281 Can We Developmentally Program the Epigenome to Improve Traits Relevant to Production in Cattle?

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 20-20
Author(s):  
Robert A Cushman ◽  
Alexandria Snider ◽  
Matthew S Crouse

Abstract While sequence variation can be informative to associate regions of the genome with specific traits and improve genetic selection, the epigenome may provide a more powerful tool to manage cattle. Identifying practices that are producer friendly and effectively control epigenetic function within animals is crucial to translating developmental programming to a production setting. Initial studies of developmental programming investigated how environmental or nutritional stresses during fetal and peri-natal development impacted performance of animals later in life. These studies demonstrated changes in methylation, alterations in transcript abundance, and negative impacts on physiology, but they also suggested that we may be able to beneficially impact the epigenome and developmentally program animals to excel in their niche in the production system. Maternal nutritional status during the third trimester influenced date of conception of female progeny in several studies but failed to do so in other studies. Transcriptomic analyses provided evidence that nutritional treatments alter mRNA abundance in brain, liver, muscle, and ovary, but does not conclusively demonstrate that this is due to functional changes in the epigenome. If developmental programming is to be applied in production systems, responses must be consistent and beneficial. Reducing nutrient intake in heifers during peri-pubertal development increased number of primordial follicles in the ovaries and reproductive longevity. While nutritional programming of the ovarian reserve in peri-pubertal heifers appears to occur consistently across locations and studies, it does not ensure that subsequent environmental stressors will not induce changes in the ovarian reserve that will negate beneficial effects. These studies demonstrate that it is possible to developmentally program the epigenome in cattle in ways that will improve production traits; however, there remains a need for studies to improve the consistency of response and to determine best practices that fit into production systems. USDA is an equal opportunity provider and employer.

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 123-123
Author(s):  
Robert A Cushman ◽  
Shelby Rosasco ◽  
Kaitlin M Epperson ◽  
Emmalee J Northrop-Albrecht ◽  
Jerica J Rich ◽  
...  

Abstract The relationship of ovarian reserve parameters to fertility in mammalian females continues to be debated. We demonstrated improved uterine function, creating an environment that is more supportive of early embryonic development in beef heifers with increased numbers of follicles. In the present study we hypothesized that timing of luteolysis differs between heifers with increased compared to heifers with diminished numbers of follicles. Angus heifers (n = 20/ group) were classified as low (14.7 ± 1.1) or high (32 ± 1.1) antral follicle number based on ovarian ultrasonography, and artificially inseminated (d0) following a Select Synch protocol. At d16 after insemination, heifers were slaughtered, and reproductive tracts collected. Tracts were flushed with 20 mL of physiological saline to determine pregnancy status by presence of a conceptus and endometrial samples from the horn ipsilateral to the CL were frozen for determination of transcript abundance. Real-time RT-PCR was performed to determine relative transcript abundance of oxytocin receptor (OXTR) and interferon-stimulated gene-15 (ISG15) with glyceraldehyde-3-phospate dehydrogenase as the endogenous reference gene. Transcript abundance was analyzed using the MIXED procedure of SAS with follicle group, pregnancy status and the interaction as fixed effects. Transcript abundance of ISG15 was greater in pregnant endometrium than non-pregnant endometrium (2.75 ± 0.25 vs 0.16 ± 0.22-fold; P < 0.0001) with no influence of follicle group or the interaction. The interaction of follicle group and pregnancy status influenced OXTR transcript abundance (P = 0.06). Luteolytic mechanisms were activated in non-pregnant heifers with diminished numbers of follicles (1.46 ± 0.25-fold) and were not activated in pregnant heifers (0.06 ± 0.22-fold) or heifers with increased numbers of follicles that were not pregnant (0.32 ± 0.30-fold). These data indicate a wider window of recognition of pregnancy in beef heifers with increased numbers of ovarian follicles. USDA is an equal opportunity provider and employer.


2021 ◽  
Vol 22 (12) ◽  
pp. 6570
Author(s):  
Yue Lv ◽  
Rui-Can Cao ◽  
Hong-Bin Liu ◽  
Xian-Wei Su ◽  
Gang Lu ◽  
...  

A better understanding of the mechanism of primordial follicle activation will help us better understand the causes of premature ovarian insufficiency (POI), and will help us identify new drugs that can be applied to the clinical treatment of infertility. In this study, single oocytes were isolated from primordial and primary follicles, and were used for gene profiling with TaqMan array cards. Bioinformatics analysis was performed on the gene expression data, and Ingenuity Pathway Analysis was used to analyze and predict drugs that affect follicle activation. An ovarian in vitro culture system was used to verify the function of the drug candidates, and we found that curcumin maintains the ovarian reserve. Long-term treatment with 100 mg/kg curcumin improved the ovarian reserve indicators of AMH, FSH, and estradiol in aging mice. Mechanistic studies show that curcumin can affect the translocation of FOXO3, thereby inhibiting the PTEN-AKT-FOXO3a pathway and protecting primordial follicles from overactivation. These results suggest that curcumin is a potential drug for the treatment of POI patients and for fertility preservation.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Sarah E. Moorey ◽  
Fernando H. Biase

Abstract The development of replacement heifers is at the core of cow-calf beef production systems. In 2020, the USDA, National Agricultural Statistics Service reported 5.771 million beef heifers, 500 pounds and over, are under development for cow replacement. A compilation of data from several studies indicate that between 85% and 95% of these heifers will become pregnant in their first breeding season. Several thousands of heifers being raised for replacement may not deliver a calf on their first breeding season and result in economic losses to cow-calf producers. Many management procedures have been developed to maximize the reproductive potential of beef heifers. Such approaches include, but are not limited to the following: nutritional management for controlled weight gain, identification of reproductive maturity by physiological and morphological indicators, and the implementation of an estrous synchronization program. The implementation of management strategies has important positive impact(s) on the reproductive efficiency of heifers. There are limitations, however, because some heifers deemed ready to enter their first breeding season do not become pregnant. In parallel, genetic selection for fertility-related traits in beef heifers have not promoted major genetic gains on this particular area, most likely due to low heritability of female fertility traits in cattle. Technologies such as antral follicle counting, DNA genotyping and RNA profiling are being investigated as a means to aid in the identification of heifers of low fertility potential. To date, many polymorphisms have been associated with heifer fertility, but no DNA markers have been identified across herds. Antral follicle count is an indication of the ovarian reserve and is an indicator of the reproductive health of a heifer. We have been working on the identification of transcriptome profiles in heifers associated with pregnancy outcome. Our current investigations integrating protein-coding transcript abundance and artificial intelligence have identified the potential for bloodborne transcript abundance to be used as indicators of fertility potential in beef heifers. In summary, there is an ongoing pressure for reducing costs and increasing efficiency in cow-calf production systems, and new technologies can help reduce the long-standing limitations in beef heifer fertility.


Author(s):  
Analia Lorena Tomat ◽  
Francisco Javier Salazar

AbstractA substantial body of epidemiological and experimental evidence suggests that a poor fetal and neonatal environment may “program” susceptibility in the offspring to later development of cardiovascular, renal and metabolic diseases.This review focuses on current knowledge from the available literature regarding the mechanisms linking an adverse developmental environment with an increased risk for cardiovascular, renal and metabolic diseases in adult life. Moreover, this review highlights important sex-dependent differences in the adaptation to developmental insults.Developmental programming of several diseases is secondary to changes in different mechanisms inducing important alterations in the normal development of several organs that lead to significant changes in birth weight. The different diseases occurring as a consequence of an adverse environment during development are secondary to morphological and functional cardiovascular and renal changes, to epigenetic changes and to an activation of several hormonal and regulatory systems, such as angiotensin II, sympathetic activity, nitric oxide, COX2-derived metabolites, oxidative stress and inflammation. The important sex-dependent differences in the developmental programming of diseases seem to be partly secondary to the effects of sex hormones. Recent studies have shown that the progression of these diseases is accelerated during aging in both sexes.The cardiovascular, renal and metabolic diseases during adult life that occur as a consequence of several insults during fetal and postnatal periods are secondary to multiple structural and functional changes. Future studies are needed in order to prevent the origin and reduce the incidence and consequences of developmental programmed diseases.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Fangui Zhao ◽  
Wenjun Wang

Diminished ovarian reserve (DOR) refers to a decrease in the number and quality of oocytes. Western treatment of DOR does not improve the ovarian reserve fundamentally, and the effect is limited. Gengnianchun recipe (GNC) is a traditional Chinese medicine formula originally applied to treat menopausal syndrome but is also found to be effective in treating clinical DOR patients. Here we aim to examine the effect of GNC in a DOR rat model induced by 4-vinylcyclohexene diepoxide (VCD), a chemical that selectively destroys ovarian small preantral follicles, and further investigate the possible mechanisms. Female SD rats were randomly divided into four groups: control group (C), model group (M), high-dose GNC group (H), and low-dose GNC group (L). Rats in M, H, and L were administered with VCD and normal saline, high-dose GNC, and low-dose GNC separately. Rat ovaries were harvested either to conduct HE staining for follicle count, immunohistochemistry, or western blot. We found that high dose of GNC significantly increased the ovarian index and sustained the number of primordial follicles and primary follicles in VCD treated rats. Moreover, high dose of GNC significantly increased the ovarian protein expression of mouse vasa homologue (MVH), anti-Müllerian hormone (AMH), follicle-stimulating hormone receptor (FSHR), and estrogen receptor β (ERβ) compared with that in the model group. Besides, high-dose GNC significantly increased ovarian AKT phosphorylation and the expression of downstream forkhead box O3 (FOXO3a). Proapoptosis proteins of Bax, cleaved caspase-3, and poly ADP-ribose polymerase (PARP) were significantly decreased after high-dose GNC treatment compared with those in the model group. Taken together, these findings suggest that high-dose GNC could protect ovarian reserve against VCD-induced toxicity via the activation of the AKT signaling pathway and reduced cell apoptosis in SD Rats. This effect could either be induced by the increased FSHR signaling or by the nontranscriptional activation of ERβ, which requires further investigation.


2008 ◽  
Vol 51 (6) ◽  
pp. 549-559 ◽  
Author(s):  
D. Jordan ◽  
S. Žgur ◽  
G. Gorjanc ◽  
I. Štuhec

Abstract. Fattening pigs are commonly kept in intensive housing systems with slatted floor which represent a very barren environment, causing poor animal welfare. To improve such conditions a small amount of straw or hay (100 g per animal per day laid daily in a rack) was used in our study as an environmental enrichment (EE). Two replications, each including 96 fattening pigs of both sexes (3 pens of 16 females and 3 pens of 16 male castrates) from 60 kg to slaughter at average 96 kg live weight, were used to test the effect of EE and sex on behaviour, growth rate, and carcass composition. EE significantly increased the proportion of total activity during the illumination period (between 6 a. m. and 2 p. m.) on account of increased occupation with substrate (P<0.01). EE also significantly reduced time spent biting pen bars and frequency of aggressive encounters (P<0.01). The EE increased total activity in female animals during the observation period, but not in male castrates. None of the EE significantly influenced pigs‘ growth rate and lean meat percentage; however females in enriched environment grew slower and had greater lean meat percentage than the castrated males. Provision of a small amount of straw or hay to pigs in intensive housing systems can enrich barren environment in inexpensive and efficient way. Therefore such enrichment can be widely used also in large commercial pig production systems.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Volodarsky-Perel ◽  
M Zajicek ◽  
D Shai ◽  
H Raanani ◽  
N Gruber ◽  
...  

Abstract Study question What is the predictive value of ovarian reserve evaluation in patients with non-iatrogenic primary ovarian insufficiency (NIPOI) for follicle detection in ovarian tissue harvested for cryopreservation? Summary answer Ovarian tissue cryopreservation (OTCP) should be considered if patients present at least one of the following parameters: detectable AMH, FSH≤20mIU/ml, detection of ≥ 1 antral follicle. What is known already In pre-pubertal girls suffering from NIPOI, which majorly has a genetic etiology, fertility preservation using OTCP is commonly practiced. When OTCP was performed in an unselected group of children and adolescents with NIPOI, only 26% of them had follicles in ovarian tissue while 74% did not benefit from the surgery. The role of preoperative evaluation of anti-müllerian hormone (AMH) serum level, follicular stimulating hormone (FSH) serum level, and trans-abdominal ultrasound for the antral follicle count to predict the detection of primordial follicles in the harvested ovarian tissue is unclear. Study design, size, duration We conducted a retrospective analysis of all patients ≤ 18 years old who were referred for fertility preservation counseling due to NIPOI at a single tertiary hospital between 2010 and 2020. If initial evaluation suggested a diminished ovarian reserve and at least one positive parameter indicating a follicular activity (AMH &gt; 0.16ng/ml, FSH ≤ 20mIU/ml, detection of ≥ 1 antral follicle by transabdominal sonography), OTCP was offered. Patients with 46XY gonadal dysgenesis were excluded. Participants/materials, setting, methods OTCP was performed laparoscopically in all cases. A fresh sample of cortical tissue was fixed in buffered formaldehyde for histological analysis. The rest of the ovarian tissue was cut into small cuboidal slices 1–2 mm in thickness and cryopreserved. After the serial sections, the histological slides were evaluated for the presence of follicles by a certified pathologist. Follicles were counted and categorized as primordial, primary, and secondary. Main results and the role of chance During the study period, 39 patients with suspected NIPOI were referred to the fertility preservation center. Thirty-seven patients included in the study were diagnosed with Turner’s syndrome (n = 28), Galactosemia (n = 3), Blepharophimosis-Ptosis-Epicanthus Inversus syndrome (n = 1), and idiopathic NIPOI (n = 6). Of 28 patients with Turner’s syndrome, 6 had 45X monosomy, 15 had mosaicism and 7 had structural anomalies in X-chromosome. One patient with gonadal dysgenesis and one with the presence of Y-chromosome in 20% of somatic cells were excluded from the study. OTCP was conducted in 14 patients with at least one positive parameter suggesting ovarian function. No complications of the surgical procedure or the anesthesia were observed. Primordial follicles were found in all patients with two or three positive parameters (100%) and in three of six cases with one positive parameter (50%). In total, of the 14 patients who underwent OTCP with at least one positive parameter, 11 (79%) had primordial follicles at biopsy (mean 23.9, range 2–47). This study demonstrates a positive predictive value of 79% for the detection of primordial follicles in patients who had at least one positive parameter of ovarian reserve evaluation. If two or three parameters were positive, the positive predictive value increased to 100%. Limitations, reasons for caution This study did not examine the negative predictive value of our protocol as OTCP was not recommended in the absence of positive parameters. The future fertility potential of cryopreserved tissue in the population with NIPOI is unclear and should be discovered in further studies. Wider implications of the findings: We suggest the evaluation of ovarian reserve by antral follicles count, AMH, and FSH serum levels prior to OTCP in patients with NIPOI. By recommendation of OTCP only if ≥ 1 parameter suggesting the ovarian function is positive, unnecessary procedures can be avoided. Trial registration number Not applicable


Author(s):  
Maria Francesca Messina ◽  
Tommaso Aversa ◽  
Giuseppina Salzano ◽  
Daria Costanzo ◽  
Concetta Sferlazzas ◽  
...  

AbstractPrimary gonadal failure may occur in most individuals with Turner syndrome (TS). Since ovaries in TS girls undergo premature apoptosis and cryopreservation of ovarian tissue is now feasible, it would be useful to identify a reliable marker of ovarian reserve in these patients. We planned to evaluate ovarian function in a group of TS patients by measuring both traditional markers and inhibin B and to compare these results with those of a control group.We enrolled 23 patients with TS and 17 age-matched healthy girls. The median age of our TS patients was 17.6 years. Three out of the 23 patients (13%) showed spontaneous pubertal development and regular menstrual cycles; the remaining 20 (86.9%) presented with primary amenorrhea.The median level of inhibin B in the TS patients with primary amenorrhea was 42 pg/mL and did not differ significantly among the different subgroups in relation to karyotype. The median inhibin B level in the control group was significantly higher than in the TS girls with primary amenorrhea (83 vs. 42 pg/mL, p<0.00001). In the three patients with TS and spontaneous menstrual cycles, the inhibin B levels were significantly higher when compared to the values of the TS girls with primary amenorrhea.TS patients with primary amenorrhea have significantly lower levels of inhibin B than TS girls with spontaneous puberty and healthy controls. Inhibin B does not correlate with follicle-stimulating hormone/luteinizing hormone. If our results are confirmed in further studies, inhibin B could become a first-line screening test for assessing ovarian reserve and a longitudinal marker of the possible decline of ovarian function in TS.


2019 ◽  
Vol 7 (1) ◽  
pp. 385-401 ◽  
Author(s):  
Mariana I. Giassetti ◽  
Michela Ciccarelli ◽  
Jon M. Oatley

The demand for food will increase to an unprecedented level over the next 30 years owing to human population expansion, thus necessitating an evolution that improves the efficiency of livestock production. Genetic gain to improve production traits of domestic animal populations is most effectively achieved via selective use of gametes from animals deemed to be elite, and this principle has been the basis of selective breeding strategies employed by humans for thousands of years. In modern-day animal agriculture, artificial insemination (AI) has been the staple of selective breeding programs, but it has inherent limitations for applications in beef cattle and pig production systems. In this review, we discuss the potential and current state of development for a concept termed Surrogate Sires as a next-generation breeding tool in livestock production. The scheme capitalizes on the capacity of spermatogonial stem cells to regenerate sperm production after isolation from donor testicular tissue and transfer into the testes of a recipient male that lacks endogenous germline, thereby allowing the surrogate male to produce offspring with the donor haplotype via natural mating. This concept provides an effective selective breeding tool to achieve genetic gain that is conducive for livestock production systems in which AI is difficult to implement.


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