# DNA Methylation in the Ovary and Uterus of Mammalian Animal Models: Implications for Reproductive Function **Authors:** Oliwia Serej, Magdalena K. Kowalik, Robert Rekawiecki PMC · DOI: 10.3390/genes17020228 · Genes · 2026-02-11 ## TL;DR This paper reviews how DNA methylation affects reproductive functions in mammalian ovaries and uteruses, highlighting its role in fertility and potential applications in veterinary medicine. ## Contribution The paper provides a comprehensive review of DNA methylation and demethylation mechanisms in reproductive tissues, emphasizing their implications for fertility and reproductive health. ## Key findings - DNA methylation regulates ovarian development and uterine function during pregnancy in mammals. - DNMTs and TET enzymes are key players in methylation and demethylation processes affecting folliculogenesis and oocyte maturation. - Understanding these epigenetic mechanisms could improve fertility preservation and reproductive health in animals. ## Abstract DNA methylation is a key epigenetic modification that regulates gene expression and maintains genome stability, particularly in mammalian reproductive tissues. This review summarizes the current knowledge of DNA methylation and demethylation fluctuations with a specific focus on the regulation of ovarian development and uterine function during pregnancy. This modification primarily occurs at CpG-rich regions and is catalyzed by DNA methyltransferases (DNMTs): DNMT1 maintains existing patterns during replication, while DNMT3A and DNMT3B establish de novo methylation. Demethylation is mediated by ten-eleven translocation enzymes (TET1, TET2, and TET3), which oxidize 5-methylcytosine, ultimately replacing it with unmethylated cytosine. These processes play essential roles in folliculogenesis, oocyte maturation, steroidogenesis, and tissue-specific gene regulation. Understanding these epigenetic mechanisms provides important insights into veterinary medicine and offers potential applications in fertility preservation across diverse mammalian species. Consequently, further research is essential to elucidate the clinical implications of these epigenetic processes for improving reproductive health outcomes in animals. ## Linked entities - **Genes:** DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786], DNMT3A (DNA methyltransferase 3 alpha) [NCBI Gene 1788], DNMT3B (DNA methyltransferase 3 beta) [NCBI Gene 1789], TET1 (tet methylcytosine dioxygenase 1) [NCBI Gene 80312], TET2 (tet methylcytosine dioxygenase 2) [NCBI Gene 54790], TET3 (tet methylcytosine dioxygenase 3) [NCBI Gene 200424] ## Full-text entities - **Genes:** Dnmt1 (DNA methyltransferase 1) [NCBI Gene 13433] {aka Cxxc9, Dnmt, Dnmt1o, MCMT, MTase, Met-1}, HSD3B1 (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1) [NCBI Gene 3283] {aka 3BETAHSD, HSD3B, HSDB3, HSDB3A, SDR11E1}, CYP19A1 (cytochrome P450 family 19 subfamily A member 1) [NCBI Gene 281740] {aka CYP19, CYP19P1}, TRDMT1 (tRNA aspartic acid methyltransferase 1) [NCBI Gene 1787] {aka DMNT2, DNMT2, MHSAIIP, PUMET, RNMT1}, ELF5 (E74 like ETS transcription factor 5) [NCBI Gene 2001] {aka ESE2}, CXXC4 (CXXC finger protein 4) [NCBI Gene 80319] {aka IDAX}, NANOG (Nanog homeobox) [NCBI Gene 79923], BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, DNMT1 (DNA methyltransferase 1) [NCBI Gene 281119] {aka DNMT}, PGR (progesterone receptor) [NCBI Gene 100848466], TET3 (tet methylcytosine dioxygenase 3) [NCBI Gene 200424] {aka BEFAHRS, hCG_40738}, ESR1 (estrogen receptor 1) [NCBI Gene 407238], CYP11A1 (cytochrome P450 family 11 subfamily A member 1) [NCBI Gene 414838], DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786] {aka ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT}, ANGPTL4 (angiopoietin like 4) [NCBI Gene 509963], PCNA (proliferating cell nuclear antigen) [NCBI Gene 5111] {aka ATLD2}, DNMT3L (DNA methyltransferase 3 like) [NCBI Gene 29947], DNMT3A (DNA methyltransferase 3 alpha) [NCBI Gene 359716], TDG (thymine DNA glycosylase) [NCBI Gene 6996] {aka hTDG}, DNMT3B (DNA methyltransferase 3 beta) [NCBI Gene 353354], STAR (steroidogenic acute regulatory protein) [NCBI Gene 395421], COL7A1 (collagen type VII alpha 1 chain) [NCBI Gene 507133], TET2 (tet methylcytosine dioxygenase 2) [NCBI Gene 538481], TET2 (tet methylcytosine dioxygenase 2) [NCBI Gene 54790] {aka IMD75, KIAA1546, MDS}, STAR (steroidogenic acute regulatory protein) [NCBI Gene 281507], INHA (inhibin subunit alpha) [NCBI Gene 281254], Dnmt3b (DNA methyltransferase 3B) [NCBI Gene 13436] {aka MmuIIIB}, SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657] {aka ANOP3, MCOPS3}, TET1 (tet methylcytosine dioxygenase 1) [NCBI Gene 80312] {aka CXXC6, LCX, bA119F7.1}, DNMT3A (DNA methyltransferase 3 alpha) [NCBI Gene 1788] {aka DNMT3A2, HESJAS, M.HsaIIIA, TBRS}, CYP19A1 (cytochrome P450 family 19 subfamily A member 1) [NCBI Gene 1588] {aka ARO, ARO1, CPV1, CYAR, CYP19, CYPXIX}, Tet3 (tet methylcytosine dioxygenase 3) [NCBI Gene 194388] {aka B430006D22Rik, D230004J03Rik}, COL1A2 (collagen type I alpha 2 chain) [NCBI Gene 282188], DNMT3B (DNA methyltransferase 3 beta) [NCBI Gene 1789] {aka FSHD4, ICF, ICF1, M.HsaIIIB}, CDKN1A (cyclin dependent kinase inhibitor 1A) [NCBI Gene 1026] {aka CAP20, CDKN1, CIP1, MDA-6, P21, SDI1}, ASCL2 (achaete-scute family bHLH transcription factor 2) [NCBI Gene 664650] {aka MASH2}, Tet1 (tet methylcytosine dioxygenase 1) [NCBI Gene 52463] {aka 2510010B09Rik, Cxxc6, D10Ertd17e, LCX, mKIAA1676}, HSD3B1 (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1) [NCBI Gene 281824] {aka HSD3B}, Tet2 (tet methylcytosine dioxygenase 2) [NCBI Gene 214133] {aka Ayu17-449, E130014J05Rik, mKIAA1546}, Dnmt3l (DNA methyltransferase 3-like) [NCBI Gene 54427] {aka D6Ertd14e, ecat7}, TET1 (tet methylcytosine dioxygenase 1) [NCBI Gene 513640], CYP11A1 (cytochrome P450 family 11 subfamily A member 1) [NCBI Gene 338048] {aka CYP11A, CYPXIA1, P450(scc), P450scc}, TET3 [NCBI Gene 538707], Dnmt3a (DNA methyltransferase 3A) [NCBI Gene 13435] {aka MmuIIIA}, POU5F1 (POU class 5 homeobox 1) [NCBI Gene 5460] {aka OCT3, OCT4, OCT4Borf1, OTF-3, OTF3, OTF4} - **Diseases:** age-related infertility (MESH:D007246), endometrial cancer (MESH:D016889), PCOS (MESH:D011085), ovarian disease (MESH:D010049), ovarian and mammary gland cancers (MESH:D010051), pregnancy loss (MESH:D000022), luteal insufficiency (MESH:D000309), reproductive system malignancies (MESH:D009369), endometriosis (MESH:D004715), CL (MESH:D010048), injury to (MESH:D014947), ICM (MESH:C536030), reproductive disorders (MESH:D060737), imprinting (MESH:C567357), developmental defects (MESH:D000094602) - **Chemicals:** 5-formylcytosine (MESH:C560973), alpha-ketoglutarate (MESH:D007656), 5-hydroxymethylcytosine (MESH:C011865), methoxychlor (MESH:D008731), 2OG (-), 5'-azacytidine (MESH:D001374), P4 (MESH:C015586), LH (MESH:D007986), steroid (MESH:D013256), E2 (MESH:D004958), oxygen (MESH:D010100), vinclozolin (MESH:C025643), 5-carboxycytosine (MESH:C000618843), 5-aza-2'-deoxycytidine (MESH:D000077209), progesterone (MESH:D011374), S-adenosylmethionine (MESH:D012436), 5-methylcytosine (MESH:D044503), cytosine (MESH:D003596) - **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Gallus gallus (bantam, species) [taxon 9031], Bos taurus (bovine, species) [taxon 9913], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Mus musculus (house mouse, species) [taxon 10090], Sus scrofa (pig, species) [taxon 9823], Ovis aries (domestic sheep, species) [taxon 9940] - **Mutations:** cytosine at position 38 ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12940562/full.md ## Figures 3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12940562/full.md ## References 74 references — full list in the complete paper: https://tomesphere.com/paper/PMC12940562/full.md --- Source: https://tomesphere.com/paper/PMC12940562