Defects in meiosis I contribute to the genesis of androgenetic hydatidiform moles
File(s)
Author(s)
Type
Journal Article
Abstract
To identify novel genes responsible for recurrent hydatidiform moles (HMs), we performed exome sequencing on 75 unrelated patients who were negative for mutations in the known genes. We identified biallelic deleterious variants in 6 genes, FOXL2, MAJIN, KASH5, SYCP2, MEIOB, and HFM1, in patients with androgenetic HMs, including a familial case of 3 affected members. Five of these genes are essential for meiosis I, and their deficiencies lead to premature ovarian insufficiency. Advanced maternal age is the strongest risk factor for sporadic androgenetic HM, which affects 1 in every 600 pregnancies. We studied Hfm1–/– female mice and found that these mice lost all their oocytes before puberty but retained some at younger ages. Oocytes from Hfm1–/– mice initiated meiotic maturation and extruded the first polar bodies in culture; however, their meiotic spindles were often positioned parallel, instead of perpendicular, to the ooplasmic membrane at telophase I, and some oocytes extruded the entire spindle with all the chromosomes into the polar bodies at metaphase II, a mechanism we previously reported in Mei1–/– oocytes. The occurrence of a common mechanism in two mouse models argues in favor of its plausibility at the origin of androgenetic HM formation in humans.
Date Issued
2024-11-15
Date Acceptance
2024-09-26
Citation
Journal of Clinical Investigation, 2024, 134 (22)
ISSN
0021-9738
Publisher
American Society for Clinical Investigation
Journal / Book Title
Journal of Clinical Investigation
Volume
134
Issue
22
Copyright Statement
Copyright: © 2024, Rezaei et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39545410
PII: 170669
Subjects
CHROMOSOME SYNAPSIS
DNA
EMBRYONIC ARREST
FEMALE INFERTILITY
GENETICS
Life Sciences & Biomedicine
Medicine, Research & Experimental
MEIOTIC PROGRESSION
MOUSE OOCYTES
MUTATIONS
Research & Experimental Medicine
Science & Technology
TROPHOBLASTIC DISEASE
VARIANTS
Publication Status
Published
Coverage Spatial
United States
Article Number
e170669
Date Publish Online
2024-11-15