The period between seasonal anoestrus and cyclicity is characterized in many mares by cyclical growth and regression of large dominant follicles. The insulin-like growth factor (IGF) system plays a key role in follicular growth and regression; therefore, we hypothesized that changes in the IGF system and its binding proteins would modulate onset of cyclicity in mares. Ovaries were obtained from pony mares on the day after detection of an actively growing 30 mm transitional anovulatory follicle, and also at the second or third oestrus of the breeding season on the day after the preovulatory follicle reached 30 mm in diameter. Size of dominant follicles at the time of removal was similar in transition (32 6 0.8 mm) and at oestrus (34 6 0.6 mm). IGF-I mRNA was present in granulosa cells, with low thecal expression, whereas IGF-II mRNA was confined to the theca layer. Expression of IGF-I and -II mRNAs, and intrafollicular concentrations of oestradiol, were lower (P < 0.01; paired t test) in transitional anovulatory follicles than in preovulatory follicles. Messenger RNA encoding IGFBP-2 was present in both theca and granulosa layers. Steady-state concentrations of mRNA encoding IGFBP-2 mRNA increased (P < 0.001) in theca in preovulatory follicles. Intrafollicular concentrations of IGFBP-2 were higher (P < 0.001) in transitional than in preovulatory follicles. The similarity in circulating concentrations of IGF-I in transitional and cyclic mares, suggested that the somatotrophic axis is not involved in transition from anovulatory to ovulatory cycles. The results suggest that the increased expression of IGF-I and -II mRNAs in preovulatory follicles, along with the decrease in IGFBP-2 concentrations, could increase the bioavailability of intrafollicular IGF in large follicles during the breeding season, and support our hypothesis that intrafollicular IGF bioavailability must exceed a threshold level before ovulation can occur.

Aims To investigate sex differences in the association of metabolic syndrome (MetS) and/or low-density lipoprotein cholesterol (LDL-C) with the incidence of cardiovascular and cerebrovascular disease (CCVD). Methods and results A total of 4 702 458 individuals, aged between 40 and 70, without a previous diagnosis of CCVD, underwent at least two health screenings between 2009 and 2011. Of them, 4 193 878 individuals (48.6% women) fulfilled the study requirements. The main outcome measured was the incidence of CCVD. By the end of 2017, 68 921 CCVD events occurred. Men in high LDL-C only, MetS only, and both MetS and high LDL-C groups had higher risks of CCVD. Women in MetS only and both MetS and high LDL-C groups, but not those in high LDL-C only group, had higher risks of CCVD than those in the reference group. The effect of the interaction between the presence of MetS and high LDL-C levels on the primary outcome was found among women (P for interaction 0.016) but not among men (P for interaction 0.897). A combination of MetS and LDL-C &gt; 3.4 mmol/L increased the risk of CCVD as compared to MetS or LDL-C &gt; 3.4 mmol/L alone in both men and women. Conclusions Metabolic syndrome confers an increased risk of CCVD irrespective of sexes; LDL-C &gt; 3.4 mmol/L alone has a greater influence on CCVD occurrence in men than in women. Metabolic syndrome and high LDL-C beget a synergistically detrimental impact on the incidence of CCVD in both men and women. Treatment of dyslipidaemia and metabolic syndrome should be tailored according to patient characteristics.

Many mares enter a period of spring transition between winter anoestrus and cyclicity when follicles may reach preovulatory size, yet fail to ovulate. The aim of the present study was to determine the morphological, functional and molecular characteristics of large dominant transitional follicles. Follicle growth was monitored regularly from February through July in 25 pony mares. In some of the mares, one of the ovaries was removed on the day after an anovulatory follicle reached 30 mm, and the contralateral ovary was removed during cyclicity on the day after the preovulatory follicle reached 30 mm. Samples of the large follicle were processed for immunohistochemistry and in situ hybridisation, and follicular fluid was frozen. Hormonal control of growth of the large transitional follicles was similar to that seen during cyclicity. However concentrations of oestradiol were significantly lower than during growth of the preovulatory follicle and LH remained low until ovulation. During growth of anovulatory follicles, uterine oedema was sometimes present along with low, but significant, elevations in oestradiol. Transitional follicles had poorly developed theca that received a scant blood supply and there was little VEGF, the main ovarian angiogenic factor, in these follicles. Transitional follicles contained only low concentrations of oestradiol and progesterone and there was low expression of mRNA encoding StAR, the steroidogenic enzymes, and LHr in the follicle walls. Our results show that the poor steroidogenic capacity of transitional follicles is directly related to low gene expression of the steroidogenic enzymes, possibly caused by the low levels of LHr and IGF mRNAs. The scant blood supply and poor development of the theca would also contribute to the steroidogenic incompetence of these follicles. Expression of IGF-I and-II mRNAs were lower in transitional anovulatory follicles than in preovulatory follicles and intrafollicular concentrations of IGFBP-2 were significantly higher in transitional than in preovulatory follicles. These results suggest that the bioavailability of intrafollicular IGF is enhanced in large preovulatory follicles during the breeding season and suggests that intrafollicular IGF bioavailability must exceed a threshold level before an ovulation can occur.