title: Proteomic analysis of testis biopsies in men treated with injectable testosterone undecanoate alone or in combination with oral levonorgestrel as potential male contraceptive.
abstract: Treatment with injectable testosterone undecanoate (TU) alone or in combination with oral levonorgestrel (LNG) resulted in marked decreases in sperm concentrations. In this study, we used proteomic analyses to examine the cellular/molecular events occurring in the human testis after TU or TU + LNG treatment. We conducted a global proteomic analysis of the human testicular biopsies before and at 2 weeks after TU alone or TU + LNG treatment. Proteins showing significant changes in expression were identified and analyzed. As a result, 17 and 46 protein spots were found with significant differential expression after the treatment with TU alone and TU + LNG, respectively. TU treatment changed the expression of heterogeneous nuclear ribonucleoprotein K (hnRNP K), proteasome inhibitor PI31 subunit (PSMF1), and superoxide dismutase [Mn] mitochondrial precursor (SOD2). These proteins inhibit "assembly", induce cell death, and promote compensatory "cell survival" in the testis. After TU + LNG treatment, "proliferation/cell survival" and "apoptosis/death" were the predominant responses in the testis. TU + LNG treatment inhibited the expression of Prolyl 4-hydroxylase beta subunit (P4HB) and Annexin A2 (Annexin II). These proteins are involved in apoptosis and cell proliferation, respectively. TU + LNG treatment also enhanced the expression of SOD2 and Parvalbumin alpha (Pvalb). These two proteins may protect testicular cells against apoptosis/death and promote cell survival. In conclusion, TU and TU + LNG treatments suppress spermatogenesis through different pathways by changing the expression of different proteins. hnRNP K, PSMF1, SOD2, P4HB, Annexin II, and Pvalb, are key proteins that may be early molecular targets responsible for spermatogenesis suppression induced by hormone treatment.
authors.affiliation: Laboratory of Reproductive Medicine, Department of Histology and Embryology, and Center of Clinical Reproductive Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yugui
authors.initials: Y
authors.lastname: Cui
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.forename: Yefei
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xuejiang
authors.initials: X
authors.lastname: Guo
authors.forename: Ran
authors.initials: R
authors.lastname: Huo
authors.forename: Xinghai
authors.initials: X
authors.lastname: Wang
authors.forename: Jiansun
authors.initials: J
authors.lastname: Tong
authors.forename: Lixin
authors.initials: L
authors.lastname: Qian
authors.forename: Zuomin
authors.initials: Z
authors.lastname: Zhou
authors.forename: Yue
authors.initials: Y
authors.lastname: Jia
authors.forename: Yan-He
authors.initials: YH
authors.lastname: Lue
authors.forename: Amiya Sinha
authors.initials: AS
authors.lastname: Hikim
authors.forename: Christina
authors.initials: C
authors.lastname: Wang
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Swerdloff
authors.forename: Jiahao
authors.initials: J
authors.lastname: Sha
mesh_terms: D000284:Administration, Oral; D001706:Biopsy; D015153:Blotting, Western; D003272:Contraceptive Agents, Male / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D006801:Humans; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D016912:Levonorgestrel / Q000008:administration & dosage*; D008297:Male; D010449:Peptide Mapping; D020543:Proteome; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013737:Testis / Q000378:metabolism* / Q000473:pathology; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D003272:Contraceptive Agents, Male; D020543:Proteome; D013739:Testosterone; D016912:Levonorgestrel; C010792:testosterone undecanoate