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Etiology of Male Infertility: an Update

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Abstract

Spermatogenesis is a complex process of germ cell division and differentiation that involves extensive cross-talk between the developing germ cells and the somatic testicular cells. Defective endocrine signaling and/or intrinsic defects within the testes can adversely affect spermatogenic progression, leading to subfertility/infertility. In recent years, male infertility has been recognized as a global public health concern, and research over the last few decades has elucidated the complex etiology of male infertility. Congenital reproductive abnormalities, genetic mutations, and endocrine/metabolic dysfunction have been demonstrated to be involved in infertility/subfertility in males. Furthermore, acquired factors like exposure to environmental toxicants and lifestyle-related disorders such as illicit use of psychoactive drugs have been shown to adversely affect spermatogenesis. Despite the large body of available scientific literature on the etiology of male infertility, a substantial proportion of infertility cases are idiopathic in nature, with no known cause. The inability to treat such idiopathic cases stems from poor knowledge about the complex regulation of spermatogenesis. Emerging scientific evidence indicates that defective functioning of testicular Sertoli cells (Sc) may be an underlying cause of infertility/subfertility in males. Sc plays an indispensable role in regulating spermatogenesis, and impaired functional maturation of Sc has been shown to affect fertility in animal models as well as humans, suggesting abnormal Sc as a potential underlying cause of reproductive insufficiency/failure in such cases of unexplained infertility. This review summarizes the major causes of infertility/subfertility in males, with an emphasis on infertility due to dysregulated Sc function.

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Abbreviations

ART:

Assisted reproductive techniques

CFTR:

Cystic fibrosis transmembrane conductance regulator

DSDs:

Disorders of sexual development

ED:

Erectile dysfunction

EDO:

Ejaculatory duct obstruction

FSH:

Follicle-stimulating hormone

Gc:

Germ cells

GnRH:

Gonadotropin-releasing hormone.

HHT:

Hypothalamic-hypophyseal-testicular

IHH:

Idiopathic hypogonadotropic hypogonadism

IVF:

in vitro Fertilization

LH:

Luteinizing hormone

PESA:

Percutaneous epididymal sperm aspiration

Sc:

Sertoli cells

SCOS:

Sertoli cell-only syndrome

SSC:

Spermatogonial stem cell

TDS:

Testicular dysgenesis syndrome

TESA:

Testicular sperm extraction

WHO:

World Health Organization

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Funding

SSM acknowledges funding from the JC Bose Fellowship (SERB-JCB/2017/000027) and DBT-NIAB. IB acknowledges financial support from the Central University of Kerala, Kasaragod, Kerala.

Author information

Authors and Affiliations

  1. Department of Zoology, Central University of Kerala, Periye Campus, Kasaragod, 671320, Kerala, India

    Indrashis Bhattacharya

  2. National Institute of Animal Biotechnology, Hyderabad, 500 032, Telangana, India

    Souvik Sen Sharma & Subeer S. Majumdar

  3. Gujarat Biotechnology University, Gandhinagar, GIFT City, Gandhinagar, 382355, Gujarat, India

    Subeer S. Majumdar

Authors
  1. Indrashis Bhattacharya
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  2. Souvik Sen Sharma
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  3. Subeer S. Majumdar
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Contributions

IB, SSS, and SSM conceived the concept. IB wrote the first draft. SSS prepared all the figures/tables with support from IB. IB, SSS, and SSM edited the manuscript to produce the final draft.

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Correspondence to Indrashis Bhattacharya or Subeer S. Majumdar.

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IB and SSS contributed equally to this work.

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Bhattacharya, I., Sharma, S.S. & Majumdar, S.S. Etiology of Male Infertility: an Update. Reprod. Sci. 31, 942–965 (2024). https://doi.org/10.1007/s43032-023-01401-x

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