Prenatal diagnosis of a 46,XY karyotype female fetus with an SRY-associated gonadal dysgenesis, conceived through an intracytoplasmic sperm injection: a case report.

BACKGROUND: Permanent progression of paternal age and development of reproductive medicine lead to increase in number of children conceived with assisted reproductive techniques (ART). Although it is uncertain if ARTs have direct influence on offspring health, advanced paternal age, associated comorbidities and reduced fertility possess significant risks of genetic disorders to the offspring. With a broad implementation of a non-invasive prenatal testing (NIPT), more cases of genetic disorders, including sex discordance are revealed. Among biological causes of sex discordance are disorders of sexual development, majority of which are associated with the SRY gene. CASE PRESENTATION: We report a case of a non-invasive prenatal testing and ultrasound sex discordance in a 46,XY karyotype female fetus with an SRY pathogenic variant, who was conceived through an intracytoplasmic sperm injection (ICSI) due to severe oligozoospermia of the father. Advanced mean age of ICSI patients is associated with risk of de novo mutations and monogenic disorders in the offspring. Additionally, ICSI patients have higher risk to harbour infertility-predisposing mutations, including mutations in the SRY gene. These familial and de novo genetic factors predispose ICSI-conceived children to congenital malformations and might negatively affect reproductive health of ICSI-patients' offspring. CONCLUSIONS: Oligozoospermic patients planning assisted reproduction are warranted to undergo genetic counselling and testing for possible inherited and mosaic mutations, and risk factors for de novo mutations.

EXTL3-interacting endometriosis-specific serum factors induce colony formation of endometrial stromal cells.

Endometriosis is a benign chronic condition characterized by the existence of endometrial-like stroma and glandular tissue in extrauterine locations. The molecular mechanisms of its pathogenesis have not been elucidated. We have studied the role of EXTL3 (exostosin-like 3) in endometriosis and found that it is expressed in endometrial tissue as well as endometriosis lesions. We have found that serum from endometriosis patients contains a factor or factors, which interact with EXTL3 resulting in strongly increased colony formation in regenerating cell culture. We also found increased anti-EXTL3 antibodies in endometriosis patients' sera. EXTL3 is an N-acetyl glucosamine (GlcNAc) transferase, performing a key step in heparan sulfate (HS) glucosaminoglycan synthesis. Many viruses replicate in regenerating epithelial cells and use HS as a receptor for cell entry. We measured antibody titres to viruses, which use HS as a receptor for cell entry, and found rarely increased titres for these viruses in endometriosis sera, whereas titres to viruses using other receptors were equally distributed in study groups. The data indicate that perturbation of HS metabolism is associated with endometriosis.