title: Ex3αERKO male infertility phenotype recapitulates the αERKO male phenotype.
abstract: Disruption of the Esr1 gene encoding estrogen receptor α (ERα) by insertion of a neomycin resistance gene (neo) into exon 2 (αERKO mice) was shown previously to cause infertility in male mice. While full-length ERα protein was not expressed in αERKO mice, alternative splicing resulted in the low-level expression of a truncated form lacking the N-terminus A/B domain and containing the DNA- and ligand-binding domains. Thus, it was unclear whether the reproductive phenotype in αERKO males was only due to the lack of full-length ERα or was affected by the presence of the variant ERα isoform. The present study examined male mice with deletion of exon 3 of Esr1 gene, lacking the DNA-binding domain, and null for ERα (Ex3αERKO). Dilation of some seminiferous tubules was apparent in male Ex3αERKO mice as early as postnatal day 10 and was pronounced in all tubules from day 20 onward. At 6 weeks of age, sperm numbers and sperm motility were lower in Ex3αERKO mice than in wild-type (WT) mice, and the rete testis and efferent ductules were dilated. Mating studies determined that adult Ex3αERKO males were infertile and failed to produce copulatory plugs. Serum testosterone levels and Hsd17b3 and Cyp17a1 transcript levels were significantly higher, but serum estradiol, progesterone, LH, and FSH levels and Cyp19a1 transcript levels were not significantly different from those in WT mice. These results confirm and extend those seen in other studies on male mice with deletion of exon 3 of Esr1 gene. In addition, the reproductive phenotype of male Ex3αERKO mice recapitulated the phenotype of αERKO mice, strongly suggesting that the αERKO male infertility was not due to the presence of the DNA-binding domain in the truncated form of ERα and that full-length ERα is essential for maintenance of male fertility.
authors.affiliation: Gamete Biology Group, Laboratory of Reproduction and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
authors.forename: Eugenia H
authors.initials: EH
authors.lastname: Goulding
authors.forename: Sylvia C
authors.initials: SC
authors.lastname: Hewitt
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakamura
authors.forename: Katherine
authors.initials: K
authors.lastname: Hamilton
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Korach
authors.forename: Edward M
authors.initials: EM
authors.lastname: Eddy
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000818:Animals; D004822:Epididymis; D004958:Estradiol / Q000097:blood / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005640:Follicle Stimulating Hormone / Q000097:blood; D007248:Infertility, Male / Q000235:genetics*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011374:Progesterone / Q000097:blood; D012152:Rete Testis; D012671:Seminiferous Tubules; D017384:Sequence Deletion; D013076:Sperm Count; D013081:Sperm Motility / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013739:Testosterone / Q000097:blood / Q000235:genetics
chemical_list: D047628:Estrogen Receptor alpha; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D015067:17-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase