FIGLA

Summary

FIGLA (folliculogenesis specific bHLH transcription factor, HGNC:24669) is a protein-coding gene on chromosome 2p13.3, encoding Factor in the germline alpha (Q6QHK4). Germline specific transcription factor implicated in postnatal oocyte-specific gene expression.

This gene encodes a protein that functions in postnatal oocyte-specific gene expression. The protein is a basic helix-loop-helix transcription factor that regulates multiple oocyte-specific genes, including genes involved in folliculogenesis and those that encode the zona pellucida. Mutations in this gene cause premature ovarian failure type 6.

Source: NCBI Gene 344018 — RefSeq curated summary.

At a glance

• Gene–disease (curated): premature ovarian failure 6 (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 88 total — 4 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 30
• MANE Select transcript: NM_001004311

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24669
Approved symbol	FIGLA
Name	folliculogenesis specific bHLH transcription factor
Location	2p13.3
Locus type	gene with protein product
Status	Approved
Aliases	bHLHc8, Figalpha
Ensembl gene	ENSG00000183733
Ensembl biotype	protein_coding
OMIM	608697
Entrez	344018

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000332372

RefSeq mRNA: 1 — MANE Select: NM_001004311 NM_001004311

CCDS: CCDS46320

Canonical transcript exons

ENST00000332372 — 5 exons

Exon	Start	End
ENSE00001296883	70787649	70787801
ENSE00001316438	70790408	70790643
ENSE00001320722	70785415	70785639
ENSE00001475245	70777637	70777671
ENSE00001754342	70777310	70777382

Expression profiles

Bgee: expression breadth broad, 75 present calls, max score 96.24.

Top tissues by expression

230 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	96.24	gold quality
secondary oocyte	CL:0000655	93.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	61.86	gold quality
body of pancreas	UBERON:0001150	49.84	gold quality
oviduct epithelium	UBERON:0004804	46.87	silver quality
mucosa of stomach	UBERON:0001199	43.38	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
myometrium	UBERON:0001296	43.22	gold quality
granulocyte	CL:0000094	42.81	silver quality
omental fat pad	UBERON:0010414	41.90	gold quality
peritoneum	UBERON:0002358	41.89	gold quality
adipose tissue of abdominal region	UBERON:0007808	41.82	gold quality
body of uterus	UBERON:0009853	41.79	gold quality
pancreas	UBERON:0001264	41.71	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
right ovary	UBERON:0002118	41.08	gold quality
sperm	CL:0000019	40.98	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-8381	yes	994.15
E-ANND-3	no	0.97

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

6 targets.

Target	Regulation
FIGLA
MIR212
TCF3	Unknown
ZP1	Unknown
ZP2	Unknown
ZP3	Unknown

JASPAR motifs

Motif	Name	Family
MA0820.1	FIGLA	Tal-related
MA0820.2	FIGLA	Tal-related
MA1934.1	ERF::FIGLA	Ets-related::Tal-related
MA1934.2	ERF::FIGLA	Ets-related::Tal-related
MA1941.1	ETV2::FIGLA	Ets-related::Tal-related
MA1941.2	ETV2::FIGLA	Ets-related::Tal-related
MA1945.1	ETV5::FIGLA	Ets-related::Tal-related
MA1945.2	ETV5::FIGLA	Ets-related::Tal-related

JASPAR matrix evidence (PMIDs): PMID:18499083, PMID:31913281, PMID:24218641

Upstream regulators (CollecTRI, top): FIGLA

Literature-anchored findings (GeneRIF, showing 7)

• Expression of mRNA observed in ovarian follicles, mature oocytes, and less frequently in preimplantation embryos. (PMID:12468641)
• These results suggest that FIGLA is involved in continued oocyte survival as primordial follicles form in the human as in the rodent ovary. (PMID:15044608)
• the p.140 delN mutation disrupted FIGLA binding to the TCF3 helix-loop-helix (HLH) domain. Our findings show that a subset of Chinese women with sporadic, premature ovarian failure harbor mutations in FIGLA. (PMID:18499083)
• may have a role in the development of primordial follicle before zona pellucida formation (PMID:18502569)
• study identified an association between FIGLA gene variants and the occurrence of premature ovarian failure(POF) in the Indian population; findings suggest that the c.427G->C and c.557C->T alleles lead to an increased risk of POF in Indian women (PMID:25314148)
• Biallelic mutations in FIGLA may be the cause of premature ovarian insufficiency (POI) . This study will aid researchers and clinicians in genetic counseling of POI and provides new insights into understanding the mode of genetic inheritance of FIGLA mutations in POI pathology. (PMID:29914564)
• Our results support the notion that bi-allelic recessive loss-of-function effects of FIGLA contribute to POI patients with short stature and expand the FIGLA-related phenotypic spectrum. (PMID:30474133)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	figla	ENSDARG00000087166
mus_musculus	Figla	ENSMUSG00000030001
rattus_norvegicus	Figla	ENSRNOG00000015877
drosophila_melanogaster	twi	FBGN0003900
caenorhabditis_elegans		WBGENE00001953

Paralogs (13): HAND1 (ENSG00000113196), TCF21 (ENSG00000118526), TWIST1 (ENSG00000122691), TCF15 (ENSG00000125878), FERD3L (ENSG00000146618), TCF23 (ENSG00000163792), HAND2 (ENSG00000164107), PTF1A (ENSG00000168267), MSC (ENSG00000178860), BHLHA9 (ENSG00000205899), TWIST2 (ENSG00000233608), SCX (ENSG00000260428), TCF24 (ENSG00000261787)

Protein

Protein identifiers

Factor in the germline alpha — Q6QHK4 (reviewed: Q6QHK4)

Alternative names: Class C basic helix-loop-helix protein 8, Folliculogenesis-specific basic helix-loop-helix protein, Transcription factor FIGa

All UniProt accessions (1): Q6QHK4

UniProt curated annotations — full annotation on UniProt →

Function. Germline specific transcription factor implicated in postnatal oocyte-specific gene expression. Plays a key regulatory role in the expression of multiple oocyte-specific genes, including those that initiate folliculogenesis and those that encode the zona pellucida (ZP1, ZP2 and ZP3) required for fertilization and early embryonic survival. Essential for oocytes to survive and form primordial follicles. The persistence of FIGLA in adult females suggests that it may regulate additional pathways that are essential for normal ovarian development. Binds to the E-box (5’-CANNTG-3’) of the ZPs (ZP1, ZP2, ZP3) promoters.

Subunit / interactions. Heterodimer with TCF3/isoform E12.

Subcellular location. Nucleus.

Tissue specificity. Germ cells. Expressed in the fetal ovary, but not by a range of other tissues. Expression increases across mid-gestation, rising some 40-fold by the time of primordial follicle formation.

Disease relevance. Premature ovarian failure 6 (POF6) [MIM:612310] An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_001004311* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR050283	E-box_TF_Regulators	Family

Pfam: PF00010

UniProt features (7 total): sequence variant 3, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6QHK4-F1	71.67	0.40

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 109 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_OOGENESIS, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_OOCYTE_DIFFERENTIATION, GOBP_FEMALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, GOMF_BHLH_TRANSCRIPTION_FACTOR_BINDING, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_E_BOX_BINDING, QI_PLASMACYTOMA_DN, GOMF_TRANSCRIPTION_FACTOR_BINDING, GSE13887_HEALTHY_VS_LUPUS_RESTING_CD4_TCELL_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, chr2p13

GO Biological Process (6): regulation of transcription by RNA polymerase II (GO:0006357), developmental process (GO:0032502), oocyte development (GO:0048599), cell differentiation (GO:0030154), positive regulation of transcription by RNA polymerase II (GO:0045944), oogenesis (GO:0048477)

GO Molecular Function (10): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), bHLH transcription factor binding (GO:0043425), protein dimerization activity (GO:0046983), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), E-box binding (GO:0070888)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), transcription regulator complex (GO:0005667)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
germ cell development	2
regulation of transcription by RNA polymerase II	2
regulation of DNA-templated transcription	1
biological_process	1
oocyte differentiation	1
cellular developmental process	1
positive regulation of DNA-templated transcription	1
female gamete generation	1
transcription cis-regulatory region binding	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor binding	1
protein binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
RNA polymerase II cis-regulatory region sequence-specific DNA binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

976 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FIGLA	NOBOX	O60393	978
FIGLA	BMP15	O95972	946
FIGLA	SOHLH1	Q5JUK2	943
FIGLA	LHX8	Q68G74	918
FIGLA	FOXL2	P58012	890
FIGLA	YBX2	Q9Y2T7	865
FIGLA	POF1B	Q8WVV4	860
FIGLA	GDF9	O60383	821
FIGLA	ZP1	P60852	749
FIGLA	ZP4	Q12836	742
FIGLA	ZP3	P21754	734
FIGLA	SOHLH2	Q9NX45	734
FIGLA	FMR1	Q06787	722
FIGLA	ZP2	Q05996	720
FIGLA	DIAPH2	O60879	715

IntAct

39 interactions, top by confidence:

A	B	Type	Score
LHX8	FIGLA	psi-mi:“MI:0915”(physical association)	0.700
FIGLA	LHX6	psi-mi:“MI:0915”(physical association)	0.560
MYOG	FIGLA	psi-mi:“MI:0915”(physical association)	0.560
MYF5	FIGLA	psi-mi:“MI:0915”(physical association)	0.560
MYOD1	FIGLA	psi-mi:“MI:0915”(physical association)	0.560
FIGLA	TCF12	psi-mi:“MI:0915”(physical association)	0.560
TCF4	FIGLA	psi-mi:“MI:0915”(physical association)	0.560
FIGLA	LHX3	psi-mi:“MI:0915”(physical association)	0.560
FIGLA	TCF23	psi-mi:“MI:0915”(physical association)	0.560
FIGLA	TCF4	psi-mi:“MI:0914”(association)	0.350
FIGLA	TCF3	psi-mi:“MI:0914”(association)	0.350
FIGLA	LHX6	psi-mi:“MI:0915”(physical association)	0.000
FIGLA	MYOG	psi-mi:“MI:0915”(physical association)	0.000
FIGLA	MYF5	psi-mi:“MI:0915”(physical association)	0.000
FIGLA	LHX8	psi-mi:“MI:0915”(physical association)	0.000
FIGLA	TCF4	psi-mi:“MI:0915”(physical association)	0.000
FIGLA	MYOD1	psi-mi:“MI:0915”(physical association)	0.000
FIGLA	TCF12	psi-mi:“MI:0915”(physical association)	0.000
FIGLA	LHX3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): FIGLA (Two-hybrid), FIGLA (Two-hybrid), FIGLA (Two-hybrid), FIGLA (Two-hybrid), FIGLA (Two-hybrid), FIGLA (Two-hybrid), FIGLA (Two-hybrid), FIGLA (Two-hybrid), TCF4 (Two-hybrid), NES (Affinity Capture-MS), TCF12 (Affinity Capture-MS), ID4 (Affinity Capture-MS), TCF3 (Affinity Capture-MS), TCF4 (Affinity Capture-MS), LHX8 (Affinity Capture-MS)

ESM2 similar proteins: A0A287BDC1, A6NFD8, A8YXY8, B1AXD8, B3F209, F1LXF1, O00287, O14503, O35185, O35779, O35780, O54972, O77638, O95644, P11274, P12755, P36956, Q0D2I5, Q13469, Q3UR85, Q50H33, Q53H80, Q5EA15, Q5RAI7, Q60591, Q60611, Q60698, Q61976, Q6AYH2, Q6NS60, Q6QB00, Q6QHK4, Q6T4P5, Q6ZWB6, Q7TS99, Q7Z6J2, Q8BXL9, Q8N228, Q8R4T5, Q8TEK3

Diamond homologs: A8E5T6, B6VQA1, O13125, O13126, O16867, O35437, O42202, O42606, O43680, O57598, O60682, O73615, O73823, O88940, O93507, O96004, O96642, P13903, P17542, P22091, P24899, P26687, P46581, P48985, P48987, P57100, P57101, P57102, P59101, P61295, P61296, P70661, P79765, P79782, P97831, P97832, Q02575, Q02576, Q02577, Q0VCE2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

88 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	2
Uncertain significance	42
Likely benign	11
Benign	26

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
2137	NM_001004311.3(FIGLA):c.15_36del (p.Gly6fs)	Pathogenic
2138	NM_001004311.3(FIGLA):c.416ACA[1] (p.Asn140del)	Pathogenic
3901241	NM_001004311.3(FIGLA):c.339T>G (p.Tyr113Ter)	Pathogenic
635131	NM_001004311.3(FIGLA):c.2T>C (p.Met1Thr)	Pathogenic
1256003	NM_001004311.3(FIGLA):c.319C>T (p.Leu107Phe)	Likely pathogenic
4292272	NM_001004311.3(FIGLA):c.164C>A (p.Ser55Ter)	Likely pathogenic

SpliceAI

753 predictions. Top by Δscore:

Variant	Effect	Δscore
2:70790407:CCCG:C	donor_gain	1.0000
2:70790414:ACGCT:A	donor_gain	1.0000
2:70790415:CG:C	donor_gain	1.0000
2:70790415:CGCT:C	donor_gain	1.0000
2:70790415:CGCTC:C	donor_gain	1.0000
2:70790418:T:A	donor_gain	1.0000
2:70785421:T:TA	donor_gain	0.9900
2:70787735:T:TA	donor_gain	0.9900
2:70790404:TCA:T	donor_loss	0.9900
2:70790406:AC:A	donor_gain	0.9900
2:70790407:C:A	donor_loss	0.9900
2:70790407:CC:C	donor_gain	0.9900
2:70790414:A:AC	donor_gain	0.9900
2:70790415:C:CC	donor_gain	0.9900
2:70790455:A:AC	donor_gain	0.9900
2:70790456:C:CC	donor_gain	0.9900
2:70785414:CCAGA:C	donor_gain	0.9800
2:70785640:C:CC	acceptor_gain	0.9800
2:70787802:C:CC	acceptor_gain	0.9800
2:70790406:A:AC	donor_gain	0.9800
2:70790407:C:CC	donor_gain	0.9800
2:70787799:TATCT:T	acceptor_loss	0.9700
2:70787801:TC:T	acceptor_loss	0.9700
2:70787803:T:A	acceptor_loss	0.9700
2:70789913:T:C	acceptor_gain	0.9700
2:70790419:C:CA	donor_gain	0.9700
2:70787638:TAC:T	donor_gain	0.9600
2:70787639:ACA:A	donor_gain	0.9600
2:70787640:CAC:C	donor_gain	0.9600
2:70787804:AGAAA:A	acceptor_loss	0.9600

AlphaMissense

1414 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:70787724:T:A	K103N	0.996
2:70787724:T:G	K103N	0.996
2:70787770:A:G	L88S	0.996
2:70787725:T:A	K103I	0.995
2:70787713:A:T	L107H	0.994
2:70787705:C:G	A110P	0.993
2:70787779:A:G	F85S	0.993
2:70790416:G:T	R75S	0.993
2:70787713:A:G	L107P	0.992
2:70790415:C:G	R75P	0.992
2:70790425:C:G	A72P	0.992
2:70790409:C:G	R77P	0.991
2:70787766:C:A	K89N	0.989
2:70787766:C:G	K89N	0.989
2:70787779:A:C	F85C	0.989
2:70787727:G:C	S102R	0.988
2:70787727:G:T	S102R	0.988
2:70787729:T:G	S102R	0.988
2:70790417:C:A	E74D	0.988
2:70790417:C:G	E74D	0.988
2:70787726:T:C	K103E	0.987
2:70787791:A:G	L81P	0.987
2:70790418:T:A	E74V	0.987
2:70790420:C:A	K73N	0.987
2:70790420:C:G	K73N	0.987
2:70787696:A:G	Y113H	0.986
2:70790419:C:T	E74K	0.986
2:70787726:T:G	K103Q	0.984
2:70787728:C:A	S102I	0.984
2:70787704:G:T	A110E	0.983

dbSNP variants (sampled 300 via entrez): RS1000268321 (2:70792177 C>G), RS1000385412 (2:70786686 T>C), RS1000735420 (2:70786445 C>A,T), RS1000766479 (2:70781540 C>A), RS1001125615 (2:70788047 C>G,T), RS1001164504 (2:70790637 A>C,G), RS1001270876 (2:70790806 G>C), RS1001500335 (2:70779075 T>C,G), RS1001791976 (2:70785231 G>A), RS1002473722 (2:70777493 A>C), RS1003507866 (2:70789575 A>G), RS1003560190 (2:70789767 A>C), RS1004110919 (2:70783377 C>A,T), RS1004183926 (2:70790042 C>G,T), RS1004376339 (2:70784125 A>T)

Disease associations

OMIM: gene MIM:608697 | disease phenotypes: MIM:612310

GenCC curated gene-disease

Disease	Classification	Inheritance
premature ovarian failure 6	Strong	Autosomal recessive

Mondo (1): premature ovarian failure 6 (MONDO:0012861)

Orphanet (1): Rare genetic premature ovarian failure (Orphanet:485382)

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000013	Hypoplasia of the uterus
HP:0000062	Ambiguous genitalia
HP:0000133	Gonadal dysgenesis
HP:0000144	Decreased fertility
HP:0000252	Microcephaly
HP:0000365	Hearing impairment
HP:0000786	Primary amenorrhea
HP:0000823	Delayed puberty
HP:0000837	Increased circulating gonadotropin level
HP:0000869	Secondary amenorrhea
HP:0000938	Osteopenia
HP:0001166	Arachnodactyly
HP:0001251	Ataxia
HP:0001470	Sex-limited expression
HP:0001939	Abnormality of metabolism/homeostasis
HP:0002206	Pulmonary fibrosis
HP:0002225	Sparse pubic hair
HP:0002750	Delayed skeletal maturation
HP:0004322	Short stature
HP:0004349	Reduced bone mineral density
HP:0005625	Osteoporosis of vertebrae
HP:0008209	Premature ovarian insufficiency
HP:0008214	Decreased serum estradiol
HP:0008222	Female infertility
HP:0008232	Elevated circulating follicle stimulating hormone level
HP:0008684	Aplasia/hypoplasia of the uterus
HP:0009888	Abnormality of secondary sexual hair
HP:0010311	Aplasia/Hypoplasia of the breasts
HP:0010464	Streak ovary
HP:0011969	Elevated circulating luteinizing hormone level

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002481_1	Acne (severe)	5.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567351	Premature Ovarian Failure 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects methylation	1
CGP 52608	increases reaction, affects binding	1
Benzo(a)pyrene	increases methylation, decreases methylation	1
Aflatoxin B1	decreases methylation	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1U4	SEES3-1V human FIGLA, clone1	Embryonic stem cell	Male
CVCL_A1U5	SEES3-1V human FIGLA, clone2	Embryonic stem cell	Male
CVCL_A1U6	SEES3-1V human FIGLA, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

2 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation