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Significance of somatic mutations and content alteration of mitochondrial DNA in esophageal cancer.

BACKGROUND: The roles of mitochondria in energy metabolism, the generation of ROS, aging, and the initiation of apoptosis have implicated their importance in tumorigenesis. In this study we aim to establish the mutation spectrum and to understand the role of somatic mtDNA mutations in esophageal cancer. METHODS: The entire mitochondrial genome was screened for somatic mutations in 20 pairs (18 esophageal squamous cell carcinomas, one adenosquamous carcinoma and one adenocarcinoma) of tumor/surrounding normal tissue of esophageal cancers, using temporal temperature gradient gel electrophoresis (TTGE), followed by direct DNA sequencing to identify the mutations. RESULTS: Fourteen somatic mtDNA mutations were identified in 55% (11/20) of tumors analyzed, including 2 novel missense mutations and a frameshift mutation in ND4L, ATP6 subunit, and ND4 genes respectively. Nine mutations (64%) were in the D-loop region. Numerous germline variations were found, at least 10 of them were novel and five were missense mutations, some of them occurred in evolutionarily conserved domains. Using real-time quantitative PCR analysis, the mtDNA content was found to increase in some tumors and decrease in others. Analysis of molecular and other clinicopathological findings does not reveal significant correlation between somatic mtDNA mutations and mtDNA content, or between mtDNA content and metastatic status. CONCLUSION: Our results demonstrate that somatic mtDNA mutations in esophageal cancers are frequent. Some missense and frameshift mutations may play an important role in the tumorigenesis of esophageal carcinoma. More extensive biochemical and molecular studies will be necessary to determine the pathological significance of these somatic mutations.

Adenocarcinoma↗

The Four-Dimensional Symptom Questionnaire (4DSQ): a validation study of a multidimensional self-report questionnaire to assess distress, depression, anxiety and somatization.

BACKGROUND: The Four-Dimensional Symptom Questionnaire (4DSQ) is a self-report questionnaire that has been developed in primary care to distinguish non-specific general distress from depression, anxiety and somatization. The purpose of this paper is to evaluate its criterion and construct validity. METHODS: Data from 10 different primary care studies have been used. Criterion validity was assessed by comparing the 4DSQ scores with clinical diagnoses, the GPs' diagnosis of any psychosocial problem for Distress, standardised psychiatric diagnoses for Depression and Anxiety, and GPs' suspicion of somatization for Somatization. ROC analyses and logistic regression analyses were used to examine the associations. Construct validity was evaluated by investigating the inter-correlations between the scales, the factorial structure, the associations with other symptom questionnaires, and the associations with stress, personality and social functioning. The factorial structure of the 4DSQ was assessed through confirmatory factor analysis (CFA). The associations with other questionnaires were assessed with Pearson correlations and regression analyses. RESULTS: Regarding criterion validity, the Distress scale was associated with any psychosocial diagnosis (area under the ROC curve [AUC] 0.79), the Depression scale was associated with major depression (AUC = 0.83), the Anxiety scale was associated with anxiety disorder (AUC = 0.66), and the Somatization scale was associated with the GPs' suspicion of somatization (AUC = 0.65). Regarding the construct validity, the 4DSQ scales appeared to have considerable inter-correlations (r = 0.35-0.71). However, 30-40% of the variance of each scale was unique for that scale. CFA confirmed the 4-factor structure with a comparative fit index (CFI) of 0.92. The 4DSQ scales correlated with most other questionnaires measuring corresponding constructs. However, the 4DSQ Distress scale appeared to correlate with some other depression scales more than the 4DSQ Depression scale. Measures of stress (i.e. life events, psychosocial problems, and work stress) were mainly associated with Distress, while Distress, in turn, was mainly associated with psychosocial dysfunctioning, including sick leave. CONCLUSION: The 4DSQ seems to be a valid self-report questionnaire to measure distress, depression, anxiety and somatization in primary care patients. The 4DSQ Distress scale appears to measure the most general, most common, expression of psychological problems.

Anxiety↗

Somatic mutation and gain of copy number of PIK3CA in human breast cancer.

INTRODUCTION: Phosphatidylinositol 3-kinases (PI3Ks) are a group of lipid kinases that regulate signaling pathways involved in cell proliferation, adhesion, survival, and motility. Even though PIK3CA amplification and somatic mutation have been reported previously in various kinds of human cancers, the genetic change in PIK3CA in human breast cancer has not been clearly identified. METHODS: Fifteen breast cancer cell lines and 92 primary breast tumors (33 with matched normal tissue) were used to check somatic mutation and gene copy number of PIK3CA. For the somatic mutation study, we specifically checked exons 1, 9, and 20, which have been reported to be hot spots in colon cancer. For the analysis of the gene copy number, we used quantitative real-time PCR and fluorescence in situ hybridization. We also treated several breast cancer cells with the PIK3CA inhibitor LY294002 and compared the apoptosis status in cells with and without PIK3CA mutation. RESULTS: We identified a 20.6% (19 of 92) and 33.3% (5 of 15) PIK3CA somatic mutation frequency in primary breast tumors and cell lines, respectively. We also found that 8.7% (8 of 92) of the tumors harbored a gain of PIK3CA gene copy number. Only four cases in this study contained both an increase in the gene copy number and a somatic mutation. In addition, mutation of PIK3CA correlated with the status of Akt phosphorylation in some breast cancer cells and inhibition of PIK3CA-induced increased apoptosis in breast cancer cells with PIK3CA mutation. CONCLUSION: Somatic mutation rather than a gain of gene copy number of PIK3CA is the frequent genetic alteration that contributes to human breast cancer progression. The frequent and clustered mutations within PIK3CA make it an attractive molecular marker for early detection and a promising therapeutic target in breast cancer.

Apoptosis↗

Physical mapping of genes in somatic cell radiation hybrids by comparative genomic hybridization to cDNA microarrays.

BACKGROUND: Somatic cell mutants can be informative in the analysis of a wide variety of cellular processes. The use of map-based positional cloning strategies in somatic cell hybrids to analyze genes responsible for recessive mutant phenotypes is often tedious, however, and remains a major obstacle in somatic cell genetics. To fulfill the need for more efficient gene mapping in somatic cell mutants, we have developed a new DNA microarray comparative genomic hybridization (array-CGH) method that can rapidly and efficiently map the physical location of genes complementing somatic cell mutants to a small candidate genomic region. Here we report experiments that establish the validity and efficacy of the methodology. RESULTS: CHO cells deficient for hypoxanthine:guanine phosphoribosyl transferase (HPRT) were fused with irradiated normal human fibroblasts and subjected to HAT selection. Cy5-labeled genomic DNA from the surviving hybrids containing the HPRT gene was mixed with Cy3-labeled genomic DNA from normal CHO cells and hybridized to a microarray containing 40,185 cDNAs, representing 29,399 genes (UniGene clusters). The DNA spots with the highest Cy5:Cy3 fluorescence ratios corresponded to a group of genes mapping within a 1 Mb interval centered near position 142.7 Mb on the X chromosome, the genomic location of HPRT. CONCLUSION: The results indicate that our physical mapping method based on radiation hybrids and array-CGH should significantly enhance the speed and efficiency of positional cloning in somatic cell genetics.

Animals↗

Androgen insensitivity syndrome: somatic mosaicism of the androgen receptor in seven families and consequences for sex assignment and genetic counseling.

Androgen insensitivity syndrome (AIS) is caused by numerous mutations of the androgen receptor (AR) gene. The phenotype may range from partial AIS (PAIS) with ambiguous genitalia to complete AIS (CAIS) with female genitalia. In 70% of the cases, AR mutations are transmitted in an X-linked recessive manner through the carrier mothers, but in 30%, the mutations arise de novo. When de novo mutations occur after the zygotic stage, they result in somatic mosaicisms, which are an important consideration for both virilization in later life-because both mutant and wild-type receptors are expressed-and genetic counseling. We report here six patients with AIS due to somatic mutations of the AR and one mother with somatic mosaicism who transmitted the mutation twice. Of the four patients with PAIS, three presented spontaneous or induced virilization at birth or puberty. These cases underline the crucial role of the remnant wild-type AR for virilization because the same mutations, when they are inherited, lead to CAIS. We also report two novel mutations of the AR, with somatic mosaicism, detected in patients with CAIS. Thus, the remnant wild-type receptor does not always lead to virilization. In one of these patients, a high ratio of wild-type to mutant AR expression was found in the gonads and genital skin fibroblasts. Although no prenatal virilization occurred, the possibility of virilization at puberty could not be excluded, and early gonadectomy was performed. A seventh patient had a CAIS with a novel germline AR mutation. The mutation was inherited from the mother, in whom mosaicism was detected in blood and who transmitted the mutation to a second, XX, offspring. The detection of somatic AR mutations is particularly important for the clinical management and genetic counseling of patients with AIS. Before definite sex assignment, a testosterone treatment trial should be performed in all patients with PAIS, but it becomes crucial when an AR mosaicism has been detected. In patients with CAIS or severe PAIS raised as female, there is no consensus about when (early childhood or puberty) gonadectomy should be performed. When somatic AR mutations are detected, however, gonadectomy should be performed earlier because of the risk of virilization during puberty. When a germline de novo mutation is identified in the index case, the risk of transmission to a second child due to a possible germ cell mosaicism in the mother cannot be excluded. However, given the high number of AR de novo mutations and the rarity of such reports, this risk appears to be very low.

Adolescent↗

5-Azacytidine affects the programming of expression of the somatic nucleus of Paramecium.

This report introduces a new system in the study of programming of genomic function during development of the somatic nucleus of Paramecium tetraurelia. Previous works have established a definite, but replaceable, role of the germ nuclei (micronuclei) in oral development in the asexual cycle; their removal from the cell generates viable amicronucleate cell lines, which characteristically suffer a transient period of growth depression marked by abnormal oral development. Such cell lines gradually recover, showing that a compensatory mechanism is activated in the absence of the germ nuclei to bring the cell back to near-normal. To test the notion that the somatic nucleus (macronucleus) is involved in this compensation, cells possessing micronuclei were treated with 5-azacytidine during sexual reproduction when new somatic nuclei develop. These cells were then propagated asexually for a number of fissions in the absence of the drug, and thereafter micronuclei were removed from them. The amicronucleate cell lines generated in this manner clearly did not suffer a depression as severe as the untreated controls did in terms of growth rate and oral development, and they recovered much sooner. This supports the notion that the somatic nucleus is the physical basis of the compensatory mechanism. This study suggests that the stomatogenic sequences in question normally become repressed in the somatic nucleus developing in sexual reproduction, and that 5-azacytidine administered to the cells at this time could alter this programme which then persists during subsequent asexual propagation. The possibility that the somatic nucleus is programmed by methylation of cytosine at the 5' position is discussed.

Animals↗

The germ line regulates somatic cyst cell proliferation and fate during Drosophila spermatogenesis.

Spermatogenesis relies on the function of germ-line stem cells, as a continuous supply of differentiated spermatids is produced throughout life. In Drosophila, there must also be somatic stem cells that produce the cyst cells that accompany germ cells throughout spermatogenesis. By lineage tracing, we demonstrate the existence of such somatic stem cells and confirm that of germ-line stem cells. The somatic stem cells likely correspond to the ultrastructurally described cyst progenitor cells. The stem cells for both the germ-line and cyst lineage are anchored around the hub of non-dividing somatic cells located at the testis tip. We then address whether germ cells regulate the behavior of somatic hub cells, cyst progenitors and their daughter cyst cells by analyzing cell proliferation and fate in testes in which the germ line has been genetically ablated. Daughter cyst cells, which normally withdraw from the cell cycle, continue to proliferate in the absence of germ cells. In addition, cells from the cyst lineage switch to the hub cell fate. Male-sterile alleles of chickadee and diaphanous, which are deficient in germ cells, exhibit similar cyst cell phenotypes. We conclude that signaling from germ cells regulates the proliferation and fate of cells in the somatic cyst lineage.

Animals↗

Expression and function of clift in the development of somatic gonadal precursors within the Drosophila mesoderm.

The gonad forms from cells of two lineages: the germline and soma. The somatic gonadal cells generate the various cell types within the testis or ovary that support gametogenesis. These cells derive from embryonic mesoderm, but how they are specified is unknown. Here, we describe a novel regulator of Drosophila gonadogenesis, clift, mutations in which abolish gonad formation. clift is expressed within somatic gonadal precursors as these cells first form, demonstrating that 9-12 cells are selected as somatic gonadal precursors within each of three posterior parasegments at early stages in gonadogenesis. Despite this early expression, somatic gonadal precursors are specified in the absence of clift function. However, they fail to maintain their fate and, as a consequence, germ cells do not coalesce into a gonad. In addition, using clift as a marker, we show that the anteroposterior and dorsoventral position of the somatic gonadal precursor cells within a parasegment are established by the secreted growth factor Wg, coupled with a gene regulatory hierarchy within the mesoderm. While loss of wg abolishes gonadal precursors, ectopic expression expands the population such that most cells within lateral mesoderm adopt gonadal precursor fates. Initial dorsoventral positioning of somatic gonadal precursors relies on a regulatory cascade that establishes dorsal fates within the mesoderm and is subsequently refined through negative regulation by bagpipe, a gene that specifies nearby visceral mesoderm. Thus, these studies identify essential regulators of gonadal precursor specification and differentiation and reveal novel aspects of the general mechanism whereby distinct fates are allocated within the mesoderm.

Alleles↗

A tissue-specific knock-out strategy reveals that lin-26 is required for the formation of the somatic gonad epithelium in Caenorhabditis elegans.

The Caenorhabditis elegans LIN-26 protein is required to specify and/or maintain the fates of all non-neuronal ectodermal cells. Here we show that lin-26 is expressed until the somatic gonad primordium stage in all cells of the somatic gonad, except in distal tip cells, and later in all uterine cells. To determine if lin-26 functions in the somatic gonad, we have generated gonad-specific lin-26 alleles obtained by integration of lin-26 promoter deletion derivatives into a lin-26 null mutant background. In this way, we rescued the lethal phenotype imparted by lin-26 null mutations and uncovered a highly penetrant sterile phenotype. Specifically, the strongest of these new alleles was characterized by the absence of lin-26 expression in the somatic gonad, the presence of endomitotic oocytes, decreased germline proliferation, a protruding vulva and a less penetrant absence of gonad arms. Lineage analysis of mutant somatic gonads and examination of several markers expressed in the spermatheca, sheath cells, distal tip cells and the uterus, suggest that LIN-26 is required in sheath, spermatheca and uterine precursors, and in uterine cells. We conclude that lin-26 performs a similar function in the non-neuronal ectoderm and the somatic gonad, a mesoderm derivative, and we speculate that lin-26 is required to express epithelial characteristics.

Animals↗

Indirect somatic embryogenesis in cassava for genetic modification purposes.

In cassava both direct and indirect somatic embryogenesis is described. Direct somatic embryogenesis starts with the culture of leaf explants on Murashige and Skoog (MS) medium supplemented with auxins. Somatic embryos undergo secondary somatic embryogenesis when cultured on the same medium. Indirect somatic embryogenesis is initiated by subculture of directly induced embryogenic tissue on auxin-supplemented medium with Gresshoff and Doy salts and vitamins. A very fine friable embryogenic callus (FEC) is formed after a few rounds of subculture and stringent selection. This FEC is maintained by subculture on auxin supplemented medium. Lowering of the auxin concentration allows the FEC to form mature somatic embryos that develop into plants when transferred to a cytokinin-supplemented medium.

Cell Culture Techniques↗

A comparison of visceral and somatic pain processing in the human brainstem using functional magnetic resonance imaging.

Evidence from both human and animal studies has demonstrated a key role for brainstem centers in the control of ascending nociceptive input. Nuclei such as the rostral ventromedial medulla and periaqueductal gray (PAG) are able to both inhibit and facilitate the nociceptive response. It has been proposed that altered descending modulation may underlie many of the chronic pain syndromes (both somatic and visceral). We used functional magnetic resonance imaging to image the neural correlates of visceral and somatic pain within the brainstem. Ten healthy subjects were scanned twice at 3 tesla, during which they received matched, moderately painful, electrical stimuli to either the midline lower abdomen or rectum. Significant activation was observed in regions consistent with the PAG, nucleus cuneiformis (NCF), ventral tegmental area/substantia nigra, parabrachial nuclei/nucleus ceruleus, and red nucleus bilaterally to both stimuli. Marked spatial similarities in activation were observed for visceral and somatic pain, although significantly greater activation of the NCF (left NCF, p = 0.02; right NCF, p = 0.01; Student's paired t test, two-tailed) was observed in the visceral pain group compared with the somatic group. Right PAG activity correlated with anxiety during visceral stimulation (r = 0.74; p < 0.05, Pearson's r, two-tailed) but not somatic stimulation. We propose that the differences in NCF and right PAG activation observed may represent a greater nocifensive response and greater emotive salience of visceral over somatic pain.

Abdomen↗

Respiratory rhythm entrainment by somatic afferent stimulation.

Respiratory and locomotor patterns are coupled during locomotion. The objectives of this study were to (1) demonstrate that respiratory rhythms are entrained by sensory input from somatic afferents, (2) establish whether the parabrachial nucleus mediates entrainment, (3) examine responses of single respiratory neurons in the ventral respiratory group (VRG) to somatic afferent stimulation, and (4) use a computational model of the pontomedullary respiratory network (Rybak et al., 2004a,b) to suggest neuronal mechanisms for entrainment. We used an in situ preparation in young rats that retained pontomedullary respiratory circuits and spinal pathways transmitting somatosensory input. We demonstrate that rhythmic stimulation of somatic afferents entrains respiratory rhythm on a 1:1 basis (1:1), increasing breathing frequency up to approximately 1.4-2.2 times greater than spontaneous frequency. Stable entrainment occurred only when stimuli were delivered during expiration. Reversible blockade of the lateral parabrachial nucleus eliminated entrainment. Somatic afferent stimulation produced significant increases in the firing rate of augmenting expiratory (E2) neurons but shortened the firing duration of postinspiratory (post-I) neurons. A computational model reproduced 1:1 entrainment and other experimental findings based on the assumption that the somatic afferents initiate early onset of inspiration via activation of medullary E2 neurons. The model also predicted that afferent stimulation evoked transient hyperpolarization of ramp-inspiratory (ramp-I) neurons. This was confirmed experimentally by intracellular recording from ramp-I neurons. Our experimental and modeling results demonstrate that an entrainment pathway from somatic afferents to the VRG via the lateral parabrachial nucleus causes resetting of respiratory rhythm through excitation of E2 and consequent inhibition of post-I neurons.

Afferent Pathways↗

An exploration of somatization among Asian refugees and immigrants in primary care.

The clinical records of Chinese, Filipino, Vietnamese, Laotian, and Mien patients in primary care were reviewed to determine the prevalence of somatization, its associated patient characteristics, and the manifested illness behavior. Patients in this study were generally poor, unemployed, and spoke little English. Somatization accounted for 35 per cent of illness visits. These visits were also more costly. Refugees had a higher rate of somatization (42.7 per cent) than immigrants (27.1 per cent). Although sociodemographic characteristics did not strongly differentiate patients with somatization from others, ethnicity and indicators of decreased resources such as large households with low income, households headed by single women, or a limited English proficiency were associated with somatization in certain ethnic groups. Somatization is thus an important health problem among Asian refugees and immigrants.

Adolescent↗

Preliminary study of a scale measuring depression and somatic symptoms.

This description concerns the development of a scale measuring depression and somatic symptoms and the selection of its items for a Taiwanese sample. 102 Taiwanese outpatients (28 men, 74 women) with major depressive disorder completed a 44-item preliminary scale. All had experienced a major depressive episode but had not been treated by antidepressants within the prior two weeks. The Hamilton Depression Rating Scale was administered to evaluate the validity of the Depression and Somatic Symptoms Scale (DSSS). Items, 12 for the Depression Subscale and 10 for the Somatic Subscale, were selected for the Depression and Somatic Symptoms Scale according to their frequency and their association with rated severity of depression and clinical practices. The mean Hamilton Depression score was 23.9 (SD = 5.2) versus 38.4 (SD = 11.3) for the total DSSS; means for the Depression subscale were 23.5 +/- 6.0 and the Somatic subscale 14.9 +/- 6.8. Cronbach alpha was .88 for the total DSSS, .78 for the Depression subscale, and .86 for the Somatic subscale. The Pearson correlation coefficient for the two scales was .59 (p <.01). The new scale had adequate internal consistency reliability and convergent validity. Much study is required to assess its structure, item characteristics, and in judging its applicability and limitations, and sensitivity to cultural differences in clinical settings.

Adult↗

Tetraploid somatic hybrids of potato (Solanum tuberosum L.) obtained from diploid breeding lines.

Intraspecific somatic hybrids between 16 different diploid breeding lines of Solanum tuberosum L. were produced by PEG-induced fusion. Manually selected heterokaryons were cultured in a Millicells-CM using a post-fusion protoplast mixture. Plants were regenerated from calli derived from heterokaryons obtained from 10 out of 38 combinations of diploid lines. Of the tested putative somatic hybrids, 14.2% were diploid, 72.8% were tetraploid and 13% pentaploid. The DNA amplification pattern obtained with RAPD or semi-random primers confirmed that 6 fusion combinations were hybrids. In most cases, the morphological traits were intermediate to those of the diploid fusion partners. About 23.0% of the tested somatic hybrids showed variation in their morphology. Of the tested somatic hybrids, 78.0% flowered and 86.0% tuberized. The cytoplasm of 9 diploid lines and 6 somatic hybrid combinations was analysed. Two of the diploid lines had W/S chloroplasts and alpha or epsilon mitochondria; the remainder contained T chloroplasts and beta mitochondria. All the analysed somatic hybrids carried T chloroplasts and beta mitochondria.

Breeding↗

A structural equation model for describing relationships between somatic cell score and milk yield in dairy goats.

The relationship between milk yield and somatic cell score (log-transformed somatic cell count) in dairy goats may involve complex pathways with recursive or simultaneous effects. Structural equation models were fitted to longitudinal data on milk yield and on somatic cell scores. Data consisted of 4 repeated records of milk production and of somatic cell score from left and right halves of the udder in each of 47 dairy goats; infection status of each of the halves at each test day was also available. Results strongly suggest the existence of a within-half, first-order autoregressive process and of simultaneity of effects between somatic cell scores from the left and right halves of the udder. This indicates that the immune response to an infection is not restricted to the half of the udder in which the infection takes place and that it tends to propagate over time. The existence of a negative effect of somatic cell score on milk yield was also supported by the results; however, evidence in favor of an effect in the opposite direction, a dilution effect, was not strong.

Animals↗

How useful is the concept of somatization in cross-cultural studies of maternal depression? A contribution from the Mothers in a New Country (MINC) study.

Somatization of depression symptoms has been assumed to characterize particular cultural groups, yet evidence for this has often been anecdotal. The Mothers in a New Country (MINC) study aimed to explore cultural assumptions about somatization in three groups of immigrant women who had recently given birth in Melbourne, Australia. Physical health (SF-36 physical health dimensions and a symptom list) and depression (EPDS, SF-36 mental health dimension and self assessment) data from personal interviews with Vietnamese (n = 104), Turkish (n = 107) and Filipino (n = 107) women, conducted in women's language of choice, six to nine months after childbirth were analyzed. Comparisons with data from a statewide postal survey of Victorian women are also made. Contrary to the study hypothesis that Turkish and Vietnamese women in particular would exhibit a high degree of somatization (leading to low depression scores on the standard measures and greater reporting of somatic symptoms), Turkish women were in fact most likely of the three groups to be assessed as depressed on the two psychological measures and by self-assessment, to report high levels of somatic symptoms, and Vietnamese and Filipino women had a low prevalence of depression on all measures and relatively lower levels of somatic symptom reporting. The MINC study findings thus call into question some common cultural assumptions about depression and demonstrate the importance of designing studies which can put hypothesized cultural differences to the test.

Asia, Southeastern↗

Relationship of somatic cell score with fertility measures.

Dairy Herd Improvement data from 284,450 cows in 37 states were used to examine the relationship of test-day somatic cell score, herd, calving year, parity, lactation stage, and calving ease score with fertility measures (rate of nonreturn to estrus by 70 d after first service, days to first service, and days open) for US Holsteins and Jerseys. Factors other than somatic cell score were examined to ensure that the estimation of the effect of somatic cell score was independent of other effects. Nonreturn rates were highest during April and May and lowest during June. Parity had a large effect on nonreturn rate, which was 6 to 7% higher for first parity than for sixth parity and later. Effect of lactation stage at first service on nonreturn rate was large; nonreturn rate increased by 8 to 13% from early to late lactation. Effect of calving ease score on nonreturn rate also was large: a 7% decline in nonreturn rate from score 1 to 5. For Holsteins, a small linear regression was found for nonreturn rate on preceding test-day somatic cell score, but this relationship was not significant for Jerseys. The magnitude of the effect of somatic cell score on fertility traits does not warrant postponing first service when somatic cell score is high.

Animals↗