Anti-Müllerian Hormone (AMH) regulates BRCA1 and BRCA2 gene expression after ovarian cortex transplantation

Abstract

Objective

To test whether recombinant anti-Müllerian hormone (rAMH) could exert an inhibitory function on BRCA1/2 expression in human ovarian cortex.

Methods

Pilot study on ovariectomized nude mice xenotransplanted with human vitrified/warmed ovarian cortex and treated with rAMH via infusion pump. Twelve nude mice were ovariectomized and Alzet pumps delivering 1.23 mcg rAMH/day to reach a serum concentration of 17.5 ng/mL, or placebo (controls), were inserted intraabdominally. Previously vitrified/warmed 2x2 mm ovarian cortex fragments were transplanted on day 7 and then harvested on day 14 after pump placement. PCR analyses determined mRNA levels for BRCA1 and BRCA2 in the human ovarian cortex.

Results

In mice treated with rAMH, BRCA1 expression was significantly lower (0.196 fg/µg RNA, IQR 0.158, 0.236) than in controls (0.544 fg/µg RNA, IQR 0.458, 0.554; p = .030), while BRCA2 expression remained similar in rAMH mice (5.355 fg/µg RNA, IQR 4.479, 6.230) and in controls (4.011 fg/µg RNA, IQR 3.650, 4.182; p = .327).

Conclusion

Administration of rAMH in the peri-transplant period caused downregulation of BRCA1, but not of BRCA2 expression, in human ovarian cortex. These results help our understanding of DNA repair mechanism in the ovarian cortex and identify AMH’s possible protective effect on ovarian reserve in BRCA1 mutation carriers.

摘要

目的：检验重组抗缪勒管激素（recombinant Anti-Müllerian Hormone, rAMH）对人卵巢皮质BRCA1 / 2表达是否具有抑制作用。方法：预试验给去卵巢裸鼠异体移植经玻璃化/加热的人卵巢皮质, 通过输注泵用rAMH进行治疗。将十二只裸鼠切除卵巢, 并在腹腔内插入Alzet泵, 每天给予1.23mcg rAMH以达到17.5ng / mL的血清浓度, 对照组给予安慰剂。先前玻璃化/加热的2x2 mm卵巢皮质碎片在在放置泵后的第7天移植, 在第14天采集。PCR分析确定人类卵巢皮质中BRCA1和BRCA2的mRNA水平。结果：BRCA1表达：rAMH组 (0.196 fg/µg RNA, IQR 0.158, 0.236)显着低于对照组(0.544 fg/µg RNA, IQR 0.458, 0.554; p = .030)；BRCA2表达：rAMH组 (5.355 fg/µg RNA, IQR 4.479, 6.230)与对照组相似(4.011 fg/µg RNA, IQR 3.650, 4.182; p = .327)。结论：围移植期给予rAMH可导致人卵巢皮质BRCA1表达下调, 但不影响BRCA2的表达。这些结果有助于我们了解BRCA1突变携带者卵巢皮质DNA修复机制, 并确定AMH对卵巢储备的潜在保护作用。

Keywords:

• Recombinant AMH
• ovarian cortex
• BRCA1
• BRCA2
• xenotransplant

Acknowledgements

The authors wish to thank the University of Tennessee Health Science Center for their unrestricted support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the University of Tennessee Health Science Center under Grant No. E07-3225-001.