Human Umbilical Cord: Information Mine in Sex-Specific Medicine

Overview

Journal Life (Basel)

Specialty Biology

Date 2021 Jan 16

PMID 33451112

Citations 10

Authors

Ilaria Campesi

Flavia Franconi

Andrea Montella

Salvatore Dessole

Giampiero Capobianco

Affiliations

Soon will be listed here.

Abstract

Biological differences between sexes should be considered in all stages of research, as sexual dimorphism starts in utero leading to sex-specific fetal programming. In numerous biomedical fields, there is still a lack of stratification by sex despite primary cultured cells retaining memory of the sex and of the donor. The sex of donors in biological research must be known because variations in cells and cellular components can be used as endpoints, biomarkers and/or targets of pharmacological studies. This selective review focuses on the current findings regarding sex differences observed in the umbilical cord, a widely used source of research samples, both in the blood and in the circulating cells, as well as in the different cellular models obtainable from it. Moreover, an overview on sex differences in fetal programming is reported. As it emerges that the sex variable is still often forgotten in experimental models, we suggest that it should be mandatory to adopt sex-oriented research, because only awareness of these issues can lead to innovative research.

Citing Articles

Phosphodiesterase Inhibitors in Fetal Growth Restriction: Do Not Forget to Consider Fetal Sex and Subcellular Compartmentation.

Peyter A, Baud D, Tolsa J Biomedicines. 2024; 12(10).

PMID: 39457641 PMC: 11505842. DOI: 10.3390/biomedicines12102329.

Enhanced fetal hematopoiesis in response to symptomatic SARS-CoV-2 infection during pregnancy.

Alkobtawi M, Ngo Q, Chapuis N, Fontaine R, El Khoury M, Tihy M Commun Med (Lond). 2023; 3(1):177.

PMID: 38082066 PMC: 10713620. DOI: 10.1038/s43856-023-00406-6.

Stratification of Amniotic Fluid Cells and Amniotic Fluid by Sex Opens Up New Perspectives on Fetal Health.

Campesi I, Capobianco G, Cano A, Lodde V, Cruciani S, Maioli M Biomedicines. 2023; 11(10).

PMID: 37893203 PMC: 10604128. DOI: 10.3390/biomedicines11102830.

Sex-Gender-Based Differences in Metabolic Diseases.

Campesi I, Ruoppolo M, Franconi F, Caterino M, Costanzo M Handb Exp Pharmacol. 2023; 282:241-257.

PMID: 37528324 DOI: 10.1007/164_2023_683.

Sex as a Biological Variable in Tissue Engineering and Regenerative Medicine.

Allen J, Ludtka C, James B Annu Rev Biomed Eng. 2023; 25:311-331.

PMID: 37104652 PMC: 10312304. DOI: 10.1146/annurev-bioeng-092222-030857.

References

Stark M, Clifton V, Wright I . Neonates born to mothers with preeclampsia exhibit sex-specific alterations in microvascular function. Pediatr Res. 2009; 65(3):292-5. DOI: 10.1203/pdr.0b013e318193edf1. View

Minghetti L, Greco A, Zanardo V, Suppiej A . Early-life sex-dependent vulnerability to oxidative stress: the natural twining model. J Matern Fetal Neonatal Med. 2012; 26(3):259-62. DOI: 10.3109/14767058.2012.733751. View

MOORE W, Ward B, Jones V, Bamford F . Sex difference in fetal head growth. Br J Obstet Gynaecol. 1988; 95(3):238-42. DOI: 10.1111/j.1471-0528.1988.tb06863.x. View

Buckberry S, Bianco-Miotto T, Bent S, Dekker G, Roberts C . Integrative transcriptome meta-analysis reveals widespread sex-biased gene expression at the human fetal-maternal interface. Mol Hum Reprod. 2014; 20(8):810-9. PMC: 4106635. DOI: 10.1093/molehr/gau035. View

Grigore D, Ojeda N, Alexander B . Sex differences in the fetal programming of hypertension. Gend Med. 2008; 5 Suppl A:S121-32. PMC: 2657344. DOI: 10.1016/j.genm.2008.03.012. View

Lavoie J, Chessex P . Gender-related response to a tert-butyl hydroperoxide-induced oxidation in human neonatal tissue. Free Radic Biol Med. 1994; 16(3):307-13. DOI: 10.1016/0891-5849(94)90031-0. View

Koller A . Perspectives: Microvascular endothelial dysfunction and gender. Eur Heart J Suppl. 2014; 16(Suppl A):A16-A19. PMC: 3966560. DOI: 10.1093/eurheartj/sut005. View

Lorenz M, Koschate J, Kaufmann K, Kreye C, Mertens M, Kuebler W . Does cellular sex matter? Dimorphic transcriptional differences between female and male endothelial cells. Atherosclerosis. 2015; 240(1):61-72. DOI: 10.1016/j.atherosclerosis.2015.02.018. View

Wallace J, Bhattacharya S, Horgan G . Gestational age, gender and parity specific centile charts for placental weight for singleton deliveries in Aberdeen, UK. Placenta. 2013; 34(3):269-74. DOI: 10.1016/j.placenta.2012.12.007. View

10.

Ruoppolo M, Scolamiero E, Caterino M, Mirisola V, Franconi F, Campesi I . Female and male human babies have distinct blood metabolomic patterns. Mol Biosyst. 2015; 11(9):2483-92. DOI: 10.1039/c5mb00297d. View

11.

Ray P, Conaghan J, Winston R, Handyside A . Increased number of cells and metabolic activity in male human preimplantation embryos following in vitro fertilization. J Reprod Fertil. 1995; 104(1):165-71. DOI: 10.1530/jrf.0.1040165. View

12.

Cattaneo M, Vanetti C, Decimo I, Di Chio M, Martano G, Garrone G . Sex-specific eNOS activity and function in human endothelial cells. Sci Rep. 2017; 7(1):9612. PMC: 5575132. DOI: 10.1038/s41598-017-10139-x. View

13.

Franconi F, Campesi I, Colombo D, Antonini P . Sex-Gender Variable: Methodological Recommendations for Increasing Scientific Value of Clinical Studies. Cells. 2019; 8(5). PMC: 6562815. DOI: 10.3390/cells8050476. View

14.

Fadini G, De Kreutzenberg S, Albiero M, Coracina A, Pagnin E, Baesso I . Gender differences in endothelial progenitor cells and cardiovascular risk profile: the role of female estrogens. Arterioscler Thromb Vasc Biol. 2008; 28(5):997-1004. DOI: 10.1161/ATVBAHA.107.159558. View

15.

Hartman R, Kapteijn D, Haitjema S, Bekker M, Mokry M, Pasterkamp G . Intrinsic transcriptomic sex differences in human endothelial cells at birth and in adults are associated with coronary artery disease targets. Sci Rep. 2020; 10(1):12367. PMC: 7378217. DOI: 10.1038/s41598-020-69451-8. View

16.

Oreal E, Mazaud S, Picard J, Magre S, Carre-Eusebe D . Different patterns of anti-Müllerian hormone expression, as related to DMRT1, SF-1, WT1, GATA-4, Wnt-4, and Lhx9 expression, in the chick differentiating gonads. Dev Dyn. 2002; 225(3):221-32. DOI: 10.1002/dvdy.10153. View

17.

Takechi K, Kuwabara Y, Mizuno M . Ultrastructural and immunohistochemical studies of Wharton's jelly umbilical cord cells. Placenta. 1993; 14(2):235-45. DOI: 10.1016/s0143-4004(05)80264-4. View

18.

Bermejo-Alvarez P, Rizos D, Rath D, Lonergan P, Gutierrez-Adan A . Epigenetic differences between male and female bovine blastocysts produced in vitro. Physiol Genomics. 2007; 32(2):264-72. DOI: 10.1152/physiolgenomics.00234.2007. View

19.

Tajiri N, Duncan K, Borlongan M, Pabon M, Acosta S, De la Pena I . Adult stem cell transplantation: is gender a factor in stemness?. Int J Mol Sci. 2014; 15(9):15225-43. PMC: 4200754. DOI: 10.3390/ijms150915225. View

20.

Kim D, Staples M, Shinozuka K, Pantcheva P, Kang S, Borlongan C . Wharton's jelly-derived mesenchymal stem cells: phenotypic characterization and optimizing their therapeutic potential for clinical applications. Int J Mol Sci. 2013; 14(6):11692-712. PMC: 3709752. DOI: 10.3390/ijms140611692. View