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Review
. 2019 Sep 1;101(3):549-566.
doi: 10.1093/biolre/ioz084.

Genetics of human female infertility†

Svetlana A Yatsenko  1   2   3   4 , Aleksandar Rajkovic  5   6   7
Affiliations
Review

Genetics of human female infertility†

Svetlana A Yatsenko et al. Biol Reprod. .

Abstract

About 10% of women of reproductive age are unable to conceive or carry a pregnancy to term. Female factors alone account for at least 35% of all infertility cases and comprise a wide range of causes affecting ovarian development, maturation of oocytes, and fertilization competence, as well as the potential of a fertilized egg for preimplantation development, implantation, and fetal growth. Genetic abnormalities leading to infertility in females comprise large chromosome abnormalities, submicroscopic chromosome deletion and duplications, and DNA sequence variations in the genes that control numerous biological processes implicated in oogenesis, maintenance of ovarian reserve, hormonal signaling, and anatomical and functional development of female reproductive organs. Despite the great number of genes implicated in reproductive physiology by the study of animal models, only a subset of these genes is associated with human infertility. In this review, we mainly focus on genetic alterations identified in humans and summarize recent knowledge on the molecular pathways of oocyte development and maturation, the crucial role of maternal-effect factors during embryogenesis, and genetic conditions associated with ovarian dysgenesis, primary ovarian insufficiency, early embryonic lethality, and infertility.

Keywords: X chromosome; female infertility; follicular development; genetics; oocyte development; preimplantation embryo; premature ovarian failure.

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Figures

Figure 1.
Figure 1.
Biological processes and genetic causes implicated in female infertility. Large X chromosome alterations are the frequent cause of ovarian dysgenesis. A less severe phenotype manifesting as primary or secondary amenorrhea as well as reduced fetal viability can be seen in patients with balanced rearrangements, submicroscopic alterations, and single gene defects. Reproductive potential in patients with genomic alterations and syndromic conditions greatly depends on diagnosis, genes affected, and concomitant manifestations. Causative genes are displayed beneath the key biological processes, however can be involved in multiple pathways, affecting several stages of oocyte development.
See this image and copyright information in PMC

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