A lack of coordination between sister-chromatids segregation and cytokinesis in the oocytes of B6.YTIR (XY) sex-reversed female mice

Abstract

The B6.YTIR (XY) mouse develops bilateral ovaries despite the expression of the testis-determining gene Sry during gonadal differentiation. We reported that the oocytes of the XY female are defective in their cytoplasm, resulting in a failure in the second meiotic division after activation or fertilization in vitro. However, the mechanism of meiotic failure or the cause of infertility remained to be clarified. In the present study, we obtained mature oocytes from XY females by superovulation and confirmed that these oocytes also fail in zygotic development. By using confocal microscopy 3D-analysis, we demonstrated that meiotic spindles were properly positioned and oriented in the MII-oocytes from XY females. After parthenogenic activation, fewer oocytes from XY females extruded the second polar body, and in those oocytes, sister-chromatids were often separated but neither set entered the second polar body. ARP2, F-actin, and ORC4, known to play roles in asymmetric meiotic division, were initially localized along the ooplasmic membrane and concentrated over the MII-spindle but lost their cortical polarity after activation while the sister-chromatids moved away from the oolemma in the oocytes from XY females. Our results indicate that the second polar body extrusion is uncoupled from the sister-chromatids separation in the oocytes from XY female mouse.

Role of the X and Y Chromosomes in the Female Germ Cell Line Development in the Mouse (Mus musculus)

“…Nonetheless, we also recognized meiotic drive in the XY oocyte; 70% of oocytes retain 19 autosomal chromosomes and univalent X or Y chromosome (35% each) [Villemure et al, 2007]. In addition, 25-40% of the euploid oocytes from XY females show PSSC [Zhu et al, 2017], consistent with the report for the XO oocyte [LeMaire-Adkins et al, 1997]. At the end, certain percentages of oocytes from XO and XY females retain single X chromosomes as expected in the oocytes of XX females.…”

“…We initially reported that the MII-spindle is bulky and orientated perpendicular, instead of parallel, to the ooplasm [Villemure et al, 2007;Obata et al, 2008]. However, we later found largely normal MII-spindle orientation in the oocytes from XY females in a constructed 3D-model using confocal microscopy [Zhu et al, 2017]. We cannot explain this discrepancy, but our recent study again confirmed the perpendicular orientation by confocal microscopy [Yamazaki and Taketo, unpubl.…”

“…Upon fertilization or parthenogenetic activation in the MII-oocytes from XX females, the MII-spindle rotates into the perpendicular orientation and the sister chromatids segregate into the oocyte and the second polar body at the second meiotic division [Mihajlović and FitzHarris, 2018;Wang et al, 2020]. The chance for the XY female mouse to produce offspring is abolished at this stage since very few MII-oocytes complete the second meiotic division or initiate zygotic development [Taketo-Hosotani et al, 1989;Amleh et al, 1996;Villemure et al, 2007;Zhu et al, 2017]. We initially reported that the MII-spindle is bulky and orientated perpendicular, instead of parallel, to the ooplasm [Villemure et al, 2007;Obata et al, 2008].…”

Tenuous Transcriptional Threshold of Human Sex Determination. I. SRY and Swyer Syndrome at the Edge of Ambiguity

“…DSD mutations in these structural elements (variously perturbing mini-core packing, tail orientation, or direct side chain/DNA contacts) result in 46, XY gonadal dysgenesis with somatic sex reversal. These elements are invariant features of eukaryotic Sox boxes (8), including a junctional aromatic residue at box position 72 (Tyr or Trp; shaded gray rectangle in Figures 1D, E); corresponding clinical mutations have been identified in the HMG boxes of several SOX factors (e.g., SOX2, SOX4, SOX5, SOX9, SOX10, SOX11, SOX17, and SOX18 (5,46,(74)(75)(76)(77)) in association with diverse phenotypes. 2 Such conservation suggests that the present structure-activity relationships, although probed only in SRY, will generalize to this broad family of architectural transcription factors (8).…”

Effects of the Sex Chromosome Complement, XX, XO, or XY, on the Transcriptome and Development of Mouse Oocytes During Follicular Growth

“…The gonadal sex is reversed because the SRY protein encoded on the Y TIR chromosome has polymorphic differences from that encoded on the Y B6 chromosome, and fails to sufficiently upregulate its target Sox9 gene on B6, which is essential for testicular differentiation (Coward et al, 1994;Taketo et al, 2005;Park et al, 2011). All stages of follicles can be seen in prepubertal B6.Y TIR (XY herein) ovaries, but very few MII-oocytes complete the second meiotic division or initiate embryonic development after fertilization (Taketo-Hosotani et al, 1989;Amleh et al, 1996;Villemure et al, 2007;Zhu et al, 2017). The failure in embryonic development can be attributed to cytoplasmic defects; when the XY oocyte nucleus has been transferred into an enucleated XX oocyte, the reconstructed oocyte develops into a healthy pup after in vitro fertilization and embryo transfer (Obata et al, 2008).…”