Protein Phosphatase 4 (PPP4) Prevents Female Reprogramming in the Mouse Testis After Sex Determination and Protects Male Fertility

Background: Impairment of lineage specification and function of gonadal somatic cells can lead to disorders of sexual development (DSDs) and fertility defects in humans. However, little is known about the function of protein phosphatases in testis development. Results: We showed that protein phosphatase 4 (PPP4) could maintain SOX9 expression in Sertoli cells and play an essential role in Sertoli cell lineage maintenance and male fertility. Conditional deletion of Ppp4c, a PPP4 catalytic subunit gene, caused the reprogramming of Sertoli cells to granulosa-like cells postnatally by inducing ectopic expression of FOXL2, which in turn led to testicular BTB structure damage, germ cell loss and ultimate testis to ovary-like gland transformation. Conclusion: Reprogramming of Sertoli cells due to absence of PPP4 may help explain the etiology of disorders of sexual differentiation and male infertility.

Congenital Adrenal Hyperplasia in Patients with Disorders of Sexual Differentiation

Congenital Adrenal Hyperplasia (CAH) is considered to be the most common cause of genital ambiguity in children. According to World’s literature, 90-95% of this disease is caused by 21-hydroxylase deficiency that impairs the synthesis of cortisol and aldosterone. The consequent excess in androgen production leads to virilization in the affected females. This study was aimed to find the number of cases with CAH (21-hydroxylase deficiency) in the children presented with disorders of sexual differentiation. For this purpose, 100 patients presented to The Children’s hospital for gender assessment were taken and their 17- OH progesterone levels were measured to confirm 21-hydroxylase deficiency, and chromosomal analysis was done to confirm chromosomal sex. Results indicated that out of 100 patients 49 were suffering from CAH. 63.2% of CAH patients were initially presented as males. Out of these, 44.8% were reassigned female gender on chromosomal analysis. So, it is concluded that the majority of patients presented with genital ambiguity in the tertiary care health facility have the ambiguity due to congenital adrenal hyperplasia.

Molecular genetic mechanisms, human sex determination levels and disorders of sexual differentiation

Annotation. The purpose of this work — an analysis and a summary of results of scientific research on problems of molecular genetic mechanisms and human sex determination levels. Literature analysis was performed in scientometric databases of Google Scholar, MedLine, Web of Science, Scopus for 2014–2018. Sex determination is a complex multi-stage process secured by functional integration of genetic determinants, products thereof, and the conditions of individual development for its realization. Sexual differentiation occurs at genetic, gonadal, hormonal, somatic, psychological and social levels, and disorders at any of them may lead to deviations from normal sex determination.

Sex assignment practice in disorders of sexual differentiation: survey results from paediatric endocrinologists in the Arab region

Background Sex assignment is a major issue in disorders of sexual differentiation (DSD). Not all conditions of DSD have clear recommendations on assignment and timing of surgery. Reports about sex assignment practice and the influence of culture and religion in the Arab region are scarce. Methods A survey questionnaire was distributed to participants in a paediatric endocrinology conference. Four DSD cases were presented. Participants were asked to fill in their answers on sex assignment choice, reasons for the particular assignment, strength of own recommendation and timing of surgery based on their practice. The cases presented were severely virilised XX congenital adrenal hyperplasia (CAH), complete androgen insensitivity syndrome (CAIS), severely undervirilised 5α reductase deficiency (5α RD) and XX ovotesticular case. Results Eighty-five endocrinologists participated in the study. Eighty (97.5%) chose a female sex to assign for the XX CAH. For the CAIS, 64 (78%) chose a female sex. Seventy-one (86.5%) voted for a male sex for the XY case of 5α RD. Forty-seven (57%) and 35 (43%) chose a female and a male sex for the ovotesticular case, respectively. The majority indicated that their advice for sex assignment is based on strong recommendations for the CAH, CAIS and 5α RD patients but they were open to the parents’ cultural and religious beliefs in their decision of the assignment for the ovotesticular case. Conclusions Practice in the Arab region appears to be in line with the international guidelines in the majority of DSD sex assignment and timing of surgery issues. However, culture and religious beliefs influence the practice in certain circumstances.