Meiosis initiation in the human ovary requires intrinsic retinoic acid synthesis.
BACKGROUND
The initiation of meiosis is crucial to fertility. While extensive studies in rodents have enhanced our understanding of this process, studies in human fetal ovary are lacking.


METHODS
We used RT-PCR and immunohistochemistry to investigate expression of meiotic factors in human fetal ovaries from 6 to 15 weeks post fertilization (wpf) and developed an organ culture model to study the initiation of human meiosis.


RESULTS
We observed the first meiotic cells at 11 wpf, when STRA8, SPO11 and DMC1 are first expressed. In culture, meiosis initiation is observed in 10 and 11 wpf ovaries and meiosis is maintained by addition of fetal calf serum. Meiosis is stimulated, compared with control, by retinoic acid (RA) (P < 0.05). No major change occurred in mRNA for CYP26B1, the RA-degrading enzyme proposed to control the timing of meiosis in mice. We did, however, observe increased mRNA levels for ALDH1A1 in human ovary when meiosis began, and evidence for a requirement to synthesize RA and thus sustain meiosis. Indeed, ALDH inhibition by citral prevented the appearance of meiotic cells. Finally, 8 wpf ovaries (and earlier stages) were unable to initiate meiosis whatever the length of culture, even in the presence of RA and serum. However, when human germ cells from 8 wpf ovaries were placed in a mouse ovarian environment, some did initiate meiosis.


CONCLUSIONS
Our data indicate that meiosis initiation in the human ovary relies partially on RA, but that the progression and regulation of this process appears to differ in many aspects from that described in mice.
Le Bouffant
R
R
CEA, DSV/DRR/SEGG/LDRG, Laboratory of Differentiation and Radiobiology of the Gonads, Unit of Gametogenesis and Genotoxicity, 18 route du panorama, F-92265 Fontenay aux Roses, France.
Guerquin
M J
MJ
Duquenne
C
C
Frydman
N
N
Coffigny
H
H
Rouiller-Fabre
V
V
Frydman
R
R
Habert
R
R
Livera
G
G
D000080462:Acyclic Monoterpenes; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D005333:Fetus; D006801:Humans; D008540:Meiosis; D051379:Mice; D039821:Monoterpenes / Q000494:pharmacology; D010053:Ovary / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010063:Ovum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050697:Retinal Dehydrogenase; D000072516:Retinoic Acid 4-Hydroxylase; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology
D000080462:Acyclic Monoterpenes; D039821:Monoterpenes; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; C000607079:CYP26B1 protein, human; C000607081:Cyp26b1 protein, mouse; D000072516:Retinoic Acid 4-Hydroxylase; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; C007076:citral