Roles of small RNAs in the effects of nutrition on apoptosis and spermatogenesis in the adult testis

Abstract

We tested whether reductions in spermatozoal quality induced by under-nutrition are associated with increased germ cell apoptosis and disrupted spermatogenesis, and whether these effects are mediated by small RNAs. Groups of 8 male sheep were fed for a 10% increase or 10% decrease in body mass over 65 days. Underfeeding increased the number of apoptotic germ cells (P < 0.05) and increased the expression of apoptosis-related genes (P < 0.05) in testicular tissue. We identified 44 miRNAs and 35 putative piRNAs that were differentially expressed in well-fed and underfed males (FDR < 0.05). Some were related to reproductive system development, apoptosis (miRNAs), and sperm production and quality (piRNAs). Novel-miR-144 (miR-98), was found to target three apoptotic genes (TP53, CASP3, FASL). The proportion of miRNAs as a total of small RNAs was greater in well-fed males than in underfed males (P < 0.05) and was correlated (r = 0.8, P < 0.05) with the proportion of piRNAs in well-fed and underfed males. In conclusion, the reductions in spermatozoal quality induced by under-nutrition are caused, at least partly, by disruptions to Sertoli cell function and increased germ cell apoptosis, mediated by changes in the expression of miRNAs and piRNAs.

Small RNA sequencing of cryopreserved semen from single bull revealed altered miRNAs and piRNAs expression between High- and Low-motile sperm populations

“…The relative expression in HM and LM fractions of several of these known miRNAs, including bta-miR-103, bta-miR-30b-5p, bta-miR-17-5p, bta-miR-106b, bta-miR-142-3p, bta-miR-34b, bta-miR-18a, bta-miR-34c, bta-miR-455-5p, bta-miR-10b, bta-miR-99b, bta-miR-1246, bta-miR-99a-5p, and bta-miR-1388-5p, was consistent with the relative abundance of their homologous miRNAs, observed in the normal vs abnormal sperm. Conversely, bta-miR-26a, bta-miR-24 and bta-miR-100 showed an opposite expression in our samples with respect to what previously described in literature [26, 27, 55]. bta-miR-122 and bta-miR-574 expression in the HM or LM fraction was only partially in agreement with what reported in previous studies [26, 27, 56].…”

“…bta-miR-122 and bta-miR-574 expression in the HM or LM fraction was only partially in agreement with what reported in previous studies [26, 27, 56]. Different miRNAs, including miR10b, miR-26, miR-34c and miR-99a, were also seen to change their expression level in underfed animals, and these variations were postulated to cause reduction in spermatozoa quality by disruption to Sertoli cell function and to increase germ cell apoptosis [55]. …”

“…The high level of miRNA conservation among species supports a direct comparison of our data with data presented in previous studies on different species. About half of the known miRNAs found in this study have been previously reported in sperm or testis tissue from other species: Ovis aries [55] and Homo sapiens [26, 27, 56]. The relative expression in HM and LM fractions of several of these known miRNAs, including bta-miR-103, bta-miR-30b-5p, bta-miR-17-5p, bta-miR-106b, bta-miR-142-3p, bta-miR-34b, bta-miR-18a, bta-miR-34c, bta-miR-455-5p, bta-miR-10b, bta-miR-99b, bta-miR-1246, bta-miR-99a-5p, and bta-miR-1388-5p, was consistent with the relative abundance of their homologous miRNAs, observed in the normal vs abnormal sperm.…”

Cellular and molecular responses of adult testis to changes in nutrition: novel insights from the sheep model

“…We found that 12 genes involved in apoptosis could be targeted by 9 miRNAs that were expressed differentially between well-fed and underfed sheep, with novelmiR-144 targeting four of the apoptosis-related genes (FASL, CASP3, BCL2L1, TP53;Guan et al 2015). These findings led us to conclude that the decline in sperm production and sperm quality induced by undernutrition in the sexually mature sheep are mediated at least partly by increased apoptosis in germ cells, and this process is mediated by changes in the expression of miRNAs .…”

“…The Sertoli cell responses, combined with nutrition-induced changes in germ cell apoptosis, affect the quantity and quality of spermatozoa produced. Modified from Guan et al (2015).…”