Table 2.

Gene descriptions of top 35 DEGs between WT & ArKO mice of both sexes. Gene name, protein name, description, and fold change in female from male counterpart for each genotype for genes expressed in Fig. 4a.

Gene	Protein	Description	Fold change in WT	Fold change in ArKO
Ddx3y	ATP-dependent RNA helicase Ddx3y	Involved in ATP binding, hydrolysis, RNA binding, and the formation of intramolecular interactions. Mutations may result in male infertility.	13.91	13.73
Kdm5d	Lysine Demthylase 5D	Linked with spermatogenic failure.	13.77	13.50
Eif2s3y	Eukaryotic translation initiation factor 2 subunit 3, Y-linked	Initiator of protein synthesis.	12.24	13.76
Uty	Histone Demethylase UTY	Male-specific histone demethylase. Associated with Kabuki syndrome, a rare autosomal dominant disorder characterized by skeletal abnormalities, short stature, heart defects, and intellectual disability, and has been affiliated with obesity.	12.07	11.90
Tmprss6	Transmembrane Serine Protease 6	May be involved in matrix remodeling in the liver. Hydrolyzes a range of proteins including: type I collagen, fibronectin, and fibrinogen.	1.31
Vcl	Vinculin	Actin filamnet binding protein invovled in cell-matrix and cell-cell adhesion.	0.34
Per3	Period Circadian Regulator 3	CLOCK gene; regulates circadian rhythm impacting metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, renal function, and locomotor activity.	0.33
Shkbpl	SH3KBP1 Binding Protein 1	Positive regulation of epidermal growth factor receptor signaling pathway.	0.31
Scara3	Scavenger Receptor Class A Member 3	Macrophage scavenger receptor-like protein. Has been shown to deplete reactive oxygen species and protect the cell from oxidative stress.	0.29
Med25	Mediator Complex Subunit 25	CC; Plays a role in chromatin modification and in preinitiation complex assembly.	0.21
Map3k13	Mitogen-Activated Protein Kinase Kinase Kinase 13	Can phosphorylate and activate MAPK8/JNK, MAP2K7/MKK7, which suggests a role in the JNK signaling pathway.	0.20
Zc3h18	Zinc Finger CCCH-Type Containing 18	Necessary for RNA binding.	0.15
Cep851	Centrosomal Protein 85 Like	A breast cancer antigen.	−0.21
Kdm5c	Lysine-specific demethylase 5C	Demethylates Lysine-4 of histone H3. Associated with two rare forms of congenital mental retardation. Related pathways include chromatin organization and chromatin regulation/acetylation.	−0.21	−0.35
Rpl38	Ribosomal protein L38	Componenet of the 60S subunit of the ribosome.		−0.24
Nabpl	Nucleic Acid Binding Protein 1	Essential for a variety of DNA metabolic processes, including replication, recombination, and detection and repair of damage.	−0.26
Scrg1	Scrapie responsive gene 1	Associated with neurodegenerative changes observed in transmissible spongiform encephalopathies.		−0.34
Slc19a2	Thiamine Transporter 1	Mutations cause thiamin-responsive megaloblastic anemia syndrome (TRMA), an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anemia, and deafness.	−0.35
Jpx	JPX Transcript, XIST Activator	Involved with X-chromosome inactivation.	−0.38	−0.42
Dchs2	Dachsous cadherin-related 2	Likely functions in cell adhesion and may be involved in Alzheimer’s disease, compressive strength index, and appendicular lean mass.		−0.40
Kdm6a	Lysine-specific demethylase 6A	Demethylates Lysine-27 of histone H3. Associated with Kabuki Syndrome. Related pathways are activation of PKN1 to stimulate androgen receptor regulated genes KLK2 and KLK3.	−0.41	−0.45
Ddx3x	ATP-dependent RNA helicase Ddx3x	,In mice expressed in oocytes. Ubiquitously found in 9 days post-conception embryo, at later stages it is restricted to brain and kidney. Associated with neutrophil degranulation in pathway analyses.	−0.43	−0.27
Prkg2	CGMP-Dependent Protein Kinase II	Regulates intestinal secretion, bone growth and renin secretion. Necessary for BH4 synthesis and thus, catecholamine synthesis.	−0.50
Ccnd1	Cyclin D1	Function as regulator of CDK kinases; interacts with tumor suppressor protein Rb; misregulated in cancer.	−0.52
P2ry1	Purinergic Receptor P2Y1	Functions as a receptor for extracellular ATP and ADP.		−0.52
Bche	Butyrylcholinesterase	Aids in the detoxification of poisons including organophosphate nerve agents, pesticides, and the metabolism of cocaine, heroin and aspirin.	−0.56
Grin3a	Glutamate Ionotropic Receptor NMDA Type Subunit 3A	Subunit of the N-methyl-D-aspartate (NMDA) receptors; functions in physiological and pathological processes in the central nervous system	−0.67
Eif2s3x	Eukaryotic translation initiation factor 2 subunit 3, X-linked	Involved in the early steps of protein synthesis. Associated with Mehmo Syndrome, an x-linked intellectual disability characterized by epilepsy, mental retardation, microcephaly, hypogenitalism, and obesity.	−0.74	−0.60
Rnd1	Rho-related GTP-binding protein Rho6	Regulates rearrangements of the actin cytoskeleton in response to extracellular growth factors	−0.75
Mid1	E3 ubiquitin-protein ligase Midline-1	Involved in formation of microtubules in the cytoplasm. Associated with Opitz Gbbb Syndrome, a congenital midline malformation syndrome.		−1.01
Ptger3	Prostaglandin E Receptor 3	Involved in many biological processes including: digestion, kidney reabsorption, and uterine contractions. Also active in the nervous system, blood coagulation, and fever generation.	−1.17
Esr1	Estrogen Receptor 1	Major isoform of the etrogen receptor (i.e., alpha), a nuclear hormone receptor. Essential for sexual development and reproductive function; present in both sexes across species.	−1.27
Ngfr	Tumor Necrosis Factor Receptor Superfamily Member 16	Low-affinity receptor. Can bind NGF, BDNF, NT-3, and NT-4. Signaling pathways include: Apoptosis modulation and signaling and beta-adrenergic signaling.	−1.75
Ebf2	EBF Transcription Factor 2	May be required for the development of dopaminergic neurons.	−2.85
Xist	X Inactive Specific Transcript	Involved in X-chromosome inactivation.	−11.37	−11.99