{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T06:16:33Z","timestamp":1787897793604,"version":"build-2784847793"},"reference-count":129,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,3]],"date-time":"2024-03-03T00:00:00Z","timestamp":1709424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Pregnancy is generally studied as a biological interaction between a mother and a fetus; however, the father, with his characteristics, lifestyle, genetics, and living environment, is by no means unrelated to the outcome of pregnancy. The half of the fetal genetic heritage of paternal derivation can be decisive in cases of inherited chromosomal disorders, and can be the result of de novo genetic alterations. In addition to the strictly pathological aspects, paternal genetics may transmit thrombophilic traits that affect the implantation and vascular construction of the feto-placental unit, lead to placenta-mediated diseases such as pre-eclampsia and fetal growth retardation, and contribute to the multifactorial genesis of preterm delivery. Biological aspects of immunological tolerance to paternal antigens also appear to be crucial for these pathologies. Finally, this review describes the biological findings by which the environment, exposure to pathogens, lifestyle, and nutritional style of the father affect fetal pathophysiological and epigenetic definition.<\/jats:p>","DOI":"10.3390\/biology13030165","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T04:36:21Z","timestamp":1709526981000},"page":"165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["The \u201cBad Father\u201d: Paternal Role in Biology of Pregnancy and in Birth Outcome"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9427-1391","authenticated-orcid":false,"given":"Stefano Raffaele","family":"Giannubilo","sequence":"first","affiliation":[{"name":"Clinic of Obstetrics and Gynaecology, Department of Clinical Sciences, Universit\u00e0 Politecnica Delle Marche, 60123 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2267-0270","authenticated-orcid":false,"given":"Daniela","family":"Marzioni","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Universit\u00e0 Politecnica Delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7003-1230","authenticated-orcid":false,"given":"Giovanni","family":"Tossetta","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Universit\u00e0 Politecnica Delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona","family":"Montironi","sequence":"additional","affiliation":[{"name":"Clinic of Obstetrics and Gynaecology, Department of Clinical Sciences, Universit\u00e0 Politecnica Delle Marche, 60123 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1845-9986","authenticated-orcid":false,"given":"Maria Liberata","family":"Meccariello","sequence":"additional","affiliation":[{"name":"Clinic of Obstetrics and Gynaecology, Department of Clinical Sciences, Universit\u00e0 Politecnica Delle Marche, 60123 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ciavattini","sequence":"additional","affiliation":[{"name":"Clinic of Obstetrics and Gynaecology, Department of Clinical Sciences, Universit\u00e0 Politecnica Delle Marche, 60123 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1093\/humrep\/deab153","article-title":"Findings from a multicentre, observational study on reproductive outcomes in women with unexplained recurrent pregnancy loss: The OTTILIA registry","volume":"36","author":"Grandone","year":"2021","journal-title":"Hum. Reprod."},{"key":"ref_2","first-page":"447","article-title":"Male factor testing in recurrent pregnancy loss cases: A narrative review","volume":"20","author":"Pourmasumi","year":"2022","journal-title":"Int. J. Reprod. Biomed."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1038\/nature01722","article-title":"The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes","volume":"423","author":"Skaletsky","year":"2003","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1093\/humrep\/14.4.1039","article-title":"Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic","volume":"14","author":"Evenson","year":"1999","journal-title":"Hum. Reprod."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1046\/j.1471-0528.2003.01490.x","article-title":"Fetuses with Down\u2019s Syndrome detected by prenatal screening are more likely to abort spontaneously than fetuses with Down\u2019s Syndrome not detected by prenatal screening","volume":"110","author":"Leporrier","year":"2003","journal-title":"BJOG"},{"key":"ref_6","unstructured":"Dimock, K., Thiel, M., and Thiel, M. (1980). Genetics in Medicine, Saunders Company. [3rd ed.]."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.tjog.2022.02.006","article-title":"Prenatal diagnosis and genetic counseling of uniparental disomy","volume":"61","author":"Chien","year":"2022","journal-title":"Taiwan J. Obstet. Gynecol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0015-0282(99)00462-8","article-title":"Sperm chromatin damage impairs human fertility. The Danish First Pregnancy Planner Study Team","volume":"73","author":"Bonde","year":"2000","journal-title":"Fertil. Steril."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1093\/molehr\/7.12.1167","article-title":"HLA-G genotypes and pregnancy outcome in couples with unexplained recurrent miscarriage","volume":"7","author":"Aldrich","year":"2001","journal-title":"Mol. Hum. Reprod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.3109\/14767058.2015.1044431","article-title":"Thrombophilic genes alterations as risk factor for recurrent pregnancy loss","volume":"29","author":"Farahmand","year":"2016","journal-title":"J. Matern Fetal Neonatal Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1111\/j.1600-0412.2011.01293.x","article-title":"Inherited thrombophilias and adverse pregnancy outcomes: A case-control study in an Australian population","volume":"91","author":"Said","year":"2012","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.clinbiochem.2008.12.003","article-title":"Association of parental hyperhomocysteinemia and C677T Methylene tetrahydrofolate reductase (MTHFR) polymorphism with recurrent pregnancy loss","volume":"42","author":"Govindaiah","year":"2009","journal-title":"Clin. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1093\/humrep\/dei466","article-title":"Genetic thrombophilic mutations among couples with recurrent miscarriage","volume":"21","author":"Jivraj","year":"2006","journal-title":"Hum. Reprod."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/j.1600-0897.2008.00630.x","article-title":"Paternal thrombophilic gene mutations are not associated with recurrent miscarriage","volume":"60","author":"Toth","year":"2008","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1093\/humrep\/13.suppl_1.45","article-title":"Chromosome anomalies and Y chromosome microdeletions as causal factors in male infertility","volume":"13","author":"Chandley","year":"1998","journal-title":"Hum. Reprod."},{"key":"ref_16","first-page":"13","article-title":"Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring","volume":"19","author":"Sharma","year":"2015","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.fertnstert.2016.07.1101","article-title":"Seminal fluid and fertility in women","volume":"106","author":"Robertson","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1097\/MOP.0b013e328332c6ab","article-title":"Maternal age and chromosomally abnormal pregnancies: What we know and what we wish we knew","volume":"21","author":"Hassold","year":"2009","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"897101","DOI":"10.3389\/fendo.2022.897101","article-title":"Advanced Paternal Age and Future Generations","volume":"13","author":"Chan","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/978-3-030-21664-1_2","article-title":"Age-Dependent De Novo Mutations during Spermatogenesis and Their Consequences","volume":"1166","author":"Cioppi","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1111\/andr.13128","article-title":"A higher preconceptional paternal body mass index influences fertilization rate and preimplantation embryo development","volume":"10","author":"Hoek","year":"2022","journal-title":"Andrology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1136\/bmj.326.7387.476","article-title":"Risk of recurrence of prolonged pregnancy","volume":"326","author":"Olesen","year":"2003","journal-title":"BMJ"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/cmi.2014.46","article-title":"Immune cells in term and preterm labor","volume":"11","author":"StLouis","year":"2014","journal-title":"Cell. Mol. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/j.1471-0528.2000.tb13234.x","article-title":"Genetic influence on birthweight and gestational length determined by studies in offspring of twins","volume":"107","author":"Clausson","year":"2000","journal-title":"BJOG"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1097\/00001648-199903000-00011","article-title":"Changing paternity and the risk of preterm delivery in the subsequent pregnancy","volume":"10","author":"Li","year":"1999","journal-title":"Epidemiology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"100353","DOI":"10.1016\/j.ajogmf.2021.100353","article-title":"The association between maternal and paternal race and preterm birth","volume":"3","author":"Green","year":"2021","journal-title":"Am. J. Obstet. Gynecol. MFM"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/s41598-021-03427-0","article-title":"Protein interaction networks define the genetic architecture of preterm birth","volume":"12","author":"Uzun","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4562","DOI":"10.2174\/092986712803306466","article-title":"Anticoagulant therapy during pregnancy for maternal and fetal acquired and inherited thrombophilia","volume":"19","author":"Giannubilo","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ogc.2013.10.005","article-title":"Inherited thrombophilias and adverse pregnancy outcomes: A review of screening patterns and recommendations","volume":"41","author":"Davenport","year":"2014","journal-title":"Obstet. Gynecol. Clin. N. Am."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/S0002-9378(97)70205-9","article-title":"Fetal carriers of the factor V Leiden mutation are prone to miscarriage and placental infarction","volume":"177","author":"Meline","year":"1997","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1002\/ana.410420316","article-title":"Leiden mutation: An unrecognized cause of hemiplegic cerebral palsy, neonatal stroke, and placental thrombosis","volume":"42","author":"Thorarensen","year":"1997","journal-title":"Ann. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jri.2010.12.010","article-title":"The etiology of preeclampsia: The role of the father","volume":"89","author":"Dekker","year":"2011","journal-title":"J. Reprod. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1080\/08820130802206066","article-title":"Trophoblast immune receptors in maternal-fetal tolerance","volume":"37","author":"Riley","year":"2008","journal-title":"Immunol. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.fertnstert.2009.09.052","article-title":"Unexplained fetal loss: The fetal side of thrombophilia","volume":"94","author":"Tranquilli","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1111\/jth.12526","article-title":"Paternal factor V Leiden and recurrent pregnancy loss: A new concept behind fetal genetics?","volume":"12","author":"Udry","year":"2014","journal-title":"J. Thromb. Haemost."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/j.mehy.2006.04.046","article-title":"The thrombophilic fetus","volume":"67","author":"Tranquilli","year":"2006","journal-title":"Med. Hypotheses"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S102","DOI":"10.1016\/j.placenta.2004.01.010","article-title":"Fetal thrombotic vasculopathy in the placenta: A thrombophilic connection between pregnancy complications and neonatal thrombosis?","volume":"25","author":"Timmer","year":"2004","journal-title":"Placenta"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.braindev.2015.07.004","article-title":"Fetal hydrocephalus and neonatal stroke as the first presentation of protein C deficiency","volume":"38","author":"Ichiyama","year":"2016","journal-title":"Brain Dev."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"M\u00e9sz\u00e1ros, B., Kukor, Z., and Valent, S. (2023). Recent Advances in the Prevention and Screening of Preeclampsia. J. Clin. Med., 12.","DOI":"10.3390\/jcm12186020"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6091","DOI":"10.1002\/jcp.27344","article-title":"Pre-eclampsia onset and SPARC: A possible involvement in placenta development","volume":"234","author":"Tossetta","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_41","first-page":"2724","article-title":"High temperature requirement A1 and fibronectin: Two possible players in placental tissue remodelling","volume":"60","author":"Tossetta","year":"2016","journal-title":"Eur. J. Histochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1080\/14767050500361653","article-title":"Risk factors for preeclampsia in multiparous women: Primipaternity versus the birth interval hypothesis","volume":"19","author":"Deen","year":"2006","journal-title":"J. Matern Fetal Neonatal Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0165-0378(99)00040-6","article-title":"Change in paternity: A risk factor for preeclampsia in multiparous women?","volume":"45","author":"Tubbergen","year":"1999","journal-title":"J. Reprod. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1136\/bmj.316.7141.1343","article-title":"Fetal and maternal contributions to risk of pre-eclampsia: Population based study","volume":"316","author":"Lie","year":"1998","journal-title":"BMJ"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ancu\u021ba, E., Zamfir, R., Martinescu, G., Crauciuc, D.V., and Ancu\u021ba, C. (2021). The Complement System, T Cell Response, and Cytokine Shift in Normotensive versus Pre-Eclamptic and Lupus Pregnancy. J. Clin. Med., 10.","DOI":"10.3390\/jcm10245722"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Wyatt, M.A., Baumgarten, S.C., Weaver, A.L., Van Oort, C.C., Fedyshyn, B., Ruano, R., Shenoy, C.C., and Enninga, E.A.L. (2021). Evaluating Markers of Immune Tolerance and Angiogenesis in Maternal Blood for an Association with Risk of Pregnancy Loss. J. Clin. Med., 10.","DOI":"10.3390\/jcm10163579"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1034\/j.1600-0897.2002.1o043.x","article-title":"Evolutionary adaptations to pre-eclampsia\/eclampsia in humans: Low fecundability rate, loss of oestrus, prohibitions of incest and systematic polyandry","volume":"47","author":"Robillard","year":"2002","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0165-0378(02)00039-6","article-title":"The partner\u2019s role in the etiology of preeclampsia","volume":"57","author":"Dekker","year":"2002","journal-title":"J. Reprod. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ejogrb.2014.09.022","article-title":"The impact of donor insemination on the risk of preeclampsia: A systematic review and meta-analysis","volume":"182","author":"Brassesco","year":"2014","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.preghy.2018.06.010","article-title":"Risk of preeclampsia in pregnancies resulting from double gamete donation and from oocyte donation alone","volume":"13","author":"Blazquez","year":"2018","journal-title":"Pregnancy Hypertens"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1055\/s-0038-1667029","article-title":"The Impact of Sperm and Egg Donation on the Risk of Pregnancy Complications","volume":"36","author":"Sibai","year":"2019","journal-title":"Am. J. Perinatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/0168-9525(96)10017-2","article-title":"X chromosome imprinting and inactivation in the early mammalian embryo","volume":"12","author":"Latham","year":"1996","journal-title":"Trends Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1053\/j.semdp.2022.07.004","article-title":"Germ Cell Tumors of the Ovary: A Review","volume":"40","author":"Ramalingam","year":"2023","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1053\/j.semdp.2022.03.002","article-title":"Gestational trophoblastic disease-rare, sometimes dramatic, and what we know so far","volume":"39","author":"Strickland","year":"2022","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/0168-9525(91)90040-W","article-title":"Genomic imprinting in mammalian development: A parental tug-of-war","volume":"7","author":"Moore","year":"1991","journal-title":"Trends Genet."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Kaltsas, A., Moustakli, E., Zikopoulos, A., Georgiou, I., Dimitriadis, F., Symeonidis, E.N., Markou, E., Michaelidis, T.M., Tien, D.M.B., and Giannakis, I. (2023). Impact of Advanced Paternal Age on Fertility and Risks of Genetic Disorders in Offspring. Genes, 14.","DOI":"10.3390\/genes14020486"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.fertnstert.2003.04.002","article-title":"Effects of age on DNA double-strand breaks and apoptosis in human sperm","volume":"80","author":"Singh","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"34","DOI":"10.5935\/1518-0557.20140002","article-title":"The effects of age on sperm quality: An evaluation of 1,500 semen samples","volume":"18","author":"Oliveira","year":"2014","journal-title":"JBRA Assist. Reprod."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Kimura, M., Cherkas, L.F., Kato, B.S., Demissie, S., Hjelmborg, J.B., Brimacombe, M., Cupples, A., Hunkin, J.L., Gardner, J.P., and Lu, X. (2008). Offspring\u2019s leukocyte telomere length, paternal age, and telomere elongation in sperm. PLoS Genet., 4.","DOI":"10.1371\/journal.pgen.0040037"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1093\/molehr\/gas028","article-title":"Divergence of sperm and leukocyte age-dependent telomere dynamics: Implications for male-driven evolution of telomere length in humans","volume":"18","author":"Aston","year":"2012","journal-title":"Mol. Hum. Reprod."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3370","DOI":"10.1093\/humrep\/det392","article-title":"In young men sperm telomere length is related to sperm number and parental age","volume":"28","author":"Ferlin","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/j.1749-6632.2009.05396.x","article-title":"Cellular aging and centrosome aberrations","volume":"1197","author":"Ohshima","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/nature11396","article-title":"Rate of de novo mutations and the importance of father\u2019s age to disease risk","volume":"488","author":"Kong","year":"2012","journal-title":"Nature"},{"key":"ref_64","first-page":"1108","article-title":"Sex ratio in normal and disomic sperm: Evidence that the extra chromosome 21 preferentially segregates with the Y chromosome","volume":"59","author":"Griffin","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.fertnstert.2016.12.019","article-title":"Is advanced paternal age a health risk for the offspring?","volume":"107","author":"Urhoj","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1177\/1557988312440718","article-title":"The effect of paternal age on fetal birth outcomes","volume":"6","author":"Alio","year":"2012","journal-title":"Am. J. Men\u2019s Health"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/01.ede.0000152526.63279.da","article-title":"Paternal age and preterm birth","volume":"16","author":"Zhu","year":"2005","journal-title":"Epidemiology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/01.ede.0000197053.61176.f4","article-title":"Paternal age and preterm birth in Italy, 1990 to 1998","volume":"17","author":"Astolfi","year":"2006","journal-title":"Epidemiology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/S0140-6736(95)91327-0","article-title":"Effect of changing the stillbirth definition on evaluation of perinatal mortality rates","volume":"346","author":"Cartlidge","year":"1995","journal-title":"Lancet"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1093\/aje\/kwh332","article-title":"Advanced paternal age and risk of fetal death: A cohort study","volume":"160","author":"Hansen","year":"2004","journal-title":"Am. J. Epidemiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1093\/humrep\/deh449","article-title":"Late paternity and stillbirth risk","volume":"19","author":"Astolfi","year":"2004","journal-title":"Hum. Reprod."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"B75","DOI":"10.1269\/jrr.47.B75","article-title":"Age and sex effects on human mutation rates: An old problem with new complexities","volume":"47","author":"Crow","year":"2006","journal-title":"J. Radiat. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1001\/archpsyc.60.7.673","article-title":"Parental age and risk of schizophrenia: A case-control study","volume":"60","author":"Byrne","year":"2003","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1136\/bmj.38243.672396.55","article-title":"Paternal age and schizophrenia: A population based cohort study","volume":"329","author":"Sipos","year":"2004","journal-title":"BMJ"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s004390050168","article-title":"High parental age is associated with sporadic hereditary retinoblastoma: The Dutch retinoblastoma register 1862\u20131994","volume":"98","author":"Moll","year":"1996","journal-title":"Hum. Genet."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1007\/s10552-012-0034-7","article-title":"Perinatal characteristics and retinoblastoma","volume":"23","author":"Heck","year":"2012","journal-title":"Cancer Causes Control"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1093\/ije\/dyl177","article-title":"Parental age and risk of childhood cancers: A population-based cohort study from Sweden","volume":"35","author":"Yip","year":"2006","journal-title":"Int. J. Epidemiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.schres.2009.06.017","article-title":"Paternal age as a risk factor for schizophrenia: How important is it?","volume":"114","author":"Torrey","year":"2009","journal-title":"Schizophr. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.schres.2011.09.027","article-title":"Advanced paternal and grandpaternal age and schizophrenia: A three-generation perspective","volume":"133","author":"Frans","year":"2011","journal-title":"Schizophr. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1177\/1753495X18823479","article-title":"The forgotten father in obstetric medicine","volume":"12","author":"Kothari","year":"2019","journal-title":"Obstet. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.fertnstert.2016.12.006","article-title":"Old, older and too old: Age limits for medically assisted fatherhood?","volume":"107","author":"Braverman","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"re1","DOI":"10.1126\/sageke.2004.3.re1","article-title":"Dear old dad","volume":"2004","author":"Glaser","year":"2004","journal-title":"Sci. Aging Knowl. Environ."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1101\/gr.239186.118","article-title":"Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes","volume":"28","author":"Maher","year":"2018","journal-title":"Genome Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e5967","DOI":"10.1097\/MD.0000000000005967","article-title":"Different RET gene mutation-induced multiple endocrine neoplasia type 2A in 3 Chinese families","volume":"96","author":"Liu","year":"2017","journal-title":"Medicine"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1038\/bjc.2015.75","article-title":"Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes","volume":"112","author":"Kratz","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Dimofski, P., Meyre, D., Dreumont, N., and Leininger-Muller, B. (2021). Consequences of Paternal Nutrition on Offspring Health and Disease. Nutrients, 13.","DOI":"10.3390\/nu13082818"},{"key":"ref_87","first-page":"184","article-title":"High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring","volume":"5","author":"Ingerslev","year":"2015","journal-title":"Mol. Metab."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Binder, N.K., Hannan, N.J., and Gardner, D.K. (2012). Paternal diet-induced obesity retards early mouse embryo development, mitochondrial activity and pregnancy health. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052304"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.theriogenology.2019.07.009","article-title":"Spermatozoal mRNAs expression implicated in embryonic development were influenced by dietary folate supplementation of breeder roosters by altering spermatozoal piRNA expression profiles","volume":"138","author":"Wu","year":"2019","journal-title":"Theriogenology"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Wu, S., Guo, W., Li, X., Liu, Y., Li, Y., Lei, X., Yao, J., and Yang, X. (2019). Paternal chronic folate supplementation induced the transgenerational inheritance of acquired developmental and metabolic changes in chickens. Proc. Biol. Sci., 286.","DOI":"10.1098\/rspb.2019.1653"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.cell.2010.12.008","article-title":"Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals","volume":"143","author":"Carone","year":"2010","journal-title":"Cell"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"H1444","DOI":"10.1152\/ajpheart.00981.2013","article-title":"Paternal low protein diet affects adult offspring cardiovascular and metabolic function in mice","volume":"306","author":"Watkins","year":"2014","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"10064","DOI":"10.1073\/pnas.1806333115","article-title":"Paternal diet programs offspring health through sperm- and seminal plasma-specific pathways in mice","volume":"115","author":"Watkins","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1016\/j.bbadis.2017.02.009","article-title":"Paternal low protein diet programs preimplantation embryo gene expression, fetal growth and skeletal development in mice","volume":"1863","author":"Watkins","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/s13058-018-1034-7","article-title":"Paternal malnutrition programs breast cancer risk and tumor metabolism in offspring","volume":"20","author":"Carney","year":"2018","journal-title":"Breast Cancer Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"27010","DOI":"10.1038\/srep27010","article-title":"Paternal under-nutrition programs metabolic syndrome in offspring which can be reversed by antioxidant\/vitamin food fortification in fathers","volume":"6","author":"McPherson","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1071\/RD11256","article-title":"Parental diet-induced obesity leads to retarded early mouse embryo development and altered carbohydrate utilisation by the blastocyst","volume":"24","author":"Binder","year":"2012","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"E236","DOI":"10.1152\/ajpendo.00095.2016","article-title":"The effects of paternal high-fat diet exposure on offspring metabolism with epigenetic changes in the mouse adiponectin and leptin gene promoters","volume":"311","author":"Masuyama","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1002\/oby.22322","article-title":"Diet-Induced Paternal Obesity Impairs Cognitive Function in Offspring by Mediating Epigenetic Modifications in Spermatozoa","volume":"26","author":"Zhou","year":"2018","journal-title":"Obesity"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"N\u00e4tt, D., Kugelberg, U., Casas, E., Nedstrand, E., Zalavary, S., Henriksson, P., Nijm, C., J\u00e4derquist, J., Sandborg, J., and Flinke, E. (2019). Human sperm displays rapid responses to diet. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000559"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/bdra.23128","article-title":"Periconceptional paternal smoking and the risk of congenital heart defects: A case-control study","volume":"97","author":"Deng","year":"2013","journal-title":"Birth Defects Res. Part A Clin. Mol. Teratol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"62055","DOI":"10.1007\/s11356-021-16331-x","article-title":"The mutagenic effect of tobacco smoke on male fertility","volume":"29","author":"Omolaoye","year":"2022","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"108827","DOI":"10.1016\/j.envres.2019.108827","article-title":"Parental tobacco smoking and risk of childhood leukemia in Costa Rica: A population-based case-control study","volume":"180","author":"Frederiksen","year":"2020","journal-title":"Environ. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1007\/s10552-015-0593-5","article-title":"Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy, and childhood acute leukemia: The ESTELLE study","volume":"26","author":"Orsi","year":"2015","journal-title":"Cancer Causes Control"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s12978-022-01378-x","article-title":"Paternal smoking and preterm birth: A population-based retrospective cohort study among non-smoking women aged 20\u201349 years in rural China","volume":"19","author":"Wang","year":"2022","journal-title":"Reprod. Health"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1136\/jech-2017-210311","article-title":"Paternal smoking and spontaneous abortion: A population-based retrospective cohort study among non-smoking women aged 20\u201349 years in rural China","volume":"72","author":"Wang","year":"2018","journal-title":"J. Epidemiol. Community Health"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1093\/ije\/dyy031","article-title":"Ageing Lungs in European Cohorts (ALEC) Study. A three-generation study on the association of tobacco smoking with asthma","volume":"47","author":"Accordini","year":"2018","journal-title":"Int. J. Epidemiol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s10815-021-02373-0","article-title":"Paternal alcohol consumption has intergenerational consequences in male offspring","volume":"39","author":"Cambiasso","year":"2022","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1186\/s12978-021-01266-w","article-title":"The impact of paternal alcohol, tobacco, caffeine use and physical activity on offspring mental health: A systematic review and meta-analysis","volume":"18","author":"Easey","year":"2021","journal-title":"Reprod. Health"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.drugalcdep.2017.10.015","article-title":"Excess mortality in children born to opioid-addicted parents: A national register study in Taiwan","volume":"183","author":"Fang","year":"2018","journal-title":"Drug Alcohol Depend."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1017\/S2045796011000564","article-title":"Maternal and paternal psychopathology increases risk of offspring ADHD equally","volume":"20","author":"Lindblad","year":"2011","journal-title":"Epidemiol. Psychiatr. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"626","DOI":"10.5534\/wjmh.200147","article-title":"Anything New about Paternal Contribution to Reproductive Outcomes? A Review of the Evidence","volume":"39","author":"Montagnoli","year":"2021","journal-title":"World J. Men\u2019s Health"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Costa-J\u00fanior, J.M., Ferreira, S.M., Kurauti, M.A., Bernstein, D.L., Ruano, E.G., Kameswaran, V., Schug, J., Freitas-Dias, R., Zoppi, C.C., and Boschero, A.C. (2021). Paternal exercise improves the metabolic health of offspring via epigenetic modulation of the germline. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010001"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1136\/oem.2008.044743","article-title":"Parental occupational exposure to organic solvents and anencephaly in Mexico","volume":"67","year":"2010","journal-title":"Occup. Environ. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s12940-015-0060-5","article-title":"Parental urinary biomarkers of preconception exposure to bisphenol A and phthalates in relation to birth outcomes","volume":"14","author":"Smarr","year":"2015","journal-title":"Environ. Health"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1007\/s00246-015-1116-6","article-title":"Parental occupational exposures to endocrine disruptors and the risk of simple isolated congenital heart defects","volume":"36","author":"Wang","year":"2015","journal-title":"Pediatr. Cardiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.envint.2013.02.011","article-title":"Parental occupational exposure to pesticides as risk factor for brain tumors in children and young adults: A systematic review and meta-analysis","volume":"56","author":"Hoet","year":"2013","journal-title":"Environ. Int."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1136\/oem.2003.009043","article-title":"Paternal exposure to agricoltural pesticides and cause specific fetal death","volume":"61","author":"Regidor","year":"2004","journal-title":"Occup. Environ. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.envint.2018.02.017","article-title":"Environment and Reproductive Health (EARTH) Study Team. Preconception and prenatal urinary concentrations of phenols and birth size of singleton infants born to mothers and fathers from the Environment and Reproductive Health (EARTH) study","volume":"114","author":"Messerlian","year":"2018","journal-title":"Environ. Int."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"e9565","DOI":"10.1097\/MD.0000000000009565","article-title":"Paternal exposure to medical-related radiation associated with low birthweight infants: A large population-based, retrospective cohort study in rural China","volume":"97","author":"Chen","year":"2018","journal-title":"Medicine"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1177\/1933719117741378","article-title":"Sex-Dependent Influence of Developmental Toxicant Exposure on Group B Streptococcus-Mediated Preterm Birth in a Murine Model","volume":"25","author":"Ding","year":"2018","journal-title":"Reprod. Sci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"S52","DOI":"10.1016\/S0140-6736(17)33190-2","article-title":"Maternal and paternal obesity and adverse pregnancy outcomes in China: A cohort study","volume":"390","author":"He","year":"2017","journal-title":"Lancet"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41366-022-01237-6","article-title":"The associations of maternal and paternal obesity with latent patterns of offspring BMI development between 7 and 17 years of age: Pooled analyses of cohorts born in 1958 and 2001 in the united kingdom","volume":"47","author":"Johnson","year":"2023","journal-title":"Int. J. Obes."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Li, J., Qiu, J., Lv, L., Mao, B., Huang, L., Yang, T., Wang, C., and Liu, Q. (2021). Paternal factors and adverse birth outcomes in lanzhou, China. BMC Preg. Childbirth, 21.","DOI":"10.1186\/s12884-020-03492-9"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1093\/biolre\/ioac066","article-title":"Paternal obesity induces placental hypoxia and sex-specific impairments in placental vascularization and offspring metabolism","volume":"107","author":"Jazwiec","year":"2022","journal-title":"Biol. Reprod."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Soubry, A., Schildkraut, J.M., Murtha, A., Wang, F., Huang, Z., Bernal, A., Kurtzberg, J., Jirtle, R.L., Murphy, S.K., and Hoyo, C. (2013). Paternal obesity is associated with IGF2 hypomethylation in newborns: Results from a Newborn Epigenetics Study (NEST) cohort. BMC Med., 11.","DOI":"10.1186\/1741-7015-11-29"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Murphy, S.K., Huang, Z., and Hoyo, C. (2012). Differentially methylated regions of imprinted genes in prenatal, perinatal and postnatal human tissues. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040924"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s10552-012-9932-y","article-title":"Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight","volume":"23","author":"Hoyo","year":"2012","journal-title":"Cancer Causes Control"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1530\/JOE-21-0301","article-title":"Paternal diabetes programs sex-dependent placental alterations and fetal overgrowth","volume":"254","author":"Fornes","year":"2022","journal-title":"J. Endocrinol."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/13\/3\/165\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:08:41Z","timestamp":1760105321000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/13\/3\/165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,3]]},"references-count":129,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["biology13030165"],"URL":"https:\/\/doi.org\/10.3390\/biology13030165","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,3]]}}}