High-fertility phenotypes: two outbred mouse models exhibit substantially different molecular and physiological strategies warranting improved fertility

Abstract

Animal models are valuable tools in fertility research. Worldwide, there are more than 400 transgenic or knockout mouse models available showing a reproductive phenotype; almost all of them exhibit an infertile or at least subfertile phenotype. By contrast, animal models revealing an improved fertility phenotype are barely described. This article summarizes data on two outbred mouse models exhibiting a 'high-fertility' phenotype. These mouse lines were generated via selection over a time period of more than 40 years and 161 generations. During this selection period, the number of offspring per litter and the total birth weight of the entire litter nearly doubled. Concomitantly with the increased fertility phenotype, several endocrine parameters (e.g. serum testosterone concentrations in male animals), physiological parameters (e.g. body weight, accelerated puberty, and life expectancy), and behavioral parameters (e.g. behavior in an open field and endurance fitness on a treadmill) were altered. We demonstrate that the two independently bred high-fertility mouse lines warranted their improved fertility phenotype using different molecular and physiological strategies. The fertility lines display female-as well as male-specific characteristics. These genetically heterogeneous mouse models provide new insights into molecular and cellular mechanisms that enhance fertility. In view of decreasing fertility in men, these models will therefore be a precious information source for human reproductive medicine. Translated abstractA German translation of abstract is freely available at

piRNA-associated proteins and retrotransposons are differentially expressed in murine testis and ovary of aryl hydrocarbon receptor deficient mice

“…Recent studies using different physiological and molecular strategies have recognized the existence of high-fertility male mice phenotypes that are probably attributable to the accumulation of endocrine (hormonal levels, e.g. testosterone), physiological (accelerated puberty) and behavioural advantages [46,47]. We therefore suggest that the fertility of AhR −/− male mice may depend on improved sperm functionality and on endocrine, physiological and/or behavioural advantages due to AhR depletion.…”

“…A previous study showed that C57BL/6-Ahr m1.2Arte null-mice (Taconic) have an accumulation of elongated spermatids and reduced fertility compared with wild-type mice in in vitro fertilization assays [36]. This difference could be explained by the fact that the in vivo assay used in our study may be a more physiological approach to determine differences in mice fertility because it is known that the mating itself and the different molecules (hormones and growth factors among others) that altogether constitute the sperm have a relevant impact in mice fertility [46,47]. In addition, the former study used C57BL/6JAhr b-1 as wild-type controls (Jackson Labs), and their different genetic background with respect to C57BL/6-Ahr m1.2Arte null-mice could have influenced the in vitro phenotypes found.…”

Testicular transcriptional signatures associated with high fertility

“…Here we focus on the FL1 mouse line, which, after more than 170 generations of breeding, has almost double the selection traits litter size, and litter birth weight in comparison to the control line (Ctrl). This is accompanied by no sign of growth retardation in the offspring litters and no alteration in pup survival after weaning (Langhammer et al 2014).…”

“…The advantage of this approach is its heterogeneity, which more closely mimics the phenotypical alterations in humans than single gene approaches like classical transgenic or knockout models. Breeding strategies and comparative data for these high-fertility mouse lines have been described previously (Dietl et al 2004, Langhammer et al 2014.…”

Oocytes lacking O ‐glycans alter follicle development and increase fertility by increasing follicle FSH sensitivity, decreasing apoptosis, and modifying GDF9:BMP15 expression

“…Overexpression of Forkhead box O3 (FOXO3) in oocytes attenuates the postnatal decline of primordial follicles resulting in enhanced fertility (46). Using a different approach, outbred mice lines with high fertility have been obtained by selective breeding for more than 40 y (47).…”