Intratesticular 13‐cis retinoic acid is lower in men with abnormal semen analyses: a pilot study

Abstract

Intratesticular retinoic acid is necessary for spermatogenesis, but the relationship between intratesticular retinoic acid and sperm quality in man has not been studied. We hypothesized that intratesticular concentrations of retinoic acid would be lower in men with abnormal semen analyses compared to men with normal semen analyses. We recruited men requiring scrotal or penile surgery in a pilot observational study examining the relationship between sperm quality and intratesticular and serum retinoic acid. Twenty‐four men provided two pre‐operative blood and semen samples, and underwent a testicular biopsy during surgery. Serum and tissue all‐trans and 13‐cis retinoic acid and reproductive hormones were measured by LC/MS/MS and radioimmunoassays, respectively. Seven men had abnormal semen analyses by at least one WHO criteria and 17 men were normal. In men with abnormal semen, the median (25th, 75th percentile) intratesticular 13‐cis retinoic acid was 0.14 (0.08, 0.25) pmol/gram tissue compared with 0.26 (0.18, 0.38) pmol/gram tissue in men with normal semen (p = 0.04). There were no significant differences in intratesticular all‐trans retinoic acid or serum reproductive hormones between men with normal and abnormal semen analyses. Intratesticular 13‐cis retinoic acid is significantly lower in men with abnormal semen analyses compared to men with normal semen analyses. Lower intratesticular 13‐cis retinoic acid concentrations may be due to decreased biosynthesis or increased metabolism in the testes. Further investigation of the relationship between intratesticular 13‐cis retinoic acid and poor sperm quality is warranted to determine if this association is present in infertile men.

Isotretinoin administration improves sperm production in men with infertility from oligoasthenozoospermia: a pilot study

“…To understand the relationship between intratesticular retinoic acid and sperm production in man, we measured tissue concentrations of all- trans and 13- cis -retinoic acid in testicular tissue from 24 men undergoing scrotal surgery, and found that concentrations of 13- cis -retinoic acid were significantly reduced in the men with abnormal sperm production (Nya-Ngatchou et al 2013). This finding suggested that some men with infertility might have reduced concentrations of retinoic acid in their testes, possibly due to deficient biosynthesis.…”

Importance of ALDH1A enzymes in determining human testicular retinoic acid concentrations

“…The fact that ALDH1A1 was the one enzyme able to form 13-cis RA is of interest because in a preliminary study of 24 men, an association between intratesticular 13-cis RA and abnormal semen was revealed, suggesting that altered intratesticular RA homeostasis may be present in infertile men ( 43 ). In addition, 13-cis RA treatment has been shown to increase sperm production in humans ( 44 ).…”

Levels of the retinoic acid synthesizing enzyme aldehyde dehydrogenase-1A2 are lower in testicular tissue from men with infertility

“…More feasibly, a low intratesticular concentration of retinoic acid could occur in an infertile man due to impaired retinoic acid biosynthesis from vitamin A or increased catabolism of retinoic acid to inactive metabolites. Recently, our group observed that concentrations of intratesticular retinoic acid were significantly lower in men with sub-normal sperm quality as compared to men with normal sperm quality (18). However, the direct measurement of testicular retinoic acid concentrations is challenging given its low concentration in tissue, the corresponding need for large samples of testicular tissue, and the specialized collection techniques required given the photo-sensitivity of retinoic acid, which rapidly degrades with light exposure.…”