Effect of estrogen deprivation on follicle/oocyte maturation and embryo development in mice

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Journal Title:
CHINESE MEDICAL JOURNAL
Issue:
Volume 117, Issue 04, 2004
DOI:
Key Word:
estrogen;progesterone;embryo and fetal development

Abstract: Background It is believed that estrogen plays pivotal roles in the regulation of follicle/oocyte maturation and oocyte fertilizability. It is also involved in the functional preparation of the fallopian tubes for subsequent gamete interaction, in early embryonic development occurring in the tubal microenvironment, and in the preparation of the uterus for implantation. This study was designed to determine whether estrogen is required for follicular and embryonic development.Methods The biosynthesis of estrogen was blocked by a daily injection of the aromatase inhibitor,Arimidex, at a dose of 100 μg/d, using 3 -4 week old C57B6 F1 female mice. Injections were continued for 3 days in experiment 1 (n = 10) and for 5 days in experiment 2 (n = 23). Mice in the control group (n = 27) were given the same amount of saline. Exogenous gonadotrophin [ 7. 5 IU pregnant mare serum gonadotrophin (PMSG)] was administered to induce follicular growth and development on the second day. In experiment 1, we tested estrogen and progesterone levels and examined ovary morphology two days later. In experiment 2, 47 hours after PMSG injection, 5 IU human chorionic gonadotropin (hCG) was given and two female mice were then caged with a male mouse overnight. Two days later, we measured estrogen and progesterone levels. We then removed the embryos, cultured them, and examined embryonic development every 24 hours for 3 days.Results Before hCG injection, estrogen levels in mice from the Arimidex group were suppressed by 94%, and progesterone levels were suppressed by 75%. There was no difference between the two groups in mean number of total follicles found per animal (30.4 follicles/animal in the control group and 27 follicles/animal in the Arimidex group). Two days after hCG injection, estrogen levels in the Arimidex group were significantly lower than that in the control group (P<0.01), while progesterone levels were not significantly lower (P>0.05). The rate of development of embryos, morulae,blastocysts, and hatching blastocysts was not significantly different between the two groups (P =0.20, 0. 10, 0.44, and 0. 38, respectively).Conclusions In the present study, by depriving mice of normal estrogen support, we have been able to rule out the absolute need for rising levels of estrogen for the completion of the follicular maturation process and the development of embryos in vitro.

  • [1]Filicori M. The role of luteinizing hormone in folliculogenesis and ovulation induction. Fertil Steril 1999 ;71:405-414.
  • [2]Galway AB, Lapolt PS, Tsafriri A, et al. Recombinant follicle-stimulating hormone induces ovulation and tissue plasminogen activator expression in hypophysectomized rats.Endocrinology 1990; 127:3023-3028.
  • [3]Schoot DC, Coelingh Bennink H J, Mannaerts BM, et al.Human recombinant follicle-stimulating hormone induces growth of preovulatory follicles without concomitant increase in androgen and estrogen biosynthesis in a woman with isolated gonadotropin deficiency. J Clin Endocrinol Metab 1992;74:1471-1473.
  • [4]Dukes M, Philip NE, Large M, et al. The preclinical pharmacology of "Arimidex" (Anastrozole; ZD1033)- a potent, selective aromatase inhibitor. J. Steroid Biochem Molec Biol 1996 ;58:439445.
  • [5]Lubahn DB, Moyer JS, Golding TS, et al. Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc Nail Acad Sci U S A 1993;90:11162-11166.
  • [6]Coney P, Yoshimura Y, Hosoi Y, et al. Effect of aromatase inhibitors on the histology of the cycling rat ovary. Gynecol Obstet Invest 1987 ;23:177-183.
  • [7]Rosenfeld CS, Murray AA, Simmer G, et al. Gonadotropin induction of ovulation and corpus luteum formation in young estrogen receptor-o knockout mice. Biol Reprod 2000;62:599-605.
  • [8]Krege JH, Hodgin JB, Couse JF, et al. Generation and reproductive phenotypes of mice lacking estrogen receptor β.Proc Nail Acad Sci U S A 1998 ;95:15677-15682.
  • [9]Zachos NC, Billiar RB, Albrecht ED, et al. Developmental regulation of baboon fetal ovarian maturation by estrogen. Biol Reprod 2002 ;67:1148-1156.
  • [10]Rabinovici, J, Blankstein J, Goldman B, et al. In vitro fertilization and primary embryonic cleavage are possible in 17alpha-hydroxylase deficiency despite extremely low intrafollicular 17 beta-estradiol. J Clin Endocrinol Metab 1989 ;68:693-697.
  • [11]Meirow D, Schenker JG, Rosler A. Ovarian hyperstimulation syndrome with low oestradiol in non-classical 17 alphahydroxylase 17, 20-1yase deficiency: what is the role of estrogens? Hum Reprod 1996; 11:2119-2121.
  • [12]Pellicer A, Miro F, Sampaio M, et al. In vitro fertilization as a diagnostic and therapeutic tool in a patient with 17, 20-desmolase deficiency. Fertil Steril 1991 ;55:970-975.
  • [13]Lutjen P, Trounson A, Leeton J, et al. The establishment and maintenance of pregnancy using in vitro fertilization and emhryo donation in a patient with primary ovarian failure.Nature 1984 ;307:174-175.
  • [14]Conte FA, Grumbach MM, Ito Y, et al. A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450 arom). J Clin Endocrinol Metab 1994 ;78:1287-1292.
  • [15]Morishima A, Grumbach MM, Simpson ER, et al. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab 1995 ;80:3689-3698.
  • [16]Hu Y, Cortvrindt R, Smitz J. Effects of aromatase inhibition on in vitro follicle and oocyte development analyzed by early preantral mouse follicle culture. Mol Reprod Dev 2002; 61:549-559.
  • [17]Zelinski-Wooten MB, Hess DL, Baughman WL, et al.Administration of an aromatase inhibitor during the late follicular phase of gonadotropin-treated cycles in rhesus monkeys: effects on follicle development, oocyte maturation,and subsequent luteal function. J Clin Endocrinol Metab 1993 ;76:988-995.
  • [18]Zelinski-Wooten MB, Hess DL, Wolf DP, et al. Steroid reduction during ovarian stimulation impairs oocyte fertilization, but not folliculogenesis, in rhesus monkeys.Fertil Steril 1994;61:1147-1155.
  • [19]Meldrum DR. Blastocyst transfer-a natural evolution. Fertil Steril 1999 ;72:216-217.
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