Anti-Müllerian hormone promotes pre-antral follicle growth, but inhibits antral follicle maturation and dominant follicle selection in primates

Abstract STUDY QUESTION What are the direct effects and physiological role of anti-Müllerian hormone (AMH) during primate follicular development and function at specific stages of folliculogenesis? SUMMARY ANSWER AMH actions in the primate ovary may be stage-dependent, directly promoting pre-antral...

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Bibliographic Details
Published in:Human reproduction (Oxford) 2016-07, Vol.31 (7), p.1522-1530
Main Authors: Xu, J., Bishop, C.V., Lawson, M.S., Park, B.S., Xu, F.
Format: Article
Language:English
Subjects:
Animals
Anti-Mullerian Hormone - blood
Anti-Mullerian Hormone - immunology
Anti-Mullerian Hormone - pharmacology
Antibodies, Neutralizing - pharmacology
Cytochrome P450 Family 19 - metabolism
Estradiol - biosynthesis
Female
Macaca mulatta
Original
Ovarian Follicle - drug effects
Ovarian Follicle - growth & development
Progesterone - blood
Random Allocation
RNA, Messenger - metabolism
Tissue Culture Techniques
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Summary:Abstract STUDY QUESTION What are the direct effects and physiological role of anti-Müllerian hormone (AMH) during primate follicular development and function at specific stages of folliculogenesis? SUMMARY ANSWER AMH actions in the primate ovary may be stage-dependent, directly promoting pre-antral follicle growth while inhibiting antral follicle maturation and dominant follicle selection. WHAT IS KNOWN ALREADY AMH is expressed in the adult ovary, particularly in developing follicles. Studies in mice suggest that AMH suppresses pre-antral follicle growth in vitro, and inhibits primordial follicle recruitment and FSH-stimulated antral follicle steroidogenesis. STUDY DESIGN, SIZE, DURATION For in vitro study, secondary follicles were isolated from ovaries of 12 rhesus macaques and cultured for 5 weeks. For in vivo study, intraovarian infusion was conducted on five monkeys for the entire follicular phase during two spontaneous menstrual cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS For in vitro study, individual follicles were cultured in a 5% O2 environment, in alpha minimum essential medium supplemented with recombinant human FSH. Follicles were randomly assigned to treatments of recombinant human AMH protein or neutralizing anti-human AMH antibody (AMH-Ab). Follicle survival, growth, steroid production, steroidogenic enzyme expression, and oocyte maturation were assessed. For in vivo study, ovaries were infused with control vehicle or AMH-Ab during the follicular phase of the menstrual cycle. Cycle length, serum steroid levels, and antral follicle growth were evaluated. MAIN RESULTS AND THE ROLE OF CHANCE AMH exposure during culture weeks 0–3 (pre-antral stage) promoted, while AMH-Ab delayed, antrum formation of growing follicles compared with controls. AMH treatment during culture weeks 3–5 (antral stage) decreased (P < 0.05) estradiol (E2) production, as well as the mRNA expression of cytochrome P450 family 19 subfamily A polypeptide 1, by antral follicles relative to controls, whereas AMH-Ab increased (P < 0.05) follicular mRNA levels of the enzyme. Intraovarian infusion of AMH-Ab during the follicular phase of the menstrual cycle increased (P < 0.05) the average levels of serum E2 compared with those of the control cycles. Three of the five AMH-Ab-treated ovaries displayed multiple (n = 2–9) medium-to-large (2–8 mm) antral follicles at the mid-cycle E2 peak, whereas only one large (4–7 mm) antral follicle was observed in all monkeys during their con
ISSN:0268-1161
1460-2350
DOI:10.1093/humrep/dew100