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International journal of molecular sciences2021; 22(22); 12116; doi: 10.3390/ijms222212116

Estrogens Regulate Placental Angiogenesis in Horses.

Abstract: A sufficient vascular network within the feto-maternal interface is necessary for placental function. Several pregnancy abnormalities have been associated with abnormal vascular formations in the placenta. We hypothesized that growth and expansion of the placental vascular network in the equine () placenta is regulated by estrogens (estrogen family hormones), a hormone with a high circulating concentration during equine gestation. Administration of letrozole, a potent and specific inhibitor of aromatase, during the first trimester (D30 to D118), decreased circulatory estrone sulfate concentrations, increased circulatory testosterone and androstenedione concentrations, and tended to reduce the weight of the fetus ( < 0.1). Moreover, the gene expression of was increased, and the expression of androgen receptor was decreased in the D120 chorioallantois (CA) of letrozole-treated mares in comparison to that of the control mares. We also found that at D120, the number of vessels tended to decrease in the CAs with letrozole treatment ( = 0.07). In addition, expression of a subset of angiogenic genes, such as , , and , were altered in the CAs of letrozole-treated mares. We further demonstrated that 17β-estradiol increases the expression of and and increases the angiogenic activity of equine endothelial cells in vitro. Our results from the estrogen-suppressed group demonstrated an impaired placental vascular network, suggesting an estrogen-dependent vasculogenesis in the equine CA during the first trimester.
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Publication Date: 2021-11-09 PubMed ID: 34829994PubMed Central: PMC8621320DOI: 10.3390/ijms222212116Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article explores how estrogens, a hormone family, regulate the growth and expansion of the vascular network in horse placentas, which is necessary for placental function. The researchers used an aromatase inhibitor, letrozole, to decrease estrogen levels during the first trimester of gestation, leading to a decrease in circulatory estrone sulfate and an increase in testosterone and androstenedione, which has affected fetal weight and influenced the expression of certain genes. The results also suggested a decrease in vessel numbers and alterations in the expression of angiogenic genes. In vitro testing further supported that 17β-estradiol, a form of estrogen, increases angiogenic activity of equine endothelial cells, indicating that estrogens are essential for placental vasculogenesis.

Objective and Hypothesis

  • The researchers aimed to investigate the role of estrogens in regulating placental angiogenesis, the process of forming new blood vessels, in horses.
  • The researchers hypothesized that the growth and expansion of the placental vascular network in horses is regulated by estrogens. These hormones have a high concentration in circulation during gestation.

Methodology

  • The researchers administered letrozole, an aromatase inhibitor, to horses during the first trimester of gestation (from day 30 to day 118). This drug is known to lower estrogen levels.
  • The impacts of letrozole on circulatory estrone sulfate, testosterone and androstenedione concentrations were measured.
  • The gene expressions of certain placental development-related genes were also examined.

Findings

  • Letrozole administration led to decreased circulatory estrone sulfate concentrations and increased circulatory testosterone and androstenedione concentrations.
  • The fetus weight was reduced, which suggests that lowered estrogen concentration might have an adverse impact on fetal development.
  • The expression of certain genes related to placental development was altered. For instance, the gene expression of was increased, and the expression of the androgen receptor was decreased.
  • Moreover, the number of vessels in the placental structures was found to have a tendency to decrease.
  • Some angiogenic genes expression was altered, suggesting that estrogen levels influence these genes and thus, angiogenesis.

Conclusion

  • In vitro experiments further demonstrated that 17β-estradiol, a type of estrogen, stimulates the expression of key genes and promotes the angiogenic activity of equine endothelial cells.
  • The results of the study support the hypothesis that estrogens regulate placental angiogenesis in horses. When estrogen levels were suppressed, an impaired placental vascular network was observed, suggesting an estrogen-dependent vasculogenesis mechanism in equine placentas during the first trimester.

Cite This Article

APA
Haneda S, Dini P, Esteller-Vico A, Scoggin KE, Squires EL, Troedsson MH, Daels P, Nambo Y, Ball BA. (2021). Estrogens Regulate Placental Angiogenesis in Horses. Int J Mol Sci, 22(22), 12116. https://doi.org/10.3390/ijms222212116

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 22
Issue: 22
PII: 12116

Researcher Affiliations

Haneda, Shingo
  • Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan.
Dini, Pouya
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
  • Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
Esteller-Vico, Alejandro
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
  • Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
Scoggin, Kirsten E
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
Squires, Edward L
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
Troedsson, Mats H
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
Daels, Peter
  • Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
Nambo, Yasuo
  • Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan.
Ball, Barry A
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.

MeSH Terms

  • Androstenedione / genetics
  • Angiopoietin-1 / genetics
  • Animals
  • Aromatase / genetics
  • Estrogens / genetics
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Horses / genetics
  • Horses / growth & development
  • Letrozole / pharmacology
  • Maternal-Fetal Relations / drug effects
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / genetics
  • Placenta / blood supply
  • Placenta / drug effects
  • Pregnancy
  • Pregnancy Trimester, First
  • Receptors, Androgen / genetics
  • Steroid 17-alpha-Hydroxylase / genetics
  • Testosterone / genetics
  • Vascular Endothelial Growth Factor A / genetics

Grant Funding

  • the Albert G. Clay Endowment and the Clay Visiting Scholar Fellowship of the University of Kentucky

Conflict of Interest Statement

The authors have no conflict of interest.

References

This article includes 54 references
  1. Ambrose CT. The Role of Capillaries in the Lesser Ailments of Old Age and in Alzheimer's Disease and Vascular Dementia: The Potential of Pro-Therapeutic Angiogenesis.. J Alzheimers Dis 2016 Jul 1;54(1):31-43.
    doi: 10.3233/JAD-160303pubmed: 27392865google scholar: lookup
  2. Liu H, Tao Y, Chen M, Yu J, Li WJ, Tao L, Li Y, Li F. 17β-Estradiol Promotes Angiogenesis of Rat Cardiac Microvascular Endothelial Cells In Vitro.. Med Sci Monit 2018 Apr 23;24:2489-2496.
    doi: 10.12659/MSM.903344pmc: PMC5936052pubmed: 29684003google scholar: lookup
  3. De Spiegelaere W, Cornillie P, Casteleyn C, Burvenich C, Van den Broeck W. Detection of hypoxia inducible factors and angiogenic growth factors during foetal endochondral and intramembranous ossification.. Anat Histol Embryol 2010 Aug;39(4):376-84.
    doi: 10.1111/j.1439-0264.2010.01005.xpubmed: 20545637google scholar: lookup
  4. Carmeliet P, Eelen G, Kalucka J. Arteriogenesis versus angiogenesis. The ESC Textbook of Vascular Biology 2017.
  5. Elkilani OA, Soliman MA. Angiogenesis mediators in women with idiopathic heavy menstrual bleeding.. Int J Gynaecol Obstet 2017 Mar;136(3):280-284.
    doi: 10.1002/ijgo.12068pubmed: 28099683google scholar: lookup
  6. Fagiani E, Christofori G. Angiopoietins in angiogenesis.. Cancer Lett 2013 Jan 1;328(1):18-26.
    doi: 10.1016/j.canlet.2012.08.018pubmed: 22922303google scholar: lookup
  7. Potente M, Gerhardt H, Carmeliet P. Basic and therapeutic aspects of angiogenesis.. Cell 2011 Sep 16;146(6):873-87.
    doi: 10.1016/j.cell.2011.08.039pubmed: 21925313google scholar: lookup
  8. Weis SM, Cheresh DA. Tumor angiogenesis: molecular pathways and therapeutic targets.. Nat Med 2011 Nov 7;17(11):1359-70.
    doi: 10.1038/nm.2537pubmed: 22064426google scholar: lookup
  9. Reynolds LP, Redmer DA. Angiogenesis in the placenta.. Biol Reprod 2001 Apr;64(4):1033-40.
    doi: 10.1095/biolreprod64.4.1033pubmed: 11259247google scholar: lookup
  10. Arroyo JA, Winn VD. Vasculogenesis and angiogenesis in the IUGR placenta.. Semin Perinatol 2008 Jun;32(3):172-7.
    pubmed: 18482617doi: 10.1053/j.semperi.2008.02.006google scholar: lookup
  11. Regnault TR, Galan HL, Parker TA, Anthony RV. Placental development in normal and compromised pregnancies-- a review.. Placenta 2002 Apr;23 Suppl A:S119-29.
    doi: 10.1053/plac.2002.0792pubmed: 11978069google scholar: lookup
  12. Dini P, Carossino M, Loynachan AT, El-Sheikh Ali H, Wolfsdorf KE, Scoggin KE, Daels P, Ball BA. Equine hydrallantois is associated with impaired angiogenesis in the placenta.. Placenta 2020 Apr;93:101-112.
    doi: 10.1016/j.placenta.2020.03.001pubmed: 32250734google scholar: lookup
  13. Mitra SC, Seshan SV, Riachi LE. Placental vessel morphometry in growth retardation and increased resistance of the umbilical artery Doppler flow.. J Matern Fetal Med 2000 Sep-Oct;9(5):282-6.
    doi: 10.1002/1520-6661(200009/10)9:5<282::AID-MFM5>3.0.CO;2-Jpubmed: 11132583google scholar: lookup
  14. BARCROFT J, BARRON DH. Observations upon the form and relations of the maternal and fetal vessels in the placenta of the sheep.. Anat Rec 1946 Apr;94:569-95.
    doi: 10.1002/ar.1090940403pubmed: 20981897google scholar: lookup
  15. Pereira RD, De Long NE, Wang RC, Yazdi FT, Holloway AC, Raha S. Angiogenesis in the placenta: the role of reactive oxygen species signaling.. Biomed Res Int 2015;2015:814543.
    doi: 10.1155/2015/814543pmc: PMC4325211pubmed: 25705690google scholar: lookup
  16. Maliqueo M, Echiburú B, Crisosto N. Sex Steroids Modulate Uterine-Placental Vasculature: Implications for Obstetrics and Neonatal Outcomes.. Front Physiol 2016;7:152.
    doi: 10.3389/fphys.2016.00152pmc: PMC4844620pubmed: 27199767google scholar: lookup
  17. Zhang L, Xiong W, Xiong Y, Liu H, Liu Y. 17 β-Estradiol promotes vascular endothelial growth factor expression via the Wnt/β-catenin pathway during the pathogenesis of endometriosis.. Mol Hum Reprod 2016 Jul;22(7):526-35.
    doi: 10.1093/molehr/gaw025pubmed: 27009232google scholar: lookup
  18. Powazniak Y, Kempfer AC, de la Paz Dominguez M, Farias C, Keller L, Calderazzo JC, Lazzari MA. Effect of estradiol, progesterone and testosterone on apoptosis- and proliferation-induced MAPK signaling in human umbilical vein endothelial cells.. Mol Med Rep 2009 May-Jun;2(3):441-7.
    doi: 10.3892/mmr_00000119pubmed: 21475848google scholar: lookup
  19. Oviedo PJ, Sobrino A, Laguna-Fernandez A, Novella S, Tarín JJ, García-Pérez MA, Sanchís J, Cano A, Hermenegildo C. Estradiol induces endothelial cell migration and proliferation through estrogen receptor-enhanced RhoA/ROCK pathway.. Mol Cell Endocrinol 2011 Mar 30;335(2):96-103.
    doi: 10.1016/j.mce.2010.06.020pubmed: 20615453google scholar: lookup
  20. Maniyar R, Chakraborty S, Suriano R. Ethanol Enhances Estrogen Mediated Angiogenesis in Breast Cancer.. J Cancer 2018;9(21):3874-3885.
    doi: 10.7150/jca.25581pmc: PMC6218769pubmed: 30410590google scholar: lookup
  21. Zhang X, Healy C, Nothnick WB. Estrogen suppresses expression of the matrix metalloproteinase inhibitor reversion-inducing cysteine-rich protein with Kazal motifs (RECK) within the mouse uterus.. Endocrine 2012 Aug;42(1):97-106.
    doi: 10.1007/s12020-012-9614-2pubmed: 22302680google scholar: lookup
  22. Hervé MA, Meduri G, Petit FG, Domet TS, Lazennec G, Mourah S, Perrot-Applanat M. Regulation of the vascular endothelial growth factor (VEGF) receptor Flk-1/KDR by estradiol through VEGF in uterus.. J Endocrinol 2006 Jan;188(1):91-9.
    doi: 10.1677/joe.1.06184pubmed: 16394178google scholar: lookup
  23. Garvin S, Nilsson UW, Huss FR, Kratz G, Dabrosin C. Estradiol increases VEGF in human breast studied by whole-tissue culture.. Cell Tissue Res 2006 Aug;325(2):245-51.
    doi: 10.1007/s00441-006-0159-7pubmed: 16568303google scholar: lookup
  24. Suzuma I, Mandai M, Takagi H, Suzuma K, Otani A, Oh H, Kobayashi K, Honda Y. 17 Beta-estradiol increases VEGF receptor-2 and promotes DNA synthesis in retinal microvascular endothelial cells.. Invest Ophthalmol Vis Sci 1999 Aug;40(9):2122-9.
    pubmed: 10440269
  25. Arnal JF, Fontaine C, Billon-Galés A, Favre J, Laurell H, Lenfant F, Gourdy P. Estrogen receptors and endothelium.. Arterioscler Thromb Vasc Biol 2010 Aug;30(8):1506-12.
    doi: 10.1161/ATVBAHA.109.191221pubmed: 20631350google scholar: lookup
  26. Augustin HG, Koh GY, Thurston G, Alitalo K. Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system.. Nat Rev Mol Cell Biol 2009 Mar;10(3):165-77.
    doi: 10.1038/nrm2639pubmed: 19234476google scholar: lookup
  27. Gu J, Zhang Y, Han Z, Gao L, Cui J, Sun Y, Niu Y, You B, Huang CP, Chang C, Wang X, Yeh S. Targeting the ERβ/Angiopoietin-2/Tie-2 signaling-mediated angiogenesis with the FDA-approved anti-estrogen Faslodex to increase the Sunitinib sensitivity in RCC.. Cell Death Dis 2020 May 14;11(5):367.
    doi: 10.1038/s41419-020-2486-0pmc: PMC7224303pubmed: 32409702google scholar: lookup
  28. Darenius K, Kindahl H, Madej A. Clinical and endocrine aspects of early fetal death in the mare.. J Reprod Fertil Suppl 1987;35:497-8.
    pubmed: 3479602
  29. Douglas R. Endocrine diagnostics in the broodmare: What you need to know about progestins and estrogens. Proc. Soc. 2004:106–115.
  30. Shikichi M, Iwata K, Ito K, Miyakoshi D, Murase H, Sato F, Korosue K, Nagata S, Nambo Y. Abnormal pregnancies associated with deviation in progestin and estrogen profiles in late pregnant mares: A diagnostic aid.. Theriogenology 2017 Aug;98:75-81.
    doi: 10.1016/j.theriogenology.2017.04.024pubmed: 28601159google scholar: lookup
  31. Raeside JI, Christie HL, Renaud RL, Waelchli RO, Betteridge KJ. Estrogen metabolism in the equine conceptus and endometrium during early pregnancy in relation to estrogen concentrations in yolk-sac fluid.. Biol Reprod 2004 Oct;71(4):1120-7.
    doi: 10.1095/biolreprod.104.028712pubmed: 15163615google scholar: lookup
  32. Daels PF, Shideler S, Lasley BL, Hughes JP, Stabenfeldt GH. Source of oestrogen in early pregnancy in the mare.. J Reprod Fertil 1990 Sep;90(1):55-61.
    doi: 10.1530/jrf.0.0900055pubmed: 2172534google scholar: lookup
  33. Daels PF, DeMoraes JJ, Stabenfeldt GH, Hughes JP, Lasley BL. The corpus luteum: source of oestrogen during early pregnancy in the mare.. J Reprod Fertil Suppl 1991;44:501-8.
    pubmed: 1665517
  34. Albrecht BA, Daels PF. Immunolocalization of 3 beta-hydroxysteroid dehydrogenase, cytochrome P450 17 alpha-hydroxylase/17,20-lyase and cytochrome P450 aromatase in the equine corpus luteum of dioestrus and early pregnancy.. J Reprod Fertil 1997 Sep;111(1):127-33.
    doi: 10.1530/jrf.0.1110127pubmed: 9370976google scholar: lookup
  35. Terqui M, Palmer E. Oestrogen pattern during early pregnancy in the mare.. J Reprod Fertil Suppl 1979;(27):441-6.
    pubmed: 289820
  36. Nett TM, Holtan DW, Liné Estergreen V. Plasma estrogens in pregnant and postpartum mares.. J Anim Sci 1973 Oct;37(4):962-70.
    doi: 10.2527/jas1973.374962xpubmed: 4747188google scholar: lookup
  37. Pashen RL, Sheldrick EL, Allen WR, Flint AP. Dehydroepiandrosterone synthesis by the fetal foal and its importance as an oestrogen precursor.. J Reprod Fertil Suppl 1982;32:389-97.
    pubmed: 6220147
  38. Pashen RL, Allen WR. The role of the fetal gonads and placenta in steroid production, maintenance of pregnancy and parturition in the mare.. J Reprod Fertil Suppl 1979;(27):499-509.
    pubmed: 289829
  39. Albrecht ED, Robb VA, Pepe GJ. Regulation of placental vascular endothelial growth/permeability factor expression and angiogenesis by estrogen during early baboon pregnancy.. J Clin Endocrinol Metab 2004 Nov;89(11):5803-9.
    doi: 10.1210/jc.2004-0479pubmed: 15531545google scholar: lookup
  40. Albrecht ED, Pepe GJ. Estrogen regulation of placental angiogenesis and fetal ovarian development during primate pregnancy.. Int J Dev Biol 2010;54(2-3):397-408.
    doi: 10.1387/ijdb.082758eapmc: PMC2804030pubmed: 19876841google scholar: lookup
  41. Esteller-Vico A, Ball BA, Troedsson MHT, Squires EL. Endocrine changes, fetal growth, and uterine artery hemodynamics after chronic estrogen suppression during the last trimester of equine pregnancy.. Biol Reprod 2017 Feb 1;96(2):414-423.
    doi: 10.1095/biolreprod.116.140533pubmed: 28203724google scholar: lookup
  42. Salafia CM, Minior VK, Pezzullo JC, Popek EJ, Rosenkrantz TS, Vintzileos AM. Intrauterine growth restriction in infants of less than thirty-two weeks' gestation: associated placental pathologic features.. Am J Obstet Gynecol 1995 Oct;173(4):1049-57.
    doi: 10.1016/0002-9378(95)91325-4pubmed: 7485292google scholar: lookup
  43. Bailey CS, Heitzman JM, Buchanan CN, Bare CA, Sper RB, Borst LB, Macpherson M, Archibald K, Whitacre M. B-mode and Doppler ultrasonography in pony mares with experimentally induced ascending placentitis.. Equine Vet J Suppl 2012 Dec;(43):88-94.
    doi: 10.1111/j.2042-3306.2012.00658.xpubmed: 23447885google scholar: lookup
  44. Volkmann D, De Cramer K. Prostaglandin E (2) as an adjunct to the induction of abortion in mares. J. Reprod. Fertil. 1991:722–723.
  45. Weidner N. Chapter 14. Measuring intratumoral microvessel density.. Methods Enzymol 2008;444:305-23.
    pubmed: 19007671doi: 10.1016/s0076-6879(08)02814-0google scholar: lookup
  46. Jadeski LC, Lala PK. Nitric oxide synthase inhibition by N(G)-nitro-L-arginine methyl ester inhibits tumor-induced angiogenesis in mammary tumors.. Am J Pathol 1999 Oct;155(4):1381-90.
    doi: 10.1016/S0002-9440(10)65240-6pmc: PMC1867009pubmed: 10514420google scholar: lookup
  47. Hedges JF, Demaula CD, Moore BD, McLaughlin BE, Simon SI, MacLachlan NJ. Characterization of equine E-selectin.. Immunology 2001 Aug;103(4):498-504.
    doi: 10.1046/j.1365-2567.2001.01262.xpmc: PMC1783268pubmed: 11529941google scholar: lookup
  48. Munro C, Stabenfeldt G. Development of a microtitre plate enzyme immunoassay for the determination of progesterone.. J Endocrinol 1984 Apr;101(1):41-9.
    doi: 10.1677/joe.0.1010041pubmed: 6368729google scholar: lookup
  49. Stabenfeldt GH, Daels PF, Munro CJ, Kindahl H, Hughes JP, Lasley B. An oestrogen conjugate enzyme immunoassay for monitoring pregnancy in the mare: limitations of the assay between days 40 and 70 of gestation.. J Reprod Fertil Suppl 1991;44:37-44.
    pubmed: 1665516
  50. Peng B, Yu RK, Dehoff KL, Amos CI. Normalizing a large number of quantitative traits using empirical normal quantile transformation.. BMC Proc 2007;1 Suppl 1(Suppl 1):S156.
    pmc: PMC2367615pubmed: 18466501doi: 10.1186/1753-6561-1-s1-s156google scholar: lookup
  51. Klein C, Rutllant J, Troedsson MH. Expression stability of putative reference genes in equine endometrial, testicular, and conceptus tissues.. BMC Res Notes 2011 Apr 12;4:120.
    doi: 10.1186/1756-0500-4-120pmc: PMC3083352pubmed: 21486450google scholar: lookup
  52. Dini P, Esteller-Vico A, Scoggin KE, Daels P, Ball BA. Extraction of RNA from formalin-fixed, paraffin-embedded equine placenta.. Reprod Domest Anim 2019 Mar;54(3):627-634.
    doi: 10.1111/rda.13406pubmed: 30659674google scholar: lookup
  53. Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma.. N Engl J Med 1991 Jan 3;324(1):1-8.
    doi: 10.1056/NEJM199101033240101pubmed: 1701519google scholar: lookup
  54. Dini P, Carossino M, Balasuriya UBR, El-Sheikh Ali H, Loux SC, Esteller-Vico A, Scoggin KE, Loynachan AT, Kalbfleisch T, De Spiegelaere W, Daels P, Ball BA. Paternally expressed retrotransposon Gag-like 1 gene, RTL1, is one of the crucial elements for placental angiogenesis in horses†.. Biol Reprod 2021 Jun 4;104(6):1386-1399.
    doi: 10.1093/biolre/ioab039pubmed: 33693478google scholar: lookup

Citations

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    doi: 10.1186/s12958-023-01102-9pubmed: 37226177google scholar: lookup
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  5. Song W, Guo Q, Puttabyatappa M, Elangovan VR, Wang J, Li F, Liu F, Bi X, Li H, Fu G, Padmanabhan V, Wu X. FGR-associated placental insufficiency and capillary angiogenesis involves disruptions in human placental miRNAs and mRNAs. Heliyon 2024 Mar 30;10(6):e28007.
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  6. Parisi F, Fenizia C, Introini A, Zavatta A, Scaccabarozzi C, Biasin M, Savasi V. The pathophysiological role of estrogens in the initial stages of pregnancy: molecular mechanisms and clinical implications for pregnancy outcome from the periconceptional period to end of the first trimester. Hum Reprod Update 2023 Nov 2;29(6):699-720.
    doi: 10.1093/humupd/dmad016pubmed: 37353909google scholar: lookup
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