View source for Oogenesis

{{Short description|Egg cell production process}}
{{Too short|date=January 2025}}
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'''Oogenesis''' ({{IPAc-en|ˌ|oʊ|.|ə|ˈ|dʒ|ɛ|n|ɪ|s|ɪ|s}}) or '''ovogenesis''' is the differentiation of the [[ovum]] (egg cell) into a cell competent to further develop when fertilized.<ref>{{Cite book|last=Gilbert|first=Scott F.|date=2000|title=Developmental Biology|edition=6th|chapter=Oogenesis|publisher=Sinauer Associates |url=https://www.ncbi.nlm.nih.gov/books/NBK10008/|language=en}}</ref> It is developed from the primary oocyte by maturation. Oogenesis is initiated during [[embryonic development]].

==Stages==
[[File:Oogenesis - Meiosis.png|thumb|left|Diagram showing the reduction in number of the [[chromosomes]] in the process of maturation of the [[ovum]]. (In mammals, the first [[polar body]] normally disintegrates before dividing, so only two polar bodies are produced.{{Citation needed|date=May 2018}})]]

In humans and other [[mammal]]s, the first part of oogenesis starts in the [[germinal epithelium (female)|germinal epithelium]], which gives rise to the development of [[ovarian follicles]], the functional unit of the [[ovary]].

Oogenesis consists of several sub-processes: '''oocytogenesis''', [[ootidogenesis]], and finally maturation to form an ovum (oogenesis proper). [[Folliculogenesis]] is a separate sub-process that accompanies and supports all three oogenetic sub-processes.

{| class="wikitable"
! Cell type !! [[ploidy]]/[[chromosomes]] !! [[chromatids]] !! Process !! Time of completion
 |- 
 | [[Oogonium]] || diploid/46(2N) || 2C|| Oocytogenesis ([[mitosis]]) || [[Pregnancy#Third trimester|Third trimester]]
 |- 
 | primary [[oocyte]] || diploid/46(2N) || 4C || [[Ootidogenesis]] ([[meiosis]] I) ([[Folliculogenesis]]) || [[Dictyate]] in prophase I for up to 50 years
 |- 
 | secondary oocyte || haploid/23(1N) || 2C || [[Ootidogenesis]] ([[meiosis]] II) || Halted in metaphase II until fertilization
 |- 
 | [[Immature ovum|Ootid]] || haploid/23(1N)  || 1C || [[Ootidogenesis]] ([[meiosis]] II) || Minutes after fertilization
 |- 
 | [[Egg cell|Ovum]] || haploid/23(1N) || 1C || ||
|}

Oogonium&nbsp;—(Oocytogenesis)—> Primary Oocyte&nbsp;—(Meiosis I)—> First [[Polar body]] (Discarded afterward) + Secondary oocyte&nbsp;—(Meiosis II)—> Second Polar Body (Discarded afterward) + Ovum

Oocyte meiosis, important to all animal life cycles yet unlike all other instances of animal cell division, occurs completely without the aid of [[Spindle apparatus|spindle]]-coordinating [[centrosomes]].<ref>{{cite journal | vauthors = Szollosi D, Calarco P, Donahue RP | year = 1972 | title = Absence of centrioles in the first and second meiotic spindles of mouse oocytes | journal = J Cell Sci | volume = 11 | issue = 2| pages = 521–541 | doi = 10.1242/jcs.11.2.521 | pmid = 5076360 }}</ref><ref>{{cite journal | pmid = 15385423 | doi=10.1095/biolreprod.104.031245 | volume=72 | issue=1 | title=Centrosome reduction during gametogenesis and its significance | date=January 2005 | journal=Biol. Reprod. | pages=2–13 | vauthors=Manandhar G, Schatten H, Sutovsky P| s2cid=37305534 | doi-access=free }}</ref>

===The creation of oogonia===
The creation of [[oogonium|oogonia]] traditionally does not belong to oogenesis proper, but, instead, to the [[Gametogenesis#Common path|common process]] of [[gametogenesis]], which, in the human female, begins with the processes of [[folliculogenesis]], oocytogenesis, and [[ootidogenesis]]. Oogonia enter meiosis during embryonic development, becoming oocytes. Meiosis begins with DNA replication and meiotic crossing over. It then stops in early prophase.

===Maintenance of meiotic arrest===
Mammalian oocytes are maintained in meiotic prophase arrest for a very long time—months in mice, years in humans.<ref name="Stringer2020">{{cite journal |last1=Stringer |first1=JM |last2=Winship |first2=A |last3=Zerafa |first3=N |last4=Wakefield |first4=M |last5=Hutt |first5=K |title=Oocytes can efficiently repair DNA double-strand breaks to restore genetic integrity and protect offspring health. |journal=Proceedings of the National Academy of Sciences of the United States of America |date=26 May 2020 |volume=117 |issue=21 |pages=11513–11522 |doi=10.1073/pnas.2001124117 |doi-access=free |pmid=32381741 |pmc=7260990 |bibcode=2020PNAS..11711513S }}</ref> Initially, the arrest is due to lack of sufficient cell cycle proteins to allow meiotic progression. However, as the oocyte grows, these proteins are synthesized, and meiotic arrest becomes dependent on [[cyclic AMP]].<ref name="dupeRef1">{{Cite journal |last1=Jaffe |first1=Laurinda A. |last2=Egbert |first2=Jeremy R. |date=2017-02-10 |title=Regulation of Mammalian Oocyte Meiosis by Intercellular Communication Within the Ovarian Follicle |journal=Annual Review of Physiology |volume=79 |issue=1 |pages=237–260 |doi=10.1146/annurev-physiol-022516-034102|pmid=27860834 |pmc=5305431 }}</ref> The cyclic AMP is generated by the oocyte by adenylyl cyclase in the oocyte membrane. The adenylyl cyclase is kept active by a constitutively active [[G protein-coupled receptor]] known as [[GPR3]] and a [[G protein]], Gs, also present in the oocyte membrane.<ref>{{Cite journal |last1=Mehlmann |first1=Lisa M. |last2=Saeki |first2=Yoshinaga |last3=Tanaka |first3=Shigeru |last4=Brennan |first4=Thomas J. |last5=Evsikov |first5=Alexei V. |last6=Pendola |first6=Frank L. |last7=Knowles |first7=Barbara B. |last8=Eppig |first8=John J. |last9=Jaffe |first9=Laurinda A. |date=2004-12-10 |title=The G<sub>s</sub>-Linked Receptor GPR3 Maintains Meiotic Arrest in Mammalian Oocytes |journal=Science |volume=306 |issue=5703 |pages=1947–1950 |doi=10.1126/science.1103974|pmid=15591206 |bibcode=2004Sci...306.1947M |s2cid=37342089 }}</ref>

Maintenance of meiotic arrest also depends on the presence of a multilayered complex of cells, known as a follicle, that surrounds the oocyte. Removal of the oocyte from the follicle causes meiosis to progress in the oocyte.<ref>{{Cite journal |last=Edwards |first=R. G. |date=October 1965 |title=Maturation in vitro of Mouse, Sheep, Cow, Pig, Rhesus Monkey and Human Ovarian Oocytes |journal=Nature |volume=208 |issue=5008 |pages=349–351 |doi=10.1038/208349a0|pmid=4957259 |bibcode=1965Natur.208..349E |s2cid=4285338 }}</ref> The cells that comprise the follicle, known as granulosa cells, are connected to each other by proteins known as gap junctions, that allow small molecules to pass between the cells. The granulosa cells produce a small molecule, [[cyclic GMP]], that diffuses into the oocyte through the gap junctions. In the oocyte, cyclic GMP prevents the breakdown of cyclic AMP by the [[PDE3|phosphodiesterase PDE3]], and thus maintains meiotic arrest.<ref>{{Cite journal |last1=Norris |first1=Rachael P. |last2=Ratzan |first2=William J. |last3=Freudzon |first3=Marina |last4=Mehlmann |first4=Lisa M. |last5=Krall |first5=Judith |last6=Movsesian |first6=Matthew A. |last7=Wang |first7=Huanchen |last8=Ke |first8=Hengming |last9=Nikolaev |first9=Viacheslav O. |last10=Jaffe |first10=Laurinda A. |date=June 2009 |title=Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte |journal=Development |volume=136 |issue=11 |pages=1869–1878 |doi=10.1242/dev.035238|pmid=19429786 |pmc=2680110 }}</ref> The cyclic GMP is produced by the guanylyl cyclase NPR2.<ref>{{Cite journal |last1=Zhang |first1=Meijia |last2=Su |first2=You-Qiang |last3=Sugiura |first3=Koji |last4=Xia |first4=Guoliang |last5=Eppig |first5=John J. |date=2010-10-15 |title=Granulosa Cell Ligand NPPC and Its Receptor NPR2 Maintain Meiotic Arrest in Mouse Oocytes |journal=Science |volume=330 |issue=6002 |pages=366–369 |doi=10.1126/science.1193573|pmid=20947764 |pmc=3056542 |bibcode=2010Sci...330..366Z }}</ref>

===Reinitiation of meiosis and stimulation of ovulation by luteinizing hormone===

As follicles grow, they acquire receptors for luteinizing hormone, a pituitary hormone that reinitiates meiosis in the oocyte and causes ovulation of a fertilizable egg. Luteinizing hormone acts on receptors in the outer layers of granulosa cells of the follicle, causing a decrease in cyclic GMP in the granulosa cells.<ref name="dupeRef1" /> Because the granulosa cells and oocyte are connected by gap junctions, cyclic GMP also decreases in the oocyte, causing meiosis to resume.<ref>{{Cite journal |last1=Shuhaibar |first1=Leia C. |last2=Egbert |first2=Jeremy R. |last3=Norris |first3=Rachael P. |last4=Lampe |first4=Paul D. |last5=Nikolaev |first5=Viacheslav O. |last6=Thunemann |first6=Martin |last7=Wen |first7=Lai |last8=Feil |first8=Robert |last9=Jaffe |first9=Laurinda A. |date=2015-03-16 |title=Intercellular signaling via cyclic GMP diffusion through gap junctions restarts meiosis in mouse ovarian follicles |journal=Proceedings of the National Academy of Sciences |volume=112 |issue=17 |pages=5527–5532 |doi=10.1073/pnas.1423598112|pmid=25775542 |pmc=4418852 |bibcode=2015PNAS..112.5527S |doi-access=free }}</ref> Meiosis then proceeds to second metaphase, where it pauses again until fertilization. Luteinizing hormone also stimulates gene expression leading to ovulation.<ref>{{Cite journal |last1=Richards |first1=JoAnne S. |last2=Ascoli |first2=Mario |date=May 2018 |title=Endocrine, Paracrine, and Autocrine Signaling Pathways That Regulate Ovulation |journal=Trends in Endocrinology & Metabolism |volume=29 |issue=5 |pages=313–325 |doi=10.1016/j.tem.2018.02.012|pmid=29602523 |s2cid=4491304 }}</ref>

[[File:Oogenesis.svg|thumb|Oogenesis in eukaryotic cells. (A) oogonium where the mitotic division occurs (B) differentiation and meiosis I begins (C) primary oocyte (D) meiosis I is completed and meiosis II begins (E) secondary oocyte (F) first polar body (G) ovulation must occur and the presence of the sperm penetration (fertilization) induces meiosis II to completion (H) ovum (I) second polar body]]
[[File:Follicle signaling.jpg|thumb]]

==In humans==
[[File:Biology Wiki Diagram -- oogensis.jpg|thumb|Oogenesis throughout a woman's life]]

In humans, oogenesis begins in [[human embryonic development|embryonic development]] with the transformation of [[oogonium|oogonia]] into primary oocytes, a process called oocytogenesis.<ref>[https://www.ncbi.nlm.nih.gov/books/NBK10008/ NCBI - The saga of the germ line]</ref> From one single oogonium, only one mature oocyte will rise, with three other cells called polar bodies. Oocytogenesis is complete either before or shortly after birth. 

=== Number of primary oocytes ===
It is commonly believed that, when oocytogenesis is complete, no additional primary oocytes are created, in contrast to the male process of spermatogenesis, where gametocytes are continuously created. In other words, primary oocytes reach their maximum development at ~20 weeks of gestational age, when approximately seven million primary oocytes have been created; however, at birth, this number has already been reduced to approximately 1-2 million per ovary. At puberty, the number of oocytes decreases even more to reach about 60,000 to 80,000 per ovary, and only about 400{{endash}}500 mature oocytes will be produced during a woman's life, the others will undergo atresia (degeneration).<ref>{{cite journal |author=Lobo RA |title=Early ovarian ageing: a hypothesis. What is early ovarian ageing? |journal=Hum. Reprod. |volume=18 |issue=9 |pages=1762–4 |date=September 2003 |pmid=12923124 |doi= 10.1093/humrep/deg377|doi-access=free |citeseerx=10.1.1.611.1482 }}</ref>  Two publications have challenged the belief that a finite number of oocytes are set around the time of birth generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood.<ref name="Johnson">{{cite journal |vauthors=Johnson J, Bagley J, Skaznik-Wikiel M, Lee HJ, Adams GB, Niikura Y, Tschudy KS, Tilly JC, Cortes ML, Forkert R, Spitzer T, Iacomini J, Scadden DT, Tilly JL |title=Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood |journal=Cell |volume=122 |issue=2 |pages=303–15 |date=July 2005 |pmid=16051153 |doi=10.1016/j.cell.2005.06.031 |url=|doi-access=free |pmc=11771209 }}</ref><ref>{{cite journal |vauthors=Johnson J, Canning J, Kaneko T, Pru J, Tilly J | title = Germline stem cells and follicular renewal in the postnatal mammalian ovary | journal = Nature | volume = 428 | issue = 6979 | pages = 145–50 | year = 2004 | pmid = 15014492 | doi = 10.1038/nature02316| bibcode = 2004Natur.428..145J | s2cid = 1124530 }}</ref> The renewal of ovarian follicles from germline stem cells (originating from bone marrow and peripheral blood) has been reported in the postnatal mouse ovary. In contrast, DNA clock measurements do not indicate ongoing oogenesis during human females' lifetimes.<ref>{{cite journal |vauthors=Forster P, Hohoff C, Dunkelmann B, Schürenkamp M, Pfeiffer H, Neuhuber F, Brinkmann B |title=Elevated germline mutation rate in teenage fathers |journal=Proc R Soc B |volume=282 |issue= 1803|article-number=20142898 |year=2015 |pmid=25694621 |doi=10.1098/rspb.2014.2898 |pmc=4345458}}</ref>
Thus, further experiments are required to determine the true dynamics of small follicle formation.

===Ootidogenesis===
The succeeding phase of '''ootidogenesis''' occurs when the [[primary oocyte]] undergoes meiosis to develop into an [[ootid]] stage of an immature ovum.<ref>{{Cite web |url=http://www.biochem.northwestern.edu/holmgren/Glossary/Definitions/Def-P/primary_oocyte.html |title=Biochem |access-date=2007-07-18 |archive-date=2010-06-15 |archive-url=https://web.archive.org/web/20100615090324/http://www.biochem.northwestern.edu/holmgren/Glossary/Definitions/Def-P/primary_oocyte.html }}</ref>

However, although this process begins at prenatal age, it stops at [[prophase I]]. In late fetal life, all oocytes, still primary oocytes, have halted at this stage of development, called the [[dictyate]]. After [[menarche]], these cells then continue to develop, although only a few do so every [[menstrual cycle]].

====Meiosis I====
[[Meiosis I]] of ootidogenesis begins during embryonic development, but halts in the [[diplotene]] stage of prophase I until puberty. The mouse oocyte in the dictyate (prolonged diplotene) stage actively repairs DNA damage, whereas DNA repair is not detectable in the pre-dictyate ([[Leptotene stage|leptotene]], [[Meiosis#Zygotene|zygotene]] and [[Meiosis#Pacytene|pachytene]]) stages of meiosis.<ref>{{cite journal | vauthors = Guli CL, Smyth DR | year = 1988 | title = UV-induced DNA repair is not detectable in pre-dictyate oocytes of the mouse | journal = Mutat Res | volume = 208 | issue = 2| pages = 115–119 | pmid = 3380109 | doi=10.1016/s0165-7992(98)90010-0}}</ref> For those primary oocytes that continue to develop in each menstrual cycle, however, [[synapsis]] occurs and [[Meiosis#Meiosis I|tetrads]] form, enabling [[chromosomal crossover]] to occur. As a result of meiosis I, the primary oocyte has now developed into the [[secondary oocyte]].

====Meiosis II====
Immediately after meiosis I, the [[haploid]] secondary oocyte initiates [[meiosis II]]. However, this process is also halted at the [[metaphase II]] stage until [[Human fertilization|fertilization]], if such should ever occur. If the egg is not fertilized, it is disintegrated and released ([[menstruation]]) and the secondary oocyte does not complete meiosis II (and does not become an [[ovum]]). When meiosis II has completed, an ootid and another polar body have now been created. The polar body is small in size.

=== Ovarian cycle ===
The ovarian cycle is divided into several phases:

* [[Folliculogenesis|Follicologenesis]]: Synchronously with ootidogenesis, the [[ovarian follicle]] surrounding the ootid has developed from a primordial follicle to a preovulatory one. The primary follicle takes four months to become a preantral, two months to become antral, and then passes to a mature (Graaf) follicle. The primary follicle has oocyte-lining cells that go from floor to cubic and begin to proliferate, increasing the [[metabolic activity]] of the oocyte and follicular cells, which release glycoproteins and proteoglycans acids that will form the [[zona pellucida]], which accompany the installation. In the preantral secondary follicle, internal and external theca cells begin to form. [[Aromatase]], produced by follicular cells, transforms [[androgen]]s produced by the inner theca into estrogens under the stimulation of FSH. LH stimulates theca cells to produce androgens. In the antral follicle, there is an antrum containing a follicle liquor, which contains estrogen, to allow the passage from the antral follicle to the Graaf follicle. The follicular antrum moves the oocyte and becomes eccentric; the oocyte is always surrounded by the pellucid zone and by follicular cells that form the [[cumulus oophorus]]. The innermost ones are called the [[corona radiata]] or radiated corona cells. At this stage, the oocyte produces [[cortical granule]]s containing acid [[glycoprotein]]s.<ref>{{Cite book |last1=Rimon-Dahari |first1=Nitzan |last2=Yerushalmi-Heinemann |first2=Lia |last3=Alyagor |first3=Liat |last4=Dekel |first4=Nava |chapter=Ovarian Folliculogenesis |series=Results and Problems in Cell Differentiation |date=2016 |title=Molecular Mechanisms of Cell Differentiation in Gonad Development |chapter-url=https://pubmed.ncbi.nlm.nih.gov/27300179/ |volume=58 |pages=167–190 |doi=10.1007/978-3-319-31973-5_7 |issn=0080-1844 |pmid=27300179|isbn=978-3-319-31971-1 }}</ref> 
* Dominant follicle selection: The follicle with more FSH receptors will be more favored, simultaneously inducing the death of the other follicles (3-10 antral follicles that enter this phase each month). Low concentration estrogen will inhibit further production of FSH by the [[pituitary gland]] with negative feedback, so the follicles left behind will accumulate in the follicular antrum instead of androgens.
* Graaf follicle: Estrogen at other concentrations induces LH release, with the peak of LH called LH surge, which induces stages that will lead to follicle burst. LH receptors also appear on follicular cells, which stimulate the oocyte to become a secondary oocyte, blocked in metaphase, waiting for fertilization. LH also stimulates oophore cumulus cells to release progesterone.
* [[Ovulation]]: bursting of the follicle, oocyte leakage with pellucid zone, and radiated corona cells. The lining membrane is thinned on the ovary where the follicle bursts and the cells attached to it emerge from the stigma. The ovary is collected from the uterine tube, where fertilization can take place in the [[ampulla|ampullate zone]], the widest part of the oviduct where fertilization typically occurs. 
* Formation of the [[corpus luteum]]: From the remaining structures of the follicle, the corpus luteum is formed. At first, there is a clot, which is then replaced by loose connective tissue; the cells that form solid cords are follicular cells and cells of the outer theca (Tecali lutein cells) and internal ([[Granulosa cell|granulosa cells]]). The luteal body increases the concentration of progesterone, which LH constantly stimulates. If the egg is not fertilized, the corpus luteum degenerates (body albicans); if it is implanted, it remains until three months of pregnancy, where its function is replaced by the [[placenta]] (production of progesterone and estrogen). The level of LH (necessary to keep the corpus luteum alive) is replaced by [[human chorionic gonadotropin]].<ref>{{Citation |last1=Betz |first1=Danielle |title=Human Chorionic Gonadotropin |date=2024 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK532950/ |access-date=2024-04-06 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30422545 |last2=Fane |first2=Kathleen}}</ref>

=== Uterine cycle ===
The uterine cycle<ref name=":0">{{Citation |last1=Thiyagarajan |first1=Dhanalakshmi K. |title=Physiology, Menstrual Cycle |date=2024 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK500020/ |access-date=2024-04-06 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=29763196 |last2=Basit |first2=Hajira |last3=Jeanmonod |first3=Rebecca}}</ref> occurs parallel to the ovarian cycle and is induced by estrogen and progesterone. The [[endometrium]], formed by a monostratified cylindrical epithelium, with [[Uterine gland|uterine glands]] (simple tubular), connective with a functional superficial layer (divided into a spongy layer, a compact layer, and a deeper basal layer, which is always maintained, presents four phases:

* Proliferative phase: From the 5th to the 14th day of the [[ovarian cycle]], it is conditioned by [[Estrogen|estrogens]]. The functional layer of the uterus is restored, with mitotic division of the basal layer.
* Secretive phase: from the 14th to the 27th day of the ovarian cycle, influenced by the [[progesterone]] produced by the [[corpus luteum]]. Cells become [[Hypertrophy|hypertrophic]], and tubular glands begin to produce glycogen
* Ischemic phase: beginning of the menstrual phase from 27 to 28 days
*  Regressive or desquamative phase from 1 to 5 days, the spiral-shaped arteries undergo [[ischemia]], and the functional layer detaches

If, instead, there is fertilization, the uterine mucosa is modified to accommodate the fertilized egg, and the secretive phase is maintained.

===Maturation into ovum===
Both polar bodies disintegrate at the end of [[meiosis II]], leaving only the ootid, which then eventually undergoes maturation into a mature ovum.

The function of forming polar bodies is to discard the extra haploid sets of chromosomes that have resulted as a consequence of meiosis.

===In vitro maturation===
{{Main article|In vitro maturation}}

''In vitro maturation'' (''IVM'') is the technique of letting [[ovarian follicle]]s mature [[in vitro]]. It can potentially be performed before an [[IVF]]. In such cases, [[Controlled ovarian hyperstimulation|ovarian hyperstimulation]] is not essential. Rather, oocytes can mature outside the body prior to IVF. Hence, no (or at least a lower dose of) gonadotropins have to be injected in the body.<ref name=vejledning>{{Cite web |url=http://www.sst.dk/publ/Publ2006/KOT/kunstig_befrugtning/Vejl_ivf_oa_dec06.pdf |title=Vejledning om kunstig befrugtning 2006 (Danish) |access-date=2011-01-29 |archive-url=https://web.archive.org/web/20120309035605/http://www.sst.dk/publ/Publ2006/KOT/kunstig_befrugtning/Vejl_ivf_oa_dec06.pdf |archive-date=2012-03-09 }}</ref> Immature eggs have been grown until maturation ''in vitro'' at a 10% survival rate, but the technique is not yet clinically available.<ref name="McLaughlinAlbertini2018">
*{{cite journal|last1=McLaughlin|first1=M|last2=Albertini|first2=D F|last3=Wallace|first3=W H B|last4=Anderson|first4=R A|last5=Telfer|first5=E E|title=Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system|journal=MHR: Basic Science of Reproductive Medicine|volume=24|issue=3|pages=135–142|year=2018|issn=1360-9947|doi=10.1093/molehr/gay002|pmid=29390119|doi-access=free|hdl=20.500.11820/55cbb793-3401-4172-80a9-44412ecdf216|hdl-access=free}}
*Further comments in [[BBC News]] article: {{cite news|url=https://www.bbc.com/news/health-42976858|title=First human eggs grown in laboratory|author=James Gallagher|date=2018-02-09|work=BBC News}}</ref> With this technique, cryopreserved ovarian tissue could possibly be used to make oocytes that can directly undergo [[in vitro fertilization]].<ref name="McLaughlinAlbertini2018"/>

===In vitro oogenesis===
By definition, it means to recapitulate mammalian oogenesis and produce fertilizable oocytes in vitro. It is a complex process involving several different cell types, precise follicular cell-oocyte reciprocal interactions, a variety of nutrients and combinations of cytokines, and precise growth factors and hormones depending on the developmental stage.<ref>{{cite journal|title=Complete in vitro oogenesis: retrospects and prospects|journal=Cell Death Differ|year=2017|volume=24|issue=11|pages=1845–1852|doi= 10.1038/cdd.2017.134|pmid=28841213|pmc=5635224|last1=Wang|first1=Jun-Jie|last2=Ge|first2=Wei|last3=Liu|first3=Jing-Cai|last4=Klinger|first4=Francesca Gioia|last5=Dyce|first5=Paul W.|last6=De Felici|first6=Massimo|last7=Shen|first7=Wei}}</ref> In 2016, two papers published by Morohaku et al. and Hikabe et al. reported in vitro procedures that appear to reproduce efficiently these conditions allowing for the production, completely in a dish, of a relatively large number of oocytes that are fertilizable and capable of giving rise to viable offspring in the mouse. This technique can be mainly benefited in cancer patients where in today's condition their ovarian tissue 
is cryopreserved for preservation of fertility. Alternatively to the autologous transplantation, the development of culture systems that support oocyte development from the primordial follicle stage represent a valid strategy to restore fertility. Over time, many studies have been conducted with the aim to optimize the characteristics of ovarian tissue culture systems and to better support the three main phases: 1) activation of primordial follicles; 2) isolation and culture of growing preantral follicles; 3) removal from the follicle environment and maturation of oocyte cumulus complexes. While complete oocyte in vitro development has been achieved in mouse, with the production of live offspring, the goal of obtaining oocytes of sufficient quality to support embryo development has not been completely reached into higher mammals despite decades of effort.<ref>{{cite journal|title=Update on oogenesis in vitro|journal= Minerva Ginecol |year=2018|volume=70|issue=5|pages=588–608|pmid=29999288|doi= 10.23736/S0026-4784.18.04273-9|s2cid=51622568|last1= Fabbri |first1= Raffaella |last2= Zamboni |first2= Chiara |last3= Vicenti |first3= Rossella |last4= MacCiocca |first4= Maria |last5= Paradisi |first5= Roberto |last6= Seracchioli |first6= Renato }}</ref>

==Ovarian aging==
[[BRCA1]] and [[ATM serine/threonine kinase|ATM]] proteins are employed in [[DNA repair|repair of DNA]] double-strand break during [[meiosis]]. These proteins appear to have a critical role in resisting [[ovary|ovarian aging]].<ref name="Turan2020">{{Cite journal |last1=Turan |first1=Volkan |last2=Oktay |first2=Kutluk |date=2020 |title=BRCA-related ATM-mediated DNA double-strand break repair and ovarian aging |journal=Human Reproduction Update |volume=26 |issue=1 |pages=43–57 |doi=10.1093/humupd/dmz043 |pmc=6935693 |pmid=31822904}}</ref>  However, [[homologous recombination]]al repair of DNA double-strand breaks mediated by BRCA1 and ATM weakens with age in [[oocyte]]s of humans and other species.<ref name = Turan2020/>  Women with BRCA1 [[mutation]]s have lower [[ovarian reserve]]s and experience earlier [[menopause]] than women without these mutations.  Even in woman without specific BRCA1 mutations, ovarian aging is associated with depletion of ovarian reserves leading to menopause, but at a slower rate than in those with such mutations.  Since older premenopausal women ordinarily have normal progeny, their capability for meiotic recombinational repair appears to be sufficient to prevent deterioration of their [[germline]] despite the reduction in ovarian reserve.  DNA damages may arise in the germline during the decades long period in humans between early oocytogenesis and the stage of meiosis in which [[homologous chromosome]]s are effectively paired ([[dictyate]] stage).  It has been suggested that such DNA damages may be removed, in large part, by mechanisms dependent on chromosome pairing, such as homologous recombination.<ref>{{Cite journal |last=Bernstein |first=C. |date=1979 |title=Why are babies young? Meiosis may prevent aging of the germ line |journal=Perspectives in Biology and Medicine |volume=22 |issue=4 |pages=539–544 |doi=10.1353/pbm.1979.0041 |pmid=573881|s2cid=38550472 }}</ref>

==Other animals and plants==
[[File:Parasite160001-fig6 - Oogenesis in Crepidostomum metoecus (Digenea) (diagram).png|thumb|Diagram of oogenesis in a [[digenea]]n ([[Platyhelminthes]])]]
{{Main article|Evolution of sexual reproduction}}

Some [[algae]] and the [[oomycete]]s produce eggs in [[oogonia]]. In the brown alga ''[[Fucus]]'', all four egg cells survive oogenesis, which is an exception to the rule that generally only one product of female meiosis survives to maturity.

In [[plant]]s, oogenesis occurs inside the female [[gametophyte]] via [[mitosis]]. In many plants such as [[bryophyte]]s, [[fern]]s, and [[gymnosperm]]s, egg cells are formed in [[archegonia]]. In [[flowering plant]]s, the female gametophyte has been reduced to an eight-celled [[embryo sac]] within the [[ovule]] inside the [[Ovary (plants)|ovary]] of the flower. Oogenesis occurs within the embryo sac and leads to the formation of a single egg cell per ovule.

In ''[[ascaris]]'', the oocyte does not even begin meiosis until the [[sperm]] touches it, in contrast to mammals, where meiosis is completed in the [[estrus]] cycle.

In female ''[[Drosophila melanogaster|Drosophila]]'' flies, [[genetic recombination]] occurs during [[meiosis]].  This recombination is associated with formation of [[DNA damage (naturally occurring)|DNA double-strand breaks]] and the [[DNA repair|repair]] of these breaks.
<ref name="Mehrotra2006">{{Cite journal |last1=Mehrotra |first1=S. |last2=McKim |first2=K. S. |date=2006-11-24 |title=Temporal analysis of meiotic DNA double-strand break formation and repair in Drosophila females |journal=PLOS Genetics |volume=2 |issue=11 |article-number=e200 |doi=10.1371/journal.pgen.0020200 |pmc=1657055 |pmid=17166055 |doi-access=free }}</ref>  The repair process leads to [[chromosomal crossover|crossover recombinants]] as well as at least three times as many noncrossover recombinants (e.g. arising by [[gene conversion]] without crossover).<ref name = Mehrotra2006/>

==See also==
*[[Anisogamy]]
*[[Archegonium]]
*[[Evolution of sexual reproduction]]
*[[Female infertility]]
*[[Female reproductive system]]
*[[Oncofertility]]
*[[Origin and function of meiosis]]
*[[Sexual reproduction]]
*[[Spermatogenesis]]

==References==
Cho WK, Stern S, Biggers JD. 1974. Inhibitory effect of dibutyryl cAMP on mouse oocyte maturation in vitro. J Exp Zool.187:383-386
{{Reflist}}
;Bibliography
* Manandhar G, Schatten H and Sutovsky P (2005). Centrosome reduction during gametogenesis and its significance. Biol Reprod, 72(1)2-13.

==External links==
*[https://web.archive.org/web/20070501202041/http://www2.ufp.pt/~pedros/qfisio/reproduction.htm Reproductive Physiology]

{{Female reproductive system}}
{{Reproductive physiology}}
{{Sex (biology)}}
{{Eggs}}

{{Authority control}}

[[Category:Developmental biology]]
[[Category:Genetics]]
[[Category:Human female endocrine system]]
[[Category:Meiosis]]