{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T17:25:13Z","timestamp":1782840313545,"version":"3.54.5"},"reference-count":85,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T00:00:00Z","timestamp":1667174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RUSA 2.0 Research, Innovation and Quality Improvement","award":["C3\/RI&QI\/RUSA-2.0\/Theme-1\/Group-4\/Award\/2021\/52"],"award-info":[{"award-number":["C3\/RI&QI\/RUSA-2.0\/Theme-1\/Group-4\/Award\/2021\/52"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Pituitary gonadotropins directly govern ovarian functions, which are in turn regulated by the ovarian steroid hormones. The precise interplay of gonadotropins and steroid hormones is critical for follicle growth and differentiation. Furthermore, autophagy regulates ovarian follicle differentiation. However, how the high-fat-high fructose (HFD-HF) diet regulates gonadotropins and facilitates autophagy-mediated follicular differentiation in the ovary is obscure. We fed prepubertal rats (PND 25) an HFD-HF diet until PND 90. The results showed diminished adenohypophyseal GnRHR, PR, and aromatase expression, whereas AR, ER\u03b1, PRLR, and inhibin were augmented, resulting in gonadotropins decline. Interestingly, autophagy biomarkers, Beclin-1, ATG5, ATG12, LC3-II, and LAMP1 were reduced but SQSTM1\/p62 was augmented in the ovaries of HFD-HF-fed rats, causing autolysosome to aggregation. The diet altered T, E2, P4, PRL, and their receptors status in the ovary, disturbed estrous cyclicity, and delayed vaginal opening. Ovarian histomorphology exhibited numerous cystic and atretic follicles, along with disturbed follicular maturation and ovulation. Moreover, the reduction of FSHR; steroidogenic proteins; receptor proteins AR, ER\u03b2, PR; and signaling proteins Wnt2 and \u03b2-catenin was also noticed in the ovary, whereas PRLR, inhibin, and pGSK3\u03b2 were augmented. In conclusion, exposure to a prepubertal HFD-HF diet leads to hypogonadotropism and the autophagy-mediated defective differentiation of ovarian follicles, abating fertility in adult rats.<\/jats:p>","DOI":"10.3390\/cells11213447","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T23:26:32Z","timestamp":1667258792000},"page":"3447","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["High Fat-High Fructose Diet Elicits Hypogonadotropism Culminating in Autophagy-Mediated Defective Differentiation of Ovarian Follicles"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6502-9814","authenticated-orcid":false,"given":"Chalikkaran Thilakan","family":"Rejani","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Dr. A.L.M. Postgraduate Institute of Basic Medical Sciences, University of Madras, Chennai 600113, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5054-4204","authenticated-orcid":false,"given":"Ajit Kumar","family":"Navin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Texas A&M Health Science Centre, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thekkey Madathil Valappil","family":"Mumthaz","sequence":"additional","affiliation":[{"name":"Department of Zoology, Sir Syed College, Kannur 670142, Kerala, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venugopal","family":"Bhuvarahamurthy","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Dr. A.L.M. Postgraduate Institute of Basic Medical Sciences, University of Madras, Chennai 600113, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"644650","DOI":"10.3389\/fnut.2021.644650","article-title":"Determinants of Junk Food Consumption Among Adolescents in Pokhara Valley, Nepal","volume":"8","author":"Bohara","year":"2021","journal-title":"Front. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"632312","DOI":"10.3389\/fnins.2021.632312","article-title":"Western Diet Consumption During Development: Setting the Stage for Neurocognitive Dysfunction","volume":"15","author":"Tsan","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_3","unstructured":"(2020, July 29). Health.gov (2015). 2015\u20132020 Dietary Guidelines, Available online: https:\/\/health.gov\/our-work\/food-nutrition\/2015-2020-dietary-guidelines\/guidelines\/."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"838","DOI":"10.3389\/fimmu.2017.00838","article-title":"The Impact of Western Diet and Nutrients on the Microbiota and Immune Response at Mucosal Interfaces","volume":"8","author":"Statovci","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mirzaei, R., Bidgoli, S.A., Khosrokhavar, R., Shoeibi, S., and Ashtiani, H.A. (2022). Increased Risk of Primary Ovarian Insufficiency by High-Fructose Diet: A 90-Day Hormonal and Immunohistochemical Study in Wistar Rats (preprint). Environ. Sci. Pollut. Res. Int.","DOI":"10.21203\/rs.3.rs-1188503\/v1"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Hajivandi, L., Noroozi, M., Mostafavi, F., and Ekramzadeh, M. (2020). Food habits in overweight and obese adolescent girls with polycystic ovary syndrome (PCOS): A qualitative study in Iran. BMC Pediatr., 20.","DOI":"10.1186\/s12887-020-02173-y"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"280S","DOI":"10.1093\/jn\/130.2.280S","article-title":"Dietary glycemic index and obesity","volume":"130","author":"Ludwig","year":"2000","journal-title":"J. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mikhael, S., Punjala-Patel, A., and Gavrilova-Jordan, L. (2019). Hypothalamic-Pituitary-Ovarian Axis Disorders Impacting Female Fertility. Biomedicines, 7.","DOI":"10.3390\/biomedicines7010005"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1530\/rep.1.00095","article-title":"Methods for quantifying follicular numbers within the mouse ovary","volume":"127","author":"Myers","year":"2004","journal-title":"Reproduction"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3389\/fendo.2018.00061","article-title":"Granulosa Cell Apoptosis in the Ovarian Follicle-A Changing View","volume":"9","author":"Regan","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e3001","DOI":"10.1038\/cddis.2017.371","article-title":"Administration of follicle-stimulating hormone induces autophagy via upregulation of HIF-1\u03b1 in mouse granulosa cells","volume":"8","author":"Zhou","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Shao, T., Ke, H., Liu, R., Xu, L., Han, S., Zhang, X., Dang, Y., Jiao, X., Li, W., and Chen, Z.J. (2022). Autophagy regulates differentiation of ovarian granulosa cells through degradation of WT1. Autophagy, 1\u201315.","DOI":"10.1080\/15548627.2021.2005415"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"E1046","DOI":"10.1210\/jc.2015-1504","article-title":"FSH Regulates IGF-2 Expression in Human Granulosa Cells in an AKT-Dependent Manner","volume":"100","author":"Baumgarten","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4845","DOI":"10.1210\/en.2013-1410","article-title":"GATA4 and GATA6 silencing in ovarian granulosa cells affects levels of mRNAs involved in steroidogenesis, extracellular structure organization, IGF-I activity, and apoptosis","volume":"154","author":"Bennett","year":"2013","journal-title":"Endocrinology."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.mce.2016.06.020","article-title":"Forkhead box O member FOXO1 regulates the majority of follicle-stimulating hormone-responsive genes in ovarian granulosa cells","volume":"434","author":"Herndon","year":"2016","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"R137","DOI":"10.1530\/REP-14-0685","article-title":"The role of WNT signaling in adult ovarian folliculogenesis","volume":"150","year":"2015","journal-title":"Reproduction"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"726","DOI":"10.7150\/ijbs.30369","article-title":"Autophagy in Ovarian Follicular Development and Atresia","volume":"15","author":"Zhou","year":"2019","journal-title":"Int. J. Biol.Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/path.2697","article-title":"Autophagy: Cellular and molecular mechanisms","volume":"221","author":"Glick","year":"2010","journal-title":"J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Leopardo, N.P., Velazquez, M.E., Cortasa, S., Gonz\u00e1lez, C.R., and Vitullo, A.D. (2020). A dual death\/survival role of autophagy in the adult ovary of Lagostomus maximus (Mammalia- Rodentia). PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0232819"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1016\/j.fertnstert.2010.06.006","article-title":"Induction of apoptotic cell death via accumulation of autophagosomes in rat granulosa cells","volume":"95","author":"Choi","year":"2011","journal-title":"Fertil.Steril."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"E4194","DOI":"10.1073\/pnas.1409323111","article-title":"Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor","volume":"111","author":"Gawriluk","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.jnutbio.2017.01.003","article-title":"Obesity alters the ovarian glucidic homeostasis disrupting the reproductive outcome of female rats","volume":"42","author":"Bazzano","year":"2017","journal-title":"J. Nutr. Biochem."},{"key":"ref_23","first-page":"S78","article-title":"Association of western diet & lifestyle with decreased fertility","volume":"140","author":"Nazni","year":"2014","journal-title":"Indian J. Med. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hussain, A., Zhang, M., \u00dc\u00e7punar, H.K., Svensson, T., Quillery, E., Gompel, N., Ignell, R., and GrunwaldKadow, I.C. (2016). Ionotropic Chemosensory Receptors Mediate the Taste and Smell of Polyamines. PLoS Biol., 14.","DOI":"10.1371\/journal.pbio.1002454"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1530\/REP-17-0584","article-title":"High-fat diet exposure from pre-pubertal age induces polycystic ovary syndrome (PCOS) in rats","volume":"155","author":"Patel","year":"2018","journal-title":"Reproduction"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1210\/er.2009-0012","article-title":"The mammalian ovary from genesis to revelation","volume":"30","author":"Edson","year":"2009","journal-title":"Endocr. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1477-7827-1-11","article-title":"Ovarian follicle counts\u2013not as simple as 1, 2, 3","volume":"1","author":"Tilly","year":"2003","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1210\/en.2005-1136","article-title":"Minireview: The neuroendocrine regulation of puberty: Is the time ripe for a systems biology approach?","volume":"147","author":"Ojeda","year":"2006","journal-title":"Endocrinology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1095\/biolreprod.111.091926","article-title":"Does a non-classical signaling mechanism underlie an increase of estradiol-mediated gonadotropin-releasing hormone receptor binding in ovine pituitary cells?","volume":"85","author":"Davis","year":"2011","journal-title":"Biol. Reprod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.ijdevneu.2012.09.001","article-title":"Prepubertal exposure to glucocorticoid delays puberty independent of the hypothalamic Kiss1-GnRH system in female rats. Int. J","volume":"30","author":"Kinouchi","year":"2012","journal-title":"Dev. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12967-015-0670-2","article-title":"G\u00f6ttingenminipig model of diet-induced atherosclerosis: Influence of mild streptozotocin-induced diabetes on lesion severity and markers of inflammation evaluated in obese, obese and diabetic, and lean control animals","volume":"13","author":"Ludvigsen","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e194","DOI":"10.1038\/nutd.2016.2","article-title":"A low-carbohydrate high-fat diet increases weight gain and does not improve glucose tolerance, insulin secretion or \u03b2-cell mass in NZO mice","volume":"6","author":"Lamont","year":"2016","journal-title":"Nutr. Diabetes."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"573","DOI":"10.11622\/smedj.2015085","article-title":"Effect of a high fat diet on ovary morphology, in vitro development, in vitro fertilisation rate and oocyte quality in mice","volume":"56","author":"Sohrabi","year":"2015","journal-title":"Singapore Med. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5438","DOI":"10.1210\/en.2010-0551","article-title":"High-fat diet causes lipotoxicity responses in cumulus-oocyte complexes and decreased fertilization rates","volume":"151","author":"Wu","year":"2010","journal-title":"Endocrinology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3389\/fendo.2017.00365","article-title":"Kisspeptin\/Kisspeptin Receptor System in the Ovary","volume":"8","author":"Hu","year":"2017","journal-title":"Front. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1095\/biolreprod.104.028175","article-title":"Estrogen actions on follicle formation and early follicle development","volume":"71","author":"Britt","year":"2004","journal-title":"Biol. Reprod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"R141","DOI":"10.1530\/JOE-14-0296","article-title":"Androgen actions in the ovary: Balance is key","volume":"222","author":"Prizant","year":"2014","journal-title":"J. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Wang, H.Q., Zhang, W.D., Yuan, B., and Zhang, J.B. (2021). Advances in the Regulation of Mammalian Follicle-Stimulating Hormone Secretion. Animals, 11.","DOI":"10.3390\/ani11041134"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1262\/jrd.2011-012","article-title":"Follicular growth and atresia in mammalian ovaries: Regulation by survival and death of granulosa cells","volume":"58","author":"Matsuda","year":"2012","journal-title":"J. Reprod Dev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1677\/joe.0.1700099","article-title":"Targeted disruption of the aromatase P450 gene (Cyp19) in mice and their ovarian and uterine responses to 17beta-oestradiol","volume":"170","author":"Toda","year":"2001","journal-title":"J. Endocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/rmb2.12371","article-title":"The role of pituitary gonadotropins and intraovarian regulators in follicle development: A mini-review","volume":"20","author":"Orisaka","year":"2021","journal-title":"Reprod. Med. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1101\/gad.9.18.2266","article-title":"Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities","volume":"9","author":"Lydon","year":"1995","journal-title":"Genes. Dev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3389\/fendo.2017.00221","article-title":"Intrinsic and Regulated Gonadotropin-Releasing Hormone Receptor Gene Transcription in Mammalian Pituitary Gonadotrophs","volume":"8","author":"Janjic","year":"2017","journal-title":"Front. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1126\/science.6250218","article-title":"Pituitary gonadotropin-releasing hormone receptors during the rat estrous cycle","volume":"209","author":"Schwartz","year":"1980","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1111\/j.1365-2826.2005.01353.x","article-title":"Regulation of expression of mammalian gonadotrophin-releasing hormone receptor genes","volume":"17","author":"Hapgood","year":"2005","journal-title":"J. Neuroendocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"162","DOI":"10.3389\/fendo.2012.00162","article-title":"Mechanisms underlying the tissue-specific and regulated activity of the Gnrhr promoter in mammals","volume":"3","author":"Schang","year":"2012","journal-title":"Front. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1210\/endo.136.3.7867555","article-title":"Roles of estrogen, progesterone, and gonadotropin-releasing hormone (GnRH) in the control of pituitary GnRH receptor gene expression at the time of the preovulatory gonadotropin surges","volume":"136","author":"Weiss","year":"1995","journal-title":"Endocrinology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1210\/endo.135.4.7925096","article-title":"Regulation of gonadotropin-releasing hormone (GnRH) receptor messenger ribonucleic acid and GnRH receptors during the early preovulatory period in the ewe","volume":"135","author":"Turzillo","year":"1994","journal-title":"Endocrinology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1095\/biolreprod43.6.1032","article-title":"Estradiol-induced increase in number of gonadotropin-releasing hormone receptors in cultured ovine pituitary cells","volume":"43","author":"Gregg","year":"1990","journal-title":"Biol. Reprod."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1210\/endo-127-1-373","article-title":"Inhibin increases and progesterone decreases receptors for gonadotropin-releasing hormone in ovine pituitary culture","volume":"127","author":"Laws","year":"1990","journal-title":"Endocrinology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1093\/humupd\/dmv059","article-title":"GnRH and GnRH receptors in the pathophysiology of the human female reproductive system","volume":"22","author":"Maggi","year":"2016","journal-title":"Hum. Reprod. Update"},{"key":"ref_52","first-page":"608","article-title":"Effects of estradiol and progesterone on gonadotropin LH\u03b2- and FSH\u03b2-subunit promoter activities in gonadotroph L\u03b2T2 cells","volume":"33","author":"Kanasaki","year":"2012","journal-title":"Neuro EndocrinolLett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1093\/humupd\/dml020","article-title":"Ovarian feedback, mechanism of action and possible clinical implications","volume":"12","author":"Messinis","year":"2006","journal-title":"Hum. Reprod. Update"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fendo.2014.00001","article-title":"Role of estrogen receptors and g protein-coupled estrogen receptor in regulation of hypothalamus-pituitary-testis axis and spermatogenesis","volume":"5","author":"Chimento","year":"2014","journal-title":"Front. Endocrinol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.mce.2009.09.003","article-title":"Hormones in synergy: Regulation of the pituitary gonadotropin genes","volume":"314","author":"Thackray","year":"2010","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"111286","DOI":"10.1016\/j.mce.2021.111286","article-title":"Androgen receptor positively regulates gonadotropin-releasing hormone receptor in pituitary gonadotropes","volume":"530","author":"Ryan","year":"2021","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1210\/en.2017-00844","article-title":"GnRH Receptor Expression and Reproductive Function Depend on JUN in GnRH Receptor\u2014Expressing Cells","volume":"159","author":"Jonak","year":"2018","journal-title":"Endocrinology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1677\/jme.1.01600","article-title":"Regulation of gonadotropin subunit gene transcription","volume":"33","author":"Burger","year":"2004","journal-title":"J. MolEndocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1530\/eje.0.1450561","article-title":"Inhibin B in male reproduction: Pathophysiology and clinical relevance","volume":"145","author":"Meachem","year":"2001","journal-title":"Eur. J. Endocrinol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1210\/endo-124-1-552","article-title":"Production and regulation of inhibin subunits in pituitary gonadotropes","volume":"124","author":"Roberts","year":"1989","journal-title":"Endocrinology."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.mce.2004.02.010","article-title":"Autocrine\/paracrine regulation of pituitary function by activin, inhibin and follistatin","volume":"225","author":"Bilezikjian","year":"2004","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"R131","DOI":"10.1530\/JME-17-0308","article-title":"Molecular regulation of follicle-stimulating hormone synthesis, secretion and action","volume":"60","author":"Das","year":"2018","journal-title":"J. Mol. Endocrinol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1210\/endo-117-3-954","article-title":"Hyperprolactinemia inhibits gonadotropin-releasing hormone (GnRH) stimulation of the number of pituitary GnRH receptors","volume":"117","author":"Garcia","year":"1985","journal-title":"Endocrinology"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Lee, E.B., Chakravarthi, V.P., Wolfe, M.W., and Rumi, M.A.K. (2021). ER\u03b2 Regulation of Gonadotropin Responses during Folliculogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910348"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.reprotox.2021.01.014","article-title":"Prenatal exposure to hexavalent chromium disrupts testicular steroidogenic pathway in peripubertal F","volume":"101","author":"Navin","year":"2021","journal-title":"Reprod. Toxicol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s12595-021-00417-y","article-title":"Hexavalent Chromium and Male Reproduction","volume":"74","author":"Navin","year":"2021","journal-title":"Proc. Zool. Soc."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/rmb2.12075","article-title":"Expression of the gonadotropin receptors during follicular development","volume":"17","author":"Kishi","year":"2018","journal-title":"Reprod Med. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1073\/pnas.1318978111","article-title":"Androgens regulate ovarian follicular development by increasing follicle stimulating hormone receptor and microRNA-125b expression","volume":"111","author":"Sen","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1095\/biolreprod62.2.310","article-title":"Expression of estrogen receptor beta is developmentally regulated in reproductive tissues of male and female mice","volume":"62","author":"Jefferson","year":"2000","journal-title":"Biol. Reprod."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1210\/en.2016-1916","article-title":"Defining the Role of Estrogen Receptor \u03b2 in the Regulation of Female Fertility","volume":"158","author":"Rumi","year":"2017","journal-title":"Endocrinology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5135","DOI":"10.1073\/pnas.1504944112","article-title":"Estrogen receptor \u03b2 exon 3-deleted mouse: The importance of non-ERE pathways in ER\u03b2 signaling","volume":"112","author":"Maneix","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1210\/me.2010-0141","article-title":"Beta-catenin (CTNNB1) promotes preovulatory follicular development but represses LH-mediated ovulation and luteinization","volume":"24","author":"Fan","year":"2010","journal-title":"Mol. Endocrinol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1095\/biolreprod.109.080903","article-title":"WNT2 regulates DNA synthesis in mouse granulosa cells through beta-catenin","volume":"82","author":"Wang","year":"2010","journal-title":"Biol. Reprod."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3789","DOI":"10.2527\/jas.2011-4696","article-title":"Follicle-stimulating hormone regulation of estradiol production: Possible involvement of WNT2 and \u03b2-catenin in bovine granulosa cells","volume":"90","author":"Stapp","year":"2012","journal-title":"J. Anim. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"730196","DOI":"10.3389\/fphys.2021.730196","article-title":"The Signaling Pathways Involved in Ovarian Follicle Development","volume":"12","author":"Li","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"12435","DOI":"10.1073\/pnas.0603006103","article-title":"Follicle-stimulating hormone\/cAMP regulation of aromatase gene expression requires beta-catenin","volume":"103","author":"Parakh","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e86432","DOI":"10.1371\/journal.pone.0086432","article-title":"Canonical WNT Signaling Inhibits Follicle Stimulating Hormone Mediated Steroidogenesis in Primary Cultures of Rat Granulosa Cells","volume":"9","author":"Stapp","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1681\/ASN.2016070731","article-title":"High-Fat Diet-Induced Lysosomal Dysfunction and Impaired Autophagic Flux Contribute to Lipotoxicity in the Kidney","volume":"28","author":"Yamamoto","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3052","DOI":"10.1096\/fj.09-144519","article-title":"Altered lipid content inhibits autophagic vesicular fusion","volume":"24","author":"Koga","year":"2010","journal-title":"FASEB J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"42534","DOI":"10.1074\/jbc.M111.242412","article-title":"Fatty acids suppress autophagic turnover in \u03b2-cells","volume":"286","author":"Las","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nrm3531","article-title":"The road to maturation: Somatic cell interaction and self-organization of the mammalian oocyte","volume":"14","author":"Li","year":"2013","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1210\/jc.2016-3960","article-title":"Premature Ovarian Insufficiency: Phenotypic Characterization Within Different Etiologies","volume":"102","author":"Jiao","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/S0140-6736(10)60355-8","article-title":"Primary ovarian insufficiency","volume":"376","author":"Devroey","year":"2010","journal-title":"Lancet"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1016\/j.fertnstert.2009.11.021","article-title":"The role of autophagy in follicular development and atresia in rat granulosa cells","volume":"93","author":"Choi","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1095\/biolreprod.111.091314","article-title":"The role of autophagy in corpus luteum regression in the rat","volume":"85","author":"Choi","year":"2011","journal-title":"Biol. 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