, Mazzocco MI et al (2016) Sex specific adaptations in placental biometry of overweight and obese women. Placenta 38:1–7. https://doi.org/10.1016/j.placenta.2015.12.008CrossRefPubMed

76.

Fattuoni C, Mandò C, Palmas F et al (2018) Preliminary metabolomics analysis of placenta in maternal obesity. Placenta 61:89–95. https://doi.org/10.1016/j.placenta.2017.11.014CrossRefPubMed

77.

Robker RL, Wu LL-Y, Yang X (2011) Inflammatory pathways linking obesity and ovarian dysfunction. J Reprod Immunol 88:142–148. https://doi.org/10.1016/j.jri.2011.01.008CrossRefPubMed

78.

Abrahams VM (2010) Thirty years of reproductive immunology: an introduction. Am J Reprod Immunol 63:411–412. https://doi.org/10.1111/j.1600-0897.2010.00849.xCrossRefPubMed

79.

Nadeau-Vallée M, Obari D, Palacios J et al (2016) Sterile inflammation and pregnancy complications: a review. Reproduction 152:R277–R292. https://doi.org/10.1530/REP-16-0453CrossRefPubMed

80.

Menon R, Behnia F, Polettini J et al (2016) Placental membrane aging and HMGB1 signaling associated with human parturition. Aging (Albany NY) 8:216–230. https://doi.org/10.18632/aging.100891

81.

Hirata Y, Katsukura Y, Henmi Y et al (2021) Advanced maternal age induces fetal growth restriction through decreased placental inflammatory cytokine expression and immune cell accumulation in mice. J Reprod Dev. https://doi.org/10.1262/jrd.2021-034CrossRefPubMedPubMedCentral

82.

Cetin I, Taricco E, Mandò C et al (2020) Fetal oxygen and glucose consumption in human pregnancy complicated by fetal growth restriction. Hypertension 75:748–754. https://doi.org/10.1161/HYPERTENSIONAHA.119.13727CrossRefPubMed

83.

Laird SM, Tuckerman EM, Cork BA et al (2003) A review of immune cells and molecules in women with recurrent miscarriage. Hum Reprod Update 9:163–174. https://doi.org/10.1093/humupd/dmg013CrossRefPubMed

84.

Lucas ES, Vrljicak P, Muter J et al (2020) Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window. Commun Biol 3:37. https://doi.org/10.1038/s42003-020-0763-1CrossRefPubMedPubMedCentral

85.

Redman CWG, Sargent IL (2010) Immunology of pre-eclampsia. Am J Reprod Immunol 63:534–543. https://doi.org/10.1111/j.1600-0897.2010.00831.xCrossRefPubMed

86.

Cox LS, Redman C (2017) The role of cellular senescence in ageing of the placenta. Placenta 52:139–145. https://doi.org/10.1016/j.placenta.2017.01.116CrossRefPubMed

87.

Menon R, Boldogh I, Hawkins HK et al (2014) Histological evidence of oxidative stress and premature senescence in preterm premature rupture of the human fetal membranes recapitulated in vitro. Am J Pathol 184:1740–1751. https://doi.org/10.1016/j.ajpath.2014.02.011CrossRefPubMed

88.

Dutta EH, Behnia F, Boldogh I et al (2016) Oxidative stress damage-associated molecular signaling pathways differentiate spontaneous preterm birth and preterm premature rupture of the membranes. Mol Hum Reprod 22:143–157. https://doi.org/10.1093/molehr/gav074CrossRefPubMed

89.

Sultana Z, Maiti K, Aitken J et al (2017) Oxidative stress, placental ageing-related pathologies and adverse pregnancy outcomes. Am J Reprod Immunol 77. https://doi.org/10.1111/aji.12653

90.

Negishi Y, Shima Y, Takeshita T et al (2021) Harmful and beneficial effects of inflammatory response on reproduction: sterile and pathogen-associated inflammation. Immunol Med 44:98–115. https://doi.org/10.1080/25785826.2020.1809951CrossRefPubMed

91.

Zenclussen AC, Kortebani G, Mazzolli A et al (2000) Interleukin-6 and soluble interleukin-6 receptor serum levels in recurrent spontaneous abortion women immunized with paternal white cells. Am J Reprod Immunol 44:22–29. https://doi.org/10.1111/j.8755-8920.2000.440104.xCrossRefPubMed

92.

Hattori Y, Nakanishi T, Ozaki Y et al (2007) Uterine cervical inflammatory cytokines, interleukin-6 and -8, as predictors of miscarriage in recurrent cases. Am J Reprod Immunol 58:350–357. https://doi.org/10.1111/j.1600-0897.2007.00516.xCrossRefPubMed

93.

Jianchun S, Dachun H, Jun C, Yundong L, Zhongmi W (2012) The correlation between unexplained recurrent spontaneous abortion and cytokine immune balance. Lab Med Clin 568–569

94.

Yan S, Lin S, Pei C, Jiaquan L, Jinchun Y (2012) The expression of interleukin-6 and interleukin-18 mRNA in villi of patients with recurrent spontaneous abortion. Guangdong Med J 33

95.

Zhang C, Deng X, Zhang X et al (2016) Association between Serum TNF-α levels and recurrent spontaneous miscarriage: a meta-analysis. Am J Reprod Immunol 75:86–93. https://doi.org/10.1111/aji.12447CrossRefPubMed

96.

Kwak-Kim JYH, Chung-Bang HS, Ng SC et al (2003) Increased T helper 1 cytokine responses by circulating T cells are present in women with recurrent pregnancy losses and in infertile women with multiple implantation failures after IVF. Hum Reprod 18:767–773. https://doi.org/10.1093/humrep/deg156CrossRefPubMed

97.

Huang N, Chi H, Qiao J (2020) Role of regulatory T cells in regulating fetal-maternal immune tolerance in healthy pregnancies and reproductive diseases. Front Immunol 11:1023. https://doi.org/10.3389/fimmu.2020.01023CrossRefPubMedPubMedCentral

98.

Menon R, Yu J, Basanta-Henry P et al (2012) Short fetal leukocyte telomere length and preterm prelabor rupture of the membranes. PLoS One 7:e31136. https://doi.org/10.1371/journal.pone.0031136CrossRefPubMedPubMedCentral

99.

Biron-Shental T, Sukenik Halevy R, Goldberg-Bittman L et al (2010) Telomeres are shorter in placental trophoblasts of pregnancies complicated with intrauterine growth restriction (IUGR). Early Hum Dev 86:451–456. https://doi.org/10.1016/j.earlhumdev.2010.06.002CrossRefPubMed

100.

Assi E, D'Addio F, Mandò C et al (2020) Placental proteome abnormalities in women with gestational diabetes and large-for-gestational-age newborns. BMJ Open Diabetes Res Care 8. https://doi.org/10.1136/bmjdrc-2020-001586

101.

Fenizia C, Biasin M, Cetin I et al (2020) Analysis of SARS-CoV-2 vertical transmission during pregnancy. Nat Commun 11:5128. https://doi.org/10.1038/s41467-020-18933-4CrossRefPubMedPubMedCentral

102.

Papageorghiou AT, Deruelle P, Gunier RB et al (2021) Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study. Am J Obstet Gynecol. https://doi.org/10.1016/j.ajog.2021.05.014CrossRefPubMedPubMedCentral

103.

Barker DJ (1998) In utero programming of chronic disease. Clin Sci (Lond) 95:115–128CrossRefPubMed

104.

Send TS, Gilles M, Codd V et al (2017) Telomere length in newborns is related to maternal stress during pregnancy. Neuropsychopharmacology 42:2407–2413. https://doi.org/10.1038/npp.2017.73CrossRefPubMedPubMedCentral

105.

Menon R, Mesiano S, Taylor RN (2017) Programmed fetal membrane senescence and exosome-mediated signaling: a mechanism associated with timing of human parturition. Front Endocrinol (Lausanne) 8:196. https://doi.org/10.3389/fendo.2017.00196CrossRefPubMed

106.

Whiteman VE, Goswami A, Salihu HM (2017) Telomere length and fetal programming: a review of recent scientific advances. Am J Reprod Immunol 77. https://doi.org/10.1111/aji.12661

107.

Louis-Jacques AF, Salihu HM, King LM et al (2016) A positive association between umbilical cord RBC folate and fetal TL at birth supports a potential for fetal reprogramming. Nutr Res 36:703–709. https://doi.org/10.1016/j.nutres.2016.01.009CrossRefPubMed

108.

May L (2015) Cardiac physiology of pregnancy. Compr Physiol 5:1325–1344. https://doi.org/10.1002/cphy.c140043CrossRefPubMed

109.

Mecacci F, Avagliano L, Lisi F et al (2020) Fetal growth restriction: does an integrated maternal hemodynamic-placental model fit better? Reprod Sci. https://doi.org/10.1007/s43032-020-00393-2CrossRefPubMed

110.

Sibai B, Dekker G, Kupferminc M (2005) Pre-eclampsia. The Lancet 365:785–799. https://doi.org/10.1016/S0140-6736(05)17987-2CrossRef

111.

Bird IM, Zhang L, Magness RR (2003) Possible mechanisms underlying pregnancy-induced changes in uterine artery endothelial function. Am J Physiol Regul Integr Comp Physiol 284:R245-58. https://doi.org/10.1152/ajpregu.00108.2002CrossRefPubMed

112.

Okada Y, Galbreath MM, Shibata S et al (2012) Relationship between sympathetic baroreflex sensitivity and arterial stiffness in elderly men and women. Hypertension 59:98–104. https://doi.org/10.1161/HYPERTENSIONAHA.111.176560CrossRefPubMed

113.

El Assar M, Angulo J, Rodríguez-Mañas L (2013) Oxidative stress and vascular inflammation in aging. Free Radic Biol Med 65:380–401. https://doi.org/10.1016/j.freeradbiomed.2013.07.003CrossRefPubMed

114.

Sattar N, Greer IA (2002) Pregnancy complications and maternal cardiovascular risk: opportunities for intervention and screening? BMJ 325:157–160. https://doi.org/10.1136/bmj.325.7356.157CrossRefPubMedPubMedCentral

115.

Galbarczyk A, Klimek M, Blukacz M et al (2021) Inflammaging: blame the sons. Relationships between the number of sons and the level of inflammatory mediators among post-reproductive women. Am J Phys Anthropol 175:656–664. https://doi.org/10.1002/ajpa.24295CrossRefPubMed

116.

Marttila S, Nevalainen T, Kananen L et al (2015) Number of sons contributes to ageing-associated inflammation. Sci Rep 5:8631. https://doi.org/10.1038/srep08631CrossRefPubMedPubMedCentral

117.

Piper KP, McLarnon A, Arrazi J et al (2007) Functional HY-specific CD8+ T cells are found in a high proportion of women following pregnancy with a male fetus. Biol Reprod 76:96–101. https://doi.org/10.1095/biolreprod.106.055426CrossRefPubMed

118.

Pollack AZ, Rivers K, Ahrens KA (2018) Parity associated with telomere length among US reproductive age women. Hum Reprod 33:736–744. https://doi.org/10.1093/humrep/dey024CrossRefPubMed

119.

Jasienska G (2009) Reproduction and lifespan: trade-offs, overall energy budgets, intergenerational costs, and costs neglected by research. Am J Hum Biol 21:524–532. https://doi.org/10.1002/ajhb.20931CrossRefPubMed

120.

Jasienska G (2020) Costs of reproduction and ageing in the human female. Philos Trans R Soc Lond B Biol Sci 375:20190615. https://doi.org/10.1098/rstb.2019.0615CrossRefPubMedPubMedCentral

121.

Lo YMD, Corbetta N, Chamberlain PF et al (1997) Presence of fetal DNA in maternal plasma and serum. The Lancet 350:485–487. https://doi.org/10.1016/S0140-6736(97)02174-0CrossRef

122.

Boddy AM, Fortunato A, Wilson Sayres M et al (2015) Fetal microchimerism and maternal health: a review and evolutionary analysis of cooperation and conflict beyond the womb. Bioessays 37:1106–1118. https://doi.org/10.1002/bies.201500059CrossRefPubMedPubMedCentral

123.

Lo YM, Tein MS, Lau TK et al (1998) Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 62:768–775. https://doi.org/10.1086/301800CrossRefPubMedPubMedCentral

124.

Scharfe-Nugent A, Corr SC, Carpenter SB et al (2012) TLR9 provokes inflammation in response to fetal DNA: mechanism for fetal loss in preterm birth and preeclampsia. J Immunol 188:5706–5712. https://doi.org/10.4049/jimmunol.1103454CrossRefPubMed

125.

Barber GN (2015) STING: infection, inflammation and cancer. Nat Rev Immunol 15:760–770. https://doi.org/10.1038/nri3921CrossRefPubMedPubMedCentral

126.

Cheng S-B, Davis S, Sharma S (2018) Maternal-fetal cross talk through cell-free fetal DNA, telomere shortening, microchimerism, and inflammation. Am J Reprod Immunol 79:e12851. https://doi.org/10.1111/aji.12851CrossRefPubMedPubMedCentral

127.

Fjeldstad HE, Johnsen GM, Staff AC (2020) Fetal microchimerism and implications for maternal health. Obstet Med 13:112–119. https://doi.org/10.1177/1753495X19884484CrossRefPubMed

128.

Sharpless NE, DePinho RA (2007) How stem cells age and why this makes us grow old. Nat Rev Mol Cell Biol 8:703–713. https://doi.org/10.1038/nrm2241CrossRefPubMed

129.

Adams Waldorf KM, Nelson JL (2008) Autoimmune disease during pregnancy and the microchimerism legacy of pregnancy. Immunol Invest 37:631–644. https://doi.org/10.1080/08820130802205886CrossRefPubMedPubMedCentral

130.

Chan WFN, Gurnot C, Montine TJ et al (2012) Male microchimerism in the human female brain. PLoS One 7:e45592. https://doi.org/10.1371/journal.pone.0045592CrossRefPubMedPubMedCentral

131.

Zeng XX, Tan KH, Yeo A et al (2010) Pregnancy-associated progenitor cells differentiate and mature into neurons in the maternal brain. Stem Cells Dev 19:1819–1830. https://doi.org/10.1089/scd.2010.0046CrossRefPubMed

132.

Barrett PM, McCarthy FP, Kublickiene K et al (2020) Adverse pregnancy outcomes and long-term maternal kidney disease: a systematic review and meta-analysis. JAMA Netw Open 3:e1920964. https://doi.org/10.1001/jamanetworkopen.2019.20964CrossRefPubMed

133.

Parikh NI, Gonzalez JM, Anderson CAM et al (2021) Adverse pregnancy outcomes and cardiovascular disease risk: unique opportunities for cardiovascular disease prevention in women: a scientific statement from the American Heart Association. Circulation 143:e902–e916. https://doi.org/10.1161/CIR.0000000000000961CrossRefPubMed

134.

Stang J, Huffman LG (2016) Position of the academy of nutrition and dietetics: obesity, reproduction, and pregnancy outcomes. J Acad Nutr Diet 116:677–691. https://doi.org/10.1016/j.jand.2016.01.008CrossRefPubMed

135.

Espinós JJ, Polo A, Sánchez-Hernández J et al (2017) Weight decrease improves live birth rates in obese women undergoing IVF: a pilot study. Reprod Biomed Online 35:417–424. https://doi.org/10.1016/j.rbmo.2017.06.019CrossRefPubMed

136.

Sim KA, Partridge SR, Sainsbury A (2014) Does weight loss in overweight or obese women improve fertility treatment outcomes? A systematic review. Obes Rev 15:839–850. https://doi.org/10.1111/obr.12217CrossRefPubMed

137.

Palomba S, Falbo A, Valli B et al (2014) Physical activity before IVF and ICSI cycles in infertile obese women: an observational cohort study. Reprod Biomed Online 29:72–79. https://doi.org/10.1016/j.rbmo.2014.03.006CrossRefPubMed

138.

Colbert LH, Visser M, Simonsick EM et al (2004) Physical activity, exercise, and inflammatory markers in older adults: findings from the Health, Aging and Body Composition Study. J Am Geriatr Soc 52:1098–1104. https://doi.org/10.1111/j.1532-5415.2004.52307.xCrossRefPubMed

139.

Coussons-Read ME, Okun ML, Nettles CD (2007) Psychosocial stress increases inflammatory markers and alters cytokine production across pregnancy. Brain Behav Immun 21:343–350. https://doi.org/10.1016/j.bbi.2006.08.006CrossRefPubMed

140.

Martucci M, Ostan R, Biondi F et al (2017) Mediterranean diet and inflammaging within the hormesis paradigm. Nutr Rev 75:442–455. https://doi.org/10.1093/nutrit/nux013CrossRefPubMedPubMedCentral

141.

Parisi F, Rousian M, Huijgen NA et al (2017) Periconceptional maternal “high fish and olive oil, low meat” dietary pattern is associated with increased embryonic growth: The Rotterdam Periconceptional Cohort (Predict) Study. Ultrasound Obstet Gynecol 50:709–716. https://doi.org/10.1002/uog.17408CrossRefPubMed

142.

Vujkovic M, de Vries JH, Lindemans J et al (2010) The preconception Mediterranean dietary pattern in couples undergoing in vitro fertilization/intracytoplasmic sperm injection treatment increases the chance of pregnancy. Fertil Steril 94:2096–2101. https://doi.org/10.1016/j.fertnstert.2009.12.079CrossRefPubMed

143.

Twigt JM, Bolhuis MEC, Steegers EAP et al (2012) The preconception diet is associated with the chance of ongoing pregnancy in women undergoing IVF/ICSI treatment. Hum Reprod 27:2526–2531. https://doi.org/10.1093/humrep/des157CrossRefPubMed

144.

Thompson JMD, Wall C, Becroft DMO et al (2010) Maternal dietary patterns in pregnancy and the association with small-for-gestational-age infants. Br J Nutr 103:1665–1673. https://doi.org/10.1017/S0007114509993606CrossRefPubMed

145.

Amati F, Hassounah S, Swaka A (2019) The impact of Mediterranean dietary patterns during pregnancy on maternal and offspring health. Nutrients 11. https://doi.org/10.3390/nu11051098

146.

Mikkelsen TB, Osterdal ML, Knudsen VK et al (2008) Association between a Mediterranean-type diet and risk of preterm birth among Danish women: a prospective cohort study. Acta Obstet Gynecol Scand 87:325–330. https://doi.org/10.1080/00016340801899347CrossRefPubMed

147.

Mocchegiani E, Costarelli L, Giacconi R et al (2014) Micronutrient-gene interactions related to inflammatory/immune response and antioxidant activity in ageing and inflammation. A systematic review. Mech Ageing Dev 136–137:29–49. https://doi.org/10.1016/j.mad.2013.12.007CrossRefPubMed

148.

Berti C, Agostoni C, Davanzo R et al (2017) Early-life nutritional exposures and lifelong health: immediate and long-lasting impacts of probiotics, vitamin D, and breastfeeding. Nutr Rev 75:83–97. https://doi.org/10.1093/nutrit/nuw056CrossRefPubMed

149.

Parisi F, Savasi VM, di Bartolo I et al (2020) Associations between first trimester maternal nutritional score, early markers of placental function, and pregnancy outcome. Nutrients 12. https://doi.org/10.3390/nu12061799

150.

Abbasi A, Aghebati-Maleki A, Yousefi M et al (2021) Probiotic intervention as a potential therapeutic for managing gestational disorders and improving pregnancy outcomes. J Reprod Immunol 143:103244. https://doi.org/10.1016/j.jri.2020.103244CrossRefPubMed

151.

Barbonetti A, Cinque B, Vassallo MRC et al (2011) Effect of vaginal probiotic lactobacilli on in vitro-induced sperm lipid peroxidation and its impact on sperm motility and viability. Fertil Steril 95:2485–2488. https://doi.org/10.1016/j.fertnstert.2011.03.066CrossRefPubMed

152.

Dawe JP, McCowan LME, Wilson J et al (2020) Probiotics and maternal mental health: a randomised controlled trial among pregnant women with obesity. Sci Rep 10:1291. https://doi.org/10.1038/s41598-020-58129-wCrossRefPubMedPubMedCentral

153.

Swartwout B, Luo XM (2018) Implications of probiotics on the maternal-neonatal interface: gut microbiota, immunomodulation, and autoimmunity. Front Immunol 9:2840. https://doi.org/10.3389/fimmu.2018.02840CrossRefPubMedPubMedCentral

154.

Barthow C, Wickens K, Stanley T et al (2016) The Probiotics in Pregnancy Study (PiP Study): rationale and design of a double-blind randomised controlled trial to improve maternal health during pregnancy and prevent infant eczema and allergy. BMC Pregnancy Childbirth 16:133. https://doi.org/10.1186/s12884-016-0923-yCrossRefPubMedPubMedCentral

Title: Role of Inflammaging on the Reproductive Function and Pregnancy
Authors: Alice Zavatta
Francesca Parisi
Chiara Mandò
Chiara Scaccabarozzi
Valeria M. Savasi
Irene Cetin
Publication date: 15-01-2022
Publisher: Springer US
Keyword: Fertility
Published in: Clinical Reviews in Allergy & Immunology / Issue 2/2023
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI: https://doi.org/10.1007/s12016-021-08907-9

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STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

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