A Disorder of Sex Development in a Holstein–Friesian Heifer with a Rare Mosaicism (60,XX/90,XXY): A Genetic, Anatomical, and Histological Study

Abstract

In this study, we describe an eighteen-month-old Holstein–Friesian heifer with a deformed vulva, located abdominally. The heifer showed typical signs of estrus. A comprehensive anatomical and histopathological examination revealed a blind-ended vagina and an additional section of urethra, which became a part of the shortened penis. Cytogenetic analysis showed the presence of two cell lines: 60,XX and 90,XXY. The frequency of the triploid cell line was low (3%) in leukocytes and elevated (35%) in fibroblasts. The molecular detection of Y-linked genes (SRY and AMELY) in the blood, skin, hair follicles, and buccal epithelial cells confirmed the presence of a cell line carrying the Y chromosome. Genotyping of 16 microsatellite markers in DNA isolated from hair follicles and fibroblast culture showed the presence of one (homozygous) or two variants (heterozygous) at all the studied loci, and allowed chimerism to be excluded. We concluded that the heifer had diploid/triploid (60,XX/90,XXY) mosaicism. To our knowledge, this is only the fifth such case to be reported worldwide in this species. Since cytogenetic studies are routinely performed on in vitro cultured leukocytes, we suspect that the prevalence of this chromosome abnormality is underestimated, as it is known from published reports that the frequency of the triploid cell line is usually very low in leukocytes.

Chromosome Abnormalities and Fertility in Domestic Bovids: A Review

“…This syndrome is very rare in both humans and animals. In domestic bovids, only four cases have been reported of cattle with 2n = 60,XX and 3n = 90,XXY mosaicism [131]. Generally, the mixoploidy depends on the type of cell in cattle and humans, triploid cells being absent or present in lower percentages in blood lymphocytes and present in higher percentages in fibroblasts or cells of the uterine body or limbs [131][132][133].…”

“…In domestic bovids, only four cases have been reported of cattle with 2n = 60,XX and 3n = 90,XXY mosaicism [131]. Generally, the mixoploidy depends on the type of cell in cattle and humans, triploid cells being absent or present in lower percentages in blood lymphocytes and present in higher percentages in fibroblasts or cells of the uterine body or limbs [131][132][133]. In humans, the few 46,XX/69,XXY cases fall into three phenotypic groups: males with testicular development, ovo-testicular disorder of sex development (DSD), or under-virilized male DSD [134].…”

“…In humans, the few 46,XX/69,XXY cases fall into three phenotypic groups: males with testicular development, ovo-testicular disorder of sex development (DSD), or under-virilized male DSD [134]. In cattle, the four cases reported so far showed various phenotypes, including aplasia of the vulva, a rudimentary penis, the presence of ovaries, an empty scrotum, and ovaries with corpus luteum [131].…”

Parental genomes segregate into distinct blastomeres during multipolar zygotic divisions leading to mixoploid and chimeric blastocysts

“…In particular, when the parental origin of one of these cell lineages is attributed to one parent only, this is called mosaic genome-wide (GW) uniparental disomy. Chimerism [28][29][30][31][32], mixoploidy [33][34][35][36][37][38][39][40][41], and mosaic GW uniparental disomy [42][43][44][45][46][47][48] have been shown to underlie rare developmental disorders in humans and cattle. They are also associated with defined clinical placental manifestations, such as placental mesenchymal dysplasia [49][50][51], and complete or partial hydatidiform moles [52,53].…”

Parental genomes segregate into different blastomeres during multipolar zygotic divisions leading to mixoploid and chimeric blastocysts

“…In a specific form called mosaic GW uniparental disomy, the parental origin of one cell lineage is attributed to one parent only. Chimerism (2)(3)(4)(5)(6), mixoploidy (7)(8)(9)(10)(11)(12)(13)(14)(15) and mosaic GW uniparental disomy (16)(17)(18)(19)(20)(21)(22) have been shown to underlie rare developmental disorders in man and cattle. They are also associated with defined clinical placental manifestations, such as placental mesenchymal dysplasia (23)(24)(25), and complete or partial hydatidiform moles in women (26).…”