Reproductive performance primarily depends on the female genotype in a two-factorial breeding experiment using high-fertility mouse lines

Mouse models showing an improved fertility phenotype are barely described in the literature. In the present study, we further characterized two outbred mouse models that have been selected for the phenotype ‘high fertility’ for more than 177 generations (fertility lines (FL) 1 and 2). In order to delineate the impact of males and females on fertility parameters, we performed a two-factorial breeding experiment by mating males and females of the three different genotypes (FL1, FL2, unselected control (Ctrl)) in all 9 possible combinations. Reproductive performance, such as number of offspring per litter or total birth weight of the entire pup, mainly depends on the female genotype. Although the reproductive performance of FL1 and FL2 is very similar, their phenotypes differ. FL2 animals of both genders are larger compared to FL1 and control animals. Females of the control line delivered offspring earlier compared to FL1 and FL2 dams. Males of FL1 are the lightest and the only ones who gained weight during the two weeks mating period. To address whether this effect is correlated with differing serum androgen levels, we measured the concentrations of testosterone, dehydroepiandrosterone, 4-androstenedione, androstanediol and dihydrotestosterone in males of all three lines by GC–MS. We measured serum testosterone between 5.0 and 6.4 ng/mL, whereas the concentrations of the other androgens were at least one order of magnitude lower, with no significant differences between the lines. Our data indicate that reproductive outcome largely depends on the genotype of the female in a two-factorial breeding experiment and supports previous findings that the phenotype ‘high fertility’ is warranted by using different physiological strategies.

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Testicular transcriptional signatures associated with high fertility

Reproduction ◽

10.1530/rep-17-0392 ◽

2018 ◽

Vol 155 (2) ◽

pp. 219-231 ◽

Cited By ~ 1

Author(s):

Marten Michaelis ◽

Alexander Sobczak ◽

Dirk Koczan ◽

Martina Langhammer ◽

Norbert Reinsch ◽

...

Keyword(s):

Litter Size ◽

Reproductive Performance ◽

Corpora Lutea ◽

High Fertility ◽

Control Line ◽

Female Side ◽

Long Run ◽

Transcriptional Alterations ◽

Selection For ◽

Reproductive Phenotype

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.

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241.Reproductive performance in Clock mutant mice

Reproduction Fertility and Development ◽

10.1071/srb04abs241 ◽

2004 ◽

Vol 16 (9) ◽

pp. 241

Author(s):

D. J. Kennaway ◽

A. Voultsios ◽

M. J. Boden

Keyword(s):

Reproductive Performance ◽

Clock Gene ◽

Mutant Mice ◽

Control Line ◽

Circadian Gene ◽

Significant Delay ◽

Clock Mutant ◽

Mutant Lines ◽

The Impact ◽

The Relationship

The relationship between circadian rhythmicity and rodent reproductive cyclicity is well established, but the impact of disrupted clock gene function on reproduction has not been investigated. This study evaluated the reproductive performance of melatonin deficient and proficient mice carrying a mutation in the core circadian gene, Clock. In natural matings, melatonin deficient Clock mutant mice took 2 to 3 days longer to mate and to subsequently deliver pups than their control line. The melatonin proficient mutants (Clock-MEL) had a smaller, but still significant delay (P < 0.05). The Clock mutation resulted in smaller median litter sizes compared to the control lines (7 v. 8 pups, P < 0.05) while melatonin proficiency reversed this difference. Survival to weaning was 84% and 80% for the melatonin deficient and proficient Clock mutant lines respectively, compared to 94 to 96% for their control lines. When immature mice were subjected to a standard PMSG/HCG superovulation protocol, Clock-MEL mice had lowered fertility and significantly fewer ovulations than their control line although embryo development appeared to be only slightly affected (Table 1, see PDF file).

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

Reproduction ◽

10.1530/rep-13-0425 ◽

2014 ◽

Vol 147 (4) ◽

pp. 427-433 ◽

Cited By ~ 8

Author(s):

Martina Langhammer ◽

Marten Michaelis ◽

Andreas Hoeflich ◽

Alexander Sobczak ◽

Jennifer Schoen ◽

...

Keyword(s):

Animal Models ◽

Mouse Models ◽

Information Source ◽

Serum Testosterone ◽

High Fertility ◽

Cellular Mechanisms ◽

Outbred Mouse ◽

Human Reproductive ◽

Almost All ◽

Mouse Lines

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 athttp://www.reproduction-online.org/content/147/4/427/suppl/DC1.

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Reproductive performance in female ClockΔ19 mutant mice

Reproduction Fertility and Development ◽

10.1071/rd04023 ◽

2004 ◽

Vol 16 (8) ◽

pp. 801 ◽

Cited By ~ 45

Author(s):

David J. Kennaway ◽

Michael J. Boden ◽

Athena Voultsios

Keyword(s):

Reproductive Performance ◽

Gene Function ◽

Clock Gene ◽

Circadian System ◽

Mutant Mice ◽

Constant Darkness ◽

Control Line ◽

Cba Mice ◽

The Impact ◽

The Relationship

The relationship between circadian rhythmicity and rodent reproductive cyclicity is well established, but the impact of disrupted clock gene function on reproduction has not been well established. The present study evaluated the reproductive performance of mice carrying the ClockΔ19 mutation that were either melatonin deficient (ClockΔ19/Δ19) or had the capacity to synthesise melatonin reinstated (ClockΔ19/Δ19+MEL). The ClockΔ19/Δ19 mice took 2–3 days longer to mate, and to subsequently deliver pups, than their control line. The melatonin-competent mutants had a smaller, but still significant (P < 0.05), delay. The ClockΔ19 mutation resulted in smaller median litter sizes compared with control lines (seven v. eight pups; P < 0.05), whereas melatonin proficiency reversed this difference. Survival to weaning was 84% and 80% for the ClockΔ19/Δ19 and ClockΔ19/Δ19+MEL lines, respectively, compared with 94–96% for the two control lines. The ClockΔ19/Δ19 mutants became behaviourally arrhythmic in constant darkness but, despite this, seven of seven became pregnant when paired with males after at least 14 days of constant darkness (five of seven within 4 days of pairing). In the ClockΔ19/Δ19+MEL mice, seven of 15 became arrhythmic in constant darkness but still became pregnant. The seven mice that free ran for at least 14 days in constant darkness with a period of 27.1 h also became pregnant. The present study has demonstrated that the ClockΔ19 mutation has significant, but subtle, effects on reproductive performance. The reintroduction of melatonin competency and/or other genes as a result of crosses with CBA mice reduced the impact of the mutation further. It would appear that redundancy in genes in the circadian system allows the reproductive cyclicity to persist in mice, albeit at a suboptimal level.

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Consideration of Gut Microbiome in Murine Models of Diseases

Microorganisms ◽

10.3390/microorganisms9051062 ◽

2021 ◽

Vol 9 (5) ◽

pp. 1062

Author(s):

Chunye Zhang ◽

Craig L. Franklin ◽

Aaron C. Ericsson

Keyword(s):

Animal Models ◽

Mouse Models ◽

Biomedical Research ◽

Gut Microbiome ◽

Close Association ◽

Disease Model ◽

Potential Contributor ◽

Potential Factors ◽

Models Of Disease ◽

The Impact

The gut microbiome (GM), a complex community of bacteria, viruses, protozoa, and fungi located in the gut of humans and animals, plays significant roles in host health and disease. Animal models are widely used to investigate human diseases in biomedical research and the GM within animal models can change due to the impact of many factors, such as the vendor, husbandry, and environment. Notably, variations in GM can contribute to differences in disease model phenotypes, which can result in poor reproducibility in biomedical research. Variation in the gut microbiome can also impact the translatability of animal models. For example, standard lab mice have different pathogen exposure experiences when compared to wild or pet store mice. As humans have antigen experiences that are more similar to the latter, the use of lab mice with more simplified microbiomes may not yield optimally translatable data. Additionally, the literature describes many methods to manipulate the GM and differences between these methods can also result in differing interpretations of outcomes measures. In this review, we focus on the GM as a potential contributor to the poor reproducibility and translatability of mouse models of disease. First, we summarize the important role of GM in host disease and health through different gut–organ axes and the close association between GM and disease susceptibility through colonization resistance, immune response, and metabolic pathways. Then, we focus on the variation in the microbiome in mouse models of disease and address how this variation can potentially impact disease phenotypes and subsequently influence research reproducibility and translatability. We also discuss the variations between genetic substrains as potential factors that cause poor reproducibility via their effects on the microbiome. In addition, we discuss the utility of complex microbiomes in prospective studies and how manipulation of the GM through differing transfer methods can impact model phenotypes. Lastly, we emphasize the need to explore appropriate methods of GM characterization and manipulation.

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The Impact of Work Hours on Depressive Symptoms among Koreans Aged 45 and Over

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18030853 ◽

2021 ◽

Vol 18 (3) ◽

pp. 853

Author(s):

Juyeong Kim ◽

Eun-Cheol Park

Keyword(s):

Older Adults ◽

Depressive Symptoms ◽

Social Services ◽

Depression Scale ◽

Epidemiological Studies ◽

Work Hours ◽

Middle Aged ◽

Health Studies ◽

Males And Females ◽

The Impact

Background: Given the documented importance of employment for middle-aged and older adults’ mental health, studies of the association between their number of work hours and depressive symptoms are needed. Objectives: To examine the association between the number of work hours and depressive symptoms in Korean aged 45 and over. Methods: We used data from the first wave to fourth wave of the Korea Longitudinal Study of Aging. Using the first wave at baseline, data included 9845 individuals. Depressive symptoms were measured using the 10-item Center for Epidemiological Studies Depression scale. We performed a longitudinal analysis to estimate the prevalence of depressive symptoms by work hours. Results: Both unemployed males and females aged 45–65 years were associated with higher depressive symptoms (β = 0.59, p < 0.001; β = 0.32, p < 0.001). Females working ≥ 69 h were associated with higher depressive symptoms compared to those working 41–68 h (β = 0.25, p = 0.013). Among those both middle-aged and older adults, both males and females unemployed were associated with higher depressive symptoms. Those middle-aged female working ≥69 h were associated with higher depressive symptoms. Conclusions: An increase in depressive symptoms was associated with unemployed males and females working ≥69 h compared to those working 41–68 h. Although this association was found among middle-aged individuals, a decrease in depressive symptoms in both sexes was associated with working 1–40 h. Depressive symptoms should decrease by implementing employment policies and social services to encourage employers to support middle-aged and older adults in the workforce considering their sex and age differences.

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Profile of a short-acting κ-antagonist, LY2795050, on self-grooming behaviors, forced swim test and locomotor activity: sex comparison in mice

Journal of Psychopharmacology ◽

10.1177/0269881121996883 ◽

2021 ◽

pp. 026988112199688

Author(s):

Eduardo R Butelman ◽

Caroline Baynard ◽

Bryan D McElroy ◽

Thomas E Prisinzano ◽

Mary Jeanne Kreek

Keyword(s):

Locomotor Activity ◽

Forced Swim Test ◽

Male And Female ◽

Short Acting ◽

Swim Test ◽

Central Nervous System Dysfunction ◽

Forced Swim ◽

Males And Females ◽

The Impact ◽

Κ Receptor

Background: Novel short-acting κ(kappa)-opioid receptor selective antagonists are translational tools to examine the impact of the κ-receptor/dynorphin system in assays related to central nervous system dysfunction (e.g., substance use disorders, anhedonia and depression). The effects of such compounds have been compared in males and females under very limited conditions. Aims: The goal of this study was to examine potential sex differences in the effects of a κ-agonist and a short-acting κ-antagonist in an ethologically relevant test of anhedonia, the “splash test” of self-grooming, and also in the forced swim test and in locomotor activity. Methods: We examined the dose-dependence of grooming deficits caused by the κ-agonist U50,488 (0.1–3.2 mg/kg intraperitoneal (i.p.)) in gonadally intact adult male and female C57BL/6J mice. We then compared the effects of the short-acting κ-antagonist LY2795050 ((3-chloro-4-(4-(((2S)-2-pyridin-3-ylpyrrolidin-1-yl)methyl) phenoxy)benzamide)); 0.032–0.1 mg/kg i.p.) in blocking grooming deficits caused by U50,488 (3.2 mg/kg). The effects of LY2795050 were also studied in the forced swim test (FST). The effects of LY2795050 in blocking the locomotor depressant effects of U50,488 (10 mg/kg) were also studied. Results: U50,488 produced dose-dependent grooming deficits in male and female mice, and LY2795050 prevented these effects. In contrast, LY2795050 decreased immobility in the FST in males at a dose of 0.1 mg/kg, but not in females, up to a dose of 0.32 mg/kg. Also, LY2795050 (0.32 mg/kg) prevented and also reversed the locomotor-depressant effects of U50,488 (10 mg/kg), in males and females. Conclusions: This study further implicates the κ-receptor system in ethologically relevant aspects of anhedonia, and confirms sexual dimorphism in some behavioral effects of novel κ-antagonists.

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129 Effects of a multi-strain Bacillus subtilis-based direct-fed microbial on growth performance, nutrient digestibility, and colonic pH in diets fed to weanling pigs

Journal of Animal Science ◽

10.1093/jas/skaa278.185 ◽

2020 ◽

Vol 98 (Supplement_4) ◽

pp. 101-102

Author(s):

Jaron R Lewton ◽

Adrienne Woodward ◽

Ronny Moser ◽

Kyan M Thelen ◽

Adam J Moeser ◽

...

Keyword(s):

Amino Acids ◽

Bacillus Subtilis ◽

Growth Performance ◽

Distal Colon ◽

Nutrient Digestibility ◽

Nursery Pigs ◽

Fiber Digestion ◽

Males And Females ◽

Dietary Treatments ◽

The Impact

Abstract A study was conducted to evaluate the effects of a multi-strain Bacillus subtilis-based direct-fed microbial (DFM) on apparent digestibility and colonic pH of nursery pigs. Eighty pigs, of equal number of barrows and gilts (initial BW: 6.99 ± 1.67 kg), were weaned at 21 ± 1 d and randomly allotted to sixteen pens, with five pigs per pen. Two dietary treatments were implemented, a basal control (CON) and a control plus DFM (DFM). Both diets were corn, soybean meal, and distillers dried grains based, formulated to meet all or exceed all nutritional requirements, and manufactured on site. Diets were fed for 42 days. Performance measures were recorded weekly. On d 21 and 42 of the experiment, one pig per pen was randomly selected and euthanized, with equal number of males and females represented. Digestibility of specific nutrients was evaluated within the duodenum, jejunum, ileum, ascending and distal colon. There were no overall differences in growth performance. Overall means ± SD were 0.51 ± 0.05 kg/d, 0.79 ± 0.05 kg/d and 0.66 ± 0.05 for ADG, ADFI, and G:F, respectively. Digestibility of tryptophan within the jejunum tended (P = 0.06) to increase with addition of DFM, as did cysteine (P = 0.12) and methionine (P = 0.10). The analysis also suggested that the impact of the DFM on the digestibility of amino acids may be early in the nursery phase. The pH of contents in ascending colon, a possible indicator of varied fiber digestion, did not differ. Likewise, no differences were observed between treatment in apparent total tract nitrogen and energy digestibility (analysis of distal colon contents). The addition of a multi-strain Bacillus subtilis-based DFM appears to impact digestibility of select amino acids depending upon location in the gastrointestinal tract.

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Summer Movements and Impact of Individual Striped Skunks, Mephitis mephitis, on Duck Nests in Saskatchewan

The Canadian Field-Naturalist ◽

10.22621/cfn.v120i3.326 ◽

2006 ◽

Vol 120 (3) ◽

pp. 342

Author(s):

Serge Larivière ◽

Lyle R. Walton ◽

François Messier

Keyword(s):

Mephitis Mephitis ◽

Direct Function ◽

Canadian Prairies ◽

Striped Skunk ◽

Intensive Observations ◽

Males And Females ◽

Foraging Movements ◽

The Impact ◽

Striped Skunks ◽

Nesting Season

Striped Skunks (Mephitis mephitis) are important predators of duck eggs in the Canadian prairies. We estimated the impact of individual Striped Skunks on duck nests by intensive observations of foraging movements and depredation of duck nests in southern Saskatchewan, 1993-1994. Nightly, skunk movements were variable (range 0-20 km per night), and did not differ among seasons for females, or between males and females during the parturition/rearing season. Overall, nightly movement of Striped Skunks averaged 7.4 km for females (SD = 5.9 km, n = 20 females) and 6.7 km for males (SD = 3.2 km, n = 5 males). During 1,873 h of radio-tracking, we observed depredation of 10 duck nests by 8 skunks (7 F, 1 M). Using our observed estimate of one depredation for every 187 h, and averaged nightly activity of 8-10 h per night, we estimated that individual skunks find one duck nest every 19-23 nights. Thus, during the 60-day nesting season for ducks (mid-May to mid-July), individual skunks probably find 2-3 duck nests. These observations reinforce the growing evidence that, at normal duck nest densities (<2.5 nests/ha), depredation of eggs by Striped Skunks is opportunistic, and the impact of Striped Skunks on duck nests is a direct function of Striped Skunk abundance.

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