China
Africa
Explore chapters and articles related to this topic
Azoospermia
Published in Botros Rizk, Ashok Agarwal, Edmund S. Sabanegh, Male Infertility in Reproductive Medicine, 2019
Medhat Amer, Emad Fakhry, Botros Rizk
Preliminary data from a recent study on three candidate genes NR5A1, DMRT1, and TEX11 have already shown that by using specific gene analyses, the etiological clarification of disturbed spermatogenesis can be significantly improved [35].
Variation of sex differentiation
Published in Joseph S. Sanfilippo, Eduardo Lara-Torre, Veronica Gomez-Lobo, Sanfilippo's Textbook of Pediatric and Adolescent GynecologySecond Edition, 2019
Anne-Marie Amies Oelschlager, Margarett Shnorhavorian
Complete gonadal dysgenesis with a 46,XY karyotype is the result of failure of the gonadal tissues to develop into functioning testicular tissue. As a result, there is no Sertoli production of AMH and no Leydig cell production of testosterone. Müllerian structures develop, and external genitalia appear typical for a female. This clinical condition is named Swyer syndrome. Often these individuals are identified with pubertal delay and elevated gonadotropins or when they present with a gonadoblastoma. SRY gene mutations have been identified in 15% of individuals with Swyer syndrome. Additional mutations associated with 46,XY complete gonadal dysgenesis have been identified in the MAP3K1, DHH, and NR5A1 genes (Table 7.1).
Testosterone signaling in spermatogenesis, male fertility and infertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Arijit Chakraborty, Vertika Singh, Kiran Singh, Rajender Singh
The steroidogenic enzyme P450scc cleaves the side chain of cholesterol (C27-sterol), resulting in the formation of C21 steroid pregnenolone followed by StAR-mediated transportation to the inner membrane of the mitochondria (8). The knockout of StAR gene has proved to be embryonically lethal, reflecting its essential function beyond steroidogenesis, such as an integral component in apoptosis, which also affects steroid hormone production (9). It has been found that the steroidogenic factor 1 (SF-1/NR5A1) and DAX-1 are critical in StAR gene regulation, especially in the endocrine tissues like the testis and the ovary (5). Subsequently, pregnenolone is released from the mitochondria into the smooth endoplasmic reticulum (SER), other enzymatic reactions take place in the SER (8). Pregnenolone is converted into the precursor of testosterone, androstenedione, by two major pathways, viz. the Δ5 or Δ4 steroid pathway through Δ5 3β-hydroxysteroid and Δ4 3-ketosteroid intermediates, respectively. The Δ5 pathway involves the production of 17α -hydroxypregnenolone and di-hydroepiandrosterone (DHEA), while the Δ4 steroid pathway involves the production of 17α-hydroxyprogesterone, from progesterone and its intermediate (10). The two pathways are also interconnected since the intermediates of Δ5 simultaneously pass through the Δ4 pathway. The 3β-hydroxysteroid dehydrogenase (3β-HSD) enzyme acts on three Δ5 intermediates—pregnenolone, 17α-hydroxypregnenolone and DHEA—and converts 3β-hydroxysteroids to 3-ketosteroids by catalysis of a 3β-hydrogenation and isomerization (11).
Molecular study and genotype–phenotype in Chinese female patients with 46, XY disorders of sex development
Published in Gynecological Endocrinology, 2021
Junke Xia, Jing Wu, Chen Chen, Zhenhua Zhao, Yanchuan Xie, Zhouxian Bai, Xiangdong Kong
The NR5A1 gene (OMIM #184757) encoding steroidogenic factor-1 (SF-1) positively regulates the expression of genes involved in male sex differentiation and modulates the expression of many factors involved in steroid hormone synthesis [25,26]. NR5A1 mutations may cause a defect in androgen biosynthesis and lead to a variable clinical phenotype of male pseudo-hermaphroditism [25]. The phenotype may range from clitoridauxe, virilization, and hypospadias to almost normal testicular function [27]. In our study, NR5A1 mutations were found in patients who presented with cryptorchidism and micropenis. The frame shift mutation p.Pro133Leufs was identified in the hinge region, which is critical for the transcriptional capacity of SF-1 [25]. The frame-shift variant forms a truncated protein with impaired protein function or is degraded by nonsense-mediated mRNA decay.
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
At this juncture, we were now curious to know whether the prevalent monogenic causes of DSD found in Indian subjects were also concordant in other populous Asian countries (like China and Japan). To validate the above, we summed up all the gene mutations causing DSD with respective ethnicity published in the research articles available at PubMed and HGMD sites for further comparison. Intriguingly, survey indicated AR mutations were the most reported not only in India but also amongst Chinese and Japanese affected subjects (Eggers et al. 2016; Zhou J and Fu 2018). On the contrary, possibility of funding or penchant could also had an effect as to these number of AR mutations that overshadowed the other gene mutations causing DSD. SRD5A2 mutations were second frequently reported with 1:3.5 from India and China, respectively. However, an international patient cohort study showed NR5A1 and SRD5A2 being the second and third highest number of variants (Eggers et al. 2016). Amongst the mutations reported in the sex-determining genes (i.e., SRY, SOX9 and DAX1) with sex reversal disease, SRY mutations were in 1: 3 from India and China, respectively, SOX9 mutations were scanty from China and Japan but none from India and DAX1 variants (20 mutations) were the highest reported from China. Other mutations (that caused defects in steroidogenesis) such as CYP17A1 [from China (15 mutations) and Japan (16 mutations)], HSD17B3 [China (4 mutations)], and CYP11A1 [China (1 mutation) and Japan (2 mutations)] were not reported from India to date. Also, Kallmann syndrome 1 gene (KAL1) mutations were the most reported from China (25 mutations) and Japan (12 mutations) but none from India.
Contemporary genetics-based diagnostics of male infertility
Published in Expert Review of Molecular Diagnostics, 2019
Alberto Ferlin, Savina Dipresa, Andrea Delbarba, Filippo Maffezzoni, Teresa Porcelli, Carlo Cappelli, Carlo Foresta
NR5A1 is a gene coding for a transcriptional activator with essential role in sexual differentiation, development of primary steroidogenic tissues and regulation of the AMH/Muellerian inhibiting substance gene [76]. Mutations in NR5A1 have been initially associated with primary adrenal insufficiency and 46,XY gonadal dysgenesis [77] but more recently with less severe phenotypes, including severe forms of male infertility with primary testicular damage, especially when associated with a history of cryptorchidism [78].