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This study aimed to estimate (co)variance components and genetic parameters for calving ease (CE) and their genetic correlations with growth, reproductive, carcass, and feed efficiency traits in Nellore cattle. Phenotypes for CE are scored in two categories: normal calving and assisted calving. The traits considered were probability of precocious calving, age at first calving, stayability, adjusted scrotal circumference at 365 days of age, accumulated cow productivity, age at puberty of males, gestation length, birth weight, adjusted weights at 210 and 450 days of age, adult cow weight, frame score, hip height, rib eye area, subcutaneous backfat thickness, rump fat thickness, intramuscular fat percentage, residual feed intake and dry matter intake. The estimation of genetic parameters was performed using a two-trait threshold-linear animal model, except for CE, stayability, and probability of precocious calving, which were evaluated through a two-trait threshold animal model. The direct (0.27) and maternal (0.19) heritability estimates for CE in heifers primiparous Nellore indicated that selecting for this trait is feasible. The selection to improve the female sexual precocity should consider CE during the selection and mating decisions to reduce calving problems. Genetic correlation estimates between CE and BW suggest that selecting low birth weight to reduce calving problems is not an appropriate strategy to improve calving ease in heifers Nellore. Therefore, adopting a multi-trait selection model with CE and BW in the Nellore breed would reduce calving difficulties, particularly in sexually precocious heifers, without impairing the growth, reproductive, feed efficiency conversion, and carcass indicator traits.

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STUDY QUESTION: Are reproductive characteristics associated with genome-wide DNA methylation and epigenetic age? SUMMARY ANSWER: Our data suggest that increasing parity is associated with differences in blood DNA methylation and small increases in epigenetic age. WHAT IS KNOWN ALREADY: A study of 397 young Filipino women (ages 20-22) observed increasing epigenetic age with an increasing number of pregnancies. STUDY DESIGN, SIZE, DURATION: We used data from 2356 non-Hispanic white women (ages 35-74) enrolled in the Sister Study cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on reproductive history were ascertained via questionnaire. Of the 2356 women, 1897 (81%) reported at least one live birth. Among parous women, 487 (26%) women reported ever experiencing a pregnancy complication. Three epigenetic clocks (i.e. Hannum, Horvath and Levine) and genome-wide methylation were measured in DNA from whole blood using Illumina's HumanMethylation450 BeadChip. We estimated association ß-values and 95% CIs using linear regression. MAIN RESULTS AND THE ROLE OF CHANCE: All three epigenetic clocks showed weak associations between number of births and epigenetic age (per live birth; Hannum: ß = 0.16, 95% CI = 0.02, 0.29, P = 0.03; Horvath: ß = 0.12, 95% CI = -0.04, 0.27, P = 0.14; Levine: ß = 0.27, 95% CI = 0.08, 0.45, P = 0.01); however, additional adjustment for current BMI attenuated the associations. Among parous women, a history of abnormal glucose tolerance during pregnancy was associated with increased epigenetic age by the Hannum clock (ß = 0.96; 95% CI = 0.10, 1.81; P = 0.03) and Levine clocks (ß = 1.69; 95% CI = 0.54, 2.84; P < 0.01). In epigenome-wide analysis, increasing parity was associated with methylation differences at 17 CpG sites (Bonferroni corrected P≤ 1.0 × 10-7). LIMITATIONS, REASONS FOR CAUTION: We relied on retrospective recall to ascertain reproductive history and pregnancy complications. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that parity is associated with small increases in epigenetic age and with DNA methylation at multiple sites in the genome. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the Intramural Research program of the NIH, National Institute of Environmental Health Sciences (Z01-ES049033, Z01-ES049032 and Z01-ES044055). None of the authors have a conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable.

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5-Aminolevulinate synthase 1 (ALAS1) is the first enzyme in the heme biosynthetic pathway and is upregulated in follicular tissue during the early stages of ovulation. In this study, we isolated the complete coding sequence of the porcine ALAS1 gene and its 2-9 intron sequence, identified a single nucleotide polymorphism (SNP; T/C) in intron 9, and developed a PCR-MspI-restriction fragment length polymorphism genotyping assay. Association of the SNP with litter size was assessed in two populations [purebred Large White and the experimental synthetic (DIV) line]. Statistical analysis demonstrated that for total number of piglets born (TNB) in all parities, pigs with the CC genotype had an additional 0.68 and 0.74 piglets compared to the TC and TT animals (P < 0.05) in the DIV line, respectively. Purebred Large White sows inheriting the CC and TC genotypes gave birth to an additional 0.96 and 0.70 piglets compared to the TT animals (P < 0.05) in all parities, respectively. In addition, for TNB in all parities, a significant additive effect of 0.48 ± 0.23 and 0.37 ± 0.17 piglets/ litter was detected in sows of both populations (P < 0.05), respectively. The highest levels of ALAS1 gene expression were observed in isolated ovarian granulosa cells 2 and 12 h after stimulation with pregnant mare serum gonadotropin human chorionic gonadotropin, which represents the time of follicular development and ovulation, respectively. Therefore, the ALAS1 gene was significantly associated with litter size in two populations and could be a useful molecular marker for the selection of increasing litter size in pigs.

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Heterospermic AI is commonly used in swine despite preventing precise evaluation of individual boar fertility. The present study compared the contribution of four boars (A, B, C and D) for reproductive performance and for paternity using homospermic and heterospermic (AB, AC, AD, BC, BD and CD) AI (n=204 for homospermic AI; n=307 for heterospermic AI). Blood samples from the four boars, from all sows inseminated with heterospermic doses and from the umbilical cords of their piglets, as well as tissue smears from mummified fetuses, were genotyped using single nucleotide polymorphisms (SNPs). Differences among boars were detected for the in vitro oocyte penetration rate and for the number of spermatozoa per oocyte (P<0.05), but not for sperm motility, mitochondrial functionality and integrity of the membrane, acrosome and DNA (P>0.05). Homospermic and heterospermic AI resulted in similar (P>0.05) farrowing rates (90.5% and 89.9%, respectively) and total litter size (12.4±0.4 and 12.7±0.7, respectively). Farrowing rate was lower for Boar B than for Boar C (P<0.05), but no other differences in reproductive performance among boars were observed with homospermic AI. The SNPs determined the paternity of 94.2% of the piglets sired by heterospermic AI. In the AC pool, paternity contribution per boar was similar (P>0.05), but differences between boars occurred in all other pools (P<0.05). Boar D achieved the greatest paternity contribution in all pools and parity categories (nearly 60%), whereas Boar B sired the fewest piglets (at most 40%). Reproductive performance was similar with homospermic and heterospermic AI, but differences in performance among boars undetected with homospermic AI were only evident after genotyping the piglets sired through heterospermic AI.

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Although RNA-Seq is an effective method for identifying and exploring novel functional genes in mammals, it has rarely been applied to study fertility-related genes in the goat. In this study, RNA-Seq was used to screen the estrus ovaries of uniparous and multiparous Anhui white goats (AWGs). In total, 15,890 genes were identified and 2201 of these were found to be differentially expressed between the genetic libraries from uniparous and multiparous goats. Compared to the uniparous library, 1583 genes were up-regulated and 618 genes were down-regulated in the multiparous library. The FER1L4 gene showed the level of highest up-regulation in the multiparous library, while SRD5A2 expression showed the greatest down-regulation. In order to determine the functions of FER1L4 and SRD5A2 in goats, the expression profiles of the two genes in different tissues from AWGs and Boer goats at diestrus were analyzed by quantitative PCR. FER1L4 and SRD5A2 showed tissue specific expression patterns and were highly expressed in ovaries from both AWGs and Boer goats. FER1L4 was more highly expressed in ovaries from multiparous than uniparous AWGs. In contrast, SRD5A2 was expressed at a lower level in multiparous AWGs. These results indicated that FER1L4 and SRD5A2 may be associated with the high fecundity of AWGs.

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O objetivo neste trabalho foi estimar herdabilidade da idade ao primeiro parto (IPP), do escore de condição corporal ao primeiro parto (EPP), do escore de condição corporal ao parto (ECP), dos pesos à desmama (PD) e aos doze meses de idade (P12) e das relações de peso do bezerro à desmama pelo peso da vaca ao parto (RPP) e peso do primeiro bezerro à desmama pelo peso da vaca ao primeiro parto (RPPP) e as correlações genéticas de IPP, EPP, PD e P12 com RPPP, em um rebanho da raça Canchim. As médias a posteriori dos componentes de (co)variância foram obtidas por inferência bayesiana, em análises uni e bicaracterísticas. Os modelos estatísticos incluíram os efeitos aleatórios genético aditivos direto e materno, de ambiente permanente e residual, e os efeitos fixos de ano e mês de nascimento ou do parto, idade da vaca ao parto e sexo do bezerro, dependendo da característica. As médias a posteriori da herdabilidade, obtidas em análises unicararacterística, foram 0,12 (IPP); 0,36 (EPP); 0,18 (ECP); 0,50 (PD); 0,46 (P12); 0,16 (RPP) e 0,40 (RPPP), indicando que as características possuem variação genética aditiva suficiente para apresentar boa resposta à seleção massal, com exceção de IPP. As correlações genéticas de IPP (-0,61), EPP (-0,36), PD (-0,20) e P12 (-0,05) com RPPP sugerem que a seleção para reduzir a idade e o escore de condição corporal ao primeiro parto deve melhorar a produtividade das fêmeas no primeiro parto, mas a seleção para modificar pesos em idades jovens não promove mudanças na eficiência produtiva das matrizes. (AU)

The objective of this study was to estimate the heritability of age at first calving (AFC), body condition score at first calving (BCF), body condition score at calving (BCC), weaning weight (WW), yearling weight (W12), weaning weight of calf/weight of cow at calving (RCC) and weaning weight of first calf/weight of cow at first calving (RCCF) ratios, and genetic correlations of AFC, BCF, WW and W12 with RCCF, in a Canchim beef cattle herd. The variance and covariance components were obtained by bayesian inference with single and two-trait analyses. The statistical models included the additive direct and maternal, the permanent environmental and the residual random effects, and the fixed effects of year and month of birth or of calving, age of cow at calving and sex of calf, depending on the trait. The posterior means of heritability, obtained by single-trait analyses, were 0.12 (AFC), 0.36 (BCF), 0.18 (BCC), 0.50 (WW), 0.46 (W12), 0.16 (RCC) and 0.40 (RCCF) indicating that these traits have enough genetic variability to show response to mass selection with the exception of AFC. The genetic correlations of AFC (-0.61), BCF (-0.36), WW (-0.20) and W12 (-0.05) with RCCF suggest that selection to reduce age and body condition score at first calving should improve the productivity trait of females at first calving, while selection for heavier females at young ages would not promote any change in the productivity of dams. (AU)

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O objetivo neste trabalho foi estimar herdabilidade da idade ao primeiro parto (IPP), do escore de condição corporal ao primeiro parto (EPP), do escore de condição corporal ao parto (ECP), dos pesos à desmama (PD) e aos doze meses de idade (P12) e das relações de peso do bezerro à desmama pelo peso da vaca ao parto (RPP) e peso do primeiro bezerro à desmama pelo peso da vaca ao primeiro parto (RPPP) e as correlações genéticas de IPP, EPP, PD e P12 com RPPP, em um rebanho da raça Canchim. As médias a posteriori dos componentes de (co)variância foram obtidas por inferência bayesiana, em análises uni e bicaracterísticas. Os modelos estatísticos incluíram os efeitos aleatórios genético aditivos direto e materno, de ambiente permanente e residual, e os efeitos fixos de ano e mês de nascimento ou do parto, idade da vaca ao parto e sexo do bezerro, dependendo da característica. As médias a posteriori da herdabilidade, obtidas em análises unicararacterística, foram 0,12 (IPP); 0,36 (EPP); 0,18 (ECP); 0,50 (PD); 0,46 (P12); 0,16 (RPP) e 0,40 (RPPP), indicando que as características possuem variação genética aditiva suficiente para apresentar boa resposta à seleção massal, com exceção de IPP. As correlações genéticas de IPP (-0,61), EPP (-0,36), PD (-0,20) e P12 (-0,05) com RPPP sugerem que a seleção para reduzir a idade e o escore de condição corporal ao primeiro parto deve melhorar a produtividade das fêmeas no primeiro parto, mas a seleção para modificar pesos em idades jovens não promove mudanças na eficiência produtiva das matrizes.

The objective of this study was to estimate the heritability of age at first calving (AFC), body condition score at first calving (BCF), body condition score at calving (BCC), weaning weight (WW), yearling weight (W12), weaning weight of calf/weight of cow at calving (RCC) and weaning weight of first calf/weight of cow at first calving (RCCF) ratios, and genetic correlations of AFC, BCF, WW and W12 with RCCF, in a Canchim beef cattle herd. The variance and covariance components were obtained by bayesian inference with single and two-trait analyses. The statistical models included the additive direct and maternal, the permanent environmental and the residual random effects, and the fixed effects of year and month of birth or of calving, age of cow at calving and sex of calf, depending on the trait. The posterior means of heritability, obtained by single-trait analyses, were 0.12 (AFC), 0.36 (BCF), 0.18 (BCC), 0.50 (WW), 0.46 (W12), 0.16 (RCC) and 0.40 (RCCF) indicating that these traits have enough genetic variability to show response to mass selection with the exception of AFC. The genetic correlations of AFC (-0.61), BCF (-0.36), WW (-0.20) and W12 (-0.05) with RCCF suggest that selection to reduce age and body condition score at first calving should improve the productivity trait of females at first calving, while selection for heavier females at young ages would not promote any change in the productivity of dams.

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We evaluated genetic and environmental factors affecting age at first farrowing of sows in the Brazilian southeast. For this purpose, 466 observations regarding the age at first farrowing were made for Dalland-C40© animals belonging to two herds. The effects of the environmental factors on this trait were assessed by means of a model that included, as random effects, the influence of the sow's father and mother and, as fixed effects, the influence the year of birth, the herd and the birth season, along with the covariable litter size at birth. The variance components were estimated using the derivative-free restricted maximum likelihood method. The estimated mean was 354.8 ± 25.87 days, with a coefficient of variation of 7.29%. Significant effects on the trait were observed for the herd, the year and the season of birth; but a linear effect of litter size at birth on the age at first farrowing was not observed. The boar did not significantly contribute to the variation occurring among the sows, whereas the sow's mother caused significant variation. The heritability estimate for the age at first farrowing was 0.44 ± 0.15, which is considered high. We concluded that herd effect and year and season of birth should be taken into consideration for an accurate genetic comparison; consequently, the animals should be joined into contemporary groups.

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OBJECTIVE: To evaluate the association of -397T>C and -351A>G single nucleotide polymorphisms (SNPs) - also called PvuII and XbaI, respectively - located on estrogen receptor alpha (ERS1) gene with age at menarche, menopause onset, fertility and miscarriage in a population of post-menopausal women. STUDY DESIGN: Cross-sectional study with 273 healthy, high miscegenated, post-menopausal women (mean age of 63.1±9.7 years old). Subjects were genotyped for PvuII and XbaI SNPs by PCR-RFLP and confirmed by automatic sequencing. Reproduction informations (age at menarche, age at menopause, number of pregnancies, fertility rate and miscarriages) were obtained by retrospective study using a questionnaire. RESULT(S): Age at menarche, menopause onset, number of pregnancies, total fertility rate, and parity did not seem to be influenced by any of the studied genotypes (chi-square, p>0.05). However, women carrying the xx genotype showed a 44% higher chance of miscarriage, whereas this value did not trespass 16% for any other genotype analyzed. It has been also observed a higher occurrence of miscarriage in association with combined xxpp genotype of ERS1 gene (chi-square, p<0.01). CONCLUSION(S): The present data indicate that the studied SNPs on ERS1 gene do not influence the menstrual cycle timing and parity but there is a strong relationship between the xx ERS1 SNP genotype and the incidence of miscarriage in the post-menopausal population analyzed.

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The objective of this study was to estimate (co)variance functions using random regression models on Legendre polynomials for the analysis of repeated measures of BW from birth to adult age. A total of 82,064 records from 8,145 females were analyzed. Different models were compared. The models included additive direct and maternal effects, and animal and maternal permanent environmental effects as random terms. Contemporary group and dam age at calving (linear and quadratic effect) were included as fixed effects, and orthogonal Legendre polynomials of animal age (cubic regression) were considered as random covariables. Eight models with polynomials of third to sixth order were used to describe additive direct and maternal effects, and animal and maternal permanent environmental effects. Residual effects were modeled using 1 (i.e., assuming homogeneity of variances across all ages) or 5 age classes. The model with 5 classes was the best to describe the trajectory of residuals along the growth curve. The model including fourth- and sixth-order polynomials for additive direct and animal permanent environmental effects, respectively, and third-order polynomials for maternal genetic and maternal permanent environmental effects were the best. Estimates of (co)variance obtained with the multi-trait and random regression models were similar. Direct heritability estimates obtained with the random regression models followed a trend similar to that obtained with the multi-trait model. The largest estimates of maternal heritability were those of BW taken close to 240 d of age. In general, estimates of correlation between BW from birth to 8 yr of age decreased with increasing distance between ages.

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