Enzyme-Disrupting Chemicals as the Elephant in the Room for Infertility

Vol.:(0123456789)1 3 The Journal of Obstetrics and Gynecology of India (July–August 2023) 73(4):293–294 https://doi.org/10.1007/s13224-023-01819-y OPINION STATEMENT Enzyme‑Disrupting Chemicals as the Elephant in the Room for Infertility Geetha Balsarkar1 Received: 21 July 2023 / Accepted: 25 July 2023 / Published online: 10 August 2023 © Federation of Obstetric & Gynecological Societies of India 2023 Endocrine-disrupting chemicals (EDCs) are defined as “Exogenous compounds or mixtures that alter function(s) of the endocrine system and consequently cause adverse effects in an intact organism, or its progeny, or (sub) popu- lations” [1]. The term “endocrine disruptor” was first proposed 30 years ago and the US Environmental Protection Agency has now identified 1,482 man-made chemicals that are consid- ered EDCs [2]. EDCs have adverse effects on various steroid-sensitive tissues, thereby causing diseases such as obesity, diabetes mellitus, cardiovascular diseases, reproductive disorders, and cancers. Among these, particular attention has been paid to the male and female reproductive system and infertility in recent years. There are increasing number of manuscripts in various journals over the years on infertility and EDCs, where EDCs affect fertility either directly or indirectly. Bisphenol A, steroid sex hormones, metal complexes, personal care products, pharmaceutical residues, flame retardants, and pesticides are examples of EDCs in day-to- day life. The mechanisms of EDCs involve divergent path- ways including estrogenic, antiandrogenic, thyroid, per - oxisome proliferator-activated receptor gamma, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways. Epigenetic modifications can ensure the pas- sage through next generations as well [1]. Route of human exposures to EDCs can be ingestion, inhalation or dermal contact through food, water, air and dust, and soil. The male reproductive toxicity includes testicular dam- age, reduction in testosterone levels, prostatic hyperplasia and inflammation, and reduction in sperm quantity. The female reproductive toxicity includes increased estrogen levels, cycle irregularity, premature menopause, ovarian damage, and reduction in fertility. Early puberty among girls depends on so many factors including nutrition, stress, and ethnicity, and recently EDCs. Such estrogenic compounds are also associated with uterine fibroids, adenomyosis, endo- metriosis, endometrial cancers, and sub-fertility in humans. Pre- and periconceptional exposure to EDCs can cross vari- ous generations through the womb [3]. COVID-19 is a virus but mimics EDCs very closely. Obesity, adipose tissue cross talk, cardiovascular diseases, endocrine disorders, and malignancies have been implicated which affect fertility adversely. The DES disaster illustrates three core principles of endo- crine disruption. First, latency between exposure and effect can be extremely long, even decades. DES-exposed babies were born healthy by all appearance, with no evidence of the reproductive consequences that would ultimately befall them. The second key principle is that the timing of expo- sure, perhaps even more than dose, drives the potential and severity of adverse outcomes. The third key principle of endocrine disruption is that the dose response of many hormones and EDCs appears to be nonlinear, and adverse outcomes might be different at low vs high doses [4, 5]. Every pregnant woman on the planet is currently carry - ing a mixture of chemicals during her pregnancy that could affect not only her daughter’s reproductive health and fertil- ity but also her granddaughter’s fertility which is a major reason why the topic of endocrine disruption must continue to receive global attention from scientists, governments, and the general public [6].Geetha Balsarkar is an Editor in Chief, Journal of Obstetrics and Gynecology of India. * Geetha Balsarkar [email protected] 1 Seth GS Medical College and KEM Hospital, Mumbai, India 294 G. Balsarkar 1 3 References 1. Diamanti-Kandarakis Evanthia, et  al. Endocrine-disrupting chemicals: an Endocrine society scientific statement. Endocr Rev. 2009;30(4):293–342. https:// doi. org/ 10. 1210/ er. 2009- 0002. 2. Segal TR, Giudice LC. Before the beginning: environmental exposures and reproductive and obstetrical outcomes. Fertil Steril. 2019;112:613–21. 3. 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