Abstract
The four human PIWI-LIKE gene family members PIWI-LIKE 1–4 play a pivotal role in stem cell maintenance and transposon repression in the human germline. Therefore, dysregulation of these genes negatively influences the genetic stability of the respective germ cell and subsequent development and maturation. Recently, we demonstrated that a lower PIWI-LIKE 2 mRNA expression in ejaculated spermatozoa is more frequent in men with oligozoospermia. In this study, we analysed how PIWI-LIKE 1–4 mRNA expression in ejaculated spermatozoa predicts ART outcome. From 160 IVF or ICSI cycles, portions of swim-up spermatozoa used for fertilization were collected, and the total RNA was isolated. PIWI-LIKE 1–4 mRNA expression was measured by qPCR using TaqMan probes with GAPDH as a reference gene. PIWI-LIKE 1 and 2 transcript levels in the spermatozoa of the swim-up fraction were positively correlated to each other (rS = 0.78; p < 0.001). Moreover, lower PIWI-LIKE 2 mRNA levels, as well as lower PIWI-LIKE 1 mRNA levels, in these spermatozoa were positively associated with a fertilization rate ≥ 50% in the respective ART cycles (p = 0.02 and p = 0.0499, Mann–Whitney U-Test). When separately analysing IVF and ICSI cycles, PIWI-LIKE 1 and 2 transcript levels were only significantly associated to increased fertilization rates in IVF, yet not in ICSI cycles. Spermatozoal PIWI-LIKE 3 and 4 transcript levels were not significantly associated to fertilization rates in ART cycles. In conclusion, lower levels of spermatozoal PIWI-LIKE 1 and 2 mRNA levels are positively associated with a higher fertilization rate in IVF cycles.
Highlights
Infertility is a major health problem worldwide, with an estimated 48.5 million couples suffering from unwilling childlessness [1]
While PIWI-LIKE 1 expression could be quantified in 96.2% and 98.2% of the patients’ samples, PIWI-LIKE 2 was measurable in 74.9% and 75.2% of the samples, respectively
In cycles with ≥ 8 inseminated oocytes, the correlation between a lower PIWI-LIKE 1 or 2 mRNA expression and a fertilization rate ≥50% was even more pronounced (p = 0.019 or p = 0.009, respectively, Mann–Whitney U-test)
Summary
Infertility is a major health problem worldwide, with an estimated 48.5 million couples suffering from unwilling childlessness [1]. Male infertility contributes to roughly half of these cases, and impacts the reproductive function, but is linked to the overall health of the affected male [2,3]. Many couples with infertile men are referred to assisted reproduction therapy (IVF or ICSI), by which the disturbances in the sperm variables are encompassed by the in vitro selection of optimal spermatozoa. The selection of human spermatozoa based on criteria such as viability, motility, and morphology does not necessarily reflect in the subsequent sperm fertilizing capacity [4,5,6].
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