Name	Male infertility
ICD	ICD-11: GB04

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	m6A modification promoted translation of PPM1A (protein phosphatase 1A, magnesium dependent, alpha isoform), a negative AMP-activated protein kinase (AMPK) regulator, but decreased expression of Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) (calcium/calmodulin-dependent protein kinase kinase 2, beta), a positive AMPK regulator, by reducing its RNA stability. Similar regulation of METTL14, ALKBH5, and m6A was also observed in LCs upon treatment with human chorionic gonadotropin (HsCG). Knock down of YTHDF1 failed to change the expression of CAMKK2 Providing insight into novel therapeutic strategies by exploiting m6A RNA methylation as targets for treating azoospermatism and oligospermatism patients with reduction in serum testosterone. knock down of YTHDF2 increased expression of Camkk2 at both mRNA and protein levels to a similar extent as knock down of METTL14 in both TM3 cells and primary LCs.
Responsed Disease	Azoospermia [ICD-11: GB04.0]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	RNA stability
	Cell autophagy
In-vitro Model	TM3	Normal	Mus musculus	CVCL_4326
In-vivo Model	Male SPF BALB/c mice (qls02-0202) were purchased from Qinglongshan animal breeding farm. Mice were sacrificed by CO2 asphyxiation and testes were obtained for following histopathological analyses.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	m6A modification promoted translation of PPM1A (protein phosphatase 1A, magnesium dependent, alpha isoform), a negative AMP-activated protein kinase (AMPK) regulator, but decreased expression of Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) (calcium/calmodulin-dependent protein kinase kinase 2, beta), a positive AMPK regulator, by reducing its RNA stability. Similar regulation of METTL14, ALKBH5, and m6A was also observed in LCs upon treatment with human chorionic gonadotropin (HsCG). Knock down of YTHDF1 failed to change the expression of CAMKK2 Providing insight into novel therapeutic strategies by exploiting m6A RNA methylation as targets for treating azoospermatism and oligospermatism patients with reduction in serum testosterone.
Responsed Disease	Azoospermia [ICD-11: GB04.0]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	RNA stability
	Cell autophagy
In-vitro Model	TM3	Normal	Mus musculus	CVCL_4326
In-vivo Model	Male SPF BALB/c mice (qls02-0202) were purchased from Qinglongshan animal breeding farm. Mice were sacrificed by CO2 asphyxiation and testes were obtained for following histopathological analyses.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	Over-expression (OE) of YTHDC2 increased G2/mitotic-specific cyclin-B2 (CCNB2) levels, reduced cell cycle arrest, and improved reproductive toxicity after Mn exposure.
Responsed Disease	Male infertility [ICD-11: GB04]
Target Regulator	YTH domain-containing protein 2 (YTHDC2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Block the G2/M phase
In-vitro Model	GC-1 spg	Normal	Mus musculus	CVCL_8872
In-vivo Model	Mice in the control group received an i.p. injections of 0.9% NaCl. Mice in the low, medium, and high Mn groups received i.p. injections of 12.5, 25, and 50 mg/kg MnCl2. The volume of administration was 5 mL/kg body weight. The injection was given daily for 2 weeks.

In total 4 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	m6A modification promoted translation of Protein phosphatase 1A (PPM1A) (protein phosphatase 1A, magnesium dependent, alpha isoform), a negative AMP-activated protein kinase (AMPK) regulator, but decreased expression of CAMKK2 (calcium/calmodulin-dependent protein kinase kinase 2, beta), a positive AMPK regulator, by reducing its RNA stability. Similar regulation of METTL14, ALKBH5, and m6A was also observed in LCs upon treatment with human chorionic gonadotropin (HsCG). Knock down of YTHDF1 failed to change the expression of CAMKK2 Providing insight into novel therapeutic strategies by exploiting m6A RNA methylation as targets for treating azoospermatism and oligospermatism patients with reduction in serum testosterone. Rapamycin could effectively inhibit phosphorylation of RPS6KB1.
Responsed Disease	Azoospermia [ICD-11: GB04.0]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	RNA stability
	Cell autophagy
In-vitro Model	TM3	Normal	Mus musculus	CVCL_4326
In-vivo Model	Male SPF BALB/c mice (qls02-0202) were purchased from Qinglongshan animal breeding farm. Mice were sacrificed by CO2 asphyxiation and testes were obtained for following histopathological analyses.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	m6A modification promoted translation of Protein phosphatase 1A (PPM1A) (protein phosphatase 1A, magnesium dependent, alpha isoform), a negative AMP-activated protein kinase (AMPK) regulator, but decreased expression of CAMKK2 (calcium/calmodulin-dependent protein kinase kinase 2, beta), a positive AMPK regulator, by reducing its RNA stability. Similar regulation of METTL14, ALKBH5, and m6A was also observed in LCs upon treatment with human chorionic gonadotropin (HsCG). Knock down of YTHDF1 failed to change the expression of CAMKK2 Providing insight into novel therapeutic strategies by exploiting m6A RNA methylation as targets for treating azoospermatism and oligospermatism patients with reduction in serum testosterone.
Responsed Disease	Male infertility [ICD-11: GB04]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	RNA stability
	Cell autophagy
In-vitro Model	TM3	Normal	Mus musculus	CVCL_4326
In-vivo Model	Male SPF BALB/c mice (qls02-0202) were purchased from Qinglongshan animal breeding farm. Mice were sacrificed by CO2 asphyxiation and testes were obtained for following histopathological analyses.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	m6A modification promoted translation of Protein phosphatase 1A (PPM1A) (protein phosphatase 1A, magnesium dependent, alpha isoform), a negative AMP-activated protein kinase (AMPK) regulator, but decreased expression of CAMKK2 (calcium/calmodulin-dependent protein kinase kinase 2, beta), a positive AMPK regulator, by reducing its RNA stability. Similar regulation of METTL14, ALKBH5, and m6A was also observed in LCs upon treatment with human chorionic gonadotropin (HsCG). Knock down of YTHDF1 failed to change the expression of CAMKK2 Providing insight into novel therapeutic strategies by exploiting m6A RNA methylation as targets for treating azoospermatism and oligospermatism patients with reduction in serum testosterone.
Responsed Disease	Azoospermia [ICD-11: GB04.0]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	RNA stability
	Cell autophagy
In-vitro Model	TM3	Normal	Mus musculus	CVCL_4326
In-vivo Model	Male SPF BALB/c mice (qls02-0202) were purchased from Qinglongshan animal breeding farm. Mice were sacrificed by CO2 asphyxiation and testes were obtained for following histopathological analyses.
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	m6A modification promoted translation of Protein phosphatase 1A (PPM1A) (protein phosphatase 1A, magnesium dependent, alpha isoform), a negative AMP-activated protein kinase (AMPK) regulator, but decreased expression of CAMKK2 (calcium/calmodulin-dependent protein kinase kinase 2, beta), a positive AMPK regulator, by reducing its RNA stability. Similar regulation of METTL14, ALKBH5, and m6A was also observed in LCs upon treatment with human chorionic gonadotropin (HsCG). Knock down of YTHDF1 failed to change the expression of CAMKK2 Providing insight into novel therapeutic strategies by exploiting m6A RNA methylation as targets for treating azoospermatism and oligospermatism patients with reduction in serum testosterone.
Responsed Disease	Azoospermia [ICD-11: GB04.0]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	RNA stability
	Cell autophagy
In-vitro Model	TM3	Normal	Mus musculus	CVCL_4326
In-vivo Model	Male SPF BALB/c mice (qls02-0202) were purchased from Qinglongshan animal breeding farm. Mice were sacrificed by CO2 asphyxiation and testes were obtained for following histopathological analyses.

Ref 1	m(6)A mRNA methylation regulates testosterone synthesis through modulating autophagy in Leydig cells. Autophagy. 2021 Feb;17(2):457-475. doi: 10.1080/15548627.2020.1720431. Epub 2020 Jan 31.
Ref 2	Protective role of m(6)A binding protein YTHDC2 on CCNB2 in manganese-induced spermatogenesis dysfunction. Chem Biol Interact. 2022 Jan 5;351:109754. doi: 10.1016/j.cbi.2021.109754. Epub 2021 Nov 22.