TERRA: A Novel Biomarker of Embryo Quality and Art Outcome

Maria Santa Rocca; Ludovica Dusi; Andrea Di Nisio; Erminia Alviggi; Benedetta Iussig; Sara Bertelle; Luca De Toni; Andrea Garolla; Carlo Foresta; Alberto Ferlin

doi:10.3390/genes12040475

Assisted Reproduction Add-Ons and Adjuncts

TERRA: A Novel Biomarker of Embryo Quality and Art Outcome

Rocca MS, Dusi L, Di Nisio A, Alviggi E, Iussig B, Bertelle S, De Toni L, Garolla A, Foresta C, Ferlin A

Published March 25, 2021 Genes

DOI 10.3390/genes12040475 PMID 33806168 PMC PMC8066328

RRM Academy Synopsis

Higher sperm TERRA went with better embryo quality in ICSI cycles

A prospective study of 35 men whose partners had ICSI, a form of IVF that injects one sperm into an egg, found that higher sperm TERRA levels went with better embryo quality in the ICSI group. The ICSI group also had lower sperm TERRA and shorter sperm telomeres than 30 fertile men. The authors call the findings preliminary.

Key Findings

Sperm TERRA expression and sperm telomere length were both lower in the 35 men in the ICSI group than in the 30 fertile controls (both p < 0.001).
TERRA expression correlated positively with embryo quality (r = 0.655, p < 0.001) and with sperm telomere length (r = 0.428, p = 0.010).
In stepwise regression, TERRA expression was the sole independent variable linked to embryo quality in the ICSI group (β = 0.578, p < 0.001) and explained 33.1% of the variance.
Blastocyst transfer took place in 7 of the 35 couples. Four transfers, all in couples with a normal semen analysis in the male partner, ended in clinical pregnancy and delivery.

Interpretation

The study compared 35 men from couples having a first fresh ICSI cycle with 30 volunteer men of proven fertility. It measured TERRA, a long non-coding RNA found at chromosome ends, in sperm. In these 35 men, correlation and regression analyses show association. The authors state that the results allow no conclusion on the overall effect of TERRA on reproductive success. They name the small sample and missing data on sperm DNA integrity as major limitations. The authors note that embryo quality also depends on egg quality, and 24 of the women had female-factor diagnoses. The two groups differed in age, but age did not correlate with TERRA.

RRM Context

The authors cite male factor in about 50% of infertility cases and say about one-third of causes remain unexplained. Restorative reproductive medicine treats unexplained infertility as undiagnosed and evaluates both partners. A sperm marker tied to embryo quality points to why conception can fail. ICSI bypasses that question. The authors suggest testing TERRA as a biomarker in fertility treatments.

Our editorial summary of this paper, not the article's abstract.

Abstract

Telomeres are considered to be an internal biological clock, and their progressive shortening has been associated with the risk of age-related diseases and reproductive alterations. Over recent years, an increasing number of studies have focused on the association between telomere length and fertility, identifying sperm telomere length (STL) as a novel biomarker of male fertility. Although typically considered to be repeated DNA sequences, telomeres have recently been shown to also include a long non-coding RNA (lncRNA) known as TERRA (telomeric repeat-containing RNAs). Interestingly, males with idiopathic infertility show reduced testicular TERRA expression, suggesting a link between TERRA and male fertility. The aim of this study was to investigate the role of seminal TERRA expression in embryo quality. To this end, STL and TERRA expression were quantified by Real Time qPCR in the semen of 35 men who underwent assisted reproductive technologies (ART) and 30 fertile men. We found that TERRA expression in semen and STL was reduced in patients that underwent ART (both p < 0.001). Interestingly, TERRA and STL expressions were positively correlated (p = 0.010), and TERRA expression was positively associated with embryo quality (p < 0.001). These preliminary findings suggest a role for TERRA in the maintenance of sperm telomere integrity during gametogenesis, and for the first time, TERRA expression was found as a predictive factor for embryo quality in the setting of assisted reproduction.

Topics

Assisted Reproduction › Add-Ons and Adjuncts › Adjunct Evidence Base · Male Fertility › Male Endocrine and Genetic Factors › Genetic Causes of Male Infertility · Genetics and Immunology › Reproductive Genetics › Epigenetics

Maria Santa Rocca, Ludovica Dusi, Andrea Di Nisio, Erminia Alviggi, Benedetta Iussig, Sara Bertelle, Luca De Toni, Andrea Garolla, Carlo Foresta, Alberto Ferlin

M Rocca, L Dusi, A Nisio, E Alviggi, B Iussig, S Bertelle, L Toni, A Garolla, C Foresta, A Ferlin

PMID 33806168 33806168 DOI 10.3390/genes12040475 10.3390/genes12040475 Rocca et al. 2021, Rocca 2021

TERRA: A Novel Biomarker of Embryo Quality and Art Outcome

Higher sperm TERRA went with better embryo quality in ICSI cycles

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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