Livestock animals to study infertility in women

Anovulation is a major cause of infertility in mammalian females. Ovarian research in humans is challenging due to the shortage of “normal tissue” that can be obtained from women that are trying to get pregnant. Livestock animals provide valuable resources to investigate the optimal intra-follicular environment required to facilitate folliculogenesis and translate to humans. Different livestock models may be more useful depending on the specific biological process studied

Letrozole: A Steroid-Free Estrous Synchronization Method

Most bovine estrous synchronization protocols utilize progesterone plus estrogen to control ovulation timing. A drug that inhibits estrogen production (Letrozole) may be an alternative, steroid-free synchronization method (not yet commercially available). However, low estrogen can negatively affect the health of follicles/oocytes and impact fertility. To determine its effects, Letrozole was administered intramuscularly while tracking follicle growth and circulating hormones. Letrozole response was variable. Two of three cows experienced delayed luteolysis/ovulation and extended progesterone production. This preliminary data indicates that Letrozole treatment allows normal follicle progression but drug response may vary and little is known about effects on oocyte quality

Attainment and maintenance of pubertal cyclicity may predict reproductive longevity in beef heifers

We hypothesized the manner that heifers achieve puberty may indicate their future reproductive longevity. Heifers with discontinued or delayed cyclicity during puberty attainment may have irregular reproductive cycles, anovulation, and infertility in their first breeding season contributing to a shorter reproductive lifespan. Therefore, plasma progesterone (P4) was measured from weaning to breeding on 611 heifers born 2012–2017 and four pubertal classifications were identified: (1) Early; P4 ≥ 1 ng/ml \u3c March 12 with continued cyclicity, (2) Typical; P4 ≥ 1 ng/ml ≥ March 12 with continued cyclicity, (3) Start-Stop; P4 ≥ 1 ng/ml but discontinued cyclicity, and (4) Non-Cycling; no P4 ≥ 1 ng/ml. Historical herd records indicated that 25% of heifers achieved puberty prior to March 12th in the 10 years prior to the study. Start-Stop and Non-Cycling yearling heifers were lighter indicating reduced growth and reproductive maturity traits compared with Early/Typical heifers. In addition, Non-Cycling/Start-Stop heifers were less responsive to prostaglandin F2 alpha (PGF2α) to initiate estrous behavior and ovulation to be artificially inseminated. Non-Cycling heifers had fewer reproductive tract score-5 and reduced numbers of calves born in the first 21-days-ofcalving during their first breeding season. Within the Start-Stop classification, 50% of heifers reinitiated cyclicity with growth traits and reproductive parameters that were similar to heifers in the Early/Typical classification while those that remained non-cyclic were more similar to heifers in the Non-Cycling group. Thus, heifers with discontinued cyclicity or no cyclicity during puberty attainment had delayed reproductive maturity resulting in subfertility and potentially a shorter reproductive lifespan

Vascular Endothelial Growth Factor A 165 rescues steroids, inflammation and follicle arrest in High Androstenedione cows

A population of cows with excess androstenedione (A4; High A4) in follicular fluid, with follicular arrest, granulosa cell dysfunction, and a 17% reduction in calving rate was previously identified. We hypothesized that excess A4 in the ovarian microenvironment caused the follicular arrest in High A4 cows and that vascular endothelial growth factor A would rescue the High A4 phenotype. In trial 1, prior to culture, High A4 ovarian cortex (n=9) had greater numbers of early stage follicles (primordial) and fewer later-stage follicles compared to controls (n=11). Culture for 7 days did not relieve this follicular arrest; instead, High A4 ovarian cortex had increased indicators of inflammation, anti-Mullerian hormone, and A4 secretion compared to controls. In trial 2, we tested if vascular endothelial growth factor A (VEGFA) angiogenic (165) and antiangiogenic (VEGFA165b) isoforms could rescue the High A4 phenotype. High A4 (n=5) and control (n=5) ovarian cortex was cultured with (1) PBS, (2) VEGFA165 (50 ng/mL), (3) VEGFA165b (50 ng/mL), or (4) VEGFA165+VEGFA165b (50 ng/mL each) for 7 days. Follicular progression increased with VEGFA165 in High A4 cows with greater early primary, primary, and secondary follicles than controls. Similar to trial 1, High A4 ovarian cortex secreted greater concentrations of A4 and other steroids and had greater indicators of inflammation compared to controls. However, VEGFA165 rescued steroidogenesis, oxidative stress, and fibrosis. Both VEGFA isoforms reduced specific pro-inflammatory cytokines in High A4 cows to control levels. Thus, VEGFA165 may be a potential therapeutic to restore the ovarian steroidogenic microenvironment to promote folliculogenesis

Livestock animals to study infertility in women

Anovulation is a major cause of infertility in mammalian females. Ovarian research in humans is challenging due to the shortage of “normal tissue” that can be obtained from women that are trying to get pregnant. Livestock animals provide valuable resources to investigate the optimal intra-follicular environment required to facilitate folliculogenesis and translate to humans. Different livestock models may be more useful depending on the specific biological process studied

Effect of Postweaning Diet, Excess Androstedione, and Vascular Endothelial Growth Factor a (VEGFA) Isoforms on Follicular Progression in Bovine Ovarian Cortical Cultures

The objective of this study was to determine the effect of changes in diet before puberty in heifers, excess A4 in cows and VEGFA isoforms on follicle progression in bovine ovarian cortex cultures. Two different studies were conducted to better understand how these factors affect bovine follicle development. The first study we evaluated the effect of changes in diets before puberty on follicle development and determined that diet treatment beef heifers had more primordial follicles than control beef heifers at 13 months of age. VEGFA165 can stimulate follicle progression independent of diet. Diet treatment had different VE-CADHERIN and NRP-1 mRNA expression in the ovarian cortex of beef heifers at 13 months. The second study we evaluated follicle development in the ovary of cows with excess A4 in the follicular fluid (FF) and found that uncultured ovarian cortex from High A4 cows had more primordial follicles and fewer primary, secondary and antral follicles when compared to control cows. However, after 7 days of culture in PBS, High A4 ovarian cortex had more primordial follicles indicating that culture conditions did not relieve the follicular arrest in High A4 ovarian cortex compared to the control cows. There was an increase in the expression of CYP17 in the stroma of High A4 cows. There was also positive staining for oxidative stress and fibrosis in the ovarian cortex of High A4 cows. In summary, we showed that (1) the postweaning diet can affect the number of primordial follicles; (2) VEGFA165 can stimulate follicle progression independent of diet; and (3) VEGFA165B can antagonize the actions of angiogenic isoform VEGFA165. We also demonstrated that cows with androgen excess in the follicular fluid: (1) have excess A4 in the culture media from ovarian cortex as well as impaired follicle development both in vivo and in vitro; (2) have increased expression of CYP17A1 in the stroma of ovarian cortex; (3) and VEGFA165 may be a potential therapeutic to restore the ovarian microenvironment and enhance follicular maturation. Thus, excess A4 environment which may be due to aberrant expression of CYP17A1 in the stroma could potentially lead to oxidative stress and fibrosis which prevents normal follicle development

Effect of supplemental rumen-protected methionine on reproduction and production of Awassi ewes

The effect of rumen-protected methionine (RPM) was investigated in Awassi ewes (0, 3 or 5 g/head/d, n = 20) on reproductive and productive performance (initial body weight [BW] = 70.9 − 71.8 kg, 3 − 5 years). Supplementation started with the flushing feeding regime (at the breeding time) and lasted for 42 d. RPM was reused during the last 60 d of pregnancy and the first 60 d of lactation. RPM increased (p < .05) progesterone concentration with a higher lambing rate at the 5RPM level. The number of lambs born for each ewe exposed to the ram was also higher (p < .05) with 3RPM and 5RPM. Methionine levels in the plasma were greater (p < .05) with RPM mainly at 5RPM level. Birth weights of the lambs were higher (p < .05) with RPM regardless of the level. Contrary to this, weaning weights and rate of gain for lambs were reduced (p < .05) with RPM addition. RPM did not affect milk production of ewes during the first 60 d of lactation or on energy corrected milk and feed to milk ratio. However, milk protein content was increased (p < .05) at the 5RPM level while milk fat content was decreased. Regardless of the level of RPM addition, milk casein content increased (p < .05). At all levels, the effect of RPM on milk fatty acid profile was minor. It can be concluded that supplementing RPM might be a valuable tool to enhance the reproductive and productive performance of ewes during their breeding season

Cows with Excess Androgen are Anovulatory and Have Differing Patterns of Progesterone Secretion

Within the physiology herd, a group of cows that have excess androgen (androstenedione, A4) in the dominant follicle and a 17% reduction in calving rate have being identified. Thus, our objective was to determine follicular dynamics (follicle growth) and progesterone (P4) concentrations in High A4 cows to determine if they were anovulatory. High A4 cows had more persistent dominant follicles and either did not display estrus and ovulated at an inappropriate time or did not ovulate compared with Low A4 cows (Controls). Furthermore, P4 concentrations had reduced peak values and were maintained longer in High vs Low A4 cows which may contribute to their failure to ovulate

Letrozole: A Steroid-Free Estrous Synchronization Method

Most bovine estrous synchronization protocols utilize progesterone plus estrogen to control ovulation timing. A drug that inhibits estrogen production (Letrozole) may be an alternative, steroid-free synchronization method (not yet commercially available). However, low estrogen can negatively affect the health of follicles/oocytes and impact fertility. To determine its effects, Letrozole was administered intramuscularly while tracking follicle growth and circulating hormones. Letrozole response was variable. Two of three cows experienced delayed luteolysis/ovulation and extended progesterone production. This preliminary data indicates that Letrozole treatment allows normal follicle progression but drug response may vary and little is known about effects on oocyte quality

Effects of medical plants on alleviating the effects of heat stress on chickens

ABSTRACT: Over the past decades, global climate change has led to a significant increase in the average ambient temperature causing heat stress (HS) waves. This increase has resulted in more frequent heat waves during the summer periods. HS can have detrimental effects on poultry, including growth retardation, imbalance in immune/antioxidant pathways, inflammation, intestinal dysfunction, and economic losses in the poultry industry. Therefore, it is crucial to find an effective, safe, applicable, and economically efficient method for reducing these negative influences. Medicinal plants (MPs) contain various bioactive compounds with antioxidant, antimicrobial, anti-inflammatory, and immunomodulatory effects. Due to the biological activities of MPs, it could be used as promising thermotolerance agents in poultry diets during HS conditions. Nutritional supplementation with MPs has been shown to improve growth performance, antioxidant status, immunity, and intestinal health in heat-exposed chickens. As a result, several types of herbs have been supplemented to mitigate the harmful effects of heat stress in chickens. Therefore, several types of herbs have been supplemented to mitigate the harmful effects of heat stress in chickens. This review aims to discuss the negative consequences of HS in poultry and explore the use of different traditional MPs to enhance the health status of chickens