Deepika Jaiswal1, Sameer Trivedi2, Neeraj K Agrawal3, Kiran Singh4. 1. Department of Molecular and Human Genetics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. 2. Department of Urology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. 3. Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. 4. Department of Molecular and Human Genetics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. Electronic address: skiran@bhu.ac.in.
Abstract
OBJECTIVE: To dissect the role of the apoptotic pathway and its regulation in the pathogenesis of male infertility in nonobstructive azoospermia. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Sixty-three infertile azoospermic patients with different histologic phenotypes were recruited (obstructive azoospermia, n = 16; hypospermatogenesis, n = 11; maturation arrest, n = 15; Sertoli cell only, n = 21). INTERVENTION(S): Testicular biopsies for histopathologic and expression analysis. MAIN OUTCOME MEASURE(S): Expression analysis by quantitative reverse transcription-polymerase chain reaction, protein localization by immunohistochemistry and apoptotic proteome array. RESULT(S): Results showed significantly increased expression of proapoptotic proteins like BAX, BAD, and BAK and comparatively lowered expression of antiapoptotic BCL2 and BCLW. Immunostaining revealed increased active caspase-3 activity and more TUNEL-positive cells in different impaired phenotypes as compared with normal. In addition, significantly increased m-RNA expression of TGFB1, P53, and FASLG along with significant down-regulation of VEGFA were observed. Expression of phosphorylated P53 at the S15 position and phosphorylated RAD17 at S635 was observed in cases with spermatogenic impairment at the translational level. CONCLUSION(S): The results clearly indicate increased levels of apoptosis along with its other regulatory factors. The balance between pro- (BAX and BAK) and antiapoptotic (BCL2 and BCLW) genes was disturbed, which may lead to altered apoptosis. Therefore, altered regulation of apoptosis might be associated with impaired spermatogenesis, eventually leading to male infertility.
OBJECTIVE: To dissect the role of the apoptotic pathway and its regulation in the pathogenesis of male infertility in nonobstructive azoospermia. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Sixty-three infertile azoospermicpatients with different histologic phenotypes were recruited (obstructive azoospermia, n = 16; hypospermatogenesis, n = 11; maturation arrest, n = 15; Sertoli cell only, n = 21). INTERVENTION(S): Testicular biopsies for histopathologic and expression analysis. MAIN OUTCOME MEASURE(S): Expression analysis by quantitative reverse transcription-polymerase chain reaction, protein localization by immunohistochemistry and apoptotic proteome array. RESULT(S): Results showed significantly increased expression of proapoptotic proteins like BAX, BAD, and BAK and comparatively lowered expression of antiapoptotic BCL2 and BCLW. Immunostaining revealed increased active caspase-3 activity and more TUNEL-positive cells in different impaired phenotypes as compared with normal. In addition, significantly increased m-RNA expression of TGFB1, P53, and FASLG along with significant down-regulation of VEGFA were observed. Expression of phosphorylated P53 at the S15 position and phosphorylated RAD17 at S635 was observed in cases with spermatogenic impairment at the translational level. CONCLUSION(S): The results clearly indicate increased levels of apoptosis along with its other regulatory factors. The balance between pro- (BAX and BAK) and antiapoptotic (BCL2 and BCLW) genes was disturbed, which may lead to altered apoptosis. Therefore, altered regulation of apoptosis might be associated with impaired spermatogenesis, eventually leading to male infertility.
Authors: Yongtong Zhu; Junting Liu; Weiqing Zhang; Jiamin Wu; Wenfeng Li; Huixi Li; Qingjun Chu; Chen Luo Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2019-09-30
Authors: Marco D'Aurora; Alberto Ferlin; Andrea Garolla; Sara Franchi; Laura D'Onofrio; Oriana Trubiani; Giandomenico Palka; Carlo Foresta; Liborio Stuppia; Valentina Gatta Journal: Sci Rep Date: 2017-03-31 Impact factor: 4.379