Genetic Causes of Male Infertility
Botros Rizk, Ashok Agarwal, Edmund S. Sabanegh in Male Infertility in Reproductive Medicine, 2019
46,XX male syndrome (de la Chapelle syndrome) is a rare syndrome that occurs in 1/10,000–20,000 of newborn males [7]. In the majority of cases, this syndrome is caused by the translocation of the sex-determining region of the Y chromosome (SRY region, which plays a crucial role in differentiation of bipotential gonads into testes) to the X chromosome or an autosome. A minority of cases are SRY negative, which presumably had another cause of activation of the testicular differentiation cascade. Clinically, 46XX men resemble KF men and present with small firm testes, hypogonadism, and azoospermia. However, unlike KF, the azoospermia in 46XX men is due to complete absence of genes located in AZF regions. Accordingly, these patients have no chance of successful testicular sperm retrieval [4].
Variation of sex differentiation
Joseph S. Sanfilippo, Eduardo Lara-Torre, Veronica Gomez-Lobo in Sanfilippo's Textbook of Pediatric and Adolescent GynecologySecond Edition, 2019
Terms such as “hermaphrodite” or calling the baby “it” should be avoided. Confusing and controversial terms, including true hermaphrodite, pseudohermaphrodite, XX male, sex reversal, testicular feminization, and undermasculinization, have been replaced with categorization by karyotype and include 46,XY DSD; 46,XX DSD; and sex chromosome DSD. Initially, the term DSD was “disorders of sex development,” but more currently, DSD is used to signify “differences of sex development,” Some patients and parents will prefer the term “intersex” to “DSD.” Refer to Table 7.6 for current terminology describing DSD conditions.49
Discovery and research
Peter S. Harper in The Evolution of Medical Genetics, 2019
The interview gives a rare glimpse of the emotional side of science from the viewpoint of the ‘loser’ in what is often perceived as the ‘winner takes all’ field of gene isolation. Understandably a losing team often do not want to write about the situation in detail, while the account of the ‘winners’ often over-stresses the exclusivity of their discovery. In this case, though, the eventual outcome (Sinclair et al. 1990) was rather different. Peter Goodfellow continues: I was devastated that David scooped us, and I'd had a group of five people working for two years in a chromosomal walk which was brutal, the Y chromosome is full of repeats. It was murderous, awful work, and we got scooped. I remember one of the post-docs in the lab, a guy called Paul Goodfellow, no relation, as we were sitting down crying, Paul was saying to me, ‘You know there are lots of people who'd like to be failures like us.’ And that was such a wise thing [laughs]. You know it's easy to feel sorry for yourself but actually there are a lot of people who would like to have been in the position of failing, that we had done, so it put it into some context. And so we sort of took a deep breath and started to think about what we would do and what experiments were worth doing when Paul said to me, ‘You know, are you absolutely sure it's right?’ And I said, ‘It looks pretty good to me.’ And he said, ‘Well, there's at least one hypothesis which you can always use to test this, which is any XX male which has been created by transfer of Y material should have the pseudoautosomal region.’ So if you could find pseudoautosomal region positive X chromosomes, then, the other way around, then you know that's how that was created. So basically we had a whole load of DNA from a number of collaborators and we found some patients from Marc Fellous, 15 of which we were able to show … had all the elements they should have but didn't have ZFY… So we had Y positive XX males who didn't have ZFY. And as soon as we found two patients like that we knew that it was a mistake, and there had been other indications. We'd done stuff which Jenny Graves. David Page, my lab and Jenny's lab had collaborated on looking for ZFY in marsupials and it wasn't on the Y chromosome in metatherians, so either metatherians were using a different gene or it wasn't the sex determinant gene. So it was beginning to be a bit of a feel that maybe there was something more complicated, but it was those patients from Marc Fellous that told us that the sex determinant gene hadn't been cloned. And we'd walked straight through it. Basically it was a very small gene which wasn't particularly well conserved and we had just walked through it, and we found it when we went back and looked more carefully …
Systematic review of hormone replacement therapy in the infertile man
Published in Arab Journal of Urology, 2018
Amr El Meliegy, Ahmad Motawi, Mohamed Ahmed Abd El Salam
The term primary hypergonadotrophic hypogonadism refers to testicular disorders and is characterised by low serum testosterone despite high levels of FSH and LH. Low testosterone production results in impaired spermatogenesis (primary testicular failure) as seen in congenital anorchia, undescended testis, Sertoli cell only syndrome (germ cell aplasia), or after testicular injury from trauma, infection, surgery, exposure to chemo/radiotherapy or drug induced (e.g. ketoconazole, flutamide, spironolactone, etc.). In addition, genetic causes for primary testicular failure are described such as numerical chromosome aberrations including: Klinefelter syndrome, XX-male syndrome, XYY syndrome and Y chromosome microdeletions [16].
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
Aneuploidies are defined by an abnormal number of chromosomes with respect to the euploid state (46,XY or 46,XX). The most frequent aneuploidies detected in infertile men involve the sex chromosomes, examples include the Klinefelter syndrome (at least one extra X chromosome), mixed gonadal dysgenesis (45,X/46,XY), and the 46,XX male syndrome.
Related Knowledge Centers
- Chromosomal Crossover
- Intersex
- Karyotype
- Phenotype
- Y Chromosome
- Autosome
- Meiosis
- Sex-Determining Region Y Protein
- Pseudoautosomal Region
- Fertilisation