Soy-based formula contains high concentrations of the isoflavone genistein. Genistein possesses estrogenic and tyrosine kinase inhibitory activity and interferes with cellular proliferation
and development. To date, the acute and chronic effects of genistein on ovarian and uterine development have not been fully elucidated. In this study, mice at postnatal day 1 were
subcutaneously injected with 100 mg/kg genistein for 10 consecutive days, and then their ovaries and uteri were collected on days 10, 21, and 90. Histological evaluation was performed after
hematoxylin and eosin staining. The proliferating activity was indicated by the proliferating indicator protein Ki67. Results showed that the subcutaneous injection of genistein to neonatal
mice induced the formation of multi-oocyte follicles and delayed the primordial follicle assembly in the ovaries. Genistein significantly enlarged the cross-sectional area of the uterine
cavity and wall and disrupted the regularity between the uterine stroma and myometrium. Genistein exposure inhibited proliferative activity because fewer Ki67-positive nuclei were detected
in ovarian and uterine cell populations than in the control. Furthermore, most ovaries from adult mice given neonatal genistein were without corpora lutea, and there appeared to be cystic
follicles and hypertrophy of the theca, and cortical and medullary layers. Considering the high concentration of isoflavone in soy-based infant formulas and livestock feed, we suggest that
the use of isoflavone-rich diets in humans and livestock receive closer examination.
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Bisphenol A (BPA) is a chemical of high production volume that is used widely in many industries and is known as a xenooestrogen and anti‐thyroid hormone endocrine disrupter. There is little information regarding the effects of BPA in the presence of thyroid hormone on porcine granulosa cell development. Thus, the primary granulosa cells were treated with thyroxine (T4, 10 nM), BPA (10 µM) or T4 plus BPA; we subsequently evaluated the effects of T4 or BPA on 17β‐estradiol synthesis, cellular proliferation and apoptosis. Our data showed that BPA significantly increased the accumulation of 17β‐estradiol and promoted granulosa cell proliferation, whereas T4 significantly decreased 17β‐estradiol and had no effect on cellular proliferation. In addition, it was noteworthy that T4 treatment induced apoptosis in porcine granulosa cells and BPA co‐incubation attenuated T4‐induced apoptosis as shown from flow cytometric assay analysis. We hypothesized that BPA attenuates T4‐induced apoptosis by regulating 17β‐estradiol accumulation and oestrogen receptor‐mediated signalling pathways. In conclusion, our results demonstrated that T4 affected 17β‐estradiol accumulation and induced cellular apoptosis, but did not affect granulosa cell proliferation. Exposure to BPA increased 17β‐estradiol accumulation, promoted granulosa cell proliferation and attenuated T4‐induced apoptosis in porcine granulosa cells in vitro.
3-nitropropionic acid (3-NPA) is known to be a mitochondrial toxin produced by plants and fungi, which may produce DNA damage in cells. However, studies of its reproductive toxicology are lacking. We know that poly(ADP-ribose) polymerase (PARP) plays an important role in a large variety of physiological processes and is involved in DNA repair pathways. The present study was therefore aimed at exploring the involvement of PARP-1 activation and cleavage after 3-NPA stimulation in female mice. We observed an increased number of atretic follicles and multi-oocyte follicles (MOFs) after treatment with 3-NPA and serum concentrations of 17β-oestradiol and progesterone were significantly reduced. Our results provide evidence that PARP-1 cleavage and activational signals are involved in pathological ovarian processes stimulated by 3-NPA. In addition, total superoxide dismutase, glutathione peroxidase and catalase activities were significantly increased, whereas succinate dehydrogenase was decreased in a dose-dependent manner. Results from our in vitro study similarly indicated that 3-NPA inhibited the proliferation of mouse granulosa cells and increased apoptosis in a dose-dependent manner. In summary, 3-NPA induces granulosa cell apoptosis, follicle atresia and MOFs in the ovaries of female mice and causes oxidative stress so as to disrupt endogenous hormonal systems, possibly acting through PARP-1 signalling.
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