“…Moreover, six DMRs (five distal intergenic and one intron) were identified in INHBA, of which five were hypo-methylated and one was hypermethylated in the LPB + vs. LPBB group. FZD1 has been confirmed to regulate certain biological processes, including oocyte maturation, female fertility (Lapointe et al, 2012), embryonic development (Tribulo et al, 2017) and ovary development (Tepekoy et al, 2019). The methylation level of the 3′-UTR of FZD1 in the HPBB group was higher than that in the LPB + group.…”
DNA methylation plays an important role in biological processes by affecting gene expression. However, how DNA methylation regulates phenotypic variation in Hu sheep remains unclear. Therefore, we generated genome-wide DNA methylation and transcriptomic profiles in the ovaries of Hu sheep with different prolificacies and genotypes (FecBB and FecB+). Results showed that ovary DNA methylome and transcriptome were significantly different between high prolificacy and low prolificacy Hu sheep. Comparative methylome analyses identified 10,644, 9,594, and 12,214 differentially methylated regions and 87, 1,121, and 2,375 genes, respectively, showing differential expression levels in three different comparison groups. Female reproduction-associated differentially methylated regions-related genes and differentially expressed genes were enriched, thereby the respective interaction networks were constructed. Furthermore, systematical integrative analyses revealed a negative correlation between DNA methylation around the transcriptional start site and gene expression levels, which was confirmed by testing the expression of integrin β2 subunit (ITGB2) and lysosome-associated protein transmembrane-4 beta (LAPTM4B) in vivo and in vitro. These findings demonstrated that DNA methylation influences the propensity for prolificacy by affecting gene expression in the ovaries, which may contribute to a greater understanding of the epigenome and transcriptome that will be useful for animal breeding.
“…Moreover, six DMRs (five distal intergenic and one intron) were identified in INHBA, of which five were hypo-methylated and one was hypermethylated in the LPB + vs. LPBB group. FZD1 has been confirmed to regulate certain biological processes, including oocyte maturation, female fertility (Lapointe et al, 2012), embryonic development (Tribulo et al, 2017) and ovary development (Tepekoy et al, 2019). The methylation level of the 3′-UTR of FZD1 in the HPBB group was higher than that in the LPB + group.…”
DNA methylation plays an important role in biological processes by affecting gene expression. However, how DNA methylation regulates phenotypic variation in Hu sheep remains unclear. Therefore, we generated genome-wide DNA methylation and transcriptomic profiles in the ovaries of Hu sheep with different prolificacies and genotypes (FecBB and FecB+). Results showed that ovary DNA methylome and transcriptome were significantly different between high prolificacy and low prolificacy Hu sheep. Comparative methylome analyses identified 10,644, 9,594, and 12,214 differentially methylated regions and 87, 1,121, and 2,375 genes, respectively, showing differential expression levels in three different comparison groups. Female reproduction-associated differentially methylated regions-related genes and differentially expressed genes were enriched, thereby the respective interaction networks were constructed. Furthermore, systematical integrative analyses revealed a negative correlation between DNA methylation around the transcriptional start site and gene expression levels, which was confirmed by testing the expression of integrin β2 subunit (ITGB2) and lysosome-associated protein transmembrane-4 beta (LAPTM4B) in vivo and in vitro. These findings demonstrated that DNA methylation influences the propensity for prolificacy by affecting gene expression in the ovaries, which may contribute to a greater understanding of the epigenome and transcriptome that will be useful for animal breeding.
“…The secreted form of FNDC4 may also act on the ovarian follicle, as a number of the receptors and pathways employed by FNDC4 described above are also present in granulosa cells, including ADGRF5 (Prömel et al 2012), Frizzled and LRP6 (Tepekoy et al 2019), fibronectin and FAK (Kitasaka et al 2018), alphaV and beta1 integrins (Burns et al 2002) and the energy sensor, AMPK (Horlock et al 2021). As dairy cattle become insulin resistant during lactation (Bossaert et al 2008), it is possible that altered secretion of FNDC4 may play a role to improve glucose uptake and mitigate the negative effects of NEB.…”
Dietary stress such as obesity and short-term changes in energy balance can disrupt ovarian function leading to infertility. Adipose tissue secretes hormones (adipokines), such as leptin and adiponectin, that are known to alter ovarian function. Muscles can also secrete endocrine factors, and one such family of myokines, the eleven Fibronectin type III Domain-Containing (FNDC) proteins, is emerging as important for energy sensing and homeostasis. In this review we summarize the known roles the FNDC proteins play in energy homeostasis and explore potential impacts on fertility in females. The most well-known member, FNDC5, is the precursor of the 'exercise hormone', irisin, secreted by both muscle and adipose tissue. The receptors for irisin are integrins, and it has recently been shown to alter steroidogenesis in ovarian granulosa cells although the effects appear to be species or context specific, and irisin may improve uterine and placental function in women and rodent models. Another member, FNDC4, is also cleaved to release a bioactive protein that modulates insulin sensitivity in peripheral tissues and whose receptor, ADGRF5, is expressed in the ovary. As obese women and farm animals in negative energy balance (NEB) both have altered insulin sensitivity, secreted FNDC4 may impact ovarian function. We propose a model in which NEB or dietary imbalance alters plasma irisin and secreted FNDC4 concentrations, which then act on the ovary through their cognate receptors to reduce granulosa cell proliferation and follicle health. Research into these molecules will increase our understanding of energy sensing and fertility, and may lead to new approaches to alleviate post-partum infertility
“…However, the long-term use of the GnRH-a leuprorelin results in decreased bone mineral density (150,151). The GnRH ant, cetrorelix inhibits the synthesis and secretion of gonadotropin by competing with GnRH receptor on the surface of pituitary cells to block GnRH secretion (152)(153)(154). In addition, clomiphene citrate, an estrogen receptor regulator, increases the secretion of GnRH in the hypothalamus by inhibiting the negative feedback regulation of estrogen.…”
Section: Effects Of Lh On Reproductive Developmentmentioning
The hypothalamus acts on the pituitary gland after signal integration, thus regulating various physiological functions of the body. The pituitary gland includes the adenohypophysis and neurohypophysis, which differ in structure and function. The hypothalamus-hypophysis axis controls the secretion of adenohypophyseal hormones through the pituitary portal vein system. Thyroid-stimulating hormone, adrenocorticotropic hormone, gonadotropin, growth hormone (GH), and prolactin (PRL) are secreted by the adenohypophysis and regulate the functions of the body in physiological and pathological conditions. The aim of this review was to summarize the functions of female-associated hormones (GH, PRL, luteinizing hormone, and follicle-stimulating hormone) in tumors. Their pathophysiology was described and the mechanisms underlying female hormone-related diseases were investigated. Contents 1. Introduction 2. Growth hormone 3. Prolactin 4. Gonadotropin 5. Conclusions
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