| Abstrakt: |
The Y chromosome–linked gene sexdetermining region (SRY) is believed to be the master initiator of male sex determination in almost all eutherian mammals, functioning to upregulate expression of its direct target gene SRY-related HMG box–containing gene 9 (SOX9). XX maleness in humans is a rare syndrome with a frequency of 1 in 20,000–25,000 males. Approximately 90% of these cases carry some amount of the Y chromosome sequences due to an illegitimate recombination between X and Y chromosomes, where most of these cases have normal male genitalia. A more severe manifestation, the remaining 10% do not have any Y-chromosome sequences, and typically have ambiguous genitalia. In this study, we report a case of an infertile bull. Physical examination of this purebred Holstein bull showed a phenotypically androgynous animal with a normal penis, cryptorchidism (2 diminutive testicles, only one descended), and with a skeletal conformation and stance usually associated with female individuals. Lymphocytes from heparin sodium anticoagulated blood were cultured, harvested, and prepared according to conventional cell culture methods revealed a normal 60, XX karyotype with no numerical or structural chromosomal aberrations. PCR analyses were negative for the SRY gene, and positive for androgen receptor gene on the X chromosome. No sperm were found in seminal fluid collected in a routine breeding soundness exam at 17 months of age. The bull was slaughtered at 18 months of age, and its reproductive tract was collected. The testicle weighed 18.9 g (descended), and 42.4 g (abdominal). Neither testicle/ epididymal unit was appropriate size or fully developed. Two very enlarged vesicular glands (43.36 g and 52.52 g, normally each ~ 20 g) were observed alongside what appeared to be uterine tissue. Histology showed no tubular grooves in the ampulla and an epididymis devoid of sperm. The development of a male phenotype in SRY-negative XX individuals suggests that in addition to SRY, there are autosomal or X-linked genes involved in the sex-determining pathway. In humans, a dose change of the SOX9 gene, loss of function mutations in the WNT4, FoxL2, and RSPO1 testicular suppressing genes, and genomic rearrangements within the regulatory region of the SRY-box transcription factor 3 (SOX3) gene have all been associated with XX male sex reversal. To investigate whether a mutation or genomic rearrangement was responsible for the male phenotype in the SRY-negative 60, XX bull, DNA was collected from the bull and his sire and dam for long-read trio sequencing. These data may provide evidence for either a loss of function mutation in a gene normally inhibiting testes formation in XX individuals, or a gain of function mutation in a gene downstream of SRY in the sex determining pathway. [ABSTRACT FROM AUTHOR] |
