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Open Access 06-11-2024 | Fertility | General Gynecology

High-altitude hypoxia exposure alters follicular metabolome and oocyte developmental potential in women

Authors: Zhengfang Xiong, Xiaolei Liu, Qingdi Wang

Published in: Archives of Gynecology and Obstetrics

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Abstract

Purpose

To explore the effects of high-altitude hypoxia on the microenvironment of oocyte development and fertilization potential, we compared the metabolomic patterns of follicular fluid from women living in different altitude areas and traced their oocyte maturation and subsequent development.

Methods

A total of 315 clinical cases were collected and divided into three groups according to their residence altitudes: 138 cases in low-altitude (< 2300 m) group, 100 cases in middle-altitude (2300–2800 m) group and 77 cases in high-altitude (> 2800 m) group. The clinical outcomes were statistically estimated, including hormonal level, oocyte maturation, in vitro fertilization, and embryo development. Meanwhile, a metabolomic analysis was performed on the follicular fluid of women from different groups using ultra-high-performance liquid chromatography and high-resolution mass spectrometry and differential metabolites were analyzed through the KEGG pathway.

Results

The clinical data indicated that the physical condition and reproductive hormone secretion were similar among different groups. Although personalized gonadotropin-releasing hormone strategies were applied, the numbers of antral follicles and obtained oocytes were not impacted by the residence altitude change. In in vitro culture, the maturing rate, fertility rate and cleavage rate of high-altitude group were compared with the other groups. However, the rates of high-quality embryo, formative blastocyst, and available blastocyst were gradually decreased with the rise of residence altitude. Metabolome analysis identified 1193 metabolites in female follicular fluid. Differential analysis indicated that metabolic components in follicular fluid were remarkably changed with the elevation of residence altitude. These differential metabolites were closely related with amino acid metabolism, protein digestion and absorption, oocyte meiosis and steroid biosynthesis.

Conclusion

The residence altitude alters the microenvironment of follicular fluid, which could damage the oocyte developmental potential. This study provides diagnostic basis and therapeutic targets for research on female oocyte and embryo development.
Literature
1.
go back to reference Giudice LC (2006) Infertility and the environment: the medical context. Semin Reprod Med 24(3):129–133PubMedCrossRef Giudice LC (2006) Infertility and the environment: the medical context. Semin Reprod Med 24(3):129–133PubMedCrossRef
3.
4.
go back to reference Practice Committee of the American Society for Reproductive Medicine (2018) Electronic address, a.a.o. and M. practice committee of the American society for reproductive, smoking and infertility: a committee opinion. Fertil Steril 110(4):611–618 Practice Committee of the American Society for Reproductive Medicine (2018) Electronic address, a.a.o. and M. practice committee of the American society for reproductive, smoking and infertility: a committee opinion. Fertil Steril 110(4):611–618
6.
go back to reference Tanbo T, Abyholm T (1991) Assisted reproductive technology. Curr Opin Obstet Gynecol 3(5):649–655PubMedCrossRef Tanbo T, Abyholm T (1991) Assisted reproductive technology. Curr Opin Obstet Gynecol 3(5):649–655PubMedCrossRef
7.
go back to reference Szamatowicz M (2016) Assisted reproductive technology in reproductive medicine–possibilities and limitations. Ginekol Pol 87(12):820–823PubMedCrossRef Szamatowicz M (2016) Assisted reproductive technology in reproductive medicine–possibilities and limitations. Ginekol Pol 87(12):820–823PubMedCrossRef
8.
go back to reference Graham ME et al (2023) Assisted reproductive technology: short- and long-term outcomes. Dev Med Child Neurol 65(1):38–49PubMedCrossRef Graham ME et al (2023) Assisted reproductive technology: short- and long-term outcomes. Dev Med Child Neurol 65(1):38–49PubMedCrossRef
9.
go back to reference Combelles CM, Racowsky C (2005) Assessment and optimization of oocyte quality during assisted reproductive technology treatment. Semin Reprod Med 23(3):277–284PubMedCrossRef Combelles CM, Racowsky C (2005) Assessment and optimization of oocyte quality during assisted reproductive technology treatment. Semin Reprod Med 23(3):277–284PubMedCrossRef
10.
go back to reference Vollenhoven B, Hunt S (2018) Ovarian ageing and the impact on female fertility. F1000Res 7:1835CrossRef Vollenhoven B, Hunt S (2018) Ovarian ageing and the impact on female fertility. F1000Res 7:1835CrossRef
11.
go back to reference Jankovic Velickovic L, Stefanovic V (2014) Hypoxia and spermatogenesis. Int Urol Nephrol 46(5):887–894PubMedCrossRef Jankovic Velickovic L, Stefanovic V (2014) Hypoxia and spermatogenesis. Int Urol Nephrol 46(5):887–894PubMedCrossRef
12.
go back to reference Fajersztajn L, Veras MM (2017) Hypoxia: from placental development to fetal programming. Birth Defects Res 109(17):1377–1385PubMedCrossRef Fajersztajn L, Veras MM (2017) Hypoxia: from placental development to fetal programming. Birth Defects Res 109(17):1377–1385PubMedCrossRef
14.
go back to reference Wray S, Alruwaili M, Prendergast C (2021) Hypoxia and reproductive health: hypoxia and labour. Reproduction 161(1):F67–F80PubMedCrossRef Wray S, Alruwaili M, Prendergast C (2021) Hypoxia and reproductive health: hypoxia and labour. Reproduction 161(1):F67–F80PubMedCrossRef
15.
16.
go back to reference Yang W et al (2021) Hypoxic in vitro culture reduces histone lactylation and impairs pre-implantation embryonic development in mice. Epigenetics Chromatin 14(1):57PubMedPubMedCentralCrossRef Yang W et al (2021) Hypoxic in vitro culture reduces histone lactylation and impairs pre-implantation embryonic development in mice. Epigenetics Chromatin 14(1):57PubMedPubMedCentralCrossRef
17.
go back to reference Ritchie HE, Oakes DJ, Kennedy D, Polson JW (2017) Early gestational hypoxia and adverse developmental outcomes. Birth Defects Res 109(17):1358–1376PubMedCrossRef Ritchie HE, Oakes DJ, Kennedy D, Polson JW (2017) Early gestational hypoxia and adverse developmental outcomes. Birth Defects Res 109(17):1358–1376PubMedCrossRef
18.
go back to reference Molinari E, Bar H, Pyle AM, Patrizio P (2016) Transcriptome analysis of human cumulus cells reveals hypoxia as the main determinant of follicular senescence. Mol Hum Reprod 22(8):866–876PubMedPubMedCentralCrossRef Molinari E, Bar H, Pyle AM, Patrizio P (2016) Transcriptome analysis of human cumulus cells reveals hypoxia as the main determinant of follicular senescence. Mol Hum Reprod 22(8):866–876PubMedPubMedCentralCrossRef
19.
go back to reference Thompson JG, Brown HM, Kind KL, Russell DL (2015) The ovarian antral follicle: living on the edge of hypoxia or not? Biol Reprod 92(6):153PubMedCrossRef Thompson JG, Brown HM, Kind KL, Russell DL (2015) The ovarian antral follicle: living on the edge of hypoxia or not? Biol Reprod 92(6):153PubMedCrossRef
20.
21.
go back to reference Azari-Dolatabad N et al (2021) Follicular fluid during individual oocyte maturation enhances cumulus expansion and improves embryo development and quality in a dose-specific manner. Theriogenology 166:38–45PubMedCrossRef Azari-Dolatabad N et al (2021) Follicular fluid during individual oocyte maturation enhances cumulus expansion and improves embryo development and quality in a dose-specific manner. Theriogenology 166:38–45PubMedCrossRef
22.
go back to reference Wang C et al (2021) Proteomic analysis of the alterations in follicular fluid proteins during oocyte maturation in humans. Front Endocrinol (Lausanne) 12:830691PubMedCrossRef Wang C et al (2021) Proteomic analysis of the alterations in follicular fluid proteins during oocyte maturation in humans. Front Endocrinol (Lausanne) 12:830691PubMedCrossRef
23.
go back to reference Lu JC, Huang YF, Lu NQ (2010) WHO laboratory manual for the examination and processing of human semen: its applicability to andrology laboratories in China. Zhonghua Nan Ke Xue 16(10):867–871PubMed Lu JC, Huang YF, Lu NQ (2010) WHO laboratory manual for the examination and processing of human semen: its applicability to andrology laboratories in China. Zhonghua Nan Ke Xue 16(10):867–871PubMed
24.
go back to reference Stimpfel M, Jancar N, Vrtacnik-Bokal E, Virant-Klun I (2019) Conventional IVF improves blastocyst rate and quality compared to ICSI when used in patients with mild or moderate teratozoospermia. Syst Biol Reprod Med 65(6):458–464PubMedCrossRef Stimpfel M, Jancar N, Vrtacnik-Bokal E, Virant-Klun I (2019) Conventional IVF improves blastocyst rate and quality compared to ICSI when used in patients with mild or moderate teratozoospermia. Syst Biol Reprod Med 65(6):458–464PubMedCrossRef
25.
go back to reference Gardner DK, Stevens J, Sheehan CB, Schoolcraft WB (2007) Analysis of blastocyst morphology. Human preimplantation embryo selection. Informa Healthcare, London, pp 79–88CrossRef Gardner DK, Stevens J, Sheehan CB, Schoolcraft WB (2007) Analysis of blastocyst morphology. Human preimplantation embryo selection. Informa Healthcare, London, pp 79–88CrossRef
26.
go back to reference Sumner LW et al (2007) Proposed minimum reporting standards for chemical analysis chemical analysis working group (CAWG) metabolomics standards initiative (MSI). Metabolomics 3(3):211–221PubMedPubMedCentralCrossRef Sumner LW et al (2007) Proposed minimum reporting standards for chemical analysis chemical analysis working group (CAWG) metabolomics standards initiative (MSI). Metabolomics 3(3):211–221PubMedPubMedCentralCrossRef
27.
go back to reference Wishart DS et al (2022) HMDB 5.0: the human metabolome database for 2022. Nucleic Acids Res 50(1):D622–D631PubMedCrossRef Wishart DS et al (2022) HMDB 5.0: the human metabolome database for 2022. Nucleic Acids Res 50(1):D622–D631PubMedCrossRef
28.
go back to reference Keefe D, Kumar M, Kalmbach K (2015) Oocyte competency is the key to embryo potential. Fertil Steril 103(2):317–322PubMedCrossRef Keefe D, Kumar M, Kalmbach K (2015) Oocyte competency is the key to embryo potential. Fertil Steril 103(2):317–322PubMedCrossRef
29.
go back to reference Homer HA (2020) The role of oocyte quality in explaining “unexplained” infertility. Semin Reprod Med 38(1):21–28PubMedCrossRef Homer HA (2020) The role of oocyte quality in explaining “unexplained” infertility. Semin Reprod Med 38(1):21–28PubMedCrossRef
31.
go back to reference Gilchrist RB, Lane M, Thompson JG (2008) Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Hum Reprod Update 14(2):159–177PubMedCrossRef Gilchrist RB, Lane M, Thompson JG (2008) Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Hum Reprod Update 14(2):159–177PubMedCrossRef
33.
go back to reference Hamazaki N et al (2021) Reconstitution of the oocyte transcriptional network with transcription factors. Nature 589(7841):264–269PubMedCrossRef Hamazaki N et al (2021) Reconstitution of the oocyte transcriptional network with transcription factors. Nature 589(7841):264–269PubMedCrossRef
34.
go back to reference Liang X, Ma J, Schatten H, Sun Q (2012) Epigenetic changes associated with oocyte aging. Sci China Life Sci 55(8):670–676PubMedCrossRef Liang X, Ma J, Schatten H, Sun Q (2012) Epigenetic changes associated with oocyte aging. Sci China Life Sci 55(8):670–676PubMedCrossRef
35.
37.
go back to reference Sang Q, Zhou Z, Mu J, Wang L (2021) Genetic factors as potential molecular markers of human oocyte and embryo quality. J Assist Reprod Genet 38(5):993–1002PubMedPubMedCentralCrossRef Sang Q, Zhou Z, Mu J, Wang L (2021) Genetic factors as potential molecular markers of human oocyte and embryo quality. J Assist Reprod Genet 38(5):993–1002PubMedPubMedCentralCrossRef
38.
go back to reference Turathum B, Gao EM, Chian RC (2021) The function of cumulus cells in oocyte growth and maturation and in subsequent ovulation and fertilization. Cells 10(9):2292PubMedPubMedCentralCrossRef Turathum B, Gao EM, Chian RC (2021) The function of cumulus cells in oocyte growth and maturation and in subsequent ovulation and fertilization. Cells 10(9):2292PubMedPubMedCentralCrossRef
39.
go back to reference Goovaerts IG, Leroy JL, Jorssen EP, Bols PE (2010) Noninvasive bovine oocyte quality assessment: possibilities of a single oocyte culture. Theriogenology 74(9):1509–1520PubMedCrossRef Goovaerts IG, Leroy JL, Jorssen EP, Bols PE (2010) Noninvasive bovine oocyte quality assessment: possibilities of a single oocyte culture. Theriogenology 74(9):1509–1520PubMedCrossRef
40.
go back to reference Wang Q, Sun QY (2007) Evaluation of oocyte quality: morphological, cellular and molecular predictors. Reprod Fertil Dev 19(1):1–12PubMedCrossRef Wang Q, Sun QY (2007) Evaluation of oocyte quality: morphological, cellular and molecular predictors. Reprod Fertil Dev 19(1):1–12PubMedCrossRef
41.
go back to reference Leroy JL et al (2011) Intrafollicular conditions as a major link between maternal metabolism and oocyte quality: a focus on dairy cow fertility. Reprod Fertil Dev 24(1):1–12PubMedCrossRef Leroy JL et al (2011) Intrafollicular conditions as a major link between maternal metabolism and oocyte quality: a focus on dairy cow fertility. Reprod Fertil Dev 24(1):1–12PubMedCrossRef
43.
go back to reference Feng Y et al (2022) Follicular free fatty acid metabolic signatures and their effects on oocyte competence in non-obese PCOS patients. Reproduction 164(1):1–8PubMedCrossRef Feng Y et al (2022) Follicular free fatty acid metabolic signatures and their effects on oocyte competence in non-obese PCOS patients. Reproduction 164(1):1–8PubMedCrossRef
44.
go back to reference Sriraman V et al (2008) Identification of ERK and JNK as signaling mediators on protein kinase C activation in cultured granulosa cells. Mol Cell Endocrinol 294(1–2):52–60PubMedCrossRef Sriraman V et al (2008) Identification of ERK and JNK as signaling mediators on protein kinase C activation in cultured granulosa cells. Mol Cell Endocrinol 294(1–2):52–60PubMedCrossRef
45.
go back to reference Tang J et al (2019) The genetic mechanism of high prolificacy in small tail han sheep by comparative proteomics of ovaries in the follicular and luteal stages. J Proteomics 204:103394PubMedCrossRef Tang J et al (2019) The genetic mechanism of high prolificacy in small tail han sheep by comparative proteomics of ovaries in the follicular and luteal stages. J Proteomics 204:103394PubMedCrossRef
Metadata
Title
High-altitude hypoxia exposure alters follicular metabolome and oocyte developmental potential in women
Authors
Zhengfang Xiong
Xiaolei Liu
Qingdi Wang
Publication date
06-11-2024
Publisher
Springer Berlin Heidelberg
Keyword
Fertility
Published in
Archives of Gynecology and Obstetrics
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-024-07695-9

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