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Summary: Progesterone signaling and uterine function are crucial in terms of pregnancy establishment. To investigate how the uterine tissue and its secretion changes in relation to puberty, we sampled tissue and uterine fluid from six pre‐ and six post‐pubertal Brahman heifers. Post‐pubertal heifers were sampled in the luteal phase. Gene expression of the uterine tissue was investigated with RNA‐sequencing, whereas the uterine fluid was used for protein profiling with mass spectrometry. A total of 4034 genes were differentially expressed (DE) at a nominal P‐value of 0.05, and 26 genes were significantly DE after Bonferroni correction (P < 3.1 × 10−6). We also identified 79 proteins (out of 230 proteins) that were DE (P < 1 × 10−5) in the uterine fluid. When we compared proteomics and transcriptome results, four DE proteins were identified as being encoded by DE genes: OVGP1, GRP, CAP1 and HBA. Except for CAP1, the other three had lower expression post‐puberty. The function of these four genes hypothetically related to preparation of the uterus for a potential pregnancy is discussed in the context of puberty. All DE genes and proteins were also used in pathway and ontology enrichment analyses to investigate overall function. The DE genes were enriched for terms related to ribosomal activity. Transcription factors that were deemed key regulators of DE genes are also reported. Transcription factors ZNF567,ZNF775,RELA,PIAS2,LHX4,SOX2,MEF2C,ZNF354C,HMG20A,TCF7L2,ZNF420,HIC1,GTF3A and two novel genes had the highest regulatory impact factor scores. These data can help to understand how puberty influences uterine function. [ABSTRACT FROM AUTHOR]

To understand genes, pathways, and networks related to puberty, we characterized the transcriptome of two tissues: the pituitary gland and ovaries. Samples were harvested from pre- and postpubertal Brahman heifers (same age group). Brahman heifers (Bos indicus) are older at puberty compared with Bos taurus, a productivity issue. With RNA sequencing, we identified differentially expressed (DEx) genes and important transcription factors (TF) and predicted coexpression networks. The number of DEx genes detected in the pituitary gland was 284 (P < 0.05), and VWC2L was the most DEx gene (fold change = 4.12, P = 0.01). The gene VWC2L promotes bone mineralization through transforming growth factor-β (TGFβ) signaling. Further studies of the link between bone mineralization and puberty could target VWC2L. In ovaries, 3,871 genes were DEx (P < 0.05). Four highly DEx genes were noteworthy for their function: SLC6A13 (a γ-aminobutyric acid [GABA] transporter), OXT (oxytocin), and NPY (neuropeptide Y) and its receptor NPY2R. These genes had higher ovarian expression in postpubertal heifers. The GABA and its receptors and transporters were expressed in the ovaries of many mammals, suggesting a role for this pathway beyond the brain. The OXT pathway has been known to influence the timing of puberty in rats, via modulation of GnRH. The effects of NPY at the hypothalamus, pituitary gland, and ovaries have been documented. Neuropeptide Y and its receptors are known factors in the release of GnRH, similar to OXT and GABA, although their roles in ovarian tissue are less clear. Pathways previously related to puberty such as TGFβ signaling (P = 6.71 × 10-5), Wnt signaling (P = 4.1 × 10-2), and peroxisome proliferator-activated receptor (PPAR) signaling (P = 4.84 × 10-2) were enriched in our data set. Seven genes were identified as key TF in both tissues: HIC2, ZIC4, ZNF219, ZSCAN26, LHX1, OLIG1, and a novel gene. An ovarian subnetwork created with TF and significant ovarian DEx genes revealed five zinc fingers as regulators: ZNF507, ZNF12, ZNF512, ZNF184, and ZNF432. Recent work of hypothalamic gene expression also pointed to zinc fingers as TF for bovine puberty. Although some zinc fingers may be ubiquitously expressed, the identification of DEx genes in common across tissues points to key regulators of puberty. The hypothalamus and pituitary gland had eight DEx genes in common. The hypothalamus and ovaries had 89 DEx genes in common. The pituitary gland and ovaries had 48 DEx genes in common. Our study confirmed the complexity of puberty and suggested further investigation on genes that code zinc fingers. [ABSTRACT FROM AUTHOR]

Puberty onset is a developmental process influenced by genetic determinants, environment, and nutrition. Mutations and regulatory gene networks constitute the molecular basis for the genetic determinants of puberty onset. The emerging knowledge of these genetic determinants presents opportunities for innovation in the breeding of early pubertal cattle. This paper presents new data on hypothalamic gene expression related to puberty in Bos indicus (Brahman) in age- and weight-matched heifers. Six postpubertal heifers were compared with 6 prepubertal heifers using whole-genome RNA sequencing methodology for quantification of global gene expression in the hypothalamus. Five transcription factors (TF) with potential regulatory roles in the hypothalamus were identified in this experiment: E2F8, NFAT5, SIX5, ZBTB38, and ZNF605. These TF genes were significantly differentially expressed in the hypothalamus of postpubertal versus prepubertal heifers and were also identified as significant according to the applied regulatory impact factor metric (P < 0.05). Two of these 5 TF, ZBTB38 and ZNF605, were zinc fingers, belonging to a gene family previously reported to have a central regulatory role in mammalian puberty. The SIX5 gene belongs to the family of homologues of Drosophila sine oculis (SIX) genes implicated in transcriptional regulation of gonadotrope gene expression. Tumor-related genes such as E2F8 and NFAT5 are known to affect basic cellular processes that are relevant in both cancer and developmental processes. Mutations in NFAT5 were associated with puberty in humans. Mutations in these TF, together with other genetic determinants previously discovered, could be used in genomic selection to predict the genetic merit of cattle (i.e., the likelihood of the offspring presenting earlier than average puberty for Brahman). Knowledge of key mutations involved in genetic traits is an advantage for genomic prediction because it can increase its accuracy. [ABSTRACT FROM AUTHOR]

This study investigated effects of maternal overnutrition on gonadal development and pituitary-gonadal gene expression in cattle fetuses at mid- and late-gestation. Twenty-seven multiparous dry cows were fed either high (ad libitum, H) or moderate (M) intake of the same diet. Twelve cows from H (n = 6) and M (n = 6) intake carrying females fetuses were euthanized at 199 and 268 d of gestation (DG; n = 3 for H or M on each DG). Fifteen cows from H (n = 6) and M intake (n = 9) carrying male fetuses were euthanized at 139, 199, and 241 DG (n = 2 for H and n = 3 for M on each DG). Fetal gonads and pituitary gland were sampled for gene expression and histological analyses. Sex-specific responses to maternal intake were observed. Primordial and total follicle numbers were lower in fetal ovaries from H than in M intake cows. These results were the reverse for preantral and antral follicles. Volumetric proportion and diameter of seminiferous cord were lower in fetal testis of H than M intake cows. The expression level of FSHB was greater in pituitary gland of the female fetus from H compared with M intake cows, irrespective of DG, whereas LHB gene expression did not differ. In males, FSHB and LHB gene expression levels were similar between maternal intake groups. Fetal ovarian expression of P450 aromatase, StAR, BMPR2, TGFBR1, GDF9, FSHR, Bax, and CASP3 genes were higher in H than in M intake cows, irrespective of DG. Fetal testicular expression of StAR, HSD17B3, IGF1, IGF2, and IGF1R genes was higher in M than in H intake cows. The differences in gene expression for steroidogenesis, folliculogenesis, and apoptosis may explain the distinct pattern of follicular growth between offspring of M and H intake cows. By contrast, the lower volumetric proportion, diameter, and length of seminiferous cord may relate to decreased gene expression in fetal testis from H intake cows. In conclusion, maternal H intake seems to affect fetal ovarian follicular growth and number of follicles, which may affect the size of ovarian reserve in their offspring. In male fetus, maternal H intake seems to disturb testicular development and may have implications on sperm production. The underlying mechanism of differential gene expression and the effect on offspring reproductive potential should be the focus of further research, especially considering larger sample size, reducing the chance for type I errors. [ABSTRACT FROM AUTHOR]

Background: Asian buffaloes (Bubalus bubalis) have an important socio-economic role. The majority of the population is situated in developing countries. Due to the scarce resources in these countries, very few species-specific biotechnology tools exist and a lot of cattle-derived technologies are applied to buffaloes. However, the application of cattle genomic tools to buffaloes is not straightforward and, as results suggested, despite genome sequences similarity the genetic polymorphisms are different. Results: The first SNP chip genotyping platform designed specifically for buffaloes has recently become available. Herein, a genome-wide association study (GWAS) and gene network analysis carried out in buffaloes is presented. Target phenotypes were six milk production and four reproductive traits. GWAS identified SNP with significant associations and suggested candidate genes that were specific to each trait and also genes with pleiotropic effect, associated to multiple traits. Conclusions: Network predictions of interactions between these candidate genes may guide further molecular analyses in search of disruptive mutations, help select genes for functional experiments and evidence metabolism differences in comparison to cattle. The cattle SNP chip does not offer an optimal coverage of buffalo genome, thereafter the development of new buffalo-specific genetic technologies is warranted. An annotated reference genome would greatly facilitate genetic research, with potential impact to buffalo-based dairy production. [ABSTRACT FROM AUTHOR]