Selected Genetic Factors Associated with Primary Ovarian Insufficiency

Abstract

Primary ovarian insufficiency (POI) is a heterogeneous disease resulting from non-functional ovaries in women before the age of 40. It is characterized by primary amenorrhea or secondary amenorrhea. As regards its etiology, although many POI cases are idiopathic, menopausal age is a heritable trait and genetic factors play an important role in all POI cases with known causes, accounting for approximately 20% to 25% of cases. This paper reviews the selected genetic causes implicated in POI and examines their pathogenic mechanisms to show the crucial role of genetic effects on POI. The genetic factors that can be found in POI cases include chromosomal abnormalities (e.g., X chromosomal aneuploidies, structural X chromosomal abnormalities, X-autosome translocations, and autosomal variations), single gene mutations (e.g., newborn ovary homeobox gene (NOBOX), folliculogenesis specific bHLH transcription factor (FIGLA), follicle-stimulating hormone receptor (FSHR), forkhead box L2 (FOXL2), bone morphogenetic protein 15 (BMP15), etc., as well as defects in mitochondrial functions and non-coding RNAs (small ncRNAs and long ncRNAs). These findings are beneficial for doctors to diagnose idiopathic POI cases and predict the risk of POI in women.

TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2

“…Several genes have been associated with POI, such as BRCA2 [ 7 ], C14orf39 [ 8 ], ZSWIM7 [ 9 ], PSMC3IP [ 10 ], NHEJ1 [ 11 ], HSF2BP [ 12 ], MSH4 [ 13 ], MSH5 [ 14 ], FIGLA [ 15 ], NOBOX [ 16 ], STAG3 [ 17 ], MCM8/9 [ 18 ], HFM1 [ 19 ], EIF4ENIF1 [ 20 ], KHDRBS1 [ 21 ], NOTCH2 [ 22 ], BNC1 [ 23 ]. These genes participate in various activities such as folliculogenesis, gonadogenesis, oocyte maturation, DNA damage, meiosis, cell apoptosis, and various other functions [ 24 ].…”

The Role of Lifestyle and Dietary Factors in the Development of Premature Ovarian Insufficiency

“…A recent review [ 12 ] highlights 107 different genes associated with POI and suggests that approximately 78% of the genes are associated with ovarian development and meiosis. New genetic technologies based on next-generation sequencing have highlighted defects in the various hormones related to folliculogenesis, reproductive hormones and mitochondria function [ 13 ]. However, there is now a growing number of genes that are implicated in DNA replication and repair, meiosis and chromosome stability that are associated with the age of menopause and POI [ 14 ].…”

Nuclear Estrogen Receptors in Prostate Cancer: From Genes to Function

“…Finally, the placenta produces estrogens during pregnancy, primarily estriol and estradiol, by aromatizing fetal steroids of an adrenal origin [ 17 , 18 ]. A deficit of estrogens may lead to a range of symptoms [ 19 , 20 ] at different grades that, at the level of the ovary, may be identified as an irregular menstrual cycle or amenorrhea [ 21 , 22 , 23 ]. Also, a deficit of estrogens is classically associated with an impaired bone metabolism and increased risk of osteoporosis [ 24 ], since these hormones regulate bone cell functions and the remodeling of this tissue [ 25 , 26 ].…”