Jiang Feng, Zhu Yong, Chen Ying, Tang Xiaofeng, Liu Liu, Chen Guowu, Liu Yulin, Sun Xiaoxi
Shanghai JIAI Genetics & IVF Institute-China USA Center, Shanghai, China.
Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
J Int Med Res. 2021 Mar;49(3):300060521999527. doi: 10.1177/0300060521999527.
This was a prospective study to investigate whether progesterone affects sperm activity by regulating the cyclic AMP-protein kinase A (cAMP-PKA) signalling pathway via α/β hydrolase domain-containing protein 2 (ABHD2).
Spermatozoa were collected from healthy and infertile men (with oligoasthenospermia or abnormal acrosome; n = 30/group). The expression of and mutations in were detected by quantitative PCR, western blot, and gene sequencing. The expression of in the presence of progesterone was detected in all groups, and cAMP and PKA levels were detected by ELISA in fertile men after treatment with ABHD2 antibody and PKA inhibitor H-89, respectively.
Expression of ABHD2 mRNA and protein were reduced in spermatozoa from infertile compared with fertile men. Four gene mutation sites were detected in spermatozoa from the infertile groups. Progesterone increased mRNA and protein levels of ABHD2 in healthy spermatozoa but not in spermatozoa from infertile men. The levels of cAMP and PKA were increased by progesterone in healthy spermatozoa, and the progesterone-increased cAMP and PKA were decreased by ABHD2 antibody and H-89, respectively.
Progesterone regulates the ABHD2-mediated cAMP-PKA signalling pathway in healthy spermatozoa, which provides a new target for clinical diagnosis and treatment of infertility.
本研究为前瞻性研究，旨在探究孕酮是否通过含α/β水解酶结构域蛋白2（ABHD2）调节环磷酸腺苷 - 蛋白激酶A（cAMP-PKA）信号通路来影响精子活性。
从健康男性和不育男性（少弱精子症或顶体异常；每组n = 30）收集精子。通过定量PCR、蛋白质印迹和基因测序检测ABHD2的表达和突变情况。检测所有组在孕酮存在下ABHD2的表达，并用ELISA分别检测ABHD2抗体和PKA抑制剂H-89处理后可育男性精子中的cAMP和PKA水平。
与可育男性相比，不育男性精子中ABHD2 mRNA和蛋白表达降低。在不育组精子中检测到4个基因突变位点。孕酮可增加健康精子中ABHD2的mRNA和蛋白水平，但不育男性精子中未出现此现象。孕酮可增加健康精子中cAMP和PKA水平，而ABHD2抗体和H-89分别降低了孕酮增加的cAMP和PKA水平。
孕酮调节健康精子中ABHD2介导的cAMP-PKA信号通路，为不孕症的临床诊断和治疗提供了新靶点。
