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Wnt signaling in spermatogenesis and male infertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Vertika Singh, Meghali Joshi, Kiran Singh, Rajender Singh
In the early embryo, mammalian gonads are indifferent. The development of Müllerian or Wolffian ducts results in the female or male reproductive system, respectively. Sry (sex determining gene Y) regulates the production of the anti-Müllerian hormone (AMH) or the Müllerian inhibiting substance (MIS) by aggregated pre–Sertoli cells, which results in the regression of the Müllerian duct and the development of the Wolffian duct. Once the sexual duct is determined and formed, the germ cells differentiate into the corresponding gametes (sperm or ova) depending on the molecular milieu. This bidirectional differentiation is finely tuned by an interplay of various signaling pathways.
Sex Chromosome Anomalies
Published in Merlin G. Butler, F. John Meaney, Genetics of Developmental Disabilities, 2019
L. Hamerton John, A. Evans Jane
SRY is a transcription factor whose function is to initiate testicular differentiation in mammalian embryogenesis. The protein contains a high mobility group box (HMG), a DNA binding motif conserved among a broad class of nuclear proteins. Almost all of the published mutations associated with sex reversal in 46,XY females are located in the HMG box and affect the structure of the DNA binding domain (146). Other loci involved in XY sex reversal include SOX9 at 17q24, a transcription factor whose duplication leads to XX sex reversal, while mutations lead to XY gonadal dysgenesis and campomelic dysplasia. Mutations in SF1 at 9q33 result in adrenal insufficiency and XY gonadal dysgenesis. Mutations in DMRT1 at 9p24 result in XY gonadal dysgenesis. Mutations at the DAX1 locus, an antitestis gene at Xp21.3, result in congenital adrenal hypoplasia, while duplications of a 160 kb region result in XY gonadal dysgenesis (158). Clearly, extensive genetic heterogeneity exists in both XX and XY sex reversal. The process of sex determination is clearly highly complex and only partially understood (153,158-160).
Prenatal Diagnosis
Published in Victor A. Bernstam, Pocket Guide to GENE LEVEL DIAGNOSTICS in Clinical Practice, 2019
Genetic studies of XY females with gonadal dysgenesis, as well as of normal males, identified mutations within the SRY gene responsible for sex reversal in the affected individuals. Amplification of SRY sequences from the DNA of XY females or normal males by PCR revealed that although SRY is required for male sex determination, this is not the “ultimate” TDF gene. A specific DNA-binding activity encoded by SRY appears to be essential for sex determination.
Augmented angiogenic transcription factor, SOX18, is associated with asthma exacerbation
Published in Journal of Asthma, 2021
Jisu Hong, Pureun-Haneul Lee, Yun-Gi Lee, George D. Leikauf, An-Soo Jang
The SOX gene family members contain high mobility group (HMG) box DNA binding regions and are related to the mammalian sex determining gene region of the Y (SRY). The gene SRY (sex determining region of the Y), located at the distal region of the short arm of the Y chromosome, is necessary for male sex determination in mammals. SOX genes play key roles during animal development (9,39–41), showing diverse and dynamic patterns of expression throughout embryogenesis and in a variety of adult tissue types. Mouse Sox 1, 2, and 3 are expressed at the highest level in the developing nervous system and human SOX 1–4, 10, 11, 14 and 22 genes are expressed in developing brain (42–47). Base on the sequence of its HMG box, human SOX18 along with SOX7 and SOX17, are classified as a member of the F subfamily (48,49).
A novel variant in LCHGR gene in 3 siblings with type 1 Leydig cell hypoplasia
Published in Gynecological Endocrinology, 2020
Amine Aktar Karakaya, Edip Unal, Aslı Beştaş, Funda Taş, Hüseyin Onay, Yusuf Kenan Haspolat
The first step in gender development is the differentiation of bipotential gonad in the direction of ovary or testicle. At the 6th week, SRY (sex-determining region Y) located on the short arm of the Y chromosome causes the gonads to develop in the direction of the testicle. With testosterone released from the testicles, internal genitalia develops, while DHT (dihydrotestosterone) differentiates the external genitalia [1]. Male sex development is due to adequate androgen production from the testicles. Problems in the early stages of this development lead to various abnormalities [2]. The luteinizing hormone (LH)/chorionic gonadotropin receptor (LHCGR) plays an important role in both male and female reproductive physiology. This receptor belongs to the family of G-protein-bound receptors. The LHCGR gene on the 2p21 chromosome consists of 12 exons. Placental human CG (hCG) or pituitary LH stimulates fetal Leydig cells via LHCGR. This activation starts Leydig cell proliferation and then fetal testosterone production begins [3,4]. Mutations in the LHCGR gene lead to LCH. Thus, testosterone production is impaired. This situation causes gender development disorder in boys. In this article, a case of three siblings with 46, XY karyotype presenting with primary amenorrhea due to a novel homozygous mutation in the LHCGR gene was reported.
Molecular diagnostics of disorders of sexual development: an Indian survey and systems biology perspective
Published in Systems Biology in Reproductive Medicine, 2019
MR Nagaraja, Satya Prakash Gubbala, C. R. Wilma Delphine Silvia, Ramars Amanchy
Human sex-determining region Y (SRY) protein (204 amino acids) coded by an intronless gene, SRY (a member of SOX gene family, cytogenetic location-Y chromosome p11.2), consists of three parts, i.e., N-terminus part (1–56 codons), high mobility group (HMG) domain (57 ± 136, 80 codons), and C-terminus part (137 ± 204, 68 codons). This DNA-binding protein is responsible for the initiation of male sex determination. In XY fetus, inactivating SRY mutation fails to activate its target genes, in turn bipotential gonad remains undifferentiated leading to complete GD (CGD) (<20% cases) evidenced by streak gonads, presence of uterine remnants (no AMH production), and female external genitalia (no androgen synthesis). These cases usually present at adolescence due to delayed pubarche and primary amenorrhea or may at later adulthood because of gonadal tumors (unilateral or bilateral dysgerminoma) or other tumors (gonadoblastoma, teratoma, or embryonal carcinoma).