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Synergistic Regulatory Effect of Inhibin and Anti-Mullerian Hormone on Fertility of Mice

ABSTRACT: Inhibin (INH) and anti-Müllerian hormone (AMH) are essential in ovarian folliculogenesis and play an inhibitory role in mammalian fertility. However, the interactive effect of INH and AMH on the animal reproduction remains unknown. This study aimed to determine the possible interaction and synergy between INH and AMH in steroidogenesis by primary granulosa cells, and investigate their synergistic effect on fertility in mice. In in vitro granulosa cell culture system, we found that the treatment of either INHA or AMH had no significant effect on basal estradiol and progesterone production, whereas both significantly attenuated FSH-induced steroid hormone secretion. Importantly, combined treatment with INHA and AMH showed additive inhibitory effect on FSH-induced estradiol and progesterone production, accompanying a significant downregulation in the expression of FSH-stimulated CYP19A1, HSD3B, CYP11A1, StAR transcripts. The interrelationship of INH and AMH combinations was further investigated through active immune neutralization strategy. Female mice were immunized against INH and AMH eukaryotic expression plasmids, and the litter size was recorded after successfully mating. We observed that both INH and AMH plasmids were able to induce either anti-AMH or anti-INH antibodies in the immunized mice. In comparison with the control group, co-immunization with INH and AMH plasmids induced higher levels of estradiol, resulting in more litter size. Moreover, there was no significant difference on the offspring's weight between each group. Collectively, the results of the present study suggest that INH and AMH have synergistic effect in regulating steroidogenesis and the litter size in mice.

SUBMITTER: Yu X

PROVIDER: S-EPMC8607300 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTo identify childhood cancer survivors (CCSs) at risk of premature ovarian insufficiency (POI) and impaired fertility is important given its impact on quality of life. The aim of this study was to assess ovarian markers and fertility outcomes in adult female CCSs. We used the Swedish and the PanCareLIFE classifications for infertility risk grouping.Methods167 CCSs, at median age 34.6 years (19.3-57.8) with a median follow-up time of 25.4 years (11.6-41.3), and 164 healthy matched controls were included in this cross-sectional study. We assessed anti-Müllerian hormone (AMH) levels, antral follicle count (AFC), ovarian volume (OV), and fertility outcomes. Based on gonadotoxic treatments given, CCSs were categorized into infertility risk groups.ResultsThe median levels of AMH, AFC and OV were lower in CCSs (1.9 vs. 2.1 ng/ml, 12.0 vs. 13.0, 6.8 vs. 8.0 cm3) compared with controls, although statistically significant only for OV (p = 0.021). AMH levels in CCSs <40 years were lower for those classified as high-risk (p = 0.034) and very high-risk (p<0.001) for infertility, based on the Swedish risk classification. Similarly, AFC was reduced in the high-risk (p<0.001) and the very high-risk groups (p = 0.003). CCSs of all ages showed a trend towards impaired fertility, especially in the very high-risk group. POI was diagnosed in 22/167 CCSs, of whom 14 were in the high- and very high-risk groups. The results according to the PanCareLIFE classification were similar.ConclusionBoth the Swedish and the PanCareLIFE infertility risk classifications are reliable tools for identifying those at risk of reduced ovarian markers and fertility, as well as POI. We recommend fertility preservation counselling for patients receiving highly gonadotoxic treatments (i.e., Cyclophosphamide Equivalent Dose ≥6 g/m2, radiotherapy exposure to ovaries or stem cell transplantation) with follow-up at a young reproductive age due to the risk of a shortened reproductive window.

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Synergistic Regulatory Effect of Inhibin and Anti-Mullerian Hormone on Fertility of Mice

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