Gene mutations associated with fertilization failure after in vitro fertilization/intracytoplasmic sperm injection

Abstract

Fertilization failure during assisted reproductive technologies (ART) is often unpredictable, as this failure is encountered only after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) have been performed. The etiology of fertilization failure remains elusive. More and more mutations of genes are found to be involved in human fertilization failure in infertile patients as high throughput sequencing techniques are becoming widely applied. In this review, the mutations of nine important genes expressed in sperm or oocytes, PLCZ1, ACTL7A, ACTL9, DNAH17, WEE2, TUBB8, NLRP5, ZP2, and TLE6, were summarized and discussed. These abnormalities mainly have shown Mendelian patterns of inheritance, including dominant and recessive inheritance, although de novo mutations were present in some cases. The review revealed the crucial roles of each reported gene in the fertilization process and summarized all known mutations and their corresponding phenotypes. The review suggested the mutations might become promising targets for precision treatments in reproductive medicine. Moreover, our work will provide some helpful clues for genetic counseling, risk prediction, and optimizing clinical treatments for human infertility by supplying the useful and timely information on the genetic causes leading to fertilization failure.

Inhibition of Prolactin Affects Epididymal Morphology by Decreasing the Secretion of Estradiol in Cashmere Bucks

“…In the present study, we found that DEGs (including ACTL7A, ACTRT3, and SPESP1 ) were significantly enriched in cell components, such as the germ cell nucleus and male germ cell nucleus. ACTL7A is essential for early embryonic development, and its reduction could lead to poor embryonic development and even infertility [ 47 , 48 , 49 , 50 ]. The deletion of SPESP1 led to an abnormal distribution of multiple proteins in mouse spermatozoa, reduced the sperm fusion capacity, and reduced the number of pups [ 51 ].…”

The Global Decline in Human Fertility: The Post-Transition Trap Hypothesis

“…As well as facilitating the vertical transmission of infertility-inducing mutations, ICSI may also result in the creation of de novo mutations in the offspring due to the aberrant repair of sperm DNA damage in the newly formed zygote [ 88 , 97 ]. Such de novo mutations may then result in compromised fertility in the offspring affecting oocyte maturation, embryo development and normal testicular function [ 98 , 99 , 100 , 101 ].…”