Steroid 5α-reductase 2 gene melting polymorphisms in male subjects with azoospermia or oligospermia

Objective: This study was designed to test the hypothesis that mutations in the gene for type 2 steroid 5α-reductase (SRD5A2) may be the cause of a phenotype characterized primarily by oligospermia or azoospermia. Study Design: Deoxyribonucleic acid from control subjects and subjects with oligospermia (n = 12) and azoospermia (n = 6) were evaluated for mutations in SRD5A2. Methods used for mutation analysis included polymerase chain reaction, Southern blotting, and denaturing gradient gel electrophoresis. Results: Denaturing gradient gel electrophoresis of all 5 amplified exons resulted in similar migration patterns in samples from both control and study subjects. Genomic deoxyribonucleic acid subjected to denaturing gradient gel electrophoresis after restriction digest revealed melting polymorphisms. Direct sequencing of the gene in a single patient with a unique melting polymorphism yielded a normal sequence. Conclusions: Melting polymorphisms for SRD5A2 were detected in a group of patients with oligospermia or azoospermia. Sequence analysis did not demonstrate functional mutations in the coding sequence of this gene. (Am J Obstet Gynecol 1999;180:1394-8.)     

A monoclonal antibody,EC-1, derived from a syngeneically multiparous mouse alters in vitro fertilization and development

A monoclonal antibody designated ‘EC-1’ was derived from a fusion of myeloma cells with lymphoid tissue from a syngeneically multiparous, but otherwise unimmunized, mouse and was selected by screening for reactivity with teratocarcinoma cells. The IgM antibody binds to the cell surface of ova, zygotes, and 2-cell embryos. Binding is not detected on the 4- or 8-cell embryo but reappears on the morula and blastocyst. EC-1 binds to the trophoblast but not to the inner cell mass of in vitro attached blastocysts and the ectoplacental cone of the peri-implantation embryo. In adult tissues, EC-1 binds to the follicular cells of the ovary, the lining epithelium of the pregnant uterus, the interstitial region of the testes and to epidydimal but not testicular sperm. In nongonadal tissues EC-1 binds to an epitope located in some, but not all, regions of connectives tissues associated with basement membrane. The antigen detected by EC-1, as expressed on teratocarcinoma-derived cell line PYS-2, is a large glycoprotein which is sensitive to reduction. EC-1 inhibits in vitro fertilization and partially inhibits in vitro development of in vitro fertilized ova. The possible implications of EC-1 binding and activity are discussed.     

17α-Hydroxylase deficiency in a genetic male and female sibling pair

The diagnosis of congenital adrenal hyperplasia due to a deficiency of the enzyme 17α-hydroxylase was made in a genetic male and female sibling pair born of parents who were first cousins. The genetic male was a phenotypic female who presented with primary amenorrhea and mild hypertension. The genetic female exhibited absence of secondary sexual characteristics and severe hypertension. The plasma steroid data confirmed the diagnosis of 17α-hydroxylase deficiency in both subjects: low 17α-hydroxyprogesterone, elevated desoxycorticosterone, elevated corticosterone and elevated progesterone. These are the first case reports of 17α-hydroxylase deficiency in a male-female sibling pair, and they add support to the hypothesis that this is an autosomal recessive disorder.     

Induction of endometrial cycles and ovulation in a woman with combined 17α-hydroxylase/17,20-lyase deficiency due to compound heterozygous mutations on the P45017α gene

Objective: To describe the case of a Japanese woman with combined 17α-hydroxylase/17,20-lyase deficiency (congenital adrenal hyperplasia type V) and to discuss possible therapeutic procedures in such patients.Design: Case report.Setting: University hospital.Patient(s): A 26-year-old woman with secondary amenorrhea and primary sterility.Intervention(s): Nucleotide sequencing of the P45017α gene (CYP17), induction of endometrial maturation with steroid hormone replacement, and ovulation induction with gonadotropin.Main Outcome Measure(s): Nucleotide sequence of CYP17, endometrial thickness and follicle diameter measured by transvaginal ultrasonography, and histologic evaluation of the endometrium.Result(s): Two different mutations were detected on CYP17: One was a deletion of the phenylalanine codon (TTC) at either amino acid 53 or 54 in exon 1, and the other was a missense mutation with the substitution of histidine (CAC) by leucine (CTC) at position 373 in exon 6. Repeated histologic evaluations performed during treatment with P consistently revealed an unripe endometrium with glands of the early secretory phase and markedly scanty stroma. Ultrasound examination revealed follicular growth and ovulation after gonadotropin administration, but insufficient thickness of the endometrium.Conclusion(s): Ovulation induction was possible in this patient with 17α-hydroxylase/17,20-lyase deficiency, but the endometrial response to steroid hormone replacement was extremely poor.