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Project description:Endocrine and molecular factors of increased female reproductive performance in mice
| PRJNA728114 | ENA
Project description:The Dummerstorf high-fertility mouse line FL1 is a worldwide unique selection experiment for increased female reproductive performance. After more than 190 generations of selection, these mice doubled the amount of offspring per litter compared to the unselected control line. FL1 females have a superior lifetime fecundity and the highest Silver fecundity index that has been described in mice, while their offspring show no signs of growth retardation. The reasons for the increased reproductive performance remained unclear. Thus, this study aims to characterize the Dummerstorf high-fertility mouse line FL1 on endocrine and molecular levels on the female side. We analyzed parameters of the hypothalamic pituitary gonadal axis on both hormonal and transcriptional levels. Gonadotropin-releasing hormone and follicle-stimulating hormone (FSH) concentrations were decreased in FL1 throughout the whole estrous cycle. Luteinizing hormone (LH) was increased in FL1 mice in estrus. Progesterone concentrations were decreased in estrus in FL1 mice and not affected in diestrus. We used a holistic gene expression approach in the ovary to obtain a global picture of how the high-fertility phenotype is achieved. We found several differentially expressed genes in the ovaries of FL1 mice that are associated with different female fertility traits. Our results indicate that ovulation rates in mice can be increased despite decreased FSH levels. Cycle-related alterations of progesterone and LH levels have the potential to improve follicular maturation, and interactions of endocrine and molecular factors lead to enhanced follicular survival, more successful folliculogenesis and therefore higher ovulation rates in female FL1 mice.
| S-EPMC9175557 | biostudies-literature
Project description:Animals in transport are exposed to both psychological and physical stressors, which affect performance and health. The objectives of this study were to investigate whether and how the transportation stress effect on female reproduction in mice, and detect differentially expressed genes association with stress response and reproductive capacity utilizing gene expression profiles. After transported mice by car to and from laboratory for a total period of 10 h, nearly 1000 km distance, measurements were carried out to explore effects of transportation stress on reproductive traits including puberty, estrous cycle, follicular number within ovaries, fertility and superovulation quality. Early life stress suffered mice before puberty promoted puberty onset, altered estrous cycle length and reduced large antral follicle number. Pubertal and adult mice exposure to transportation stress induced their pregnancy rate decline. Furthermore, adult stressed mice showed an obvious reduction in fertility with less litter size and litter weight in birth, which may cause reduced ovulation oocytes identified by superovulation. Assuming ovulated oocytes number as reproductive parameter, genes differently expressed between mice with extremely high and extremely low oocytes were compared within control and stress group separately.
2020-03-07 | GSE146528 | GEO
Project description:Both environmental and genetic factors can dramatically affect reproductive performance in mice. In this study we have focused on the identification of genetic regions, quantitative trait loci (QTL), which affect the breeding capacity of female mice. We have identified polymorphic microsatellite markers for the mouse strains used and performed a genomewide scan on 237 females from a gene-segregating backcross between a high breeder and a relatively poor breeder. The high-breeder mouse strain we used is the inbred NFR/N mouse (MHC haplotype H-2q), which has extraordinary good breeding properties. The moderate breeder chosen for F(1) and N2 progeny was B10.Q, which is a genetically well-characterized MHC-congenic mouse of the H-2q haplotype. Each of the 237 females of the N2 generation was allowed to mate twice with MHC-congenic B10.RIII (H-2r) males and twice with B10.Q males. A predetermined number of phenotypes related to reproductive performance were recorded, and these included litter size, neonatal growth, and pregnancy rate. Loci controlling litter size were detected on chromosomes 1 (Fecq3) and 9 (Fecq4). The neonatal growth phenotype was affected by Fecq3 and a locus on chromosome 9 (Neogq1). On chromosome 11 two loci affecting the pregnancy rate (Pregq1 and Pregq2) were identified. Furthermore, on chromosomes 13 and 17 we found loci (Pregq3 and Pregq4) influencing the outcome of allogeneic pregnancy (allogeneic by means of MHC disparity between mother and fetuses). A locus on chromosome 1 affecting maternal body weight was also identified and has been denoted Bwq7. It is well known that reproductive performance is polygenically controlled, and the identification of the major loci in this complex process opens the possibility of investigating the natural genetic control of reproduction.
| S-EPMC1526510 | biostudies-literature
Project description:Ovarian development requires coordinate communications among oocytes, granulosa cells, and theca cells. Two Hedgehog (Hh) pathway ligands, Desert hedgehog (Dhh) and Indian hedgehog (Ihh), are produced by the granulosa cells and work together to regulate theca cell specification and development. Mice lacking both Dhh and Ihh had loss of normal ovarian function, which raised the question of which biological actions are specifically controlled by each ligand during folliculogenesis. By comparing the reproductive fitness, hormonal profiles, and ovarian transcriptomes among control, Dhh single-knockout (KO), Ihh KO, and Dhh/Ihh double-knockout (DKO) mice, we examined the specific roles of Dhh and Ihh in these processes. Dhh/Ihh DKO female mice were infertile because of a lack of theca cells and their steroid product androgen. Although Dhh and Ihh KO mice were fertile with normal folliculogenesis, they had decreased androgen production and alterations in their ovarian transcriptomes. Absence of Ihh led to aberrant steroidogenesis and elevated inflammation responses, which were not found in Dhh KO mouse ovaries, implicating that IHH has a greater impact than DHH on the activation of the Hh signaling pathway in the ovary. Our findings provide insight into not only how the Hh pathway influences folliculogenesis but also the distinct and overlapping roles of Dhh and Ihh in supporting ovarian development.
| S-EPMC6287595 | biostudies-literature
Project description:IntroductionReproductive endocrine disorders (RED), including polycystic ovary syndrome (PCOS), endometriosis (EMs), and female infertility (FI), significantly affect women's health globally, with varying prevalence across different regions. These conditions can be addressed through medication, surgical interventions, and lifestyle modifications. However, the limited understanding of RED's etiology and the substantial economic burden of its treatment highlight the importance of investigating its pathogenesis. Metabolites play a critical role in metabolic processes and are potentially linked to the development of RED. Despite existing studies suggesting correlations between metabolites and RED, conclusive evidence remains scarce, primarily due to the observational nature of these studies, which are prone to confounding factors.MethodsThis study utilized Mendelian Randomization (MR) to explore the causal relationship between metabolites and RED, leveraging genetic variants associated with metabolite levels as instrumental variables to minimize confounding and reverse causality. Data were obtained from the Metabolomics GWAS Server and the IEU OpenGWAS project. Instrumental variables were selected based on their association with the human gut microbiota composition, and the GWAS summary statistics for metabolites, PCOS, EMs, and FI were analyzed. The MR-Egger regression and random-effects inverse-variance weighted (IVW) methods were employed to validate the causal relationship. Cochran's Q test was employed to evaluate heterogeneity, sensitivity analysis was performed using leave-one-out analysis, and for pleiotropy analysis, the intercept term of MR-Egger's method was investigated.ResultsThe MR analysis revealed significant associations between various metabolites and RED conditions. For instance, a positive association was found between 1-palmitoylglycerophosphocholine and PCOS, while a negative association was noted between phenylacetate and FI. The study identified several metabolites associated with an increased risk and others with protective effects against PCOS, EMs, and FI. These findings highlight the complex interplay between metabolites and RED, suggesting potential pathways through which these conditions could be influenced or treated.ConclusionThis MR study provides valuable insights into the causal relationship between metabolites and female reproductive endocrine disorders, suggesting that metabolic alterations play a significant role in the pathogenesis of PCOS, EMs, and FI, and offering a foundation for future research and therapeutic development.
| S-EPMC11560792 | biostudies-literature
Project description:The aim of this study was to evaluate the effect of an environmental enrichment (EE) plan on the reproductive performance of Swiss Webster mice and their female offspring used as recipients for embryo transfer. A total of 54 breeder mice and 60 F1 females, used as foster mothers, were allocated in two experimental groups to receive or not receive EE for physical well-being. Reproductive outcomes of the Swiss trios such as birth rate and pup number, litter size, pups' weight at weaning, interlitter interval and time to first litter were analyzed. Environmental enrichment significantly increased pups weight from breeding trios compared to the control group (14.4 ± 0.1 vs. 13.8g ± 0.1, EE vs. control, respectively; p < 0.01). Other parameters did not differ between both groups. Reproductive parameters of female offspring used as recipients for embryo transfer did not differ among groups subjected or not to EE. These data demonstrate that the EE protocol applied in Swiss Webster breeder mice positively enhanced pups weight, and did not interfere with other reproductive outcomes. In conclusion, this study supports the implementation of EE plans usually applied for animal welfare in mouse facilities with slight improvement in reproductive performance.
| S-EPMC7460265 | biostudies-literature
Project description:Epidemiology shows women have a higher incidence of osteoarthritis (OA) than men. However, there is not enough evidence to suggest a direct correlation between female reproductive factors and OA. Therefore, this study will employ Mendelian randomization (MR) analysis to investigate whether there is a causal relationship between the 2. This study used a 2-sample MR analysis with single nucleotide polymorphisms significantly associated with female reproductive factors as instrumental variables (IV). We used inverse variance weighted (IVW), MR-Egger regression, weighted median method to infer a causal relationship between female reproductive factors and OA, Cochran Q heterogeneity test by IVW and MR-Egger method, MR PRESSO method and IVW-radial method to detect outliers, MR_pleiotropy_test function and MR PRESSO method for multivariate validity test, and calculation of F-value was used to assess the presence of weak IVs. Finally, the stability of the findings was assessed using the leave-one-out method. Our research shows that there is no reliable causal relationship between an increase in Age at menarche (years) (AAM) and Age at menopause (years) (AM) and OA, that an increase in Age first had sexual intercourse (years) (AFS) is associated with a decreased risk of knee OA and/or hip OA and hand OA, that an increase in Age at first live birth (years) (AFB) is associated with a decreased risk of knee OA and/or hip OA and knee OA, and that an increase in Number of live births (NOB) is associated with an increased risk of knee OA and/or hip OA. This study provides genetic support for an increase in AFS as a reduced knee OA and/or hip OA and hand OA risk factor, an increase in AFB as a reduced knee OA and/or hip OA and knee OA risk factor, and an increase in NOB as an increased knee OA and/or hip OA risk factor. Further studies are needed to elucidate the potential mechanisms underlying the causal associations between AFS, AFB, and NOB and site-specific OA.
| S-EPMC11789898 | biostudies-literature
Project description:Transportation stress suppress reproductive performance in female mice and relevant genes detection
| PRJNA610822 | ENA
Project description:Out of millions of ejaculated sperm, a few reach the fertilization site in mammals. Flagellar Ca2+ signaling nanodomains, organized by multi-subunit CatSper calcium channel complexes, are pivotal for sperm migration in the female tract, implicating CatSper-dependent mechanisms in sperm selection. Here using biochemical and pharmacological studies, we demonstrate that CatSper1 is an O-linked glycosylated protein, undergoing capacitation-induced processing dependent on Ca2+ and phosphorylation cascades. CatSper1 processing correlates with protein tyrosine phosphorylation (pY) development in sperm cells capacitated in vitro and in vivo. Using 3D in situ molecular imaging and ANN-based automatic detection of sperm distributed along the cleared female tract, we demonstrate that spermatozoa past the utero-tubal junction possess the intact CatSper1 signals. Together, we reveal that fertilizing mouse spermatozoa in situ are characterized by intact CatSper channel, lack of pY, and reacted acrosomes. These findings provide molecular insight into sperm selection for successful fertilization in the female reproductive tract.
| S-EPMC7707823 | biostudies-literature