Impact of ovarian fetal tissue xenotransplantation associated with in vitro embryo production in annual genetic gain estimates for cattle weight traits

The present paper aims to estimate the impact of the reduction of the generation interval, based on the model of fetal ovarian tissue xenotransplantation associated with in vitro embryo production to estimate the annual genetic gain of weight traits in a bovine herd. Weigh data and genealogy of Brahman animals were used to estimate the annual direct genetic gain for weight at birth, weight at 120 days, at 210 days, and at 550 days of age. The genetic parameters were obtained by animal model, via Bayesian inference, by Markov Chain Monte Carlo (MCMC) methods. For the estimates, different generation intervals were defined as the average value between the supposed maternal generation intervals and the average sire generation interval based on the analyzed data (9.6 years). The shortest generation interval considered was 5.1 years, outlined from the average of 0.66 year (corresponds to 8 fetal months, an assumption defined based on the use of fetal ovarian tissue xenotransplantation associated with in vitro embryo production) and 9.6 years (sire generation interval). The remaining intervals considered were 6.7, 8.7 and 10.2 years. The estimate of annual direct genetic gain for all the evaluated traits was higher when considering the generation interval outlined based on the model of fetal ovarian tissue xenotransplantation associated with in vitro embryo production. The estimates were lower as the generation interval increased. The use of fetal ovarian tissue xenotransplantation associated with in vitro embryo production, may favor the reduction of the generation interval and successively generate a positive impact on the annual direct genetic gain estimates.


Introduction
The estimate of expected direct genetic gain in a trait under selection consists in the heritable portion of the difference between the average of the group of animals selected for next generation parents, and the average of the entire population (PEREIRA, 2014). It is represented by "∆G" and directly depends on the selection intensity (i), heritability (h²) and phenotypic standard deviation (σ p ), and inversely on the generation interval (L) (LIRA et al., 2013). The generation interval, defined as the time that elapses between the birth of the animal and its progeny (CARNEIRO JUNIOR, 2009), will then impact the genetic evolution of the herd and their productivity.
It is expected that a high interval of generations will result in less genetic gain, and thus, less economic return and genetic progress of animal breeding programs (MALHADO et al., 2008). High generation intervals result from the use of old animals as breeders, a situation that can be aggravated by the inadequate mating strategies by encouraging the use of old bulls' genetic material through artificial insemination. However, when well applied, biotechnologies tend to support the genetic progress. An example of this kind of well application is the use of reproductive tissue xenotransplantation.
According to Barros et al. (2014), xenotransplantation is the process of collecting tissue from an animal of one species and inserting it into a receptor of another. The use of this biotechnology in cattle breeding intends to minimize the loss of ovarian follicles from high genetic value females, in order to use existing oocytes in ovaries that would be sentenced to low utilization, or even to disposal, in cases of donor death (BEZERRA et al., 2011).
When performed with fetal bovine ovarian tissue, xenotransplantation may optimize the use of genetic material from high genetic value female calves even before birth, as in cases of pregnant cow death during the gestation (MORAES et al., 2018). In the future, with the use of this Silva, Abreu, Valente, Moraes Impact of ovarian fetal tissue xenotransplantation associated… xenotransplanted material for the in vitro embryo production (IVEP) it is expected that there will be genetic progress in traits of economic impact, such as weight traits, present in several animal breeding programs.
Measurement and selection for weight traits, such as birth weight (BW), weight at 120, 210, and 550 days of age (W120, W210, and W550, respectively), are essential, because producers seek animals that have fast development and growth, which shortens the production cycle, and enables greater economic return (BOLIGON et al., 2009). In this context, the aim was to estimate the impact of the reduction of the generation interval, based on the model of xenotransplantation of fetal ovarian tissue associated with IVEP to estimate the annual genetic direct gain of weight traits in a bovine herd.

Methodology
Data from Brahman cattle provided by a breeding farm located in Uberlândia (State of Minas Gerais, Brazil) were analyzed. The data provided refers to weights' traits collected between 2005 and 2017, and also included genealogical information of all animals with phenotypic data.
After data consistency analysis and formation of contemporary groups (CG), performed in the SAS 9.0 software, data of BW from 1438 animals, W120 from 800 animals, W210 from 931 animals, and W550 from 786 animals were included in the analysis. As it is a herd which carries out the commercialization of animals with high genetic potential, there is a different amount of data per animal. The CG was defined by concatenating the effects of sex, time, and year of birth. Time of birth was considered: Rainy = January, February, March, October, November, and December, and Dry = April, May, June, July, August, and September. CG with less than three animals and data 3.5 standard deviations above or below the characteristic average were excluded. Then, 28 CG were used in the analysis of the trait BW, 41 CG in the analysis of the W120 trait, 44 CG in the analysis of the W210 trait, and 37 CG in the analysis of the W550 trait.
The relationship matrix used in the analysis was constructed from the pedigree information of the animals with phenotypic data, constituting a database of 4,306 animals. The variation component was estimated by Samples of a posteriori distributions of variance estimates were generated from 1,100,000 cycles, in which the first 100,000 were discarded, and the samples stored at every 100 cycles. The convergence was checked with the graphic inspection of the sampled values versus interactions and by the criterion proposed by Geweke (1992). This criterion was estimated using the Bayesian Output Analysis (BOA) statistical package of the R program (R Core Team, 2015). For all traits, the a posteriori distribution means, estimated at each analysis, were used for the posteriori mean heritability (h²) estimation.
Samples of the posteriori distributions of annual direct genetic gain were obtained from the samples of the variance components. Selection of 5% was initially considered (selection intensity = 2.06). The responses to direct selection (annual direct genetic gain) were calculated as the associated with IVEP was used as a model, so that biotechnology represented inspiration for the mathematic model of the smallest generation interval outlined. For that, time was standardized in months and then transformed into years. When the generation interval between the mother and the progeny is three years, for example, this data should be interpreted as three years of age plus nine months of fetal life for this animal, therefore, 45 months or 3.75 years.
Therefore, the groups of generation intervals used in the annual direct genetic gain calculations were defined as the average between the supposed maternal generation intervals and the average paternal generation interval based on the analyzed data (9.6 years). In this context, Table 1 shows the different average generation intervals outlined to be used in annual direct genetic gain equation. Table 1 -Average generation intervals outlined to be used in annual direct genetic gain equation, based on the average value between the supposed maternal generation intervals and the paternal generation interval.
Outlined L Maternal L (supposed) Paternal L 5.1 years 0.66 years = 8 fetal months* 9.6 years 6.7 years 3.75 years = 3 years + 9 fetal months 9.6 years 8.7 years 7.75 years = 7 years + 9 fetal months 9.6 years 10.2 years 10.75 years = 10 years + 9 fetal months 9.6 years L = generation interval; *8 fetal months = definition based on the use of fetal ovarian tissue xenotransplantation biotechnology associated with in vitro embryo production.

Results and discussion
The results of mean phenotypic values and standard deviations for the analyzed traits in this study (Table 2) were similar to other studies that also studied Brahman (BONIFÁCIO et al., 2009;FARIA et al., 2011;MAGNABOSCO et al., 2017). Weight traits and weight gain at different ages are good indicators of animals' growth potential, and as they have medium to high magnitude heritability values, they stand out as selection criteria in breeding genetic programs (LAUREANO et al., 2011). Magnabosco et al. (2017), also evaluating Brahman animals, demonstrated that male calves have higher BW (36.6 ± 1.9 kg) than female calves (35.8 ± 1.8 kg), values higher than those found in this study. A few years ago, Holland and Odde (1992) already pointed out that when they are too small at birth, calves may lack vigor, tolerance to thermal stress, or resistance to pathological agents, while when they are too big at birth they can cause degrees of dystocia, leading to increased asphyxia at birth, metabolic and respiratory acidosis, in addition to depressed immunoglobulin Impact of ovarian fetal tissue xenotransplantation associated… absorption and increased susceptibility to disease.
The W120 is related to milk production and the quantity offered to the calf (JUNG et al., 2012). According to Paneto et al. (2002), this trait demonstrates the potential for weight gain and, therefore, allows for the selection of precocious animals. W210, or weaning weight, according to Ribeiro et al. (2004), is a measure related to the annual production of the beef cow. Weight gains achieved up to that period have lower cost than those obtained at older ages. Bonifácio et al. (2009) (Table 3). As there was an increase in the outlined generation intervals, there was a decrease in the estimates of annual direct genetic gain for all the analyzed weight traits (Graph 1). Malhado et al. (2008), points out that reducing generation interval in breeding programs increases the genetic gain, and consequently provides a greater economic return to the producer. It is worth noting that if the time elapsed between the birth of the parents (sire and dam) and their progenies was lower, the estimates of genetic gains would be even higher. ∆GBW = Annual direct genetic gain for birth weight (kg); ∆GW120 = Annual direct genetic gain for weight at 120 days of age (kg); ∆GW210 = Annual direct genetic gain for weight at 210 days of age (kg); ∆GW550 = Annual direct genetic gain for weight at 550 days of age (kg). kg = kilogram.
Graph 1 -Estimated annual direct genetic gain for weight traits evaluated in the Brahman cattle, according to different outlined generation intervals. ∆GBW = Annual direct genetic gain for birth weight; ∆GW120 = Annual direct genetic gain for weight at 120 days of age; ∆GW210 = Annual direct genetic gain for weight at 210 days of age; ∆GW550 = Annual direct genetic gain for weight at 550 days of age. kg = kilogram Fetal bovine ovarian tissue xenotransplantation has the potential to enable the in vivo cultivation of ovarian follicles in another recipient species (FIGUEIREDO et al., 2008), so that they can subsequently be submitted to other reproductive biotechnologies. Studies of Bezerra et al. (2011), conducted with fetal bovine ovaries, showed that there was activation of primordial follicles, with spontaneous growth of preantral ovarian follicles and emergence of antral follicles after 30 days of transplantation with oocytes of appropriate size for in vitro maturation.
This situation demonstrates that follicles from fetal bovine ovarian tissue xenotransplantation could be submitted to maturation and later to in vitro fertilization. Thus, in the future it is expected that it will be possible to perform in vitro embryo production, resulting from material from this culture. The association of these biotechnologies will then allow for the shortest possible generation interval, significantly increasing the estimates of the annual genetic gain of the herds, and consequently the productivity of the cattle.

Conclusion
The use of the biotechnology fetal ovarian tissue xenotransplantation associated with the in vitro embryo production, may favor the reduction of the generation interval and successfully generate a positive impact on the annual direct genetic gain estimates.

Acknowledgement
To Uberbrahman Farm for providing the data.