Skip to main content
SpringerLink
Log in

Placental vascular lesions differ between male and female fetuses in early-onset preeclampsia

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

A growing body of evidence accumulate pointing to sex-specific differences in placental adaptation to pregnancy complications. We aimed to study if there is a difference in placental histopathology lesions, between female and male fetuses in pregnancies complicated with preeclampsia.

Methods

The medical files of all patients with preeclampsia, were reviewed. Placental lesions were classified to lesions related to maternal or fetal malperfusion lesions (MVM, FVM), vascular and villous changes, and inflammatory lesions. Comparison was performed between the male and the female groups.

Results

The study included 441 preeclamptic patients. Women in the male preeclampsia group (n = 225) had higher rate of chronic hypertension (p = 0.05) and diabetes mellitus (p < 0.005), while women in the female preeclampsia group (n = 216) had higher rate of thrombophilia. There were no between groups differences in neonatal outcome or placental histopathology lesions. The early preeclampsia cohort included 91 patients. Placentas from the female early preeclampsia group (n = 44) had more vascular changes related to MVM lesions (decidual arteriopathy), as compared to the male early preeclampsia group (n = 47), 50% vs. 25%, p = 0.01.

Conclusions

Higher rate of placental MVM lesions in the female as compared to male group correspond with sex-specific difference of placental pathophysiological adaptation, in early preeclampsia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Duley L (2009) The global impact of pre-eclampsia and eclampsia. Semin Perinatol. https://doi.org/10.1053/j.semperi.2009.02.010

    Article  PubMed  Google Scholar 

  2. Mol BWJ, Roberts CT, Thangaratinam S, Magee LA, De Groot CJM, Hofmeyr GJ (2016) Pre-eclampsia. Lancet. https://doi.org/10.1016/S0140-6736(15)00070-7

    Article  PubMed  Google Scholar 

  3. Brosens I, Pijnenborg R, Vercruysse L, Romero R (2011) The, “great obstetrical syndromes” are associated with disorders of deep placentation. Am J Obstet Gynecol. https://doi.org/10.1016/j.ajog.2010.08.009

    Article  PubMed  Google Scholar 

  4. Garrido-Gomez T, Dominguez F, Quiñonero A, Diaz-Gimeno P, Kapidzic M, Gormley M et al (2017) Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.1706546114

    Article  PubMed  PubMed Central  Google Scholar 

  5. Khong Y, Brosens I (2011) Defective deep placentation. Best Pract Res Clin Obstet Gynaecol. https://doi.org/10.1016/j.bpobgyn.2010.10.012

    Article  PubMed  Google Scholar 

  6. Redline RW (2008) Placental pathology: a systematic approach with clinical correlations. Placenta. https://doi.org/10.1016/j.placenta.2007.09.003

    Article  PubMed  Google Scholar 

  7. Clifton VL (2010) Review: sex and the human placenta: mediating differential strategies of fetal growth and survival. Placenta 31:S33–S39. https://doi.org/10.1016/j.placenta.2009.11.010

    Article  CAS  PubMed  Google Scholar 

  8. Stark MJ, Clifton VL, Wright IMR (2009) Neonates born to mothers with preeclampsia exhibit sex-specific alterations in microvascular function. Pediatr Res. https://doi.org/10.1203/PDR.0b013e318193edf1

    Article  PubMed  Google Scholar 

  9. Stark MJ, Clifton VL, Wright IMR (2008) Sex-specific differences in peripheral microvascular blood flow in preterm infants. Pediatr Res. https://doi.org/10.1203/01.pdr.0000304937.38669.63

    Article  PubMed  Google Scholar 

  10. Elsmén E, Källén K, Maršál K, Hellström-Westas L (2006) Fetal gender and gestational-age-related incidence of pre-eclampsia. Acta Obstet Gynecol Scand 85:1285–1291. https://doi.org/10.1080/00016340600578274

    Article  PubMed  Google Scholar 

  11. Schalekamp-Timmermans S, Arends LR, Alsaker E, Chappell L, Hansson S, Harsem NK et al (2017) Fetal sex-specific differences in gestational age at delivery in pre-eclampsia: a meta-analysis. Int J Epidemiol 46:632–642. https://doi.org/10.1093/ije/dyw178

    Article  PubMed  Google Scholar 

  12. Vatten LJ, Skjærven R (2004) Offspring sex and pregnancy outcome by length of gestation. Early Hum Dev. https://doi.org/10.1016/j.earlhumdev.2003.10.006

    Article  PubMed  Google Scholar 

  13. Tsao PN, Wei SC, Su YN, Chou HC, Chen CY, Hsieh WS (2005) Excess soluble fms-like tyrosine kinase 1 and low platelet counts in premature neonates of preeclamptic mothers. Pediatrics. https://doi.org/10.1542/peds.2004-2240

    Article  PubMed  Google Scholar 

  14. Espinoza J, Vidaeff A, Pettker CM, Simhan H (2020) Gestational hypertension and preeclampsia: ACOG practice bulletin, Number 222. Obstet Gynecol;135. https://doi.org/10.1097/AOG.0000000000003891

  15. Kovo M, Schreiber L, Ben-Haroush A, Cohen G, Weiner E, Golan A et al (2013) The placental factor in early- and late-onset normotensive fetal growth restriction. Placenta. https://doi.org/10.1016/j.placenta.2012.11.010

    Article  PubMed  Google Scholar 

  16. Miremberg H, Gindes L, Schreiber L, Raucher Sternfeld A, Bar J, Kovo M (2019) The association between severe fetal congenital heart defects and placental vascular malperfusion lesions. Prenat Diagn. https://doi.org/10.1002/pd.5515

    Article  PubMed  Google Scholar 

  17. Dollberg S, Haklai Z, Mimouni FB, Gorfein I, Gordon ES (2005) Birthweight standards in the live-born population in Israel. Isr Med Assoc J 7:311–314

    PubMed  Google Scholar 

  18. Redline RW (2015) Classification of placental lesions. Am J Obstet Gynecol 213:S21–S28. https://doi.org/10.1016/j.ajog.2015.05.056

    Article  PubMed  Google Scholar 

  19. Khong TY, Mooney EE, Ariel I, Balmus NCM, Boyd TK, Brundler MA et al (2016) Sampling and definitions of placental lesions Amsterdam placental workshop group consensus statement. Arch Pathol Lab Med 140:698–713. https://doi.org/10.5858/arpa.2015-0225-CC

    Article  PubMed  Google Scholar 

  20. Pinar H, Sung CJ, Oyer CESD (1996) Reference values for singleton and twin placental weights. Pediatr Pathol Lab Med. https://doi.org/10.1080/15513819609168713

    Article  PubMed  Google Scholar 

  21. Stark MJ, Wright IMR, Clifton VL (2009) Sex-specific alterations in placental 11β-hydroxysteroid dehydrogenase 2 activity and early postnatal clinical course following antenatal betamethasone. Am J Physiol Regul Integr Comp Physiol. https://doi.org/10.1152/ajpregu.00175.2009

    Article  PubMed  Google Scholar 

  22. Mastrogiannis DS, O’Brien WF, Krammer J, Benoit R (1991) Potential role of endothelin-1 in normal and hypertensive pregnancies. Am J Obstet Gynecol. https://doi.org/10.1016/0002-9378(91)90020-R

    Article  PubMed  Google Scholar 

  23. Orbak Z, Zor N, Energin VM, Selimoǧlu MA, Handan ALP, Akçay F (1998) Endothelin-1 levels in mothers with eclampsia—pre-eclampsia and their newborns. J Trop Pediatr. https://doi.org/10.1093/tropej/44.1.47

    Article  PubMed  Google Scholar 

  24. Walker BR, Connacher AA, Webb DJ, Edwards CRW (1992) Glucocorticoids and blood pressure: a role for the cortisol/cortisone shuttle in the control of vascular tone in man. Clin Sci 83:171–178. https://doi.org/10.1042/cs0830171

    Article  CAS  Google Scholar 

  25. Trivers RL, Willard DE (1973) Natural selection of parental ability to vary the sex ratio of offspring. Science (80-). https://doi.org/10.1126/science.179.4068.90

    Article  Google Scholar 

  26. Catalano R, Bruckner T (2006) Secondary sex ratios and male lifespan: Damaged or culled cohorts. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.0510567103

    Article  PubMed  PubMed Central  Google Scholar 

  27. Murji A, Proctor LK, Paterson AD, Chitayat D, Weksberg R, Kingdom J (2012) Male sex bias in placental dysfunction. Am J Med Genet Part A. https://doi.org/10.1002/ajmg.a.35250

    Article  PubMed  Google Scholar 

  28. Brown RN (2016) Maternal adaptation to pregnancy is at least in part influenced by fetal gender. BJOG An Int J Obstet Gynaecol. https://doi.org/10.1111/1471-0528.13529

    Article  Google Scholar 

  29. Parra-Saavedra M, Crovetto F, Triunfo S, Savchev S, Peguero A, Nadal A et al (2014) Neurodevelopmental outcomes of near-term small-for-gestational-age infants with and without signs of placental underperfusion. Placenta. https://doi.org/10.1016/j.placenta.2014.01.010

    Article  PubMed  Google Scholar 

  30. Parra-Saavedra M, Crovetto F, Triunfo S, Savchev S, Peguero A, Nadal A et al (2014) Association of Doppler parameters with placental signs of underperfusion in late-onset small-for-gestational-age pregnancies. Ultrasound Obstet Gynecol. https://doi.org/10.1002/uog.13358

    Article  PubMed  Google Scholar 

Download references

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Departments of Obstetrics and Gynecology, The Edith Wolfson Medical Center, P.O Box 5, 58100, Holon, Israel

    Hadas Miremberg, Hadas Ganer Herman, Mor Bustan, Eran Weiner, Jacob Bar & Michal Kovo

  2. Department of Pathology, The Edith Wolfson Medical Center, Holon, Israel

    Letizia Schreiber

  3. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Hadas Miremberg, Hadas Ganer Herman, Mor Bustan, Eran Weiner, Letizia Schreiber, Jacob Bar & Michal Kovo

Authors
  1. Hadas Miremberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hadas Ganer Herman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mor Bustan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eran Weiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Letizia Schreiber
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jacob Bar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michal Kovo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HM and MK: protocol development and methodology, manuscript writing and editing. MB: data collection and management. HGH and LS: data analysis, management and data interpretation. JB and EW: manuscript writing and editing.

Corresponding author

Correspondence to Hadas Miremberg.

Ethics declarations

Ethical approval

Approval for the study was obtained from the local ethics committee (decision number 0042-10-WOMC). In all the cases, the placentas were sent to histopathology for evaluation, in accordance with our departmental policy that routinely performs placental analyses in complicated pregnancies.

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

The institutional ethics committee exempted the authors from obtaining individual informed consent.

Data statement

Data available on request due to privacy/ethical restrictions.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Miremberg, H., Ganer Herman, H., Bustan, M. et al. Placental vascular lesions differ between male and female fetuses in early-onset preeclampsia. Arch Gynecol Obstet 306, 717–722 (2022). https://doi.org/10.1007/s00404-021-06328-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-021-06328-9

Keywords

Search

Navigation