Breeding schemes with optimum-contribution selection or truncation selection for beef cattle destined for use on dairy females

We tested the hypothesis that the size of a beef cattle population destined for use on dairy females is smaller under optimum-contribution selection (OCS) than under truncation selection (TRS) at the same genetic gain (ΔG) and the same rate of inbreeding (ΔF). We used stochastic simulation to estimate true ΔG realized at a 0.005 ΔF in breeding schemes with OCS or TRS. The schemes for the beef cattle population also differed in the number of purebred offspring per dam and the total number of purebred offspring per generation. Dams of the next generation were exclusively selected among the one-year-old heifers. All dams were donors for embryo transfer and produced a maximum of 5 or 10 offspring. The total number of purebred offspring per generation was: 400, 800, 1,600 or 4,000 calves, and it was used as a measure of population size. Rate of inbreeding was predicted and controlled using pedigree relationships. Each OCS (TRS) scheme was simulated for 10 discrete generations and replicated 100 (200) times. The OCS scheme and the TRS scheme with a maximum of 10 offspring per dam required approximately 783 and 1,257 purebred offspring per generation to realize a true ΔG of €14 and a ΔF of 0.005 per generation. Schemes with a maximum of 5 offspring per dam required more purebred offspring per generation to realize a similar true ΔG and a similar ΔF. Our results show that OCS and multiple ovulation and embryo transfer act on selection intensity through different mechanisms to achieve fewer selection candidates and fewer selected sires and dams than under TRS at the same ΔG and a fixed ΔF. Therefore, we advocate the use of a breeding scheme with OCS and multiple ovulation and embryo transfer for beef cattle destined for use on dairy females because it is favorable both from an economic perspective and a carbon footprint perspective.     

Neurotrophic control of ovarian development

Substantial evidence now exists indicating that the neurotrophins, a family of growth factors required for the survival, development, and differentiation of various neuronal populations of the nervous system, are also important for the development of nonneuronal tissues. Such a function was first suggested by studies showing the presence of high-affinity neurotrophin receptors in a variety of nonneuronal tissues including those of the cardiovascular, endocrine, immune, and reproductive systems. Within the latter, the gonads appear to be a preferential site of neurotrophin action as suggested by the presence in the mammalian ovary of at least four of the five known neurotrophins and all of the neurotrophin receptors thus far identified. While the various functions that the neurotrophins may have in the ovary are still being elucidated, it is now clear that in addition to recruiting the ovarian innervation, they play a direct role in the regulation of two different maturational periods that are critical for the acquisition of female reproductive function: early follicular development and ovulation. Neurotrophins facilitate the development of newly formed follicles by promoting the initial differentiation and the subsequent growth of primordial follicles. These actions appear to be related to the ability of neurotrophins to sustain the proliferation of both mesenchymal and granulosa cells, and to induce the synthesis of follicle stimulating hormone (FSH) receptors. At the time of the first ovulation, neurotrophins contribute to the ovulatory cascade by increasing prostaglandin E(2) release, reducing gap junction communication, and inducing cell proliferation within the thecal compartment of preovulatory follicles.     

Effect of manipulating progesterone before timed artificial insemination on reproductive and endocrine outcomes in high-producing multiparous Holstein cows

Our objective was to evaluate the effect of manipulating progesterone (P4) concentrations before timed artificial insemination (TAI) on reproductive and endocrine outcomes in high-producing Holstein cows. Multiparous lactating Holstein cows (n = 80) were synchronized for first TAI using a Double-Ovsynch protocol and were randomly assigned to receive 25 mg of PGF_2α 1 d after the first GnRH treatment of the Breeding-Ovsynch protocol that included a once-used P4 insert (low-P4 group) or to receive 2 new P4 inserts during the Breeding-Ovsynch protocol (high-P4 group). Blood samples were collected thrice weekly from ?10 to 32 d relative to TAI for all cows and from 32 to 67 d after TAI for pregnant cows and were analyzed for P4 and pregnancy-specific protein B (PSPB) concentrations. Expression of IFNτ-stimulated gene 15 (ISG15) was assessed in blood leukocytes 18 and 20 d after TAI. As expected, P4 concentrations were greater for high-P4 cows than for low-P4 cows from 3 to 8 d before TAI. Incidence of double ovulation was 3-fold greater for low-P4 cows than for high-P4 cows (33 vs. 10%), which resulted in more twin pregnancies 32 d after TAI for low-P4 cows than for high-P4 cows (29 vs. 0%). Low-P4 cows had larger preovulatory follicles at the last GnRH treatment of the Double-Ovsynch protocol and greater P4 concentrations than high-P4 cows after TAI. Relative expression of ISG15 mRNA 18 and 20 d after TAI was greater for low-P4 cows than for high-P4 cows and for pregnant cows than for nonpregnant cows. Overall, PSPB concentrations tended to be greater for low-P4 cows than for high-P4 cows, and pregnant cows had greater P4 concentrations than nonpregnant cows. In summary, cows with low P4 before TAI had increased preovulatory follicle diameter, PSPB concentrations, relative expression of ISG15 mRNA 18 and 20 d after TAI, double ovulations, and twinning compared with cows with high P4 before TAI. Increasing P4 before TAI may effectively decrease double ovulation and twinning in high-producing multiparous Holstein cows.     

Assessing ovulation detection performance in commercial dairy herds using progesterone concentrations from limited numbers of strategically collected milk samples

It is important to assess ovulation detection performance in commercial dairy herds both to investigate low reproductive performance and to enable herd managers to monitor the effectiveness of their system for detecting ovulations. A method was developed to assess ovulation detection performance that uses limited numbers of strategically collected milk samples, assesses performance over the period when herd managers are making maximal effort to detect ovulations, and when assessing proportions of ovulations detected, accounts for false positive diagnoses of estrus and for cows that have not recommenced postpartum ovulatory cycles. Milk was sampled from cows not diagnosed in estrus early in the breeding program (about d 26 in year-round calving herds and d 22 in seasonal calving herds); milk samples were also collected from cows on the day of insemination. Cows with high milk progesterone concentrations were assumed to have had undetected ovulations and false positive diagnoses of estrus, respectively. The method was successfully implemented in 161 of 167 commercial dairy herds. Positive predictive values (PPV; the proportions of ovulation diagnoses where ovulation was, in fact, imminent) were generally high in both year-round and seasonal calving herds (median values were 0.96 and 0.97, respectively), but 25% of herds had PPV <0.95. Ovulation detection sensitivities (ODS) were low in most year-round calving herds, but many seasonal calving herds had high ODS values; median ODS were 0.73 and 0.94, respectively. However, in 25% of seasonal calving herds, ODS was <0.91. These findings indicate that this method for assessing ovulation detection performance can be successfully implemented in commercial dairy herds with appropriate professional support. The wide range of ODS and the absence of correlation between ODS and PPV suggest that it is possible for managers of many commercial herds in Australia to achieve increased reproductive efficiency through increases in ODS and PPV.     

Thermosensitive bioadhesive gels for the vaginal delivery of sildenafil citrate: in vitro characterization and clinical evaluation in women using clomiphene citrate for induction of ovulation

Objective: The objective of this study is to develop and characterize in situ thermosensitive gels for the vaginal administration of sildenafil as a potential treatment of endometrial thinning occurring as a result of using clomiphene citrate for ovulation induction in women with type II eugonadotrophic anovulation. While sildenafil has shown promising results in the treatment of infertility in women, the lack of vaginal pharmaceutical preparation and the side effects associated with oral sildenafil limit its clinical effectiveness.

Methods: Sildenafil citrate in situ forming gels were prepared using different grades of Pluronic^® (PF-68 and PF-127). Mucoadhesive polymers as sodium alginate and hydroxyethyl cellulose were added to the gels in different concentrations and the effect on gel properties was studied. The formulations were evaluated in terms of viscosity, gelation temperature (T_sol-gel), mucoadhesion properties, and in vitro drug release characteristics. Selected formulations were evaluated in women with clomiphene citrate failure due to thin endometrium (Clinicaltrial.gov identifier NCT02766725).

Results: The T_sol-gel decreased with increasing PF-127 concentration and it was modulated by addition of PF-68 to be within the acceptable range of 28–37?°C. Increasing Pluronic® concentration increased gel viscosity and mucoadhesive force but decreased drug release rate. Clinical results showed that the in situ sildenafil vaginal gel significantly increased endometrial thickness and uterine blood flow with no reported side effects. Further, these results were achieved at lower frequency and duration of drug administration.

Conclusion: Sildenafil thermosensitive vaginal gels might result in improved potential of pregnancy in anovulatory patients with clomiphene citrate failure due to thin endometrium.     

Cyclical changes in volatile acidic metabolites of human vaginal secretions and their relation to ovulation

The major volatile constituents in human vaginal secretions were identified. Data collected during the course of 29 cycles from 9 subjects showed that the nature and abundance of the vaginal organic constituents differed with respect to subject. Only 3 of 9 subjects investigated consistently had C₃-C₅ aliphatic acids; acetic acid was present in all subjects. Lactic acid was the major acidic compound consistently found in the vaginal secretion of all subjects near the time of ovulation. Cyclical changes in the acidic constituents were demonstrated.     

Genetic impacts of using female-sorted semen in commercial and nucleus herds

This study was designed to investigate the genetic effects of using sorted semen in a dairy cattle population. Progress was monitored in elite and commercial animals over 20 yr of selection. To study the genetic impact of using sorted semen in commercial herds, a scenario was evaluated in which female-sorted semen was available to commercial herds. Second, to study the genetic impact of using sorted semen in nucleus herds, scenarios were simulated in which female-sorted semen was used only in a centralized nucleus herd, in which multiple ovulation and embryo transfer (MOET) took place. Because of the additional advantage of marker-assisted selection when sorted semen was used in nucleus herds, a second scenario was simulated in which both sorted semen and marker-assisted selection were implemented. In the scenario in which female-sorted semen was used in commercial herds, a large genetic advantage was observed early in commercial cows. The average superiority in first-lactation cows exceeded 30% in yr 11, relative to a base scheme with regular semen, but continued to decrease until it reached 9% in yr 20. The increased selection intensity in commercial cows contributed to the genetic merit of future cows (cow-to-cow contribution), but the contribution of the nucleus grew over time and gradually marginalized the cow-to-cow contribution. The genetic advantage of gender control in MOET schemes was minimal except when marker-assisted selection was also available. Two factors that affected the contribution of marker-assisted selection were studied: 1) within- vs. across-family selection of donors, and 2) the number of loci in the quantitative trait locus component. Schemes that selected donors regardless of their family structure were superior, and the quantitative trait locus component with more loci increased the effectiveness of sorted semen. Finally, we studied a reduced MOET scheme in which the number of harvested females was reduced from 42 to 25/yr. The reduced scheme in combination with female-sorted semen was not found to be genetically inferior to the large scheme in combination with regular semen.     

Level of circulating concentrations of progesterone during ovulatory follicle development affects timing of pregnancy loss in lactating dairy cows

The objective of this experiment was to determine the effect of high versus low progesterone (P4) during the pre-dominance or dominance phase (or both) of ovulatory follicle development on follicular dynamics and fertility of lactating dairy cows. Progesterone (P4) was manipulated to reach high (H) or low (L) serum concentrations during the pre-dominance phase (d 0 to 4 of the wave) and dominance phase (d 5 to 7 of the wave) of a second follicular wave ovulatory follicle, creating 4 treatments: H/H, H/L, L/H, and L/L. Luteolysis was induced with PGF_2α on d 7 of the wave and ovulation was induced with GnRH 56 h after PGF_2α. Cows (n = 558) received artificial insemination (AI) 16 h following GnRH. Pregnancy was determined at 6 intervals during gestation and at calving to quantify pregnancy loss beginning at d 23 post-AI utilizing pregnancy-specific protein B (PSPB) in novel within-cow comparisons. Cows with single ovulations assigned to the L/L treatment had greater pre-ovulatory follicle diameter compared with cows assigned to the L/H or H/L treatments. Cows with single ovulations had greater pre-ovulatory follicle diameter compared with cows with double ovulations. Low P4 in H/L, L/H, and L/L increased double ovulation rate compared with H/H. Cows with double ovulations had greater pregnancies per AI (P/AI) on d 23 post-AI compared with cows with single ovulations but had greater losses if ovulations were unilateral. Cows with low P4 during the entire period of the ovulatory follicle development also had greater P/AI on d 23 post-AI compared with cows with high P4 during both phases. However, full-term P/AI was not different between treatments. This was a result of the greater incidence of pregnancy losses between d 35 and 56 of gestation for cows with unilateral double ovulations compared with bilateral double ovulations and single ovulatory cows. Cows with single ovulation and low circulating P4 during the dominance period of follicle development had increased pregnancy losses between d 35 and 56 of gestation compared with cows with single ovulations and high P4. The PSPB measurements on d 16 and 23 post-AI were highly accurate in the prediction of pregnancy at d 28. The PSPB differed on d 23 and 28 between cows that had versus cows that did not have pregnancy losses between d 28 and 35 of gestation. In summary, circulating concentrations of P4 during ovulatory follicle development affected numbers of follicles ovulated and timing of subsequent pregnancy losses.     

Effect of estrous expression on timing and failure of ovulation of Holstein dairy cows using automated activity monitors

The aim of this study was to determine if estrous expression, as measured by an automated activity monitor (AAM), affects timing and failure of ovulation of lactating Holstein dairy cows. Cows were equipped with 2 AAM, 1 neck-mounted (AAM_C) and 1 leg-mounted (AAM_L), by 10 d postpartum and enrolled into the trial when their activity crossed the alert threshold on the AAM_C. A total of 850 episodes of estrus from 293 different cows were used for this study. When cows were enrolled, their ovaries were scanned by transrectal ultrasonography and gait and body condition scored. Ovaries of cows detected in estrus were scanned twice daily for a maximum of 3 d to determine the disappearance of the preovulatory follicle (ovulation) and the interval from estrus to ovulation was calculated. Physical activity data recorded from the AAM were used to determine estrus behavior using 2 traits: (1) peak activity and (2) duration. Peak activity was only available for the AAM_L. Peak activity was defined as the maximum activity during an estrus episode. Duration of estrus was defined as the time the activity of the cow exceeded threshold values set by the AAM software. The AAM_C correctly identified 87.8% of the estrus alerts, with 12.2% false positives. The average (±standard deviation) intervals from activity alert to ovulation were 25.8 ± 10.2 and 24.7 ± 9.3 h for the AAM_C and AAM_L, respectively. Changes in estrous expression were associated with differences in the interval from alert to ovulation. Cows with short intervals to ovulation were found to have less intense estrous expression than cows with medium and long length intervals to ovulation using the AAM_C, whereas using the AAM_L, cows with short intervals to ovulation exhibited less intense estrous expression than cows with medium but the same as those with long intervals to ovulation. Furthermore, irrespective of the AAM, estrus events with less estrous expression had increased odds of having a short interval to ovulation (below the median of 20 h) when compared with those having greater estrous expression (2.6 and 1.9 increased odds for the AAM_C and AAM_L, respectively). Ovulation failure was affected by estrous expression because estrus events with greater peak activity or longer duration had reduced ovulation failure compared with those with less estrous expression (AAM_C peak activity: 1.9 ± 1.4 vs. 9.5 ± 1.7%; AAM_L peak activity: 2.3 ± 1.4 vs. 6.2 ± 1.5%; AAM_C duration: 2.1 ± 1.4 vs. 8.9 ± 1.7%). In addition, cows with more estrous expression had greater pregnancy per artificial insemination than those with less estrous expression with both the AAM_C (42.3 ± 0.4 vs. 31.7 ± 0.4%) and the AAM_L (43.1 ± 0.4 vs. 36.3 ± 0.4%). Pregnancy per artificial insemination results were consistent even when removing cows that failed to ovulate. In conclusion, expression of estrus was highly associated with ovulation timing, ovulation failure, and fertility when using 2 different AAM. Cows with greater estrous expression have longer intervals from activity alert to ovulation, experience less ovulation failure, and have greater pregnancy per artificial insemination.