Inbreeding depression is expected to be more pronounced in fitness-related traits, such as pig litter size. Recent studies have suggested that the genetic determinism of inbreeding depression may be heterogeneous across the genome. Therefore, the objective of this study was to conduct a genomic scan of the whole pig autosomal genome to detect the genomic regions that control inbreeding depression for litter size in two varieties of Iberian pigs (Entrepelado and Retinto). The datasets consisted of 2069 (338 sows) and 2028 (327 sows) records of litter size (Total Number Born and Number Born Alive) for the Entrepelado and Retinto varieties. All sows were genotyped using the Geneseek GGP PorcineHD 70 K chip. We employed the Unfavorable Haplotype Finder software to extract runs of homozygosity (ROHs) and conducted a mixed-model analysis to identify highly significant differences between homozygous and heterozygous sows for each specific ROH. A total of eight genomic regions located on SSC2, SSC5, SSC7, SSC8, and SSC13 were significantly associated with inbreeding depression, housing some relevant genes such as FSHR, LHCGR, CORIN, AQP6, and CEP120.

Pre-replication complex (pre-RC) is critical for DNA replication initiation. CDT1 and MCM2 are the subunits of pre-RC, and proper regulation of CDT1 and MCM2 are necessary for DNA replication and cell proliferation. The present study aimed to explore the role of CDT1 and MCM2 in oocyte meiotic maturation and early embryonic development. The depletion and overexpression of Cdt1 and Mcm2 in oocyte and zygote were achieved by microinjecting specific siRNA and mRNA to explored their functions in oocyte meiotic maturation and embryonic development. Then, we examined the effect of CDT1 and MCM2 on other signal pathways by immunostaining the expression of related maker genes. We showed that neither depletion nor overexpression of Cdt1 affected oocyte meiotic progressions. The CDT1 was degraded in S phase and remained at a low level in G2 phase of zygote. Exogenous expression of Cdt1 in G2 phase led to embryo attest at zygote stage. Mechanistically, CDT1 overexpression induced DNA re-replication and thus DNA damage check-point activation. Protein abundance of MCM2 was stable throughout the cell cycle, and embryos with overexpressed MCM2 could develop to blastocysts normally. Overexpression or depletion of Mcm2 also had no effect on oocyte meiotic maturation. Our results indicate that pre-RC subunits CDT1 and MCM2 are not involved in oocyte meiotic maturation. In zygote, CDT1 but not MCM2 is the major regulator of DNA replication in a cell cycle dependent manner. Furthermore, its' degradation is essential for zygotes to prevent from DNA re-replication in G2 stage.

Development of the complex structure of the vertebrate limb requires carefully orchestrated interactions between multiple regulatory pathways and proteins. Among these, precise regulation of 5' Hox transcription factor expression is essential for proper limb bud patterning and elaboration of distinct limb skeletal elements. Here, we identified Geminin (Gmnn) as a novel regulator of this process. A conditional model of Gmnn deficiency resulted in loss or severe reduction of forelimb skeletal elements, while both the forelimb autopod and hindlimb were unaffected. 5' Hox gene expression expanded into more proximal and anterior regions of the embryonic forelimb buds in this Gmnn-deficient model. A second conditional model of Gmnn deficiency instead caused a similar but less severe reduction of hindlimb skeletal elements and hindlimb polydactyly, while not affecting the forelimb. An ectopic posterior SHH signaling center was evident in the anterior hindlimb bud of Gmnn-deficient embryos in this model. This center ectopically expressed Hoxd13, the HOXD13 target Shh, and the SHH target Ptch1, while these mutant hindlimb buds also had reduced levels of the cleaved, repressor form of GLI3, a SHH pathway antagonist. Together, this work delineates a new role for Gmnn in modulating Hox expression to pattern the vertebrate limb.

Adult mammals are unable to regenerate their hearts after cardiac injury, largely due to the incapacity of cardiomyocytes (CMs) to undergo cell division. However, mammalian embryonic and fetal CMs, similar to CMs from fish and amphibians during their entire life, exhibit robust replicative activity, which stops abruptly after birth and never significantly resumes. Converging evidence indicates that formation of the highly ordered and stable cytoarchitecture of mammalian mature CMs is coupled with loss of their proliferative potential. Here, we review the available information on the role of the cardiac cytoskeleton and sarcomere in the regulation of CM proliferation. The actin cytoskeleton, the intercalated disc, the microtubular network and the dystrophin-glycoprotein complex each sense mechanical cues from the surrounding environment. Furthermore, they participate in the regulation of CM proliferation by impinging on the yes-associated protein/transcriptional co-activator with PDZ-binding motif, β-catenin and myocardin-related transcription factor transcriptional co-activators. Mastering the molecular mechanisms regulating CM proliferation would permit the development of innovative strategies to stimulate cardiac regeneration in adult individuals, a hitherto unachieved yet fundamental therapeutic goal.

Zygotic chromatin undergoes extensive reprogramming immediately after fertilization. It is generally accepted that maternal factors control this process. However, little is known about the underlying mechanisms. Here we report that maternal RAD9A, a key protein in DNA damage response pathway, is involved in post-zygotic embryo development, via a mouse model with conditional depletion of Rad9a alleles in oocytes of primordial follicles. Post-zygotic losses originate from delayed zygotic chromatin decondensation after depletion of maternal RAD9A. Pronucleus formation and DNA replication of most mutant zygotes are therefore deferred, which subsequently trigger the G2/M checkpoint and arrest development of most mutant zygotes. Delayed zygotic chromatin decondensation could also lead to increased reabsorption of post-implantation mutant embryos. In addition, our data indicate that delayed zygotic chromatin decondensation may be attributed to deferred epigenetic modification of histone in paternal chromatin after fertilization, as fertilization and resumption of secondary meiosis in mutant oocytes were both normal. More interestingly, most mutant oocytes could not support development beyond one-cell stage after parthenogenetic activation. Therefore, RAD9A may also play an important role in maternal chromatin reprogramming. In summary, our data reveal an important role of RAD9A in zygotic chromatin reprogramming and female fertility.

Reproduction across mammalian species is conserved with a general pattern of fertilization followed by nascent embryo development in transcriptional silence for a variable length of time, a series of cleavage divisions that occur without growth in size of the embryo, compaction to form a morula, and production of a blastocyst. Following blastocyst formation, the embryo may implant immediately or after substantial differentiation of the epiblast and hypoblast layers. In this chapter, the shared and unique properties of several species, commonly used in studies of reproduction and embryology, are outlined.