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Environmental factors in declining human fertility

Nature Reviews Endocrinology volume 18, pages 139–157 (2022)Cite this article

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Abstract

A severe decline in child births has occurred over the past half century, which will lead to considerable population declines, particularly in industrialized regions. A crucial question is whether this decline can be explained by economic and behavioural factors alone, as suggested by demographic reports, or to what degree biological factors are also involved. Here, we discuss data suggesting that human reproductive health is deteriorating in industrialized regions. Widespread infertility and the need for assisted reproduction due to poor semen quality and/or oocyte failure are now major health issues. Other indicators of declining reproductive health include a worldwide increasing incidence in testicular cancer among young men and alterations in twinning frequency. There is also evidence of a parallel decline in rates of legal abortions, revealing a deterioration in total conception rates. Subtle alterations in fertility rates were already visible around 1900, and most industrialized regions now have rates below levels required to sustain their populations. We hypothesize that these reproductive health problems are partially linked to increasing human exposures to chemicals originating directly or indirectly from fossil fuels. If the current infertility epidemic is indeed linked to such exposures, decisive regulatory action underpinned by unconventional, interdisciplinary research collaborations will be needed to reverse the trends.

Key points

  • Industrialized regions have birth rates so low that their populations cannot be sustained; declines in birth rates are generally ascribed to socioeconomic and cultural factors, although human infertility is widespread.

  • Decreasing fertility rates were already recorded around 1900 in Denmark, a few decades after the beginning of utilization of fossil fuels that were, and still are, drivers of modern industrialization and wealth.

  • We hypothesize that declines in fertility rates might be linked to exposures to chemicals originating from fossil fuels causing human reproductive problems and cancer; early gestation might be a sensitive period.

  • The current unsustainable birth rates will eventually result in decreasing populations.

  • A key research challenge remains: how to distinguish biological from socioeconomic and behavioural factors?

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Fig. 1: Total fertility rates in the European Union, Japan and the USA, 1960–2018.
Fig. 2: Total fertility rate, Denmark, 1901–2019.
Fig. 3: Changes in average sperm concentrations 1973–2011.
Fig. 4: Testicular cancer incidence trends in selected countries/regions worldwide.
Fig. 5: Illustration of epigenetic drift.
Fig. 6: Adverse outcome pathway network for the induction of male reproductive malformations.
Fig. 7: Expression of the embryonic marker OCT4 in adult germ cell neoplasia in situ is similar to expression in germ cells (gonocytes) in normal fetal gonads.
Fig. 8: Testicular dysgenesis syndrome.
Fig. 9: Levels of unsustainable fertility rates and population sizes (newborn babies) over three generations.

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Acknowledgements

We thank M. Laversanne from the International Agency for Research on Cancer for assistance with the first draft of Fig. 4. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization. The authors acknowledge financial support from the Innovation Fund Denmark, Danish Ministry of Environment (CEHOS), Danish Ministry of Health, The ReproUnion consortium/EU Interreg ÖKS, Brazilian institutions (CNPq and CAPES) and Minas Gerais State Foundation (FAPEMIG). Finally, the authors thank A. Wahlberg, Department of Anthropology, University of Copenhagen, and K. Kjær, GLOBE Institute, University of Copenhagen, for most valuable discussions prior to writing the paper.

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Authors and Affiliations

  1. Department of Growth and Reproduction, Copenhagen University Hospital — Rigshospitalet, Copenhagen, Denmark

    Niels E. Skakkebæk, Anna-Maria Andersson, Niels Jørgensen, Katharina M. Main, Lærke Priskorn, Stine A. Holmboe, Elvira V. Bräuner, Kristian Almstrup & Anders Juul

  2. International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Niels E. Skakkebæk, Anna-Maria Andersson, Niels Jørgensen, Katharina M. Main, Lærke Priskorn, Stine A. Holmboe, Elvira V. Bräuner, Kristian Almstrup & Anders Juul

  3. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

    Niels E. Skakkebæk, Katharina M. Main, Øjvind Lidegaard & Anders Juul

  4. Department of Public Health, University of Southern Denmark, Odense, Denmark

    Rune Lindahl-Jacobsen

  5. School of Public Health, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel

    Hagai Levine

  6. Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Øjvind Lidegaard

  7. Department of Morphology, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil

    Luiz R. Franca

  8. Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France

    Ariana Znaor

  9. Division of Environmental Sciences, Brunel University London, Uxbridge, UK

    Andreas Kortenkamp

  10. Division of Obstetrics and Gynaecology, University of Western Australia, Perth, Western Australia, Australia

    Roger J. Hart

  11. Fertility Specialists of Western Australia, Bethesda Hospital, Claremont, Western Australia, Australia

    Roger J. Hart

Authors
  1. Niels E. Skakkebæk
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  2. Rune Lindahl-Jacobsen
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  3. Hagai Levine
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  4. Anna-Maria Andersson
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  5. Niels Jørgensen
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  6. Katharina M. Main
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  7. Øjvind Lidegaard
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  8. Lærke Priskorn
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  9. Stine A. Holmboe
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  10. Elvira V. Bräuner
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  11. Kristian Almstrup
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  12. Luiz R. Franca
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  13. Ariana Znaor
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  14. Andreas Kortenkamp
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  15. Roger J. Hart
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  16. Anders Juul
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Contributions

N.E.S., R.L.-J., A.-M.A., S.A.H., E.V.B., K.A., L.R.F., A.Z., R.J.H. and A.J. researched data for the article, contributed substantially to discussion of the content, wrote the article and reviewed and/or edited the manuscript before submission. H.L., N.J., K.M.M., Ø.L. and A.K. contributed substantially to discussion of the content, wrote the article and reviewed and/or edited the manuscript before submission. L.P. researched data for the article, contributed substantially to discussion of the content and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Niels E. Skakkebæk.

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Competing interests

R.J.H. is the Medical Director of Fertility Specialists of Western Australia and has equity interests in Western IVF. The other authors declare no competing interests.

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Nature Reviews Endocrinology thanks A.-S. Parent and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Related links

Databank, World Development Indicators: https://databank.worldbank.org/reports.aspx?source=world-development-indicators

Family Planning 2020: https://www.familyplanning2020.org/

Statistics Denmark: http://www.statistikbanken.dk/statbank5a/default.asp?w=1600

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Skakkebæk, N.E., Lindahl-Jacobsen, R., Levine, H. et al. Environmental factors in declining human fertility. Nat Rev Endocrinol 18, 139–157 (2022). https://doi.org/10.1038/s41574-021-00598-8

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