{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T19:31:39Z","timestamp":1780083099989,"version":"3.54.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,22]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In human in vitro fertilization, the main uncertainty factor impacting on success is oocyte quality, which largely depends on the follicular status at the time of collection. Decades of debate ensued to find the perfect stimulation protocol demonstrated the complexity of the ovarian response to exogenous gonadotropins and the dynamic nature of late folliculogenesis. Although several follicular markers, proteins, RNA from granulosa cells or microRNA, and follicular fluid metabolites have been associated with outcome, the possibility to influence them during stimulation remains elusive. The heterogeneity of the follicle\u2019s maturity following control ovarian stimulation is also an important factor to explain average poor oocyte quality still observed today. In this review, the analogy between the apple ripening on the tree and follicular development is presented to focus the attention on a biphasic process: growth and differentiation. The molecular analysis of the progressive follicular differentiation indicates two competing phenomena: growth and differentiation, where a delicate balance must operate from one to the other to ensure proper maturity at ovulation. As long as follicle-stimulating hormone (FSH) stimulates growth, follicles remain green, and it is only when FSH is replaced by luteinizing hormone that the ripening process begins, and \u201capples\u201d become red. Both fruits, follicles and apples, depend on a perfect timing of events to generate offspring.<\/jats:p>","DOI":"10.1093\/biolre\/ioab236","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T12:02:17Z","timestamp":1640260937000},"page":"230-234","source":"Crossref","is-referenced-by-count":10,"title":["The two-step process of ovarian follicular growth and maturation in mammals can be compared to a fruit ripening where quality depends on the second step"],"prefix":"10.1093","volume":"106","author":[{"given":"Marc-Andr\u00e9","family":"Sirard","sequence":"first","affiliation":[{"name":"Centre de recherche en reproduction, d\u00e9veloppement et sant\u00e9 interg\u00e9n\u00e9rationnelle (CRDSI), Universit\u00e9 Laval, Qu\u00e9bec, Canada"},{"name":"D\u00e9partement des Sciences Animales, Facult\u00e9 des sciences de l\u2019agriculture et de l\u2019alimentation, Universit\u00e9 Laval, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"2022022215241919500_ref1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ando.2010.02.021","article-title":"Human ovarian follicular development: from activation of resting follicles to preovulatory maturation","volume":"71","author":"Gougeon","year":"2010","journal-title":"Ann Endocrinol"},{"key":"2022022215241919500_ref2","doi-asserted-by":"crossref","first-page":"S170","DOI":"10.1105\/tpc.019158","article-title":"Genetic regulation of fruit development and ripening","volume":"16","author":"Giovannoni","year":"2004","journal-title":"Plant Cell"},{"key":"2022022215241919500_ref3","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0378-4320(03)00093-9","article-title":"Mechanism of follicle deviation in monovular farm species","volume":"78","author":"Ginther","year":"2003","journal-title":"Anim Reprod 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