Sex-determining events in the mouse preimplantation embryo: Testis determining gene expression and XX/XY growth rate dimorphism

Abstract

The differentiation of the gonads begins at mid-gestation when sex differences are first identified histologically. Prior to gonadal differentiaton, male and female embryos are phenotypically indistinguishable. After gonadal differentiation, males are identified by the presence of testes and females by the presence of ovaries. The Sry gene located on the Y chromosome has been identified as the testis determining gene. Evidence of Sry's role as the testis determining gene being both necessary and sufficient was proven by the development of testes in XX female mice transgenic for Sry. Transcription of Sry, thought to be critical for testicular differentiation, is hypothesized to be limited to the male gonad at the time of gonadal differentiation. We will demonstrate that transcription of Sry is not limited to the time of gonadal differentiation, but is detectable throughout the preimplantation period. Therefore, detection of transcription of Sry may be indicative of sex determining events occurring prior to gonadal differentiation in the preimplantation mouse embryo. This dissertation addresses the expression and function of Sry in the mouse preimplantation embryo. Furthermore, this dissertation addresses the sex dimorphism of a faster growth rate in male versus female embryos and a hypothesized relationship between growth rate and gonadal differentiation. Our hypotheses are that sex determining events occur prior to gonadal differentiation in the preimplantation embryo and/or that Sry has additional developmental roles in embryogenesis. Furthermore, the faster growth of males predisposes the XY gonad to differentiate into a testis. My conclusions are: (1) That Sry transcription is not limited to the time of gonadal differentiation, thus sex determining events may occur earlier. This is based on my findings that Sry mRNA is detectable throughout the preimplantation period and that at the blastocyst stage the linear Sry transcript is found on polyribosomes. In addition, my findings indicate that the faster growth of the male preimplantation embryo may contribute to the male gonad differentiating into a testis. (2) That Sry or Sry-like Sox genes play a developmental role in ovarian differentiation. This is based on my creation of female mice transgenic for an antisense oriented Sry transgene developing supernumerary ovaries.