TY - JOUR
T1 - Prenatal exposure to Di(2-ethylhexyl) phthalate and high-fat diet synergistically disrupts gonadal function in male mice
AU - Barakat, Radwa
AU - Lin, Po-Ching Patrick
AU - Bunnell, Mary
AU - Oh, Ji-Eun
AU - Rattan, Saniya
AU - Arnieri, Cyrus
AU - Flaws, Jodi A
AU - Ko, CheMyong J
PY - 2024/4/1
Y1 - 2024/4/1
N2 - Prenatal exposure to Di (2-ethylhexyl) phthalate (DEHP) impairs the reproductive system and causes fertility defects in male offspring. Additionally, high-fat (HF) diet is a risk factor for reproductive disorders in males. In this study, we tested the hypothesis that prenatal exposure to a physiologically relevant dose of DEHP in conjunction with HF diet synergistically impacts reproductive function and fertility in male offspring. Female mice were fed a control or HF diet 7 days prior to mating and until their litters were weaned on postnatal day 21. Pregnant dams were exposed to DEHP or vehicle from gestational day 10.5 until birth. The male offspring’s gross phenotype, sperm quality, serum hormonal levels, testicular histopathology, and testicular gene expression pattern were analyzed. Male mice born to dams exposed to DEHP + HF had smaller testes, epididymides, and shorter anogenital distance compared with those exposed to HF or DEHP alone. DEHP + HF mice had lower sperm concentration and motility compared with DEHP mice. Moreover, DEHP + HF mice had more apoptotic germ cells, fewer Leydig cells, and lower serum testosterone levels than DEHP mice. Furthermore, testicular mRNA expression of Dnmt1 and Dnmt3a was two to eight-fold higher than in DEHP mice by qPCR, suggesting that maternal HF diet and prenatal DEHP exposure additively impact gonadal function by altering the degree of DNA methylation in the testis. These results suggest that the combined exposure to DEHP and high-fat synergistically impairs reproductive function in male offspring, greater than exposure to DEHP or HF diet alone. Summary Sentence The combined exposure to DEHP and high-fat synergistically impairs reproductive function in maleoffspring, greater than exposure to DEHP or HF diet alone.
AB - Prenatal exposure to Di (2-ethylhexyl) phthalate (DEHP) impairs the reproductive system and causes fertility defects in male offspring. Additionally, high-fat (HF) diet is a risk factor for reproductive disorders in males. In this study, we tested the hypothesis that prenatal exposure to a physiologically relevant dose of DEHP in conjunction with HF diet synergistically impacts reproductive function and fertility in male offspring. Female mice were fed a control or HF diet 7 days prior to mating and until their litters were weaned on postnatal day 21. Pregnant dams were exposed to DEHP or vehicle from gestational day 10.5 until birth. The male offspring’s gross phenotype, sperm quality, serum hormonal levels, testicular histopathology, and testicular gene expression pattern were analyzed. Male mice born to dams exposed to DEHP + HF had smaller testes, epididymides, and shorter anogenital distance compared with those exposed to HF or DEHP alone. DEHP + HF mice had lower sperm concentration and motility compared with DEHP mice. Moreover, DEHP + HF mice had more apoptotic germ cells, fewer Leydig cells, and lower serum testosterone levels than DEHP mice. Furthermore, testicular mRNA expression of Dnmt1 and Dnmt3a was two to eight-fold higher than in DEHP mice by qPCR, suggesting that maternal HF diet and prenatal DEHP exposure additively impact gonadal function by altering the degree of DNA methylation in the testis. These results suggest that the combined exposure to DEHP and high-fat synergistically impairs reproductive function in male offspring, greater than exposure to DEHP or HF diet alone. Summary Sentence The combined exposure to DEHP and high-fat synergistically impairs reproductive function in maleoffspring, greater than exposure to DEHP or HF diet alone.
KW - DEHP
KW - high-fat diet
KW - male fertility
KW - Maternal exposure
UR - http://www.scopus.com/inward/record.url?scp=85193309509&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85193309509&partnerID=8YFLogxK
U2 - 10.1093/biolre/ioae029
DO - 10.1093/biolre/ioae029
M3 - Article
C2 - 38381622
SN - 0006-3363
VL - 110
SP - 1025
EP - 1037
JO - Biology of reproduction
JF - Biology of reproduction
IS - 5
M1 - ioae029
ER -