Hexachlorobenzene, a pollutant in hypothyroidism and reproductive aberrations: a perceptive transgenerational study.

Hexachlorobenzene (HCB), a widespread environmental pollutant, contributes to endocrine disruption resulting in hypothyroidism. We investigated the effect of chronic exposure of HCB to explore the functional interconnection between hypothyroidism and infertility. All observations were made through the F1 and F2 generations. Thyroidectomy was also performed to evaluate the contribution of the thyroid gland in affecting ovarian dysfunction and reproductive aberrations. We confirmed that the preconception exposure of HCB leads to hypothyroidism which was reflected by an increase in the body weight, alteration in the thyroid hormones, and alteration of the lipid profile. Hypothyroid female rats exhibited a poor reproductive profile with altered steroidogenic pathways, altered estrus cyclicity, reduced litter size, and stunted growth. The external supplementation of thyroxine in thyroidectomized animals rescues the reproductive aberrations confirming the protective role of the thyroid gland in reproductive biology. All results highlight the jeopardizing functional connection of the thyroid and ovary due to HCB, leading to serious consequences on upcoming generations.

Phosphodiesterase 8B Polymorphism rs4704397 Is Associated with Infertility in Subclinical Hypothyroid Females: A Case-Control Study.

BACKGROUND: Subclinical hypothyroidism (SCH) remains largely unnoticed as a major cause of infertility due to asymptomatic. Polymorphisms of phosphodiesterase 8B gene (PDE8B) have been linked with various diseases, including female infertility. Hence, we aimed to study prevalence of SCH, in infertile females, explore association of PDE8B rs4704397 A/G and rs6885099 G/A polymorphisms with infertility in females suffering from SCH and genotype-phenotype correlation of the polymorphisms with thyroid stimulating hormone (TSH) levels in Gujarat population. MATERIALS AND METHODS: In this retrospective study, TSH level was estimated from plasma of 230 infertile and 100 control females by enzyme-linked fluorescence immunoassay (ELFA) to find out the prevalence of SCH. Further, based on TSH levels, thyroid function test (TFT) was performed in controls and infertile females with subclinical hypothyroidism (IF-SCH). PDE8B rs4704397 and rs6885099 polymorphisms were genotyped by PCR-RFLP and ARMS-PCR, respectively in 74 controls and 60 IF-SCH females. RESULTS: We observed i. significantly high prevalence of SCH (32%) in the infertile females, ii. significantly lower frequency of 'G' allele (P=0.006), while the frequency of 'A' allele (P<0.0001) was higher in IFSCH females, compared to the controls, for rs4704397 A/G SNP, iii. no significant difference in the genotype (P=0.214; OR=2.51; CI=0.74-8.42) and the allele frequency (P=0.129; OR=1.51; CI=0.92-2.47) of rs6885099 G/A SNP, iv) low linkage disequilibrium for the polymorphisms, v. significantly higher frequency of 'AA' haplotype (P=0.0001; OR=3.84; CI=1.86-8.01),while the 'GG' haplotype (P=0.0023; OR=0.33; CI=0.16-0.69) was significantly lower in IF-SCH females and vi. no significant difference in the TSH level of IF-SCH females with respect to the genotypes. CONCLUSION: The present study reports an association of PDE8B rs4704397 polymorphism with infertility in SCH females. The study categorically shows a higher prevalence of SCH in infertile females of Gujarat and advocates the importance of screening for SCH in infertility management.