臨床婦人科産科72巻12号

2018年12月発行

今月の臨床 女性のアンチエイジング─老化のメカニズムから予防・対処法まで

部位別 : 老化のメカニズムと予防・対処法

卵巣・卵子の老化

著者： 髙井泰¹

所属機関： ¹埼玉医科大学総合医療センター

ページ範囲：P.1220 - P.1227

文献概要

●卵巣中の卵子は加齢とともに量と質が低下していくと考えられており，質の低下が「卵子老化」といわれている．

●卵子老化の原因としてミトコンドリアの量・質の低下やDNA修復能の低下が推測されているが，現状では治療法や予防法は確立していない．

●DHEA併用ARTの有効性が示唆されているほか，種々の生殖幹細胞の臨床応用も期待されている．

参考文献

1）Nelson SM, et al : The ageing ovary and uterus : new biological insights. Hum Reprod Update 19 : 67─83, 2013

2）May-Panloup P, et al : Ovarian ageing : the role of mitochondria in oocytes and follicles. Hum Reprod Update 22 : 725─743, 2016

3）Selesniemi K, et al : Prevention of maternal aging-associated oocyte aneuploidy and meiotic spindle defects in mice by dietary and genetic strategies. Proc Natl Acad Sci U S A 108 : 12319─12324, 2011

4）Wu LL, et al : High-fat diet causes lipotoxicity responses in cumulus-oocyte complexes and decreased fertilization rates. Endocrinology 151 : 5438─5445, 2010

5）Moawad AR, et al : l-carnitine supplementation during vitrification of mouse germinal vesicle stage-oocytes and their subsequent in vitro maturation improves meiotic spindle configuration and mitochondrial distribution in metaphase II oocytes. Hum Reprod 29 : 2256─2268, 2014

6）Bentov Y, et al : The aging oocyte--can mitochondrial function be improved? Fertil Steril 99 : 18─22, 2013

7）Pacella-Ince L, et al : Mitochondrial SIRT3 and its target glutamate dehydrogenase are altered in follicular cells of women with reduced ovarian reserve or advanced maternal age. Hum Reprod 29 : 1490─1499, 2014

8）Zhao HC, et al : Role of Sirt3 in mitochondrial biogenesis and developmental competence of human in vitro matured oocytes. Hum Reprod 31 : 607─622, 2016

9）Winship AL, et al : The importance of DNA repair for maintaining oocyte quality in response to anti-cancer treatments, environmental toxins and maternal ageing. Hum Reprod Update, 2018［Epub ahead of primt］

10）Titus S, et al : Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans. Sci Transl Med 5 : 172ra121, 2013

11）Stolk L, et al : Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. Nat Genet 44 : 260─268, 2012

12）AlAsiri S, et al : Exome sequencing reveals MCM8 mutation underlies ovarian failure and chromosomal instability. J Clin Invest 125 : 258─262, 2015

13）Kujjo LL, et al : Enhancing survival of mouse oocytes following chemotherapy or aging by targeting Bax and Rad51. PLoS One 5 : e9204, 2010

14）Rinaldi VD, et al : Pharmacological inhibition of the DNA damage checkpoint prevents radiation-induced oocyte death. Genetics 206 : 1823─1828, 2017

15）Casson PR, et al : Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders : a case series. Hum Reprod 15 : 2129─2132, 2000

16）Narkwichean A, et al : Effects of dehydroepiandrosterone on in vivo ovine follicular development. Hum Reprod 29 : 146─154, 2014

17）Lin LT, et al : Dehydroepiandrosterone as a potential agent to slow down ovarian aging. J Obstet Gynaecol Res 43 : 1855─1862, 2017

18）Zhang M, et al : Dehydroepiandrosterone treatment in women with poor ovarian response undergoing IVF or ICSI : a systematic review and meta-analysis. J Assist Reprod Genet 33 : 981─991, 2016

19）Kotb MM, et al : Does dehydroepiandrosterone improve pregnancy rate in women undergoing IVF/ICSI with expected poor ovarian response according to the Bologna criteria? A randomized controlled trial. Eur J Obstet Gynecol Reprod Biol 200 : 11─15, 2016

20）Chern CU, et al : Dehydroepiandrosterone（DHEA）supplementation improves in vitro fertilization outcomes of poor ovarian responders, especially in women with low serum concentration of DHEA-S : a retrospective cohort study. Reprod Biol Endocrinol 16 : 90, 2018

21）Narkwichean A, et al : Efficacy of Dehydroepiandrosterone（DHEA） to overcome the effect of ovarian ageing（DITTO） : A proof of principle double blinded randomized placebo controlled trial. Eur J Obstet Gynecol Reprod Biol 218 : 39─48, 2017

22）Johnson J, et al : Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 428 : 145─150, 2004

23）Zou K, et al : Production of offspring from a germline stem cell line derived from neonatal ovaries. Nat Cell Biol 11 : 631─636, 2009

24）White YA, et al : Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med 18 : 413─421, 2012

25）Ding X, et al : Human GV oocytes generated by mitotically active germ cells obtained from follicular aspirates. Sci Rep 6 : 28218, 2016

26）Silvestris E, et al : In vitro differentiation of human oocyte-like cells from oogonial stem cells : single-cell isolation and molecular characterization. Hum Reprod 33 : 464─473, 2018

27）Telfer EE, et al : In vitro development of ovarian follicles. Semin Reprod Med 29 : 15─23, 2011

28）McLaughlin M, et al : Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system. Mol Hum Reprod 24 : 135─142, 2018

29）Woods DC, et al : The next（re） generation of ovarian biology and fertility in women : is current science tomorrow's practice? Fertil Steril 98 : 3─10, 2012

30）Fakih MH, et al : The AUGMENTSM Treatment : physician reported outcomes of the initial global patient experience. JFIV Reprod Med Genet 3 : 154, 2015

31）Hayashi K, et al : Offspring from oocytes derived from in vitro primordial germ cell-like cells in mice. Science 338 : 971─975, 2012

32）Nakaki F, et al : Induction of mouse germ-cell fate by transcription factors in vitro. Nature 501 : 222─226, 2013

33）Yamashiro C, et al : Generation of human oogonia from induced pluripotent stem cells in vitro. Science, 2018［Epub ahead of primt］