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1.
FASEB J ; 36(9): e22479, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35920200

RESUMEN

Meiosis has a principal role in sexual reproduction to generate haploid gametes in both sexes. During meiosis, the cell nucleus hosts a dynamic environment where some genes are transcriptionally activated, and some are inactivated at the same time. This becomes possible through subnuclear compartmentalization. The sex body, sequestering X and Y chromosomes during male meiosis and creating an environment for the meiotic sex chromosome inactivation (MSCI) is one of the best known and studied subnuclear compartments. Herein, we show that MRNIP forms droplet-like accumulations that fuse together to create a distinct subnuclear compartment that partially overlaps with the sex body chromatin during diplotene. We demonstrate that Mrnip-/- spermatocytes have impaired DNA double-strand break (DSB) repair, they display reduced sex body formation and defective MSCI. We show that Mrnip-/- undergoes critical meiocyte loss at the diplotene stage. Furthermore, we determine that DNA DSBs (induced by SPO11) and synapsis initiation (facilitated by SYCP1) precede Mrnip expression in testes. Altogether, our findings indicate that in addition to an emerging role in DNA DSB repair, MRNIP has an essential function in spermatogenesis during meiosis I by forming drop-like accumulations interacting with the sex body.


Asunto(s)
Espermatocitos , Espermatogénesis , Animales , Cromatina/genética , Cromatina/metabolismo , Femenino , Fertilidad , Masculino , Meiosis , Ratones , Espermatocitos/metabolismo , Espermatogénesis/genética , Cromosoma Y/genética
2.
PLoS Genet ; 16(8): e1008954, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32785227

RESUMEN

The flagellum is essential for sperm motility and fertilization in vivo. The axoneme is the main component of the flagella, extending through its entire length. An axoneme is comprised of two central microtubules surrounded by nine doublets, the nexin-dynein regulatory complex, radial spokes, and dynein arms. Failure to properly assemble components of the axoneme in a sperm flagellum, leads to fertility alterations. To understand this process in detail, we have defined the function of an uncharacterized gene, Cfap97 domain containing 1 (Cfap97d1). This gene is evolutionarily conserved in mammals and multiple other species, including Chlamydomonas. We have used two independently generated Cfap97d1 knockout mouse models to study the gene function in vivo. Cfap97d1 is exclusively expressed in testes starting from post-natal day 20 and continuing throughout adulthood. Deletion of the Cfap97d1 gene in both mouse models leads to sperm motility defects (asthenozoospermia) and male subfertility. In vitro fertilization (IVF) of cumulus-intact oocytes with Cfap97d1 deficient sperm yielded few embryos whereas IVF with zona pellucida-free oocytes resulted in embryo numbers comparable to that of the control. Knockout spermatozoa showed abnormal motility characterized by frequent stalling in the anti-hook position. Uniquely, Cfap97d1 loss caused a phenotype associated with axonemal doublet heterogeneity linked with frequent loss of the fourth doublet in the sperm stored in the epididymis. This study demonstrates that Cfap97d1 is required for sperm flagellum ultra-structure maintenance, thereby playing a critical role in sperm function and male fertility in mice.


Asunto(s)
Axonema/genética , Proteínas del Citoesqueleto/genética , Dineínas/genética , Infertilidad Masculina/genética , Animales , Chlamydomonas/genética , Cilios/genética , Cilios/patología , Fertilización In Vitro , Humanos , Infertilidad Masculina/patología , Masculino , Ratones , Ratones Noqueados , Motilidad Espermática/genética , Cola del Espermatozoide/metabolismo , Cola del Espermatozoide/patología , Espermatozoides/crecimiento & desarrollo , Espermatozoides/patología , Testículo/crecimiento & desarrollo , Testículo/patología
3.
Artículo en Inglés | MEDLINE | ID: mdl-36141528

RESUMEN

One Health, a multidisciplinary approach to public health, which integrates human, animal, and environmental studies, is prudent for circumpolar Arctic health research. The objective of our bibliometric review was to identify and compare research in select infectious diseases in Arctic wildlife species with importance to human health indexed in English language databases (PubMed, Scopus) and the Russian database eLibrary.ru. Included articles (in English and Russian languages) needed to meet the following criteria: (1) data comes from the Arctic, (2) articles report original research or surveillance reports, (3) articles were published between 1990 and 2018, and (4) research relates to naturally occurring infections. Of the included articles (total n = 352), most were from Russia (n = 131, 37%), Norway (n = 58, 16%), Canada (n = 39, 11%), and Alaska (n = 39, 11%). Frequently reported infectious agents among selected mammals were Trichinella spp. (n = 39), Brucella spp. (n = 25), rabies virus (n = 11), Echinococcus spp. (n = 10), and Francisella tularensis (n = 9). There were 25 articles on anthrax in eLibrary.ru, while there were none in the other two databases. We identified future directions where opportunities for further research, collaboration, systematic reviews, or monitoring programs are possible and needed.


Asunto(s)
Animales Salvajes , Enfermedades Transmisibles , Alaska/epidemiología , Animales , Regiones Árticas , Bibliometría , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/veterinaria , Humanos , Mamíferos
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