Exploring novel function of Gpx5 antioxidant activity: Assisting epididymal cells secrete functional extracellular vesicles.

Glutathione peroxisomal-5 (Gpx5) promotes the elimination of H2O2 or organic hydrogen peroxide, and plays an important role in the physiological process of resistance to oxidative stress (OS). To directly and better understand the protection of Gpx5 against OS in epididymal cells and sperm, we studied its mechanism of antioxidant protection from multiple aspects. To more directly investigate the role of Gpx5 in combating oxidative damage, we started with epididymal tissue morphology and Gpx5 expression profiles in combination with the mouse epididymal epithelial cell line PC1 (proximal caput 1) expressing recombinant Gpx5. The Gpx5 is highly expressed in adult male epididymal caput, and its protein signal can be detected in the sperm of the whole epididymis. Gpx5 has been shown to alleviate OS damage induced by 3-Nitropropionic Acid (3-NPA), including enhancing antioxidant activity, reducing mitochondrial damage, and suppressing cell apoptosis. Gpx5 reduces OS damage in PC1 and maintains the well-functioning extracellular vesicles (EVs) secreted by PC1, and the additional epididymal EVs play a role in the response of sperm to OS damage, including reducing plasma membrane oxidation and death, and increasing sperm motility and sperm-egg binding ability. Our study suggests that GPX5 plays an important role as an antioxidant in the antioxidant processes of epididymal cells and sperm, including plasma membrane oxidation, mitochondrial oxidation, apoptosis, sperm motility, and sperm-egg binding ability.

Insertion/Deletion (InDel) Variants within the Sheep Fat-Deposition-Related PDGFD Gene Strongly Affect Morphological Traits.

Platelet-derived growth factor D (PDGFD) is a member of the PDGF gene family, and it plays an important role in the regulation of adipocyte development in mammals. Furthermore, genome-wide association studies (GWAS) have previously identified it as a candidate gene associated with fleece fiber variation, body size, and the fat-tail phenotype in domestic Chinese sheep. In this study, a total of 1919 indigenous Chinese sheep were genotyped to examine the association between nucleotide sequence variations in PDGFD and body morphology. Our results detected both a 14 bp insertion in intron 2 and a 13 bp deletion in intron 4 of PDGFD. Moreover, these two InDel loci had low to moderate polymorphism. Notably, the 13 bp deletion mutation of PDGFD was found to significantly affect sheep body size. Yearling rams in the Luxi black-headed sheep (LXBH) containing a heterozygous genotype (insertion/deletion, ID) were found to have larger body length, chest depth, and body weight than those with wild genotypes. Furthermore, adult ewes in the Guiqian semi-fine wool sheep (GSFW) containing a homozygous mutation (deletion/deletion, DD) were found to have smaller chest width than their peers. Moreover, yearling ewes in this group with the same homozygous mutation were found to have lower body weight, chest width, and cannon circumference compared to those of other individuals. This study demonstrates that PDGFD InDel polymorphisms have the potential to be effective molecular markers to improve morphological traits in domestic Chinese sheep.

New insight into copy number variations of goat SMAD2 gene and their associations with litter size and semen quality.

Copy number variations (CNV) contribute significantly to genetic variations. Numerous studies have shown that CNV affects phenotypic traits in livestock. The SMAD family member 2 (SMAD2) is a leading candidate gene in reproduction and has a crucial effect on litter size. Additionally, SMAD2 is also required for male reproduction and influences male germ cell development. However, there are no reports on investigating the effect of CNVs in the SMAD2 gene on reproductive traits in goat. Therefore, the goal of this study was to explore associations between CNV of the SMAD2 gene and litter size and semen quality in Shaanbei white cashmere (SBWC) goats. In this study, two CNVs within the SMAD2 were identified in 352 SBWC goats (50 males and 302 females). The association analysis revealed that only CNV2 was significantly associated with female goat first-born litter size (P = 3.59 × 10-4), male semen concentration (P < 0.01), ejaculation volume, live sperm count, and sperm deformity rate (P < 0.05). In terms of phenotypic performance, the individuals with loss genotypes outperformed those with other genotypes. CNV1 and CNV2 genotype combinations containing their dominant genotypes were also associated with goat litter size (P = 1.7 × 10-5), but no differences in semen quality were found. In summary, CNV2 of the SMAD2 gene is useful for molecular marker-assisted selection breeding, as it is associated with essential goat reproductive traits.

Investigation on mRNA expression and genetic variation within goat SMAD2 gene and its association with litter size.

The SMAD family member 2 (SMAD2), a member of the TGF-beta superfamily, executes a significant part in the oogenesis and ovulation process. A genome-wide selective sweep analysis also found SMAD2 was different in the fertility groups of Laoshan dairy goats; whether this gene was linked to litter size was unknown. Therefore, SMAD2 was chosen to study its effects on Shaanbei white cashmere goat reproduction and mRNA expression profile. Herein, the mRNA expression level of SMAD2 was firstly determined in female goat tissues, revealing significant differences in mRNA levels of different tissues (p < 0.05), including ovary tissue, indicating a potential role for SMAD2 in goat prolificacy. Then, using six pairs of primers, only one indel locus (P3-Del-12-bp) was found to be polymorphic in goat SMAD2 (n = 501). ANOVA also revealed that a P3-Del-12-bp deletion was significantly related to first-born litter size (p = 0.037). The Chi-square (χ2) test revealed that the ID genotype was significantly more prevalent in mothers with multiple lambs (p = 0.01), indicating that heterozygous individuals (ID) are more likely to produce multiple lambs. Our findings suggest that the SMAD2 gene's P3-Del-12-bp deletion could be used to improve goat breeds by assisting with litter size selection.

Goat CLSTN2 gene: tissue expression profile, genetic variation, and its associations with litter size.

Calsyntenin-2 (CLSTN2) is involved in cell proliferation, differentiation, cell death, tumorigenesis, and follicular expression. Although CLSTN2 has been identified as a potential candidate gene for sheep prolificacy, no studies have been done on its effect on goat prolificacy. The purpose of this study was to identify mRNA expression and genetic variation within goat CLSTN2, and its association with prolificacy. Herein, we uncovered significant differences in mRNA levels of the CLSTN2 gene in different tissues in female goats (p < 0.01), including ovary tissue. Nine putative indels were designed to investigate their correlation to litter size, but only one 16-bp deletion was discovered in female Shaanbei white cashmere goats (n = 902). We discovered that a 16-bp deletion within the CLSTN2 gene was significantly correlated with first-born litter size (p = 0.0001). As shown by the chi-squared test, the genotypic II of single-lambs and multi-lambs was dramatically higher than with genotype ID (p = 0.005). Our findings suggest that indel within the CLSTN2 gene is a candidate gene affecting prolificacy in goats and may be used for Marker Assisted Selection (MAS) in goats.

Association of melatonin receptor 1 A with litter size in sheep: A review.

Sheep are a valuable livestock species worldwide, providing meat, milk, and various dairy products. This article aims to review the latest literature on the melatonin receptor 1A (MTNR1A) gene as a potential candidate gene associated with reproductive traits, particularly the litter size trait in sheep, by searching various databases for available literature. Studies have shown that different parts of the MTNR1A gene play various roles in sheep. By identifying marker genes associated with reproductive traits in MTNR1A polymorphisms linked to the litter size trait, breeders can achieve a faster selection response in sheep breeding by recognizing the genomic region where these genes are located and understanding their physiological functions. Therefore, highlighting the literature on these functions and their association with reproductive traits may contribute to improving the genetic makeup during sheep breeding.

The 12-bp indel in the SMAD family member 2 gene is associated with goat growth traits.

SMAD family member 2 (SMAD2) is a member of the TGFß signaling pathway and functions as an essential regulator in the processes of development, cell proliferation, and bone formation. A previous observation reported that a 12-bp deletion of this gene affected the litter size in goats. However, according to our knowledge, no study has reported an association between this polymorphism and goat body measurement traits. The purpose of this study was to investigate the association of the insertion/deletion (indel) within the SMAD2 gene with the growth traits of goats. The indel polymorphism was found to be significantly associated with chest width and bust (p < 0.05), while cannon circumference was significantly the strongest compared to other traits (p < 0.01) and individuals with the DD genotypes were more dominant genotypes than other genotypes. In summary, we found evidence that the 12-bp indel within the SMAD2 gene could improve goat body measurement traits, paving the way for marker-assisted selection in the field of goat genetics and breeding.

Exploring the physiological roles of circular RNAs in livestock animals.

Circular RNAs (circRNAs) are a recently identified class of RNAs produced via back-splicing and covalent linkage between RNA ends, resulting in a circularized RNA molecule. Physiologically, circRNAs are known to influence a variety of biological pathways, and can also regulate transcription, post-transcription, RNA splicing, or interaction with other proteins or microRNAs (miRNAs). Functionally, circRNAs are known to competitively bind to various other RNA molecules including miRNAs and other competing endogenous RNA such as long noncoding RNA, thereby significantly influencing gene expression. Since gene expression is a crucial factor that underlies economically important livestock traits, it is likely that circRNAs significantly influence livestock traits like growth, milk production, reproduction, meat quality, hair follicle growth, and gametogenesis. Thousands of circRNAs have been recognized in different species of animals, and some of these circRNAs have also been shown to regulate stress responses that may be crucial for animal welfare. Therefore, in this review, we aim to highlight the biogenesis of circRNAs, along with its potential implications for livestock. The presented summary would offer a fundamental understanding of the molecular machinery that underlies circRNAs and associated biological phenomena and emphasize the need for further explorations into the role of circRNAs in the other productive, reproductive, and physiological attributes in animals.

Goat SMAD family member 1 (SMAD1): mRNA expression, genetic variants, and their associations with litter size.

SMAD family member 1 (SMAD1) is phosphorylated and activated by the BMP receptors, which help regulate ovulation rate, cell growth, apoptosis, and development. Previously, the genome-wide association study revealed that it has been associated with fecundity in sheep. However, its effect on litter size has not been investigated in goats. Therefore, this study aimed to determine the level of SMAD1 mRNA expression in various tissues and to identify its polymorphisms and their association with litter size in Shaanbei white cashmere goat (SBWC). As a result, RT-qPCR analysis showed that SMAD1 was expressed in various tissues in female SBWC goats, including the ovary (P < 0.05). Importantly, the mRNA expression level in the ovaries of mothers of multi-lambs had a higher level than the mothers of single lambs (P < 0.05). Moreover, two InDels (18-bp and 7-bp) in intron 1 of SMAD1 were polymorphic among ten potential loci. Both 18-bp and 7-bp InDels were significantly correlated with litter size (P = 0.014) and (P = 0.0001), respectively. As shown by the chi-squared test, genotypic distributions of 18-bp and 7-bp were significantly distinct between single-lamb (P = 0.02) and multi-lamb mothers (P = 0.002). Our findings confirm that two InDels in SMAD1 were significantly associated with litter size and suggest that they could be used to improve fertility traits in goat breeding strategies.

Genetic polymorphisms within the ETAA1 gene associated with growth traits in Chinese sheep breeds.

Ewing tumor-associated antigen 1 (ETAA1) is an important candidate gene for fat deposition in sheep. This study aimed to investigate the indel variations in the ETAA1 gene and their associations with growth traits in the 1619 sheep. The polymorphism information content of this indel ranged from 0.308 to 0.375, with medium genetic diversity (0.25 ≤ polymorphism information content ≤ 0.5). The correlation analysis showed that an 8-bp insertion within the ETAA1 gene was significantly associated with growth traits in Luxi Blackhead sheep (LXBH), Lanzhou fat-tailed sheep, Hu sheep, Tong sheep, and Tan sheep (p < 0.05). Furthermore, the ETAA1 gene was significantly associated with several growth traits (p < 0.01), such as chest width and paunch girth of LXBH, Tong, and Tan rams. It was significantly related to the body morphometric traits of LXBH, Lanzhou fat-tailed sheep, Hu, Tong, and Tan ewes. In conclusion, the detected 8-bp indel within the ETAA1 gene was confirmed in sheep, significantly affecting the growth traits, and might be a potential DNA marker for the selection of high-quality individuals in marker-assisted selection for sheep breeding.

Genetic variations of bovine PCOS-related DENND1A gene identified in GWAS significantly affect female reproductive traits.

Genome-wide association studies (GWAS) have identified DENND1A as a potential candidate gene linked to the fertility-related phenotypes in dairy cows. However, to date, no studies have examined the association of the DENND1A insertion/deletions (indels) to bovine fertility on a large scale. Herein, two indel sites, including P4-del-26-bp and P8-ins-15-bp were identified in 1064 Holstein cows. The values of the minor allelic frequency (MAF) ranged between 0.471 (deletion) and 0.230 (deletion), respectively, and combined four different haplotypes by analyzing the haplotype combination. It is noteworthy that P4-del-26-bp is associated with the ovarian width (P = 0.0004) and corpus luteum diameter (P = 0.004). Meanwhile, P8-ins-15-bp was found to have a significant association with the ovarian width (P = 0.020), ovarian weight (P = 0.004), the number of mature follicles (P = 0.020), and diameter of the mature follicles (P = 0.016). Furthermore, the combinatorial analysis showed that the two indel combined-genotypes were significantly related to several reproductive traits (ovarian width, ovarian weight, etc.). Collectively, our findings indicated that these two novel indels and their combinations are correlated with the reproductive traits, and hence, they can serve in the marker-assisted selection (MAS) in cattle breeding. Nevertheless, further functional experiments are needed for understanding the mechanisms of these indels in cattle reproduction in a better way.