ISSN on-line: 2358-288X
Reprodução & Climatério Reprodução & Climatério
Reprod Clim 2017;32:109-19 - Vol. 32 Núm.2 DOI: 10.1016/j.recli.2016.11.002
Review article
Reports on in vivo and in vitro contribution of medicinal plants to improve the female reproductive function
Relatos sobre a contribuição in vivo e in vitro de plantas medicinais na melhora da função reprodutiva feminina
Gildas Tetaping Mbemyaa, Luis Alberto Vieiraa, Francisca Geovania Canafistulaa, Otília Deusdênia Loiola Pessoab, Ana Paula Ribeiro Rodriguesa,,
a Laboratório de Manipulação de Oócitos e Folículos Ovarianos Pré-antrais (LAMOFOPA), Faculdade de Veterinária (FAVET), Universidade Estadual do Ceará (UECE), Fortaleza, CE, Brazil
b Laboratório de Análise Fitoquímica de Plantas Medicinais (LAFIPLAN I), Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil
Recebido 26 Outubro 2016, Aceitaram 26 Novembro 2016

Medicinal plants are known as a prolific source of secondary metabolites which have important function both in vivo and in vitro during the ovarian folliculogenesis and steroidogenesis in many animal species. Some secondary metabolites can act as antioxidants generally through their ability to scavenge reactive oxygen species (ROS) or can regulate ovarian hormonal production. In general, these properties are responsible for the medicinal functions to treat woman infertility disorder. Some plants are constituted of biological actives substances which have been used to treat reproductive dysfunction. However, until recently, little was known about the implication of plants and/or their secondary metabolites on in vitro folliculogenesis and steroidogenesis. With the development of the technology, there is an increase implication of those substances in assisted reproductive technology (ART). The present review highlights some medicinal plants used in the treatment of woman disorders related to infertility. In addition, it provides an in vivo and in vitro overview of herbs and their active compounds with claims for improvement of ovarian activity thus showing their implication in female reproductive health care.


Sabe-se que as plantas medicinais são uma fonte abundante de metabólitos secundários que têm função importante tanto in vivo quanto in vitro durante a foliculogênese e a esteroidogênese ovarianas em muitas espécies animais. Alguns metabólitos secundários podem atuar como antioxidantes, geralmente através de sua capacidade de eliminar espécies reativas de oxigênio (ROS) ou podem regular a produção hormonal ovariana. Em geral, essas propriedades são responsáveis pelas funções medicinais usadas para tratar distúrbios da infertilidade feminina. Algumas plantas contêm substâncias biológicas ativas que têm sido utilizadas para tratar a disfunção reprodutiva. No entanto, até recentemente, pouco se sabia sobre o efeito das plantas e/ou seus metabólitos secundários na foliculogênese e na esteroidogênese in vitro. Com o desenvolvimento da tecnologia, há uma implicação crescente dessas substâncias na tecnologia de reprodução assistida (TRA). A presente revisão destaca algumas plantas medicinais utilizadas no tratamento de distúrbios femininos relacionados à infertilidade. Além disso, fornece uma visão in vivo e in vitro de ervas e seus compostos ativos com alegações de melhora da atividade ovariana, mostrando assim seu envolvimento nos cuidados de saúde reprodutiva feminina.

Phytotherapy, Antioxidants, Women infertility, Ovarian follicles
Fitoterapia, Antioxidantes, Mulheres infertilidade, Folículos ovarianos

Infertility is a disease of the reproductive system which affects both men and women with almost equal frequency. It is a global phenomenon affecting an average of 10% of human reproductive age population.1 Many conditions can be associated to this problem, including intrinsic (anatomic, genetic, hormonal and immunological disorders) and extrinsic factors such as sexually transmitted infections (STIs), infections after parturition or surgery, tuberculosis of the pelvis, and obesity.2,3

There are a range of medical treatment options for infertility, such as the use of commercial treatments to stimulate “superovulation” which correspond to the development and release of more than one egg per ovulatory cycle. In addition, ART is commonly applied to solve infertility problems, including procedures to bring about conception without sexual intercourse. Among the available techniques, in vitro maturation (IVM), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and intrauterine insemination (IUI)4 are frequently applied. As an alternative, medicinal plants can also be used to solve part of the reproductive problems. Due to their chemical composition, many plants have showed beneficial properties in the folliculogenesis and steroidogenesis through their antioxidant properties and regulation of some enzyme of the steroidogenesis.5–8

For a better understanding of the medicinal properties of crude plant extract or secondary metabolites on the regulation of reproductive function (folliculogenesis and steroidogenesis), many in vivo studies have been performed.5,6,8,9 Several studies showed that the plant secondary metabolites act either directly on ovarian cells to eliminate the ROS or through action on several enzymes such as catalase, glutathione, superoxide dismutase and glutathione peroxidase.10–12 On the other hand, plants (infusion, decoction, beverages, crude extracts) showed their implication during the steroidogenesis through their capacity to mimic the biologic effects of endogenous hormones. These plant medicine derivatives can act by binding to their nuclear receptor or regulating the activities of key enzymes of their metabolisms.6,13

The present review is an attempt to consummate the available scientific information on various medicinal plants, which have been evaluated for their effect on female reproduction. Among all the female reproductive organs, only the ovary is discussed on this review since it is the site of the folliculogenesis and steroidogenesis.14 The review also includes known evidences collected for the involvement of plant extracts in vivo and in vitro. A number of plants and/or secondary metabolites have been discussed in detail and a few others were only tabulated; a major criterion for this arrangement was the ethnopharmacological relevance of the plant.

Mammalian ovary, folliculogenesis and ovarian follicles

The mammalian ovary is the female gonad which contains germ cells responsible for the perpetuation of the species. Furthermore, it is also the reproductive gland controlling many aspects of female development and physiology.15 That is why it is important for the reproductive biologists to understand not only the normal functioning of the ovary but also the pathophysiology and genetics of diseases such as infertility.

The ovary consists of many types of differentiated cells, which work together, promoting an ideal environment to perform the endocrine and exocrine functions. Those functions are performed by different factors such as autocrine, paracrine, juxtacrine and endocrine are essential for ovarian folliculogenesis.16 Folliculogenesis is the result of a complex and closely integrated series of events which start generally soon after conception. This process can be defined as the formation, growth and maturation of follicle, starting with the formation of the oocyte surrounding by the granulosa cells which formed the primordial follicles.17

Besides the granulosa cells, the thecal cells are recruited to the oocyte and are directly or indirectly necessary for the oocyte development, physiology and survival. The dynamic of the ovarian folliculogenesis is classified in different stages known as: (a) formation of the primordial follicles; (b) recruitment into the growing pool to form a primary, secondary, and tertiary follicles; (c) lastly ovulation and subsequent formation of a corpus luteum.18 In most species, the mammalian ovary shows extensive variation mainly in relation to the interstitial tissue of the organ, the so-called interstitial gland, and the degree of gonad regionalization, which implies the existence of a cortex and a medulla.15 The internal part consists of fibroelastic connective tissues, nerve and vascular tissues (medula) whereas the external part called the cortex is located at the outer layer and is surrounded by the germinal epithelium, which contains the ovarian follicles and corpora lutea in various stages of development or in regression16 (Fig. 1).

Fig. 1.

Schematic representation of the ovarian structure. Adapted from

The follicle which represents the morphological and functional unit of the mammalian ovary consists of an oocyte surrounded by somatic cells (granulosa and/or theca) organized or demarcaded by the basement membrane.

Before formation of an ovarian follicle, oocytes are present within germ cell clusters. Primordial follicle formation occurs when oocytes that survive the process of germ cell cluster breakdown are individually surrounded with squamous pre-granulosa cells. This process takes place during the latter half of fetal development in humans and in the days immediately following birth in mice.18,20 In mammals, the population of primordial follicles serves as a resting and finite pool of oocytes available during the female reproductive life span. Germ cell cluster breakdown, primordial follicle formation, and subsequent recruitment remain the least understood steps of folliculogenesis, that is why key regulators of these initial stages of follicle development continue to be identified. Furthermore, despite many unanswered questions during this crucial period, the concept of ovarian cross talk between oocytes and somatic cells is apparent from the formation of primordial follicles onward.21,22 After differentiation of the primordial germ cells, oogonia undergo mitotic proliferation with incomplete cytokinesis, leaving daughter cells connected by intercellular bridges. The majority of germ cells in a cluster divide synchronously such that a single germ cell cluster contains 2n germ cells.23 Germ cells subsequently enter meiosis, becoming oocytes. Individual oocytes within these nests lack surrounding somatic cells, and the majority of the oocytes will undergo apoptosis as the germ cell clusters break down to give rise to primordial follicles.

The primordial follicles represent the first category of follicles. After their formation, the granulosa cells stopped multiplying and enter a period of quiescence. Throughout the life of the female, a small group of follicles is stimulated to grow gradually, forming the activation follicular phase. The first sign of activation of primordial follicles is the resumption of proliferation of granulosa cells. Upon activation, a series of events that increases the number of granulosa cells, formation of the zona pellucida and oocyte diameter increased leading to the formation of other categories of preantral follicles, primary and secondary follicles occurs. Once activated, the follicles enter a pre-programmed course of development and maturation which is necessary for successful ovulation and fertilization or alternatively are lost through the process of atresia.24 The second category of follicles is characterized by the organization of granulosa cells in several layers and formation of a cavity filled with follicular fluid called antrum. This follicular fluid consists of water, electrolytes, serum proteins and high concentrations of steroid hormones secreted by granulosa cells.25 However, throughout the life of the female, only a small group of follicles, approximately 0.1%, reached ovulation,26 thus reducing the reproductive potential of the female. In several pathological conditions, the woman can suffer of premature ovarian failure (POF) caused by different factors: endocrine, paracrine, genetic and metabolic factors such as high production of ROS.27,28

ROS production in the ovary

Oxidative metabolism is indispensable for energy production of ovarian follicle, which in turn results in generation of ROS (oxygen hydroxide, superoxide ion, heavy metals and free radicals). Although a critical amount of ROS is essential for their physiological activities, excessive amount of them causes oxidative stress,29 damage to mitochondria and also to cellular structures such as the membrane lipids, damage to nucleic acids and proteins.27 It does become necessary to use antioxidants to counteract this overproduction of ROS.30

Prevention of oxidative stress is vital in order to maintain normal reproductive function.31 Sources of ROS during ART procedures could either be endogenously from gametes or via exogenous environmental factors.32 However, unless measures are taken to curb ROS production, both the endogenous and exogenous sources of ROS will ultimately lead to the development of oxidative stress, which would then have negative impact on follicles development, oocyte maturation, fertilization rates and pregnancy outcome. Valorization of natural compounds of plants could improve and be an alternative to reduce the cost of ART.


Phytotherapy can be defined as the use of medicinal plants in the prevention, relief or cure of diseases. A plant can be considered as medicinal when the whole plant or at least one of its parts has one or more medical properties.33 Medicinal plants are used by the people to treat several diseases, including to solve infertility problems. In this context, some plants are rich in compounds which exhibit regulator effect on reproductive function acting directly or indirectly on the hypothalamic–pituitary–ovarian axis by induction or inhibition of ovulation and steroidogenesis disrupting hormonal functioning of the hypothalamus and pituitary gland.5 Their use can bring direct answers to some health problems such as reproductive disorders. The use of medicinal plants (Fig. 2) in response to reproductive problems can be seen as an alternative to manufactured drugs, especially in developing countries where they are expensive and/or inaccessible.34

Fig. 2.

General scheme and sequence (from 1 to 8) of studying the in vitro and in vivo effects of plant extracts.

Several studies have shown the beneficial implication of natural compounds on the woman reproduction acting directly on the reproductive organs or indirectly regulated physiological process. For example, studies by Telefo et al.35 showed that the aqueous extract of the mixture of Aloe buettneri, Dicliptera verticillata, Hibiscus macranthus and Justicia insularis, is used in traditional medicine to normalize the menstrual cycle increasing female fertility. In addition, Acanthus montanus, Aloe vera, Carica papaya, Citrus aurantifolia, Elaeis guineensis, and Panax quiquefolius, Eremomastax speciosa are used in Nkam (Littoral region in Cameroon) with the same purpose.36Asystasia vogeliana, Crinum distichum, Crinum jagus, Crassocephalum biafrae, Scoparia dulcis, Solanum torvum, Aframomum letestuanum, Aloe buettneri and Eremomastax speciosa make part of the cast of plants most widely used to treat diseases of the reproductive system.37 Generally, medicinal plants used for the improvement of the reproductive functions have more than one property. Table 1 illustrates some traditional medicinal plants used in the treatment of female reproductive disorders.

Table 1.

Medicinal plants and their in vivo therapeutic utilization on female reproductive function.

Plants  Family  Major phytochemical compounds  Used parts  Therapeutic utilization  References 
Moringa oleifera  Moringaceae  Lutein, carotene xanthins, kaempferol, quercetin  Leaves  Sexual libido  Cajuday and Pocsidio,38 2010 
Adiantum concinnum  Adiantaceae  No report  Leaves and stems  Menstrual regulation  Bussmann and Glenn,39 2010 
Petroselinum crispum  Apiaceae  Flavonoids  Whole plant  Menstrual regulation  Nielsen et al.,40 1999; Bussmann and Glenn,39 2010 
Musa sapientium  Musaceae  No report  Leaves  Menstrual regulation  Chifundera,41 1998 
Scabiosa atropurpurea  Dipsacaceae  No report  Leaves  Menstrual regulation  Bussmann and Glenn,39 2010 
Cassia alata  Fabaceae  Tannins, saponins, flavonoids, steroids, terpenoids, alkaloids  Root  Infertility  Ramaraj et al.,42 2014; Koch et al.,43 2015 
Ximenia americana  Olacaceae  Saponins, glycosides anthraquinones  Whole plant  Menstrual regulation  James et al.,44 2007, Bussmann and Glenn,39 2010 
Eremomastax speciosa  Acanthaceae  Flavonoids, alkaloids, saponins, tannins  Leaves  Infertility  Adjanohoun et al.,45 1996; Priso et al.,36 2006 
Justicia insularis  Acanthaceae  Flavonoids, alkaloids, glycosides  Leaves and stem  Infertility, menstruation unrest  Adjanohoun et al.,45 1996; Telefo et al.,5 1998 
Crinum distichum  Amaryllidaceae  No report  Whole plant  Amenorrhea infertility  Priso et al.,36 2006 
Ageratum conyzoides  Asteraceae  Flavonoids, alkaloids, benzofuranes, terpenes  Leaves  Infertility, infections of the genital device  Adewole,46 2002 
Senecio biafrae  Asteraceae  Dihydroisocoumarins, terpenoids, sesquiterpens, amino acids, mineral salts  Leaves and stem  Infertility  Tabopda et al.,47 2009; Tacham,37 2000 
Emilia coccinia  Asteraceae  No report  Whole plant  Dysmenorrhea  Adjanohoun et al.,45 1996 
Zehnaria scabra  Cucurbitaceae  No report  Leaves and stem  Infertility, dysmenorrhea  Adjanohoun et al.,45 1996 
Euphorbia tirucalli  Euphorbiaceae  No report  Stem  Gonorrhea  Arbonnier,48 2002 
Jatropha curcas  Euphorbiaceae  No report  Leaves and stem  Infertility  Igoli et al.,49 2002 
Aloe buettneri  Liliaceae  Glycosides, quinines, coumarins, anthraquinonic derivatives  Leaves  Infertility, painful menstruations, dysmenorrhoea  Telefo et al.,6 2004; Tacham,37 2000 
Paulinia pinnata  Sapindaceae  No report  Leaves  Infertility, amenorrhea, gonorrhea  Arbonnier,48 2002 
Solanum torvum  Solanaceae  Flavonoids, alkaloids, saponins, glycosides, tannins  Fruit  Infertility, genital infections  Tacham,37 2000 
Ampelocissus Pentaphylla  Vitaceae  No report  Leaves  Infertility  Tacham,37 2000 
Pelargonium odoratisimum  Geraniaceae  No report  Whole plant  Inflammation of the ovaries and womb  Bussmann and Glenn,39 2010 
Pelargonium roseum  Geraniaceae  No report  Flowers and leaves  Hemorrhages, uterus pain  Bussmann and Glenn,39 2010 
Krameria lappacea  Krameriaceae  No report  Leaves and root  Inflammation of the ovaries  Bussmann and Glenn,39 2010 

As can be seen from Table 1, various medicinal, plants belonging to different families showed therapeutic effects. Traditionally, rural women have used plant medicines rather than modern medicine for their personal ailments due to lack of modern facilities in the regions. Bannu region in Pakistan was ranked first having large number of gynecological plant to medical treatment of female reproductive system: uterus, vagina, and ovaries.50 Moreover, many women in Costa Rica consider menopause as a natural phenomenon and treat the symptoms with herbs. Interestingly, Latina women in the United States also tend not to use hormone therapy (estrogenic and/or progesteronic compounds) opting for natural remedies for menopause such as diet, exercise and herbal remedies.51 More detailed scientific studies are desperately needed to evaluate the efficacy and safety of the remedies employed traditionally.

Secondary metabolites of plants: description and medicinal propertiesDescription

Secondary metabolites are structurally diverse; their classification is mainly derived from their biosynthetic pathways. In pharmacognosy, secondary metabolites are classifying in: (a) phenolic; (b) alkaloids and (c) terpenoids compounds,52 as described below.

Phenolic compounds

Phenolic compounds are among the most widespread class of secondary metabolites in nature. This class of compounds are synthesized from a common precursor: the amino acids phenylalanine or tyrosine. Phenolic compounds consist of flavonoids, tannins, coumarins, quinones and anthocyanins and are regarded as the widest spread phytochemicals. Phenolic compounds may assume a wide range of structures from simple ones containing one aromatic ring only, to very complex polymeric forms.53 The term flavonoid is a collective name for plant pigments, mostly derived from benzo-δ-pyrone.54 They are widely distributed in plants contain free hydroxyl groups attached to the aromatic rings (Table 2). Flavonoids such as rutin, present in certain buckwheat (Fagopyrum esculentum) species are known to inhibit lipid oxidation by radicals scavenging.55

Table 2.

Basic structures of some pharmacologically plant derived flavonoids, alkaloids and terpenoids.

Class  Examples  References 
Flavone    Kumar and Abhay,59 2013 
Alkaloids    Sarker and Nahar,60 2007 
Terpenoids    Sarker and Nahar,59 2007 
Alkaloids compounds

Alkaloids are nitrogenated compounds synthesized by living organisms. In general, they contains heterocyclic rings (Table 2) and due the presence of one or more nitrogen atoms, they present basic properties. The name alkaloid is directly related to the fact that nearly all alkaloids are basic (alkaline) compounds. Derived from amino acids, in general, they are pharmacologically active. Alkaloids constitute ‘a very large group of secondary metabolites, with more than 12,000 substances isolated. A huge variety of structural formulas, coming from different biosynthetic pathways and presenting diverse pharmacological poperties.56

Terpenoids compounds

The terpenoids comprising monoterpenes, sesquiterpenes, sesterterpenes and triterpenes, besides steroids, saponins and cardiac glycosides. They are considered be the phytochemicals having the most diverse chemical structures.57 Terpenoids are the largest and most diverse family of natural products, ranging in structure from linear to polycyclic molecules and in size from the five carbon hemiterpenes to natural rubber, comprising thousands of isoprene units (Table 2). The monoterpenes and sesquiterpenes are common in essential oils produced by plants.58

Medicinal properties

Crude extracts or secondary metabolites from medicinal plants can act as antioxidant agents generally through their ability to scavenge ROS or as a regulator of ovarian hormonal production. These properties can be responsible for their medicinal functions.

Gouveia et al.61 identified and quantified five substances from Amburana cearensis, namely: protocatechuic acid (PCA), epicatechin, p-coumaric acid, gallic acid and kaempferol, which were identified by high performance liquid chromatography (HPLC) from the crude ethanolic extract of A. Cearensis. Gallic acid is a well known antioxidant compound, was the main compound found in A. cearensis.62 Gallic acid prevents in vivo and in vitro DNA oxidative increasing the activities of antioxidant enzymes (superoxide dismutase, GPx and glutathion-S-transferase-π) and decreasing the intracellular ROS concentrations.63 Another compound found in the A. cearensis extract was the PCA, commonly found in several vegetables and fruits.64 PCA acts in vitro by increasing the activities of antioxidant enzymes such as superoxide dismutase, scavenging ROS or inhibiting their formation, and consequently reducing oxidative stress damage.64–66 One of the prominent and most useful properties of the flavonoids is their ability to scavenge ROS.67 They are considered more efficient antioxidants than vitamins C and E.68 Coumarins, another group of phenolic compound (1,2-benzopyrone) are natural antioxidant compounds widely distributed in plants.69,70 Studies have reported that coumarins inhibit lipid peroxidation, decreasing the injury caused by oxidative stress and decreasing the levels of ROS in different types of cells.71,72 Likewise, anethole a constituent of essential oil (terpenoids) from Croton-zehntneri, a medicinal plant popularly known as “canela de cunhã” or “canelinha” in the Northeast of Brazil, decreased the levels of ROS both in vivo73,74 using mice model, and in vitro during culture of cell lines isolated from the peripheral blood of male patient with acute myeloblastic leukemia.75 Sá et al.76 showed that addition of anethole (300 and 2000μg/mL) to the in vitro culture medium was able to improve the development of goat preantral follicles by reducing concentrations of ROS and increasing the percentage of oocytes able to resume meiosis. In addition to their antioxidant activity, compounds from plant can have an important role during the steroidogenesis.

Many compounds (flavonoids, lignans, coumestans) derived from plants have ability to mimic the biologic effects of endogenous hormones by binding to their nuclear receptor or regulating the activities of key enzymes of their metabolisms such as cytochrome P450 aromatase, and 17β-hydroxysteroid dehydrogenase which is a key enzyme of the steroidogenesis.13 The estrogenic effects of some compounds are often related to the stimulation of the hypothalamus–pituitary complex increasing the follicle stimulating hormone (FSH), which will thereafter induce ovarian steroidogenesis. Flavanoids with estrogenic potential have been reported to inhibit aromatase activity in various tissues.77

The best-described property of almost plants is their capacity to act as antioxidants. For instance, flavones and catechins seem to be the most powerful flavonoids for protecting the body against ROS. Follicular cells are continuously threatened by the damage caused by free radicals and ROS, which are produced during normal oxygen metabolism or are induced by exogenous damage.78 The mechanisms and the sequence of events by which free radicals interfere with cellular functions are not fully understood, but one of the most important events seems to be the lipid peroxidation, which results in cellular membrane damage. This cellular damage causes a shift in the net charge of the cell, changing the osmotic pressure, leading to swelling and eventually cell death.79 The ROS produced during the metabolism are made inactive according the following equation, where R is a free radical and O is an oxygen free radical.


Nowadays, medicinal plants are widely used around the world as an alternative to pharmaceutical drugs. Although herbal products are considered to have fewer adverse effects compared with synthetic drugs, they are not completely free of indesejable effects. The volatile terpenoids camphor, a compound of the essential oil of Artemisia kopetdaghensis crosses the placenta and may lead to abortion.80 In another study, Linjawi81 reported that camphor induces significant structural changes on uterus of pregnant rats. Therefore, it is rational to assume that camphor is involved in the abortifacient effect of A. kopetdaghensis. Results from Oliaee et al.82 using female rats as animal model showed that continuous consumption of 800μg/mL of A. kopetdaghensis in pregnancy may increase the risk of abortion and also may have toxic effect on some cells of body. Therefore, its continuous use is not recommended in pregnancy.

Implication of plant extracts or compounds in ovarian cells cultured in vitro

With the aim to elucidate their properties, plant extracts or its secondary metabolites have been used in the culture of various types of cells including follicles and granulosa cells. Hsia et al.83 demonstrated that the partitioned fractions of Coix lachryma-jobi (Adlay), a traditional Chinese medicine used for the dysfunction of endocrine system extracts possess hypogonadal effect in vitro conditions. This plant shows a great capacity to reduce the production of progesterone (P4) and estradiol (E2) by decreasing the activity of cholesterol side-chain cleavage enzyme (P450scc) and 3beta-Hydroxysteroid dehydrogenase (3β-HSD). In contrary, the use of leaves mixture of Aloe buettneri, Justicia insularis, Dicliptera verticillata and Hibiscus macranthus (ADHJ) in vitro attest the direct effects of some chemical components on rat ovarian steroidogenesis. Indeed, alkaloids, coumarins glycosides, flavonoids and quinones from ADHJ are more effective when the plant extract (130g/ml) is combined to 0.1IU/mL of human chorionic gonadotropin (hCG) during 2h of incubation. In these conditions, estradiol production increased by 13-fold compared to the medium without hCG and the plant extract; and by 5-fold compared to the medium containing only the plant extract (130g/ml) or hCG (0.1IU/mL).6

Studies with quercetin, a flavonoid present in several plants, as well as nonsteroidal compounds known as phytoestrogens84 affects porcine granulosa cell function by interfering with steroidogenic activity and redox status as well as by inhibiting vascular endothelial growth factor output.85 This phytoestrogen represents a potential modulator of ovarian functions through inhibition of steroidogenic enzymes.77,86

Suppressive action of phytoestrogen on cytochrome P450 (enzyme that catalyzed the conversion of cholesterol to pregnenolone) represents a rate-limiting step in the steroidogenic pathway. Several studies87,88 showed that phytoestrogen induced decrease of P4 production in granulosa cells. This decrease is due to the inhibition of 3β-hydroxysteroid enzyme. Furthermore, Santini et al.89 revealed the inhibitory effect of quercetin on aromatase activity. It has been suggested that the action of phytoestrogen on aromatase activity could be mediated by nitric oxide (NO). In fact, this free radical seems to represent an autocrine regulator of granulosa cells E2 production.90 However, molecular studies should be done to better understand the mechanism of action of phytoestrogen on steroidogenic enzymes.

Implication of plants extract or compounds on oocyte maturation

During in vitro oocyte culture, the levels of antioxidants are lower than in vivo because the oocytes are divorced from the donor body and do not benefit from the maternal antioxidant protection.90 The addition of an antioxidant to the medium, therefore, may be important for in vitro oocyte maturation.

Reports from Rajabi-Toustani et al.91 shows that supplementation of appropriate concentrations of Papaver rhoeas extract (50μg/mL) in maturation medium (bicarbonate-buffered TCM 199 supplemented with 10% FBS, 0.2mM sodium pyruvate 0.1IU/mL hMG, 100IU/mL penicillin and 100μg/mL streptomycin) improve the sheep oocyte maturation rate. Similar results have been obtained when maturation medium of mouse oocyte was supplemented with 5μg/mL of Crocus sativus92 or when supplemented with 20μg/mL of Phoenix dactylifera pollen grain.93 Improvement maturation rate of oocytes treated with P. rhoeas extract may be partly due to increase of intracellular glutathione (GSH) levels in oocytes91 or super oxide dismutase (SOD) activity.94 Anthocyanins protect cells against free radicals by gamma-glutamylcysteine synthetase (γ-GCS) activation, while of γ-GCS elevates GSH levels in medium.95 Increased GSH levels through oocyte maturation are associated with improvement in subsequent embryo development.96 On the other hand, the reduction on in vitro maturated oocytes to metaphase II stage might be due to deleterious effects of excessive concentrations (200μg/ml of P. rhoeas extract), because some flavonoids displayed toxic effects91,97 by changing the cell membrane structure and consequently damage cell polarization.98 Locklear et al.99 demonstrated that extract of Justicia pectoralis acts as an E2 and P4 agonists on the cellular membrane and inhibits the activity of the cyclooxygenase 2 (COX-2) enzyme in vitro. The COX-2, is the rate-limiting enzyme in the biosynthesis of prostaglandins (PGs) which are considered to participate in follicular rupture during ovulation.100J. pectoralis is a medicinal plant commonly used by women in Costa Rica to treat symptoms associated with premenstrual syndrome (common forms of hormonal imbalance affecting women) and menopause. Table 3 shows some in vitro implications of medicinal plants from different species on folliculogenesis and steroidogenesis process.

Table 3.

In vitro implication of some medicinal plants on folliculogenesis and steroidogenesis in different species.

Plants  Chemicals compounds  Used parts  Effects  Species  References 
Amburana cearensis  Protocatechuic acid, epicatechin, p-coumaric acid gallic acid, kaempferolin  Leaves  Maintained follicular survival and promoted the development of isolated secondary follicles.  Ovine  Barberino et al.,11 2015 
Moringa oleifera  β-Carotene, protein, vitamin C, calcium, potassium  Leaves  Improved the oocyte maturation rate  Ovine  Ibrahim et al.,101 2015 
Croton zehntneri  Anethole  Leaves  Improved the development and oocyte maturation rate of isolated secondary preantral follicles.  Caprine  Sá et al.,76 2015 
DPP  Flavonoids, phenolic acid, diterpenes  Grain  Improved the oocyte maturation rate  Mice  Abdollahi et al.,93 2015 
Yucca shidigera  Sarsapogenin, milagenin, markogenin, samogenin, gitogenin, neogitogenin  Bark  Reduced ovarian cell proliferation, promoted ovarian cell apoptosis, stimulated P4 and inhibited testosterone release.  Swine  Štochmaľová et al.,102 2014 
Gundelia tournefortii  Phenolic compounds  Leaves  Improved oocyte maturation rate  Murine  Abedi et al.,103 2014 
Crocus sativus  Crocin, crocetin, dimethyl crocetin, safranal, flavonoids.  Stigmas  Improved the IVM, IVF, and early embryo development  Murine  Maleki et al.,104 2012 
Coix lachryma-jobi  Coixenolides, coixans A, B, and C  Seed  Decreased P4 and E2 levels.  Murine  Hsia et al.,83 2007 
ADHJ  Alkaloids, flavonoids, glycosides, coumarins and quinones  Leaves mixture  Induced E2 synthesis  Murine  Telefo et al.,6 2004 

IVM, in vitro maturation; IVF, in vitro fertilization; ADHJ, mixture of Aloe buettneri, Dicliptera verticillata, Hibiscus macranthus and Justicia insularis; DPP, Phoenix dactylifera pollen grain.

Final considerations

Female reproductive problems continue to be a major health challenge worldwide. An impressive number of plant species is traditionally used to remedy such disorder. Those plants mainly constituted of secondary metabolites have been used over decades for the treatment of diseases which affect woman reproduction leading to infertility. These substances widely distributed over the world are constituted of compounds whose concentrations and compositions vary among plants and between the same genus. Several factors affect the plants composition among which the season, site and time of harvest. With the development of technology, an interest of plant is reported due to their antioxidant capacity and their ability to mimic the effect of steroidogenic enzymes. But little remain unknown about their implication in vitro which represents alternative studies of the in vivo studies. Finally, further studies should be performed to better understand the mechanism of action of plant and/or secondary metabolites. The discovery may also help to reduce the cost and improve the results of treatments normally applied.

Conflicts of interest

The authors declare no conflicts of interest.

F. Zegers-Hochschild,G.D. Adamson,J. De Mouzon,O. Ishihara,R. Mansour,K. Nygren
The International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary on ART terminology
Hum Reprod, 24 (2009), pp. 2683-2687
A.S. Daar,Z. Merali
Infertility and social suffering: the case of ART in developing countries
Current practices and controversies in assisted reproduction. Report of a meeting on medical, ethical and social aspects of assisted reproduction, pp. 15-21
S.H. Larsen,G. Wagner,B.L. Heitmann
Sexual function and obesity
Int J Obes, 31 (2007), pp. 1189-1198
G. Breart,J. De Mouzon
AMP vigilance
Notice Natl Acad Med, 179 (1995), pp. 1759-1764
P.B. Telefo,P.F. Moundipa,A.F. Tchana,D.C. Tchouanguep,F.T. Mbiapo
Effects of aqueous extract of Aloe buettneri, Dicliptera verticillata, Hibiscus macranthus, and Justicia insularis on some biochemical and physiological parameters of reproduction in immature female rat
J Ethnopharmacol, 63 (1998), pp. 193-200
P.B. Telefo,P.F. Moundipa,F.M. Tchouanguep
Inductive effects of the leaf mixture extract of Aloe buettneri, Justicia insularis, Dicliptera verticillata and Hibicus macranthus on in vitro production of oestradiol
J Ethnopharmacol, 90 (2004), pp. 225-230
L. Leal,J.H.V. Nobre,G.M.A. Cunha,M.O. Moraes,C. Pessoa,R.A. Oliveira
Amburoside A, a glucoside from Amburana cearensis, protects mesencephalic cells against 6-hydroxydopamine-induced neurotoxicity
Neurosci Lett, 388 (2005), pp. 86-90
U. Jha,M. Asad,B.M.S. Asdaq,K.A. Das,P.S.V. Satya
Fertility inducing effect of aerial parts of Coccinia cordifolia L. in female rats
J Ethnopharmacol, 127 (2010), pp. 561-564
F.P. Moundipa,P. Kamtchouing,N. Koueta,F. Mbiapo,J. Tantchou
Effects of aqueous extract of Hibiscus macranthus and Basela alba Linn. Immature rat testis function. Andrology in the nineties
International symposium on male infertility and assisted reproduction, pp. 21-24
W. Bors,M. Saran,C. Michel
Radical intermediates involved in the bleaching of the carotenoid crocin. Hydroxyl radicals, superoxide anions and hydrated electrons
Int J Radiat Biol Relat Stud Phys Chem Med, 41 (1982), pp. 493-501
R.S. Barberino,V.R.P. Barros,V.G. Menezes,L.P. Santos,V.R. Araújo,M.A.A. Queiroz
Amburana cearensis leaf extract maintains survival and promotes in vitro development of ovine secondary follicles
K. Jung-Taek,H.M. Joon,C. Ji-Yei,J.P. Sol,J.K. Su,M.S. Islam
Effect of antioxidant flavonoids (quercetin and taxifolin) on in vitro maturation of porcine oocytes
Asian Australas J Anim Sci, 29 (2016), pp. 352-358
M.S. Kurzer,X. Xu
Dietary phytoestrogens
Annu Rev Nutr, 17 (1997), pp. 353-381
J. Hutt Karla,David F. Albertini
An oocentric view of folliculogenesis and embryogenesis
Reprod BioMed Online, 14 (2007), pp. 758-764
Ovarian organogenesis in mammals: mice cannot tell us everything
Sex Dev, 3 (2009), pp. 291-301
A.A. Mohammadpour
Comparative histomorphological study of ovary and ovarian follicles in Iranian Lori-Bakhtiari sheep and native goat
Pak J Biol Sci, 10 (2007), pp. 673-675
J.L. Juengel,H.R. Sawyer,P.R. Smith,L.D. Quirke,D.A. Heath,S. Lun
Origins of follicular cells and ontogeny of steroidogenesis in ovine fetal ovaries
Mol Cell Endocrinol, 191 (2002), pp. 1-10
M.A. Edson,A.K. Nagaraja,M.M. Matzuk
The mammalian ovary from genesis to revelation
Endocr Rev, 30 (2009), pp. 624-712
A.N. Hirshfield
Development of follicles in the mammalian ovary international
Int Rev Cytol, 124 (1991), pp. 43-101
J.J. Eppig
Oocyte control of ovarian follicular development and function in mammals
Reproduction, 122 (2001), pp. 829-838
M.M. Matzuk,K.H. Burns,M.M. Viveiros,J.J. Eppig
Intercellular communication in the mammalian ovary: oocytes carry the conversation
Science, 296 (2002), pp. 2178-2180
M.E. Pepling,A.C. Spradling
Female mouse germ cells form synchronously dividing cysts
Development, 125 (1998), pp. 3323-3328
E.A. Mc Gee,A.J. Hsueh
Initial and cyclic recruitment of ovarian follicles
Endocr Rev, 21 (2000), pp. 200-214
K.R. Barnett,C. Schilling,C.R. Greenfeld,D. Tomic,J.A. Flaws
Ovarian follicle development and transgenic mouse models
Hum Reprod, 12 (2006), pp. 537-555
F. Nuttinck,P. Mermillod,A. Massip,F. Dessy
Characterization of in vitro growth of bovine preantral ovarian follicles – a preliminary study
Theriogenology, 39 (1993), pp. 811-821
R.A.P. Costa,C.D. Romagna,J.L. Pereira,N.C. Souza-pinto
The role of mitochondrial DNA damage in the cytotoxicity of reactive oxygen species
J Bioenerg Biomembr, 43 (2011), pp. 25-29
Y.E. Şükür,B.K. İçten,Ö. Batuhan
Ovarian aging and premature ovarian failure
J Turk Ger Gynecol Assoc, 15 (2014), pp. 190-196
R.H. Engel,A.M. Evens
Oxidative stress and apoptosis: a new treatment paradigm in cancer
Front Biosci, 11 (2006), pp. 300-312
G.M. Silva,V.R. Araújo,A.B.G. Duarte,R.N. Chaves,C.M.G. Silva,C.H. Lobo
Influences of FSH and EGF on primordial follicles during in vitro culture of caprine ovarian cortical tissue
Theriogenology, 61 (2004), pp. 1691-1704
S. Gupta,N. Malhotra,D. Sharma,A. Chandra,A. Agarwal
Oxidative stress and its role in female infertility and assisted reproduction: clinical implications
Int J Fertil Steril, 2 (2009), pp. 147-164
S.S. Du Plessis,K. Makker,N.R. Desai,A. Agarwal
Impact of oxidative stress on IVF
Expert Rev Obstet Gynecol, (2008), pp. 539-554
G. Akoka,A. Akoka
Med Encycl, 3 (1972), pp. 692
S.M.K. Rates
Plants as source of drugs
Toxicon, 39 (2001), pp. 603-613
P.B. Telefo,P.F. Moundipa,F.M. Tchouanguep
Influence of aqueous extract of Aloe buettneri, Dicliptera verticillata, Hibiscus macranthus, Justicia insularis on fertility and some biochemical parameters of reproduction in rats
J Cam Acad Sc, 3 (2001), pp. 144-150
R.J. Priso,N. Din,S.A. Konglong,A. Amougou
Inventory of some medicinal plants for the conception of pregnancy in some localities of the Department of Nkam
Book program and abstracts – XIII annual conference of biosciences,
108 pp.
W. Tacham
An ethnobotanical survey of plants used to treat diseases of the reproductive system in Foreke-Dschang and Fongo-Tongo in the Menoua division
Université de Dschang, (2000)pp. 22-24
Plant Master's Dissertation
L.A. Cajuday,G.L. Pocsidio
Effects of Moringa oleifera Lam. (Moringaceae) on the reproduction of male mice (Mus musculus)
J Med Plants Res, 12 (2010), pp. 1115-2112
R.W. Bussmann,A. Glenn
Medicinal plants used in Northern Peru for reproductive problems and female health
J Ethnobiol Ethnomed, 6 (2010), pp. 1-12
S.E. Nielsen,J.F. Young,B. Daneshvar,S.T. Lauridsen,P. Knuthsen,B. Sandstro
Effect of parsley (Petroselinum crispum) intake on urinary apigenin excretion, blood antioxidant enzymes and biomarkers for oxidative stress in human subjects
Br J Nutr, 81 (1999), pp. 447-455
K. Chifundera
Livestock diseases and the traditional medicine in the Bushi area, Kivu Province, Democratic Republic of Congo
Afr Study Monogr, 19 (1988), pp. 13-33
E. Ramaraj,S. Thamburaj,R. Samiraj,P. Subban
Studies on the antibacterial and nucleic acid degradation property of Cassia alata
Int J Drug Dev Res, 6 (2014), pp. 44-53
M. Koch,D.A. Kehop,B. Kinminja,M. Sabak,G. Wavimbukie,K.M. Barrows
An ethnobotanical survey of medicinal plants used in the East Sepik Province of Papua New Guinea
J Ethnobiol Ethnomed, 11 (2015), pp. 79
D.B. James,E.A. Abu,A.U. Wurochekke,G.N. Orji
Phytochemical and antimicrobial investigation of the aqueous and methanolic extracts of Ximenia americana
J Med Sci, 2 (2007), pp. 284-288
J.E. Adjanohoun,N. Aboubakar,K. Dramane,M.E. Ebot,J.A. Ekpere,E.G. Enow-Orock
Traditional medicine and pharmacopoeia
Contribution to ethnobotanical floristic studies in Cameroon, CNPMS Porto-Novo Benin, (1996)
22 pp.
L.O. Adewole
Ageratum conyzoides L. (Asteraceae)
Fitoterapia, 73 (2002), pp. 1-16
T.K. Tabopda,G.W. Fotso,J. Ngoupayo,A.C. Mitaine-Offer,B.T. Ngadjui,M.A. Lacaille-Dubois
Antimicrobial dihydroisocoumarins from Crassocephalum biafrae
Planta Med, 75 (2009), pp. 1258-1261
M. Arbonnier
Shrubs and lianas of the drylands of West Africa
2nd ed., CIRAD-MNHN, (2002)
549 pp.
J.O. Igoli,T.A. Tornyiin,S.S. Usman,H.O.A. Oluma,N.P. Igoli
Folkmedicines of the lower Benue valley of Nigeria
Recent progress in medicinal plants: Vol. 7. Ethnomedicine and pharmacognosy II, pp. 327-338
M. Adnan,A. Tariq,S. Mussarat,S. Begum,N.M. AbdEIsalam,R. Ullah
Ethnogynaecological assessment of medicinal plants in Pashtun's Tribal Society
BioMed Res Int, (2015)pp. 9
B.J. Doyle,J. Frasor,L.E. Bellows,T.D. Locklear,A. Perez,J.G. Laurito
Estrogenic effects of herbal medicines from Costa Rica used for the management of menopausal symptoms
J.B. Harborne
Classes and functions of secondary products
Chemicals from plants, perspectives on secondary plant products, pp. 1-25
G.E. Trease,W.C. Evans
11th ed., Baillière Tindall, (1996)pp. 75-76
A. Hassig,W.X. Liang,H. Schwabl,K. Stampfli
Flavonoids and tannins: plant-based antioxidants with vitamin character
Med Hyp, 47 (1999), pp. 9-81
P. Jiang,F. Burczynski,C. Campbell,G. Pierce,J.A. Austria,C.J. Briggs
Rutin and flavonoid contents in three buckwheat species Fagopyrum esculentum, F. tataricum, and F. homotropicum and their protective effects against lipid peroxidation
Food Res Int, 40 (2007), pp. 356-364
F. Bourgaud,A. Gravot,S. Milesi,E. Gontier
Production of plant secondary metabolites: a historical perspective
Plant Sci, 16 (2001), pp. 839-851
M. Saxena,J. Saxena,R. Nema,D. Dharmendra Singh,A. Gupta
Phytochemistry of medicinal plants
J Pharmacogn Phytochem, 1 (2013), pp. 168-182
N. Dudareva,E. Pichersky,J. Gershenzon
Biochemistry of plant volatiles
Plant Physiol, 135 (2004), pp. 1893-1902
S. Kumar,A.K. Pandey
Chemistry and biological activities of flavonoids: an overview
Sci World J, 2013 (2013), pp. 162750
S.D. Sarker,L. Nahar
Chemistry for pharmacy students general, organic and natural product chemistry
John Wiley & Sons, (2007)pp. 283-359
B.B. Gouveia,V.R.P. Barros,L.P. Santos,R.J.S. Gonçalves,M.H.T. Matos
Immunohistochemical localization of fibroblast growth factor-2 in the sheep ovary and its effects on pre-antral follicle apoptosis and development in vitro
Reprod Domest Anim, 49 (2014), pp. 222-228
H.R. Tang,A.D. Covington,R.A. Hancock
Structure–activity relationships in the hydrophobic interactions of polyphenols with cellulose and collagen
Biopolymers, 70 (2003), pp. 403-413
F. Ferk,A. Chakraborty,W. Jager,M. Kundi,J. Bichler,M. Michle
Potent protection of gallic acid against DNA oxidation: results of human and animal experiments
S. Guan,D. Ge,T.Q. Liu,X. Ma,Z.F. Cui
Protocatechuic acid promotes cell proliferation and reduces basal apoptosis in cultured neural stem cells
Toxicol in Vitro, 23 (2009), pp. 201-208
L.J. An,S. Guan,G.F. Shi,Y.M. Bao,Y.L. Duan,B. Jiang
Protocatechuic acid from Alpiniaoxyphylla against MPP+ induced neurotoxicity in PC12 cells
Food Chem Toxicol, 44 (2006), pp. 436-443
G.F. Shi,L.J. An,B. Jiang,S. Guan,Y.M. Bao
Alpiniaprotocatechuic acid protects against oxidative damage in vitro and reduces oxidative stress in vivo
Neurosci Lett, 403 (2006), pp. 206-210
P.F. Wang,R.L. Zheng
Inhibitions of the autoxidation of linoleic acid by flavonoids in micelles
Chem Phys Lipids, 63 (1992), pp. 37-40
Z. Gao,K. Huang,H. Xu
Protective effects of flavonoids in the roots of Scutellaria baicalensis Georgi against hydrogen peroxide-induced oxidative stress in HS-SY5Y cells
Pharmacol Res, 4 (2001), pp. 173-178
D. Egan,R. O’Kennedy,E. Moran,D. Cox,E. Prosser,R.D. Thornes
The pharmacology, metabolism, analysis and application of coumarin, and coumarin related compounds
Drug Metab Rev, 22 (1990), pp. 503-529
B.G. Lake
Coumarin metabolism, toxicity and carcinogenicity: relevance for human risk assessment
Food Chem Toxicol, 37 (1999), pp. 423-453
S. Martin-Aragón,J.M. Benedi,A.M. Villar
Effects of the antioxidant (6,7-ihydroxycoumarin) esculetin on the glutathine system and lipid peroxidation in mice
Gerontology, 44 (1998), pp. 21-25
T. Kaneko,N. Baba,M. Matsuo
Protection of coumarins against linoleic acid hydroperoxide-induced cytotoxicity
Chem Biol Interact, 142 (2000), pp. 239-254
J.H. Leal-Cardoso,M.C. Fonteles
Pharmacological effects of essential oils plants of the Northeast of Brazil
An Acad Bra Ciênc, 71 (1999), pp. 207-213
R.S. Freire,S.M. Morais,F.E. Catunda-Junior,D.C. Pinheiro
Synthesis and antioxidant, anti-inflammatory and gastroprotector activities of anethole and related compounds
Bioorg Med Chem, 13 (2005), pp. 4353-4358
G.B. Chainy,S.K. Manna,M.M. Chaturvedi,B.B. Aggarwal
Anethole blocks both early and late cellular responses transduced by tumor necrosis factor: effect on NF kappa B, AP-1, JNK, MAPKK and apoptosis
Oncogene, 19 (2000), pp. 2943-2950
N.A.R. Sá,V.R. Araújo,H.H.V. Correia,A.C.A. Ferreira,D.D. Guerreiro,A.M. Sampaio
Anethole improves the in vitro development of isolated caprine secondary follicles
C. Pelissero,M.J.P. Lenczowski,D. Chinzi,C.B. Davail,J.P. Sumpter,A. Fostier
Effects of flavonoids on aromatase activity, an in vitro study
J Steroid Biochem Mol Biol, 57 (1996), pp. 215-223
P.A. Grace
Ischaemia-reperfusion injury
Br J Surg, 81 (1994), pp. 637-647
J.N. Robert,V.N. Els,E.C. Danny,G.B. Petra,V.N. Klaske,A.M. Paul
Flavonoids: a review of probable mechanisms of action and potential applications
Am J Clin Nutr, 74 (2001), pp. 418-425
W. Rabl,F. Katzgraber,M. Steinlechner
Camphor ingestion for abortion (case report)
Forensic Sci Int, 89 (1997), pp. 137-140
S.A. Linjawi
Effect of camphor on uterus histology of pregnant rats
J King Abdulaziz Univ, 16 (2009), pp. 77-90
D. Oliaee,T.B. Mohammad,O. Naiime,G. Ahmad
Evaluation of cytotoxicity and antifertility effect of Artemisia kopetdaghensis
Adv Pharmacol Sci, (2014), pp. 5
M. Hsia,Y. Chih-Lan,K. Yueh-Hsiung,S.W. Paulus,C. Wenchang,K.J. Hutt
An oocentric view of folliculogenesis and embryogenesis
Reprod Biomed Online, 14 (2007), pp. 758-764
P. Moutsatsou
The spectrum of phytoestrogens in nature: our knowledge is expanding
Hormones, 6 (2007), pp. 173-193
L. Dusza,R. Ciereszko,D.J. Skarzyński,L. Nogowski,M. Opałka,K. Barbara
Mechanism of phytoestrogen action in reproductive processes of mammals and birds
Reprod Biol, 6 (2006), pp. 151-174
E.D. Lephart
Modulation of aromatase by phytoestrogen
Enzym Res, (2015), pp. 11
A. Krazeisen,R. Breitling,G.M. Oller,J. Adamski
Phytoestrogens inhibit human 17β-hydroxysteroid dehydrogenase type 5
Mol Cell Endocrinol, 171 (2001), pp. 151-162
S.A. Whitehead,M. Lacey
Phytoestrogens inhibit aromatase but not 17β-hydroxysteroid dehydrogenase (HSD) type 1 in human granulosa-luteal cells: evidence for FSH induction of 17β-HSD
Hum Reprod, 18 (2003), pp. 487-494
S.E. Santini,G. Basini,S. Bussolati,F. Grasselli
The phytoestrogen quercetin impairs steroidogenesis and angiogenesis in swine granulosa cells in vitro
J Biomed Biotechnol, 6 (2007), pp. 173-193
V.B.J. Voorhis,M.S. Dunn,G.D. Snyder
Nitric oxide: an autocrine regulator of human granulosa-luteal cell steroidogenesis
Endocrinology, 135 (1994), pp. 1799-1806
R. Rajabi-Toustani,R. Motamedi-Mojdehi,M. Mehr,R. Motamedi-Mojdehi
Effect of Papaver rhoeas L. extract on in vitro maturation of sheep oocytes
Small Rumin Res, 114 (2013), pp. 146-151
S. Tavana,H. Eimani,M. Azarnia,A. Shahverdi,P. Eftekhari-Yazdi
Effects of saffron (Crocus sativus L.) aqueous extract on in vitro maturation fertilization and embryo development of mouse oocytes
Cell J, 13 (2012), pp. 259-264
F.S. Abdollahi,J. Baharara,K. Nejad Shahrokhabadi,F. Namvar,E. Amini
Effect of Phoenix dactylifera pollen grain on maturation of preantral follicles in NMRI mice
J Herbmed Pharmacol, 4 (2015), pp. 93-97
F.D. Moghadam,J. Baharara,S.Z. Balanezhad,M. Jalali,E. Amini
Effect of Holothuria leucospilota extracted saponin on maturation of mice oocyte and granulosa cells
Res Pharma Sci, 13 (2016), pp. 1-7
M.C. Myhrstad,H. Carlsen,O. Nordström,R. Blomhoff,J. Moskaug
Flavonoids increase the intracellular glutathione level by transactivation of the gamma-glutamylcysteine synthetase catalytical subunit promoter
Free Radic Bio Med, 32 (2002), pp. 386-393
D.G. De Matos,C.C. Furnus
The importance of having high glutathione (GSH) level after bovine in vitro maturation on embryodevelopment: effect of beta-mercaptoethanol, cysteine and cystine
Theriogenology, 53 (2000), pp. 761-771
Z. Wu,Y. Yang,Y. Chen,G. Xia,R. Zhang
Effects of subcutaneous administration of daidzein on blastocyst implantation in rats
Food Chem Toxicol, 43 (2005), pp. 167-172
R.C. Sprong,A.M. Winkelhuyzen-Janssen,C.J. Aarsman,J.F. Van Oirschot,T. Van der Bruggen,B.S. Van Asbeck
Low-dose N-acetylcysteine protects rats against endotoxin-mediated oxidative stress, but high-dose increases mortality
Am J Respir Crit Care Med, 157 (1998), pp. 1283-1293
T.D. Locklear,H. Yue,F. Jonna,J.D. Brian,P. Alice,G.L. Jorge
Estrogenic and progestagenic effects of extracts of Justicia pectoralis, an herbal medicine from Costa Rica used for the treatment of menopause and PMS
H. Lim,C. Bibhash,B.C. Paria,S.K. Das,R.L. Dinchuk,J.M. Trzaskos
Multiple female reproductive failures in cyclooxygenase 2-deficient mice
Cell, 91 (1997), pp. 197-208
A.H. Ibrahim,B. Barakata,W.K.B. Khalilb,A.R. Al-Himaidi
Moringa oleifera extract modulates the expression of fertility related genes and elevation of calcium ions in sheep oocytes
Small Rumin Res, 130 (2015), pp. 67-75
A. Štochmaľová,A. Kadasi,R. Alexa,R. Grossman,A. Sirotkin
The effect of yucca on proliferation, apoptosis, and steroidogenesis of porcine ovarian granulosa cells
Potravinarstvo, 8 (2014), pp. 1-5
A. Abedi,L. Rouhi,A.G. Pirbalouti
Effect of Gundelia tournefortii leaves extract on in immature mouse oocytes
J Herb Drugs, 5 (2014), pp. 84-89
E.M. Maleki,H. Eimani,M.R. Bigdeli,B. Ebrahimi,A.H. Shahverdi,A.G. Narenji
A comparative study of saffron aqueous extract and its active ingredient, crocin on the in vitro maturation, in vitro fertilization, and in vitro culture of mouse oocytes
Taiwan J Obstet Gynecol, 53 (2014), pp. 21-25
Corresponding author. (Ana Paula Ribeiro Rodrigues
Copyright © 2016. Sociedade Brasileira de Reprodução Humana
Reprod Clim 2017;32:109-19 - Vol. 32 Núm.2 DOI: 10.1016/j.recli.2016.11.002