ACP-HIP(Quest PharmaTech)

Exposure to individual phthalates disrupts ovarian function; however, the direct effects of phthalate mixture exposure on ovulation is unknown, especially in women. Human granulosa cells were used to test the hypothesis that exposure to a phthalate mixture (PHTmix; derived from women's urinary phthalate levels) disrupts the function of prostaglandins (PGs), which are vital mediators of ovulation. Additionally, cAMP supplementation was tested as a method to circumvent phthalate toxicity. Granulosa cells from women undergoing in vitro fertilization were acclimated in culture to regain responsiveness to human chorionic gonadotropin (hCG; clinical luteinizing hormone analogue). Granulosa cells were treated with or without hCG, with or without PHTmix (1-500 µg/ml; DMSO=vehicle control), and with or without 8-Br-cAMP (stable cAMP analogue) for 6-36 hr. Exposure to hCG+PHTmix decreased ovulatory PGE₂ and PGF_2α levels when compared to hCG. The mechanism by which the PHTmix decreased PG levels was via decreased synthesis (decreased PTGS2 and PTGES levels) and increased metabolism (increased AKR1C1, AKR1C3, and HPGD levels). Exposure to hCG+PHTmix also impaired PG function by altering levels of PG transporters (ABCC4 and SLCO2A1) and receptors (PTGER2, PTGER3, and PTGFR) when compared to hCG. Supplementation with cAMP in the hCG+PHTmix 500 µg/ml group restored PGE₂ and PGF_2α levels comparable to and beyond hCG control levels. These findings suggest that phthalates inhibit the ovulatory increase in PGs in human granulosa cells via decreased synthesis and increased metabolism. Restored PG levels with cAMP supplementation further establishes a mechanism of toxicity by providing demonstration of a potential cellular target of phthalate-induced ovulatory defects in women.

Testosterone is the primary male hormone, which is essential for sexual differentiation, spermatogenesis, and the development of male sexual characteristics. It has been recommended for therapeutic use for symptomatic hypogonadism as androgen replacement therapy. However, the misuse and abuse of testosterone and other anabolic androgenic steroids (AAS) are detrimental to cardiovascular and psychological health, with a serious risk to male reproductive health. Testosterone abuse adversely impacts male fertility by suppressing the hypothalamic-pituitary-gonadal axis, leading to reduced intratesticular testosterone levels, impaired spermatogenesis, testicular atrophy and azoospermia. Additionally, chronic testosterone abuse induces oxidative stress and DNA damage in sperm cells, and may lead to sexual dysfunction. Recovery for fertility parameters after cessation of abuse is often prolonged and may be incomplete in many cases. Diagnostic approaches include clinical profile, hormonal assessment, semen analysis, genetic testing, and imaging techniques. Management involves cessation of AAS use, pharmacological interventions such as human chorionic gonadotropin and selective estrogen receptor modulators, lifestyle modifications, and assisted reproductive techniques for refractory infertility. Prevention measures focus on public awareness campaigns targeting athletes and young individuals to raise awareness about the adverse effects of testosterone abuse on fertility as well as overall health. This article discusses the physiological functions of testosterone and its therapeutic applications. Also, the article explains the mechanisms through which testosterone abuse exerts its negative effect on reproductive and general health. Additionally, the article explores the effects of the current pandemic of testosterone on male fertility. Further, the latest advancements and future directions to tackle this menace of testosterone abuse and minimise its effects on spermatogenesis have been deliberated.