Regulation of steroidogenesis in fetal bovine ovaries: differential effects of LH and FSH

This study was designed to investigate the protective effect of CD4+CD25+ regulatory T cells (Tregs) against zona pellucida glycoprotein 3 peptide (pZP3) immunization‐induced premature ovarian insufficiency (POI) in mice. A mouse POI model was induced by two subcutaneous injections of pZP3 (50 nmol/L). Mice in the pZP3‐Treg group were intraperitoneally injected with 5 × 105 CD4+CD25+ Tregs after the POI model was established. Sex hormone levels, follicle numbers, apoptotic events, and the Akt/FOXO3a signaling pathway molecules in the ovaries were assessed. Compared with control group, the weight of ovaries in both pZP3 group and pZP3‐Treg group was decreased and no difference was found between them. The number of follicles in the Treg transferred mice, like in pZP3 group, was significantly reduced compared to the control group, but showed a modest improvement when compared the pZP3 group alone. Significantly lower serum concentrations of follicle‐stimulating hormone, luteinizing hormone, and anti‐zona pellucida antibodies (AZPAbs) were found, while the concentrations of estradiol and anti‐Mullerian hormone increased. In mechanism, Treg cell transfer to ZP3 treated mice restored the levels of Caspase3 to control levels, and partially restored Bax, however, had no effect on Bcl‐2. Moreover, Treg cell transfer to ZP3 treated mice partially restored the levels of Akt and FOXO3a, and partially restored the ratios of p‐Akt/Akt and p‐FOXO3a/FOXO3a. In conclusion, Treg cells improved some aspects of ZP3‐induced POI which may be mediate by suppressing ovarian cells apoptosis and involving the Akt/FOXO3a signaling pathway. Therefore, Treg cells may be protective against autoimmune POI.

Section: Discussionmentioning

confidence: 99%

Adoptive transfers of CD4⁺CD25⁺ Tregs partially alleviate mouse premature ovarian insufficiency

Liú

Chi-bing

et al. 2020

“…There is a paucity of information on T production by fetal ovaries in cattle, but evidence indicates that T is secreted in 40 to 125‐day‐old fetuses and stays relatively stable during fetal growth (Dominguez, Liptrap, & Basrur, ). Nevertheless, we consider fetal ovaries as a secondary source of T in the NR model, because their T production is limited and A4 is the major androgen produced by fetal ovaries (Allen, Herrick, & Fortune, ). Further, the high aromatase activity in the placenta results in rapid conversion of androgens to estrogens (Conley & Hinshelwood, ) and therefore placental androgens may have only contributed slightly to the transiently increased T concentrations in the NR mothers.…”

Section: Androgens In Women and Female Cattlementioning

confidence: 99%

“…There is a paucity of information on T production by fetal ovaries in cattle, but evidence indicates that T is secreted in 40 to 125-day-old fetuses and stays relatively stable during fetal growth (Dominguez, Liptrap, & Basrur, 1988). Nevertheless, we consider fetal ovaries as a secondary source of T in the NR model, because their T production is limited and A4 is the major androgen produced by fetal ovaries (Allen, Herrick, & Fortune, 2016).…”

Section: Androgens In Women and Female Cattlementioning

confidence: 99%

Undernutrition and hyperandrogenism during pregnancy: Role in programming of cardiovascular disease and infertility

Mossa

Latham

Ireland

et al. 2019

Maternal nutritional status programs the development of several systems in female offspring, with effects that depend on the severity, duration, and window of development when the nutritional perturbation is imposed. On the basis of the developmental origins of health and disease concept, we hypothesize that gestational low caloric intake may induce maternal subclinical hyperandrogenism during early pregnancy and compromise cardiovascular health and fertility in the female offspring. To examine this possibility, a literature search for human and animal studies was conducted using two electronic databases, PubMed and Cochrane until April 2019 to address the following questions: (a) Do androgens have a developmental role in cardiovascular and ovarian development? (b) Is excess maternal testosterone linked to cardiovascular disease and infertility? and (c) Could early pregnancy undernutrition enhance maternal androgen production and compromise health and fertility in female offspring? The observations reviewed, establish a potential causative link between maternal undernutrition and subclinical hyperandrogenism with hypertension and reduced ovarian reserve in the progeny. Further studies in appropriate models are needed to better understand whether low energy intake and subclinical maternal hyperandrogenism during early pregnancy can negatively affect the health of the female offspring.

“…Both luteinizing hormone and follicle stimulating hormone stimulated steroid production in fetal bovine ovarian tissue in vitro (Allen, Herrick, & Fortune, ), but the regulation of fetal ovarian steroidogenesis is still poorly understood. Several growth factors are expressed in fetal ovaries and/or stimulate preantral follicle development.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor 18 regulates steroidogenesis in fetal bovine ovarian tissue in vitro

Silva

Yang

Caixeta

et al. 2019

In cattle and other species, the fetal ovary is steroidogenically active before follicular development commences, and there is evidence that estradiol and progesterone inhibit follicle formation and activation. Estradiol levels decline sharply around the time of follicle formation. In the present study, we hypothesized that FGF10 and FGF18, which inhibit estradiol secretion from granulosa cells of antral follicles, also regulate fetal ovarian steroid production. Fetuses were collected at local abattoirs, and age determined by crown‐rump length measurements. Real‐time polymerase chain reaction assays with RNA extracted from whole ovaries revealed that the abundance of CYP19A1 messenger RNA (mRNA) decreased from 60 to 90 days of gestation, which is consistent with the decline in estradiol secretion previously observed. Immunohistochemistry revealed the presence of FGF18 in ovigerous cords in early gestation and in oocytes later in fetal age (≥150 days). The abundance of FGF18 mRNA increased after Day 90 gestation. Addition of recombinant FGF18 to fetal ovarian pieces inhibited estradiol and progesterone secretion in vitro, whereas FGF10 was without effect. Consistent with these results, FGF18 decreased levels of mRNA for CYP19A1 and CYP11A1 in ovarian pieces in vitro. These data suggest that FGF18 may be an intraovarian factor that regulates steroidogenesis in fetal ovaries.