{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T16:05:35Z","timestamp":1784131535578,"version":"3.55.0"},"reference-count":75,"publisher":"Bioscientifica","issue":"7","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Animal models of enhanced fertility are rare, as most genetically modified mouse models with reproductive phenotype display subfertility or infertility. Here, we describe the ovarian phenotype of the Dummerstorf line 2 (FL2) mouse strain, which exhibits high fertility and has been selectively bred for increased fertility over more than 190 generations. This long-term selection, outbred mouse line almost doubled the litter size to 21.5 (FL2) compared with 11.3 (unselected control line, ctrl), without showing any signs of growth retardation in the offspring. Here, we show that FL2 females ovulate 25.0 oocytes per cycle compared with 13.2 in ctrl. FL2 mice remain in the estrus phase for a shorter period during a 12-day observation period. Follicle-stimulating hormone (FSH) levels are decreased, both in estrus and diestrus, compared with ctrl, whereas luteinizing hormone levels are unaffected. The mRNA expression levels in the pituitary gland correspond to the gonadotropin levels in the blood. Progesterone levels are decreased in estrus in FL2. Hypothalamic expression levels of gonadotropin-releasing hormone (GnRH) are decreased in diestrus. Holistic gene expression analysis indicates complex and differential regulation in estrus and diestrus in ovaries of FL2 compared with ctrl. In particular, genes of the TGF-\u03b2 pathway (such as Bmp3, Bmp7, and Inhba) and the Wnt pathway (such as Sfrp4 and Mkrn1) are differentially expressed in ovaries of FL2 females. These data indicate that reduced activity of the hypothalamic\u2013pituitary\u2013gonadal axis (in particular, lower levels of GnRH, FSH, and progesterone), combined with altered gene transcription in the ovaries, leads to higher ovulation rates in order to achieve the breeding objective of improved fertility.<\/jats:p>","DOI":"10.1530\/ec-26-0242","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T14:43:38Z","timestamp":1782744218000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":0,"title":["Dampened HPG axis activity and altered ovarian gene transcription in Dummerstorf high-fertility mouse line FL2"],"prefix":"10.1530","volume":"15","author":[{"given":"Carolin L M","family":"Ludwig","sequence":"first","affiliation":[{"name":"Research Institute for Farm Animal Biology (FBN) 1 , ,","place":["Dummerstorf, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Bohleber","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Biochemie und Molekularbiologie (IBMB), Uniklinikum, Universit\u00e4t Bonn 2 , ,","place":["Bonn, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Baufeld","sequence":"additional","affiliation":[{"name":"Research Institute for Farm Animal Biology (FBN) 1 , ,","place":["Dummerstorf, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva K","family":"Wirth","sequence":"additional","affiliation":[{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Department of Endocrinology and Metabolism 3 , ,","place":["Berlin, Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin 4 , ,","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Langhammer","sequence":"additional","affiliation":[{"name":"Research Institute for Farm Animal Biology (FBN) 1 , ,","place":["Dummerstorf, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Schweizer","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Biochemie und Molekularbiologie (IBMB), Uniklinikum, Universit\u00e4t Bonn 2 , ,","place":["Bonn, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5430-7740","authenticated-orcid":true,"given":"Marten","family":"Michaelis","sequence":"additional","affiliation":[{"name":"Research Institute for Farm Animal Biology (FBN) 1 , ,","place":["Dummerstorf, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4073-6691","authenticated-orcid":true,"given":"Joachim M","family":"Weitzel","sequence":"additional","affiliation":[{"name":"Research Institute for Farm Animal Biology (FBN) 1 , ,","place":["Dummerstorf, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"2026071511220867000_bib1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1093\/humrep\/deac011","article-title":"The changing tide of human fertility","volume":"37","author":"Aitken","year":"2022","journal-title":"Hum Reprod"},{"key":"2026071511220867000_bib2","doi-asserted-by":"crossref","first-page":"4837","DOI":"10.1210\/endo.137.11.8895354","article-title":"Targeted overexpression of Bcl-2 in ovaries of transgenic mice leads to decreased follicle apoptosis, enhanced folliculogenesis, and increased germ cell tumorigenesis","volume":"137","author":"Hsu","year":"1996","journal-title":"Endocrinology"},{"key":"2026071511220867000_bib3","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/ng.593","article-title":"Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies","volume":"42","author":"Zhu","year":"2010","journal-title":"Nat Genet"},{"key":"2026071511220867000_bib4","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1530\/rep.1.00118","article-title":"Components of litter size in mice after 110 generations of selection","volume":"127","author":"Holt","year":"2004","journal-title":"Reproduction"},{"key":"2026071511220867000_bib5","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s12033-012-9530-y","article-title":"An integrative genomic analysis of the superior fecundity phenotype in QSi5 mice","volume":"53","author":"Wei","year":"2013","journal-title":"Mol Biotechnol"},{"key":"2026071511220867000_bib6","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1530\/REP-20-0563","article-title":"Two mouse lines selected for large litter size display different lifetime fecundities","volume":"161","author":"Langhammer","year":"2021","journal-title":"Reproduction"},{"key":"2026071511220867000_bib7","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1530\/REP-13-0425","article-title":"High-fertility phenotypes: two outbred mouse models exhibit substantially different molecular and physiological strategies warranting improved fertility","volume":"147","author":"Langhammer","year":"2014","journal-title":"Reproduction"},{"key":"2026071511220867000_bib8","first-page":"285","article-title":"Endocrine and molecular factors of increased female reproductive performance in the Dummerstorf high-fertility mouse line FL1","volume":"69","author":"Ludwig","year":"2022","journal-title":"J Mol Endocrinol"},{"key":"2026071511220867000_bib9","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13048-023-01113-5","article-title":"Alterations in gonadotropin, apoptotic and metabolic pathways in granulosa cells warrant superior fertility of the Dummerstorf high fertility mouse line 1","volume":"16","author":"Ludwig","year":"2023","journal-title":"J Ovarian Res"},{"key":"2026071511220867000_bib10","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/BF00264485","article-title":"Selection for fertility in mice \u2013 the selection plateau and how to overcome it","volume":"70","author":"Sch\u00fcler","year":"1985","journal-title":"Theor Appl Genet"},{"key":"2026071511220867000_bib11","doi-asserted-by":"crossref","first-page":"595","DOI":"10.5194\/aab-47-595-2004","article-title":"Model simulations for genetic random drift in the outbred strain Fzt:DU","volume":"47","author":"Dietl","year":"2004","journal-title":"Arch Anim Breed"},{"key":"2026071511220867000_bib12","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0035538","article-title":"Mouse estrous cycle identification tool and images","volume":"7","author":"Byers","year":"2012","journal-title":"PLoS One"},{"key":"2026071511220867000_bib13","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1177\/0192623315570339","article-title":"Vaginal cytology of the laboratory rat and mouse: review and criteria for the staging of the estrous cycle using stained vaginal smears","volume":"43","author":"Cora","year":"2015","journal-title":"Toxicol Pathol"},{"key":"2026071511220867000_bib14","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res"},{"key":"2026071511220867000_bib15","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/30.9.e36","article-title":"Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR","volume":"30","author":"Pfaffl","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"2026071511220867000_bib16","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1262\/jrd.10-021O","article-title":"Endocrine effects of GnRH agonist application to early pregnant gilts","volume":"57","author":"Br\u00fcssow","year":"2011","journal-title":"J Reprod Dev"},{"key":"2026071511220867000_bib17","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1186\/s12864-017-4288-z","article-title":"Selection for female traits of high fertility affects male reproductive performance and alters the testicular transcriptional profile","volume":"18","author":"Michaelis","year":"2017","journal-title":"BMC Genom"},{"key":"2026071511220867000_bib18","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"2026071511220867000_bib19","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1471-2164-10-22","article-title":"BioMart \u2013 biological queries made easy","volume":"10","author":"Smedley","year":"2009","journal-title":"BMC Genom"},{"key":"2026071511220867000_bib20","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"2026071511220867000_bib21","doi-asserted-by":"crossref","first-page":"e1005752","DOI":"10.1371\/journal.pcbi.1005752","article-title":"mixOmics: an R package for 'omics feature selection and multiple data integration","volume":"13","author":"Rohart","year":"2017","journal-title":"PLoS Comput Biol"},{"key":"2026071511220867000_bib22","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780195075540.001.0001","volume-title":"Mouse Genetics \u2013 Concepts and Applications","author":"Silver","year":"1995"},{"key":"2026071511220867000_bib23","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s12915-022-01248-9","article-title":"Genomic characterization of the world\u2019s longest selection experiment in mouse reveals the complexity of polygenic traits","volume":"20","author":"Palma-Vera","year":"2022","journal-title":"BMC Biol"},{"key":"2026071511220867000_bib24","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/ng0993-83","article-title":"Primary amenorrhoea and infertility due to a mutation in the beta-subunit of follicle-stimulating hormone","volume":"5","author":"Matthews","year":"1993","journal-title":"Nat Genet"},{"key":"2026071511220867000_bib25","first-page":"264","article-title":"Development of recombinant follicle-stimulating hormone for the superovulation of cattle: a review","volume":"12","author":"Zhang","year":"2025","journal-title":"Vet Sci"},{"key":"2026071511220867000_bib26","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.anireprosci.2004.05.013","article-title":"Endocrine and paracrine control of follicular development and ovulation rate in farm species","volume":"82-83","author":"Hunter","year":"2004","journal-title":"Anim Reprod Sci"},{"key":"2026071511220867000_bib27","doi-asserted-by":"crossref","first-page":"4432","DOI":"10.1210\/en.2007-0046","article-title":"Rising follicle-stimulating hormone levels with age accelerate female reproductive failure","volume":"148","author":"McTavish","year":"2007","journal-title":"Endocrinology"},{"key":"2026071511220867000_bib28","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/78161","article-title":"Insertion of Inhbb into the Inhba locus rescues the Inhba-null phenotype and reveals new activin functions","volume":"25","author":"Brown","year":"2000","journal-title":"Nat Genet"},{"key":"2026071511220867000_bib29","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1210\/me.2007-0146","article-title":"Intraovarian activins are required for female fertility","volume":"21","author":"Pangas","year":"2007","journal-title":"Mol Endocrinol"},{"key":"2026071511220867000_bib30","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1095\/biolreprod.106.059121","article-title":"Impaired progesterone production in Nr5a2+\/\u2212 mice leads to a reduction in female reproductive function","volume":"77","author":"Labelle-Dumais","year":"2007","journal-title":"Biol Reprod"},{"key":"2026071511220867000_bib31","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1210\/en.2008-1519","article-title":"Absence of nuclear receptors for oxysterols liver X receptor induces ovarian hyperstimulation syndrome in mice","volume":"150","author":"Mouzat","year":"2009","journal-title":"Endocrinology"},{"key":"2026071511220867000_bib32","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1210\/me.2006-0277","article-title":"Multiple roles of the nuclear receptors for oxysterols liver X receptor to maintain male fertility","volume":"21","author":"Volle","year":"2007","journal-title":"Mol Endocrinol"},{"key":"2026071511220867000_bib33","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1262\/jrd.18125","article-title":"Reproductive phenotypes in mice with targeted disruption of the 20\u03b1-hydroxysteroid dehydrogenase gene","volume":"53","author":"Ishida","year":"2007","journal-title":"J Reprod Dev"},{"key":"2026071511220867000_bib34","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1210\/me.2005-0462","article-title":"Premature luteinization and cumulus cell defects in ovarian-specific Smad4 knockout mice","volume":"20","author":"Pangas","year":"2006","journal-title":"Mol Endocrinol"},{"key":"2026071511220867000_bib35","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0925-4773(02)00237-X","article-title":"SMAD1 signaling is critical for initial commitment of germ cell lineage from mouse epiblast","volume":"118","author":"Hayashi","year":"2002","journal-title":"Mech Dev"},{"key":"2026071511220867000_bib36","first-page":"3609","article-title":"Mouse embryos lacking Smad1 signals display defects in extra-embryonic tissues and germ cell formation","volume":"128","author":"Tremblay","year":"2001","journal-title":"Dev Camb Engl"},{"key":"2026071511220867000_bib37","doi-asserted-by":"crossref","first-page":"4975","DOI":"10.1073\/pnas.1721957115","article-title":"COBLL1 modulates cell morphology and facilitates androgen receptor genomic binding in advanced prostate cancer","volume":"115","author":"Takayama","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026071511220867000_bib38","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1210\/en.2016-1629","article-title":"BMP7 induces uterine receptivity and blastocyst attachment","volume":"158","author":"Monsivais","year":"2017","journal-title":"Endocrinology"},{"key":"2026071511220867000_bib39","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1530\/REP-17-0436","article-title":"Regulation of porcupine-dependent Wnt signaling is essential for uterine development and function","volume":"155","author":"Farah","year":"2018","journal-title":"Reproduction"},{"key":"2026071511220867000_bib40","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nature10192","article-title":"Fancd2 counteracts the toxic effects of naturally produced aldehydes in mice","volume":"475","author":"Langevin","year":"2011","journal-title":"Nature"},{"key":"2026071511220867000_bib41","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1093\/humrep\/deaa020","article-title":"Non-classic cytochrome P450 oxidoreductase deficiency strongly linked with menstrual cycle disorders and female infertility as primary manifestations","volume":"35","author":"Papadakis","year":"2020","journal-title":"Hum Reprod"},{"key":"2026071511220867000_bib42","doi-asserted-by":"crossref","first-page":"829","DOI":"10.21451\/1984-3143-AR2018-0146","article-title":"Transforming growth factor-beta family members are regulated during induced luteolysis in cattle","volume":"16","author":"Haas","year":"2019","journal-title":"Anim Reprod"},{"key":"2026071511220867000_bib43","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1128\/MCB.23.1.272-279.2003","article-title":"Carcinoembryonic antigen-related cell adhesion molecule 10 expressed specifically early in pregnancy in the decidua is dispensable for normal murine development","volume":"23","author":"Finkenzeller","year":"2003","journal-title":"Mol Cell Biol"},{"key":"2026071511220867000_bib44","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0089547","article-title":"The catalytic subunit of the system L1 amino acid transporter (slc7a5) facilitates nutrient signalling in mouse skeletal muscle","volume":"9","author":"Poncet","year":"2014","journal-title":"PLoS One"},{"key":"2026071511220867000_bib45","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1002\/dvdy.21046","article-title":"Global growth deficiencies in mice lacking the ribosomal protein HIP\/RPL29","volume":"236","author":"Kirn-Safran","year":"2007","journal-title":"Dev Dyn"},{"key":"2026071511220867000_bib46","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3389\/fendo.2018.00119","article-title":"Potential functions of IGFBP-2 for ovarian folliculogenesis and steroidogenesis","volume":"9","author":"Spitschak","year":"2018","journal-title":"Front Endocrinol"},{"key":"2026071511220867000_bib47","doi-asserted-by":"crossref","first-page":"5205","DOI":"10.1210\/endo.139.12.6367","article-title":"Expression of mouse ovarian insulin growth factor system components during follicular development and Atresia","volume":"139","author":"Wandji","year":"1998","journal-title":"Endocrinology"},{"key":"2026071511220867000_bib48","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1093\/hmg\/ddm264","article-title":"Lack of fibulin-3 causes early aging and herniation, but not macular degeneration in mice","volume":"16","author":"McLaughlin","year":"2007","journal-title":"Hum Mol Genet"},{"key":"2026071511220867000_bib49","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1095\/biolreprod.108.070649","article-title":"Mouse TEX14 is required for embryonic germ cell intercellular bridges but not female fertility","volume":"80","author":"Greenbaum","year":"2009","journal-title":"Biol Reprod"},{"key":"2026071511220867000_bib50","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.trsl.2020.10.009","article-title":"Novel role of CXCL14 in modulating STAR expression in luteinized granulosa cells: implication for progesterone synthesis in PCOS patients","volume":"230","author":"Qi","year":"2021","journal-title":"Transl Res"},{"key":"2026071511220867000_bib51","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3390\/cells15020124","article-title":"Estrogen-induced hypermethylation silencing of RPS2 and TMEM177 inhibits energy metabolism and reduces the survival of CRC cells","volume":"15","author":"Abi","year":"2026","journal-title":"Cells"},{"key":"2026071511220867000_bib52","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.1038\/ncomms3816","article-title":"Mutations in the Gabrb1 gene promote alcohol consumption through increased tonic inhibition","volume":"4","author":"Anstee","year":"2013","journal-title":"Nat Commun"},{"key":"2026071511220867000_bib53","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.mad.2016.02.013","article-title":"Infertility and recurrent miscarriage with complex II deficiency-dependent mitochondrial oxidative stress in animal models","volume":"155","author":"Ishii","year":"2016","journal-title":"Mech Ageing Dev"},{"key":"2026071511220867000_bib54","doi-asserted-by":"crossref","first-page":"8529","DOI":"10.3390\/ijms26178529","article-title":"Protease-activated receptor F2R is a potential target for new diagnostic\/prognostic and treatment applications for patients with ovarian cancer","volume":"26","author":"Khetan","year":"2025","journal-title":"Int J Mol Sci"},{"key":"2026071511220867000_bib55","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41419-021-04374-4","article-title":"CPEB3 deficiency in mice affect ovarian follicle development and causes premature ovarian insufficiency","volume":"13","author":"Fang","year":"2021","journal-title":"Cell Death Dis"},{"key":"2026071511220867000_bib56","doi-asserted-by":"crossref","first-page":"17008","DOI":"10.1523\/JNEUROSCI.3043-13.2013","article-title":"Deletion of CPEB3 enhances hippocampus-dependent memory via increasing expressions of PSD95 and NMDA receptors","volume":"33","author":"Chao","year":"2013","journal-title":"J Neurosci"},{"key":"2026071511220867000_bib57","doi-asserted-by":"crossref","first-page":"3942","DOI":"10.1073\/pnas.93.9.3942","article-title":"Metalloelastase is required for macrophage-mediated proteolysis and matrix invasion in mice","volume":"93","author":"Shipley","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026071511220867000_bib58","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1210\/en.2019-00212","article-title":"SFRP4 is a negative regulator of ovarian follicle development and female fertility","volume":"160","author":"Zamberlam","year":"2019","journal-title":"Endocrinology"},{"key":"2026071511220867000_bib59","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1210\/en.2010-1351","article-title":"Genetic ablation of Sfrp4 in mice does not affect serum phosphate homeostasis","volume":"152","author":"Christov","year":"2011","journal-title":"Endocrinology"},{"key":"2026071511220867000_bib60","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1095\/biolreprod.113.116947","article-title":"Loss of the proapoptotic BH3-only protein BCL-2 modifying factor prolongs the fertile life span in female mice","volume":"90","author":"Liew","year":"2014","journal-title":"Biol Reprod"},{"key":"2026071511220867000_bib61","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.3390\/cancers16152676","article-title":"IFNgamma-Induced Bcl3, PD-L1 and IL-8 signaling in ovarian cancer: mechanisms and clinical significance","volume":"16","author":"Reddy","year":"2024","journal-title":"Cancers"},{"key":"2026071511220867000_bib62","doi-asserted-by":"crossref","first-page":"314","DOI":"10.21037\/atm-22-393","article-title":"RAF1 mediates the FSH signaling pathway as a downstream molecule to stimulate estradiol synthesis and secretion in mouse ovarian granulosa cells","volume":"10","author":"Luo","year":"2022","journal-title":"Ann Transl Med"},{"key":"2026071511220867000_bib63","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1210\/me.2003-0323","article-title":"Aberrant intracellular cholesterol transport disrupts pituitary and ovarian function","volume":"18","author":"G\u00e9vry","year":"2004","journal-title":"Mol Endocrinol"},{"key":"2026071511220867000_bib64","doi-asserted-by":"crossref","first-page":"11535","DOI":"10.1073\/pnas.0903011106","article-title":"Loss of phosphatidylinositol 4-kinase 2\u03b1 activity causes late onset degeneration of spinal cord axons","volume":"106","author":"Simons","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026071511220867000_bib65","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1093\/nsr\/nwaa023","article-title":"MKRN3 regulates the epigenetic switch of mammalian puberty via ubiquitination of MBD3","volume":"7","author":"Li","year":"2020","journal-title":"Natl Sci Rev"},{"key":"2026071511220867000_bib66","article-title":"A novel role of IGFBP7 in mouse uterus: regulating uterine receptivity through Th1\/Th2 lymphocyte balance and decidualization","volume":"7","author":"Liu","year":"2012","journal-title":"PLoS One"},{"key":"2026071511220867000_bib67","doi-asserted-by":"crossref","first-page":"7397","DOI":"10.1038\/s41598-021-86956-y","article-title":"CXCL12 enhances pregnancy outcome via improvement of endometrial receptivity in mice","volume":"11","author":"Koo","year":"2021","journal-title":"Sci Rep"},{"key":"2026071511220867000_bib68","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.ydbio.2006.04.442","article-title":"Dose-dependent Smad1, Smad5 and Smad8 signaling in the early mouse embryo","volume":"296","author":"Arnold","year":"2006","journal-title":"Dev Biol"},{"key":"2026071511220867000_bib69","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1101\/gad.1202604","article-title":"In vivo convergence of BMP and MAPK signaling pathways: impact of differential Smad1 phosphorylation on development and homeostasis","volume":"18","author":"Aubin","year":"2004","journal-title":"Genes Dev"},{"key":"2026071511220867000_bib70","doi-asserted-by":"crossref","DOI":"10.1210\/endocr\/bqac043","article-title":"BMP\/SMAD1\/5 signaling in the endometrial epithelium is essential for receptivity and early pregnancy","volume":"163","author":"Tang","year":"2022","journal-title":"Endocrinology"},{"key":"2026071511220867000_bib71","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1210\/jc.2018-00544","article-title":"The HMGA2-IMP2 pathway promotes granulosa cell proliferation in polycystic ovary syndrome","volume":"104","author":"Li","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"2026071511220867000_bib72","doi-asserted-by":"crossref","DOI":"10.1093\/g3journal\/jkab417","article-title":"Hmga2 deficiency is associated with allometric growth retardation, infertility, and behavioral abnormalities in mice","volume":"12","author":"Lee","year":"2022","journal-title":"G3"},{"key":"2026071511220867000_bib73","first-page":"4279","article-title":"The chemokine SDF1\/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival","volume":"130","author":"Molyneaux","year":"2003","journal-title":"Dev Camb Engl"},{"key":"2026071511220867000_bib74","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1111\/j.1600-0897.2005.00307.x","article-title":"The chemokine SDF-1\/CXCL12 contributes to T lymphocyte recruitment in human pre-ovulatory follicles and coordinates with lymphocytes to increase granulosa cell survival and embryo quality","volume":"54","author":"Kryczek","year":"2005","journal-title":"Am J Reprod Immunol"},{"key":"2026071511220867000_bib75","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.placenta.2022.09.003","article-title":"Matrix metalloproteinase -12: a marker of preeclampsia?","volume":"129","author":"Yakovleva","year":"2022","journal-title":"Placenta"}],"container-title":["Endocrine Connections"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ec.bioscientifica.com\/view\/journals\/ec\/aop\/EC-26-0242\/EC-26-0242.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ec.bioscientifica.com\/downloadpdf\/journals\/ec\/aop\/EC-26-0242\/EC-26-0242.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/ec\/article-pdf\/doi\/10.1530\/EC-26-0242\/519653\/ec-26-0242.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/ec\/article-pdf\/doi\/10.1530\/EC-26-0242\/519653\/ec-26-0242.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T15:22:20Z","timestamp":1784128940000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/ec\/article\/15\/7\/e260242\/77503\/Dampened-HPG-axis-activity-and-altered-ovarian"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,29]]},"references-count":75,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7,1]]}},"URL":"https:\/\/doi.org\/10.1530\/ec-26-0242","relation":{},"ISSN":["2049-3614"],"issn-type":[{"value":"2049-3614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,29]]},"article-number":"e260242"}}