Intergenerational effects on fertility in male and female mice after chronic exposure to environmental doses of NSAIDs and 17α-ethinylestradiol mixtures

Philibert, Pascal; Stévant, Isabelle; Déjardin, Stéphanie; Girard, Mélissa; Sellem, Eli; Durix, Quentin; Messager, Aurélie; Gonzalez, Anne-Alicia; Mialhe, Xavier; Pruvost, Alain; Poulat, Francis; Boizet-Bonhoure, Brigitte

doi:10.1016/j.fct.2023.114085

Cited by 2 publications

(7 citation statements)

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“…Also, endometrial atrophy has been associated with adverse pregnancy complications [77]. Thus, our results might explain the subfertility of F1 and F2 females after 4-5 months of age [53].…”

Section: Discussionmentioning

confidence: 55%

“…females (exposed) and also in their F2 offspring [53]. However, the effects of these chemicals on the uterus morphology/physiology remain unclear.…”

Section: Exposure To Nsaid and Ee2 Mixtures Induces Adenomyosis Lesio...mentioning

confidence: 99%

“…Recently, we showed that chronic exposure to a mixture containing IBU, 2h-IBU, DCF, and EE2 at two environmentally relevant doses, intergenerationally impairs ovary development and physiology in F1 mice and their offspring. This leads to early puberty onset in F1-exposed postnatal females and their F2 offspring [52] and altered reproductive organ maturation in adult F1 and F2 females [53]. F1 and F2 females also showed irregular estrous cyclicity, although 17βestradiol (E2) concentration in serum was not significantly affected [53].…”

Section: Introductionmentioning

confidence: 99%

“…This leads to early puberty onset in F1-exposed postnatal females and their F2 offspring [52] and altered reproductive organ maturation in adult F1 and F2 females [53]. F1 and F2 females also showed irregular estrous cyclicity, although 17βestradiol (E2) concentration in serum was not significantly affected [53]. Consequently, fertility (number of pups per litter and number of days between litters) decreased with age in F1 females (exposed) and also in their F2 offspring [53].…”

Section: Introductionmentioning

confidence: 99%

“…F1 and F2 females also showed irregular estrous cyclicity, although 17βestradiol (E2) concentration in serum was not significantly affected [53]. Consequently, fertility (number of pups per litter and number of days between litters) decreased with age in F1 females (exposed) and also in their F2 offspring [53]. However, the effects of these chemicals on the uterus morphology/physiology remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Adenomyotic Lesions Are Induced in the Mouse Uterus after Exposure to NSAID and EE2 Mixtures at Environmental Doses

Boizet-Bonhoure,

Déjardin,

Girard

et al. 2024

IJMS

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The aim of this study was to assess the long-term effect of exposure to environmentally relevant doses of non-steroidal anti-inflammatory drugs (NSAIDs; ibuprofen, and diclofenac) and 17β-ethinylestradiol (EE2) on the mouse uterus. NSAID-EE2 mixtures were administered in the drinking water from gestational day 8 until 8 weeks post-birth (i.e., during embryo development, lactation, puberty, and sexual maturity). The incidence of adenomyosis lesions (presence of endometrial glands in the inner myometrium) increased up to 60% in the uterus of 8-week-old exposed females (F1) and to 85% in F2 females (exposed father). Histological analysis revealed aberrant proliferation and apoptosis, vacuolization of epithelial cells, and increased incidence of abnormal glands in the luminal and glandular epithelium in F1 and F2 uteri. Moreover, myofibroblast proportion (alpha-smooth muscle actin (α-SMA) expression analysis) and collagen expression (Picrosirius red stain; a fibrosis hallmark) were increased in F1 and F2 endometrium. Connexin-43 was aberrantly distributed in the endometrial stroma and glands of F1 and F2 uteri. Conversely, uterine 17β-estradiol and progesterone levels were not affected in F1 and F2 females. These findings demonstrated that in mice, chronic exposure to NSAID and EE2 mixtures at environmental doses intergenerationally affects uterine physiology, particularly the endometrium. It may serve as a model to study the pathophysiology of human adenomyosis.

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Section: Discussionmentioning

confidence: 55%

“…females (exposed) and also in their F2 offspring [53]. However, the effects of these chemicals on the uterus morphology/physiology remain unclear.…”

Section: Exposure To Nsaid and Ee2 Mixtures Induces Adenomyosis Lesio...mentioning

confidence: 99%