No abstract

Altrenogest with gonadotropins is commonly used to synchronize the estrous cycle, but it can also lead to follicular cyst formation, especially in prepubertal gilts. Here, we aimed to investigate how maturity and altrenogest treatment affect the development, endocrine milieu, and molecular control of ovarian follicles. Crossbred prepubertal and mature gilts were challenged or not (control) with altrenogest, and ovaries were collected in the morning on the first day of behavioral estrus. In prepubertal gilts, altrenogest decreased the percentage of primordial and atretic small follicles, but increased large antral follicles when compared to controls. In mature gilts, altrenogest reduced the percentage of primary follicles and elevated the total number of antral follicles. Maturity affected the estradiol level in the follicular fluid of preovulatory follicles, LH-stimulated cAMP generation, and LH receptor mRNA expression in granulosa. Moreover, cytochrome P45017A1 (CYP17A1) mRNA levels in the theca layer were affected and correlated with follicular androstendione and estradiol concentration. Altrenogest negatively affected follicular fluid progesterone concentration and decreased levels of prostaglandin (PG) E2 in prepubertal gilts and PGF2α metabolite in mature gilts. LH-stimulated cAMP release in granulosa cells of mature gilts as well as hCG- and forskolin-induced cAMP were also affected. In addition, altrenogest down-regulated CYP17A1 mRNA in the prepubertal theca layer and PGF2α synthase expression in the granulosa and theca layer of mature gilts. To the best of our knowledge, this is the first study to report multiple effects of maturity and altrenogest on the endocrine milieu and molecular regulations governing ovarian follicle development in gilts.

Background Androgens are involved in the regulation of ovarian development during fetal/neonatal life. Environmental chemicals displaying anti-androgenic activities may affect multiple signal transduction pathways by blocking endogenous androgen action. The aim of the current study was to examine effects of the anti-androgen flutamide on the expression of coding transcripts and long non-coding RNAs (lncRNAs) in neonatal porcine ovaries. By employing RNA-Seq technology we aimed to extend our understanding of the role of androgens in neonatal folliculogenesis and examine the impact of the anti-androgen flutamide on ovarian function. Method Piglets were subcutaneously injected with flutamide (50 mg/kg BW) or corn oil (controls) between postnatal days 1 and 10 ( n = 3/group). Ovaries were excised from the 11-day-old piglets and total cellular RNAs were isolated and sequenced. Results Flutamide-treated piglet ovaries showed 280 differentially expressed genes (DEGs; P -adjusted < 0.05 and log 2 fold change ≥1.0) and 98 differentially expressed lncRNAs (DELs; P -adjusted < 0.05 and log 2 FC ≥ 1.0). The DEGs were assigned to GO term, covering biological processes, molecular functions and cellular components, which linked the DEGs to functions associated with cellular transport, cell divisions and cytoskeleton. In addition, STRING software demonstrated strongest interactions between genes related to cell proliferation. Correlations between DEGs and DELs were also found, revealing that a majority of the genes targeted by the flutamide-affected lncRNAs were associated with intracellular transport and cell division. Conclusions Our results suggest that neonatal exposure of pigs to flutamide alters the expression of genes involved in ovarian cell proliferation, ovarian steroidogenesis and oocyte fertilization, which in turn may affect female reproduction in adult life. Electronic supplementary material The online version of this article (10.1186/s40104-019-0340-y) contains supplementary material, which is available to authorized users.

Simple Summary:The ovarian development and the establishment of ovarian reserve during fetal and/or neonatal life is critical for future reproductive success. Many environmental chemicals are known to negatively affect development and physiology of human and animal ovaries by interfering with endocrine systems, resulting in aberrant reproductive functions. The present study shows the long-term impact of neonatal exposure to agonists and antagonists of sex steroid receptors on AMH and FSH signalling in the ovary of adult pigs. Our findings suggest alteration in ovarian follicle recruitment from ovarian reserve arising from neonatal disruption of androgen/estrogen signalling induced by environmental endocrine active compounds. Everyday use of many endocrine disruptors is already prohibited after their harmful impacts on normal physiology have become known. Nevertheless, market introduction of new chemicals with potential deleterious influence on reproductive physiology has continued. Our outcomes confirm that a neonatal window plays an essential role in the physiological programming of ovarian function in adult pigs. The influence of environmental chemicals on this critical neonatal window needs to be investigated in order to gain a comprehensive view of deleterious interactions between endocrine disrupting chemicals and ovarian function.Abstract: In this study piglets were injected with testosterone propionate (TP, an androgen), flutamide (FLU, an antiandrogen), 4-tert-octylphenol (OP, an estrogenic compound), ICI 182,780 (ICI, an antiestrogen) or corn oil (controls) between postnatal days 1 and 10 (N = 5/group). Then plasma anti-Müllerian hormone (AMH) and follicle stimulating hormone (FSH) concentration and the expression of their receptors were examined in the adult pig ovary. TP and FLU decreased plasma AMH and FSH concentration. In preantral follicles, TP resulted in upregulation of AMHR2 and FSHR expression, but decreased AMH protein abundance. FLU upregulated AMHR2 expression, while OP increased FSHR mRNA. In small antral follicles, OP upregulated ACVR1 and BMPR1A expression, while FLU increased BMPR1A mRNA. FLU and ICI resulted in upregulation of AMHR2 expression. TP and FLU upregulated AMH expression, while it was downregulated in response to OP or ICI. Moreover, OP and ICI resulted in downregulation of FSHR expression, while FLU decreased FSHR protein abundance. In conclusion, neonatal exposure to either agonist or antagonist of androgen receptor affected AMH and FSH signalling systems in preantral follicles. In small antral follicles these systems were influenced by compounds with estrogenic, antiestrogenic, and antiandrogenic activity. Consequently, these hormonal agents may cause an accelerated recruitment of primordial follicles and affect the cycling recruitment of small antral follicles in pigs.

No abstract