biostudies-literatureQigen XNational Natural Science Foundation of ChinaMedical Research Funding of Guangdong70https://www.ebi.ac.uk/biostudies/studies/S-EPMC12465185biostudies-literatureUnknown16(1)<h4>Background</h4>Emerging evidence suggests that genetic variants and environmental toxicants may synergistically contribute to DSD. To test this hypothesis, we employed Lhcgr^W495X/+ (luteinizing hormone/chorionic gonadotropin receptor) male mice subjected to prenatal Di-(2-ethylhexyl) phthalate (DEHP) exposure, a model designed to investigate steroidogenic gene expression in gene-environment interactions.<h4>Methods</h4>Pregnant wild-type (WT) dams (mated with Lhcgr^W495X/+ heterozygote (HET) received varying levels of DEHP: no exposure, low-dose (100 mg/kg/d) DEHP, and high-dose (1000 mg/kg/d) DEHP during gestation, which led to prenatal exposure in male offspring. Male offspring were divided into HET (Lhcgr^W495X/+) and WT groups based on genotype in thrBiology of sex differencesGenetic variants (Lhcgr&lt;sup&gt;W495X/+&lt;/sup&gt;) and environmental toxicants (DEHP) synergistically induce DSD by interfering with steroidogenic gene expression.PMC12465185A202249981971314Qigen XHaiming CKai XYong GZhe XChunhua DfalseGenetic variants (Lhcgr&lt;sup&gt;W495X/+&lt;/sup&gt;) and environmental toxicants (DEHP) synergistically induce DSD by interfering with steroidogenic gene expression.<h4>Background</h4>Emerging evidence suggests that genetic variants and environmental toxicants may synergistically contribute to DSD. To test this hypothesis, we employed Lhcgr^W495X/+ (luteinizing hormone/chorionic gonadotropin receptor) male mice subjected to prenatal Di-(2-ethylhexyl) phthalate (DEHP) exposure, a model designed to investigate steroidogenic gene expression in gene-environment interactions.<h4>Methods</h4>Pregnant wild-type (WT) dams (mated with Lhcgr^W495X/+ heterozygote (HET) received varying levels of DEHP: no exposure, low-dose (100 mg/kg/d) DEHP, and high-dose (1000 mg/kg/d) DEHP during gestation, which led to prenatal exposure in male offspring. Male offspring were divided into HET (Lhcgr^W495X/+) and WT groups based on genotype in thr2025-01-01T00:00:00Z2025 Sep2026-05-02T03:16:56.045Z2026-05-02T03:08:43.613ZS-EPMC124651854101375710.1186/s13293-025-00753-0