Testicular transcriptional signatures associated with high fertility

Abstract

Factors of high fertility are poorly described. The majority of transgenic or knockout models with a reproductive phenotype are subfertile or infertile phenotypes. Few genotypes have been linked to improved reproductive performance (0.2%) or increased litter size (1%). In this study, we used a unique mouse model, fertility line FL1, selected for 'high fertility' for more than 170 generations. This strain has almost doubled the number of littermates as well as their total birth weight accompanied by an elevated ovulation rate and increased numbers of corpora lutea compared to a randomly mated and unselected control line (Ctrl). Here, we investigate whether the gonadal tissue of FL1 males are affected by 'co-evolution' after more than 40 years of female-focused selection. Using microarrays, we analysed the testicular transcriptome of the FL1 and Ctrl mice. These data were also compared with previously published female gonadal transcriptional alterations. We detected alterations in testicular gene expression, which are partly associated with female reproductive performance. Thus, female-focused selection for litter size has not only affected the female side, but also has been manifested in transcriptional alterations on the male gonadal organ. This suggests consequences for the entire mouse lines in the long run and emphasizes the perspective of inevitably considering both genders about mechanisms of high fertility.

Altered testicular cell type composition in males of two outbred mouse lines selected for high fertility

“…Elevated numbers of Leydig cells in FL1 are not accompanied by significantly increased intestinal area (Figure 4B) and are not associated with Leydig cell hyperplasia and decreased fertility as it has been described for several knockout mouse models 27‐29 . Accelerated gene transcription of Leydig cell markers in FL1 has already been reported in previous work 15,18 . Based on this observation, one might suggest elevated testosterone concentrations in FL1 males compared to Ctrl and FL2 males.…”

“…Since we noticed slightly elevated progesterone and corticosterone levels in FL1, 16 the effect of unaffected steady‐state androgen concentrations might be explained by an accelerated metabolic turnover rate in these animals. In line with this assumption, we noticed altered steady‐state transcript levels of steroid hormone clearance enzymes (such as Sult1e1) in holistic gene expression analysis from FL1 testis 15 …”

“…Since our gene expression data indicate elevated Leydig cell‐specific gene transcripts (eg Cyp11, Cyp17) from testis of FL1 compared to Ctrl and FL2 bucks, 15,18 we tested the hypothesis whether these increased diploid cell population might be Leydig cells. To this end, we incubated testicular cell populations from Ctrl, FL1 and FL2 with an antibody directed against Cyp17 and counter stained the entire cell population by propidium iodide.…”

“…These selection criteria prevent any signs of developmental failures in newborn puppies. After > 40 years and 170 generations of selection these mouse lines almost doubled the amount of offspring per litter up to 20.5 and 21.1, respectively 14,15 …”

“…The rationale of the present study was to clarify whether long‐term selection of a primarily female‐derived trait of high fertility (increased litter size) also leads to alterations on the male side. We described differences in physiological and behavioural parameters as well as in endocrine and molecular markers between males of the FLs compared to control bucks 14,15,17 . Since we noticed elevated Leydig cell‐specific gene transcription in FL1 bucks 18 but neither in FL2 nor in control (Ctrl) males, we were interested to address this question in more details.…”