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Maternal selection of human embryos in early gestation: Insights from recurrent miscarriage

Journal

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
Volume 131, Issue -, Pages 14-24

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2022.01.007

Keywords

Miscarriage; Embryo; Aneuploidy; Endometrium; Decidualization; Placenta; Selection

Funding

  1. Tommy's Baby Charity, United Kingdom
  2. National Institutes of Health (NIH), United States of America [R35GM133747]
  3. Wellcome Trust Investigator Award, United Kingdom [212233/Z/18/Z]
  4. Wellcome Trust [212233/Z/18/Z] Funding Source: Wellcome Trust

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Compared to other mammals, human pregnancy is unique in its involvement of chromosomally diverse embryos and the cyclical breakdown and regeneration of the uterine mucosa. Understanding the mechanisms behind miscarriage can provide insights into the maternal selection of embryos during early gestation.
Compared to most mammals, human pregnancy is unusual in that it involves chromosomally diverse embryos, cyclical breakdown and regeneration of the uterine mucosa, and intimate integration of fetal and maternal cells at the uteroplacental interface. Not surprisingly, pregnancy often falters in early gestation. Whether these losses result in clinical miscarriages depends on the origins and impacts of chromosomal errors on fetal development and the ability of the decidualizing endometrium to engage in embryo biosensing and selection. Aneuploidy originating in oocytes during meiosis drives the age-related risk of miscarriage. By contrast, the frequency of endometrial cycles with an impaired decidual response may account for the stepwise increase in miscarriage rates with each pregnancy loss independently of maternal age. Additional physiological mechanisms operate in early gestation to ensure that most failing pregnancies are lost before vascular maternal-fetal connections are established by the end of the first trimester. Here, we summarise how investigations into the mechanisms that cause miscarriage led to new insights into the processes that govern maternal selection of human embryos in early gestation.

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