Disease relevance of Sex Differentiation

• The LuRKO mouse is a close phenocopy of recently characterized human patients with inactivating LHR mutations, although the lack of pseudohermaphroditism in LuRKO males suggests that the intrauterine sex differentiation in this species is not dependent on LH action [1].
• AMH serum concentrations were significantly decreased in infants with disorders of sex differentiation, particularly testicular dysgenesis, and increased in patients with delayed puberty [2].
• These data suggest that in the Frasier syndrome, XY sex reversal and renal failure could be the result of either faulty gene(s) located downstream in the sex differentiation pathway during embryogenesis, or impaired SRY regulation [3].

Psychiatry related information on Sex Differentiation

• Administration of testosterone propionate (TP) to castrated (neonatally) males during a critical period (days 6-13) imprinted for the subsequent sex differentiation of HCLA sites, whereas TP administration at other times did not [4].

High impact information on Sex Differentiation

• The mammalian Y chromosome encodes a testis-determining factor (termed TDF in the human), a master regulator of sex differentiation [5].
• Müllerian inhibiting substance (MIS) is a key element required to complete mammalian male sex differentiation [6].
• Taken together, our results suggest that AMH plays a pivotal role in both morphological and endocrine gonadal sex differentiation [7].
• Lod scores for 18 families informative for Lu:Se gave no evidence for sex differentiation in recombination fraction: theta for males was 0.07, and for females, .08 [8].
• Sox9 is expressed during chondrocyte differentiation and is up-regulated in male and down-regulated in female genital ridges during sex differentiation [9].

Chemical compound and disease context of Sex Differentiation

• To ascertain whether styrene monomer and trimer induce an estrogen-like effect, all-male tadpoles of Rana rugosa were exposed to dilute solutions of styrene monomer and trimer (2,4,6-tripfenyl-1-hexene) at concentrations of 0.1, 1, or 10 microM during days 19-23 after fertilization, which is the critical period of gonadal sex differentiation [10].

Biological context of Sex Differentiation

• The zinc-finger proteins ZFX and ZFY, encoded by genes on the mammalian X and Y chromosomes, have been speculated to function in sex differentiation, spermatogenesis, and Turner syndrome [11].
• Androgens drive sex differentiation, bone and muscle development, and promote growth of hormone-dependent cancers by binding the nuclear androgen receptor (AR), which recruits coactivators to responsive genes [12].
• Our study shows that some cases of CAIS are explained by an inability to form a functional AR-steroid complex and hence, the AR is unable to activate transcription of genes essential for male sex differentiation during fetal development [13].
• We review what is known about ATRX as a chromatin remodeling protein, and its role in mammalian sex differentiation [14].
• These studies demonstrate an early imprinting period during which androgen exposure programs for postpubertal development of sex differentiation of HCLA binding sites [4].

Anatomical context of Sex Differentiation

• Based on the sexually dimorphic expression of Ad4BP/SF-1 in the fetal gonads, the factor is also likely to be involved in the gonadal sex differentiation [15].
• Anti-Müllerian hormone plays a key role in sex differentiation by inducing the regression of Müllerian ducts in the male fetus [16].
• Furthermore, we demonstrated that both Tra2 mRNAs were predominantly expressed in germ cells of both sexes before the onset of sex differentiation, suggesting that both Tra2 homologues might be involved in the sex differentiation in medaka [17].
• Anti-Müllerian hormone (AMH) produced by fetal Sertoli cells is responsible for regression of Müllerian ducts, the anlage for uterus and Fallopian tubes, during male sex differentiation [18].
• To address the role of MIS on gonadal sex differentiation in fishes, we isolated a MIS cDNA from the Japanese flounder testis and examined the expression pattern of MIS mRNA in gonads of both sexes during sex differentiation period [19].

Associations of Sex Differentiation with chemical compounds

• The distinct phenotypic variation in AIS here is explained by differences in the availability of 5alpha-dihydrotestosterone during embryonic sex differentiation [20].
• The 5alpha-reductase-2 encoded by the SRD5A2 gene plays a critical role in male sex differentiation by converting testosterone into 5alpha dihydrotestosterone in the peripheral target tissues [21].
• Association between plasma level of growth hormone and sex differentiation of hepatic steroid metabolism in the rat [22].
• Polymorphic variants in genes controlling androgen synthesis and action may modulate androgenic effects on sex differentiation [23].
• In this regard, the expression of the estrogen-producing enzyme, aromatase, has been shown to be temperature-sensitive in species where temperature can reverse sex differentiation, especially in our model, the amphibian Pleurodeles waltl [24].

Gene context of Sex Differentiation

• The expression of Mullerian inhibiting substance (MIS), a key molecule in sex differentiation and reproduction, is tightly regulated [25].
• ATRX and sex differentiation [14].
• Conservation of the function of DMRT1 regulatory sequences in mammalian sex differentiation [26].
• Ad4BP/SF-1, however, is also involved in the sex differentiation of the gonad at later stages, such as the regulation of steroid hormones and MIS [27].
• In this study, we tested the possibility of Sox8 being important for sex determination or sex differentiation in the red-eared slider turtle Trachemys scripta, in which sex is determined by egg incubation temperature between stages 15 and 20 [28].

Analytical, diagnostic and therapeutic context of Sex Differentiation

• Aromatase and estrogen receptor gene expression was studied in rainbow trout by semi-quantitative RT-PCR in gonads sampled before, during and after sex-differentiation [29].
• Using immunocytochemistry we have described the distribution and ontogeny of three distinct gonadotropin-releasing hormone (GnRH) neural systems, emphasizing the analysis during the period of sex differentiation in the South American cichlid fish Cichlasoma dimerus [30].
• To clarify the effect of exogenous estradiol-17beta (E2) on sex differentiation, the E2 content of developing eggs of Oryzias latipes was measured by radioimmunoassay [31].

References