bims-gamemb Biomed News
on Gamete and embryo metabolism
Issue of 2022–01–02
nine papers selected by
Cameron A. Schmidt, East Carolina University



  1. Syst Biol Reprod Med. 2021 Dec 28. 1-8
      Cumulus cell (CC) clumps that associate with oocytes provide the oocytes with growth and signaling factors. Thus, the metabolism of the CCs may influence oocyte function, and CC metabolism may be predictive of oocyte competence for in vitro fertilization. CCs are thought to be highly glycolytic, but data on the use of other potential carbon substrates are lacking in humans. This prospective and blinded cohort study was designed to examine the substrate utilization of CCs by age and oocyte competence. Individual sets of CC clumps from participants were removed after oocyte retrieval procedure then, incubated with stable isotope labeled substrates, and analyzed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) for isotopologue enrichment of major metabolic intermediates, including acetyl-CoA. The acyl-chain of acetyl-CoA contains 2 carbons that can be derived from 13C-labeled substrates resulting in an M + 2 isotopologue that contains 2 13C atoms. Comparing the fate of three major carbon sources, mean enrichment of M + 2 acetyl-CoA (mean, standard deviation) was for glucose (3.6, 7.7), for glutamine (9.4, 6.2), and for acetate (20.7, 13.9). Due to this unexpected high and variable labeling from acetate, we then examined acetyl-CoA mean % enrichment from acetate in 278 CCs from 21 women ≤34 (49.06, 12.73) decreased with age compared to 124 CCs from 10 women >34 (43.48, 16.20) (p = 0.0004, t-test). The CCs associated with the immature prophase I oocytes had significantly lower enrichment in M + 2 acetyl CoA compared to the CCs associated with the metaphase I and metaphase II oocytes (difference: -6.02, CI: -1.74,-13.79, p = 0.013). Acetate metabolism in individual CC clumps was positively correlated with oocyte maturity and decreased with maternal age. These findings indicate that CC metabolism of non-glucose substrates should be investigated relative to oocyte function and age-related fertility.Abbreviations: CCs: cumulus cells; COC: cumulus-oocyte complex; LC-MS: liquid chromatography-mass spectrometry; acetyl-CoA: acetyl-Coenzyme A; CoA: Coenzyme A.
    Keywords:  Cumulus cells; acetate metabolism; metabolism; oocyte
    DOI:  https://doi.org/10.1080/19396368.2021.2003479
  2. J Reprod Dev. 2021 Dec 25.
      Metabolism is an important cellular process necessary not only for producing energy and building blocks for cells, but also for regulating various cell functions, including intracellular signaling, epigenomic effects, and transcription. The regulatory roles of metabolism have been extensively studied in somatic cells, including stem cells and cancer cells, but data regarding germ cells are limited. Because germ cells produce individuals of subsequent generations, understanding the role of metabolism and its regulatory functions in germ cells is important. Although limited information concerning the specific role of metabolism in germ cells is available, recent advances in related research have revealed specific metabolic states of undifferentiated germ cells in embryos as well as in germ cells undergoing oogenesis and spermatogenesis. Studies have also elucidated the functions of some metabolic pathways associated with germ cell development and the non-genomic heritable machinery of germ cells. In this review, we summarized all the available knowledge on the characteristic metabolic pathways in germ cells, focusing on their regulatory functions, while discussing the issues that need to be addressed to enhance the understanding of germ cell metabolism.
    Keywords:  Epigenome; Germ cells; Metabolism; Oogenesis; Spermatogenesis
    DOI:  https://doi.org/10.1262/jrd.2021-137
  3. BJOG. 2021 Dec 25.
       BACKGROUND: Normal mature sperm have a considerably reduced number of mitochondria which provide the energy required for progressive sperm motility. Literature suggests that disorders of sperm motility may be linked to abnormal sperm mitochondrial number and function.
    OBJECTIVES: To summarize the evidence from literature regarding the association of mitochondrial DNA copy numbers and semen quality with a particular emphasis on the spermatozoa motility.
    SEARCH STRATEGY: Standard methodology recommended by Cochrane.
    SELECTION CRITERIA: All published primary research reporting on the association between mitochondrial DNA copy numbers and semen quality.
    DATA COLLECTION AND ANALYSIS: Using standard methodology recommended by Cochrane we pooled results using a random effects model and the findings were reported as a standardised mean difference.
    MAIN RESULTS: We included 10 studies. The primary outcome was sperm mitochondrial DNA copy numbers. A meta-analysis including five studies showed significantly higher mitochondrial DNA copy numbers in abnormal semen analysis as compared to normal semen analysis(SMD 1.08, 95% CI 0.74-1.43). Seven studies included in the meta-analysis showed a significant negative correlation between mitochondrial DNA copy numbers and semen parameters. The quality of evidence was assessed as good to very good in 60% of studies.
    CONCLUSIONS: Our review demonstrates significantly higher mitochondrial DNA in human sperm cells of men with abnormal semen analysis in comparison to men with normal semen analysis.
    Keywords:  Mitochondrial DNA; abnormal semen parameters; sperm motility
    DOI:  https://doi.org/10.1111/1471-0528.17078
  4. Front Cell Dev Biol. 2021 ;9 723978
      Abnormal uptake or metabolism of folate increases risk of human pregnancy complications, though the mechanism is unclear. Here, we explore how defective folate metabolism influences early development by analysing mice with the hypomorphic Mtrr gt mutation. MTRR is necessary for methyl group utilisation from folate metabolism, and the Mtrr gt allele disrupts this process. We show that the spectrum of phenotypes previously observed in Mtrr gt/gt conceptuses at embryonic day (E) 10.5 is apparent from E8.5 including developmental delay, congenital malformations, and placental phenotypes. Notably, we report misalignment of some Mtrr gt conceptuses within their implantation sites from E6.5. The degree of misorientation occurs across a continuum, with the most severe form visible upon gross dissection. Additionally, some Mtrr gt/gt conceptuses display twinning. Therefore, we implicate folate metabolism in blastocyst orientation and spacing at implantation. Skewed growth likely influences embryo development since developmental delay and heart malformations (but not defects in neural tube closure or trophoblast differentiation) associate with severe misalignment of Mtrr gt/gt conceptuses. Typically, the uterus is thought to guide conceptus orientation. To investigate a uterine effect of the Mtrr gt allele, we manipulate the maternal Mtrr genotype. Misaligned conceptuses were observed in litters of Mtrr +/+ , Mtrr +/gt , and Mtrr gt/gt mothers. While progesterone and/or BMP2 signalling might be disrupted, normal decidual morphology, patterning, and blood perfusion are evident at E6.5 regardless of conceptus orientation. These observations argue against a post-implantation uterine defect as a cause of conceptus misalignment. Since litters of Mtrr +/+ mothers display conceptus misalignment, a grandparental effect is explored. Multigenerational phenotype inheritance is characteristic of the Mtrr gt model, though the mechanism remains unclear. Genetic pedigree analysis reveals that severe conceptus skewing associates with the Mtrr genotype of either maternal grandparent. Moreover, the presence of conceptus skewing after embryo transfer into a control uterus indicates that misalignment is independent of the peri- and/or post-implantation uterus and instead is likely attributed to an embryonic mechanism that is epigenetically inherited. Overall, our data indicates that abnormal folate metabolism influences conceptus orientation over multiple generations with implications for subsequent development. This study casts light on the complex role of folate metabolism during development beyond a direct maternal effect.
    Keywords:  MTRR; conceptus misalignment; decidua; grandparental effect; transgenerational epigenetic inheritance; trophoblast; twinning
    DOI:  https://doi.org/10.3389/fcell.2021.723978
  5. Front Plant Sci. 2021 ;12 781734
      Seed germination is crucial for the life cycle of plants and maximum crop production. This critical developmental step is regulated by diverse endogenous [hormones, reactive oxygen species (ROS)] and exogenous (light, temperature) factors. Reactive oxygen species promote the release of seed dormancy by biomolecules oxidation, testa weakening and endosperm decay. Reactive oxygen species modulate metabolic and hormone signaling pathways that induce and maintain seed dormancy and germination. Endosperm provides nutrients and senses environmental signals to regulate the growth of the embryo by secreting timely signals. The growing energy demand of the developing embryo and endosperm is fulfilled by functional mitochondria. Mitochondrial matrix-localized heat shock protein GhHSP24.7 controls seed germination in a temperature-dependent manner. In this review, we summarize comprehensive view of biochemical and molecular mechanisms, which coordinately control seed germination. We also discuss that the accurate and optimized coordination of ROS, mitochondria, heat shock proteins is required to permit testa rupture and subsequent germination.
    Keywords:  embryogenesis and endosperm; heat shock proteins (HSPs); mitochondria; reactive oxygen species (ROS); seed germination and dormancy
    DOI:  https://doi.org/10.3389/fpls.2021.781734
  6. J Vis Exp. 2021 Dec 13.
      Early Drosophila embryos are large cells containing a vast array of conventional and embryo-specific organelles. During the first three hours of embryogenesis, these organelles undergo dramatic movements powered by actin-based cytoplasmic streaming and motor-driven trafficking along microtubules. The development of a multitude of small, organelle-specific fluorescent probes (FPs) makes it possible to visualize a wide range of different lipid-containing structures in any genotype, allowing live imaging without requiring a genetically encoded fluorophore. This protocol shows how to inject vital dyes and molecular probes into Drosophila embryos to monitor the trafficking of specific organelles by live imaging. This approach is demonstrated by labeling lipid droplets (LDs) and following their bulk movement by particle image velocimetry (PIV). This protocol provides a strategy amenable to the study of other organelles, including lysosomes, mitochondria, yolk vesicles, and the ER, and for tracking the motion of individual LDs along microtubules. Using commercially available dyes brings the benefits of separation into the violet/blue and far-red regions of the spectrum. By multiplex co-labeling of organelles and/or cytoskeletal elements via microinjection, all the genetic resources in Drosophila are available for trafficking studies without the need to introduce fluorescently tagged proteins. Unlike genetically encoded fluorophores, which have low quantum yields and bleach easily, many of the available dyes allow for rapid and simultaneous capture of several channels with high photon yields.
    DOI:  https://doi.org/10.3791/63291
  7. Plants (Basel). 2021 Nov 26. pii: 2590. [Epub ahead of print]10(12):
      Citrus fruit is one of the most important contributors to the ascorbic acid (AsA) intake in humans. Here, we report a comparative analysis of AsA content and transcriptional changes of genes related to its metabolism during development of petals, leaves and fruits of Valencia Late oranges (Citrus sinensis). Petals of close flowers and at anthesis contained the highest concentration of AsA. In fruits, AsA content in the flavedo reached a maximum at color break, whereas the pulp accumulated lower levels and experienced minor fluctuations during development. AsA levels in leaves were similar to those in the flavedo at breaker stage. The transcriptional profiling of AsA biosynthetic, degradation, and recycling genes revealed a complex and specific interplay of the different pathways for each tissue. The D-galacturonic acid pathway appeared to be relevant in petals, whereas in leaves the L-galactose pathway (GGP and GME) also contributed to AsA accumulation. In the flavedo, AsA content was positively correlated with the expression of GGP of the L-galactose pathway and negatively with DHAR1 gene of the recycling pathway. In the pulp, AsA appeared to be mainly controlled by the coordination among the D-galacturonic acid pathway and the MIOX and GalDH genes. Analysis of the promoters of AsA metabolism genes revealed a number of cis-acting elements related to developmental signals, but their functionalities remain to be investigated.
    Keywords:  Citrus; ascorbic acid; fruit; leaf; maturation; orange; petal; vitamin C
    DOI:  https://doi.org/10.3390/plants10122590
  8. Comp Biochem Physiol A Mol Integr Physiol. 2021 Dec 27. pii: S1095-6433(21)00235-X. [Epub ahead of print] 111127
      Planaria are known for their ability to completely regenerate upon fissioning or experimental amputation. Yet, metabolic costs of regeneration have not been directly measured in planaria. Our goal was to establish the relationships between oxygen consumption (V̇O2), regeneration, and reproductive mode for asexual and sexual strains of Schmidtea mediterranea. We hypothesized that V̇O2 would vary by regeneration day for both sexual and asexual S. mediterranea, reflecting different costs of tissue reconstruction, but with an additional cost for regenerating sexual organs. Testes regeneration and body mass, as indicators of regeneration progress, and routine mass-specific V̇O2 as a function of maturity, regeneration, and reproductive mode, were measured over a 22-day regeneration period. Testes growth was highest in sexually mature adults, ~1/2 that in 14-day post-amputation sexual adults, and not detectable in juveniles and hatchlings. Mass-specific routine V̇O2 in sexuals was highest in mature controls at ~23 μl O2/g/h, but only half that in juveniles, hatchlings, and 14 day post-amputation adults. Both intact and 14-day post-amputation asexuals had a mass-specific routine V̇O2 of ~10-12 μl O2/g/h. The sum of V̇O2 of all amputated sections was ~100% higher than pre-amputation levels in the first 6 days of regeneration in asexuals, but not sexuals. There was no significant difference in V̇O2 of head, middle, and tail sections during regeneration. Overall, the highest metabolic costs associated with regeneration occurred during the initial 1-6 days of regeneration in both strains, but regeneration costs for sexual structures were not reflected in major V̇O2 differences between sexual and asexual strains.
    Keywords:  Asexual reproduction; Cost of reproduction; Oxygen consumption; Planaria; Regeneration; Sexual reproduction
    DOI:  https://doi.org/10.1016/j.cbpa.2021.111127
  9. Mol Hum Reprod. 2021 Dec 25. pii: gaab071. [Epub ahead of print]
      Sperm DNA damage is considered a predictive factor for the clinical outcomes of patients undergoing ART. Laboratory evidence suggests that zygotes and developing embryos have adopted specific response and repair mechanisms to repair DNA damage of paternal origin. We have conducted a systematic review in accordance with guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to identify and review the maternal mechanisms used to respond and repair sperm DNA damage during early embryonic development, how these mechanisms operate and their potential clinical implications. The literature search was conducted in Ovid MEDLINE and Embase databases until May 2021. Out of 6297 articles initially identified, 36 studies were found to be relevant through cross referencing and were fully extracted. The collective evidence in human and animal models indicate that the early embryo has the capacity to repair DNA damage within sperm by activating maternally driven mechanisms throughout embryonic development. However, this capacity is limited and likely declines with age. The link between age and decreased DNA repair capacity could explain decreased oocyte quality in older women, poor reproductive outcomes in idiopathic cases, and patients who present high sperm DNA damage. Ultimately, further understanding mechanisms underlying the maternal repair of sperm DNA damage could lead to the development of targeted therapies to decrease sperm DNA damage, improved oocyte quality to combat incoming DNA insults or lead to development of methodologies to identify individual spermatozoa without DNA damage.
    Keywords:  ARTs; DNA repair; embryo; oocytes; sperm DNA damage; sperm DNA fragmentation
    DOI:  https://doi.org/10.1093/molehr/gaab071